Malignant Mixed Müllerian Tumor of the Uterus. Features Favoring its Origin from a Common Cell Clone and an Epithelial-to-Mesenchymal Transformation Mechanism of Histogenesis

Abstract

A similar immunoreactivity for p53 in both carcinomatous and sarcomatous components, expression of epithelial markers in the sarcomatous cells, and disruption of the basement membrane profile in areas of transition between carcinomatous and sarcomatous tissue, would all suggest, as has been postulated for extragenital sarcomatoid carcinomas, an origin from a common epithelial clone and an epithelial-to-mesenchymal transformation-based mechanism of development for this MMMT. In addition, these findings provide further analogies between these categories of tumors, supporting a unifying nosological concept for MMMTs and sarcomatoid carcinomas of non-genital tract origin.

Primary Mesenteric Malignant Mixed Mesodermal (Müllerian) Tumor with Neuroendocrine Differentiation

“…This "conversion hypothesis" implies a common stem cell precursor with two phenotypically different tumor cell populations diverging at a rather late stage in clonal evolution (43). These data complement initial clinical, histological, immunohistochemical and ultrastructural studies (44,(47)(48)(49)(50)(51), leading to the current view that these tumors should be regarded as "sarcomatoid" or "metaplastic" carcinomas, and treated accordingly (52).…”

“…Over the last decade, evidence from molecular genetic studies has accumulated towards a histogenetical epithelial-to-mesenchymal transformation mechanism of histogenesis for MMMT (43)(44)(45)(46). This "conversion hypothesis" implies a common stem cell precursor with two phenotypically different tumor cell populations diverging at a rather late stage in clonal evolution (43).…”

Role of p53 Pathway Alterations in Uterine Carcinosarcomas (Malignant Mixed Müllerian Tumors)

“…2). Similarities regarding p53 expression of both components strongly argue that an epithelial-mesenchymal mechanism is responsible for the development for female genital tract CSs [52,53]. An inverse relationship was reported between p53 overexpression with metastasis suppressor gene KAI-1 immunoreactivity in most of the studied uterine sarcomas [96].…”

“…The sarcomatous component probably develops from the carcinomatous component throughout a progression of genetic abnormalities or both components develop independently through the genetic diversion [44,45,52,53]. This divergence occurs late during tumorigenesis because a limited number of CSs are collision tumors [53].…”

Carcinosarcoma of the ovary

“…2 The pathogenesis of carcinosarcomas remains under debate but immunologic studies and molecular studies have suggested that both malignant elements (carcinoma and sarcoma) originate from a common epithelial stem cell (the combination theory) as opposed to two distinct malignant cell populations of different origin (the collision theory). 1,[3][4][5][6][7][8][9][10][11][12][13][14] To our knowledge there are few studies published to date regarding ovarian carcinosarcomas involving large numbers of patients and the behavior and management of these tumors remains controversial. Generally, they present in a manner similar to carcinomas of the ovary with abdominal distension, pain, nausea, emesis, and weight loss.…”