Skin Nonmelanocytic tumors
Other tumors of skin
Granular cell tumor

Author: Jarish Cohen, M.D., Ph.D.
Senior Author: Philip LeBoit, M.D.
Editor-in-Chief Review: Debra Zynger, M.D.

Revised: 4 December 2018, last major update November 2018

Copyright: (c) 2002-2018, PathologyOutlines.com, Inc.

PubMed Search: Cutaneous granular cell [title] tumor

Cite this page: Cohen, J., LeBoit, P. Granular cell tumor. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/skintumornonmelanocyticgct.html. Accessed December 13th, 2018.
Definition / general
  • A dermal or subcutaneous tumor with abundant granular cytoplasm and Schwannian differentiation
  • Nonneural variant (primitive polypoid granular cell tumor) shows similar granular cytomorphology but does not have immunohistochemical evidence of Schwannian differentiation
Essential features
  • A predominantly dermal based tumor composed of cells with abundant eosinophilic to basophilic granular cytoplasm
  • Often have an infiltrative configuration
  • Tumors demonstrate Schwannian differentiation (S100+, SOX10+)
  • Epidermis can exhibit pseudocarcinomatous hyperplasia in a subset of cases
Terminology
ICD coding
  • D23.9: other benign neoplasm of skin, unspecified
Epidemiology
Sites
  • Common sites are trunk, upper limbs and head / neck
  • Also arise on feet, hands, anogenital region and breast
Pathophysiology
  • Pathogenesis of conventional granular cell tumors is unknown
  • A subset of nonneural granular cell tumors (S100-) harbor ALK gene fusions (Am J Surg Pathol 2018;42:1133)
Etiology
Clinical features
Diagnostic criteria
  • Fanberg-Smith et al. proposed criteria for atypical and malignant tumors (Am J Surg Pathol 1998;22:779):
    • Increased nuclear / cytoplasmic ratio
    • Nuclear pleomorphism
    • Necrosis, tumor type
    • Spindling of tumor cells
    • Vesicular nuclei with prominent nucleoli
    • > 2 mitoses per 10 high power fields
    • Atypical: 1 - 2 features
    • Malignant: > 2 features
  • Nasser et al. proposed criteria for granular cell tumor of uncertain malignant potential and malignancy (Pathol Res Pract 2011;207:164):
    • Necrosis, single cell or en masse
    • > 2 mitoses per 10 high power fields
    • Uncertain malignant potential: 1 - 2 features
    • Malignant: evidence of metastatic disease
Case reports
Treatment
Clinical images

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Pedunculated buttock lesion

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Subcutaneous waist lesion

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Soft tissue swelling on the back

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Hyperchromic nodule on right cubital fossa

Gross description
  • Greyish-white to pale yellow
  • Oftentimes not well circumscribed
Gross images

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Rough surface, ulceration and necrosis

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Lobulated, solid leg mass

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Infiltrative paraspinal tumor

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Solid supraclavicular tumor

Microscopic (histologic) description
  • Infiltrative or circumscribed architecture
  • Can involve the subcutis
  • Large polygonal cells with abundant eosinophilic granular cytoplasm and small, central nuclei
  • Epidermis can show pseudocarcinomatous hyperplasia
  • Lysosomal macro-inclusions (pustulo-ovoid bodies of Milian) are usually present (J Cutan Pathol 2007;34:405)
  • Can exhibit accentuation around arrector pili muscles or peripheral nerves (J Clin Pathol 2014;67:19)
  • Nonneural granular cell tumors (S100-) can exhibit nucleomegaly, pleomorphism and variable mitotic activity (Am J Surg Pathol 1991;15:48, Histopathology 2005;47:179)
Microscopic (histologic) images

Images hosted on PathOut server:

Contributed by Jarish Cohen, M.D., Ph.D.

Dermal wedge shaped tumor

Nests and cords

Pustulo-ovoid bodies

Infiltrative array

Accentuation around arrector pili



Abundant granular cytoplasm

SOX10

Deep dermal tumor

Tumor surrounds nerve

Granular pink cytoplasm


Nonneural granular cell tumor


Atypical granular cell tumor

Positive stains
Negative stains
Electron microscopy description
Electron microscopy images

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Basal lamina

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Lamellar structures

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Abundant secondary lysosomes

Molecular / cytogenetics description
Differential diagnosis
Board review question #1
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    A 40 year old woman presents with a nodule on her trunk. The lesion is biopsied and shows a dermal based proliferation of cells with abundant eosinophilic granular cytoplasm. Which of the following statements is false?

  1. The abundant granular cytoplasm is indicative of numerous membrane bound cytoplasmic granules containing aggregates of lysosomes.
  2. An S100 or SOX10 stain is positive in most tumors and is reflective of Schwannian differentiation.
  3. Perineural accentuation of cellularity is a feature of malignancy.
  4. These tumors can display infiltrative architecture and can sometimes involve the subcutaneous fat.
Board review answer #1
C. Perineural accentuation of cellularity is a feature of malignancy.

This is false since lesional cells of granular cell tumors can show a proclivity for peripheral nerves and arrector pili muscles. No studies have demonstrated increased malignant potential of granular cell tumors that exhibit these features.
Board review question #2
    Which of the following statements about granular cell tumors is false?

  1. A subset are negative for S100 and other neural markers and can have a polypoid appearance.
  2. Atypical features include necrosis, increased mitotic activity and nuclear pleomorphism.
  3. NF1 is commonly mutated in conventional granular cell tumors.
  4. Tumors can mimic granular cell variants of leiomyosarcoma, atypical fibroxanthoma and dermatofibroma.
Board review answer #2
C. NF1 is commonly mutated in conventional granular cell tumors.

This statement is false since the pathogenesis of granular cell tumors with Schwannian derivation has not been elucidated to date. A subset of nonneural granular cell tumors that are negative for neural markers (S100 negative) harbor ALK gene fusions.

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