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

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.

Thoracic SMARCA2-deficient But SMARCA4-preserved Tumors With Undifferentiated Morphology Combined With Claudin-4 Negativity

“…NSCLC with this phenotype usually exhibits a morphology of adenocarcinoma or squamous cell carcinoma 19. However, a subset of SMARCA2-deficient NSCLC was designated as undifferentiated carcinoma with variably rhabdoid cells in previous studies 21. Some may be classified as undifferentiated/sarcomatoid tumors rather than carcinoma based on the diagnostic criteria of this study.…”

Caecal Metastasis: An Exceptional Manifestation Mode Revealing Small Cell Lung Carcinoma: Clinical Case and Review of the Literature

“…No histological type seems more conducive to the occurrence of digestive metastasis, however, different autopsy studies have shown that squamous cell carcinoma is the most common with a rate of 33%, followed by large cell (20 to 29%), and small cell lung cancer [13 to 23%) [5,8]. Yet, other more recent papers have observed that poorly differentiated pulmonary adenocarcinomas and large cell undifferentiated carcinomas seem to have a particular predilection for the GI tract [9].…”

What Is New in Biomarker Testing at Diagnosis of Advanced Non-Squamous Non-Small Cell Lung Carcinoma? Implications for Cytology and Liquid Biopsy

“…A relatively new type of thoracic cancer, in particular lung cancer, with a poor prognosis has been identified to have mutations in SMARCA4 [250][251][252][253][254][255][256][257][258]. These mutations have been found in about 5% to 10% of NSCLC patients, mostly NS-NSCLC patients [259].…”

“…Mutations in SMARCA4 constitute a family of mutations present in the SWI/SNF complex, in which other mutations exist, including mutations in SMARCA2 [271]. Morphological and phenotypical characteristics can point sometimes to such mutations, since these cancers can contain rhabdoid cells or even poorly differentiated cells associated with islets of epidermoid cells [250,251]. One of the key diagnostic elements is the absence of expression in the majority of cases of TTF1 on tumor cells [250,251].…”

“…Morphological and phenotypical characteristics can point sometimes to such mutations, since these cancers can contain rhabdoid cells or even poorly differentiated cells associated with islets of epidermoid cells [250,251]. One of the key diagnostic elements is the absence of expression in the majority of cases of TTF1 on tumor cells [250,251]. Thus, all the lung adenocarcinomas that do not express TTF1 must be examined for mutations in SMARCA4.…”