Small Cell Breast Cancer
Small Cell breast cancer is a very rare, yet highly aggressive variant of a neuroendocrine carcinoma, which sometimes presents in the breast. Small cell cancers most commonly develop in the lung, and then possibly metastasize to the breast, so a full and exhaustive staging study is usually necessary when this type of cancer presents in the breast. Small cell breast cancer has alternatively been referred to as ‘oat cell‘ carcinoma of the breast, small cell neuroendocrine carcinoma of the breast, and small cell undifferentiated breast carcinoma.
I just want to let you know that I have created a newer version of this page with more up-to-date information on Small Cell Breast Carcinoma. However, this page still has very great research material, and I would still use it.
It is such a rare breast cancer that it is difficult to make generalizations, but it has been known to present in women ranging from the early 40s to the 70s, and occasionally in men.
Brief overview of ‘small cells‘ and the other common ‘cell types‘ in breast cancers
Breast cancers are described by various means; perhaps where they are located, by the name of the person who first identified a particular strain, by similarities to other known cancers, characteristic cell formations and patterns, and, or course, the types and shapes of cells which seem to be most involved. “Small cells“, are indeed, smaller than normal cells, and the most common small cell cancer is lung cancer, and many small cell cancers are highly aggressive.
Other common breast cancer cells
Other common cell types in breast cancers include “clear cells“, commonly associated with ovarian and uterine cancers, in which, simply, the inside of the cell appears clear.
“Spindle cells“, often associated with mesenchymal cells forming muscle and connective tissues, are narrower at both ends than the center, and look like a spindle.
“Large cells“, are simply larger than normal cells. Large cells are not common in breast cancers, and most commonly associated with lung cancers affecting the bronchioles.
“Squamous cells“, are flat in appearance, and are most commonly associated with skin cancers.
“Adenocarcinoma” cells look like cells that are usually associated with glandular and secretive functions, and these are common in lung, gastric, and endometrial cancers, as well as breast cancers.
Diagnosis of Small Cell Breast Cancer
The first challenge in the proper diagnosis of small cell breast cancer is to determine whether it is breast primary, or whether it is in fact a ‘secondary‘ site metastasized from another cancer elsewhere in the body, (and the lung would be the first place to look). It is impossible to distinguish metastatic and primary small cell breast cancer on the basis of histological evaluation, so a women with small cell breast carcinoma can expect a whole cohort of scans and samples from other areas of the body.
If small cell breast cancer is clinically palpable, it is usually found to be a small to medium sized lump, and very firm. Sometimes small cell breast carcinomas appear in the ‘axillary tail‘ of the breast.
Mammographically, small cell breast cancer will probably appear as a discrete round mass with increased density, usually without spiculation. Some small cell breast tumors are well-circumscribed and others have ill-defined borders, possibly with microlobulations. These kinds of features are highly suspicious of malignancy, but cannot really be distinguished from other breast cancers such as papillary breast carcinoma, medullary breast carcinoma, or colloid breast cancer. Sonographically, small cell breast carcinoma will often appear as a solid hypoechoic mass with low homogeneous echoes. They may show mild posterior acoustic enhancement, and microlobulated contours.
Histological features and differentiation of small cell breast carcinoma
Small cell breast cancer is very similar histologically to pulmonary small cell carcinoma, so morphological features (form and structure of the tumor) are very important to the diagnosis. Cytology will typically reveal loosely cohesive cell groups of variable size, (sometimes forming into islands and nests, common in neuroendocrine tumors) and often with evidence of ‘molding‘. (Nuclear molding means that adjacent cell nuclei conform to one another, or ‘stick together‘).
Dysmorphic appearance histologically
Some small cell breast tumors may have a ‘dysmorphic‘ histologic appearance, which means that the tumor has two distinct cell types (in this case likely a group of very small cells, and a group of cells that are not as small). Small cell breast cancer tumors often have infiltrative borders, and may contain lymphatic tumor embolism. (The presence of lymph embolism within a breast tumor would indicate that a kind of ‘clot‘ of lymph has migrated from another area of the body, and would probably indicate that the tumor was secondary and not primary to the breast).
Small cell carcinoma of the breast typically has ‘scant cytoplasm‘ (or a very high nuclear-cytoplasmic ratio). Cells will typically have either a round or oval shape, with hyper chromatic nuclei. Nuclei are very small (with a diameter approximately the width of three lymphocytes), with evenly distributed and finely granular chromatin (looking kind of like ‘salt and pepper‘) Nucleoli are often absent or inconspicuous. Cell mitosis is very frequent and necrosis is common.
Immunoreactive markers commonly associated with small cell breast carcinoma
Certain neuro-endocrine markers are commonly expressed in small cell breast carcinoma, but not on a consistent basis. The most important neuro-endocrine marker for helping to confirm the small cell differentiation of this breast tumor is probably neuron-specific enolase, common to all neuro-endocrine cancers. Small cell breast cancer tumors are usually positive for CK7, and commonly also express CD56, chromogranin A, and synaptophysin.
