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Glycogen-Rich Clear Cell Carcinoma of Breast


Microscopic pathology image showing clear cell carcinoma.

What are the other Names for this Condition? (Also known as/Synonyms)

  • Glycogen-Rich (Clear Cell) Carcinoma of Breast
  • GRCC of Breast
  • Mammary Glycogen-Rich (Clear Cell) Carcinoma

What is Glycogen-Rich Clear Cell Carcinoma of Breast? (Definition/Background Information)

  • Breast cancer is the most common type of cancer diagnosed in women. It is a type of cancer in which certain cells in the breast become abnormal, grow uncontrollably, and form a malignant mass (tumor). There are various types of breast cancers which include ductal carcinoma and lobular carcinoma
  • Glycogen-Rich Clear Cell Carcinoma (GRCC) of Breast is a rare type of carcinoma of breast, which is mostly observed in women after the age of 40 years. A majority of the cells of this tumor have glycogen in their cytoplasm, which can be observed during a histopathological examination of a breast biopsy specimen by the pathologist
  • The signs and symptoms of Glycogen-Rich Clear Cell Carcinoma of Breast, which resembles ductal carcinoma NOS, include the presence of a lump in the breast, swelling or skin thickening around the region of the lump, and change in breast profile
  • Complications from this cancer type includes the spread of cancer from the breast to other locations and treatment side effects that may include nausea, vomiting, and hair loss
  • In order to treat Glycogen-Rich Clear Cell Carcinoma of Breast, the healthcare provider may use a combination of therapies that may include surgery, chemotherapy, radiation therapy and targeted therapy, depending on the stage of the tumor
  • The prognosis of Glycogen-Rich Clear Cell Carcinoma of Breast is much worse than ductal carcinoma. An early diagnosis and adequate treatment can significantly improve the outcomes

Who gets Glycogen-Rich Clear Cell Carcinoma of Breast? (Age and Sex Distribution)

  • Glycogen-Rich Clear Cell Carcinoma of Breast represents approximately 1-3% of all breast cancer types
  • GRCC of Breast is generally seen in middle-aged and older adults in the 41-78 year age category; younger individuals (up to 30 years) may be affected. The mean age of presentation is around 57 years
  • All racial and ethnic groups are affected and no specific predilection is seen
  • Developed countries (the affluent nations) show a higher prevalence rate for breast cancer than developing countries. Thus, America, Europe, Australia have greater incidences than Asia (including India, China, and Japan) and Africa

What are the Risk Factors for Glycogen-Rich Clear Cell Carcinoma of Breast? (Predisposing Factors)

The risk factors for Glycogen-Rich Clear Cell Carcinoma of Breast may include:

  • Gender: Women have a higher risk for developing the condition than men
  • Age: The risk increases for women over the age of 40 years
  • History of breast cancer
  • Family history of breast cancer: Women with a mother, sister, or daughter diagnosed with breast cancer have a higher risk of developing the condition
  • Inherited gene mutations: Mutations in certain genes (BRCA1 or BRCA2), can lead to a much higher risk
  • Radiation therapy: Receiving radiation therapy to the chest or breast area can also increase the risk
  • Obesity: Being overweight or obese increases the risk after menopause
  • Alcohol consumption
  • Menstrual cycle: Women who got their period before the age of 12 years, and those who reached menopause after age 55 have a higher risk. The longer the duration between menarche and menopause, the greater is the risk. This is due to hormonal influences during the reproductive period on the breast tissue
  • Postmenopausal hormone therapy: Women taking hormone replacement therapy medications containing both estrogen and progesterone for menopause, have a higher risk of developing breast cancer
  • Reproductive history: Having the first child after the age of 35, or never having a child
  • Physical inactivity: A lack of physical exercise (leading a sedentary life), can increase your risk
  • Not breastfeeding the child

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases ones chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Glycogen-Rich Clear Cell Carcinoma of Breast? (Etiology)

The exact cause of development of Glycogen-Rich Clear Cell Carcinoma of Breast is currently not clearly known.

  • Studies have shown that such tumors may be caused by hormonal influence
  • Certain gene mutations have also been reported in the tumors. Research is being performed to determine how these mutations contribute to the formation of the tumors

Some reports indicate that GRCC may be a variant of apocrine carcinoma.

