Bladder, ureter & renal pelvis

Neuroendocrine neoplasms

Large cell neuroendocrine carcinoma

Last author update: 1 December 2016
Last staff update: 29 November 2022 (update in progress)

Copyright: 2003-2022,, Inc.

PubMed Search: renal large cell neuroendocrine

Daniel Anderson, M.D., M.B.A.
Maria Tretiakova, M.D., Ph.D.
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Cite this page: Anderson D, Tretiakova M. Large cell neuroendocrine carcinoma. website. Accessed December 10th, 2022.
Definition / general
  • An extremely rare, high grade neuroendocrine carcinoma
  • Less than 10 cases of large cell neuroendocrine carcinoma, purportedly primary to the kidney, have been reported
  • According to the current WHO criteria, would fit into the category of Neuroendocrine carcinoma, NOS
Essential features
  • High grade neoplasm with neuroendocrine growth pattern such as organoid nesting, palisading, rosettes, trabeculae or solid growth pattern
  • Frequent mitosis: > 3 per 10 high power field
  • Has features of non small cell carcinoma such as large cell size, low nuclear to cytoplasmic ratio, vesicular / fine chromatin, frequent nucleoli
  • Positive immunohistochemical staining for one or more neuroendocrine markers (Indian J Urol 2009;25:155)
  • Equal gender distribution; peak age of incidence for neuroendocrine tumors is between the fifth and sixth decades (Indian J Urol 2009;25:155)
  • It is thought that neuroendocrine tumors arise from pluripotent primitive stem cells capable of neuroendocrine differentiation (Urologia 2014;81:57)
  • The pathogenesis of renal neuroendocrine tumors in controversial as neuroendocrine cells have so far not been found in the renal parenchyma, but only in the pelvis; possible origins of neuroendocrine kidney tumors include metastasis from an occult primary tumor site, activation of aberrant genes in pluripotent cells that differentiate into neuroendocrine cells and congenital abnormalities (Indian J Urol 2009;25:155)
Clinical features
Radiology images

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10 × 8 × 7 cm

Prognostic factors
Case reports
  • Many are currently treated with radical surgical resection and platinum based chemotherapy similar to lung large cell neuroendocrine carcinoma (LCNEC)
  • Due to rarity, no standard treatments have been approved for locally advanced disease or metastasis (Indian J Urol 2009;25:155)
  • May not be amenable to treatment due to advanced stage
Gross description
  • Large (median 8 cm) irregular solid or lobulated, firm, grayish tan tumor (Indian J Urol 2009;25:274, Urologia 2014;81:57)
  • Often necrotic and extends into renal sinus and perirenal tissues
  • When small, tumors occur adjacent to renal pelvis or within renal sinus
Gross images

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Various images

Microscopic (histologic) description
  • High grade carcinoma with non small cell features such as large cell size, low nuclear to cytoplasmic ratio, vesicular / fine chromatin or frequent nucleoli
  • Neuroendocrine growth pattern such as organoid nesting, palisading, rosettes, trabeculae or solid growth pattern
  • Frequent mitosis, > 3 per 10 high power fields (Indian J Urol 2009;25:155), usually > 10 per high power fields (Indian J Urol 2009;25:274)
  • Frequent necrosis and vascular emboli
Microscopic (histologic) images

Contributed by Daniel Anderson, M.D., M.B.A.



CD56 (40x)

Ki67 (40x)

Synaptophysin (40x)

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Fig b



Cytology description
  • Similar to LCNEC of the lung with the following features:
    • Pleomorphic medium to large cells
    • Cells are round or polygonal in shape with abundant cytoplasm
    • Nuclei round, oval or polygonal with thin and smooth nuclear membranes
    • Chromatin finely or coarsely granular
    • Nucleoli may be prominent or inconspicuous
    • Cells may appear in clusters, rosettes or singly
    • Necrosis in background and nuclear streaking may be present (Lung Cancer 2005;48:331)
    • Nuclear pleomorphism, molding and mitosis, peripheral nuclear palisading and naked nuclei may also be present (Cancer 2008;114:180)
Cytology images

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Positive stains
Negative stains
Differential diagnosis
  • Metastasis, with the lung being most likely primary site (usually multifocal)
  • Poorly differentiated / undifferentiated carcinoma, particularly renal or urothelial (Indian J Urol 2009;25:274)
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