ER and PR receptors are not common
Estrogen receptors (ER) and progesterone receptors (PR) are not that common in small cell breast cancers, found at a rate of approximately 35% and 50% respectively. Small cell carcinoma of the breast will most commonly test negative in terms of immuno-reactivity for epithelial cell markers, such as cytokeratin AE1/3, CAM5.2, and epithelial membrane antigen (EMA). Small cell cancers of the breast tend to test negative for HER2 receptors.
Treatment and prognosis for small cell carcinoma of the breast
Because of the relative rarity of breast cancer with a small cell differentiation, there really are no clear statistics as to a generalized benign vs. aggressive course for the disease. The factor most likely to influence the coarse and evolution of small cell carcinoma of the breast is the cancer stage and grade at the time of diagnosis, and that holds common to all invasive breast cancers.
Small cell cancer of the breast is usually treated with mastectomy
Small cell breast cancer is usually treated with modified radical mastectomy and axillary lymph node dissection, often followed by radiation at the surgery sites and peripheral lymphatics. Metastasis might be anticipated in around 20% of cases, but, small cell breast cancers have shown to be highly responsive to chemotherapy, and to radiation therapy. Treatment by taxol, cisplatin, etoposide, and VP-16 have shown to be highly effective against the spread and recurrence of small cell breast carcinoma.
The 5 year survival rate is similar to other breast cancers of the same stage and grade
Small cell breast carcinoma has generally been thought to be just as aggressive as the pulmonary form of small cell carcinoma (lung cancer). Although survival statistics for lung cancer are generally quite poor, it tends to be discovered at a later stage than breast cancer, and patient’s overall health is generally much poorer.
About 65-70% of patients with small cell lung cancer have disseminated or extensive diseases at the time of presentation, and the subsequent 5 year survival rate, even for cases of limited spread, is less than 20%. With small cell cancer of the breast, the size of the tumor at the time of treatment is considered to be a particularly important factor in terms of prognosis. Long range survival statistics are generally similar to other breast cancers of similar stage and grade, but recent research is suggesting that the outlook for small cell breast carcinoma might be a little better than expected.
For further reading, I suggest you visit this page with information on neuroendocrine breast carcinoma, and go to this page for neuroendocrine markers that are positive differentiation of neuroendocrine breast carcinoma.
- Shin SJ, DeLellis RA, Ying L, Rosen PP.Small cell carcinoma of the breast: a clinicopathologic and immunohistochemical study of nine patients. Am J Surg Pathol. 2000 Sep;24(9):1231-8.
- Mariscal, A., Balliu, E., Diaz, R., Casa, JD., Gallart, AM. Primary Oat Cell Carcinoma of the Breast: Imaging Features. AJR 2004; 183:1169-1171
- Chua RS, Torno RB, Vuletin JC. Fine needle aspiration cytology of small cell neuroendocrine carcinoma of the breast. Acta Cytol 1997;41:1341 -1344
- Kelly C, Henderson D, Corris P. Breast lumps: rare presentation of oat cell carcinoma of lung. J Clin Pathol1988; 41:171 -172
- Sebenik M, Nair SG, Hamati HF.,Primary small cell anaplastic carcinoma of the breast diagnosed by fine needle aspiration cytology: a case report. Acta Cytol. 1998 Sep-Oct;42(5):1199-203.
- Adegbola T, Connolly CE, Mortimer G., Small cell neuroendocrine carcinoma of the breast: a report of three cases and review of the literature. J Clin Pathol. 2005 Jul;58(7):775-8.
- Kitakata H, Yasumoto K, Sudo Y, Minato H, Takahashi Y., A case of primary small cell carcinoma of the breast. Breast Cancer. 2007;14(4):414-9.
- Hojo T, Kinoshita T, Shien T, Terada K, Hirose S, Isobe Y, Ikeuchi S, Kubochi K, Matsumoto S, Sadako AT.,Primary small cell carcinoma of the breast. Breast Cancer. 2009;16(1):68-71. Epub 2008 May 27.
- Ibrahim NBN, Briggs JC, Corbishley CM. Extrapulmonary oat cell carcinoma. Cancer. 1984;54:1645-1661.
- Papotti M, Gherardi G, Eusebi V, Pagani A, Bussolati G. Primary oat cell (neuroendocrine) carcinoma of the breast. Virchows Arch A Pathol Anat Histopathol. 1991;420:103-108.
- Ali SZ, Miller BT. Small cell neuroendocrine carcinoma: cytologic findings in a breast aspirate. Acta Cytol. 1997;41:1237-1240.
- Samli, B., Celik, S., Evrensel, T., Orhan, B., Tasdelen, I., Primary neuroendocrine small cell carcinoma of the breast. Arch Pathol Lab Med. 2000;124:296-298.
- Cakir, E.; Demirag, F.; Aydin, M. (Feb 2010). "Cytopathologic differential diagnosis of small cell carcinoma and poorly differentiated non-small cell carcinoma in bronchial lavage specimens using a regression analysis." APMIS 118 (2): 150–5
- Maghfoor, I., Perry, M., Lung Cancer, Oat Cell (Small Cell). http://emedicine.medscape.com/article/280104-overview
- Ahmedin Jemal, DVM, PhD, Rebecca Siegel, MPH, Elizabeth Ward, et al. Cancer
Statistics, 2008. CA Cancer J Clin. 2008;58:71-96.