Spindle cell carcinoma of the breast
Spindle cell breast carcinoma is a rare sub-type of breast cancer, that falls within the general category of metaplastic breast carcinoma. There are really no clinical symptoms that would distinguish spindle cell carcinoma from other types of breast cancers, so diagnosis is dependent on the histological evaluation of tissue samples obtained from a biopsy. Spindle cell breast carcinoma tumors will tend to be dominated by spindle shape cells, along with some other component of either squamous cells, lobular carincoma, ductual carcinoma, or perhaps an 'in situ' ductal component. The working definition of spindle cell breast carcinoma is still a little bit vague, which is to be expected in a tumor which features a mixture of various elements. There is also lack of clarity as to the genetic origin of the spindle cell component in spindle cell breast cancers. Some researchers feel that malignant spindle cells are of a myoepithelial cell origin, while others maintain that malignant spindle cells originate a epithelial cells which have somehow genetically evolved into spindle cells.
Spindle cell carcinoma of the breast has often been referred to synonymously as 'squamous carcinoma with spindle metaplasia', pseudosarcoma, sarcomatoid carcinoma, and carcinosarcoma, evidence of the ambiguous and varied presentation of this sub-type of breast cancer. Spindle cells are generally thought to evolve from mesenchymal cells, which are the building blocks of connective and muscle tissue, while epithelial cells are generally form membranes and linings. Myo-epithelial cells are more-or-less a combination of the two, and give strength and resilience to the breast duct lining. But more and more evidence suggests that spindle-cell breast carcinoma is a unique sub category of metaplastic breast cancer, with its own differential diagnosis, prognosis and treatment strategies. A clinical finding of a large and well-circumscribed tumor, especially with accompanying cyst formation, would be strongly suggestive of spindle cell carcinoma.
There are a wide variety of spindle cell tumors
Within the category of breast tumors identified as spindle cell carcinoma, there is still a wide spectrum of variability, with cellular features ranging from overtly malignant to mildly atypical. A majority of spindle cell breast carcinoma tumors may contain a spindle cell component greater than 80%, with the remaining 20% or so of the tumor is composed of conventional invasive ductal carcinoma. A predominately spindle cell tumor with even a small amount of confirmed ductal carcinoma in situ will usually also be referred to as spindle cell carcinoma.
Spindle cell tumors of the breast tend to be described as grossly nodular, hard, and well-circumscribed, frequently with one or more cysts. There is also some data to suggest that spindle cell tumors tend to be a little bit larger than other breast cancer tumors. Spindle cell carcinoma is actually more common in the oral cavity and the larynx than in the breast. The incidence rate for spindle cell breast carcinoma is very low, estimated at between 0.2% and 0.5% of all breast cancers. Spindle cell breast carcinoma tends to affect post-menopausal women, but not exclusively. The average age for developing spindle cell breast carcinoma tends to be around 68 years of age, but there is quite a wide age range. The average tumor size tends to be between 4-5 cm at time of diagnosis. The prognosis for spindle cell carcinoma varies, depending mostly on the grade of the tumor, but even low grade spindle cell carcinoma tumors have shown some potential to metastize. However, it is speculated that the tendency for the tumor to metastize is probably related to the amount of conventional invasive ductal carcinoma component present.
Histological aspects of spindle cell carcinoma of the breast
Microscopically, spindle cell breast carcinoma tumors tend to be characterized by sheets of spindle cells which often contain squamous epithelial islands. Spindle cell breast cancer tumors frequently show numerous cystic spaces lined by epidermoid carcinoma (the ductal carcinoma component) or benign-appearing squamous epithelium. In almost all cases, spindle cell breast carcinoma tumors will show 'areas of transition' from the malignant spindle cells to the regions of squamous epithelium or epidermoid carcinoma.
The ratio of spindle cell vs epithelial cell elements is variable
The ratio of the spindle cell component to the ductal-carcinomatous component is variable. Sometimes they are in a 1:1 ratio, ranging right up to an 8:1 ratio or higher, but if the ductal carcinoma element is higher than 50%, the tumor might be named differently. Even though elements of ductal, lobular, and squamous patterns are often present, sometimes there is a pure spindle cell pattern in spindle cell carcinoma tumors. When this is the case, differential diagnosis become more difficult and more important. Pure spindle-cell presentations must be differentiated from primary sarcoma, nodular fasciitis, myofibroblastic lesions, Phyllodes tumor, and inflammatory pseudotumors.
Cell necrosis is commonly seen
The spindle cells may be benign appearing, low-grade cells, or may they have a high-grade, sarcoma-like appearance. Malignant spindle-shaped cells will likely show atypical nuclei, and evidence of high mitotic activity. Evidence of necrosis is evident in almost all spindle cell breast carcinoma tumors, and cysts frequently contain elements of hemorrhage, necrosis, and exudates. Cysts within spindle cell breast carcinoma tumors are often partially surrounded by tumor cells and granulation tissues.
