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Invasive Cystic Hypersecretory Carcinoma of the Breast
Wentao Yang, MD, Ph.D.
Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China
E-Mail: [email protected]
Clinical features
A 37-year-old woman presented with persistent induration and tenderness in the right
breast. Physical examination revealed a tender, palpable, ill-defined dense area in the
upper quadrant of right breast. Mammography showed heterogeneous dense breast that
corresponded to the area of palpable abnormity. Ultrasound revealed an ill-defined
heterogenous hypoechoic area in the entire outer quadrant of the right breast. A
lumpectomy was performed first. After confirmed as cystic hypersecretory carcinoma
(CHC) with invasion, right mastectomy and axillary lymph node dissection was
performed.
Morphology
Gross examination:
Grossly, a 9.06.03.0cm, ill-defined, gray-tan lesion with multiple cystic spaces were
found in the submitted lumpectomy specimen. The cystic nodules were of variable size
and filled with light brown, thick, gelatinous secretion. In the mastectomy specimen,
cystic lesion measuring 2.52.52cm was also identified. 17 lymph nodes were found in
the axillary specimen.
Microscopic examination:
Many of the ducts were markedly dilated and contained thick, eosinophilic secretions
resembling thyroid colloid. The secretions were pink, acellular and positive for periodic
acid-Schiff (PAS) staining. Retraction of the secretion from the surrounding epithelium
was a prominent feature. Different morphology was found in the secretion. Most
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secretion was homogenous and eosinophilic. But small punched-out holes were seen in
some part of the secretion. Linear cracking artifact was also present in the secretion.
Cyst rupture resulted in a surrounding inflammatory reaction containing histiocytes and
lymphocytes. The lobules around cystic hypersecretory lesions showed hypersecretory
change with similar intraluminal secretion.
Some of the dilated cysts were lined by a single layer of flat or cuboidal cells devoid of
cytological atypia. Epithelial hyperplasia without any cellular or architectural atypia
was present. The above morphology features were those of cystic hypersecretory
hyperplasia (CHH). CHH with atypia was also observed in the leison. The proliferated
epithelial cells were crowded with enlarged nuclear and hyperchromasia. Nucleoli and
mitotic figures were rare. Short epithelial tufts to complex branching fronds consistent
with micropapillary pattern was observed in atypical CHH, mainly involving part of the
cysts .
Tumor cells in DCIS were crowded with prominent nucleoli and sparse cytoplasm.
Mitotic figures were occasionally found. The DCIS was mainly of micropapillary or
solid pattern with intermediate to high nuclear grade. In the solid area, the ducts did not
contain secretion. Multiple foci of invasive component were present adjacent to DCIS
after thorough sampling. The diameter of the largest invasive foci was 0.6cm. The
invasive component was invasive ductal carcinoma, intermediate grade, with similar
nuclear grade to the adjacent intraductal carcinoma. The invasive carcinoma was of
small solid nest pattern without secretory features. Metastatic carcinoma involved 1 of
17 lymph nodes dissected. Metastatic foci in the axillary lymph node did not contain
prominent secretion.
Immunohistochemistry of this case showed triple-negative phenotype in both in situ and
invasive components. Ki67 was 20% in the invasive component.
Discussion
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CHC was first described by Rosen and Scott in 1984[1]. Since its initial description,
more than 60 cases of CHC have been reported in the literature, majority of which as
intraductal carcinomas. The age of the reported patients ranging from 34-79 years. In
most patients, the presenting symptom has been a mass or other palpable abnormality.
Mammographic findings of intraductal CHC in most cases are reported as an irregular
density with or without associated microcalcification. Ultrasound examination may
show an ill-defined, hypoechoic lesion with internal small cysts or dilated ducts. [2-8].
Grossly, CHC tends to be an ill-defined, firm and visibly distinct, gray-brown to brown
lesion with a number of cysts of variable sizes. The cysts are filled with sticky mucoid
to gelatinous secretions. It is quite difficult to distinguish between CHC from CHH on
gross examination.
Microscopically, cystic hypersecretory lesions of the breast span the morphological
spectrum from CHH to atypical hyperplasia to carcinoma[2]. CHH was lined by
flatterned or stratified cuboidal to columnar epithelium with bland nuclei and without
any evidence of architectural atypia. The cysts are filled with ensinophilic secretions
resembling thyroid colloid which is positive for PAS staining. The secretions appear
retracted from the cyst lining, with exaggerated linear cracking artifact.
Atypical CHH area demonstrates some degree of cytological atypia with epithelial
crowding, enlarged nuclei, loss of nuclear polarity, nuclear hyperchromasia. Mitotic
figures are uncommon. Rigid micropapillary pattern, roman bridge or cribriform pattern
is the most common architectural atypia. CHC is very uncommon, especially for those
with invasion. In CHC, the cysts are lined by malignant-appearing cells with enlarged,
hyperchromatic and/or pleomorphic nuclei. The architectural abnormality was usually
of the micropaillary type or clinging variant. Solid variant can also be identified. In the
published reports, most of the invasive cases were poorly-differentiated with a solid
growth pattern.
The main differential diagnosis includes fibrocystic change, juvenile papillomatosis,
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pregnancy-like hyperplasia, columnar cell lesion, mucocele-like lesion, clinging type
DCIS, mucinous carcinoma and metastatic thyroid carcinoma.
In our case, tumor cells were triple-negative in both in-situ and invasive components. In
the literature, the hormone receptor and HER2 status of CHC are variable. Shin et al
reported that ER and/or PR expression were positive in 80% of their cases. However,
the only microinvasive carcinoma in their series was ER and PR negative in both in situ
and invasive components. In the published reports, most of the CHC were HER2
negative. But Skalova reported HER2 overexpression in 2 of invasive CHC [9].
Since the common coexistence of CHC with CHH and atypical CHH in the same mass,
it can be problematic in core needle biopsy or frozen section diagnosis. As CHC can be
only a small fraction of the whole lesion, if CHH is reported in core neelde biopsy,
further excisional biopsy and extensive sampling is recommended to exclude areas with
atypia or CHC. False negative cases may be encountered with biopsy or excision
specimens if sampling is inadequate. Besides, since the CHH or CHC lesion is usually
ill-defined, it can be challenging with the evaluation of the margin. D'Alfonso et al
recommended that clear margin status should be achieved in CHC cases but not for
CHH cases[8]. Since atypia and CHC could be very focal in a background of CHH, we
consider CHH at the margin worrisome.
Because most reported CHC cases are intraductal, it seems that CHC has an indolent
clinical course with long term disease-free survival. However, CHC tends to behave
aggressively in patients with invasive component. About one-half of the patients with
invasive CHC have metastases in axillary lymph nodes.
References
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Pathol 1984;8:31-41
2) Guerry P, Erlandson RA, Rosen PP. Cystic hypersecretory hyperplasia and cystic
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hypersecretory carcinoma of the breast: pathology, therapy and follow up of 39
patients. Cancer 1988;61:1611-1620
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Philadelphia, PA: Lippincott Williams & Wilkins; 2014.
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