Salivary glands
Primary salivary gland neoplasms - malignant
Neuroendocrine carcinoma


Topic Completed: 8 November 2019

Revised: 19 November 2019

Copyright: 2003-2019, PathologyOutlines.com, Inc.

PubMed Search: salivary neuroendocrine carcinoma [TIAB]

Lulu Sun, M.D., Ph.D.
Rebecca Chernock, M.D.
Page views in 2019: 699
Page views in 2020 to date: 158
Cite this page: Sun L, Chernock R. Neuroendocrine carcinoma. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/salivaryglandsLCNC.html. Accessed February 18th, 2020.
Definition / general
Essential features
  • Rare tumor type found predominantly in parotid gland
  • Two morphologies (high grade tumors): small cell neuroendocrine carcinoma and large cell neuroendocrine carcinoma
  • Positive for neuroendocrine IHC markers, also CK20 positive (Am J Surg Pathol 1997;21:226)
  • Can be difficult to distinguish from metastatic Merkel cell carcinoma (Am J Surg Pathol 2019;43:682)

Terminology
  • Small cell neuroendocrine carcinoma of the salivary gland
  • Large cell neuroendocrine carcinoma of the salivary gland

ICD coding
  • ICD-10: C08.9 - malignant neoplasm of major salivary gland, unspecified
Epidemiology
  • Adults
Sites
  • Majority occur in the parotid gland, followed by the submandibular gland
Pathophysiology
Etiology
  • Unknown at this time
Clinical features
  • Most common clinical presentation: rapidly growing neck mass
Diagnosis
  • Fine needle aspiration or core biopsy of mass
Radiology images

Images hosted on other servers:

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Parotid mass

Prognostic factors
  • Unknown
Case reports
  • 48 year old woman with a right cheek mass (small cell carcinoma ex pleomorphic adenoma) (Head Neck Pathol 2012;6:502)
  • 57 year old woman, 59 year old man and 82 year old woman with right parotid swelling (moderately differentiated neuroendocrine carcinoma / atypical carcinoid) (Head Neck Pathol 2013;7:295)
  • One patient in a series of 25 acinic cell carcinomas with high grade transformation had small cell carcinoma ex acinic cell carcinoma of the parotid gland (Head Neck Pathol 2016;10:152)
  • Family with low grade neuroendocrine carcinoma of salivary glands, severe sensorineural hearing loss and enamel hypoplasia on the Isle of Man (Am J Med Genet 1999;83:183)
Treatment
Gross description
  • Mass lesion within the resected salivary gland
  • Solid cut surface
  • Areas of necrosis may be noted
Microscopic (histologic) description
  • Small cell neuroendocrine carcinoma (Head Neck Pathol 2018;12:13)
    • Sheets, trabeculae or nests of small, blue tumor cells
    • High nuclear to cytoplasmic ratios with scant cytoplasm
    • Hyperchromatic, finely granular chromatin
    • Nuclear molding and crush artifact common
    • Occasional rosettes
    • Brisk mitotic activity (> 10 mitoses/10 hpf)
    • Apoptotic debris and areas of geographic necrosis may be present
  • Large cell neuroendocrine carcinoma (Head Neck Pathol 2018;12:13)
    • More abundant cytoplasm
    • Larger nuclei with course chromatin and often prominent nucleoli
    • Palisading at periphery of tumor nests may be seen
    • Occasional rosettes
    • Brisk mitotic activity (> 10 mitoses/10 hpf)
    • Apoptotic debris and areas of geographic necrosis may be present
Microscopic (histologic) images

Contributed by Lulu Sun, M.D., Ph.D. and Rebecca Chernock, M.D.

Small cell neuroendocrine carcinoma

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Infiltration of salivary parenchyma

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Necrosis

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Nuclear features

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Chromogranin


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Synaptophysin

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Cytokeratin 5/6

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MCPyV IHC




Large cell neuroendocrine carcinoma

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Nested architecture

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Necrosis

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Cytologic features

Cytology description
  • Small cell neuroendocrine carcinoma (J Cytol 2016;33:34)
    • Tumor cell clusters and single cells
    • High nuclear to cytoplasmic ratios with scant cytoplasm
    • Nuclear molding and crush artifact common
    • Granular “salt and pepper” chromatin with inconspicuous nucleoli
    • Nuclear breakdown or apoptotic bodies / necrotic background
  • Large cell neuroendocrine carcinoma (Auris Nasus Larynx 2005;32:89)
    • Tumor cell clusters and single cells
    • Larger cells with more abundant cytoplasm
    • Granular “salt and pepper” chromatin with inconspicuous nucleoli
    • Nuclear breakdown or apoptotic bodies / necrotic background
Positive stains
  • Neuroendocrine markers (may not stain with every antibody, recommend panel of neuroendocrine markers): synaptophysin, chromogranin, CD56
  • CK20 (perinuclear dot-like pattern, some cases)
Negative stains
  • TTF1 (occasionally positive)
  • CK7
  • Merkel cell polyomavirus (MCPyV)
Molecular / cytogenetics description
Sample pathology report
  • Salivary gland, right parotid, parotidectomy:
    • Small cell neuroendocrine carcinoma (see comment)
    • Comment: Histologic sections show a small cell neuroendocrine carcinoma involving the parotid gland. The tumor cells are positive for synaptophysin, chromogranin and cytokeratin 20. TTF1 is negative. Immunohistochemistry for Merkel cell polyomavirus (MCPyV) is also negative. The majority of high grade neuroendocrine carcinomas located in the parotid gland represent metastases, usually from the head and neck skin, rather than primary salivary carcinomas. Correlation with clinical history and physical exam findings is recommended to exclude a metastasis. Even in the absence of an identifiable cutaneous primary, occult metastatic Merkel cell carcinoma is still more likely. In the future, mutational signature analysis may aid in determining tumor origin as a UV signature would favor a metastasis from a cutaneous primary.
Differential diagnosis
Board review style question #1

    A 70 year old man presented with an enlarging mass in the left cheek soft tissue. The mass was removed and shows the histology above. The tumor is positive for CK20 (dot-like) and synaptophysin and is negative for CK7. Which of the following features would favor a salivary primary over a metastasis from an occult cutaneous primary tumor?

  1. History of multiple head and neck skin cancers
  2. Adjacent pleomorphic adenoma
  3. Positive immunohistochemistry for MCPyV
  4. Molecular analysis showing a UV signature
Board review answer #1
B. Adjacent pleomorphic adenoma

Reference: Salivary neuroendocrine carcinomas

Comment Here
Board review style question #2
    Which of the following is true about primary neuroendocrine tumors of the salivary gland?

  1. They are usually low grade
  2. The most common site is in the sublingual gland
  3. They often stain positively with CK20 in a perinuclear dot-like pattern
  4. They do not stain with classical neuroendocrine markers (synaptophysin and chromogranin)
Board review answer #2
C. They often stain positively with CK20 in a perinuclear dot-like pattern

Reference: Salivary neuroendocrine carcinomas

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