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November 6–9, 2014
Chicago Hilton & Towers | Chicago, IL USA
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ASDP
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The American Society of Dermatopathology
Oral Abstract Session 1
3:45 p.m. – 3:55 p.m.
Diagnostic Utility of SOX11 Immunohistochemistry in Low Grade
Cutaneous B-cell Lymphomas
Andy Hsi, MD
3:55 p.m. – 4:05 p.m.
Whole Genome Single Nucleotide Polymorphism Array in
Spitzoid Neoplasms
Kari Sufficool, MD
4:05 p.m. – 4:15 p.m.
Comparison Between Melanoma Gene Expression Score and
Fluorescence in-situ Hybridization for the Classification of
Melanocytic Lesions
Eugen Minca, MD, PhD
4:15 p.m. – 4:25 p.m.
Eosinophils in Lichen Sclerosus et Atrophicus
Phillip Keith, MD
4:25 p.m. – 4:35 p.m.
MXA Expression in Acute Graft Versus Host Disease,
Morbilliform Drug Eruption and Viral Exanthem
Garrett Desman, MD
4:35 p.m. – 4:45 p.m.
Characterization of the Immune Infiltrate During Early
Melanomagenesis Reveals an Influx of Regulatory T cell
Coinciding with the Invasion of Subcutaneous Structures
Andrea Boni, MD
4:45 p.m. – 4:55 p.m.
Clinicopathologic Features of IgG/IgA Pemphigus in Comparison
With Classic (IgG) and IgA Pemphigus
Siavash Toosi, MD
4:55 p.m. – 5:05 p.m.
Diagnostic Utility of C3d Immunohistochemical Staining in the
Diagnosis of Bullous Pemphigoid
Roberto Novoa, MD
5:05 p.m. – 5:15 p.m.
Perineural Granulomas in Cutaneous Sarcoidosis
William Robert Munday, MD
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of heterozygosity (LOH) in spitzoid neoplasms. Methods: DNA
samples obtained from cases representing SN (n=18), AST (n=5)
or SMM (n=14) were analyzed by the OncoScan FFPE assay
kit and processed using manufacturer-recommended software,
with detection of LOH regions >5Mb. Results: Numerous gains
and losses were found across all chromosomes. SMM showed
chromosomal gains at multiple loci including 3q, 3q14-q13
(MITF), 6p, 6q27, 7p11 (EGFR), 8q24, 10q23 (PTEN), 11p13-p12,
11q21, 12p12-p11, 12q21-q22, 13q14 (RB1), 13q33-q34, 15q,
16q12-q21, 17q24-q25, 19p13, 21q22, and 22q11 and losses
in chromosome 3p21, 5p12-p11, 6q25-q27, 7p11-q11, 9 (9p),
11p11, 11q21-q22, 13q11-q12, 15q11, 16p, 19, and 20q11 in
more than 1/3 of the samples. In contrast, chromosomal gains in
3p13 (MITF), 6q27, 8q24, 17q25 and 22q11 and losses in 9q33,
10p11, 14q32, 19p12, 19q13 and 22q11 were observed in more
than 1/3 of SN. AST demonstrated gains in 1p32, 2q24, 3q, 4p15,
6p, 6q27, 7p21, 7p11 (EGFR), 8q23-q24, 9p21, 10p15, 10q22,
10q23, 11p15, 11p13-p12, 11q21, 12q13, 14q24, 15q13-q24,
16q23-q24, 17q25, 19p13, 20q12, 21q22 and 22q11 and losses
in 1p32, 1q21, 3p21 (DOCK3), 7p11-q11, 9p24-p23, 9q21,
9q34, 12q24, 13q11-q12, 15q11, 16p13, 16q23, 17p13, 19p and
19q13. Tetrasomy of chromosome 4 was seen in 1 SMM. High
copy gains (5-20 copies) in chromosomes 1, 5 and 7 were seen in
2 SMM. Eight SMM had LOH in most chromosomes; 2 AST and
12 SN had LOH in 7 and 15 segments, respectively. In SN, there
was recurrence of LOH in chromosomes 11 (2 cases) and 16 (4
cases). In addition, somatic mutations in BRAF p.V600E (1 SN),
NRAS p.Q61R (1 SN,1 SMM), TP53 p.Y220C (1 SMM) and TP53
p.G245S (3 SN, 2 SMM, 1 AST) were identified. Conclusion: The
chromosomal signatures of SN, AST and SMM are similar, but
demonstrate a spectrum of increasing genomic complexity. SMM
has increased CNV and LOH compared to SN, with AST showing
a genomic profile similar to SMM. The OncoScan FFPE assay
allows for recognition of subtle genomic changes.
Diagnostic utility of SOX11 immunohistochemistry in
low grade cutaneous B-cell lymphomas
Andy Hsi, MD
Andy Hsi, MD1; Maria Hurley, MD2; Valerie Viele, MS1; Amanda
Kelley, BS1; Andras Schaffer, MD, PhD1
1
Washington University School of Medicine, St. Louis, Missouri, USA
2
Saint Louis University School of Medicine, St. Louis, Missouri, USA
B-cell lymphomas account for approximately 30% of primary
cutaneous lymphomas. Morphologic and immunophenotypic
distinctions between small mature B-cell lymphomas, especially mantle cell lymphoma (MCL), chronic lymphocytic leukemia/
small lymphocytic lymphoma (CLL), and marginal zone lymphoma (MZL), can be challenging. Primary cutaneous MCL and
CLL are exceeding rare. However, secondary involvement has
been described in up to 20% of these lymphomas and may be
the initial presentation of disease. Both MCL and CLL express
surface CD5. MCL is further characterized as cyclin D1 (CCND1)+
and CD23-, while CLL is CD23+ and CCND1-. However, CCND1MCL cases have been recently described, and CD23 expression in CLL is frequently dim or show only rare positivity, further
confounding the diagnosis. MZL, while traditionally recognized
as CD5-, can occasionally be CD5+. SOX11 is a neuronal transcription factor recently described as a specific marker for nodal
MCL. However, its utility in differentiating cutaneous MCL from
other mature B-cell lymphomas has not been addressed. The
purpose of this study was to evaluate the diagnostic utility of
SOX11 in differentiating cutaneous MCL from other cutaneous
mature B-cell lymphomas. Immunohistochemical staining with
monoclonal anti-SOX11 antibody was performed on 6 cases of
cutaneous CCND1+ MCL, 8 CLL, and 4 MZL. Nuclear SOX11
expression was seen in 5 (83%) of MCL and none of the CLL or
MZL cases. All cases also showed non-specific cytoplasmic or
perinuclear dot-like staining, which was considered as negative.
The sensitivity and specificity for SOX11 in MCL are 83% and
100%, respectively. The positive and negative predictive values
of SOX11 in MCL are 100% and 92%, respectively. Our results
showed that SOX11 is a reliable and specific marker for distinguishing cutaneous MCL from CLL and MZL.
Comparison between melanoma gene expression
score and fluorescence in-situ hybridization for the
classification of melanocytic lesions
Eugen Minca, MD, PhD
Eugen Minca, MD, PhD1; Angela Collie, MD, PhD1; Jennifer Ko,
MD, PhD1; Steven Billings, MD1
Whole genome single nucleotide polymorphism array
in spitzoid neoplasms
1
Kari Sufficool, MD
Kari Sufficool, MD1; Vishwanathan Hucthagowder, PhD2; Shashikant Kulkarni, PhD, FACMG2; Andras Schaffer, MD, PhD2
Washington University School of Medicine/Barnes-Jewish Hospital, Saint
Louis, Missouri, USA
1
2
Cleveland Clinic, Cleveland, Ohio, USA
Background: Melanoma is responsible for the majority of skin
cancer related deaths, and has an increasing incidence. Accurate diagnosis of melanoma and distinction from atypical nevi is
critical, but often challenging histologically. Fluorescence in-situ
hybridization (FISH) and melanoma gene expression score have
been recently developed as adjunct molecular tools for melanoma detection. Data correlating these molecular methods is
scarce. Here we compared melanoma gene expression score
(Myriad Genetics) with clinical melanoma FISH on a series of
cases from our institution. Design: The study included 15 formalin-fixed paraffin embedded skin biopsies diagnosed histologically as atypical nevus (n=4), Spitz lesion (n=5) and melanoma (n=6).
Melanoma FISH was performed on all samples using probes for
Washington University School of Medicine, Saint Louis, Missouri, USA
Background: Differentiating Spitz nevus (SN), atypical spitz
tumor (AST) and spitzoid malignant melanoma (SMM) presents a diagnostic challenge. We utilized a new platform, which
requires low DNA input, covers >900 cancer genes, detects
somatic mutations, and has a high dynamic range (10+ copies),
to identify mutations, copy number variation (CNV) and loss
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6p25 (RREB1), 6q23 (MYB), CEP6, 11q13 (CCND1), 8q24 (MYC)
and 9p21 (CDKN2A) and the results were interpreted as positive
or negative. All samples also underwent melanoma gene expression score analysis and were classified as “likely benign”, “indeterminate” or “likely malignant”. Results: By FISH, 5 samples
showed melanoma specific genomic abnormalities (5/6 melanomas) and 10 were negative (1/6 melanoma, 5/5 Spitz lesions, 4/4
atypical nevi). By gene expression score 4 samples were classified as “likely malignant” (3/6 melanoma, 1/4 atypical nevus), 7
as “likely benign” (2/6 melanoma, 5/5 Spitz lesions), 3 as “indeterminate” (1/6 melanoma, 2/4 atypical nevi) and 1 could not be
analyzed. 3 discordant cases, 2 FISH-positive and 1 FISH-negative, were classified as “likely benign” and “likely malignant” by
gene expression score respectively. The overall concordance of
the melanoma gene expression score with melanoma FISH was
73% in this limited series. Conclusion: Melanoma gene expression score and FISH are valuable ancillary diagnostic tools for
melanoma detection. Further larger studies are warranted to
compare the accuracy of these methods for the classification of
melanocytic lesions.
MXA expression in acute graft versus host disease,
morbilliform drug eruption, and viral exanthem
Garrett Desman, MD
Garrett Desman, MD1; Harp Joanna, MD1; Sarah Coates, MD1
Weill Cornell Medical College of Cornell University, New York, New York,
USA
1
Aim: In some cases, distinguishing between acute graft versus host disease (GVHD), morbilliform drug eruption, and viral
exanthem may be difficult both clinically and histopathologically.
The latter two entities are histopathologically characterized by
delayed dermal hypersensitivity reactions (Th2 and Th1, respectively) and the former by vacuolar interface dermatitis. Occasionally, eosinophils may be present in viral exanthems and GVHD,
and conversely eosinophils may be absent in drug eruptions.
Vacuolar interface dermatitis may be present all three entities.
Myxovirus resistance gene A (MXA) is an immunohistochemical marker known to be positive in type I interferon-mediated
immune reactions, including the response to viral infections as
well as collagen vascular disease. While this marker has been
well documented in collagen vascular disease and lesional viral
eruptions (i.e. HSV, molluscum), no study has evaluated the use
of this marker in distinguishing between GVHD, morbilliform drug,
and viral exanthem. Methods: We retrospectively examined 3
cases of GVHD, 5 cases of morbilliform drug eruption, and 5 cases of viral exanthem. The diagnosis of all cases was verified by
systemic findings, viral titers, and clinical course. MXA immunohistochemical staining was performed in all cases. Skin samples
from discoid lupus and allergic contact dermatitis were used as
positive and negative controls, respectively. Results: All cases of
viral exanthem positively expressed MXA within epidermal keratinocytes and scattered inflammatory cells. All cases of GVHD and
drug eruption were negative for MXA staining. Conclusion: MXA
expression is a useful diagnostic adjunct in distinguishing viral
exanthem from GVHD and drug eruption.
Eosinophils in Lichen sclerosus et atrophicus
Phillip Keith, MD
Phillip Keith, MD1; Michael Wolz, BMBCH, JD1; Margot Peters,
MD1
1
Mayo Clinic, Rochester, Minnesota, USA
The classic histopathological features of lichen sclerosus et
atrophicus (LS) include a band of mainly lymphoplasmacytic
inflammation below a zone of dermal edema and sclerosis. The
presence of eosinophils in LS has received little attention. It has
been suggested that the finding of tissue eosinophils, particularly
eosinophilic spongiosis, may be a marker for the coexistence of
bullous pemphigoid and LS. We sought to determine whether the
histopathological finding of dermal eosinophils and/or eosinophilic spongiosis in biopsies from patients with LS is associated with
autoimmune bullous disease, nonbullous autoimmune disease, or
allergic contact dermatitis, by retrospective review of the histopathology and medical records of 253 patients with LS. Twenty-eight percent of biopsy specimens contained dermal eosinophils. Only one case had dermal eosinophils and eosinophilic
spongiosis, and this patient had bullous pemphigoid. We found
a similar incidence of autoimmune diseases (bullous or nonbullous) and allergic contact dermatitis in patients who had LS with
eosinophils and those who had LS without eosinophils. Although
our study does not exclude such associations, the presence of
eosinophils in LS does not appear to be a marker for bullous or
nonbullous autoimmune disease or allergic contact dermatitis.
The clinical or pathogenic significance of eosinophils and eosinophilic spongiosis is uncertain, but our data suggest that the
finding of tissue eosinophils is not per se sufficient to prompt an
extensive work-up for additional diagnoses.
Characterization of the immune infiltrate during early
melanomagenesis reveals an influx of regulatory T cell
coinciding with the invasion of subcutaneous
structures
Andrea Boni, MD
Andrea Boni, MD1; Tamer Chabanet, PhD1; Mary Jo Turk, PhD1
1
Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, USA
The immune system plays a critical role in the development
of malignant melanoma. Melanoma tumors have the ability to
induce an immune suppressive microenvironment that actively
promotes immune evasion and tumor escape. Regulatory T cells
(Treg) are key mediators of tumor immune suppression and have
been shown to universally correlate with tumor progression and
poor clinical outcome. Established melanomas show increased
numbers of Tregs, although little is known about when Treg accumulation occurs during the process of melanoma tumorigenesis.
In the present study, we characterized the endogenous immune
infiltrate following induction of melanoma in an autochthonous
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murine melanoma model. Upon topical administration of tamoxifen, mice concomitantly lose the melanocyte-specific expression
of the tumor suppressor Pten while inducing expression of the
constitutively active oncogene BRAFV600E, driving melanoma
tumorigenesis. As early as 16 days post induction, melanocytic
proliferations were visible in the skin in a perifollicular pattern
with increased pigmentation and pigment incontinence. At day
21, mice developed a nodular infiltrate that expanded the dermis
and displaced the adnexal structures, while minimally involving
the epidermis. Invasion of the stratum carnosum, the muscular
layer that delimitates the mouse skin, was observed 26 days post
induction. This event coincided with a significant increase in the
absolute numbers and frequency of intratumoral Tregs, compared
to earlier time points or normal skin. The present study provides
an important insight into the kinetics of the lymphocyte response
following melanoma tumor inception and also underscores the
prevalence of Treg-mediated tumor immune suppression.
Diagnostic utility of C3d immunohistochemical staining
in the diagnosis of bullous pemphigoid
Roberto Novoa, MD
Roberto Novoa, MD1; Emily Chu, MD, PhD1
1
Bullous pemphigoid (BP) is the most common of the immunobullous disorders, but may pose a diagnostic challenge in early or
atypical cases. In recent times, serum enzyme-linked immunosorbent assays (ELISAs) for pathogenic antibodies to BP180 and
BP230 have emerged as highly sensitive and specific diagnostic
tests. In the past six years, C3d immunohistochemical staining on formalin-fixed tissue has been used as well, with linear
deposition along the basement membrane zone described as
characteristic of BP. Here, we report the diagnostic accuracy of
C3d staining using pooled ELISA results as the gold standard.
