Glycogen-rich clear cell carcinoma of the breast
Glycogen-rich clear cell breast carcinoma is a rare neoplasm, which accounts for approximately 2% – 3% of all cases of breast cancers. These breast tumors have a distinct morphology quite different from the more common breast cancers, but do share certain characteristics with clear cell carcinomas of the kidneys, salivary glands, lung, endometrium, cervix, and ovary.
This page is a little bit out-of-date, but still very useful. However, even though you can still use this page, I have created a newer version that you can use as well, which has more up-to-date information on Glycogen-rich Breast Carcinoma.
Glycogen-rich clear cell breast carcinomas are considered to be members of a heterogeneous group of breast neoplasms which include secretory and lipid-rich carcinomas of the breast and signet-ring breast cancer. Women who develop glycogen-rich clear cell breast carcinoma tend to range in age from 35 to 78 years. The average age for the development of glycogen-rich clear cell carcinoma of the breast is about 52 years.
Clear cytoplasm, as a result of the abundant glycogen
Glycogen-rich clear cell carcinomas of the breast are generally composed with many cells containing abundant glycogen, and this usually results in clear cytoplasm. This glycogen is extracted when the tissue is processed for histological sections, leaving vacuolated cytoplasm.
Cells with clear, vacuolated cytoplasm are rarely found in benign breast lesions, such as clear cell hindradenoma, eccrine spiradenoma, acrospiroma and benign mammary myoepithelioma, so one has to be suspicious for glycogen-rich clear cell breast carcinomas when these elements are present. Certain histological characteristics of the tumor will tend to confirm a glycogen-rich clear cell carcinoma.
Clinical and Mammographic features commonly associated with Glycogen-rich clear cell carcinoma of the breast
Glycogen-rich clear cell carcinoma of the breast often presents with a mass that is sometimes accompanied by skin dimpling, nipple retraction or pain. Most tumors measure between 2 and 5 cm in diameter, but have been found up to 10 cm in clinical examination.
Glycogen-rich clear cell tumors can be mistaken for fibroademona
Glycogen-rich clear cell breast carcinoma can sometimes be originally misdiagnosed as fibroadenoma from a screening mammogram. The x-ray image above shows a lobulated, circumscribed mass with no evidence of malignancy, more suggestive of a fibroadenoma. Later, it was revealed to be an early-stage glycogen-rich clear cell breast carcinoma. The subtraction MRI image below reveals a well defined glycogen-rich clear cell breast tumor, confirmed later on histological evaluation.
Histological features of glycogen rich clear cell breast carcinoma
The malignant cells of glycogen rich clear cell breast carcinoma tend to be of an average size, with well-defined borders and polygonal, rather than rounded contours. Tumor cells are often moderately pleomorphic. Neoplastic cells in glycogen rich clear cell breast cancers will often form a matrix of solid, lobular, acinar and rarely papillary areas, quite often with a fine vascular network in between.
It is not uncommon to see foci of linear, trabecular and tubular growth patterns. The cytoplasm of glycogen rich clear cell breast carcinomas will tend to be clear and curiously placed. Hyperchromatic nuclei with a low mitotic number are also to be expected, but one might encounter cells with mildly eosinophilic cytoplasm, nuclear pleomorphism and higher mitotic number. Necrosis will generally be absent. Light microscopic examination of glycogen rich clear cell breast carcinoma will frequently reveal both intraductal papillary growth and stromal invasion.
Neoplastic cells will usually contain massive quantities of non-membrane-bound particulate glycogen and cells that form numerous acini. Intervening stroma in a glycogen rich clear cell breast carcinoma will often show a moderate degree of chronic inflammatory cell infiltration.
Glycogen rich clear cell breast cancers are frequently ER positive and PR negative
In terms of immunohistochemistry, many of the cells in glycogen rich clear cell breast carcinoma will test positive for keratins, AE1/AE3, EMA and Cytokeratin 7, but often negative for c-erb-b2 (score 0), Cytokeratin 20, melanosomes and vimentin. Glycogen rich clear cell breast tumors will tend to be negative for markers of myoepithelial cells, such as smooth muscle actin-SMA and S-100.
