Signet Ring Cell carcinoma of the Breast
Specialists originally grouped signet ring cell carcinoma as a variation of mucinous carcinoma. However, signet ring cell carcinoma was later recognized as a distinctive cancer subtype.
The most striking feature of signet ring cell carcinoma, aside from the characteristic ‘signet-ring’ shape of the cells, is the abundant accumulation of intracellular mucin. Signet ring cell carcinoma of the breast accounts for only between 2% and 4.5% of all breast cancers.
I would like to inform you that I have a newer version of this page with more up-to-date information. However, this page is still a good summary.
In terms of clinical presentation, the average age of patients with signet ring cell carcinoma of the breast tends tend to be a little older than for other breast cancers. Quite often, women with signet ring cell breast cancer also present with a more advanced disease state.
Signet ring cells occur in various types of cancer, not just breast cancer
Signet Ring cells can actually occur in many different types of cancer tumors. Signet-ring cells tend to arise in tumors that originate in the glands. When a cancer pathologist sees signet ring cells in a breast tumor, they tend to immediately think of lobular breast carcinoma, rather than ductal carcinoma.
Medics sometimes misdiagnose signet ring cell carcinoma of the Breast
It is quite easy to either miss or misdiagnose signet ring cells in a tumor because they are very small and often seem inconspicuous in the tissue.
For patients with lobular carcinoma, the doctors will usually have a close inspection of the lymph nodes. This is because often signet ring cells are located in the lymph nodes.
Signet-ring cell carcinoma of the breast is a subtype of adenocarcinoma
Signet-ring cell breast carcinoma is really a unique subtype of mucin-producing adenocarcinoma. Indeed, this type of cancer can arise in virtually any organ. For example, the breast, stomach, and colon.
However, signet ring cell carcinoma nonetheless comprises about 90% of all cases of this particular cancer subtype. A majority of breast signet-ring cell carcinomas are in fact infiltrating lobular carcinomas, although ductal carcinomas are not uncommon.
Diagnosis of breast signet ring cell carcinoma
Signet ring cell carcinoma is given the name because the cells under a microscope look like a signet ring. The nucleus appears to be ‘pushed over’ (kind of like a stone in a ring). So, the remainder cell membrane actually forms the outside ‘ring’ shape.
Usually the cells appear small and uniform under the microscope. They are composed of a clear, vacillated cytoplasm with a compressed nucleus situation at the base of the cell. Signet ring cells can take up as much as 99% of a breast cancer lesion, but often occur in a lesser proportion.
Specialists will call a tumor, a signet ring cell carcinoma if the amount of signet ring cells is ‘significant’ enough. However, this is a little bit of a judgement call.
Some people still use the term signet ring cell carcinoma when there are as little as 20% signet ring cells. Generally speaking nowadays the term signet ring cell breast carcinoma would not be used unless the signet ring cells comprise between 20% and 50% of the tumor mass. However, 50% of signet cell rings seems to be the most common figure in usage. The specific label would, of course, also depend upon other findings and characteristics of the tumor.
Metastasis shows a unique aspect of signet ring cell carcinoma of the breast
One of the unique aspects of breast signet-ring cell carcinoma is its pattern of metastasis.
A significantly greater number of metastatic breast signet ring cell carcinomas are found in the
- gastrointestinal tract,
- gynecologic organs
than in just about any other type of breast cancer.
Studies have also shown that metastatic signet ring cell carcinoma will have virtually the same immunohistochemical profile as the primary breast carcinoma.
But regardless of the site of origin of signet ring cell carcinoma (breast, colon, stomach) they are all highly prone to metastasize to the regional lymph nodes, (as well as the ovaries, lung, and peritoneal surfaces).
Breast signet ring cell carcinomas do show a greater extent of axillary lymph node involvement than many other types of breast cancer. When they occur in the lymph nodes they tend to display a ‘sinus catarrh’ pattern.
Histological features common to Signet ring cell breast carcinoma
The biologic hallmark of signet-ring cell carcinoma of the breast is mucin production. There are various different types of mucins (MUC1, MUC2, MUC3, etc.) and different combinations and strengths of mucins have been widely used to histologically differentiate between the various different types of adenocarcinomas.
The nature of this mucin is basically acid mucosubstances consisting mainly of sialomucin with lesser amounts of sulphomucin.
Mucins produced due to the decreased production and thus immunoreactivity for E-cadherin occurs in about 75% of breast lobular carcinomas (with signet ring cells). Most breast signet ring cell carcinomas are positive for estrogen receptors, and negative for E-cadherin, and just about all cases will express MUC1.
Most signet ring cell breast carcinomas also express the CK7 protein. Unlike the other primary sites of signet ring cell carcinoma, breast signet ring cell carcinoma will tend to show intracytoplasmic lunima containing siolomucin, while the other types have more extended and ‘clear’ cytoplasmic acid mucin.
Outlook for patients with signet ring cell carcinoma of the breast
Unfortunately, the prognosis for breast signet ring cell carcinoma is generally poorer than for other breast cancers.
One of the reasons that is important to distinguish between mucinous breast carcinoma and signet ring cell breast carcinoma is because the latter is generally associated with a more aggressive clinical course, and ultimately a poorer prognosis.
- Chu, PG, Wiess, LM. (2002) Immunohistochemical Characterization of Signet-Ring Cell Carcinomas of the Stomach, Breast, and Colon . Am J Clin Pathol2004;121:884-892. https://www.ncbi.nlm.nih.gov/pubmed/15198362
- Liu, SM, Chen DR. (2000) Signet-ring cell carcinoma of the breast. Pathology International, Volume 50, Number 1, January 2000 , pp. 67-70
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