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.

• Keywords
• Anaplastic carcinoma, Gastrointestinal, Intestine, Large cell carcinoma, Metastasis, NSCLC, Rhabdoid carcinoma, SMARCA4, SWI/SNF, Undifferentiated carcinoma,
• MeSH
• Biopsy MeSH
• Cell Dedifferentiation * MeSH
• Molecular Diagnostic Techniques MeSH
• Diagnosis, Differential MeSH
• Middle Aged MeSH
• Humans MeSH
• Mutation MeSH
• Biomarkers, Tumor analysis   genetics   MeSH
• Lung Neoplasms chemistry   genetics   pathology   MeSH
• Carcinoma, Non-Small-Cell Lung chemistry   genetics   secondary   MeSH
• Predictive Value of Tests MeSH
• Prognosis MeSH
• Rhabdoid Tumor chemistry   genetics   pathology   MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Intestinal Neoplasms chemistry   genetics   secondary   MeSH
• Carcinoma, Large Cell chemistry   genetics   pathology   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Biomarkers, Tumor MeSH

Loss of the SWI/SNF chromatin remodeling complex has been recently implicated in the pathogenesis of dedifferentiated carcinomas from different organs, but its possible role in undifferentiated urothelial carcinoma (UC) has not been studied to date. In this study, we analyzed by immunohistochemistry 14 undifferentiated UCs (11 from bladder and 3 from renal pelvis) with a nondescript anaplastic or rhabdoid morphology, using commercially available antibodies against the SWI/SNF components SMARCB1 (INI1), SMARCA2, SMARCA4, SMARCC1, SMARCC2, and ARID1A. Patients were eight females and six males aged 40 to 84 years (median, 65). All tumors were muscle-invasive (9 were T3-4). A conventional UC component was seen in eight cases and varied from in situ to papillary. The undifferentiated component comprised 60-100 % of the tumors. Histologically, most tumors showed diffuse dyscohesive or pseudoalveolar growth of variably sized cells with frequent rhabdoid features. Transition from conventional to undifferentiated UC was abrupt, except in one case. The undifferentiated component almost always expressed pan-cytokeratin AE1/AE3 (13/14) and variably vimentin (8/14) and GATA3 (9/14). Complete loss of at least one SWI/SNF subunit limited to the undifferentiated component was detected in 10/14 cases (71 %). SMARCA2 was most frequently lost (six) followed by ARID1A (four), SMARCB1/INI1 (two), SMARCA4 (one), and SMARCC1 (one). This is the first study exploring SWI/SNF expression in undifferentiated UC of the urinary tract. Our results are in line with recent studies reporting involvement of the SWI/SNF complex in the dedifferentiation process of a variety of epithelial neoplasms in different organs, including the urinary tract, and association with aggressive clinical course.

• Keywords
• ARID1A, Renal pelvis, Rhabdoid carcinoma, SMARCA2, SMARCB1, SWI/SNF, Undifferentiated carcinoma, Urinary bladder, Urothelial carcinoma,
• MeSH
• DNA-Binding Proteins MeSH
• DNA Helicases metabolism   MeSH
• Adult MeSH
• SMARCB1 Protein metabolism   MeSH
• Immunohistochemistry methods   MeSH
• Nuclear Proteins metabolism   MeSH
• Carcinoma, Transitional Cell metabolism   pathology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Urinary Tract metabolism   pathology   MeSH
• Rhabdoid Tumor diagnosis   metabolism   pathology   MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Transcription Factors metabolism   MeSH
• Urologic Neoplasms diagnosis   metabolism   pathology   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• ARID1A protein, human MeSH Browser
• DNA-Binding Proteins MeSH
• DNA Helicases MeSH
• SMARCB1 Protein MeSH
• Nuclear Proteins MeSH
• SMARCA2 protein, human MeSH Browser
• SMARCA4 protein, human MeSH Browser
• SMARCB1 protein, human MeSH Browser
• SMARCC1 protein, human MeSH Browser
• Transcription Factors MeSH