Nasal cavity, paranasal sinuses, nasopharynx

Sinonasal carcinoma

High grade neuroendocrine carcinoma


Editorial Board Member: Ruta Gupta, M.D.
Deputy Editor-in-Chief: Kelly Magliocca, D.D.S., M.P.H.
Bin Xu, M.D., Ph.D.

Last author update: 19 February 2024
Last staff update: 19 February 2024

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PubMed Search: High grade neuroendocrine carcinoma

See Also: Laryngeal neuroendocrine neoplasm, Middle ear neuroendocrine tumor, Oropharnygeal neuroendocrine carcinoma, Salivary neuroendocrine carcinoma

Bin Xu, M.D., Ph.D.
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Cite this page: Xu B. High grade neuroendocrine carcinoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/nasalsmallcell.html. Accessed February 26th, 2024.
Definition / general
  • High grade / poorly differentiated neuroendocrine carcinoma, characterized by high mitotic count and (comedo type) tumor necrosis, morphologically similar to high grade neuroendocrine carcinoma occurring in other body sites
Essential features
  • Diagnosis dependent on histologic and immunohistochemical evidence of neuroendocrine differentiation
  • Can be further classified as small cell (neuroendocrine) carcinoma and large cell neuroendocrine carcinoma
  • May be combined with another type of nonneuroendocrine carcinoma, most frequently squamous cell carcinoma, termed as combined carcinoma
Terminology
  • Poorly differentiated neuroendocrine carcinoma
  • Small cell carcinoma
  • Small cell neuroendocrine carcinoma
  • Large cell neuroendocrine carcinoma
  • Neuroendocrine carcinoma, large cell type
ICD coding
  • ICD-O
    • 8013/3 - large cell neuroendocrine carcinoma
    • 8041/3 - small cell carcinoma, NOS
    • 8045/3 - combined small cell carcinoma
Epidemiology
Sites
Etiology
Clinical features
  • Nasal congestion and obstruction and epistaxis are the most common presenting symptoms, followed by facial pain, palpable facial mass and exophthalmos (Int Forum Allergy Rhinol 2016;6:744)
Diagnosis
  • Diagnosis relies on demonstration of neuroendocrine differentiation, histologic features of small cell or large cell neuroendocrine carcinoma, high mitotic index (> 10 per 2 mm2) and tumor necrosis
Radiology description
  • Destructive soft tissue mass of the sinonasal tract
Radiology images

Images hosted on other servers:
Mass of maxillary sinus

Mass of maxillary sinus

Prognostic factors
  • Diagnosis designates a poor prognosis: 5 year disease specific survival of sinonasal small cell carcinoma is 46% (Oral Oncol 2016;63:1)
  • Frequent local recurrence and distant metastasis despite multimodal therapy
  • Stage does not appear to affect the prognosis (Oral Oncol 2016;63:1)
Case reports
Treatment
  • There are no specific management guidelines due to rarity of the tumor
  • Multimodality treatment has been used with variable results
Clinical images

Images hosted on other servers:
Expansile swelling of maxilla

Expansile swelling of maxilla

Microscopic (histologic) description
  • High grade neuroendocrine carcinoma (general features)
    • Mitotic index > 10 mitoses per 2 mm2, frequent apoptotic bodies and tumor necrosis
    • Solid sheets or trabeculae of tumor cells, sometimes with peripheral palisading or rosette formation
  • Small cell carcinoma
    • Small to medium sized cells: the diameter of tumor cells is < 3 times the diameter of a lymphocyte
    • Scanty cytoplasm and indistinct cell boundary
    • Finely granular salt and pepper chromatin
    • No or inconspicuous nuclei
    • Nuclear molding (conformity of adjacent nuclei to one another), nuclear spindling and crush artifacts of the nuclei may be seen
  • Large cell neuroendocrine carcinoma
    • Large sized cells: the diameter of tumor cells is > 3 times the diameter of a lymphocyte
    • Abundant amphophilic to eosinophilic cytoplasm and distinct cell membrane
    • Large nuclei with prominent nucleoli; chromatin pattern is variable, ranging from granular, vesicular, to coarse
  • Combined neuroendocrine carcinoma
    • Tumor that is composed of a high grade neuroendocrine carcinoma and a nonneuroendocrine carcinoma, commonly a squamous cell carcinoma
Microscopic (histologic) images

Contributed by Bin Xu, M.D., Ph.D.