Methods: We performed a query of our pathology database,
retrieving all patients with ELISA results for BP180 and 230 who
had also undergone a skin biopsy for rash within 2 years of serologic testing. A chart review was performed to determine C3d
staining results, defined as positive or negative. In cases lacking
C3d stains, the tissue block was retrieved, with new slides
generated for C3d immunostaining and interpreted by a dermatopathologist blinded to the final diagnosis. Results: Preliminary
results demonstrated 79 patients with both ELISA results and
skin biopsies for rash, with 101 total biopsies. 48.5% of biopsies
came from BP(-) patients, while 51.5% of biopsies came from
BP(+) patients. C3d immunostaining had a sensitivity of 69%
and a specificity of 96%, for a positive predictive value of 94.7%.
False negative tests occurred more frequently in the setting of
low antibody titers and in biopsies performed far in advance of
ELISAs, potentially underestimating sensitivity. Conclusions: C3d
immunostaining appears to be a highly specific test for bullous
pemphigoid
Clinicopathologic features of IgG/IgA pemphigus in
comparison with classic (IgG) and IgA pemphigus
Siavash Toosi, MD
Siavash Toosi, MD1; Jeffrey Collins, D.O.2; Christine Lohse,
M.S.1; Michael Wolz, B.M.B.Ch.1; Carilyn Wieland, MD1; Michael
Camilleri, MD1; Alison Bruce, M.B., Ch.B.1; Marian McEvoy, MD1;
Julia Lehman, MD1
1
Mayo Clinic, Rochester, Minnesota, USA
2
Good Samaritan Regional Medical Center, Corvallis, Oregon, USA
University of Pennsylvania, Philadelphia, Pennsylvania, USA
Background: The pemphigus group is classically characterized by
the presence of circulating immunoglobulins (Ig) against epidermal desmosomes. Prior reports of patients with IgG/IgA pemphigus are sparse. Whether IgG/IgA pemphigus is best classified
as a subtype of IgG (classic) pemphigus or IgA pemphigus, or
as a distinct entity, has yet to be determined. Objective: We
compared the clinicopathological features of patients with IgG/
IgA pemphigus to those of IgG pemphigus and IgA pemphigus.
Methods: We performed a retrospective study on patients with
IgG, IgG/IgA and IgA pemphigus evaluated at our clinic (19932013). Results: We included 26, 13, and 7 patients with IgG, IgG/
IgA, and IgA pemphigus, respectively. Patients with IgG/IgA pemphigus did not differ significantly from IgG pemphigus patients in
terms of clinical and microscopic features, direct immunofluorescence (DIF) findings, anti-desmoglein antibody values, and treatments required. However, patients with IgG/IgA pemphigus were
significantly different from IgA pemphigus patients with regards
to intertriginous distribution (P = 0.038) and pustular lesions (P <
0.001), acantholysis (P = 0.043), and presence of intercellular C3
deposits on DIF (P < 0.001). Limitations: Retrospective design;
low sample size, due to rarity of IgG/IgA and IgA pemphigus.
Conclusion: Comparative clinicopathologic data imply that IgG/
IgA pemphigus may best be regarded as a variant of IgG pemphigus and distinct from IgA pemphigus.
Perineural granulomas in cutaneous sarcoidosis
William Munday, MD
William Munday, MD1; Jennifer McNiff, MD2; Kalman Watsky,
MD2; Anjela Galan, MD2
1
Yale-New Haven Hospital, New Haven, Connecticut, USA
2
Yale School of Medicine, New Haven, Connecticut, USA
Perineural granulomas in cutaneous sarcoidosis have been
scarcely reported in the literature and their clinical significance
has yet to be evaluated. Recently, a 27- year-old male presented
with multiple pink papules on the flank and lower back, accompanied by a painful, burning sensation. Biopsies showed well-defined granulomas consistent with sarcoidosis and involving small
cutaneous nerves. This finding prompted further investigation. We
hypothesized that perineural granulomas may be an under-recognized feature of cutaneous sarcoidosis, and may be responsible
for sensory disturbances. To estimate the incidence and clinical
significance of perineural involvement in sarcoidosis, we reviewed
cases from 29 consecutive patients with cutaneous sarcoidosis
with a total of 40 biopsies. Perineural granulomas were identified
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Oral Abstract Session 1
in 18/29 (62%) patients and in 22/40 (55%) biopsies. By site,
perineural granulomas were identified in 7/9 biopsies from the
proximal upper extremity, 1/3 from the distal upper extremity,
7/12 from the head and neck, including 4/4 from the nose, 5/9
from the back, 1/2 from the flank, and 1/5 from the lower extremity. Clinically, pain was noted in three cases, and in each case,
perineural granulomas were present. Interestingly, the body site
distribution pattern we identified mirrors the entity known as
“sarcoidosis small-fiber neuropathy” (SSFN), in which sarcoidosis
patients experience sensory disturbances of unknown etiology,
primarily involving the face, proximal extremities, and trunk. In
conclusion, our results suggest that perineural granulomas in cutaneous sarcoidosis are more common than previously appreciated; primarily involve the head, proximal upper extremities, and
back; and may be responsible for neurological manifestations.
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The American Society of Dermatopathology
15th Annual Duel in Dermatopathology Resident Abstract Competition
5:15 p.m. – 5:20 p.m.
Incidental Finding of Scurvy in the Setting of Leukocytoclastic
Vasculitis
Abha Soni, DO, MPH
5:20 p.m. – 5:25 p.m.
Zoonotic Onchocerca Lupi Infection Presenting as a Subcutaneous
Nodule in a 10-Year-Old Girl: Report of the Second Case in the United
States and a Review of the Literature
Ryan Berry, MD
5:25 p.m. – 5:30 p.m.
Fungal Mimickers in Drug Induced Systemic Lupus Erythematosus and
Vasculitis
Paul Haun, MD
5:30 p.m. – 5:35 p.m.
Aggressive HPV Positive Penile Squamous Cell Carcinoma with
Sarcomatoid and Basaloid Features
Kelly Park, MD, MSL
5:35 p.m. – 5:40 p.m.
Cutaneous Lymphoid Hyperplasia (pseudolymphoma): A Rare Adverse
Reaction Following Injection with Botulinum Toxin Type A for Glabellar
Lines
Agnieszka Kubica, MD
5:40 p.m. – 5:45 p.m.
Epstein-Barr Virus-associated Smooth Muscle Tumors in an HIV
Patient; a Spindle Cell Diagnostic Pitfall
Ifeoma Nwadei, MD
5:45 p.m. – 5:50 p.m.
Petechial Patches in a 29-year-old: Autoimmune Hemolytic Anemia
in Eosinophilic Granulomatosis with Polyangitis (AKA Churg-Strauss
syndrome)
Christopher Soon, MD
5:50 p.m. – 5:55 p.m.
The BAP1 Cancer Syndrome: A Case of Metastatic Melanoma and
Characteristic Atypical Melanocytic Lesions
Katherine Roy, MD
5:55 p.m. – 6:00 p.m.
INI-1 Negative Dermal Neuromas in a Child with Multiple Occurrences
of Epithelioid Sarcoma
William James Tidwell, MD
6:00 p.m. – 6:05 p.m.
Infantile GM1 Gangliosidosis: Clinicopathologic and Ultrastructural
Findings in the Skin
Andrea Primiani, MD
6:05 p.m. – 6:10 p.m.
Myxoinflammatory Fibroblastic Sarcoma/Hemosiderotic
Fibrolipomatous Tumor: A Rare Translocation-associated Hybrid Tumor
with Marked Spatial Variation.
Andrew Rand, MD
6:10 p.m. – 6:15 p.m.
Giant Cell Fibroblastoma Recurring as Dermatofibrosarcoma
Protuberans in Patient with PTEN Hamartoma Tumor Syndrome
Emily Hoffman Smith, MD
6:15 p.m. – 6:20 p.m.
Extensive Cutaneous Involvement of an Extranodal NK/T-Cell
Lymphoma, Nasal Type with Hemophagocytic Lymphohistiocytosis
Conor Dolehide, MD
6:20 p.m. – 6:25 p.m.
A Novel ETV3-NCOA2 Fusion in a Case of Indeterminate Cell
Histiocytosis
Ryanne Brown, MD, MBA
6:25 p.m. – 6:30 p.m.
Granulomatous Arteritis: A Rare Post-Varicella Zoster Virus
Manifestation
Brianne Hisako Daniels, DO
6:30 p.m. – 6:35 p.m.
Congenital Nevi Versus Metastatic Melanoma in a Newborn to a Mother Ahmed Alomari, MD
with Malignant Melanoma – Diagnosis Supported by Sex Chromosome
Analysis and Imaging Mass Spectrometry
6:35 p.m. – 6:40 p.m.
Atypical Chromhidrosis with Elevated Cutaneous Iron Excretion:
Report of a Case and Literature Review
Ryan Romano, DO
6:40 p.m. – 6:45 p.m.
An Exceptional Case of X-linked Protoporphyria in a Female patient
Michelle Gatica-Torres, MD
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The American Society of Dermatopathology
15th Annual Duel in Dermatopathology Resident Abstract Competition
is transmitted to humans. This is an uncommon event with
only 21 cases being reported worldwide; five of these were
due to Onchocerca lupi, for which only one occurred in the
United States. Herein, we report the second case of zoonotic
onchocerciasis in the United States due to O. lupi. The patient
was a 10-year-old girl that presented with a 2-3 month history
of an erythematous, mildly tender nodule on the right side of
her scalp clinically suspicious for a pilar cyst. An excision was
performed which revealed the presence of a parasitic worm that
was morphologically consistent with Onchocerca lupi. Molecular
studies confirmed the diagnosis. O. lupi is an uncommon and
relatively poorly understood parasitic infection that primarily
affects the eyes of dogs, and rarely cats. However, there appears
to be a recent emergence of zoonotic infections in humans with
five published case reports in the past two years. Of the five
previously reported cases of zoonotic O. lupi, four involved the
subconjunctiva while the other involved soft tissue of the anterior
extradural space at the level of C2-C4. This is the first report
of O. lupi in humans presenting as a subcutaneous nodule.
Clinicians should be aware of this recently reported entity in the
United States and its clinical and pathologic features.
Incidental finding of Scurvy in the setting of
Leukocytoclastic Vasculitis
Abha Soni, DO, MPH
Abha Soni, DO, MPH1; Charles Knapp III, MD1; Kristopher McKay, MD1
1
University of Alabama in Birmingham, Birmingham, Alabama, USA
We present the case of a 52-year-old male with past medical
history of cirrhosis secondary to hepatitis C and alcohol
abuse who developed diffuse erythematous palpable purpuric
lesions over his abdomen and bilateral extremities. On physical
exam, the process appeared to represent leukocytoclastic
vasculitis (LcV), thought to be related to hepatitis C. The punch
biopsy demonstrated fibrinoid necrosis of superficial vessels
with perivascular inflammatory infiltrate and leukocytoclasis,
consistent with LcV. However, on a second punch biopsy,
in addition to typical changes of LcV, there was evidence
of perifollicular and intrafollicular hemorrhage and follicular
hyperkeratosis with a corkscrew-like hair, raising the possibility
of vitamin C deficiency. The finding prompted evaluation of the
patient’s diet, which over the last five years consisted of one
chicken hamburger per day with the balance of caloric intake
from ethanol. His serum ascorbic acid level was <0.12 mg/
dL Scurvy is caused by a dietary deficiency in vitamin C, which
is necessary for collagen synthesis. The diagnosis is rare in
populations with access to an adequately varied diet and limited
to patients with nutritional imbalance or intake of a single food
low in vitamin C. These patients present with symptoms such as
fatigue, purpuric rash and anemia. Scurvy has been reported to
occasionally masquerade histopathologically as LcV. Since it is
a rare diagnosis, it is less likely to be appreciated as the cause of
a purpuric rash resembling cutaneous vasculitis. If left untreated,
this disease is invariably fatal. This case study emphasizes the
importance of recognizing scurvy, a rare but potentially fatal
disease, which can mimic cutaneous vasculitis. Although its
diagnosis is rare in the current era, it is important to recognize the
clinicopathologic features of this disease.
Fungal mimickers in drug induced systemic lupus
erythematosus and vasculitis
Paul Haun, MD
Paul Haun, MD1; Kaylan Weese, MD1; Nicole Fett, MD1; Kevin
White, MD1
1
Zoonotic onchocerca lupi infection presenting as a
subcutaneous nodule in a 10-year-old girl: report of
the second case in the United States and a review of
the literature
Ryan Berry, MD
Ryan Berry, MD1; Shelly Stepenaskie, MD2; Walter Dehority, MD,
MSc1; Marcos de Almeida, PhD3; Blaine Mathison, BA, M(ASCP)3;
Henry Bishop, MD1; Mark Eberhard, PhD3
University of New Mexico School of Medicine, Albuquerque, New
Mexico, USA
1
2
TriCore Reference Laboratories, Albuquerque, New Mexico, USA
3
Centers for Disease Control and Prevention, Atlanta, Georgia, USA57
Oregon Health and Science University, Portland, Oregon, USA
A 66 year old female presented with an acute eruption of
tender, eroded vesiculopapules on the face, oral ulcerations,
hemorrhagic erosions on the hard palate, and rapid subsequent
development of pink papules on the extremities and groin, with
tender red firm papules on the acral surfaces. Review of systems
was positive for fatigue, myalgias, and new onset delirium, as
well as history of fever approximately 24 hours after a vascular
procedure. Given her presentation there was concern for a
disseminated infectious process. Histopathology showed diffuse
neutrophilic infiltrate with subepidermal pustules, vasculitis,
and spore-like structures, some of which were PAS positive;
GMS was universally negative. Fluconazole was empirically
started. Subsequent tissue culture was negative. Three weeks
later, she was re-hospitalized for fatigue and worsening anemia.
A vasculitis workup revealed +ANA at 1:2560 in homogenous
and speckled patterns, +p-ANCA, +MPO, elevated CRP
and ESR, + Coombs test and + anti-histone antibodies. A
diagnosis of hydralazine-induced systemic lupus erythematosus
and ANCA-associated vasculitis was made. Hydralazine
was discontinued, her cutaneous findings resolved, and her
systemic symptoms continue to improve. The combination of
hydralazine induced SLE and hydralazine induced vasculitis is
very rare. This case highlights the varied autoimmune sequelae
induced by hydralazine. Additionally, this case highlights the
rare histologic phenomenon of abundant acelluar bodies in
neutrophilic dermatoses, which can closely simulate deep fungal
infection. Our patient’s findings further illustrate this possible
Onchocerciasis is an infection caused by the parasitic filarial
nematodes (roundworms) of the genus Onchocerca. Most
human infections are caused by O. volvulus (river blindness),
for which humans are the only known natural host. Zoonotic
onchocerciasis occurs when an animal Onchocerca species
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dermatopathologic pitfall and the need to recognize this rare
entity when an infectious workup has been exhausted.
body macrophages within the germinal centers, and several
cells with plasmacytoid cytomorphology. Results from a panel
of immunohistochemical stains supported a reactive process.
Therefore, a diagnosis of cutaneous lymphoid hyperplasia (CLH;
pseudolymphoma) following injection with botulinum toxin type
A was rendered. While prior case reports have documented
CLH localized to tattoo that was treated with laser and to a
vaccination site, CLH has not been reported as a reaction to
botulinum toxin type A injection, to our knowledge. This adverse
reaction is of particular clinical significance, because persistent,
cosmetically undesirable sequelae from elective procedures can
be troublesome to patients.
