Carcinosarcoma (CS), also known as metaplastic breast carcinoma with mesenchymal differentiation, is one of the five distinct subtypes of metaplastic breast cancer. It is considered as a mixed, biphasic neoplasm consisting of a carcinomatous component combined with a malignant nonepithelial element of mesenchymal origin without an intermediate transition zone. Although cellular origin of this neoplasm remains controversial, most researchers declare that neoplastic cells derive from a cellular structure with potential biphasic differentiation. Despite recent research on the therapeutic strategies against CS neoplastic disorders, surgical resection appears the only potentially curative approach. Since CS metastasize by the lymphatic route, axillary assessment with sentinel lymph node biopsy and/or axillary lymph node dissection is always implemented. Nevertheless, the tumor also presents a hematogenous metastatic pattern including pleural, pulmonary, liver, brain and less commonly bone metastases. Thus, surgical removal of breast CS does not necessarily ensure patient's long-term recovery. Moreover, alternative therapies, such as radio- and chemotherapy proved insufficient and 5-year survival rate is limited. Nevertheless, there is evidence that following surgery, the combination of radio and chemotherapy is associated with a better prognosis than either treatment alone. The aim of this review is to evaluate the results of surgical treatment for breast CS with special reference to the extent of its histological spread. Clinical features, histogenesis, morphological and immunochemical findings are discussed, while the role of current diagnostic and therapeutic management of this aggressive neoplasm is emphasized.

Secretory carcinomas are low-grade translocation-driven carcinomas occurring in patients over a wide age range. These tumors most frequently arise in the breast and salivary gland, but may occasionally arise at other anatomic sites, such as the skin, the thyroid gland or the upper or lower respiratory tract. In concert with their low-grade morphology, secretory carcinomas most often follow an indolent clinical course. However, rare cases have shown dedifferentiation (also known as high-grade transformation) and aggressive clinical behavior. To date, the dedifferentiated component in all molecularly confirmed cases of secretory carcinoma has taken the form of a high-grade carcinoma. Here we present a case of an ETV6-NTRK3 fusion-positive secretory carcinoma of the breast with sarcomatous dedifferentiation. The sarcomatous component showed an infantile or adult fibrosarcoma-like morphology including a herringbone fascicular pattern and a hemangiopericytic vascular pattern. By immunohistochemistry, the sarcomatous component showed focal CD34 immunoreactivity and loss of all of the markers expressed in the conventional secretory carcinoma component, including SOX10, S100, GATA-3, AE1/AE3 and E-cadherin. Fluorescence in situ hybridization analysis revealed that the sarcomatous component retained the ETV6-NTRK3 fusion, but also acquired homozygous deletion of CDKN2A. The tumor followed an aggressive clinical course and the patient eventually succumbed to her disease 14 months after diagnosis. The histomorphologic and molecular genetic features of this tumor are discussed, including its ability to mimic kinase-rearranged infantile or adult fibrosarcomas at extramammary sites and the theragnostic importance of its distinction from conventional metaplastic spindle cell carcinomas in the breast.