Undifferentiated large cell/rhabdoid carcinoma presenting in the intestines of patients with concurrent or recent non-small cell lung cancer (NSCLC): clinicopathologic and molecular analysis of 14 cases indicates an unusual pattern of dedifferentiated metastases

Abbas Agaimy,Michal Michal,Mona W Schmidt,Robert Stoehr,Arndt Hartmann,Gregory Y Lauwers,Ondrej Daum

doi:10.1007/s00428-021-03032-6

Abstract

Undifferentiated carcinoma metastatic to the bowel is uncommon in surgical pathology practice and might be confused with primary gastrointestinal carcinoma, melanoma, lymphoma, and others. We present 14 cases of uni- (n = 9) or multifocal (n = 5) undifferentiated large cell/rhabdoid carcinoma presenting in the bowel of patients with concurrent (n = 9) or recent (diagnosed 1 to 25 months earlier; median, 4) non-small cell lung cancer (NSCLC). Patients were 6 females and 8 males, aged 52 to 85 years. Primary NSCLC was verified histologically in 10 cases and by imaging in 4. The undifferentiated histology was present in the lung biopsy in 4/10 patients (as sole pattern in 3 and combined with adenocarcinoma in 1) and was limited to the intestinal metastases in the remainder. PDL1 was strongly expressed in 7/9 cases (CPS: 41 to 100). Loss of at least one SWI/SNF subunit was detected in 7/13 cases (54%). SMARCA2 loss (n = 6) was most frequent and was combined with SMARCA4 loss in one case. PBRM1 loss was observed in one tumor. Successful molecular testing of 11 cases revealed BRAF mutations in 4 (3 were non-V600E variants), KRAS mutations in 3, and wildtype in 4. None had EGFR mutations. Analysis of 4 paired samples revealed concordant KRAS (2) and BRAF (1) mutations or wildtype (1). Our study indicates that undifferentiated carcinoma within the intestines of patients with concurrent/recent NSCLC represents dedifferentiated metastasis from the NSCLC. Recognition of this unusual presentation is cardinal to avoid misdiagnosis with inappropriate therapeutic and prognostic implications.

Highlights

Primary undifferentiated and rhabdoid carcinoma of the small bowel is rare [1]
Not uncommon at autopsy, clinically symptomatic secondary tumors of the gastrointestinal (GI) tract are relatively uncommon in surgical pathology practice; many representing contiguous invasion of the bowel in the setting of peritoneal carcinomatosis [7]
In one study comparing clinical and autopsy cases of GI metastases, melanoma (30%), ovarian (15%), bladder (11%), breast (8%), and lung (7%) cancers were the major tumor types encountered in surgical cases [7]

Summary

Introduction

Primary undifferentiated and rhabdoid carcinoma of the small bowel is rare [1]. Evidence that the neoplasm originates from preexisting adenomatous epithelial or intraepithelial neoplasia and/or presence of a conventional (intestinal) differentiated tumor component is helpful in confirming a primary cancer and excluding a metastasis [1]. The frequent multifocal presentation of these cases prompted us to check carefully the clinical records to exclude the possibility of metastasis from another primary. We retrospectively identified one case with a clinical diagnosis of nonsmall cell lung cancer (NSCLC) based on characteristic imaging findings which lead to its exclusion from that series [4].

Methods

Results

Conclusion