Kidney tumor

Non-renal cell tumors

Well differentiated neuroendocrine tumor (carcinoid)



Last author update: 7 November 2024
Last staff update: 7 November 2024

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PubMed Search: Well differentiated neuroendocrine tumor

Lin Cheng, M.D., Ph.D.
Maria Tretiakova, M.D., Ph.D.
Page views in 2024 to date: 379
Cite this page: Cheng L, Tretiakova M. Well differentiated neuroendocrine tumor (carcinoid). PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/kidneytumormalignantcarcinoid.html. Accessed December 4th, 2024.
Definition / general
  • Well differentiated epithelial neoplasm that arises from renal parenchyma and shows neuroendocrine differentiation
Essential features
  • Rare tumor that arises from renal parenchyma; associated with horseshoe kidney and mature teratoma of kidney
  • Expresses neuroendocrine markers histologically but most are clinically nonfunctional
  • Distant metastasis is common at diagnosis and Dual Tracer positron emission tomography (PET) imaging (DOTATATE scan) can help identify metastases
Terminology
  • Antiquated names: carcinoid tumor, atypical carcinoid tumor
  • Well differentiated neuroendocrine carcinoma is not a recommended term
ICD coding
  • ICD-O: 8240/3 - neuroendocrine tumor, well differentiated
  • ICD-10: C7A.093 - malignant carcinoid tumor of the kidney
  • ICD-11: 2C90.Y - other specified malignant neoplasms of kidney, except renal pelvis
Epidemiology
Sites
  • Arises from renal parenchyma; can extend into renal pelvis and inferior vena cava (Urology 2020;135:e2)
Pathophysiology
Etiology
  • Uncertain
Diagrams / tables

Images hosted on other servers:
Overall and disease specific survival by histology

Overall and disease specific survival by histology

Clinical features
Diagnosis
  • Imaging study followed by histological examination of biopsy or resection specimen
Laboratory
Radiology description
Radiology images

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Right renal mass

Right renal mass

Enhancing right renal mass

Enhancing right renal mass

Tumor extending into inferior vena cava

Tumor extending into inferior vena cava

Cystic tumor

Cystic tumor


Slightly hyperdense tumor

Slightly hyperdense tumor

Metastases on DOTATATE scan

Metastases on DOTATATE scan

CT and MRI showing left renal mass in a horseshoe kidney CT and MRI showing left renal mass in a horseshoe kidney

CT and MRI showing left renal mass in a horseshoe kidney

Prognostic factors
  • Unfavorable prognostic factors
    • Age: > 40 years
    • Size: > 4 cm
    • > 1 mitotic figure/10 high power fields (HPF)
    • Metastasis at diagnosis
    • Extension throughout renal capsule
  • Reference: J Urol 2006;176:2359
Case reports
Treatment
Gross description
  • Well circumscribed, soft, brown-tan mass with focal hemorrhage, necrosis or cystic degeneration
Gross images

Contributed by Jennifer Jeung, M.D. (Case #204)
Tan, soft, well encapsulated mass in lower pole Tan, soft, well encapsulated mass in lower pole

Tan, soft, well encapsulated mass in lower pole



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Tumor in horseshoe kidney

Tumor in horseshoe kidney

Renal mass with hemorrhage

Renal mass with hemorrhage

Necrotic renal mass

Necrotic renal mass

Tumor involving sinus fat

Tumor involving sinus fat

Cystic renal mass

Cystic renal mass

Microscopic (histologic) description
  • Variable architecture: tightly packed cords with minimal stroma (most common, 81%), sheet-like / solid pattern, nests / organoid pattern, trabeculae, ribbons, pseudo glands, etc. (Am J Surg Pathol 2007;31:1539)
  • Round to oval / elongated nuclei with stippled / speckled chromatin, inconspicuous nucleoli and moderate eosinophilic / granular cytoplasm
  • Occasional calcifications (5/21, 24%) of variable sizes (Am J Surg Pathol 2007;31:1539)
  • Usually lack of necrosis and low mitotic activity (< 4/10 HPF)
  • Grading of neuroendocrine neoplasms in nonendocrine organs by measuring proliferation either by mitotic count or Ki67 index assessment
    • WHO grade 1: < 2 mitoses/2 mm2 or Ki67 index < 3%
    • WHO grade 2: 2 - 20 mitoses/2 mm2 or Ki67 index 3 - 20%
    • WHO grade 3: > 20 mitoses/2 mm2 or Ki67 > 20%
Microscopic (histologic) images

Contributed by Maria Tretiakova, M.D., Ph.D., Leandro Freitas, M.D., Ana Grizotto, M.D., Athanase Billis, M.D.,
the Genitourinary Pathology Society (Case #521) and Sleiman Khalil, M.D.

