VIN - University of Virginia

11/4/2014
VIN: it’s not so SIMPLE
November 7, 2014
Mary-Margaret B. Noland, M.D.
Assistant Professor Dermatology
University of Virginia Department of Dermatology
PRW Laboratories Dermatopathologist
Vulvar Intraepithelial Neoplasia
• First introduced as a terminology in
1980 by the International Society for
the Study of Vulvar Disease (ISSVD)
– Human Papilloma Virus induced dysplasia
– Classified as VIN I,II, and III (I= mild dysplasia
II=moderate dysplasia, and III= severe dysplasia or
Carcinoma in situ) based on the degree of epidermal
atypia and maturation
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Vulvar Intraepithelial Neoplasia
• Designation to replace prior terminology atypia,
dysplasia, Bowen’s disease, bowenoid papulosis,
erythroplasia of Queyrat, carcinoma in situ, and
carcinoma in situ simplex type
• Revised Classification of VIN in 2004 by the ISSVD
– Suggests the modification/elimination of VIN 1 and reserves VIN for
what was previously VIN2/3- high grade dysplasia (although most
experts still feel that VIN 1 holds value as a diagnostic terminology)
– Breaks VIN down into two subclassifications VIN
classic/usual/basaloid/warty type and VIN differentiated type/simplex
type
– Addresses VIN in both an HPV and HPV negative form
Why the elimination of VIN I?
• Intraobserver variability in diagnosis
• VIN 1 is HPV induced; however, is no
longer considered precancerous.
• Unlike VIN2 and VIN 3, VIN 1 is most
often caused by low risk HPV subtypes 6
and 11 in contrast to high risk HPV
strands, 16,18 (31,33) that are isolated
from VIN 2/3 in over 90%.
• VIN 2/3 show a more direct progression to
squamous cell carcinoma.
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Clinical Presentation of classic/
usual/ warty/ or basaloid VIN
• Multifocal vulvar lesions
• Often associated with other areas of
involvement of the female
genitourinary tract
• Hyperkeratotic papules and plaques,
erythroplasia, leukoplasia, erosions, or
hyperpigmented papules.
VIN 1
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VIN 3
VIN 2/3
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VIN III- Bowenoid Papulosis variant
Histopathology of Classic/Basaloid/
Warty VIN
• Epidermal dysmaturation with 2/3 to
full thickness atypia
• High N:C ratio
• Hyperchromatic, pleomorphic nuclei
• Increased mitotic activity with atypical
mitoses
• P16INK4A positive, P53 negative
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VIN I
VIN 2
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VIN 3
VIN 3
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VIN 3
What is VIN
Simplex/Differentiated Type?
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Clinical Presentation VIN
Differentiated/Simplex Type
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Difficult to recognize and often missed both clinically and
histologically
Under biopsied due to clinical presentation mimicking benign
dermatoses
May mimic prurigo nodules, lichen simplex chronicus, or a
hyperkeratotic area in lichen sclerosis
Most often a solitary lesion within an area of dermatitis- ie
not multifocal.
Occurs in areas of chronic dermatitis, most often patients with
lichen sclerosis, but also in lichen simplex chronicus and
eczematous dermatitis.
Occurs in an older patient population (Mean Age 66.8 years)
Often flanks invasive keratinizing squamous cell carcinoma in
vulvectomy specimens.
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Histopathology of Simplex or
Differentiated
• Highly differentiated form of VIN 3
• Atypia is confined to the basal layer
• Maturation of the superficial layers of the epidermis is
preserved
• Parakeratosis with acanthosis characterized by
elongated and anastamosing rete ridges
• Premature keratinization in the suprabasilar region of
rete ridges with eosinophilic cytoplasm and squamous
pearls
• Prominent intracellular bridges
• Often associated with an underlying chronic
inflammatory infiltrate
• Negative for P16INK4A and the majority show positive
suprabasalar staining for P53
VIN 3 Differentiated/Simplex
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VIN 3 Simplex
VIN 3 Simplex
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VIN 3 Simplex
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So Why does it Matter?
Why does it matter?
• 65% of squamous cell carcinomas of the vulva
are classified as keratinizing type.
• VIN differentiated/simplex type is felt to
represent a direct precursor lesion to
keratinizing squamous cell carcinoma of the
vulva and is often found in vulvectomy
specimens flanking invasive squamous cell
carcinoma.
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Why does it matter?
• Classic VIN 2/3 more commonly progresses to
basaloid squamous cell carcinoma.
• Abell believed that VIN Simplex has a shorter in situ
phase with more rapid evolution to invasive
squamous cell carcinoma than
classic/warty/bowenoid VIN.
• VIN Simplex continues to be under-diagnosed in its
primary form, i.e. unassociated with invasive
squamous cell carcinoma
Speculation and
Recommendations
• Although VIN Simplex is not the most common
form of VIN, it is aggressive and remains difficult
to diagnose.
• VIN Simplex may show a more rapid and direct
progression to invasive squamous cell
carcinoma.
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Speculation and
Recommendations
• Dermatologists should routinely be performing
vulvar exams and can aid in the diagnosis of VIN
Simplex.
•
• Dermatologists are more familiar with the
inflammatory dermatoses of the vulva and may
more easily recognize an anomaly in
presentation.
Speculation and
Recommendations
• Clinicians should have a high degree of suspicion
in patients with background longstanding
inflammation, older patients, or those
unresponsive to conventional treatment.
• Biopsy all vulvar dermatoses not responsive to
conventional treatment in an appropriate time
course.
• Send vulvar biopsies to a dermatopathologist or
GYN pathologist with a strong understanding of
VIN and its variants.
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• Special thanks to Dr. Mark Stoler and
Dr. Barbara Wilson Dr. James
Lampros for their assistance with this
presentation.
References
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Reyes MC1, Cooper K. An update on vulvar intraepithelial neoplasia: terminology and a practical
approach to diagnosis. J Clin Pathol. 2014 Apr;67(4):290-4.
Taube JM1, Badger J, Kong CS, Dadras SS. Differentiated (simplex) vulvar intraepithelial neoplasia: a
case report and review of the literature. Am J Dermatopathol. 2011 May;33(3):e27-30.
Mulvany NJ1, Allen DG. Differentiated intraepithelial neoplasia of the vulva. Int J Gynecol Pathol. 2008
Jan;27(1):125-35.
Ordi J, Alejo M, Fusté V, Lloveras B, Del Pino M, Alonso I, Torné A. HPV-negative vulvar intraepithelial neoplasia
(VIN) with basaloid histologic pattern: an unrecognized variant of simplex (differentiated) VIN. Am J Surg
Pathol. 2009 Nov;33(11):1659-6523.
Hart WR. Vulvar intraepithelial neoplasia: historical aspects and current status. Int J Gynecol Pathol. 2001
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Yang B, Hart WR. Vulvar intraepithelial neoplasia of the simplex (differentiated) type: a clinicopathologic study
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van de Nieuwenhof HP1, Bulten J, Hollema H, Dommerholt RG, Massuger LF, van der Zee AG, de Hullu JA, van
Kempen LC. Differentiated vulvar intraepithelial neoplasia is often found in lesions, previously
diagnosed as lichen sclerosus, which have progressed to vulvar squamous cell carcinoma. Mod
Pathol. 2011 Feb;24(2):297-305.
Mills, SE. Sternberg’s Diagnostic Surgical Pathology. 5th Edition. (51) pp2105-2110.
Robboy S. Robboy’s Pathology of the Female Reporductive Tract 2nd Edition 2008
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