24.10.12

Micropapillary Carcinoma of the Breast



-Micropapillary breast carcinoma (or invasive micropapillary carcinoma IMPC) is a type of otherwise 'typical' invasive ductal carcinoma which exhibits a unique and characteristic growth pattern.
 -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 invovlement (skin retraction) is another occassional feature of invasive micropapillary carcinoma of the breast, and is observed in about 20-23% of all cases.


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.
- 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 accumlate 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 metastize 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.

Factors most likely to affect 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 metastized to the lymph nodes.
-Skin invasion is a signficant 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.

Treatment for invasive micropapillary carcinoma of the breast
-Invasive micropapillary breast carcinoma is a highly aggressive from of breast cancer which requires the earliest possible diagnosis and aggressive intervention and 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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Interesting Case

Clinical History:

53 years male,History of hypertension and tachycardia,MRI abdomen:-Left adrenal mass:- size 5.8 cm Right renal mass:- size-3.0cm Microscopic examination of the renal mass showed vascular tumor with diffuse sheets of clear cells having Fuhrman grade III nuclei. There was no evidence of necrosis within the tumor. There was no evidence of extraparenchymal invasion.
Gross examination of the left adrenal gland revealed cortically centered, solid and multinodular mass measuring 6.5 x 6.0 x 5.0 cm and weighing 122 grams. The tumor was encapsulated but showed evidence of extraparenchymal penetration. The tumor had golden brown cut surface with areas of hemorrhage and necrosis. The partial nephrectomy showed 3.0cm x 3.0cm x 3.0 cm yellow solid mass which did not invade into the perinephric adipose tissue.
Microscopically, the adrenal mass had predominant diffuse sheets and focal trabecular arrangements. The former pattern was present in about third of tumor. The cells had clear cytoplasm and round to ovoid nuclei with conspicuous nucleoli. Mitotic rate was 9/50 HPF and included atypical forms. Gross necrosis and capsular invasion were documented microscopically. There was no evidence of lymphovascular invasion. Considering the above mentioned features, a Weiss histopathologic score2 of 7/9 was applied.



Discussion:

The differential diagnosis included Renal Cell Carcinoma (RCC) with contralateral adrenal metastasis, Adrenocortical carcinoma (ACC) with contralateral renal metastasis, synchronous RCC and ACC or synchronous RCC and adrenocortical adenoma. A panel of immunohistochemical stains was performed to sort out the diagnosis. Adrenal tumor demonstrated strong Vimentin positivity and is negative for CK7, CK20, E1/AE3, EMA, Synaptophysin and S100.Renal cell carcinoma was positive for CK7, AE1/AE3, EMA (weak) and Vimentin. It was negative for CK20, Synaptophysin and S100. The difference of immunoprofile between the two tumors documented that they originated from two different primaries.

Final Diagnosis:

The diagnosis of synchronous RCC and ACC rather than metastasis influences the prognosis.

Prognosis:

The longest disease free interval after removal of contralateral adrenal metastasis was 12.1 years8 and the longest crude survival was 14.3 years. In contrast non metastazing RCC has an excellent prognosis if no metastasis developed.