Well demarcated tumor

Well demarcated tumor

Nests and pseudoglands

Nests and pseudoglands

Monotonous tumor cells

Monotonous tumor cells

Classic appearance

Classic appearance

Prominent stroma

Prominent stroma

Areas of solid growth

Areas of solid growth


Gland-like lumina

Gland-like lumina

Positive synaptophysin

Positive synaptophysin

Positive chromogranin

Positive chromogranin

Positive CD99

Positive CD99

Synaptophysin, chromogranin, CAM5.2

Synaptophysin, chromogranin, CAM5.2

Cytology description
Cytology images

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Monotonous cells

Monotonous cells

Positive synaptophysin stain

Positive synaptophysin stain

Granular cytoplasm

Granular cytoplasm

Positive stains
Negative stains
Electron microscopy description
  • Presence of dense core neurosecretory granules
Electron microscopy images

Contributed by Jennifer Jeung, M.D. (Case #204)
TEM of tumor cells

TEM of tumor cells

Prominent neurosecretory granules

Prominent neurosecretory granules

Molecular / cytogenetics description
  • Genetic alterations are variable and none of them are specific
  • Most frequently observed genetic changes are mutations in CDH1 and TET2
  • Reference: Histopathology 2019;75:104
Sample pathology report
  • Right kidney, core biopsy:
    • Well differentiated neuroendocrine tumor, likely renal primary (see comment)
    • Comment: The tumor cells show nested growth pattern, with round to oval nuclei, stippled chromatin and eosinophilic granular cytoplasm. No mitosis or necrosis is seen. Immunohistochemistry studies show that the tumor cells are positive for CK AE1 / AE3, synaptophysin and chromogranin and negative for PAX8, TTF1, CDX2 and GATA3. The overall findings are consistent with a well differentiated neuroendocrine tumor. Given the radiographic finding of solitary renal mass and lack of clinical history of neuroendocrine tumors elsewhere, this tumor is most likely a renal primary.
Differential diagnosis
  • Metastatic well differentiated neuroendocrine tumor:
    • Clinical history of well differentiated neuroendocrine tumor in other body sites
    • May show TTF1 or CDX2 positivity
  • Paraganglioma:
    • Zellballen / organoid growth pattern
    • Sustentacular cells are positive for S100 and chief cells are positive for neuroendocrine markers
    • Negative for cytokeratin and positive for GATA3 (Mod Pathol 2013;26:1365)
  • Metanephric adenoma:
    • Composed of tightly packed tubules, ducts and abortive glomeruli; psammomatous calcifications are common
    • Positive for PAX8, BRAF and WT1
  • Nested variants of urothelial carcinoma:
    • Variable sized anastomosing nests with irregular projection into stroma
    • Positive for CK7, CK20, GATA3 and uroplakin II
  • Poorly differentiated neuroendocrine carcinomas of kidney:
    • High grade cytological atypia, necrosis is common; brisk mitotic activity and high Ki67 proliferative index
    • Positive for cytokeratin and neuroendocrine markers
    • Small cell carcinoma: high N:C ratios, hyperchromatic nuclei, nuclear molding
    • Large cell carcinoma: large nuclei, abundant cytoplasm, prominent nucleoli
  • Ewing sarcoma:
    • Usually in children or young adults < 20 years old
    • Small round blue cell tumor, CD99 positive
    • Gene rearrangements involving FET and ETS families of genes (most commonly EWSR1::FLI1 gene rearrangement)
Board review style question #1

A 45 year old man presented with hematuria. Computed tomography (CT) showed a well demarcated 3 cm left renal mass in the lower pole. Core biopsy was performed and the H&E slide is shown above. Immunostains show that the tumor cells are positive for CK8/18, synaptophysin and chromogranin and negative for PAX8, GATA3 and S100. What is the diagnosis of this tumor?

  1. Metanephric adenoma
  2. Nested variant of urothelial carcinoma
  3. Papillary renal cell carcinoma
  4. Paraganglioma
  5. Well differentiated neuroendocrine tumor
Board review style answer #1
E. Well differentiated neuroendocrine tumor. Both the histological features and the immunostain profile are consistent with well differentiated neuroendocrine tumor. Answer A is incorrect because metanephric adenomas are usually composed of tightly packed tubules, ducts and abortive glomeruli. They are PAX8 and WT1 positive and negative for neuroendocrine markers. Answer B is incorrect because nested variant of urothelial carcinomas are commonly seen in the urinary bladder. They are usually positive for CK7, CK20 and GATA3, while negative for PAX8 and neuroendocrine markers. Answer C is incorrect because papillary renal cell carcinomas usually show papillary architecture, with positive staining for CK7 and PAX8 and negative staining for WT1 and neuroendocrine markers. Answer D is incorrect because paragangliomas are positive for S100 in sustentacular cells and negative for cytokeratin.

Comment Here

Reference: Well differentiated neuroendocrine tumor of kidney (carcinoid)
Board review style question #2
Which of the following immunostains is usually negative in well differentiated neuroendocrine tumor but positive in paraganglioma?

  1. CD56
  2. CD99
  3. Chromogranin
  4. GATA3
  5. Synaptophysin
Board review style answer #2
D. GATA3 is usually negative in neuroendocrine tumors. Answers A, B, C and E are incorrect because all of these immunostains can be positive in neuroendocrine tumors.

Comment Here

Reference: Well differentiated neuroendocrine tumor of kidney (carcinoid)
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