Mixed neuroendocrine and squamous cell carcinoma of the colon: A case report and literature review

Elkbuli, Adel; Dowd, Brianna; McKenney, Mark; Boneva, Dessy

doi:10.1016/j.ijscr.2019.06.060

Cited by 7 publications

(7 citation statements)

References 13 publications

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“…Neuroendocrine differentiation was confirmed by strong immunohistochemical positivity for synaptophysin, which has been approved as the best single marker for neuroendocrine tumours [27]. In accordance with one previous study, we found remarkably strong nuclear expression of CDX2 and β-catenin in over 90% of tumour cells of both carcinoma cases as well as in both components (neuroendocrine and squamous) of the tumours [7]. The high Frequencies of genetic alterations (in percent) of colorectal adenocarcinomas (AC), MiNENs, neuroendocrine carcinomas (NEC) in three studies (The Cancer Genome Atlas Program 2012 (TCGA, [16]), Jesinghaus et al [48] and Woischke et al [47]) in comparison with the genetic alterations of the two cases of mixed large cell neuroendocrine carcinoma and squamous cell carcinoma.…”

Section: Woischke Et Alsupporting

confidence: 91%

“…In accordance with the new World Health Organization Classification from 2019, mixed large cell neuroendocrine carcinoma and squamous cell carcinoma in the colorectum is subsumed under the category of MiNENs, formerly named MANECs, in which each component accounts for ≥30% of the neoplasm [24]. Although three case reports of mixed neuroendocrine carcinoma and squamous cell carcinoma of the colorectum in literature do exist [5][6][7], only one of Values indicate the existence (1) or non-existence (0) of significant co-occurrence, or significant mutual exclusivity between the listed mutated genes in three different data sets according to The Cancer Genome Atlas Program 2012 (TCGA, [16]), TCGA Pan Cancer Atlas Study [17] and Memorial Sloan Kettering Cancer Center Study (MSKCC, [18]). No significant finding is shown in red, significant correlation in one data set is marked in orange and significant findings in two or more data sets are highlighted in green.…”

Section: Discussionmentioning

confidence: 99%

“…Here we present two cases of mixed large cell neuroendocrine carcinoma and squamous cell carcinoma in the colon. Previously, only three cases with an identical histology were described in the caecum, rectum and the descending colon [5][6][7], but extensive immunohistochemical and molecular profiling was not performed. This is the first report of this rare type of carcinoma that also defines its typical molecular genetic features.…”

Section: Introductionmentioning

confidence: 99%

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Mixed large cell neuroendocrine carcinoma and squamous cell carcinoma of the colon: detailed molecular characterisation of two cases indicates a distinct colorectal cancer entity

Woischke

Jung

Kumbrink

et al. 2020

The Journal of Pathology CR

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We present two rare cases of mixed large cell neuroendocrine carcinoma and squamous cell carcinoma of the colon. A literature search revealed only three published cases with similar histology but none of these reports provided profound molecular and mutational analyses. Our two cases exhibited a distinct, colon-like immunophenotype with strong nuclear CDX2 and β-catenin expression in more than 90% of the tumour cells of both components. We analysed the two carcinomas regarding microsatellite stability, RAS, BRAF and PD-L1 status. In addition, next-generation panel sequencing with Ion AmpliSeq™ Cancer Hotspot Panel v2 was performed. This approach revealed mutations in FBXW7, CTNNB1 and PIK3CA in the first case and FBXW7 and RB1 mutations in the second case. We looked for similar mutational patterns in three publicly available colorectal adenocarcinoma data sets, as well as in collections of colorectal mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs) and colorectal neuroendocrine carcinomas. This approach indicated that the FBXW7 point mutation, without being accompanied by classical adenoma-carcinoma sequence mutations, such as APC, KRAS and TP53, likely occurs at a relatively high frequency in mixed neuroendocrine and squamous cell carcinoma and therefore may be characteristic for this rare tumour type. FBXW7 codifies the substrate recognition element of an ubiquitin ligase, and inactivating FBXW7 mutations lead to an exceptional accumulation of its target β-catenin which results in overactivation of the Wnt-signalling pathway. In line with previously described hypotheses of dedifferentiation of colon cells by enhanced Wnt-signalling, our data indicate a crucial role for mutant FBXW7 in the unusual morphological switch that determines these rare neoplasms. Therefore, mixed large cell neuroendocrine and a squamous cell carcinoma can be considered as a distinct carcinoma entity in the colon, defined by morphology, immunophenotype and distinct molecular genetic alteration(s).