What are the Signs and Symptoms of Glycogen-Rich Clear Cell Carcinoma of Breast?

The signs and symptoms of Glycogen-Rich Clear Cell Carcinoma of Breast may be similar to that of ductal carcinomas (NOS type) and may include:

  • A lump in the breast or underarm area; size range of the tumor is between 1-8 cm
  • The tumors are hard/firm when felt by touch
  • Thickening or swelling of part of the breast; change in the size or shape of the breast
  • Inversion of the nipple (pulling-in of nipple into the breast)
  • Bloody discharge from the nipple
  • Changes to the skin covering the breast or nipple area, including dimpling, irritation, redness, scaling, peeling, or puckering
  • In some cases, pain in the breast

How is Glycogen-Rich Clear Cell Carcinoma of Breast Diagnosed?

Glycogen-Rich Clear Cell Carcinoma of Breast may be diagnosed in the following manner:

  • Complete physical examination with comprehensive medical and family history evaluation
  • The following information may be sought by the healthcare provider:
    • Family history of breast cancer and ovarian cancer
    • Family history of BRCA 1 or BRCA 2 mutation
    • History of pregnancy
    • History of breastfeeding (lactational history)
    • Prior history of breast cancer (if any)
    • Prior history of breast trauma
    • Prior history of breast biopsy/surgery; history of any breast implantation may also be included
    • History of radiation therapy (in the past)
    • History of chemotherapy (in the past)
    • History of hormonal therapy (in the past)
    • History of autoimmune disorders
  • Breast exam to check for any lumps or unusual signs in the breasts
  • Blood tests including complete blood count (CBC)
  • Mammogram: A mammogram uses X-rays to provide images of the breast. These benign tumors are identified as a mammogram mass, which may or may not be associated with microcalcification. The mammography findings may raise enough suspicion to warrant a tissue biopsy
  • Galactography: A mammography using a contrast solution, mostly used to analyze the reason behind a nipple discharge
  • Breast ultrasound scan: Using high-frequency sound waves to produce images of the breast, the type of tumor, whether fluid-filled cyst or solid mass type, may be identified
  • Computerized tomography (CT) or magnetic resonance imaging (MRI) scan of the breast
  • Positron emission tomography (PET) scan to help determine, if the cancer has spread to other organ systems
  • Breast biopsy:
    • A biopsy of the tumor is performed and sent to a laboratory for a pathological examination. A pathologist examines the biopsy under a microscope. After putting together clinical findings, special studies on tissues (if needed) and with microscope findings, the pathologist arrives at a definitive diagnosis. Examination of the biopsy under a microscope by a pathologist is considered to be gold standard in arriving at a conclusive diagnosis
    • Biopsy specimens are studied initially using Hematoxylin and Eosin staining. The pathologist then decides on additional studies depending on the clinical situation
    • Sometimes, the pathologist may perform additional studies, which may include immunohistochemical stains and molecular studies to assist in the diagnosis

Biopsies are the only methods used to determine whether an abnormality is benign or cancerous. These are performed by inserting a needle into a breast mass and removing cells or tissues, for further examination. There are different types of biopsies:

  • Fine needle aspiration biopsy (FNAB) of breast mass: In this method, a very thin needle is used to remove a small amount of tissue. FNAB cannot help definitively diagnose GRCC of Breast. It only helps determine if the tumor is malignant or benign. This can help the healthcare provider discuss and plan the next steps (with respect to diagnosis and treatment)
  • Core needle biopsy of breast mass: A wider needle is used to withdraw a small cylinder of tissue from an abnormal area of the breast. A definitive diagnosis on a core biopsy may be difficult. Hence, a follow-up surgical procedure to obtain a larger breast biopsy specimen (such as through a lumpectomy) is often performed
  • Open tissue biopsy of breast mass: A surgical procedure used less often than needle biopsies, it is used to remove a part or all of a breast lump for analysis

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Glycogen-Rich Clear Cell Carcinoma of Breast?

