Pulmonary Carcinomas With Mucinous and Neuroendocrine Differentiation

Weissferdt, Annikka

doi:10.1097/pas.0000000000001127

Cited by 10 publications

(6 citation statements)

References 22 publications

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“…Napsin A was previously considered not to be expressed in LCNEC, but recent reporting of napsin A positivity in LCNEC, 25,57 and cases that are borderline AC-LCNEC, 58 or borderline basaloid SqCC-LCNEC, 59 questions its diagnostic use. In our borderline cases (solid AC with more than 1 positive NE marker) we included data from previous mutation analyses, as it may be argued that RB1 mutations (or loss) favor a true NE lineage (''SCLC-like''), while cases with KRAS/STK11/KEAP1 or PI3K/AKT/mTOR mutations more resemble NSCLC on a molecular level (''NSCLClike'').…”

Section: Discussionmentioning

confidence: 99%

Diagnostic Value of Insulinoma-Associated Protein 1 (INSM1) and Comparison With Established Neuroendocrine Markers in Pulmonary Cancers

Staaf

Tran²,

Söderlund³

et al. 2020

Archives of Pathology &Amp; Laboratory Medicine

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Context.— The diagnostic distinction of pulmonary neuroendocrine (NE) tumors from non–small cell lung carcinomas (NSCLCs) is clinically relevant for prognostication and treatment. Diagnosis is based on morphology and immunohistochemical staining. Objective.— To determine the diagnostic value of insulinoma-associated protein 1 (INSM1), in comparison with established NE markers, in pulmonary tumors. Design.— Fifty-four pulmonary NE tumors and 632 NSCLCs were stained for INSM1, CD56, chromogranin A, and synaptophysin. In a subset, gene expression data were available for analysis. Also, 419 metastases to the lungs were stained for INSM1. A literature search identified 39 additional studies with data on NE markers in lung cancers from the last 15 years. Seven of these included data on INSM1. Results.— A positive INSM1 staining was seen in 39 of 54 NE tumors (72%) and 6 of 623 NSCLCs (1%). The corresponding numbers were 47 of 54 (87%) and 14 of 626 (2%) for CD56, 30 of 54 (56%) and 6 of 629 (1%) for chromogranin A, and 46 of 54 (85%) and 49 of 630 (8%) for synaptophysin, respectively. Analysis of literature data revealed that CD56 and INSM1 were the best markers for identification of high-grade NE pulmonary tumors when considering both sensitivity and specificity, while synaptophysin also showed good sensitivity. INSM1 gene expression was clearly associated with NE histology. Conclusions.— The solid data of both our and previous studies confirm the diagnostic value of INSM1 as a NE marker in pulmonary pathology. The combination of CD56 with INSM1 and/or synaptophysin should be the first-hand choice to confirm pulmonary high-grade NE tumors. INSM1 gene expression could be used to predict NE tumor histology.

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Section: Discussionmentioning

confidence: 99%

Diagnostic Value of Insulinoma-Associated Protein 1 (INSM1) and Comparison With Established Neuroendocrine Markers in Pulmonary Cancers

Staaf

Tran²,

Söderlund³

et al. 2020

Archives of Pathology &Amp; Laboratory Medicine

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“…Carcinomas with co-existing NE and mucinous differentiation in the same cell rather than in distinct geographic areas (so-called amphicrine carcinomas) do rarely occur in the lung 112 , although they are better described in the digestive tract 113 . The WHO taxonomy for these is currently lacking, but conceptually such tumor may be regarded as a type of combined carcinomas.…”