Aggressive HPV positive penile squamous cell
carcinoma with sarcomatoid and basaloid features
Kelly Park, MD, MSL
Kelly Park, MD, MSL1; David Eilers, MD2; Madhu Dahiya, MD2
1
Loyola University Medical Center, Maywood, Illinois, USA
2
Edward Hines Jr. VA Hospital, Hines, Illinois, USA
A 67-year-old Caucasian male with significant cardiac history
presented with a three-month history of a rapidly growing
penile mass. Physical examination was significant for a shiny
fungating 4 cm x 9 cm tumor with yellow crusting, fibrinous
debris, erosions, and ulcerations on the right base of the penile
shaft. There was no inguinal lymphadenopathy. Biopsy by
shave technique showed a poorly differentiated squamous cell
carcinoma with sarcomatoid and basaloid features, with a focally
ulcerated surface that demonstrated squamous cell carcinomain-situ, and an invasive dermal tumor. The spindled sarcomatoid
component was extremely pleomorphic and atypical. The
basaloid areas had basaloid cells, focal keratin pearls and
dyskeratosis, while in other areas, there was a markedly
pleomorphic spindle cell proliferation that was mitotically active
and associated with foci of dermal mucin. It strongly and diffusely
expressed Cytokeratin AE1/AE3 and p16. In the basaloid
areas, focal EMA and BerEP4 staining were positive. HPV
immunostaining was positive. After biopsy, the tumor was noted
to be recurring extremely quickly, and definitive management
with wide local excision was performed in the dermatology clinic.
Margins were clear on histology. Sarcomatoid squamous cell
carcinoma of the penis is a rarely reported entity with a poor
prognosis. This case is unique in that the tumor was both HPV
and p16 positive, features seen in basaloid carcinomas rather
than sarcomatoid carcinomas, and that it clinically behaved
like the typically aggressive sarcomatoid variant. Very rarely
sarcomatoid carcinoma originates in basaloid carcinoma and may
account for the presentation of this patient’s tumor.
Epstein-Barr virus-associated smooth muscle tumors
in an HIV patient; a spindle cell diagnostic pitfall
Ifeoma Nwadei, MD
Ifeoma Nwadei, MD1; Adam Vogt, MD1; Douglas Parker, MD,
D.D.S.1
1
Emory University School of Medicine, Atlanta, Georgia, USA
Of the HIV-associated non-AIDS defining neoplasms, EpsteinBarr Virus-associated smooth muscle tumors (EBV-SMTs)
are rare but distinct entities now found increasingly among
this cohort. With only 64 published cases since the 1990s,
predicting the biological behavior of this heterogenous group
of tumors continues to pose a clinical challenge. A 35-year-old
female with HIV-AIDS off antiretroviral therapy presented with
a 4-month history of intermittent fevers and tender nodules
on her left forearm and right pre-auricular area. Physical exam
demonstrated a 0.7 cm firm mobile subcutaneous nodule on her
left dorsal forearm and a secondary 0.5 cm pre-auricular lesion.
A punch biopsy of the left forearm mass demonstrated a wellcircumscribed, spindle cell proliferation with variable cellularity
and a focal fascicular growth pattern. The neoplastic cells
exhibited moderate nuclear pleomorphism with abundant mitotic
figures. The differential diagnosis included leiomyosarcoma and
dermatofibroma. Immunohistochemical stains were diffusely
positive for smooth muscle actin and focally positive for desmin
and negative for S-100, CD34, and HHV-8. Epstein-Barr
encoding region in-situ hybridization (EBER-ISH) was diffusely
positive in tumor cells. A diagnosis of an Epstein-Barr-associated
smooth muscle tumor was established. Biopsy of the right preauricular lesion demonstrated a cellular dermatofibroma. Our
case highlights the importance of distinguishing EBV-driven
smooth muscle neoplasms from their histologic mimics, including
leiomyosarcoma and dermatofibroma.
Cutaneous lymphoid hyperplasia (pseudolymphoma):
a rare adverse reaction following injection with
botulinum toxin type A for glabellar lines
Agnieszka Kubica, MD
Agnieszka Kubica, MD1; Julia Lehman, MD1
Mayo Clinic, Rochester, Minnesota, USA
1
We report a 56-year-old woman who presented with an
asymptomatic 1-mm shiny erythematous papule present for
one year on the central glabella. This papule arose shortly
following injection of the exact site with botulinum toxin type
A for treatment of glabellar lines. Given the persistence and
indeterminate nature of the lesion, punch biopsy was performed.
Histopathologic examination revealed the presence of multiple
superficial dermal lymphoid follicles, zonation and tingible-
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gene. We present a case of a 36-year-old female with a history of
Stage IV metastatic melanoma in the setting of multiple primary
cutaneous melanomas and numerous characteristic atypical
melanocytic proliferations of uncertain malignant potential. Many
of her previously excised melanocytic lesions (both nevi and
melanomas) were clinically benign-appearing, often presenting
as pink papules mimicking intradermal nevi. Histologically, these
demonstrated an unusual but characteristic spitzoid morphology
with marked pleomorphism, ranging from banal nevoid cells to
highly atypical cells, often seen in the setting of a background
nevus; all features suggestive of typical BAP1-syndromeassociated lesions. Immunohistochemical staining performed on
tissue from several of these unusual neoplasms confirmed loss
of BAP1 nuclear staining. In addition, these same lesions (as well
as her metastatic melanoma tissue) were found to be positive for
the BRAF V600E mutation, which is also commonly observed in
BAP1 syndrome-associated tumors. At the time of presentation,
several new banal appearing pink nevi were identified on exam,
which again histologically displayed the atypical spitzoid cells
and previously noted characteristic features of her prior lesions.
Interestingly, these sites, as well as several other nevi appear to
have clinically fully resolved in the setting of recent combination
treatment with dabrafenib and tremetinib. Although it is
impossible to discern which of the patient’s primary cutaneous
melanomas lead to her metastatic disease, she has fortunately
experienced a complete response to 12 cycles of this targeted
therapy.
Petechial patches in a 29-year-old: Autoimmune
hemolytic anemia in eosinophilic granulomatosis with
polyangitis (AKA Churg-Strauss syndrome)
Christopher Soon, MD
Christopher Soon, MD1; Jison Hong, MD1; Jozef Lazar, MD2;
Justin Ko, MD2; William Robinson, MD, PhD1; Jinah Kim, MD,
PhD1
1
Stanford University Medical Center, Stanford, California, USA
2
Stanford University Medical Center, Redwood City, California, USA
A 29-year-old woman with a history of asthma presented with a
3-week history of progressive fatigue, shortness of breath, nonproductive cough, upper gastrointestinal pain, vomiting, watery
diarrhea and lower extremity edema. On physical examination,
the patient had well-defined 1.5 cm urticarial plaques present
on her bilateral thighs and a 4 cm non-blanching agminated
petechial patch on her left thigh. A complete blood count
was notable for a leukocytosis (31.9 K/µL) with a prominent
eosinophilia (67%, 21.3 K/µL). Two biopsies of the left thigh were
performed that demonstrated superficial and deep perivascular
eosinophilic small vessel necrotizing vasculitis. There was
marked deposition of eosinophil granules within the vessel walls.
Interestingly, extravascular, palisaded necrotizing granulomas
were not identified in either biopsy, and the lesions lacked
significant histiocytic infiltrates. Eosinophilic granulomatosis
with polyangitis (formerly known as Churg-Strauss syndrome)
is a rare systemic necrotizing vasculitis predominantly affecting
small vessels and characterized by a constellation of asthma,
peripheral eosinophilia, and tissue infiltration by eosinophils.
The histopathologic differential diagnosis includes parasitic
infestation, eosinophilic cellulitis, and urticarial vasculitis. In this
case, the patient developed a warm IgM autoimmune hemolytic
anemia (AIHA), which is a rare clinical finding that may be
mediated by elevated IL-4 and IL-5 production. Our patient was
treated with systemic glucocorticoids and IV cyclophosphamide
for the eosinophilic granulomatosis with polyangitis and
plasmapheresis, eculizumab, and rituximab for the AIHA with
significant improvement of her symptoms. We hope to raise
awareness of the clinical and cutaneous histopathologic features
of eosinophilic granulomatosis with polyangiitis and its rare
association with autoimmune-mediated hemolytic anemia.
INI-1 negative dermal neuromas in a child with multiple
occurrences of epithelioid sarcoma
William Tidwell, MD
William Tidwell, MD1; Paul Googe, MD2; Edward Primka, MD3;
Herbert Schwartz, MD4; Andrew Rosenberg, MD5
1
University of Tennessee, Knoxville, Tennessee, USA
2
Knoxville Dermatopathology Laboratory, Knoxville, Tennessee, USA
3
Dermatology Associates of Knoxville, Knoxville, Tennessee, USA
4
Vanderbilt University, Nashville, Tennessee, USA
5
University of Miami, Miami, Florida, USA
Epithelioid sarcoma is rare malignancy. Genetically, it has
alterations of 22q11-12 with loss of expression of integrase
interactor 1 (INI-1); patients with epithelioid sarcoma are not
prone to develop other types of neoplasms. Our patient who had
Turner’s syndrome developed an epithelioid sarcoma of the right
fourth finger at the age of 8 years. The finger was amputated
with negative margins. Six years later, an epithelioid sarcoma
presented on the right third finger along with multiple dermal
neuromas isolated to the posterior aspects of both hands. The
dermal neuromas were histologically similar to mucocutaneous
neuromas of MEN2b and PTEN syndromes, however, the
patient does not have other manifestations of these syndromes.
Immunohistochemistry confirmed loss of expression of INI-1 in
both the epithelioid sarcoma and the neuromas. While loss of INI1 expression is a feature of epithelioid sarcoma, this phenomenon
has not been reported in dermal neuromas. The loss of INI-1
The BAP1 cancer syndrome: a case of metastatic
melanoma and characteristic atypical melanocytic
lesions
Katherine Roy, MD
Katherine Roy, MD1; Daniel Zedek, MD1; Nancy Thomas, MD, PhD1
University of North Carolina Hospitals, Chapel Hill, North Carolina, USA
1
The recently described BAP1 Cancer Syndrome is characterized
by development of uveal and cutaneous melanomas, specific
characteristic atypical melanocytic lesions with spitzoid
morphology, and malignant mesothelioma. This inherited
syndrome is believed to result from a loss of function mutation
in the BRCA1-Associated Protein 1 (BAP1) tumor suppressor
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which occurs in sporadic schwannoma, schwanommatosis, and
epithelioid sarcoma is likely related to SMARCB1 gene mutation
on 22q11-12. This patient with multiple epithelioid sarcomas and
dermal neuromas with loss of expression for INI-1 is a unique
case and suggests a tumor syndrome related to SMARCB1 gene
mutation.
Myxoinflammatory fibroblastic sarcoma/hemosiderotic
fibrolipomatous tumor: a rare translocation-associated
hybrid tumor with marked spatial variation
Andrew Rand, MD
Andrew Rand, MD1; Rex Bentley, MD1; Brian Brigman, MD1;
William Eward, MD, DVM1; Christina Cramer, MD1; Nicole Larrier,
MD, MS1; Diana Cardona, MD1
Infantile GM1 gangliosidosis: clinicopathologic and
ultrastructural findings in the skin
1
Myxoinflammatory fibroblastic sarcoma (MIFS) and hemosiderotic
fibrolipomatous tumor (HFLT) are typically morphologically
distinct lesions of the distal extremities; however, a common
origin is suggested by recent studies showing a consistent t(1;10)
(p22;q24) translocation in both entities. We present the case
of a 46-year-old man who first noticed pain and swelling of his
left medial ankle while training for a half-marathon. During the
subsequent 3 years, he saw several healthcare professionals
for his symptoms. A dermatologist then performed a shave
biopsy of a vesicular lesion on his left ankle. The pathology
was interpreted as a myxoid neoplasm, most consistent with a
myxofibrosarcoma. One month later, the patient was evaluated
at our institution and physical examination showed an 18 cm
expanse of bluish discoloration and multiple vesicles over the
left medial foot, ankle, and lower leg. There was very mild
swelling but no discrete mass identified by palpation or MRI.
A left below-knee amputation revealed an ill-defined 31 x 20
x 1.3 cm infiltrative tumor involving the dermis and superficial
subcutaneous tissue. While small superficial areas had a myxoid
appearance and cytologic atypia resembling the shave biopsy,
the bulk of the mass was composed of mature adipose tissue
traversed by relatively bland, CD34+ spindle cells, extensive
hemosiderin deposition, and patchy chronic inflammation. Foci
with large atypical, Reed-Sternberg-like cells were also identified.
The morphology was diagnostic of a hybrid MIFS/HFLT. No
radiation therapy or chemotherapy was performed. One year
later, the patient is ambulating with a prosthesis and has no
evidence of recurrent or metastatic disease. We add this case
to the small collection of tumors in the literature demonstrating
hybrid features of MIFS and HFLT. We emphasize the marked
spatial variation of this translocation-associated tumor, and thus
the importance of ample tissue sampling to ensure accurate
diagnosis.
Andrea Primiani, MD
Andrea Primiani, MD1; Daniela Kroshinsky, MD, MPH1; Rosalynn
Nazarian, MD1
1
Duke University Medical Center, Durham, North Carolina, USA
Massachusetts General Hospital, Boston, Massachusetts, USA
Lysosomal storage diseases are rare systemic disorders due to
specific enzyme deficiencies resulting in lysosomal accumulation
of undegraded metabolites. We report a case of a 9-month-old
female who presented with a left neck “growth” that became
larger and redder over four months. Exam revealed a 1.0 cm
erythematous, firm nodule on her left neck; the clinical differential
diagnosis included pilomatricoma and Spitz nevus. Skin biopsy
showed a dense dermal infiltrate of vacuolated histiocytes
without Touton giant cells. Immunostains revealed positive
staining for CD163 and faint staining for S100 within the cells of
interest, which were negative for HMB45. No microorganisms or
intracytoplasmic granules were identified on Giemsa and PAS/D
stains, respectively. Ultrastructural examination performed to help
differentiate a histiocytosis, such as xanthogranuloma, revealed
numerous intracytoplasmic vacuoles within many cell types,
including histiocytes, endothelial cells, fibroblasts, melanocytes,
and keratinocytes, consistent with cutaneous involvement by
GM1 gangliosidosis. Clinical manifestations in gangliosidoses
result from the massive storage of GM1 ganglioside and related
glycoconjugates in different tissues. Signs and symptoms
of central nervous system involvement are typically present;
however, involvement of other organ systems, including the
skin, is variable and often manifests as dermal melanocytosis or
angiokeratomas. Of note, prior biopsy of a 5.0 cm blue-brown
patch on this patient’s buttock revealed dermal melanocytosis
and molecular analysis revealed a heterozygous mutation in the
GLB1 gene resulting in beta-galactosidase enzyme deficiency.
We describe a unique case of a patient with GM1 gangliosidosis
to highlight the clinicopathologic and ultrastructural features in
the skin. Awareness of these skin manifestations is important
as it can alert the pathologist and clinician to the possibility of
inherited lysosomal disease.
Dermatofibrosarcoma protuberans in a patient with
PTEN hamartoma tumor syndrome
Emily Smith, MD
Emily Smith, MD1; Douglas Fullen, MD1; May Chan, MD1
1
University of Michigan Health System, Ann Arbor, Michigan, USA
Dermatofibrosarcoma protuberans (DFSP) is a rare soft tissue
tumor characterized by a dermal spindle cell proliferation with
entrapment of subcutaneous fat, positive CD34 immunostaining,
and a COL1A1-PDGFB gene fusion. We report a 21-year-old
male with PTEN hamartoma tumor syndrome (PHTS) manifested
as multiple sclerotic fibromas, mucosal papillomas, punctate
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keratoses, multinodular goiter, colonic ganglioneuromas and
ependymoma who presented with an enlarging, tender, firm,
pink nodule on the right parietal scalp. Excision revealed a
spindle cell tumor in the deep dermis and subcutis with a
storiform growth pattern and entrapment of fat in a honeycomb
fashion. The spindle cells were positive for CD34 and negative
for S-100 and factor XIIIa immunostains. A diagnosis of DFSP
was made. Due to positive margins, the patient subsequently
underwent wide local re-excision with 2-cm margins and delayed
reconstruction via full thickness skin grafting. No recurrence
of the DFSP has been noted to date. To our knowledge, this
is the first report of DFSP in a patient with PHTS. PHTS is
associated with an increased risk of developing breast, thyroid,
and endometrial malignancies, however its association with
DFSP has not been documented. While the exact molecular
relationship is unknown, failure to suppress the platelet-derived
growth factor (PDGF) pathway by the mutant PTEN protein may
have potentially contributed to the tumorigenesis of DFSP in this
patient.
