Colorectal Choriocarcinoma in a Patient with Probable Lynch Syndrome

Abstract

BackgroundPersonalized therapy of colorectal cancer is influenced by morphological, molecular, and host-related factors. Here, we report the comprehensive clinicopathological and molecular analysis of an extra-gestational colorectal choriocarcinoma in a patient with probable Lynch syndrome.Case presentationA 61-year-old female with history of gastric cancer at age 36 presented with a transmurally invasive tumor of the right hemicolon and liver metastasis. A right hemicolectomy was performed. Histopathological analysis showed a mixed trophoblastic and syncytiotrophoblastic differentiation, consistent with choriocarcinoma. Disease progression was rapid under oxaliplatin, capecitabine, irinotecan, and bevacizumab. Molecular phenotyping identified loss of mismatch-repair protein immunostaining for PMS2, microsatellite instability, a lack of MLH1 promoter methylation, and lack of BRAF mutation suggestive of Lynch syndrome. Targeted next-generation sequencing revealed an ataxia telangiectasia mutated (p.P604S) missense mutation. A bleomycin, etoposide, and cisplatin treatment protocol targeting germ cell neoplasia lead to disease remission and prolonged survival of 34 months.ConclusionComprehensive immunohistochemical and genetic testing is essential to identify uncommon cancers possibly related to Lynch syndrome. For rare tumors, personalized therapeutic approaches should take both molecular and morphological information into account.

Lineage-Specific Alterations in Gynecologic Neoplasms with Choriocarcinomatous Differentiation: Implications for Origin and Therapeutics

“…Likewise, another report used comparative genomic hybridization and FISH to elucidate the genetic changes in colorectal adenocarcinoma and associated choriocarcinoma, revealing a loss of chromosomal regions 8p21-pter as well as 18q21-pter, and a gain of 5p and 20q, in both tumor parts (11). At a molecular level, targeted NGS demonstrated an ataxia telangiectasia mutated (p.P604S) missense mutation present in a gastric carcinoma and subsequent colorectal choriocarcinoma (32). Another report genotyped an endometrioid carcinoma with a choriocarcinomatous component and found that the patterns in both components were nearly identical, with all alleles shared by both tumors (22).…”

Morphology and Molecular Features of Rare Colorectal Carcinoma Histotypes

“…Patients are usually younger than conventional CRC (median 54 years, range 12–74; 45% are <50 years of age) with no gender predilection. Symptoms are similar to conventional CRC however most patients have increased serum βHCG levels (which may be used as a biomarker) [83]. Three cases have been found to be associated with Crohn’s disease or ulcerative colitis.…”

Primary Rectal Tumor With Extensive Choriocarcinoma Differentiation in a Woman With Lung, Liver and Disseminated Peritoneal Disease: A Primary Rectal Adenocarcinoma With Extensive Choriocarcinoma Differentiation or Primary Rectal Choriocarcinoma?

“…[1][2][3][4][5][6][7][8][9][10][11][12][18][19][20][21][22][23][24][25] In adenocarcinomas of the gastrointestinal tract, choriocarcinomatous differentiation can manifest in different forms. [1][2][3][4][5][6][7][8][9][10][11][12][16][17][18][19][20][21][22][23][24][25] This can range from isolated β-HCG-positive malignant syncytiotrophoblastic giant cells in poorly differentiated adenocarcinomas, through mixed tumors, to pure choriocarcinoma. [1][2][3][4][5][6][7][8][9]...…”

“…[1][2][3][4][5][6][7][8][9][10][11][12][16][17][18][19][20][21][22][23][24][25] This can range from isolated β-HCG-positive malignant syncytiotrophoblastic giant cells in poorly differentiated adenocarcinomas, through mixed tumors, to pure choriocarcinoma. [1][2][3][4][5][6][7][8][9][10][11][12][16][17][18][19][20][21][22][23][24][25] Previous publications have proposed that most choriocarcinomas arise through the dedifferentiation process from a prior carcinoma or adenocarcinoma. [6][7][8][9][10][11]…”

“…While molecular alterations in colorectal adenocarcinomas are well-understood, only a handful of studies have addressed molecular findings in rare colorectal carcinoma variants like adenocarcinoma with choriocarcinomatous differentiation. 25 In this context, we present the morphological, immunohistochemical, and molecular findings of an atypical case of rectal neoplasia characterized by extensive choriocarcinomatous differentiation.…”