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Section: Woischke Et Alsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Mixed large cell neuroendocrine carcinoma and squamous cell carcinoma of the colon: detailed molecular characterisation of two cases indicates a distinct colorectal cancer entity

Woischke

Jung

Kumbrink

et al. 2020

The Journal of Pathology CR

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“…Although, there are a few reports of mixed neuroendocrine non-neuroendocrine neoplasms (MiNEN) and NEC collision with SCC in the esophagus (Mendoza-Moreno et al, 2018 ; Choe et al, 2020 ); to the best of our knowledge, the current case is the first to be reported wherein a metachronous development of NEC and SCC is seen in the EGJ. In previous reports of MiNEN and collision carcinoma (Elkbuli et al, 2019 ; Kaneko et al, 2019 ; Choe et al, 2020 ), SCC was found on the surface of the mucosa, while NEC was found at a deeper level in the pathological sample. In the present case, NEC was found on the surface of the mucosa without any SCC components or adenocarcinoma, suggesting that NEC primarily occurred in the EGJ.…”

Section: Discussionmentioning

confidence: 84%

Case Report: A Rare Case of Esophagogastric Junctional Squamous Cell Carcinoma After the Successful Treatment of Neuroendocrine Carcinoma: Clonal Tumor Evolution Revealed by Genetic Analysis

et al. 2021

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Neuroendocrine carcinoma (NEC) of the esophagogastric junction (EGJ) is a rare disease with no established treatments. Herein, we describe a case of recurrent squamous cell carcinoma (SCC) after achieving complete response to chemotherapy against NEC of the EGJ. A 67-year-old man was referred to our hospital because of epigastric discomfort. Computed tomography imaging and esophagogastroduodenoscopy revealed ulcerated tumors at the EGJ. Endoscopic biopsy revealed small tumor cells with a high nuclear/cytoplasmic ratio, suggesting small-cell NEC. Immunohistochemistry (IHC) analysis showed tumor cells with an MIB-1 index of 80%. The patient achieved complete response after 10 cycles of chemotherapy. Follow-up endoscopic examination revealed small red-colored mucosal lesions in the center of the cicatrized primary lesion. Re-biopsy detected cancer cells harboring large eosinophilic cytoplasm with keratinization and no evidence of NEC components. IHC of the cells were cytokeratin 5/6-positive and p53-negative. The tumor persisted without evidence of metastases after chemoradiotherapy, and total gastrectomy with lymph node dissection was performed. Pathological assessment of the resected specimens revealed SCC, without evidence of NEC. The patient survived without a recurrence for >3 years after the initial presentation. Somatic mutation profiles of the primary NEC and recurrent SCC were analyzed by targeted amplicon sequencing covering common cancer-related mutations. Both tumors possessed TP53 Q192X mutation, whereas SMAD4 S517T was found only in SCC, suggesting that both tumor components originated from a founder clone with a stop-gain mutation in TP53. The somatic mutation profile of the tumors indicated that that loss of heterozygosity (LOH) at the TP53 gene might have occurred during the differentiation of the founder clone into NEC, while a SMAD4 mutation might have contributed to SCC development, indicating branching and subclonal evolution from common founder clone to both NEC and SCC. The mutation assessments provided valuable information to better understand the clonal evolution of metachronous cancers.