A novel ETV3-NCOA2 fusion in a case of indeterminate
cell histiocytosis
Ryanne Brown, MD, MBA
Ryanne Brown, MD, MBA1; Bernice Kwong, MD1; Kerri Rieger,
MD, PhD1
1
Extensive cutaneous involvement of an extranodal
NK/T-cell lymphoma, nasal type with hemophagocytic
lymphohistiocytosis
Conor Dolehide, MD
Conor Dolehide, MD1; Vijaya Reddy, MD1
1
Stanford University Medical Center, Stanford, California, USA
Indeterminate cell histiocytosis (ICH) is a rare and controversial
disorder characterized by a non-epidermotropic histiocytic
infiltrate with an immunophenotype that overlaps with Langerhans
cells (LCs) and non-Langerhans cells of monocyte-macrophagedendritic cell lineage. The gold standard for distinguishing ICH
from Langerhans cell histiocytosis (LCH) is demonstration of
the absence of Birbeck granules on electron microscopy (EM).
Langerin immunohistochemistry, which is positive in LCH, often
serves as a diagnostic proxy for EM. It is unclear whether ICH
is distinct from LCH, or rather, represents a different stage in
histiocytic development along a spectrum that includes both
diseases. One prevailing explanation for how indeterminate cells
(ICs) and LCs relate to each other is that ICs are LCs that have
lost their Birbeck granules, arresting in the dermis before they
can travel to the paracortical zone of lymph nodes to serve an
antigen presenting role to naïve T cells. Another theory is that
ICs are early LCs that have not yet developed Birbeck granules.
We examine a case of a 62 year old female who presented with
an over 30 year history of dome-shaped reddish brown papules
and nodules involving her face, chest, back, and extremities.
Biopsy demonstrated a dermal-based monomorphous infiltrate
of mononuclear histiocytes, positive for CD1a and CD68, and
negative for langerin. S100 was positive in 5% of the infiltrate.
Birbeck granules were absent on EM, confirming the diagnosis of
ICH. Genome sequencing identified an alteration of the NCOA2
gene resulting from an ETV3-NCOA2 fusion. NCOA2 encodes
the protein TIF2, a transcriptional coactivator of steroid and
nuclear receptors. Fusion of NCOA2 with other genes has been
reported in angiofibroma of soft tissue, rhabdomyosarcoma,
mesenchymal chondrosarcoma, and acute leukemia, although
a common pathway for oncogenesis has not been identified.
Further investigation is necessary to determinate the diagnostic
and therapeutic implications of this novel ETV3-NCOA2 fusion in
ICH.
Rush University, Oak Lawn, Illinois, USA
Extranodal natural killer (NK)/T-cell lymphoma, nasal type, is a
rare lymphoma. It is less common in North America than in Asia,
South America, or Central America. Ebstein-Barr virus is highly
associated with the disease. It is also commonly associated with
hemophagocytic lymphohistiocytosis (HLH) or hemophagocytic
syndrome, which follows an aggressive clinical course. The
skin is the second most common site of involvement after the
nasopharynx. We present a 30-year-old Caucasian male with
widespread violaceous plaques and nodules. Many of the lesions
were centrally necrotic. More than ten percent of his body surface
area was involved. Biopsies demonstrated a superficial and deep
infiltrate of highly atypical lymphoid cells. Angiocentricity was a
prominent feature. Immunohistochemical studies were positive
for CD3, CD10, and CD56. The cells were negative for CD20
and CD30. In situ hybridization for EBV-encoded RNA (EBER)
was positive. EBV viral load was greater than 250,000 copies.
Peripheral blood flow cytometry showed that NK cells comprised
the majority of the lymphocytes. Ferritin was significantly
elevated (24,855 ng/mL), which is specific for HLH. He also had
fevers, pancytopenia, low fibrinogen, elevated triglycerides,
and splenomegaly. Thus he met criteria for a diagnosis of HLH.
Despite treatment, the patient passed away due to septic shock
and extensive tumor burden. This case illustrates a Caucasian
male in the United States who presented with extensive
cutaneous involvement of an extranodal NK/T-cell lymphoma,
nasal type as well as HLH.
Granulomatous arteritis: A rare post-varicella zoster
virus manifestation
Brianne Daniels, DO
Brianne Daniels, DO1; Timothy McCalmont, MD1
1
UCSF, San Francisco, California, USA
Varicella zoster virus (VZV) is a neurotropic herpesvirus. When
reactivated, the virus classically manifests in the skin as a
painful dermatomally distributed vesicular rash. Post-zoster
reactions can present in other organs and tissues in the central
and peripheral nervous system, the respiratory tract as well
as in large vessels. In some cases, the virus manifests as a
vasculitis in which the virus travels down nerve fibers to large
vessels, producing an arteritis. Herein, we report a rare post-
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mother’s lesion showed protein expression indicative of malignant
melanoma, whereas the lesions in the newborn showed features
indicative of benign nevi. This case demonstrates the usefulness
of genotyping and mass spectrometry as adjuncts to diagnosis in
this scenario.
zoster reaction presenting as a granulomatous arteritis in an
82-year-old immunocompetent woman. The patient presented
with a one month history of a progressively growing plaque (up
to 4-5 inches) on the right temple and forehead that did not
cross the midline. She had no history of underlying systemic
granulomatous disease, such as sarcoidosis, systemic vasculitis
or lymphoma. The differential diagnosis based on routinelystained sections included temporal arteritis, granulomatous
post-zoster reaction, granulomatous manifestation of a systemic
disease, or so-called “atypical necrobiosis lipoidica of the face”.
Given the clinical suspicion for a post-zoster reaction, PCR
analysis was done and proved to be positive, with documentation
of DNA sequences specific for varicella zoster virus and a lack of
herpes simplex viral DNA. Recognition of this rare dermatologic
post-zoster reaction presenting as a granulomatous arteritis
is important for clinical management as the virus is potentially
treatable with intravenous acyclovir. Excluding this entity as a
cause of granulomatous arteritis is also important since treatment
of other causes in the differential diagnosis (e.g. steroids
for temporal arteritis) could worsen the patient’s condition.
Dermatopathologists should have a high index of suspicion for
the possibility of underlying herpesvirus infection in the context of
granulomatous vasculitis.
Atypical chromhidrosis with elevated cutaneous iron
excretion: report of a case and literature review
Ryan Romano, DO
Ryan Romano, DO1; Rebecca Jones, MD2; David Garby, MS1;
David Murray, MD/PhD1; Jean Henneberry, MD3
Atypical chromhidrosis is a rare benign disorder of unknown
etiology characterized by the excretion of pigmented sweat. It
may involve apocrine or eccrine glands and its presentation is
widely variable. We present a 55 year old woman who developed
orange sweat following a traumatic liver injury. Her medications
included levothyroxine, citalopram, amitriptyline, vitamin D,
and calcium. Immediately after the injury, her ferritin levels
were markedly elevated. Iron studies were normal. Within 4
months, she developed orange discoloration of her hair, nails
and sweat, the latter was most pronounced in the upper chest,
back, hands and feet. Dietary history was non-contributory.
Physical examination revealed a pink-orange hue of her hair,
skin, and nails. Orange discoloration of clothing and linens was
noted. Several skin biopsies were performed from the back, one
showing classic features of lichen planus; and the two remaining
biopsies showed mild eccrine gland dilatation. A histochemical
stain for iron was negative. Apocrine glands were not identified.
Serum ferritin levels declined but remained elevated. No other
clinical laboratory abnormalities were identified. Ultraviolet/
visible spectrophotometry performed on the sweat exhibited a
single peak with maximum absorbance at 352 nm. Inductively
coupled plasma mass spectrometry of the sweat revealed
markedly elevated iron levels (3872.4 ppb; 3.87 mg/L). Infrared
spectrometry, high performance liquid chromatography and
gas chromatography/mass spectrometry were unrevealing.
Chromhidrosis is a rare but distressing condition. Ours is the first
report to include a detailed chemical analysis of chromogenic
sweat and suggests that clinicopathologic correlation may be
enhanced by such analyses.
Ahmed Alomari, MD1; Earl Glusac, MD1; Jennifer Choi, MD1;
Pei Hui, MD, PhD1; Erin Seeley, PhD2; Richard Caprioli, PhD2;
Rossitza Lazova, MD1
Yale University, New Haven, Connecticut, USA
Vanderbilt University, Nashville, Tennessee, USA
Baystate Medical Center, Brattleboro, Vermont, USA
Baystate Medical Center/ Tufts Medical Center, Springfield,
Massachusetts, USA
Ahmed Alomari, MD
2
Mayo Clinic, Rochester, Minnesota, USA
2
3
Congenital nevi versus metastatic melanoma in a
newborn to a mother with malignant melanoma –
diagnosis supported by sex chromosome analysis and
imaging mass spectrometry
1
1
A 37-year-old pregnant woman presented with a 2 cm irregular
brown nodule of her left upper arm during the 35th week of
gestation. A biopsy from the lesion showed a 2.2 mm thick
malignant melanoma with intravascular invasion, 25 mitosis/
mm2 and no ulceration. Following induction of labor during
39th week of gestation, the patient underwent wide local
excision with sentinel lymph node (LN) biopsy. This showed no
residual melanoma and no LN metastasis. The newborn boy
had multiple pigmented lesions on the trunk, some of which
were large and with irregular borders. Two were biopsied and
histologic examination showed a dense dermal proliferation of
medium sized melanocytes with, multiple mitotic figures and no
maturation with their descent into the dermis, raising suspicion
of transplacental metastases. Examination of the placenta failed
to show metastatic lesions. Multiplex PCR based genotyping,
including testing for amelogenin locus for sex chromosome
determination, demonstrated the presence of Y chromosome
material in the melanocytes of the newborn’s lesions excluding
maternal origin. A diagnosis of congenital nevi was rendered.
Subsequently, imaging mass spectrometric analysis of the
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An exceptional case of X-linked protoporphyria in a
female patient
Michelle Gatica-Torres, MD
Michelle Gatica-Torres, MD1; Humberto Paredes Martínez
de Arredondo, MD1; Amparo Hernández-Salazar, MD1; Ma.
Guadalupe Ortiz-Pedroza, MD1; Marcela Saeb-Lima, MD1
Instituto Nacional de Ciencias Médicas y Nutrición Salvador
Zubirán, Mexico City, Mexico
1
A 20-year-old woman presented with chronic liver failure and
a history of cutaneous photosensitivity acutely after sunlight
exposure experienced since early childhood. Vertical grooving
of the lips and waxy scars were noted on the nose, chin and
cheeks. The dorsal aspect of both arms and hands showed
lichenification and hyperkeratosis. Photoonycholysis was present
on the first, second and third digit of both hands. The skin
biopsy revealed thickened blood vessel walls, some with luminal
narrowing secondary to a deposition of a strongly eosinophilic
PAS positive hyaline material, which could also be observed
in the upper dermis. Free erythrocyte protoporphyrin level was
increased as well as the proportion of zinc protoporphyrin. The
diagnosis of X-linked protoporphyria (XLP) was established.
XLP, an uncommon variant of erythropoietic protoporphyria
(EPP), is a non-blistering photosensitivity disorder caused by
a gain-of-function mutation of the delta-aminolevulinic acid
synthase (ALAS2). This disorder affects mainly males but if
lyonization affecting the normal X chromosome occurs, females
are exceptionally affected. Histologic changes, which are similar
to the changes in other cutaneous porphyrias, result from the
deposition of protoporphyrin around blood vessels and the
dermo-epidermal junction. Less than 5% of patients with EPP
develop liver failure and the prognosis is determined by the
hepatic involvement. In severe cases sequential hepatic and bone
marrow transplantation are advised.
14
Abstract Book Oral Presentations
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ASDP
annual meeting
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The American Society of Dermatopathology
Oral Abstract Session 2
1:30 p.m. – 1:40 p.m.
Expression of K-Type Human Endogenous Retroviral Element in
Melanocytic Lesions Correlates with Anatomic Site
1:40 p.m. – 1:50 p.m.
Differential Expression of GATA3 Expression in Cutaneous Squamous Khaled Hassan, MD
Cell Carcinoma Progression in Sun-Protected and Sun-Exposed Sites
1:50 p.m. – 2:00 p.m.
P16 Immunohistochemical Staining May Be a Useful Diagnostic
Adjunct in High-Risk HPV Positive Cutaneous Lesions
Erick Jacobson-Dunlop, MD
2:00 p.m. – 2:10 p.m.
Therapy-related Leukemia Cutis is Associated with Poorer Clinical
Outcome.
Vishwas Parekh, MD
2:10 p.m. – 2:20 p.m.
Secondary Syphilis in HIV Positive Individuals: Correlation with
Histologic Findings, CD4 Counts and Amount of Treponemes on
Histologic Sections
Gabriela Rosa, MD
2:20 p.m. – 2:30 p.m.
Atypical Melanocytic Proliferations Associated with Therapeutic
BRAF Inhibition
Mark Mochel, MD
2:30 p.m. – 2:40 p.m.
The Epidemic of Cutaneous Leishmaniasis among Syrian Refugees
in Lebanon
Ibrahim Khalifeh, MD
2:40 p.m. – 2:50 p.m.
Use of in-vivo Reflectance Confocal Microscopy for Evaluation
of Mycosis Fungoides and Sézary Syndrome: Histopathology
Correlation and Feasibility of Use Study.
Silvia Mancebo, BS
2:50 p.m. – 3:00 p.m.
Dermatopathologic Findings in Severe Combined Immunodeficiency
(SCID): A Study of 53 Patients with a Subset Received BCG Vaccine.
Tariq Al-Zaid, MD
15
Liliana Rincon, MD
Abstract Book Oral Presentations
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annual meeting
st
The American Society of Dermatopathology
Oral Abstract Session 2
disease (BP/BD) of the perineum (n=15) were evaluated for
GATA3 protein expression using immunohistochemistry. We
found that GATA3 expression is progressively lost in sun-exposed
skin as squamous neoplasia progresses from pre-cancerous
AKs, conventional SCCIS-A, and ultimately to invasive SCCs
in all differentiation stages. In contrast, GATA3 expression was
retained in transformed keratinocytes at sun-protected sites as
seen in all cases of SCCIS-B and BP/BD. Together, our findings
show that GATA3 expression is decreased during keratinocyte
transformation in sun-damaged but not sun-protected skin and
thus reflects on divergent oncogenic pathways utilized by the
distinct histologic phenotypes of squamous cell carcinoma.
Expression Of K-type human endogenous retroviral
element In melanocytic lesions correlates with
anatomic site
Liliana Rincon, M.D
Liliana Rincon, M.D1; Elizabeth McQuitty, M.D2; Michael P.
Sedrak, M.D2; Jianli Dong, MD, PhD2
1
University of Texas Medical Branch, League City, Texas, USA
2
University of Texas Medical Branch, Galveston, Texas, USA
The K-type human endogenous retroviral element (HERV-K) has
been implicated in melanomagenesis. Expression of HERV-K
GAG and ENV proteins correlates with activation of MEK-ERK
pathway, and inhibition of MEK can block HERV-K activation. A
recent report suggests that UV radiation can activate HERV-K.
We hypothesize that the pattern of HERV-K expression in
melanocytic lesions mimics that observed for BRAF mutation,
a main driver of MEK-ERK activation in melanoma cells. We
examined the anatomic site, histologic subtype, and HERV-K
expression of 26 melanomas and 34 benign nevi. HERV-K GAG
and ENV proteins were highly expressed in lesions located in
melanomas of the upper extremities (40%) and in benign nevi
of the back (60%), with lower expression in other sites including
head and neck, chest, abdomen and extremities (0-20 %). This
pattern is similar with that of BRAF mutation status. Superficial
spreading melanomas had the highest expression of HERV-K
GAG and ENV proteins (50%) of histologic subtypes. Our study
warrants further investigation of the regulatory and functional
interactions between BRAF mutation, HERV-K activation,
anatomic location, and UV exposure pattern in the development
of melanoma.