The complications of Glycogen-Rich Clear Cell Carcinoma of Breast may include:

  • Emotional distress due to the presence of breast cancer
  • Metastasis of the tumor to local and regional sites; metastasis to axillary lymph nodes is generally seen at a higher rate than ductal breast cancers
  • Side effects of chemotherapy, which may include nausea, vomiting, hair loss, decreased appetite, mouth sores, fatigue, low blood cell counts, and a higher chance of developing infections
  • Side effects of radiation therapy that may include sunburn-like rashes, where radiation was targeted, red or dry skin, heaviness of the breasts, and general fatigue
  • Lymphedema (swelling of an arm) may occur after surgery or radiation therapy, due to restriction of flow of lymph fluid resulting in a build-up of lymph. It may form weeks to years after treatment that involves radiation therapy to the axillary lymph nodes

How is Glycogen-Rich Clear Cell Carcinoma of Breast Treated?

Treatment options available for individuals with Glycogen-Rich Clear Cell Carcinoma of Breast are dependent upon the following:

  • Type of cancer
  • The staging of the cancer
  • Whether the cancer cells are sensitive to certain particular hormones, and
  • Personal preferences

In general, breast cancer stages range from 0 to IV. 0 may indicate a small and non-invasive cancer, while IV indicates that the cancer has spread to other areas of the body. Briefly, as per National Cancer Institute (at the National Institutes of Health), breast cancer is staged as follows:

  • Stage 0 (carcinoma in situ): The abnormal cancer cells are confined to their site of origin (the breast duct linings, lobules, or nipples)
  • Stage I: The tumor is 2 centimeters in diameter or less, and has not spread outside the breast
  • Stage II: The tumor may be up to 5 centimeters in diameter and may have spread to lymph nodes. Another criteria is that the tumor may be larger than 5 centimeters in diameter, but has not spread to surrounding lymph nodes
  • Stage III: The tumor may be more than 5 centimeters in diameter and may have spread to several axillary lymph nodes, or to the lymph nodes near the breastbone. The cancer may also have spread to the breast skin/chest wall, causing ulcer-like sores, or a swelling
  • Stage IV: The tumor has spread outside the breast and to other organs, such as the bones, liver, lungs, or brain, regardless of its size

If breast cancer is diagnosed, staging helps determine whether it has spread and which treatment options are best for the patient.

Surgery: Surgery is the most common form of treatment involving the removal of the tumor. Various types of surgery, to remove the cancer include:

  • Lumpectomy: Breast-sparing surgery (least invasive breast cancer surgery) in which the tumor, as well as a small portion of the surrounding tissue is removed
  • Mastectomy: Surgery to remove all of the breast tissue; it may be simple (removal of the breast, nipple, areola, sentinel lymph nodes) or radical mastectomy (removal of the breast, nipple, areola, all axillary lymph nodes, and underlying muscle of the chest wall)
  • Sentinel node biopsy: Procedure done to examine the “sentinel lymph node,” or lymph node(s) closest to the tumor, as this is the most likely location, where cancer cells may have spread to. This lymph node is removed and tested for cancerous cells
  • Axillary node dissection: This procedure is performed to remove some axillary lymph nodes in the underarm area, to allow dissection and examination. This helps in establishing whether the cancer has spread to more than one lymph node

Chemotherapy: Using the help of drugs to either kills the cancer cells or shrink the tumor.

  • Chemotherapy may be recommended after surgery, for a tumor with a high probability of returning or metastasizing (spreading) in what is termed as adjuvant chemotherapy. The procedure kills any remaining cancer cells, following a surgery for the cancer
  • Chemotherapy may also be suggested before surgery, for women with large cancers to reduce the size of the tumor. This allows for easier removal during surgery and is termed neoadjuvant chemotherapy
  • The use of chemotherapy is also an option for women with advanced cancer, which that has already spread outside the breast

Radiation therapy: Using high-energy beams, including x-rays, radiation therapy aims to kill cancerous cells.

  • Radiation therapy can be done externally (external beam radiation) using a large machine, to target rays at the cancerous area
  • It may also be administered internally (internal beam radiation) using a radioactive substance that collects at the site, where the cancer originated
  • It is commonly recommended after a lumpectomy, when the cancer is still in its early stages

Hormone therapy:

