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25 January 2006 - Case #35

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This case was contributed by Dr. Lisa A. Cerilli, Assistant Professor of Pathology, University of New Mexico Health Sciences, USA.


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Case #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

Microscopic images:



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Diagnosis: Cystic hypersecretory ductal carcinoma in situ

Discussion:
In 1984 Rosen and Scott described a distinctive, rare form of intraductal carcinoma of the breast, which they called cystic hypersecretory duct carcinoma (Am J Surg Pathol 1984;8:31). To date, < 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 (Am J Surg Pathol 2004;28:789, Arch Pathol Lab Med 2005;129:e79, Ceska Gynekol 2005;70:73). Metastases to axillary lymph node have also been reported (Am J Surg Pathol 2004;28:789, Ceska Gynekol 2005;70:73, Cancer 1988;61:1611).

The clinical manifestations or mammographic features of cystic hypersecretory lesions are nonspecific. 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 (Arch Pathol Lab Med 2005;129:e79, Ceska Gynekol 2005;70:73). 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.

References: Am J Surg Pathol 1984;8:31, Am J Surg Pathol 2004;28:789, Arch Pathol Lab Med 2005;129:e79, Ceska Gynekol 2005;70:73, Cancer 1988;61:1611


Image 01 Image 02