Hereditary Syndromes Manifesting as Endometrial Carcinoma: How Can Pathological Features Aid Risk Assessment?

Abstract

Endometrial carcinoma is the most common gynecological tumor worldwide. It can be the presenting malignancy, acting as the harbinger, of an undiagnosed hereditary syndrome. Up to 50% of females with Lynch syndrome present in this manner. Differentiation between Lynch, Muir-Torre, and Cowden syndromes can at times be challenging due to the overlapping features. Our review emphasizes on the strengths, pitfalls, and limitations of microscopic features as well as immunohistochemical and polymerase chain reaction- (PCR-) based tests used by laboratories to screen for DNA mismatch repair (MMR) and PTEN gene mutations in patients to enable a more targeted and cost effective approach in the use of confirmatory gene mutational analysis tests. This is crucial towards initiating timely and appropriate surveillance measures for the patient and affected family members. We also review the evidence postulating on the possible inclusion of uterine serous carcinoma as part of the spectrum of malignancies seen in hereditary breast and ovarian carcinoma syndrome, driven by mutations in BRCA1/2.

Primary giant cell tumor of the female breast: a diagnostic red herring with therapeutic implications

“…These features can be a useful clue for the unwary pathologist while handling the breast excision specimens. Positive family history of endometrial carcinoma was seen in the index case. Lynch, Muir‐Torre, and Cowden syndromes are the common familial cancer syndromes associated with endometrial and breast carcinomas . Giant cell tumors (of any site) are not known to be associated with these syndromes.…”

Phenotypic Features of Endometrial Tumors in Patients With Family History of Cancer

“…On the basis of clinical and genealogical analysis of families of EC patients from the Kyiv region, the contribution of the genetic component to the development of EC is 53.2%, indicating the significant importance of hereditary factors in the occurrence of this pathology [3]. The incidence of hereditary malignant tumors of the reproductive system in women, including EC, varies from 5.0 to 10.0% [4][5][6]. To date, there are a number of hereditary cancer syndromes, with a systemic predisposition to the emergence of EC.…”

“…Most often, EC develops in patients with Lynch syndrome (hereditary non-polyposis colorectal cancer), the development of which is associated with inactivation of genes responsible for the repair of unpaired DNA bases (MSH2, MLH1, MSH3, MSH6, PMS1, PMS2). In addition, this oncopatho logy is observed in Lee-Fraumeni syndrome (mutation in the TP53 gene), Cowden syndrome (a mutation in the PTEN gene), BRCA-associated breast and ovarian cancer syndrome (BRCA gene inactivation), and others [4,7,8].…”

“…Exp Oncol 2017 39,4,[312][313][314][315][316][317][318] According to current views on the pathogenesis of tumors of the female reproductive system, genetic factors play an important role in shaping the biological characteristics of malignant tumors that may determine prognosis. According to some authors, sporadic and hereditary forms of breast and ovarian cancer are characterized by certain morphological, clinical and functional differences, in particular, the degree of malignancy, the hormone receptor phenotype, the course of the disease, etc.…”

“…According to some authors, sporadic and hereditary forms of breast and ovarian cancer are characterized by certain morphological, clinical and functional differences, in particular, the degree of malignancy, the hormone receptor phenotype, the course of the disease, etc. [4,7,8]. Despite the achievements in the field of oncology, to this time in clinical practice insufficient attention is paid to the assessment of the role of hereditary factors that determine the biological features of malignant neoplasms and the clinical polymorphism of the disease.…”