Staining for chromogranin may be positive in some cells and synaptophysin is quite often present most cells, indicating a certain amount degree of neuroendocrine activity some of these tumors. Usually, glycogen rich clear cell breast carcinomas will be strongly positive for estrogen receptors (ER) and negative for progesterone receptors (PgR).
Prognosis and treatment for glycogen-rich clear cell breast cancer
Glycogen-rich clear cell carcinoma of the breast is a rare breast tumor, but tends to have an aggressive clinical course and a poor prognosis. The outlook is similar to or worse than that of ordinary invasive ductal carcinoma, all other ‘stage-matched‘ elements being equal.
The ‘clear cell morphology‘ does not appear to influence the clinical outcome once stage and grade are taken into account. The aggressiveness of glycogen-rich clear cell breast cancer will be moderated by special characteristics of the tumor such as a low grade and strongly positive ER expression.
Once lymph node metastasis occurs, the outlook is less positive
Most patients with glycogen-rich clear cell carcinoma of the breast are treated with mastectomy and axillary dissection. Patients are often treated with an aromatase inhibitor at the time of surgery. More than half of these breast cancers develop metastatic tumor in the axillary lymph nodes.
It is rare for women with glycogen-rich clear cell carcinoma of the breast and axillary lymph node metastases to survive beyond 7 years following the diagnosis. However, there are still many cases of glycogen-rich clear cell breast carcinoma which demonstrate a favorable outlook.
For further reading, I suggest you visit this page which has a little bit of information about lipid-rich breast carcinoma, go to this page as well for the histological workup for breast cancer diagnosis and treatment, and last but not least, this page, that has information on cytoplasm.
- Markopoulos C, Mantas D, Philipidis T, Kouskos E, Antonopoulou Z, Hatzinikolaou M, Gogas H. Glycogen-rich clear cell carcinoma of the breast. World J Surg Oncol. 2008 Apr 29; 6:44.
- Rosen PP: Glycogen-rich carcinoma. Rosen’s Breast Pathology. Lippincot-Raven 2001 , 557-559.
- Toikkanen S, Juensuu H: Glycogen rich clear cell carcinoma of the breast: a clinicopathologic and flow cytometric study. Hum Pathol 1991 , 22(1):81-83.
- Hayes MMM, Seidman JD, Asthon MA: Glycogen rich clear cell carcinoma of the breast. A clnicopathologic study of 21 cases. Am J Surg Pathol 1995 , 19:904-911.
- Hull MT, Priest JB, Broadie TA, Ransburg RC, McCarthy LJ: Glycogen-rich clear cell carcinoma of the breast: a light and electron microscopic study. Cancer 1981 , 48:2003-2009.
- Suzanne ES, Carlos TE, Ian PT, Elaine EW, Brain W. Clear cell carcinoma of the breast with immunohistochemical evidence ofdivergent differentiation. Annals of Diagnostic Pathology 2002 Aug;6(4):250-6.
- Kim WS, Lee WM, Hong EK, Park MH, Lee ID. Fine needle aspiration cytology of glycogen-rich clear cell carcinoma of the breast: A report of two cases. Korean J cytopathology 1998 Dec;9(2):213-9.
- Hyun JS, Sung HS, Sang YL, Woo SM. Glycogen-rich clear cell mammary malignant myoepithelioma. The Breast 2004 Dec;13(6):506-9.
- Sorensen FB, Paulsen SM. Glycogen rich clear cell carcinoma of the breast: a solid variant with mucus, a light microscopic immunohistochemical and ultra structural study of a case. Histopathology
- Di Tommaso, Pasquinelli G, Portincasa G, Santini D. Glycogen-rich clear cell breast carcinoma with neuroendocrine differentiation features. Pathologica 2001;93:675-80.
- Kuroda H, Sakamoto G, Ohnisi K, Itoyama S. Clinical and pathological features of Glycogen-rich clear cell carcinoma of the breast. Breast Cancer 2005;12:189-95.