Immunohistochemical reactivity typical of spindle cell breast cancer tumors
In terms of the immunohistochemical staining profile for spindle cell breast carcinoma, virtually all of them will will show reactivity for keratin. Around half of all spindle cell breast cancers will be reactive for S-100. Many spindle cell breast cancer tumors will exhibit immunoreactivity for smooth muscle actin, vimentin, CD10, and cytokeratin 14, which leads some researchers to conclude that these breast cancers are of a myoepithelial cell origin. This, however, is still a disputed claim. Despite the sarcomatous features of spindle cell breast carcinoma, most researcher still believe that the spindle cells are likely to be derived from epithelial cells of mammary glands. Spindle cell breast cancer tumors are almost uniformly negative ER, PR and Her-2/neu receptors.
Spindle cell breast cancers often show reactivity for p63.
Immunohistochemical staining with a broad spectrum cytokeratin is thought to be crucial for the diagnosis of spindle cell carcinoma of the breast. The use of nuclear antigens specifically aimed at idenfiying p63 are now being used in histological studies of spindle cell breast carcinoma, as p63 has been shown to be present in 40% of spindle cell breast cancer tumors, and probably more. "p63" is also called 'transformation-related protein 63' and is a member of the p53 family of transcription factors. It is a member of the p53 gene family, based on structural similarities, but was discovered 20 years after p53. Overexpression of the p53-related genes tends to be involved in the tumorigenesis of both components (spindle cell and ductal epithelial) of spindle cell breast cancers, but some researchers now suggest that the spindle cell component tends to show higher degree of proliferative activity than the carcinomatous component, which is why p63 staining is so beneficial in diagnosis.
Treatment for spindle cell breast carcinoma
First of all, diagnosis of spindle cell breast carcinoma usually required a wide excisional biopsy, and fine needle aspiration biopsies are unreliable. (This is to be expected, given the mixed-element presentation of spindle cell breast tumors. It would be very easy to 'miss' one of the elements and come up with a wrong diagnosis.) Most spindle cell breast carcinomas are treated either by surgical excision, or mastecomy. Axillary node dissection is usually required for evaluative purposes. Chemotherapy is utilized in most treatments of spindle cell breast cancer, as sometimes adjuvant endocrine therapy with taximofen is also used. Post operative radiation therapy is used in most cases, in hopes of preventing local recurrence or metastasis.
Prognosis for women with spindle cell breast cancer
Spindle cell breast cancers seem to grow expansively within their circumscribed boundary, and the rate of lymph node metastasis is actually comparitively low. Spindle cell breast carcinoma tumors tend to be a bit larger than other typical breast cancers, but the malignant potential is lower than one might expect based upon tumor size. The prognosis for spindle cell breast cancer is basically similar to the prognosis for other more common breast carcinomas, though at times it can be a highly aggresive neoplasm. The cumulative 5-year survival rate for spindle cell carcinoma of the breast has been estimated at around 65%, which is a little better than survival rates usually reported for most metaplastic breast cancers.
Higher ratios of spindle cell components generally leads to a better prognosis
However, the relative amounts of spindle cell versus ductal carcinoma elements can have a bearing on the outlook. Spindle cell breast carcinoma tumors which are composed almost entirely of spindle cells ('pure' spindle cell carcinoma) have been shown to exhibit a significantly lower rate of nodal metastases than conventional ductal and lobular breast carcinomas. But spindle cell breast cancer tumors with a more even split of spindle cell and ductal carcinoma elements have a higher rate of extranodal metastases, and a poorer prognosis. The rate of metastasis for spindle cell breast carcinoma shows no consistent statistical trend at this time. Some studies show the rate of metastasis as high as 46%, with the most common sites being to the lungs, followed by the bone, and the liver. The rate of lymph node metastasis of spindle cell breast carcinoma is actually quite low, estimated at around 6%. However, a very high percentage of women who develop lymph node metastasis of spindle cell breast cancer, eventually die from the disease. (It is believed that the lymph node metastasis of spindle cell breast carcinoma is mostly related to the 'ductal carcinoma' component of the tumor and not the spindle cell component.) Local recurrence is not nearly such an ominous sign, as over 70% of women who experience local recurrence of spindle cell breast carcinoma still manage to survive the disease.
If metastasis occurs, survival rates are less positive
A comparison of various case studies suggests that the mortality rate for spindle cell breast carcinoma ranges between 40% and 50%, and the average survival time after diagnosis is between 11 and 18 months. Higher tumor grade tends to correlate with poorer survival for spindle cell carcinoma of the breast, with absence of complete microscopic circumscription and the size of tumors which eventually recurr, as significant negative prognostic indicators. Some women even with low grade tumors have been known to succumb to spindle cell breast carcinoma. However, studies have also shown that as many as 33% of women with spindle cell breast cancer may survive completely free of metastatic or recurrent disease.
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Copyright Steven B. Halls, MD Last edited 08-August-2011