Poorly Cohesive Carcinoma of the Nonampullary Small Intestine

Abstract

Poorly cohesive carcinomas (PCCs) are neoplasms characterized by a dyshesive cell invasion pattern featuring single-cell or cord-like stromal infiltration. Although they have been extensively studied in the stomach and other digestive system organs, limited data regarding nonampullary small bowel poorly cohesive carcinomas (SB-PCCs) are hitherto available. The aims of our study were to analyze the clinicopathologic and immunophenotypical features of SB-PCCs (PCC pattern accounting for > 50% of the neoplasm) and to compare them with small bowel adenocarcinomas (SBAs), not otherwise specified (SBAs-NOS) and with cancers with a histologically distinct PCC component accounting for 10% to 50% of the neoplasm (mixed-poorly-cohesive-glandular-SBAs). Fifteen SB-PCCs were identified and compared with 95 SBAs-NOS and 27 mixedpoorly-cohesive-glandular-SBAs. Most SB-PCCs (67%) were composed of < 10% of signet-ring cells, and all but 1 SB-PCCs exhibited loss of membranous expression of E-cadherin. Compared with SBAs-NOS, SB-PCCs showed a significantly younger patient age at diagnosis, and a stronger association with Crohn disease, and both SB-PCCs and mixed-poorly-cohesive-glandular-SBAs featured a higher rate of lymphovascular and perineural invasion and a lower percentage of mismatch repairdeficient cases. Importantly, the cancer-specific survival of SB-PCC (hazard ratio: 3.81; 95% confidence interval: 1.90-7.64; P < 0.001) and mixed-poorly-cohesive-glandular-SBA (4.12; 2.20-7.71; P < 0.001) patients was significantly worse compared with SBAs-NOS cases. This study provides objective evidence to the World Health Organization (WHO) 2019 introduction of SB-PCC as a distinctive subtype of nonampullary SBA, by virtue of its unique clinical and histologic features, and suggests that both SB-PCCs and mixed-poorly-cohesive-glandular-SBAs should be separated from SBAs-NOS.

Molecular Landscape and Association With Crohn Disease of Poorly Cohesive Carcinomas of the Nonampullary Small Bowel

“…In the present study, we have gained insights into the molecular landscape of SB-PCCs, thus contributing to the characterization of this histologic subtype of nonampullary SBAs with distinct clinicopathologic (including frequent association with Crohn disease) and prognostic features in comparison with conventional SBAs. 5 A different SB-PCC molecular profile, compared with the SBAs in general and with conventional-type or SRC CRCs, emerged, particularly for (1) the lack of KRAS and PIK3CA point mutations, (2) the rarity of the MMR deficiency/MSI profile, and (3) the presence of the RHOA mutation, typical of PCCs of the stomach.…”

“…We investigated 15 surgically resected, primary nonampullary, nonhereditary SB-PCCs, all of which had already been included in previous studies of the Small Bowel Cancer Italian Consortium (accounting for 9.7% of the entire cohort of 154 SBA cases). 5 , 17-22 …”

“…SB-PCCs were defined as small bowel adenocarcinomas with a poorly cohesive pattern (ie, a dyshesive cell invasion pattern, characterized by a single cell or cord-like stromal invasion with or without an SRC component) representing more than 50% of the tumor, as previously described. 5 …”

“… 12 Finally, immunohistochemistry for mismatch repair proteins was recorded, as previously described. 5 …”

“…3 , 4 A recent study from our group proved that, when compared with conventional-type glandular SBAs (ie, SBAs not otherwise specified [SBAs-NOS]), small bowel PCCs (SB-PCCs) are characterized by unique clinicopathologic features, such as a younger age at diagnosis, a more frequent association with Crohn disease as a predisposing condition, a higher rate of perineural and lymphovascular invasion, and a worse prognosis. 5 …”