P16 immunohistochemical staining may be a useful
diagnostic adjunct in high-risk HPV positive cutaneous
lesions
Erick Jacobson-Dunlop, MD
Erick Jacobson-Dunlop, MD1; Dirk Elston, MD1
1
Ackerman Academy of Dermatopathology, New York, New York, USA
Background: P16 immunohistochemical (P16 IHC) staining is a
useful diagnostic adjunct in squamous dysplasia of the uterine
cervix. Whereas basilar staining is seen in low-grade cervical
intraepithelial neoplasia (CIN1), stronger more diffuse staining
is seen in higher-grade lesions (CIN2-3). The role of P16 IHC in
cutaneous genital lesions, however, is not well studied. Because
verruca vuglaris (VV), condyloma accuminatum (CA), Bowenoid
papulosis (BP) and Bowen’s disease (BD) can all harbor high-risk
HPV, demonstrating that P16 staining correlates histopathologic
diagnosis (basilar staining in VV and CA, and more diffuse
staining in BP and BD) could help guide diagnosis in equivocal,
high-risk positive cases. Materials and Methods: Sixteen archived
cases of high-risk HPV positive lesions were identified (VV (2), CA
(3), BP (9) and BD (2)). HPV high and low risk in-situ hybridization
and P16 IHC were performed on all cases. All material, including
hematoxylin and eosin stained slides, HPV high and low risk
in-situ hybridization, and P16 IHC were analyzed. Results: P16
staining correlated with histopathologic diagnosis irrespective of
high-risk HPV positivity in 15 of 16 cases (94%). All cases of BD
and BP showed staining that involved at least the bottom 2/3 of
epidermal keratinocytes and most showed areas of full-thickness
epidermal staining. By contrast, only one case of CA showed any
staining at all above the basal layer and none of the VV cases
showed staining above the basal layer. Conclusion: In cutaneous
genital squamous proliferations positive for high-risk HPV, P16
shows a strong trend toward correlating with histopathologic
diagnosis.
Differential expression of GATA3 expression in
cutaneous squamous cell carcinoma progression in
sun-protected and sun-exposed sites
Khaled Hassan, MD
Khaled Hassan, MD1; Andy Hsi, MD1; Ilana Rosman, MD1; Valerie
Viele, BS1; Sena Lee, MD, PhD1; Andras Schaffer, MD, PhD1
Washington University School of Medicine, St Louis, Missouri, USA
1
The GATA3 transcription factor, a master gene regulator in
lymphoid tissues and epithelia, is expressed in human epidermis
and follicular structures. Within the epidermis, it is differentially
expressed in the different sub-strata, suggesting that levels of
GATA3 are closely tied to normal keratinocyte differentiation.
GATA3 is also a target of the Notch pathway, a prominent
signaling pathway that is down-regulated in squamous cell
carcinoma pathogenesis. GATA3 has not been extensively
studied in cutaneous neoplasias. Here, we investigated the
expression of GATA3 in premalignant and invasive cutaneous
squamous cell carcinomas from sun exposed and sunprotected skin. Actinic keratoses (AKs) (n=20), in-situ squamous
cell carcinomas with bowenoid features (SCCIS-Bs) (n=17),
conventional in-situ squamous cell carcinomas with actinic
features (SCCIS-As) (n=10), well-, moderately- and poorlydifferentiated SCCs (n=36), and bowenoid papulosis or Bowen’s
16
Abstract Book Oral Presentations
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annual meeting
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The American Society of Dermatopathology
Oral Abstract Session 2
HIV and syphilis, with histologic findings and with the number of
treponemes on skin biopsies by immunohistochemistry (IHC). A
search of one institution over 21 years yielded 13 patients with a
diagnosis of secondary syphilis on skin biopsy and either positive
syphilis serology or syphilis IHC. Ten patients had evidence of
HIV infection, either by HIV viral load, ELISA or Western blot,
within 30 days of the skin biopsy. CD4 T cell counts were
available in all HIV positive patients within 17 days of the biopsy.
Two patients had negative HIV testing by ELISA the same date
as their skin biopsy and 1 patient was not tested for HIV. A silver
stain and syphilis immunohistochemistry (IHC) was performed
in all cases. The sensitivity of IHC to detect treponemes was
64% and of silver stain was 7% (p-value 0.002). The number
of treponemes on the biopsies was estimated by IHC. There
was a slight negative correlation, with increased treponemes
as CD4 counts decreased (Pearson’s correlation coefficient
-0.47). All cases were assessed for various histologic features,
including spongiosis, ice-pick epithelial hyperplasia, degree
of inflammation and ulceration. No reliable histologic pattern
was associated with varying CD4 counts. Although the study
is small, it may support the role of decreased cellular immunity
in co-infection with HIV and syphilis, as more treponemes were
visible in patients with lower CD4 counts. Also, our study further
emphasizes the importance of testing syphilis patients for HIV, as
most patients with syphilis on skin biopsy had concomitant HIV
infection.
Therapy-related leukemia cutis is associated with
poorer clinical outcome
Vishwas Parekh, MD
Vishwas Parekh, MD1; Taylor Deal, MD1; Kristopher McKay, MD1;
Deniz Peker, MD1
1
University of Alabama at Birmingham, Birmingham, Alabama, USA
Leukemia cutis (LC) is an uncommon form of myeloid neoplasm
characterized by leukemic cells infiltrating the skin. While
considered highly aggressive (12-14 months median survival),
the predisposing conditions, prognostic factors and optimal
treatment modalities for this entity have been poorly defined
due to the rarity of this disease. However, rarer still are the LC
cases that develop as a complication of prior cytotoxic therapy
and are only anecdotally reported. We investigated LC cases
with or without their inception in prior cytotoxic therapy and
compared the clinical outcomes. A retrospective review of cases
between 2003 and 2013 was carried out. Cases of LC with or
without concurrent leukemia were included in the study. Based
on the presence or absence of prior history of cytotoxic therapy
for solid or hematologic malignancies, patients were divided
into two cohorts. Cohort 1 consisted of 31 LC cases without
a history of preceding treatment (LC). Cohort 2 consisted of 6
cases with a preceding treatment history (t-LC). Cohort 1 (LC)
patients had a median age of 56 years (range: 22-92 years) at the
time of diagnosis and male to female ratio of 2.4. Cohort 2 (t-LC)
patients had a median age of 44.5 years (range: 37- 81 years)
at the time of diagnosis and male to female ratio of 0.2. Among
the six t-LC cases, the most common prior malignancy was
breast carcinoma (n=4), followed by follicular lymphoma (n=1)
and Hodgkin’s lymphoma (n=1). Five patients had previously
received chemotherapy with or without radiation and one patient
had received only radiotherapy. The survival analysis revealed a
significantly shorter overall survival (OS) in the Cohort 2 patients
(median survival of 6.5 months) compared to Cohort 1 (median
survival of 16 months), p value: 0.050. The results of our study
suggest that t-LC is a distinct entity with a significantly poorer
prognosis compared to LC. Our study outcome also suggests
a need for larger-scale collaborative studies to investigate
prognostication and optimal treatment for this highly aggressive
disease.
Atypical melanocytic proliferations associated with
therapeutic BRAF inhibition: a clinicopathologic study
of 20 lesions from 10 patients
Mark Mochel, MD
Mark Mochel, MD1; Adriano Piris, MD1; Mai Hoang, MD1
1
Background: Selective BRAF inhibition has become a common
therapeutic option for patients with metastatic melanoma with
detectable BRAFV600E mutations. Although atypical nevi and
primary melanomas arising in the setting of this therapy have
been reported, there are limited histopathologic descriptions
of these lesions. Methods: From 5/2010 to 3/2014, 20 new or
changing melanocytic lesions were biopsied from 10 patients
undergoing therapeutic BRAF inhibition. Histologic slides were
reviewed. Results: Patients included 4 males and 6 females with
a median age of 53 years (range: 25-73 years). The indications
for BRAF inhibition included metastatic melanoma (7), metastatic
colonic adenocarcinoma (2), and metastatic papillary thyroid
carcinoma (1). The average duration of BRAF inhibition prior
to excision of clinically concerning nevi was 8 months (range:
2mo to 2yr7mo). Three lesions developed following therapy, 9
lesions were pre-existing and changed clinically during therapy,
and for 8 lesions the relationship to therapy was unknown. While
18 lesions were determined to be atypical nevi, two cases were
diagnosed as malignant melanoma (MM). Among the atypical
nevi, the locations included the trunk (5), head and neck (4), legs
(7), and arms (2). Histologic features frequently associated with
these nevi included pigmented junctional melanocytes (83%),
Secondary syphilis in HIV positive individuals:
correlation with histologic findings, CD4 counts and
amount of treponemes on histologic sections
Gabriela Rosa, MD
Gabriela Rosa, MD1; Gary Procop, MD1; Melissa Piliang, MD1
1
Massachusetts General Hospital, Boston, Massachusetts, USA
Cleveland Clinic, Cleveland, Ohio, USA
Although syphilis is rare, infection rates are much higher in HIVinfected individuals than the general population. A proposed
explanation is impaired cellular immunity with HIV infection,
in particular decreased CD4 positive T cells. Lues maligna is
an ulcerative type of secondary syphilis, associated with HIV
infection. We correlated CD4 counts in patients co-infected with
17
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The American Society of Dermatopathology
Oral Abstract Session 2
hyperpigmented keratinocytes (83%), pigment within stratum
corneum (59%), pagetoid spread (44%), follicular extension
(77%), features of congenital onset (59%), dermal pigment
incontinence (100%), and a pattern of abrupt dermal maturation
from plump epithelioid cells to type-B melanocytes (44%). The
two MMs were diagnosed on the chest and cheek in a single
patient. Conclusion: A majority of the atypical nevi excised
during anti-BRAF therapy showed prominently pigmented
junctional melanocytes, hyperpigmented epidermal keratinocytes,
pigment within stratum corneum, and a dermal component
often exhibiting abrupt maturation. Additional study is needed
to further delineate these lesions to avoid the misdiagnosis of
malignancy which may impact therapeutic decisions.
Use of in-vivo reflectance confocal microscopy for
evaluation of mycosis fungoides and sezary syndrome:
Histopathology correlation and feasibility of use study
Silvia Mancebo, B.S.
Silvia Mancebo, B.S.1; Miguel Cordova, MD1; Sarah Jawed, MD1;
Anna Skripnik, RN1; Patricia Myskowski, MD1; Eileen Flores,
MS1; Klaus Busam, MD1; Milind Rajadhyaksha, PhD1; Christiane
Querfeld, MD, PhD1
Memorial Sloan Kettering Cancer Center, New York, New York, USA
1
Mycosis fungoides/Sezary Syndrome (MF/SS) often requires
multiple skin biopsies to establish a definitive diagnosis. Invivo reflectance confocal microscopy (RCM) is a non-invasive
imaging modality that provides high-resolution cellular detail of
the skin. Our objective was to (a) characterize the RCM findings
of MF/SS skin lesions, (b) correlate RCM features of MF/SS with
histopathologic findings, and (c) assess the feasibility of RCM
in selecting the histologically most diagnostic skin biopsy site.
Forty-one patients were prospectively recruited and 83 lesions
(median 2 per patient) received RCM imaging, with a subset
(n=29) histologically assessed. The most commonly identified
RCM features included atypical lymphocytes appearing as
weakly reflective cells with irregular cellular contours in the
epidermis and superficial dermis and Pautrier’s microabscesses
appearing as dark round, sharply demarcated intra-epidermal
structures containing weakly reflective cells. Correlation of
RCM and histopathologic findings showed high agreement
for atypical lymphocytes in the epidermis (PABAK=0.90) and
moderate agreement for Pautrier’s microabscess (PM) (K=0.32,
p=0.03). Our RCM results revealed significant differences among
various lesion morphologies. Compared to patches, plaques
were significantly more likely to show Pautrier’s microabscess
(p=0.002) and epidermal dendritic processes (p<0.001).
Erythematous patches showed increased fibrosis (p=0.01) and
blood vessel dilation (p=0.001), while hyperpigmented patches
had a significantly higher number of melanophages in the dermis
(p<0.001). Lesions with Pautrier’s microabscess identified using
RCM were significantly more likely to have positive clonal TCR
gene rearrangement studies (p=0.04) and to score higher on
the Guitart et al. grading scale for MF/SS diagnosis (p=0.003).
Our findings demonstrate the potential diagnostic applicability
of RCM in MF/SS. RCM may aid clinicians in skin biopsy site
selection and in monitoring treatment response.
The Epidemic of Cutaneous Leishmaniasis among
Syrian Refugees in Lebanon
Ibrahim Khalifeh, MD
Ibrahim Khalifeh, MD1
1
American University of Beirut Medical Center, Beirut, Lebanon
Background: Cutaneous leishmaniasis (CL), a potentially chronic
and disfiguring condition, has been thrust in to the spotlight
following reports among military personnel returning from the
Near East. Lebanon (LB), a non-endemic area, is now suffering
a health care crisis in the wake of a CL epidemic brought from
endemic Syria through the displacement of over 1,500,000
refugees into LB. Materials and Methods: 1275 patients from
158 displaced families with CL were examined. Punch biopsies
(1 patient sampled/displaced family, n=158) were taken for
histologic examination (parasitic index) and molecular speciation
by PCR. Demographics, migration patterns, lesion number
and characteristics including presence of extensive disease
(ED) were documented. ED was defined as having ≥1 of the
following: Disfiguring, threatening the function of vital sensory
organs, lesion present for >12 months, >3cm, ≥5 lesions and
special forms of CL (i.e. sporotrichoid). Results: 1275 refugees
with CL had been in LB 5 months on average and 77% of them
reported the appearance of the first lesion after being in LB
for > 2 months (average incubation period 2-8 weeks). Of the
158 sampled patients, PCR resulted in 135 cases of L. tropica
and 23 L. major types. In this special conflict population, the
preponderance of patients sampled were under 18 years old
(80%) and an average of 52% members were affected/family
(mean number of members = 6). The majority of patients met
criteria for ED (59%) including: 27.3% with disease compromising
a sensory organ, 9% special forms, 37.3% disfiguring, 49%
>3cm, 20% > 5 lesions and 9% chronic lesions. Parasitic index,
molecular subtype and geographic location were similar for ED
versus non-ED. ED was more prevalent among children (median
9 vs. 21 years; p=0.002) and was more frequently observed on
the face and lower extremities (p=0.002). Both age and anatomic
location were predictors of ED by multivariate logistic regression.
Conclusion: In studying this epidemic, we are seeing a new face
of CL in times of war; stressful and unsanitary living conditions
may account for the uncharacteristically high number patients
with ED.
