Urinary Large Cell Neuroendocrine Carcinoma

Wang, Gang; Ren, Yuan; Zhou, Chen; Guo, Charles C.; Villamil, Carlos F.; Hayes, Malcolm; Eigl, Bernhard J.; Black, Peter C.

doi:10.1097/pas.0000000000001740

Cited by 19 publications

(32 citation statements)

References 44 publications

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“…From the immunohistochemical point of view, it should be noted that the expression of CD56, chromogranin A, and INSM1 was absent, although that of NSE and synaptophysin was frequently present. It is also significant that LCNEC of the skin/conjunctiva does not express TTF1, although 44% of pulmonary LCNEC cases 24 and 100% of urinary LCNEC cases 7 express TTF1. Interestingly, there was only one case (case 2) expressing p40, which may be similar to the small group of p40/p63-positive Merkel cell carcinoma.…”

Section: Discussionmentioning

confidence: 99%

“…[4][5][6] Although the lung is the most common organ for LCNEC, it can also be seen in the gastrointestinal tract, biliary tract, gynecologic tract, urogenital organs, thymus, and head and neck. [7][8][9] In the skin, Merkel cell carcinoma 10 and endocrine mucin-producing sweat gland carcinoma [11][12][13] are well known as primary cutaneous neoplasms with neuroendocrine differentiation. Sweat-gland carcinoma with neuroendocrine differentiation (SCAND), previously known as low-grade neuroendocrine carcinoma of the skin, was recently established as a distinct third entity of primary cutaneous tumors with neuroendocrine differentiation.…”

Section: Introductionmentioning

confidence: 99%

“…4–6 Although the lung is the most common organ for LCNEC, it can also be seen in the gastrointestinal tract, biliary tract, gynecologic tract, urogenital organs, thymus, and head and neck. 7–9…”

Section: Introductionmentioning

confidence: 99%

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Large Cell Neuroendocrine Carcinoma of the Skin/Conjunctiva: A Series of 6 Cases including 1 Combined Case With Squamous Cell Carcinoma

Goto

Yoshikawa

Kiyohara

et al. 2022

The American Journal of Dermatopathology

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This study sought to reveal the clinicopathologic characteristics of large cell neuroendocrine carcinoma (LCNEC) of the skin/conjunctiva. The retrieved patients included 3 men and 3 women with a median age of 85 (63-95) years. All lesions occurred on the face, including the ears, with a median tumor size of 11.5 (7-65) mm. Lymph node metastasis was observed in 5 (83%) of 6 cases, and distant metastasis was noted in 2 (33%). One patient (17%) who had a 13-mm-sized tumor died of the tumor 13 months after excision. All tumors were mainly located in the dermis, and one of them also exhibited intraepithelial spreading. The cytology resembled that of an LCNEC in other organs. No adnexal differentiation was observed. Five cases were of the pure type, but one had a component of squamous cell carcinoma. Immunoreactivities for CAM5.2, CK7, CK19, BerEP4, epithelial membrane antigen, neuron-specific enolase, synaptophysin, c-KIT, GATA3, and bcl-2 were frequently present, but CK20, neurofilament, Merkel cell polyomavirus large T antigen, mammaglobin, estrogen receptor, HER2, and TTF1 were completely negative in all cases. Mutant-pattern immunostaining of p53, PTEN, and Rb was frequently observed. The Ki67 rate exceeded 70% in all cases. LCNEC of the skin/conjunctiva is a morphologically-defined group of primary cutaneous/conjunctival neuroendocrine neoplasm, although it may be heterogeneous similar to other-site LCNEC or Merkel cell carcinoma. This study highlighted the predominant location for the face, high metastatic and lethal potential, possible combination with other tumor components, and frequent mutant-type immunoexpressions of p53, PTEN, and Rb in this tumor group.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Large Cell Neuroendocrine Carcinoma of the Skin/Conjunctiva: A Series of 6 Cases including 1 Combined Case With Squamous Cell Carcinoma

Goto

Yoshikawa

Kiyohara

et al. 2022

The American Journal of Dermatopathology

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“… 2 – 5 EP-NECs can originate from any organ system, including gastrointestinal tract, hepatopancreatobiliary (HBP) tract, genitourinary (GU) system, gynecologic tract (GYN) and head and neck (HN), or unknown primary site. 6 – 10 …”

mentioning

confidence: 99%

“…Although most NECs arise from the lower respiratory tract, extrapulmonary neuroendocrine carcinomas (EP-NECs) account for about 2% to 9% of all NECs 2–5. EP-NECs can originate from any organ system, including gastrointestinal tract, hepatopancreatobiliary (HBP) tract, genitourinary (GU) system, gynecologic tract (GYN) and head and neck (HN), or unknown primary site 6–10…”

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confidence: 99%

Molecular Classification of Extrapulmonary Neuroendocrine Carcinomas With Emphasis on POU2F3-positive Tuft Cell Carcinoma

