Sarcomas associated with hereditary nonpolyposis colorectal cancer: broad anatomical and morphological spectrum

Abstract

Hereditary nonpolyposis colorectal cancer (HNPCC) is primarily linked to colorectal and endometrial cancer, but is associated with a broad tumor spectrum. Though not formally part of the syndrome, occasional sarcomas have been reported in individuals with HNPCC. We used the national Danish HNPCC-register to identify HNPCC families in which sarcomas had been diagnosed. Fourteen sarcomas were identified in families with mutations in MSH2, MSH6, and MLH1. The median age at sarcoma diagnosis was 43 (15-74) years. Soft tissue sarcomas predominated followed by uterine sarcomas and eight histopathological subtypes were represented with recurrent diagnoses of liposarcoma, leiomyosarcoma, and carcinosarcoma. Tumor tissue from eight cases was available for analysis of mismatch-repair (MMR) status using immunohistochemical staining and analysis of microsatellite instability, which revealed MMR defects in six of the eight tumors investigated. This suggests that sarcomas may be part of the HNPCC tumor spectrum and that colorectal cancer should be considered in the family history of sarcoma patients.

Turcot Syndrome with Gliosarcoma: A rare variation of a Lynch Syndrome Phenotype

“…Interestingly, there have been two other documented cases of gliosarcomas in Turcot syndrome: one in a 24 year old female and the other in a 32 year old male in a Danish Lynch syndrome cohort [8,14], both with mutations in MSH2. We here report a third case of Turcot syndrome in a 34 year old man with gliosarcoma and synchronous colorectal neoplasms, also with a mutation in MSH2.…”

Intimal Sarcoma of the Pulmonary Artery in a Patient with Lynch Syndrome

“…To our knowledge, no published cases of PAS in this population of patients have been previously described. Previous anecdotic cases report malignant association between Lynch Syndrome and sarcomas non cardiacrelated [1][2][3][4][5]. Intimal sarcoma of the pulmonary artery is a rare and highly lethal tumor, usually presenting as vascular obstruction related to the intraluminal growth, and the associated thrombosis.…”

“…In this setting, primary Pulmonary Artery Sarcomas (PAS) are often misdiagnosed with a poor prognosis due to their extreme aggressiveness [1][2][3]. Conversely, Lynch Syndrome is an inherited disorder with an increased risk of developing colorectal cancer, and a well defined spectrum of extracolonic tumors [4,5]. Even when localized in other anatomic districts, sarcomas are not included in the classic tumor spectrum of Lynch Syndrome [4,5].…”

“…Conversely, Lynch Syndrome is an inherited disorder with an increased risk of developing colorectal cancer, and a well defined spectrum of extracolonic tumors [4,5]. Even when localized in other anatomic districts, sarcomas are not included in the classic tumor spectrum of Lynch Syndrome [4,5].…”

Loss of Heterozygosity and Microsatellite Instability Are Rare in Sporadic Dedifferentiated Liposarcoma: A Study of 43 Well-Characterized Cases

“…Defects in mismatch repair frequently result in colorectal and endometrial adenocarcinoma. 1,2 However, other malignancies have been demonstrated to arise less frequently in Lynch syndrome and include tumors of the ovary, biliary tract, upper gastrointestinal tract, and urothelium, as well as soft tissue sarcomas. [1][2][3][4][5][6] Although various sarcomas are associated with Lynch syndrome, including leiomyosarcoma and undifferentiated pleomorphic sarcoma, liposarcoma seems to be the most common.…”