Dermatopathologic findings in severe combined
immunodeficiency (SCID): a study of 53 patients with a
subset received BCG vaccine
Tariq Al-Zaid, MD
Tariq Al-Zaid, MD1; Jihad Alrehaili, MD2
King Faisal Specialist Hospital, Riyadh, Saudi Arabia
1
Immam University, Riyadh, Saudi Arabia
2
Background: Severe combined immunodeficiency (SCID)
is a heterogeneous group of disorders characterized by
defects in the function of B cells and T cells. Hematopoietic
18
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The American Society of Dermatopathology
Oral Abstract Session 2
stem cell transplantation is the main modality of treatment
in these patients. In this study, we sought to evaluate the
dermatopathologic findings in a series of cases referred to our
center of medical evaluation and treatment. Methods: 53 patients
were identified in our database. A total of 73 skin biopsies
were available for evaluation. A subset of patients received
BCG vaccine at birth as part of routine vaccination. Results:
(18/73; 25%) biopsies showed granulomatous dermatitis. It was
ill formed with foamy histiocytes in (6/18;33%) biopsies and
well formed in (11/18;61%). The histiocytes were completely
spindled with acid fast bacilli in (1/18;6%). The granulomatous
inflammation was admixed with variable number of neutrophils
in (16/18;89%) cases. It was focally suppurative in (2/18;11%)
and predominantly suppurative in (2/18; 11%). Acid fast bacilli
were present in (17/18; 94%) cases. Other non-BCG related
findings include spongiotic dermatitis (11/73; 15%), dermal
hypersensitivity reaction (5/73;7%), folliculitis (5/73;7%),
GVHD due to maternal engraftment (2/73; 3%), GVHD due
to bone marrow transplantation (15/73; 21%), lichenoid drug
reaction (4/73; 5%), viral exanthem (3/73;4%), cryptococcal
infection (1/73;1%), toxic epidermal necrolysis (1/73;1%),
calcinosis cutis (1/73;1%), superficial fungal infection (1/73;1%),
ichthyosis (1/73;1%), lichen planus (1/73;1%), dermal abscess
(1/73;1%) and giant cell fibroblastoma (1/73;1%). Conclusion:
Grnaulomatous inflammation in SCID due BCG vaccination is
usually admixed with acute inflammatory cells. Occasionally,
the granulomatous inflammation is focally or predominantly
suppurative. Unusual morphology is completely spindled
histiocytes. Special stains for AFB is important to be considered
in this setting even if the inflammation does not look typically
grnaulomatous.
19
Abstract Book Oral Presentations
5
ASDP
annual meeting
st
The American Society of Dermatopathology
Fellows’ Case Presentations
Time
Title
Speaker
1:45 p.m. – 1:55 p.m.
Rapid onset Cutaneous Squamous Cell Carcinoma with Wart-Like
Morphology during Advanced Melanoma BRAF-inhibition Therapy with
Associated Viral and UV-Radiation Effects
Daniel Cohen, MD, PhD
1:55 p.m. – 2:05 p.m.
Quantitative Analysis of Immunophenotypical Profiles of Benign Dermatoses
versus Early Patch or Plaque Stage Mycosis Fungoides: Does a Difference
Truly Exist?
Gretchen Frieling, MD
2:05 p.m. – 2:15 p.m.
Non-specific staining for BRAFV600E immunohistochemistry in anorectal
mucosa: an important pitfall when evaluating anorectal melanoma
Julie Tse, MD
2:15 p.m. – 2:25 p.m.
Utility of a Standard Immunohistochemical Panel in Distinguishing
Subcutaneous Panniculitis-Like T-cell Lymphoma from Lupus Panniculitis
Robert LeBlanc, MD
2:25 p.m. – 2:35 p.m.
Mutations in adenosine deaminase 2 in cutaneous polyarteritis nodosa.
Tania Gonzalez Santiago, MD
2:35 p.m. – 2:45 p.m.
Correlation between MelaFind and histologic assessment in evaluation of
clinically ambiguous pigmented lesions
Ivanka Kovalyshyn, DO
2:45 p.m. – 2:55 p.m.
P40 staining in normal skin and adnexal neoplasms
Matthew Tilson, MD
2:55 p.m. – 3:05 p.m.
Squamomelanocytic tumors: a case series with fluorescence in-situ
hybridization (FISH) studies and long-term clinical follow-up to assess
etiology and biologic behavior
Sapna Amin, MD
3:05 p.m. – 3:15 p.m.
41 Cases of Subcutaneous Panniculitis Like T-cell Lymphoma;
a Bi-institutional Study
Erica Syklawer, MD
3:15 p.m. – 3:25 p.m.
myPathTM (MELANOMA ASSAY) IN OUR PRACTICE: IS IT HELPFUL?
George Garib, MD
3:25 p.m. – 3:35 p.m.
Worse outcome in melanoma patients recently pregnant: decreased T-cell
programmed death receptor-1 (PD-1) expression in primary tumors
suggests immune ignorance
Jennifer Ko, MD, PhD
3:35 p.m. – 3:45 p.m.
Assessment of VE1 (BRAF p.V600E) immunohistochemical staining patterns
in post- BRAF inhibitor therapy melanoma specimens
Carlos Prieto-Granada, MD
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Abstract Book Oral Presentations
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ASDP
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st
The American Society of Dermatopathology
Fellows’ Case Presentations
Rapid onset cutaneous squamous cell carcinoma
with wart-like morphology during advanced melanoma
BRAF-inhibition therapy with associated viral and
UV-radiation effects
Quantitative analysis of immunophenotypical
profiles of benign dermatoses versus early patch or
plaque stage mycosis fungoides: does a difference
truly exist?
Daniel Cohen, MD, PhD
Gretchen Frieling, MD
Daniel Cohen, MD, PhD ; Daniel Cohen, MD, PhD ; Steven
Lawson, BS3; Liping Du, PhD3; Harrison Nguyen, BA4; Qin He,
MD4; James Prescott, PhD5; Douglas Johnson, MD3; Pranil
Chandra, DO5; Jason Robbins, MD6; Jeffrey Zwerner, MD, PHD3;
Alan Boyd, MD3; Steven Tyring, MD, PhD, MBA4; Peter Rady, MD,
PhD4; James Chappell, MD, PhD3; Yu Shyr, PhD3; Jeffrey Infante,
MD7; Jeffrey Sosman, MD3
1
1
Gretchen Frieling, MD1; Sara Shalin, MD, PhD2; Alireza Sepehr,
MD3; M Angelica Selim, MD4; Christopher Shea, MD5; Bruce
Smoller, MD6; Martin Mihm Jr, MD7; Thomas Horn, MD, MBA8;
Thomas Ahern, PhD1; Seth Rosenthal, MD9
2
University of Vermont College of Medicine, Fletcher Allen Healthcare,
Burlington, Vermont, USA
1
University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA
2
Mayo Clinic, Rochester, Minnesota, USA
DermDX New England and Beacon Pathology, Brighton, Massachusetts, USA
3
Mayo Clinic and Vanderbilt University Medical Center, Rochester,
Minnesota, USA
2
3
4
5
Duke University, Durham, North Carolina, USA
4
University of Chicago, Chicago, Illinois, USA
5
Vanderbilt University Medical Center, Nashville, Tennessee, USA
University of Rochester School of Medicine, Rochester, New York, USA
6
University of Texas Medical School, Houston, Texas, USA
Co-Director Dana Farber and Brigham and Women’s Cancer Center,
Harvard Medical School, Boston, Massachusetts, USA
7
PathGroup, Nashville, Tennessee, USA
Vanderbilt University Medical Center and Pathology Associates of St.
Thomas, Nashville, Tennessee, USA
8
Sarah Cannon Research Institute and Tennessee Oncology, Nashville,
Tennessee, USA
9
6
Massachusetts General Hospital and Harvard Medical School, Boston,
Massachusetts, USA
7
Miraca Life Sciences and Tufts University School of Medicine, Newton,
Massachusetts, USA
Purpose: Molecularly targeted therapy for advanced melanoma
by BRAF-inhibition (BRAFi) carries a high rate of cutaneous
squamous cell carcinoma (cSCC) and rare malignancies in other
tissues. Ultraviolet (UV) radiation drives cSCC in healthy individuals
while α-genus human papillomavirus (α-HPV) infection causes
SCC of the oropharynx, larynx and cervix. Hypothesis: Host
and environmental factors collaborate in BRAFi induced cSCC
(BRAFi-cSCC). Experimental Design: DNA isolated from primary
cSCC arising in patients undergoing BRAFi therapy at two cancer
centers were assessed for the presence of potentially oncogenic
HPV and host cancer gene mutations. Diagnostic tissue biopsies
were subjected to consensus dermatopathology review. UV–
exposure as represented by the lesion site and clinical course
were statistically analyzed in relation to histopathology. Results:
Twenty-nine patients contributed 69 cSCC lesions, 22% of which
displayed wart-like features (WF). Controlling for gender and UV
exposure, a linear mixed-effects model showed that, on average
cSCC-WF arose 11.6 weeks sooner than conventional cSCC
(conv.-cSCC) among patients receiving Vem therapy (P=0.03).
Additionally, conv.-cSCC arising on UV-exposed sites during Vem
therapy developed 14 (median) weeks sooner than UV-protected
conv.-cSCC (P=0.02). Six of 10 BRAFi- cSCC demonstrating
characterized mutations in cancer genes harbored RAS mutations
(4 HRAS, 2 KRAS). ß-genus HPV-17 (n = 25 lesions), HPV-38 (n =
29), and HPV-111 (n=14) were most frequently isolated, and three
putative novel ß-HPV genotypes were discovered in cSCC- WF.
Conclusions: We examined clinical, histopathologic, and molecular
parameters in BRAFi-cSCC to shed new light on the biology of
cSCC in these patients and to broaden general knowledge of
multifactorial mediators of oncogenesis. Our findings suggest
that UV exposure and ß-HPV or other factors that cause wart-like
growth cooperate with pharmacologic inhibitors of mutant BRAF to
accelerate neoplastic transformation of keratinocytes.
Cases of early mycosis fungoides (MF) are frequently complex
and difficult, and with the advent of increasingly available
immunohistochemical stains (IHC), costly to assess. It has
arguably become the standard of care to use progressively
increased numbers of stains included in a broad panel, in addition
to traditional morphological assessment. While IHC can be
helpful in ambiguous cases, many experts find that IHC fails to
clarify the majority of such cases. Many studies have addressed
the use of IHC in MF. However, a comprehensive comparison
of morphological and IHC parameters between MF and benign
dermatitides has yet to be performed. We conducted a blinded
analysis of centrally-diagnosed cases of early or mild eczematous
dermatitis (n=100) and cases of early MF (n=100) to assess the
contribution of IHC stains to morphological classification of MF.
Seven expert dermatopathologists rendered diagnoses based
solely on morphological characteristics, and at least six months
later, based only on IHC parameters. The two sets of physician
diagnoses were compared with centrally-diagnosed MF status
using agreement and classification statistics and receiver-operating
characteristic (ROC) curves. Diagnoses based on morphological
parameters showed modest agreement with diagnoses based on
IHC stains (kappa=0.44, 95% CI: 0.31,0.56). Diagnosis based on
morphological parameters was superior to diagnosis based on IHC
parameters in classifying centrally-diagnosed MF (sensitivity=0.85
and specificity=0.70 for morphological; sensitivity=0.73 and
specificity=0.71 for IHC). In the regression of centrally diagnosed
MF on the individual morphological and IHC parameters, the
area under the ROC curve (AUC) for morphological parameters
alone equaled 0.78; addition of IHC parameters increased the
AUC to 0.84 (difference in AUC=0.059; 95% CI: 0.015, 0.103). In
conclusion, morphological evaluation yields adequate classification
of MF status. The cost of including IHC stains may outweigh the
modest increase in classification accuracy they afford.
21
Abstract Book Oral Presentations
5
ASDP
annual meeting
st
The American Society of Dermatopathology
Fellows’ Case Presentations
Non-specific staining for BRAFV600E
immunohistochemistry in anorectal mucosa: an
important pitfall when evaluating anorectal melanoma
Utility of a standard immunohistochemical panel in
distinguishing subcutaneous panniculitis-like T-cell
lymphoma from lupus panniculitis
Julie Tse, MD
Robert LeBlanc, MD
Julie Tse, MD ; Lawrence Zukerberg, MD ; May Chan, MD ;
Rosalynn Nazarian, MD2
Robert LeBlanc, MD1; Jinah Kim, MD, PhD1
Harvard Hospitals Dermatopathology Fellowship Program, Boston,
Massachusetts, USA
The clinical and histopathologic distinctions between lupus
erythematosus panniculitis (LEP) and subcutaneous panniculitislike T-cell lymphoma (SPTCL) are sometimes challenging but
necessary for the purposes of prognosis and management.
Standard molecular clonality data aid this distinction but may
be difficult to interpret in the context of autoimmune diseases,
such as lupus, in which clones infrequently emerge. In our
cohort, the most reproducible histologic findings included hyaline
lipomembranous necrosis and plasmacytoid cell clusters in
LEP, and adipocyte rimming and lymphocyte atypia in SPTCL.
These findings are not entirely disease specific, however,
and the novel and potentially valuable markers CD123 and
CCL5 are not routinely evaluated in many laboratories. This
study details an algorithmic approach to the use of a standard
immunohistochemical panel (CD4, CD8, CD20, and Ki-67)
as a helpful adjunct for diagnostic classification. Biopsies
were included from 21 patients with clinicopathologically and
molecularly annotated SPTCL (9) and LEP (12). SPTCL infiltrates
exhibited an inverted CD4:CD8 ratio (mean 1:4) with neoplastic
CD8+ cells rimming degenerative adipocytes. LEP infiltrates
revealed a preserved to increased CD4:CD8 ratio (mean 3:1)
with dense CD4+ cell aggregates splaying adipocyte lobules
and CD8+ cells punctuating the aggregates and at least focally
surrounding adipocytes in a manner reminiscent of SPTLC.
CD20+ B-cell aggregates were present more often in LEP (8
of 9 cases) than in SPTCL (1 of 7 cases). In LEP, Ki-67 indices
were low (mean 6.8%) with staining uniformly distributed. In
SPTCL, Ki-67 demonstrated heterogeneous staining distributions
with “hotspot” accentuation of adipotropic lymphocytes (mean
57.8%). Ki-67 evaluation within the adipocentric hotspots,
determination of the overall CD4:CD8 ratio, and the detection
of CD20+ B-cell aggregates may help to distinguish LEP from
SPTCL.
1
2
3
1
1
Massachusetts General Hospital Department of Pathology, Boston,
Massachusetts, USA
2
University of Michigan Department of Pathology, Ann Arbor, Michigan,
USA
3
Anorectal melanoma is an aggressive malignancy with few
effective therapeutic options. Localized tumors are surgically
resected while unresectable and metastatic anorectal melanoma
with specific mutations may be treated with targeted therapies.
Despite molecular studies showing BRAF mutations in only 5% of
anorectal melanoma, BRAFV600E mutation analysis of anorectal
melanoma is often requested by clinicians given the availability
of vemurafenib, a FDA-approved BRAF inhibitor for use in the
treatment of metastatic melanoma harboring the mutation. The
mutant-specific BRAFV600E (clone VE1) antibody developed
for immunohistochemistry on formalin-fixed paraffin-embedded
tissue has been validated to have high sensitivity and specificity
for the BRAFV600E mutation. We report the results of VE1
immunostaining in 9 cases of anorectal melanoma and 17 cases
of control anorectal mucosa. None of the anorectal melanoma
expressed VE1, however, we observed strong non-specific
nuclear and weak cytoplasmic positivity for VE1 in anorectal
glands in all anorectal melanoma and control cases. The staining
was noted to have a gradient of positivity, with strongest staining
at the luminal aspect of the glands and weakest staining at the
crypt base. To our knowledge, a similar pattern of VE1 expression
in gastrointestinal glands has been previously mentioned in the
context of staining for colorectal carcinoma. We wish to raise
awareness of this nonspecific staining pattern as a potential
pitfall in the interpretation of VE1 when evaluating BRAFV600E
mutation status in anorectal melanoma.
Stanford University School of Medicine, Stanford, California, USA
Mutations in adenosine deaminase 2 in cutaneous
polyarteritis nodosa
Tania Gonzalez Santiago, MD
Tania Gonzalez Santiago, MD1; Lawrence Gibson, MD1
Mayo Clinic, Rochester, Minnesota, USA
1
In recent studies, a recessive loss of function mutation in
ADA2, a growth factor, has been identified as a cause of
polyarteritis nodosa (PAN). ADA2 is known to be essential for
the development and maintenance of the immune system;
however, the full physiological role of ADA2 is not yet completely
understood. Mutated ADA2 leads to highly varied clinical
expression and manifestations can range from fatal systemic
vasculitis in children to limited cutaneous manifestations in
22
Abstract Book Oral Presentations
5
ASDP
annual meeting
st
The American Society of Dermatopathology
Fellows’ Case Presentations
middle-aged persons. We described 2 Caucasian siblings with
a history of primary immune deficiency who presented with
deep, painful, subcutaneous nodules on the lower extremities.
