Glycogen-rich clear cell carcinoma of the breast

Glycogen-rich clear cell breast carcinoma is a rare neoplasm, which accounts for approximately 2% to 3% of all cases of breast cancers.

These breast tumors have a distinct morphology quite distinct from the more common breast cancers. However, glycogen-rich clear cell cancer of the breast shares certain characteristics with clear cell carcinomas of the:-

kidneys
salivary glands
lung
endometrium
cervix
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This page is a little bit out-of-date, but still very useful.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 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 carcinoma breast-xray

Specialists consider glycogen-rich clear cell breast carcinoma to be a member 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 cancer of the breast tend to range in age from 35 to 78 years. However, the average age for the development of this type of cancer is about 52 years.

Clear Cytoplasm, as a result of the abundant Glycogen

Glycogen-rich clear cell breast cancer is generally composed of many cells containing abundant glycogen, and this usually results in clear cytoplasm.

Pathologists extract this glycogen when processing the tissue for histological sections, leaving vacuolated cytoplasm.

Cells with clear, vacuolated cytoplasm are rarely found in benign breast lesions, such as:-

clear cell hidradenoma
eccrine spiradenoma
acrospiroma
benign mammary myoepithelioma

So, one has to be suspicious for glycogen-rich clear cell breast cancer when these elements are present. Certain histological characteristics of the tumor will tend to confirm the diagnoisis.

Clinical and Mammographic features

Like other breast cancers, the glycogen rich clear cell type often presents as a mass. Sometimes there is also 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

Doctors can sometimes misdiagnose glycogen-rich clear cell breast cancer as a fibroadenoma from a screening mammogram.

glycogen-rich-clear-cell-breast-carcinoma-mri

The x-ray image above shows a lobulated, circumscribed mass with no evidence of malignancy, more suggestive of a fibroadenoma.

Later, however, additional tests show the mass to be an early-stage glycogen-rich clear cell cancer. The subtraction MRI image below reveals a well defined glycogen-rich clear cell breast tumor. Histological evaluation later confirms the diagnosis.

Histological Features

The malignant cells of glycogen rich clear cell cancer tend to have:-

an average size
well-defined borders
polygonal, rather than rounded contours.

glycogen-rich-clear-cell-breast-carcinoma-cells

These tumor cells are often moderately pleomorphic.

In addition, the cells in glycogen rich clear cell breast cancers will often form a matrix of solid, lobular, acinar and rarely papillary areas. Quite often there will be 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 common. 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 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
Cytokeratin 7

Conversely, the cells in glycogen rich clear cell carcinoma of the breast will often test negative for:-

c-erb-b2 (score 0)
Cytokeratin 20
melanosomes
vimentin.

Glycogen rich clear cell breast tumors will tend to be also 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 in most cells. So, this indicates a certain degree of neuroendocrine activity in some of these tumors.

Usually, glycogen rich clear cell carcinoma of the breast 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, when all other ‘stage-matching’ elements are 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

The treatment for most patients with glycogen-rich clear cell carcinoma of the breast is a mastectomy and axillary dissection.

In addition, doctors may often prescribe an aromatase inhibitor at the time of surgery. More than half of these breast cancers develop metastatic tumors 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 carcinoma of the breast that demonstrate a favorable outlook.

References

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 of divergent 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
1987 Aug;11(8):857-69.
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.