25 January 2006 – Case of the Week #35


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We thank Dr. Lisa A. Cerilli, Assistant Professor of Pathology, University of New Mexico Health Sciences (USA) for contributing this case and the discussion.  We invite you to contribute a Case of the Week by sending an email to

NPernick@PathologyOutlines.com with microscopic images (any size, we will shrink if necessary) in JPG or GIF format, a short clinical history, your diagnosis and any other images (gross, immunostains, EM, etc.) that you have and that may be helpful or interesting.  We will write the discussion (unless you want to), list you as the contributor, and send you a check for $35 (US) for your time after we send out the case.  Please only send cases with a definitive diagnosis. 


Case of the Week #35


Clinical History


A 54 year old woman presented with a large palpable left breast mass in the upper outer quadrant and mild intermittent nipple discharge.  Examination was negative for overlying skin changes or axillary nodal enlargement.  Her older sister had breast cancer at age 55.  An excisional biopsy was performed. 


Image 1: Multiple variably sized cysts, containing an eosinophilic homogeneous secretion similar to colloid in thyroid gland follicles


Image 2:  Many of the cysts are lined by benign-looking flattened epithelium, with dense intervening intracystic stroma


Image 3:  The intraluminal secretions show characteristic microscopic artifacts - fine, parallel cracks and shrinkage of the cyst content with peripheral scalloping


Image 4: Other cysts were lined by multilayered micropapillary intracystic proliferations composed of atypical ductal epithelial cells with highly pleomorphic nuclei


What is your diagnosis? 


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Cystic hypersecretory ductal carcinoma in situ




In 1984 Rosen and Scott described a distinctive, rare form of intraductal carcinoma of the breast, which they called cystic hypersecretory duct carcinoma (1).  To date, less than 40 cases of cystic hypersecretory lesions have been described, mostly as case reports.  Most of these lesions are intraductal carcinomas; however, benign proliferative lesions, called cystic hypersecretory hyperplasia, have also been described.  Some cases of hypersecretory duct carcinoma demonstrate invasive areas of frankly malignant epithelial cells into the stroma (2-4).  Metastases to axillary lymph node have also been reported (2, 4, 5).


The clinical manifestations or mammographic features of cystic hypersecretory lesions are non-specific.  They consist of a palpable breast mass and occasionally nipple discharge.  There is a mammographic asymmetric density, with occasional microcalcifications.


Grossly, cystic hypersecretory hyperplasia and carcinoma are indistinguishable and they resemble juvenile papillomatosis of the breast.  There is a large, ill-defined firm to rubbery spongy mass of fibrous tissue containing multiple small cysts.  One diagnostic hint is the presence of abundant thick, sticky mucin within the cysts.


Cystic hypersecretory lesions are composed entirely of cystic structures of various sizes, some quite large and convoluted.  The cystic material resembles colloid, often with parallel fracture lines, a retraction halo around the intraluminal contents, and overlapping due to processing.  The cyst wall lining varies from a bland, attenuated low cuboidal, simple epithelium to a highly tufted, micropapillary proliferation.  These latter areas warrant a diagnosis of ductal carcinoma in situ.  In their absence, a diagnosis of cystic hypersecretory hyperplasia is rendered.  These lesions should be generously sampled to exclude the presence of an invasive component.


The histological differential diagnosis includes benign intraductal proliferative lesions, juvenile papillomatosis, mucocele-like lesions, mucinous cystadenocarcinoma, columnar cell lesions, secretory carcinoma, and pregnancy-like hyperplasia.  However, the microscopic features on excision are invariably specific enough to avoid misinterpretation. 


Cystic hypersecretory ductal carcinoma of the breast represents a diagnostic pitfall on fine needle aspiration (FNA).  The multicystic appearance and often bland cytological features can cause a false-negative diagnosis of fibrocystic changes.   Most reported FNA cytology cases are either negative or reveal cells suggestive of malignancy, without the possibility of establishing a specific diagnosis (3, 4).  If abundant thyroid colloid-like secretions accompanying atypical cells are aspirated, this diagnosis can be considered.


In summary, cystic hypersecretory ductal carcinoma of the breast is a rare distinctive variant of ductal carcinoma in situ that typically behaves in a low-grade fashion for many years, but nevertheless has a potential for invasive growth and metastases.   Challenges include differentiation from other breast lesions, recognition by cytologic examination, and avoiding underdiagnosis as a benign proliferative breast lesion on limited histological material.




1.  Rosen PP, Scott M.  Cystic hypersecretory duct carcinoma of the breast.  Am J Surg Pathol 1984;8:31.


2.  Shin SJ, Rosen PP.  Carcinoma arising from preexisting pregnancy-like and cystic hypersecretory hyperplasia lesions of the breast: a clinicopathologic study of 9 patients.  Am J Surg Pathol 2004;28:789.


3.  Resetkova E, Padula A, Albarraccin CT, Sneige N.  Pathologic quiz case: a large, ill-defined cystic breast mass.  Invasive cystic hypersecretory duct carcinoma.  Arch Pathol Lab Med 2005;129:e79.


4.  Skalova A, Ryska A, Kajo K, Kinkor Z.  Cystic hypersecretory carcinoma: rare and potentially aggressive variant of intraductal carcinoma of the breast.  Report of five cases.  Ceska Gynekol 2005;70:73.


5.  Guerry P, Erlandson RA, Rosen PP.  Cystic hypersecretory hyperplasia and cystic hypersecretory duct carcinoma of the breast.  Pathology, therapy, and follow-up of 39 patients.  Cancer 1988;61:1611.







Nat Pernick, M.D.
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