Section: Combined Neuroendocrine Carcinomasmentioning

confidence: 99%

Lung neuroendocrine neoplasms: recent progress and persistent challenges

Rekhtman

2022

Modern Pathology

106

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This review summarizes key recent developments relevant to the pathologic diagnosis of lung neuroendocrine neoplasms, including carcinoids, small cell lung carcinoma (SCLC), and large cell neuroendocrine carcinoma (LCNEC). Covered are recent insights into the biological subtypes within each main tumor type, progress in pathological diagnosis and immunohistochemical markers, and persistent challenging areas. Highlighted topics include highly proliferative carcinoids and their distinction from small cell and large cell neuroendocrine carcinomas (NECs), the evolving role of Ki67, the update on the differential diagnosis of NEC to include thoracic SMARCA4-deficient undifferentiated tumors, the recent data on SCLC transcriptional subtypes with the emergence of POU2F3 as a novel marker for the diagnosis of SCLC with low/negative expression of standard neuroendocrine markers, and the update on the diagnosis of LCNEC, particularly in biopsies. There has been remarkable recent progress in the understanding of the genetic and expression-based profiles within each type of lung neuroendocrine neoplasm, and it is hoped that these insights will enable the development of novel diagnostic, prognostic, and predictive biomarkers to aid in the pathologic assessment of these tumors in the future.

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“…As early as 1988, Müller K et al rst proposed the so-called amphicrine cells which contain mucous vacuoles as well as granules of neurosecretory type, found in goblet cell hyperplasia and in basal cells [10]. Weissferdt A et al reported 3 cases of pulmonary carcinomas with mucinous and neuroendocrine differentiation, expanding the spectrum of amphicrine carcinomas [11],…”

Section: Discussionmentioning

confidence: 99%

A rare case of non-small cell lung carcinoma with diffuse coexpression of TTF1 and p40 in the same tumour cells

Guo

Dong

Liu

et al. 2022

Preprint

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Background: Three cases of non-small cell lung carcinoma (NSCLC) with diffuse co-expression of TTF1 and p40 in the same tumour cells have been reported since 2015, which may be an underrecognized new entity of the lung. All of the cases were aged male smoking patients, with poorly differentiated carcinomas, and a similar molecular signature harboring TP53 mutation. Case Presentation: A 75-year-old man who underwent lung cancer surgery was diagnosed as NSCLC with diffuse co-expression of TTF1 and p40 in the same tumour cells. Microscopically, the tumor showed solid growth pattern with patchy necrosis. Neither glandular nor squamous pattern were found. The carcinoma cells were round or polygonal shaped with obvious nucleoli and numerous mitoses. In some areas, the carcinoma cells proliferated within the bronchial epithelium. Spread through air spaces (STAS) and visceral pleura invasion can be observed. Immunohistochemistry(IHC) showed intense diffuse positivity for both TTF-1(8G7G3/1) and p40 in the same tumor cells. Tumor cells were positive for p63, CK7, CK20, E-cadherin, GPC-3, Oct3/4, focally positive for CK5/6, Vimentin, EGFR, and negative for NapsinA, CDX-2, SATB2, chromogranin, synaptophysin and PD-L1(22C3). Negative P53 IHC staining indicated mutational status and Ki-67 index was 80%. Molecular investigation was performed by Whole Exome Sequencing, and TP53, Notch2 and STK11 mutations were detected. The patient remained alive over a follow-up period of 21 months and was free of tumour recurrence or metastasis.Conclusions: NSCLC with diffuse co-expression of TTF-1 and p40 in the same tumor cells may be a new unique entity. Expression of both “adenocarcinoma” and “squamous” markers may be an implication for classification and clinical therapy. Our case offers further insight into this rare tumor.

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Pulmonary Carcinomas With Mucinous and Neuroendocrine Differentiation

Cited by 10 publications

References 22 publications

Diagnostic Value of Insulinoma-Associated Protein 1 (INSM1) and Comparison With Established Neuroendocrine Markers in Pulmonary Cancers

Diagnostic Value of Insulinoma-Associated Protein 1 (INSM1) and Comparison With Established Neuroendocrine Markers in Pulmonary Cancers

Lung neuroendocrine neoplasms: recent progress and persistent challenges

A rare case of non-small cell lung carcinoma with diffuse coexpression of TTF1 and p40 in the same tumour cells

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