Micropapillary Breast Cancer
Micropapillary breast cancer (or invasive micropapillary carcinoma IMPC) is a type of otherwise ‘typical‘ invasive ductal carcinoma which exhibits a unique and characteristic growth pattern. Representing approximately 6% of all breast cancers, the invasive micropapillary breast carcinoma ‘pattern‘ is one in which the tumor develops fairly prominent clear spaces, into which the tumor cells form into cohesive clusters.
Invasive micropapillary breast carcinoma is a very aggressive form of breast cancer, with a very high rate of lymph node metastasis. (The rate of lymph node involvement is estimated at between 75% and 100%). Skin involvement (skin retraction) is another occasional feature of invasive micropapillary carcinoma of the breast, and is observed in about 20-23% of all cases. The average age range for development of invasive micropapillary breast carcinoma is typically around the early 60s.
Invasive micropapillary carcinoma of the breast is discovered as a palpable mass in over 90% of cases. And, for no apparent reason, micropapillary breast carcinoma tends to affect the left breast more frequently than the right breast, or about 65% of the time.
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A ‘pure‘ invasive micropapillary breast tumor is rarely seen. Usually micropapillary breast carcinoma is mixed-in with invasive ductal carcinoma, NOS.(not otherwise specified), with the relative amount of the ‘micropapillary component‘ ranging from 20% to 80% of the total tumor mass. In a majority of cases, the micropapillary component is less than 25%, however the relative amount of micropapillary features does not seem to have a significant bearing on the behavior of the tumor. Micropapillary breast cancer is of an ‘angioinvasive‘ phenotype, which means it has a tendency to develop and spread into blood-supply elements, and all breast cancers which have this predisposition will tend to have higher rates of metastasis.
Histological aspects of invasive micropapillary carcinoma of the breast
Histologically, invasive micropapillary breast carcinoma is characterized by clusters of cohesive tumor cells within quite prominent ‘clear spaces‘, which resemble dilated angiolymphatic vessels. The nuclei of tumor cells around the periphery can often bulge with a kind of ‘knobby‘ appearance. Sometimes micropapillary breast tumors are referred to as ‘hedgehog‘ tumors because of this feature definition. It is also quite common to see lymphatic involvement with invasive micropapillary breast cancers.
The aggressiveness of invasive micropapillary carcinoma may be related to the inverse polarity of the tumor cell clusters and lymphotropism
Invasive micropapillary breast carcinoma tumors will often show lymphocytic infiltration. They tend to accumulate in the breast stroma, often forming a lymphoid follicle. The presence of lymphocytes within the tumor will tend to suggest a more aggressive cancer; more likely to metastasize to the lymph nodes.
Invasive micropapillary breast cancer is also characterized histologically by an ‘inverse polarity‘ of the tumor cell clusters. To clarify, within the breast the ‘functional unit‘ of the breast duct wall is a ‘polar‘ double-layered tube consisting of luminal epithelial cells surrounded by myoepithelial cells and a basement membrane. In other words, there is an order; an asymmetrical organization from ‘outer to inner‘, and without this polarity, the breast ducts would not able to properly excrete and transport breast milk. But with micropapillary breast carcinoma (and some other breast cancers) this polarity is reversed. The clusters of malignant cells which formed have the myoepithelial cells outside of the epithelial-derived cells, with the basal layer exposed.
Hormone receptor status is high for micropapillary breast cancer, somewhat against the norm
Breast cancers which have higher positive rates for various hormone receptors are usually considered to have a more positive outlook. For one thing, they tend to be more responsive to chemotherapy. With invasive micropapillary breast cancers, about 70% tend to be ER positive and around 60% are positive for progesterone receptors. HER2 overexpression may be anticipated in approximately 40% of cases. For most breast cancers this degree of positive hormone receptivity would be a hopeful indicator. In invasive micropapillary breast carcinoma, however, hormone receptor status appears to have no particular significance to the outlook.
Research has also identified the expression of MUC1 in invasive micropapillary breast carcinoma, particularly in the stroma-facing surface of the cells clusters. MUC1 is a glycoprotein which is typically expressed in the apical surface of normal epithelial cells. It is likely that MUC1 helps maintain the formation of the lumen, and it is believed that the unexpected presense or secretion of the this protein might be responsible for the ‘accentuated‘ outlines of the micropapillary cellular units. In conventional breast carcinomas, MUC1 expression tends to be either apical, intracytoplasmic, or intercellular.
Mammographic features of invasive micropapillary breast carcinoma suggest malignancy, but are not specific
At the present time, no specific mammographic, sonographic, or MR imaging characteristics have been identified for micropapillary breast carcinoma. However, all imaging characteristics of micropapillary breast cancer are highly suggestive of malignancy.
Mammographic studies of invasive micropapillary carcinoma of the breast tend to show a high density, irregular or round solid mass (Irregular shapes are somewhat more common). Micropapillary breast carcinoma tumors tend to have spiculated margins, (between 50%-70% of the time) and are variably associated with microcalcifications, occuring more or less 50% of the time. Microcalcifications, when present, tend to be either pleomorphic, punctate, or both, and their distribution tends to be either segmental or clustered.
MRI may be a useful tool in diagnosing micropapillary breast cancer
MRI (magnetic resonance imaging) may or may not be used to evaluate invasive micropapillary breast cancer tumors, but it can be a useful ‘preoperative‘ tool for defining the extent of the tumor and excluding the possibility of multifocality. MRI imaging can also frequently show associated findings such as skin thickening, lymphadenopathy, and chest wall invasion, which would not be apparent through other diagnostic modalities.
Ultrasound images of invasive micropapillary breast tumors will tend to show a solid hypoechoic mass, with either irregular or microlobulated margins. Over 90% will tend to show a homogeneous echo texture, and around 60% may show posterior acoustic shadowing. The sonogram of invasive micropapillary breast carcinoma shown below features a round, hypoechoic, solid mass (about 1 cm in diameter) with irregular margins and prominent posterior acoustic shadowing.
Factors most likely to effect the prognosis of invasive micropapillary breast cancer
The mortality rate for micropapillary breast cancer is unfortunately quite high, at over 40%. The average interval between full presentation of the disease and death is about 3 years.
The factors which seem most likely to affect a poor prognosis are skin involvement, and nodal status. However, once lymph node metastasis is confirmed, the outlook for invasive micropapillary breast cancer does not differ significantly from other breast cancers which have metastasized to the lymph nodes. Skin invasion is a significant predictor of a poor prognosis with invasive micropapillary breast cancer, leading to mortality in about 50% of all cases in which it occurs. Aspects of the tumor which are most likely to influence the risk of metastasis are the histologic grade (based on the number of atypical cells and the rate of mitosis), lymphocyte infiltration, and lymphatic vessel density. Low grading or high grade also has an influence.
Treatment for invasive micropapillary carcinoma of the breast
Invasive micropapillary breast carcinoma is a highly aggressive form of breast cancer which requires the earliest possible diagnosis and aggressive intervention, as well as management. The high rate of local recurrence and high probability of lymph node metastasis will usually prompt the surgeon to suggest either a modified or full radical mastectomy, though breast conserving surgery is attempted in a minority of situations. Axillary dissection will usually accompany a modified or radical mastectomy. Adjuvant treatment with chemotherapy is often utilized as well, but usually only if there is evidence of axillary node metastasis, or when there is not yet lymph node metastasis but the tumor is larger than 1 cm.
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