Bladder, ureter & renal pelvis
Neuroendocrine neoplasms
Large cell neuroendocrine carcinoma
Topic Completed: 1 December 2016
Minor changes: 1 August 2020
Copyright: 2003-2020, PathologyOutlines.com, Inc.
PubMed Search: renal large cell neuroendocrine
Table of Contents
Definition / general | Essential features | Epidemiology | Pathophysiology | Clinical features | Radiology images | Prognostic factors | Case reports | Treatment | Gross description | Gross images | Microscopic (histologic) description | Microscopic (histologic) images | Cytology description | Cytology images | Positive stains | Negative stains | Differential diagnosisCite this page: Anderson D, Tretiakova M. Large cell neuroendocrine carcinoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/kidneytumormalignantlargecell.html. Accessed August 7th, 2020.
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 (PubCan)
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)
Epidemiology
- Equal gender distribution; peak age of incidence for neuroendocrine tumors is between the fifth and sixth decades (Indian J Urol 2009;25:155)
Pathophysiology
- 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
- Often present with locally advanced disease, flank pain, flank mass (BJU Int 2007;100:1030), hydronephrosis (Urologia 2014;81:57), hematuria (Indian J Urol 2009;25:274)
- May have distant metastases with associated symptoms (Indian J Urol 2009;25:155)
Radiology images
Images hosted on other servers:
Heterogenous,
exophytic
10 × 8 × 7 cm
mass
Prognostic factors
- Poor prognosis despite treatment; 75% dead of disease within 1 year (Indian J Urol 2009;25:155, BJU Int 2007;100:1030)
Case reports
- 23 year old man with primary renal large cell neuroendocrine carcinoma (J Clin Diagn Res 2014;8:ND08)
- 35 year old man and 75 year old woman who died within 6 and 5 months after surgery despite radical nephrectomy and chemotherapy (Ann Pathol 2000;20:357)
- 40 year old woman with asymptomatic right sided large cell renal neuroendocrine carcinoma (Indian J Urol 2009;25:274)
- 56 year old man with primary renal large cell neuroendocrine carcinoma (Pathol Oncol Res 2010;16:139)
- 79 year old with primary large cell neuroendocrine carcinoma of renal pelvis associated with a high grade urothelial carcinoma (Urologia 2014;81:57)
- Large cell neuroendocrine carcinoma with urothelial carcinoma of kidney (Zhonghua Bing Li Xue Za Zhi 2016;45:480)
Treatment
- 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
Images hosted on other servers:
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.
20x
40x
CD56 (40x)
Ki67 (40x)
Synaptophysin (40x)
Images hosted on other servers:
10x
20x
Fig b
Chromogranin
Synaptophysin
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
Images hosted on other servers:
Lung
Positive stains
- Synaptophysin, CD56, CD57 (Pathol Oncol Res 2010;16:139), NSE and Leu 7 (Indian J Urol 2009;25:274), variable chromogranin (Pathol Oncol Res 2010;16:139)
- Focal AE1 / AE3, vimentin and CD10 have been reported (BJU Int 2007;100:1030)
- CD10 has been reported to be "rarely positive" and vimentin to be negative (BJU Int 2007;100:1030)
Negative stains
- Cytokeratins, CAM 5.2, 34 beta E12, BerEP4; CK7, CK20, TTF1, calretinin, serotonin, somatostatin, gastrin, calcitonin, glucagon, insulin (Pathol Oncol Res 2010;16:139), S100 (Indian J Urol 2009;25:155) and EMA (BJU Int 2007;100:1030)
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)