  • Hormone therapy is typically recommended for estrogen receptor positive (ER positive) or progesterone receptor positive (PR positive) breast cancers. The cells of these cancers are receptive to hormones, which help stimulate cancer growth
  • Hormone therapy drugs act as inhibitors or blockers, preventing cancer cells from receiving the hormones needed, to promote their development
  • Tamoxifen, the most common hormone therapy drug, works by blocking estrogen from binding to the estrogen receptors on cancer cells. It thus prevents cancer cells, from receiving signals to grow and multiply. Side effects may include hot flashes, night sweats, or vaginal discharge. More serious risks include blood clots, stroke, or uterine cancer
  • Aromatase inhibitors, stop the production of estrogen in postmenopausal women. Thus, lower levels of estrogen are available to promote cancer cell growth. Examples of these inhibitors include anastrozole, letrozole, and exemestane. Possible side effects may include joint or muscle pain, and a higher risk for osteoporosis
  • In premenopausal women, surgery to remove the ovaries is an option to prevent estrogen production, as the ovaries are the main source of estrogen, before menopause

Targeted therapy: Targeted therapy drugs attack cancer cells in a specific manner.

  • Trastuzumab (Herceptin) is a drug that targets human growth factor receptor 2 (HER2), a protein that is made by some breast cancer cells to stimulate their growth, blocking HER2 causes cancer cells to die off. Side effects may include heart damage, headaches, nausea, vomiting, skin rashes, and breathing problems
  • Lapatinib (Tykerb) is a targeted therapy drug that targets HER2 proteins, to help slow the growth of cancer cells. Lapatinib is usually recommended after other treatment options have been attempted, but have been found ineffective in slowing the cancer progress. Side effects may include nausea, vomiting, diarrhea, mouth sores, fatigue, pain in the hands and feet, and skin rashes
  • Bevacizumab (Avastin) works by preventing the tumors from creating new blood vessels that could nourish the tumor, cutting off the supply of nutrients to cancer cells. Potential side effects may include high blood pressure, fatigue, headaches, heart or kidney damage, slow healing of wounds, mouth sores, and blood clots

How can Glycogen-Rich Clear Cell Carcinoma of Breast be Prevented?

The following measures may help in reducing the risk for Glycogen-Rich Clear Cell Carcinoma of Breast:

General lifestyle changes:

  • Maintain a healthy weight and exercise regularly; physical activity can reduce risk, especially in post-menopausal women
  • Implement and follow a well-balanced diet; a high intake of fiber via fresh fruits and vegetables can reduce the risk
  • Drink alcohol in moderation; limit to one or (maximum) two drinks a day
  • Limit combination hormone therapy used to treat symptoms of menopause. It is advised that individuals be aware of the potential benefits and risks of hormone therapy
  • Cancer screenings can help detect any breast cancer, at its earliest stages
  • Learn to do ‘breast self-exams’, in order to help identify any unusual lumps, signs in the breasts

In women with a high risk for developing Glycogen-Rich Clear Cell Carcinoma of Breast, the physician may suggest the following:

  • Preventative medications: The medications tamoxifen and raloxifene (Evista) are estrogen-blocking drugs that can help prevent the onset of breast cancer in women at high risk. Both drugs have potential side effects; including being at a higher risk for blood clots
  • Preventative mastectomy: Prophylactic mastectomy, a procedure to surgically remove healthy breasts, is another possible preventative option for women, at a high risk for breast cancer 

What is the Prognosis of Glycogen-Rich Clear Cell Carcinoma of Breast? (Outcomes/Resolutions)

  • Glycogen-Rich (Clear Cell) Carcinoma of Breast is a type of invasive breast cancer. Even though it presents similarity to ductal carcinomas (non-specific type), current reports indicate that the prognosis of GRCC is much worse than ductal carcinomas (though some studies seem to indicate that they are nearly the same)
  • The prognosis of breast cancer, in general, depends upon a set of several factors that include:
    • The grade of the breast tumor such as grade1, grade2, and grade 3. Grade1 indicates a well-defined tumor, whereas grade 3 indicates a poorly-defined tumor
    • The size of the breast tumor: Individuals with small-sized tumors fare better than those with large-sized tumors
    • Stage of breast cancer: With lower-stage tumors, when the tumor is confined to site of origin, the prognosis is usually excellent with appropriate therapy. In higher-stage tumors, such as tumors with metastasis, the prognosis is poor
    • Hormone-receptor status of the breast cancer such as estrogen receptor (ER), progesterone receptor (PR), and HER2/neu
    • Presence of tumor indicators, such as HER2 proteins (growth-promoting proteins). In general, if the tumor produces HER2/neu proteins, the prognosis is worse
    • Cell growth rate of breast cancer
    • Menopausal status
    • Overall health of the individual: Individuals with overall excellent health have better prognosis compared with those with poor health
    • Age of the individual: Older individuals generally have poorer prognosis than younger individuals
    • Individuals with bulky disease of the breast cancer have a poorer prognosis
    • Involvement of the lymph node, which can adversely affect the prognosis
    • Involvement of vital organs may complicate the condition
    • The surgical respectability of the tumor (meaning, if the tumor can be removed completely)
    • Whether the tumor is occurring for the first time, or is a recurrent tumor. Recurring tumors have worse prognosis compared to tumors that do not recur
    • Response to treatment of breast cancer: Tumors that respond to treatment have better prognosis compared to tumors that do not respond to treatment
    • Progression of the condition makes the outcome worse
  • An early diagnosis and prompt treatment of the tumor generally yields better outcomes than a late diagnosis and delayed treatment
  • The combination chemotherapy drugs used, may have some severe side effects (like cardio-toxicity). This chiefly impacts the elderly adults, or those who are already affected by other medical conditions. Tolerance to the chemotherapy sessions is a positive influencing factor