In both cases, skin biopsies demonstrated medium vessel
vasculitis confirming a diagnosis of cutaneous PAN. Extensive
infectious work up for etiology of their vasculitis as well as
imaging studies was negative. Given that recent reports indicated
genetic mutations as a possible cause of cutaneous PAN further
investigations were undertaken. ADA2 levels for both cases
were low. Whole exome sequencing showed biallelic mutation
in CECR1, the gene that encodes ADA2. Based on these
findings both patients were diagnosed with cutaneous PAN
secondary to deficiency of ADA2. Current diagnostic criteria
for PAN are not well established and are often subjectively
interpreted. Identification of CERC1 mutations with concomitant
low levels of ADA2, in the appropriate clinical setting, can
considerably expedite the diagnosis and hold a potential for
better management. This can also serve as a potential screening
tool for family members who present with milder disease and less
specific symptomatology.
Correlation between MelaFind and histologic
assessment in evaluation of clinically ambiguous
pigmented lesions
Ivanka Kovalyshyn, DO
Ivanka Kovalyshyn, DO1; Ivanka Kovalyshyn, DO1; Natasha
Mesinkovska, MD; PhD1; Philip Bailin, MD1; Wilma Bergfeld, MD1
1
Cleveland Clinic Foundation, Cleveland, Ohio, USA
Background: MelaFind is computer-assisted diagnostic device
designed to assist in early detection of melanoma. Objective:
Correlation and assessment of the “high disorganization” score
on MelaFind with degree of histologic atypia in evaluating
ambiguous pigmented lesions. Design: Single-center prospective
study. Patients: The study population included 42 high risk
patients (i.e., atypical mole syndrome, large number of moles
±personal history of melanoma). Each patient had a total body
skin exam with subsequent evaluation of clinically atypical
lesions with a handheld dermatoscope. All ambiguous pigmented
lesions were then scanned with MelaFind. Those lesions which
displayed “high disorganization” score on MelaFind were chosen
for a biopsy. All biopsies were reviewed by 3 independent
dermatopathologists. Results: A total of 261 ambiguous
pigmented lesions were evaluated with MelaFind, resulting in
total of 92 lesions displaying “high disorganization” MelaFind
score, ranging from 0.3 to 6.8, with the mean score of 2.20 and
median of 2. Of 92 lesions with “high disorganization” scores, 52
(57%) were banal nevi, 35 (38%) were atypical nevi (the majority
of which had mild cytologic atypia), 4(4%) were lentigines and
1 (1%) was melanoma in situ. Interestingly, inflamed pigmented
lesions and those displaying prominent melanoderma had higher
disorganization scores. Conclusions: Our data indicate that
MelaFind has a high rate of false positive results. Our results
require validation in a larger series. Further studies are needed to
determine which histologic features may result in false- positive
rate and lead to “high disorganization” MelaFind score.
P40 staining in normal skin and adnexal neoplasms
Matthew Tilson, MD
Matthew Tilson, MD1; Janis Taube, MD1
1
Johns Hopkins University, Baltimore, Maryland, USA
P63 is routinely used in the diagnosis of adnexal neoplasms.
P40 recognizes the squamous-specific ΔNp63 isoform of p63.
P40 has been shown to be superior to p63 when used as
part of an immunohistochemical (IHC) panel in organ systems
such as the lung and head and neck. Most recently, p40 has
demonstrated utility in differentiating adnexal carcinomas from
cutaneous metastases. Yet, the staining pattern of p40 in
normal skin and adnexal neoplasms has not been described
in detail. The purpose of this study is to establish p40 staining
patterns in normal skin and adnexal neoplasms as compared
to p63. Sixty-four (64) adnexal neoplasms including sebaceous
carcinoma (n=19), microcystic adnexal carcinoma (n=4),
acrospiroma/hidradenoma (n=11), spiradenoma (n=8), poroma
(n=6), trichoblastoma/trichoepithelioma (n=5), syringoma
(n=4), sebaceous adenoma (n=3), benign mixed tumor (n=2),
hidradenoma papilliferum (n=1) and cylindroma (n=1) were
collected. P63 and p40 IHC stains were performed on each
specimen. Patterns of p40 and p63 expression were assessed
in background normal skin and lesional tissue. Percent nuclei
staining (at 10% intervals) as well as intensity (0, 1+, 2+, 3+) of
staining was graded for each case. Normal skin demonstrated
strong staining in the lower 2/3 of the epidermis, myoepithelial
cells and follicular epithelium. Secretory cells of both eccrine and
apocrine type were negative. In sebaceous glands, germinative
cells were positive while mature sebocytes were negative.
Intermediate sebocytes showed variable positivity. Adnexal
neoplasms showed comparable staining between p63 and p40,
with no notable differences in percent cells staining or staining
intensity (p>0.05). In keeping with their lines of differentiation,
we observed positive staining in adnexal neoplasms of follicular
origin and in those with myoepithelial or germinative epithelial
components but not in areas with secretory cells (apocrine or
eccrine) or cells with clear sebaceous differentiation. P40 stains
comparatively to p63 in normal skin and adnexal neoplasms,
both benign and malignant. With an established staining profile
and improved specificity for discriminating between primary and
metastatic lesions, the preferential use of p40 over p63 may be
considered in certain dermatopathology applications.
23
Abstract Book Oral Presentations
5
ASDP
annual meeting
st
The American Society of Dermatopathology
Fellows’ Case Presentations
Squamomelanocytic tumors: a case series with
fluorescence in-situ hybridization (FISH) studies and
long-term clinical follow-up to assess etiology and
biologic behavior
Sapna Amin, MD
Sapna Amin, MD1; Chelsea Cooper, B.A.1; Joan Guitart, MD1;
Pedram Gerami, MD1
Northwestern University School of Medicine, Chicago, Illinois,
USA
1
Squamomelanocytic tumors (SMT) are uncommon cutaneous
neoplasms comprised of two distinct cellular phenotypes:
melanocytic and squamous epithelial. There are a limited
number of cases reported to date. It is controversial whether
these tumors represent collision tumors or dual differentiation
from one common cell type. In addition to questions of etiology,
the biologic behavior of these tumors has yet to be determined,
partially due to their rarity. To address these issues, we studied
a series of 14 SMTs diagnosed at our institution. Fluorescence
in-situ hybridization (FISH) studies were performed to assess for
chromosomal copy number alterations in both tumor components
and long-term clinical follow-up was reviewed. Fifty percent of
cases tested showed alterations in chromosomal copy numbers:
2/10 cases showed gains in 6p25 in the melanocytic component,
another 2 cases showed gains in 11q13 (cyclin D1), and 1 case
showed gains in both 6p25 and 11q13. One of these cases
showed gains in 11q13 in both the melanocytic and squamous
components. These findings support the malignant nature of
SMTs over reactive melanocytic or epithelial hyperplasia, as
similar chromosomal alterations have been described in other
types of melanoma and skin cancers on chronically sun-damaged
skin. The finding of 11q amplification in both components of one
case may also support the theory of dual differentiation from a
common progenitor cell. Finally, based on an average follow up
time of 49.5 months, we found that only 1 of 14 cases reported
significant adverse outcomes, suggesting that these tumors do
not behavior more aggressively than non-combined tumors.
41 cases of subcutaneous panniculitis like T-cell
lymphoma; a bi-institutional study
Erica Syklawer, MD
Erica Syklawer, MD1; Brian Connolly, MD1; Patricia Myskowski,
MD1; Steven Horwitz, MD1; Stephanie Hu, MD2; Christiane
Querfeld, MD1; Hideko Kamino, MD2; Melissa Pulitzer, MD1;
Achim AchimJungbluth, MD, PhD1
Memorial Sloan-Kettering Cancer Center, New York, New York, USA
1
New York University, New York, New York, USA
2
Subcutaneous panniculitis like T-cell lymphoma (SPTCL) is a
rare, indolent post-thymic cytotoxic T-cell lymphoma in the
subcutis, with clonal T-cell receptor (TCR) gene rearrangements
and characteristic antigen expression, e.g. a TCRαβ
immunophenotype. Classifying SPTCL is not straightforward;
inconsistent clinicopathologic features may obfuscate the
diagnosis. To better characterize clinicopathologic features
of SPTCL, with IRB approvals, we studied 41 subcutaneous
lymphomas from our pathology/dermatopathology databases,
favored to be SPTCL via clinicopathologic consensus. Of 41
patients, 22 were male, 19 female. 31/41 were Caucasian. The
mean age at diagnosis was 45.3 years (range 2-81). Two patients
had hemophagocytic syndrome (HPS); two had suspected
HPS (not confirmed). Three of these four died within one year
of diagnosis; the fourth died within two years. Nine patients
who died in follow-up had a mean survival after diagnosis of
40 months (range: 1-149). Features distinguishing patients
who died in follow-up versus those who did not were older
age at diagnosis (mean 58 vs 39 years), cytopenia (7/9, 78%
vs 10/18, 50%), and multiple skin sites (9/9, 100% vs 10/18,
56%). Seven patients were ANA+ or known to have connective
tissue disease (CTD). Six patients had negative evaluations for
CTD. 19/35 well-documented patients had a chemical exposure,
including tobacco smoking and/or occupational exposure. All
cases (41) localized to the subcutis, some with slight dermal
involvement (25/41, 61%), focal exocytosis (7/41, 17%), and/
or ulceration (5/41, 14%). 29/41 (71%) showed adipocyte
rimming. Angio-invasion (25/41, 61%) dermal mucin (9/36, 25%)
and plasma cells (15/41, 37%) were not infrequently noted.
25/25 immunohistochemically evaluated cases expressed T-cell
antigens; 18 CD4+/CD8+; six CD4-/CD8+; and one CD4-/CD8-.
46% contained CD56+ cells. 10/12 cases tested for BetaF1 were
positive. No case (11 tested) showed unequivocal gamma-tcr
staining. 13/26 (50%) of cases studied showed clonal TCR gene
rearrangements; two TCR beta, seven TCR gamma, and four
both. In conclusion, SPTCL remains a diagnostic conundrum,
and may exhibit clinical or pathologic behavior of high grade
lymphoma and/or CTD. Cytopenias, multiple skin sites, or older
age at diagnosis may be useful in predicting course.
myPathTM (melanoma assay) in our practice: is it
helpful?
George Garib, MD
George Garib, MD1; Evan Ariano, M.D1; Robert Quirey, MD2;
Kumaran Mudaliar, M.D1; Jodi Speiser, MD1; Kelli Hutchens, MD1
1
Loyola University Medical Center, Maywood, Illinois, USA
2
Ameripath, Indianapolis, Indiana, USA
While the majority of melanocytic proliferations can be fairly
easily characterized, a subset may be difficult to categorize
with certainty and may result in an ambiguous diagnosis and
possible mistreatment. Adjunctive molecular assays have
repeatedly been studied to differentiate between ambiguous
benign melanocytic lesions and melanomas. The myPathTM
melanoma assay created by Myriad Genetics combines 23
unique molecular markers that they have demonstrated to be
effective at differentiating between benign nevi and melanoma
with a sensitivity of 89% and a specificity of 93%. The aim of
our study was to determine the correlation of the myPathTM
assay with our histologic diagnosis (HD), determine the utility
of the test for indeterminate melanocytic proliferations, and
its prognostic value for dysplastic nevi (DN). We randomly
selected 71 melanocytic lesions diagnosed at our institution
24
Abstract Book Oral Presentations
5
ASDP
annual meeting
st
The American Society of Dermatopathology
Fellows’ Case Presentations
which consisted of 35 DN, 8 melanoma in situ (MIS), 9
melanomas, 5 indeterminate neoplasms, and 14 nevi. Patient
results obtained from Myriad were entered into a de-identified
database along with the histological diagnosis previously
rendered. Non-concordance results were verified by a blinded
second dermatopathologist. Results Summary: 11/71 tests were
unsatisfactory due to insufficient RNA (15.49%). 53/60 (88.33%)
concurred with our HD of benign or malignant. 4 cases were
discordant. 2/4 cases were had benign myPathTM but HD of
MIS and 2/4 had malignant myPathTM results but HD of DN (1
severe; 1 moderate). 3 cases (5%) had indeterminate scores
on myPathTM. 1/3 was also HD indeterminate on retrospective
review. There was no significant difference in the mean
myPathTM score between moderate DN and severe DN (T-test
-5.69; -4.93). Our study supports the data supplied by Myriad
on the performance of the myPathTM test. Interestingly, we
found the test to have similar results for moderate and severely
dysplastic nevi which in our practice are treated quite differently
clinically.
Worse outcome in melanoma patients recently
pregnant: decreased T-cell programmed death
receptor-1 (PD-1) expression in primary tumors
suggests immune ignorance
Jennifer Ko, MD, PhD
Jennifer Ko, MD, PhD1; Brian Gastman, MD1; Alejandra Tellez
Diaz Trujillo, MD1; Wilma Bergfeld, MD1; Natasha Mesinkovska,
MD, PhD1
1
Cleveland Clinic, Cleveland, Ohio, USA
Melanoma is particularly immunogenic, with most novel therapies
directed toward immune modulation. Pregnancy depends
on tolerance of immunologically foreign fetuses via Th1 T-cell
suppression. PD-1 is a negative regulatory co-stimulator critical
for the regulation of peripheral tolerance and autoimmunity.
As such, it is expressed upon T-cell activation to contract the
T-cell response. Melanoma outcomes in n=645 women of
child-bearing age with ≥24 months follow-up [n=49 women
with childbirth within 1-year of diagnosis (CB1Y), and n=596
non-pregnant (NP) age-matched controls] were investigated.
In patients with CB1Y compared to NP, there was a higher
incidence of melanoma local recurrence (12.5% and 1.4%,
p<0.001), metastasis (25% and 12.7%, p=0.03) and mortality
(20% and 10.3%, p=0.06). CB1Y patients had a 9.2, 6.7, and 5.1
increased odds of local recurrence (p=0.01), metastasis (p=0.01),
and melanoma death (p=0.03). Immunohistochemical studies
of immunologic markers (CD68, CD3, and PD1), and blood/
lymphatic microvessel (CD31, D2-40) density was compared
in CB1Y and NP. The available tissue included n=17 CB1Y: pT
stage= 8 stage 0, 6 stage 1, 1 stage 2, and 2 stage 4; and n=14
NP controls: 7 stage 0, 5 stage 1, and 2 stage 2. We found
reduced PD-1 expression in CB1Y tumors (mean= 18.3 vs. 45
cells/hpf; p=0.03) and a trend toward decreased CD3 infiltrate
(mean= 191.7 vs. 265.7 cells/hpf; p=0.1) and increased CD3/
PD1 ratio (mean= 57.4 vs. 8.3; p=0.1). As PD-1 expression is
induced during T-cell activation, the data suggest that immune
ignorance may predominate in CB1Y. Further scientific efforts are
required to identify interventions which may promote an inflamed
phenotype in such patients.
Assessment of VE1 (BRAF p.V600E)
immunohistochemical staining patterns in post- BRAF
inhibitor therapy melanoma specimens
Carlos Prieto-Granada, MD
Carlos Prieto-Granada, MD1; Leslie Turner, MD2; Sarah Sloot,
MD3; Geoffrey Gibney, MD4; Jane Messina, MD1
1
University of South Florida/Moffiitt Cancer Center, Tampa, Florida, USA
James A Haley VA Medical Center Department of Pathology, Tampa,
Florida, USA
2
3
University Medical Center Groningen, Groningen, Netherlands
4
Moffitt Cancer Center, Tampa, Florida, USA
Immunohistochemistry for BRAF p.V600E using the VE1 clone
has proven to be not only a highly sensitive and specific marker
but also has also exhibited an excellent correlation with molecular
studies. Recent publications describe occasional intratumoral
and intertumoral homogeneity of VE1 expression, but post
treatment heterogeneity and response have not been correlated.