Koh

Kim

Moon

et al. 2022

American Journal of Surgical Pathology

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Extrapulmonary neuroendocrine carcinomas (EP-NECs) are associated with a poor clinical outcome, and limited information is available on the biology and treatment of EP-NECs. We studied EP-NECs by applying the recent novel findings from studies of pulmonary neuroendocrine carcinomas, including POU2F3, the master regulator of tuft cell variant of small cell lung carcinomas. A cohort of 190 patients with surgically resected EP-NECs or poorly differentiated carcinomas (PDCs) were established. Immunohistochemistry (IHC) for POU2F3 along with ASCL1, NEUROD1, YAP1, and conventional neuroendocrine markers was performed on tissue microarrays. Selected cases with or without POU2F3 expression were subjected to targeted gene expression profiling using nCounter PanCancer Pathway panel. POU2F3-positive tuft cell carcinomas were present in 12.6% of EP-NEC/PDCs, with variable proportions according to organ systems. POU2F3 expression was negatively correlated with the expression levels of ASCL1, NEUROD1, and conventional neuroendocrine markers (P<0.001), enabling IHC-based molecular classification into ASCL1-dominant, NEUROD1-dominant, POU2F3-dominant, YAP1-dominant, and not otherwise specified subtypes. Compared wih POU2F3-negative cases, POU2F3-positive tuft cell carcinomas showed markedly higher expression levels of PLCG2 and BCL2, which was also validated in the entire cohort by IHC. In addition to POU2F3, YAP1-positive tumors were a distinct subtype among EP-NEC/PDCs, characterized by unique T-cell inflamed microenvironment. We found rare extrapulmonary POU2F3-positive tumors arising from previously unappreciated cells of origin. Our data show novel molecular pathologic features of EP-NEC/PDCs including potential therapeutic vulnerabilities, thereby emphasizing the need for focusing on unique features of EP-NEC/PDCs.

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Clinicopathologic characteristics and prognostic factors of patients with surgically treated high‐grade neuroendocrine carcinoma of the cervix: A multicenter retrospective study

Lyu,

Liu,

Han

et al. 2024

Intl J Gynecology & Obste

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ObjectiveTo evaluate the prognostic factors and survival outcomes of patients with surgically treated high‐grade neuroendocrine carcinoma of the cervix (NECC).MethodsThis multicenter, retrospective study involved 98 cervical cancer patients with stage IA2–IIA2 and IIIC1/2p high‐grade NECC. We divided the patients into two groups based on histology: the pure and mixed groups. All clinicopathologic variables were retrospectively evaluated. Cox regression and Kaplan–Meier methods were used for analysis.ResultsIn our study, 60 patients were in the pure group and 38 patients were in the mixed group. Cox multivariate analysis showed that mixed histology was a protective factor impacting overall survival (OS) (P = 0.026) and progression free survival (PFS) (P = 0.018) in surgically treated high‐grade NECC. Conversely, survival outcomes were negatively impacted by ovarian preservation (OS: HR, 20.84; 95% CI: 5.02–86.57, P < 0.001), age >45 years (OS: HR, 4.50; 95% CI: 1.0–18.83, P = 0.039), tumor size >4 cm (OS: HR, 6.23; 95% CI: 2.34–16.61, P < 0.001), parity >3 (OS: HR, 4.50; 95% CI: 1.02–19.91, P = 0.048), and perineural invasion (OS: HR, 5.21; 95% CI: 1.20–22.53, P = 0.027). Kaplan–Meier survival curves revealed notable differences in histologic type (OS: P = 0.045; PFS: P = 0.024), chemotherapy (OS: P = 0.0056; PFS: P = 0.0041), ovarian preservation (OS: P = 0.00031; PFS: P = 0.0023), uterine invasion (OS: P < 0.0001; PFS: P < 0.0001), and depth of stromal invasion (OS: P = 0.043; PFS: P = 0.022).ConclusionPatients with mixed histologic types who undergo surgery for high‐grade NECC have a better prognosis. Meanwhile, ovarian preservation, tumor size >4 cm, parity >3, age >45 years and perineural invasion were poor prognostic predictors. Therefore, patients with high‐risk factors should be considered in clinical practice.

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Urinary Large Cell Neuroendocrine Carcinoma

Abstract: Supplemental Digital Content is available in the text.

Cited by 19 publications

References 44 publications

Large Cell Neuroendocrine Carcinoma of the Skin/Conjunctiva: A Series of 6 Cases including 1 Combined Case With Squamous Cell Carcinoma

Large Cell Neuroendocrine Carcinoma of the Skin/Conjunctiva: A Series of 6 Cases including 1 Combined Case With Squamous Cell Carcinoma

Molecular Classification of Extrapulmonary Neuroendocrine Carcinomas With Emphasis on POU2F3-positive Tuft Cell Carcinoma

Clinicopathologic characteristics and prognostic factors of patients with surgically treated high‐grade neuroendocrine carcinoma of the cervix: A multicenter retrospective study

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