Additional and Relevant Useful Information for Glycogen-Rich Clear Cell Carcinoma of Breast:

  • Japan is an exception of a developed nation with lowered cases of breast cancer, unlike European nations and America
  • Current studies have shown that aromatase inhibitors, medications that block estrogen hormonal effects in the body, reduce the risk of recurrence of breast cancer. Recent studies (ASCO 2016, Chicago) have shown that treatment using aromatase inhibitors can be given up to 10 years without affecting the quality of life of women
  • Tumors that are negative for estrogen receptor, progesterone receptor, and HER2/neu have worse prognosis. Such tumors are called “triple-negative” tumors

The following DoveMed website links are useful resources for additional information:



References and Information Sources used for the Article:

Lakhani, S. R. (Ed.). (2012). WHO classification of tumours of the breast. International Agency for Research on Cancer.

http://womenshealth.gov/breast-cancer/what-is-breast-cancer/index.html (accessed on 06/20/16)

http://www.cdc.gov/cancer/breast/basic_info/index.htm (accessed on 06/20/16)

http://www.mayoclinic.com/health/breast-cancer/DS00328 (accessed on 06/20/16)

http://breast-cancer.ca/glyc-riches/ (accessed on 06/20/16)

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2386120/ (accessed on 06/20/16)

Helpful Peer-Reviewed Medical Articles:

Malla, S., Shakya, G., Regi, S., & Mudvari, D. S. (2008). Glycogen rich clear cell carcinoma of breast. Journal of Nepal Health Research Council,6(2), 117-119.

Mudvari, D. S., Malla, S., Shakya, G., & Regi, S. (2009). Glycogen Rich Clear Cell Carcinoma of Breast. Journal of Nepal Health Research Council.

Markopoulos, C., Mantas, D., Philipidis, T., Kouskos, E., Antonopoulou, Z., Hatzinikolaou, M. L., & Gogas, H. (2008). Glycogen-rich clear cell carcinoma of the breast. World journal of surgical oncology, 6(1), 1.

Gürbüz, Y., & Özkara, S. K. (2003). Clear cell carcinoma of the breast with solid papillary pattern: a case report with immunohistochemical profile.Journal of clinical pathology, 56(7), 552-554.

Tavassoli, F. A., & Devilee, P. (2003). Pathology and genetics of tumours of the breast and female genital organs. Iarc.

Murakata, L. A., Ishak, K. G., & Nzeako, U. C. (2000). Clear cell carcinoma of the liver: a comparative immunohistochemical study with renal clear cell carcinoma. Modern Pathology, 13(8), 874-881.

Takekawa, Y., Kubo, A., Morita, T., Kameda, K., Kimura, M., Sakakibara, M., ... & Yamashita, Y. (2006). Histopathological and immunohistochemical findings in a case of glycogen-rich clear cell carcinoma of the breast.Rinsho byori. The Japanese journal of clinical pathology, 54(1), 27-30.

Akbulut, M., Zekioglu, O., Kapkac, M., Erhan, Y., & Ozdemir, N. (2008). Fine needle aspiration cytology of glycogen-rich clear cell carcinoma of the breast. Acta cytologica, 52(1), 65-71.


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