Small cell carcinoma
Finely granular chromatin

Finely granular chromatin

Frequent mitoses and nuclear molding

Frequent mitoses and nuclear molding

CAM5.2 (dot-like pattern)

CAM5.2 (dot-like pattern)

Synaptophysin

Synaptophysin


Chromogranin

Chromogranin

INSM1

INSM1

Elevated Ki67 proliferation index

Elevated Ki67 proliferation index

TTF1

TTF1



Large cell neuroendocrine carcinoma
Large tumor cells

Large tumor cells

Synaptophysin

Synaptophysin

Chromogranin

Chromogranin



Combined small cell carcinoma and squamous cell carcinoma
squamous and neuroendocrine component Squamous and neuroendocrine component

Squamous and neuroendocrine component

p40

p40

Cytology description
  • Small cell carcinoma: hypercellular sample, individual cells or small loose clusters, hyperchromatic nuclei, no nucleoli, nuclear molding, crush artifact and necrotic background
Cytology images

Contributed by Bin Xu, M.D., Ph.D.
Small cell carcinoma Small cell carcinoma

Small cell carcinoma

Positive stains
Negative stains
Molecular / cytogenetics description
Sample pathology report
  • Nasal cavity, biopsy:
    • Small cell carcinoma (high grade neuroendocrine carcinoma, small cell carcinoma type) (see comment)
    • Comment: Immunohistochemistry studies show that the tumor is diffusely positive for synaptophysin, chromogranin, INSM1, cytokeratin AE1 / AE3 and CAM5.2, whereas it is negative for S100 and NUT. Immunoexpression of SMARCA2, SMARCA4 and SMARCB1 is retained in this tumor. Ki67 proliferation index is > 90%. The overall histologic features and immunoprofile support the diagnosis.
Differential diagnosis
Board review style question #1

A biopsy was performed from a nasal cavity mass of a 60 year old man. The H&E, CAM5.2 and synaptophysin immunohistochemistry slides are shown above. What is the diagnosis?

  1. Large cell neuroendocrine carcinoma
  2. Olfactory neuroblastoma
  3. Sinonasal undifferentiated carcinoma
  4. Small cell carcinoma
Board review style answer #1
D. Small cell carcinoma. The tumor shows diffuse synaptophysin expression and perinuclear dot-like expression of CAM5.2. The tumor cells have scanty cytoplasm, salt and pepper chromatin, inconspicuous nuclei, frequent mitoses and apoptotic bodies. Answer C is incorrect because diffuse synaptophysin expression excludes a diagnosis of sinonasal undifferentiated carcinoma. Answer B is incorrect because olfactory neuroblastoma is cytokeratin negative, while this tumor expresses CAM5.2. Answer A is incorrect because the tumor cells lack abundant cytoplasm and prominent nucleoli.

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Reference: High grade neuroendocrine carcinoma
Board review style question #2
Which of the following statements is true for high grade neuroendocrine carcinoma of the sinonasal tract?

  1. It is generally positive for INSM1 and S100
  2. It is universally negative for high risk human papillomavirus (HPV), distinguishing it from HPV related squamous cell carcinoma and HPV related multiphenotypic sinonasal carcinoma
  3. It may coexist with a squamous cell carcinoma
  4. Ki67 proliferation index is between 2% and 20%
Board review style answer #2
C. It may coexist with a squamous cell carcinoma. High grade neuroendocrine carcinoma may coexist with a nonneuroendocrine carcinoma component (i.e., combined carcinoma). Answer B is incorrect because a subset can be positive for high risk human papillomavirus. Answer D is incorrect because Ki67 by definition should be > 20%. Answer A is incorrect because it is generally negative for S100.

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Reference: High grade neuroendocrine carcinoma
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