We report herein VE1 immunostaining patterns in specimens
from 7 patients with advanced stage melanoma (Stage III: 4
patients and Stage IV: 3 patients) that were positive for BRAF
V600E by pyrosequencing and RT-PCR and who received BRAF
inhibitor (BRAFi) therapy including 2 with concomitant MEK
inhibition. Specimens were stained with VE1 antibody (Ventana,
Tucson AZ) and evaluated for intensity (Negative 0 to Strong +4)
and distribution (focal, patchy 50%). There were 4 males and
3 females; mean age 59 years. All had lymph node metastases
(4 axillary, 3 inguinal and pelvic basins). Mean tumor size was
6.5 cm; all tumors displayed epithelioid cell morphology. Six
specimens were from lymph node dissections and one was a
cutaneous metastasis, with mean treatment time of 5.8 months
(range 0.4 – 8.8) before resection. Viable tumor was present in 4/7
patients, all of these tumors were immunoreactive for VE1 with
three cases exhibiting strong (4+) and diffuse (>50%) staining and
one case showing moderate (3+) and patchy (<50%) positivity.
In 3 patients, specimens showed necrosis, fibrosis and tumoral
melanosis but no residual tumor. All 3 cases with therapy related
changes exhibited a blush of VE1 immunoreactivity highlighting
the areas of necrosis and ghost tumor cells. After a mean follow
up of 12.7 months, three patients had no evidence of disease,
two were alive with disease and two died of disease. The
outcomes had no relationship to VE1 staining pattern, further
emphasizing melanoma tumor homogeneity in VE1 staining, even
after BRAFi therapy.
25
Abstract Book Oral Presentations
5
ASDP
annual meeting
st
The American Society of Dermatopathology
Oral Abstract Session 3
7:30 a.m. – 7:40 a.m.
PD-1, S-100, and CD1a Expression in Pseudolymphomatous Folliculitis, Amrita Goyal, AB
Primary Cutaneous Marginal Zone B-cell Lymphoma (MALT lymphoma),
and Cutaneous Lymphoid Hyperplasia
7:40 a.m. – 7:50 a.m.
Loss of miR-211 Expression by microRNA in situ Hybridization (mISH)
Discriminates Melanoma from Nevus
Sam Dadras, MD, PhD
7:50 a.m. – 8:00 a.m.
Distinct Peacock Plumage Pattern of Human Polyomavirus 7
Associated Plaques in Two Transplant Patients
Jonhan Ho, MD
8:00 a.m. – 8:10 a.m.
Histopathology of Spontaneous Melanoma in tg(mitfa:BRAF(V600E));
p53-/- Transgenic Zebrafish
Anneli Bowen, MD
8:10 a.m. – 8:20 a.m.
High-throughput Sequencing of T cell Receptor Gene Rearrangement:
Improving Diagnosis in Cutaneous T cell Lymphoma
Jinah Kim, MD, PhD
8:20 a.m. – 8:30 a.m.
A Comparative Analysis of the Clinical, Histologic, and Molecular
Features of Proliferative Nodules and Melanoma
Pedram Gerami, BS, MD
26
Abstract Book Oral Presentations
5
ASDP
annual meeting
st
The American Society of Dermatopathology
Oral Abstract Session 3
PD-1, S-100, and CD1a expression in
pseudolymphomatous folliculitis, primary cutaneous
marginal zone B-cell lymphoma (MALT lymphoma), and
cutaneous lymphoid hyperplasia
Amrita Goyal, AB
Amrita Goyal, AB1; Johanna Moore, MD1; Devon Gimbel, MD1; Joi
Carter, MD1; Daniela Kroshinsky, MD, MPH1; Judith Ferry, MD1;
Nancy Harris, MD1; Lyn Duncan, MD1
Massachusetts General Hospital, Harvard Medical School, Boston,
Massachusetts, USA
1
Pseudolymphomatous folliculitis (PLF) is a non-neoplastic
lymphoid proliferation that clinically and histopathologically
mimics primary cutaneous extranodal marginal zone lymphoma
of mucosa-associated lymphoid tissue (MALT lymphoma).
In this study we assessed the diagnostic value of three
immunohistochemical markers: PD-1, CD1a, and S100. We
hypothesized that immunohistochemical staining patterns of
these markers would be diagnostically informative. We evaluated
25 cases of cutaneous lymphoid proliferations including
9 patients with PLF, 11 with MALT lymphoma, and 5 with
cutaneous lymphoid hyperplasia. The clinical, histopathologic,
and immunohistochemical features of each case were reviewed
and three major characteristics assessed: 1) the proportion of
T cells expressing PD-1, 2) the pattern of expression of CD1a
by dendritic cells, and 3) the pattern of expression of S100 by
dendritic cells. We found PLF to have a significant increase in
PD-1+ T cells compared to MALT lymphoma (p<0.0001). The
pattern of CD1a staining is also informative: MALT lymphoma is
significantly more likely to demonstrate a peripheral concentration
of CD1a+ dendritic cells in lymphoid nodules than PLF (p<0.0003)
or CLH (p<0.05). PLF is more likely to demonstrate an interstitial
pattern than is MALT lymphoma (p<0.04). Notably, S100 staining
was not helpful in differentiating these conditions. Therefore,
histopathological factors including PD-1 and CD1a staining
patterns may allow for more certainty in distinguishing PLF from
MALT lymphoma.
Loss of miR-211 expression by microRNA in situ
hybridization (mISH) discriminates melanoma from
nevus
Sam Dadras, MD, PhD
Sam Dadras, MD-PhD1; Sankhiros Babapoor, PhD1; Shauna
Levinson, BS2; Weijing Wang, BS2; Botoul Maqsodi, BS2; Manoj
Gandhi, MD-PhD2; Quan Nguyen, PhD2; Sam Dadras, MD-PhD1
1
UCONN, Farmington, Connecticut, USA
2
Affymetrix, Inc., Santa Clara, California, USA
To date, no immunohistochemical stain can reliably distinguish
melanoma from nevus cells. Previously, next-generation
sequencing of microRNA (miRNA) transcriptome in biopsies of
common melanocytic nevi (CN) and invasive primary cutaneous
melanomas (PCM) identified a set of top miRNAs, which properly
classified benign from malignant lesions. Among these, miR211 (hosted by Melastatin-1 gene) expression was significantly
decreased in PCM vs. CN. miRNAs are small noncoding RNAs
(18 to 24 nucleotides) and potent regulators of gene expression.
When deregulated during tumorigenesis, miRNAs can function
predominately as tumor suppressor genes and some as
oncogenes in a number of human malignancies including
melanoma. To validate miR-211 as a diagnostic marker, we
established both fluorescent and chromogenic methodologies for
mISH by testing normal skin (n=8), CN (n=31) and PCM (n=22)
all prepared from formalin-fixed paraffin-embedded (FFPE) full
sections and tissue microarrays. Qualitatively, miR-211 was
strongly and diffusely expressed in the cytoplasm of nevus cells
and epidermal keratinocytes whereas the signal was strikingly
reduced or was absent in melanoma cells by both light and
fluorescent microscopy. The measured fluorescence for miR-211
was significantly lower in melanomas than in nevi (P < 5.60712
e-06). Given the retained stability of miRNAs in FFPE biopsies
and the relative ease of interpreting its results, mISH could
provide a novel ancillary diagnostic tool in melanoma diagnosis.
Distinct peacock plumage pattern of human
polyomavirus 7 associated plaques in two transplant
patients
Jonhan Ho, MD
Jonhan Ho, MD1; Jaroslaw Jedrych, MD1; Ezra Mirvish, MD1;
Lisa Grandinetti, MD1; August Natalie, MD1; Feng Huichen, MD1;
Christopher Buck, PhD2; Diana Pastrana, PhD2; Patrick Moore,
MD, MPH1; Yuan Chang, MD1
1
University of Pittsburgh, Pittsburgh, Pennsylvania, USA
2
National Institute of Health, Bethesda, Maryland, USA
INTRODUCTON: Polyomaviridea constitute a family of small
(~45nm) icosahedral non-enveloped viruses with approximately
5 kilobase double-stranded circular DNA. Although some of the
family members are well-known to be causative agents in disease
among immunosuppressed and immunocompetent patients, the
pathogenic role of most of these viruses is not established in
humans. Human Polyomavirus 7 (HPyV7) was only discovered
4 years ago through new genomics sequencing technologies,
and is known to be present on the skin of asymptomatic
individuals. Approximately 64% of adults show seropositivity
for HPyV7. METHODS: We identified two Caucasian males in
their seventies with lung transplants and several years history of
and immunosuppression who presented with similar appearing
skin eruptions of several months duration composed of severely
pruritic hyperpigmented velvety plaques disseminated on
the trunk and extremities. Tissues were evaluated by light
microscopy, electron microscopy, immunohistochemistry, and
molecular techniques. RESULTS: Light and electron microscopy
revealed a distinctive pattern of hyperkeratosis with viropathic
keratinocytes scattered throughout the stratum corneum and
spinosum, reminiscent of peacock plumage. The involved
cells displayed enlarged hyperchromatic nuclei with smudgy
chromatin. Electron microscopy studies confirmed the presence
of 36-45 nm icosahedral capsids densely-packed in keratinocyte
nuclei. Rolling circle amplification and polymerase chain reaction
testing were positive for encapsidated human polyomavirus
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The American Society of Dermatopathology
Oral Abstract Session 3
7 (HPyV7) DNA in skin and peripheral blood of both patients.
HPyV7 early and capsid proteins were abundant in affected
tissues by immunohistochemical studies. In addition, HPyV7 was
present in gastric antral mucosa for one patient with nausea and
odynophagia. CONCLUSION: For the first time, we recognized a
new infectious disease manifesting in lung transplant recipients
as a chronic velvety skin plaques and viral dissemination of
the recently-discovered HPyV7. The disease is manifested by
a distinctive clinical presentation and unique histopathologic
pattern. Considering the pool of organ transplant recipients, it is
plausible that a substantial number of patients with this disease
remains undetected worldwide.
High-throughput sequencing of T cell receptor gene
rearrangement: Improving diagnosis in cutaneous T
cell lymphoma
Jinah Kim, MD, PhD
Jinah Kim, MD, PhD1; Sima Rozati, MD1; Wen Kai Weng, MD1;
Mahkam Tavallaee, MD1; Ilan Kirsch, MD2; Youn Kim, MD1
Histopathology of spontaneous melanoma in
tg(mitfa:BRAF(V600E); p53-/- transgenic zebrafish
Anneli Bowen, MD
Anneli Bowen, MD1; James Goodman, BS2; Amanda Truong, BS2;
Rodney Stewart, PhD2; Douglas Grossman, MD, PhD2
1
University of Utah, Salt Lake City, Utah, USA
2
Huntsman Cancer Institute, Salt Lake City, Utah, USA
Zebrafish are an increasingly popular model system for
cancer genetics analysis. A transgenic zebrafish melanoma
model was published recently by Ceol et al in which mutant
BRAF(V600E) is expressed in melanocytes on a p53-deficient
background. Since the histopathology of the resulting
melanomas has not been well described, we analyzed 34 tumors
from 26 tg(mitfa:BRAF(V600E)); p53-/- fish by H and E and
immunohistochemistry. Tumors presented most commonly on
the back (14/34) followed by the caudal region (11/34) and head
(9/34). With the exception of two tumors of the eye, melanoma
arose on the epidermis in 32 tumors, infiltrated underlying muscle
in 29 and surrounded the brain or spinal column in 23. Invasion
into neural tissue or brain was not appreciated. 30 of 34 tumors
demonstrated melanin production, while 4 were amelanotic.
Tumor cells were plump, spindled cells that demonstrated a
random and sometimes storiform arrangement with no nesting.
Associated stromal or inflammatory reaction was not appreciated.
Nuclear pleomorphism was common with mitotic activity ranging
from 0-17/HPF. Five tumors demonstrated focal necrosis. Of
the cases subjected to immunohistochemistry for conventional
melanoma markers, all four demonstrated stippled, cytoplasmic
Melan-A staining but were negative for S100 and HMB-45. This
study demonstrates that BRAF-driven melanomas in zebra fish
share some features with human melanoma including melanin
production, predominantly epidermal origin and Melan-A staining.
They differ in the absence of nesting, inflammatory and stromal
responses as well as lack of S100 and HMB-45 reactivity. These
zebrafish melanomas are, on the whole, more cytologically
pleomorphic and locally infiltrative than human melanoma.
1
Stanford, Stanford, California, USA
2
Adaptive Biotechnologies Corp, Seattle, Washington, USA
The accurate diagnosis of mycosis fungoides (MF) and Sézary
syndrome (SS) is often challenging because of the clinical and
histopathologic similarities with inflammatory disorders. In
addition, T-cell receptor (TCR) gene rearrangement, as assessed
by standard polymerase chain reaction (PCR) may yield confusing
results with demonstration of clonal proliferations in reactive
conditions. Routine TCR PCR may not identify true clonal TCR
gene rearrangement especially in low-burden disease. Highthroughput sequencing (HTS) is a technology that analyzes
TCR gene rearrangement with real-time high sensitivity that can
detect 1 SC in >50,000 PBMCs. Previously, we have shown
that TCR HTS is superior to other clinical methods in monitoring
minimal residual disease after allogeneic transplantation. In this
study, we assessed the utility and performance of this emerging
technique in the diagnostic setting by examining genomic DNA
extracted from PBMC’s and paraffin-embedded or fresh tissue
specimens with TCR HTS, as compared to standard diagnostic
TCR PCR and flow cytometry in 20 patients with MF/ SS. These
results are compared to reactive inflammatory conditions. TCR
HTS confirmed identical dominant sequences in blood and/
or skin in all cases where a clonal process was suggested by
TCR PCR and/or flow cytometry. Furthermore, TCR HTS was
able to identify tumor clones where standard TCR PCR failed to
demonstrate clear evidence of clonality.
A comparative analysis of the clinical, histologic,
and molecular features of proliferative nodules and
melanoma
Pedram Gerami, BS, MD
Pedram Gerami, BS, MD1
1
Northwestern University, Chicago, Illinois, USA
Proliferative nodules which commonly occur in congenital nevi
in children can have many overlapping histologic features with
melanoma, including high grade cytologic atypia, frequent
mitotic activity, and expansile nodular growth. Distinguishing
benign proliferative nodules from melanoma has significant
consequences as proliferative nodules maybe large deep and
bulky and if misclassified as melanoma would have an elevated
Tumor stage. This could result in unnecessary aggressive
surgical and possibly medical management of an infant or young
child. In this study we reviewed the clinical, histomorphologic
and molecular findings from 22 proliferative nodules and compare
them to three lethal melanomas developing in congenital nevi
of children. We present the typical clinical findings from the
proliferative nodules, the spectrum of morphologic changes
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ASDP
annual meeting
st
The American Society of Dermatopathology
Oral Abstract Session 3
including findings such as epithelioid blue nevus like nodules,
rhabdomyosarcomatous changes, undifferentiated spindle cell
nodules, spitzoid nodules and other patterns and compare
these to the lethal melanomas. Among the proliferative nodules,
the average mitotic count was 4.5 and ranged from 0 to 20.
Expansile nodular growth was present by definition, 2 of 22
cases showed severe nuclear atypia and 2 of 22 cases resulted
in ulceration. In the lethal melanomas the average mitotic count
was 10 and three cases had uniformly high grade/severe nuclear
atypia throughout and 2 of the 3 cases had ulceration. We also
report the results of molecular analysis with FISH and CGH for
copy number changes in both the proliferative nodules and the
melanoma group. The proliferative nodules were either negative
for copy number changes or had whole copy number changes or
a limited number of partial chromosomal copy number changes.
Alternatively the lethal melanomas had significantly more
complex karyotypes with 2 of the 3 lethal melanoma having more
than 4 partial chromosomal copy number aberrations.
29
Abstract Book Oral Presentations

第527回難研セミナー/第100回難治疾患共同研究拠点セミナー（2014年

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Tolerability and encouraging clinical activity of SHP

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DERMATOPHILOSIS IN CROSS

Early Detection, Causes and Screening of Oral

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