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“…Alternative thresholds of 10% or 20% as discriminatory cut of criterion need to be explored as even the presence of small focus of NEC can be associated with aggressive behavior and metastases[ 18 , 20 ]. Most neuroendocrine neoplasms (NEN) in high grade cancers are PDNEC either large (82.2%) or small cell (17.8%) admixed with a non-neuroendocrine component-epithelial tumor usually adenocarcinoma NOS or mucinous/signet ring cell adenocarcinoma (92.2%), though squamous cell carcinoma (2.5%) and other variants such as adenosquamous (< 1%), AFP negative hepatoid carcinoma (< 1%)have also been reported[ 18 , 20 , 84 , 86 , 90 , 91 , 94 , 102 , 103 ]. Histologically, the poorly differentiated neuroendocrine component resembles small or large cell NEC tumors.…”

Section: Discussionmentioning

confidence: 99%

Mixed epithelial endocrine neoplasms of the colon and rectum – An evolution over time: A systematic review

Kanthan¹,

Tharmaradinam²,

Asif³

et al. 2020

WJG

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BACKGROUND Mixed tumors of the colon and rectum, composed of a combination of epithelial and endocrine elements of benign and malignant potential are rare neoplasms. These can occur anywhere in the gastrointestinal tract and are often diagnosed incidentally. Though they have been a well-documented entity in the pancreas, where the exocrine-endocrine mixed tumors have been known for a while, recognition and accurate diagnosis of these tumors in the colon and rectum, to date, remains a challenge. This is further compounded by the different terminologies that have been attributed to these lesions over the years adding to increased confusion and misclassification. Therefore, dedicated literature reviews of these lesions in the colon and rectum are inconsistent and are predominantly limited to case reports and case series of limited case numbers. Though, most of these tumors are high grade and of advanced stage, intermediate and low grade lesions of these mixed tumors are also increasingly been reported. There are no established independent consensus based guidelines for the therapeutic patient management of these unique lesions. AIM To provide a comprehensive targeted literature review of these complex mixed tumors in the colon and rectum that chronicles the evolution over time with summarization of historical perspectives of terminology and to further our understanding regarding their pathogenesis including genomic landscape, clinicoradiological features, pathology, treatment, prognosis, the current status of the management of the primary lesions, their recurrences and metastases. METHODS A comprehensive review of the published English literature was conducted using the search engines PubMed, MEDLINE and GOOGLE scholar. The following search terms [“mixed tumors colon” OR mixed endocrine/neuroendocrine tumor/neoplasm/lesion colon OR adenocarcinoma and endocrine/neuroendocrine tumor colon OR mixed adenocarcinoma and endocrine/neuroendocrine carcinoma colon OR Amphicrine tumors OR Collision tumors] were used. Eligibility criteria were defined and all potential relevant items, including full articles and/or abstracts were independently reviewed, assessed and agreed upon items were selected for in-depth analysis. RESULTS In total 237 full articles/abstracts documents were considered for eligibility of which 45 articles were illegible resulting in a total of 192 articles that were assessed for eligibility of which 139 have been selected for reference in this current review. This seminal manuscript is a one stop article that provides a detailed outlook on the evolution over time with summarization of historical perspectives, nomenclature, clinicoradiological features, pathology, treatment, prognosis and the current status of the management of both the primary lesions, their recurrences and metastases. Gaps in knowledge have also been identified and discussed. An important outcome of this manuscript is the justified prop...

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Mixed neuroendocrine and squamous cell carcinoma of the colon: A case report and literature review

Cited by 7 publications

References 13 publications

Mixed large cell neuroendocrine carcinoma and squamous cell carcinoma of the colon: detailed molecular characterisation of two cases indicates a distinct colorectal cancer entity

Mixed large cell neuroendocrine carcinoma and squamous cell carcinoma of the colon: detailed molecular characterisation of two cases indicates a distinct colorectal cancer entity

Case Report: A Rare Case of Esophagogastric Junctional Squamous Cell Carcinoma After the Successful Treatment of Neuroendocrine Carcinoma: Clonal Tumor Evolution Revealed by Genetic Analysis

Mixed epithelial endocrine neoplasms of the colon and rectum – An evolution over time: A systematic review

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