Skin nonmelanocytic tumor

Neural tumors

Granular cell tumor

Editorial Board Member: Hillary Rose Elwood, M.D.
Deputy Editor-in-Chief: Jonathan D. Ho, M.B.B.S., D.Sc.
Editor-in-Chief: Debra L. Zynger, M.D.
Jarish Cohen, M.D., Ph.D.
Philip LeBoit, M.D.

Last author update: 25 January 2023
Last staff update: 7 February 2023

Copyright: 2002-2023,, Inc.

PubMed Search: Cutaneous granular cell tumor

Jarish Cohen, M.D., Ph.D.
Philip LeBoit, M.D.
Page views in 2022: 13,669
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Cite this page: Cohen J, LeBoit P. Granular cell tumor. website. Accessed September 21st, 2023.
Definition / general
  • 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
ICD coding
  • ICD-10: D23.9 - other benign neoplasm of skin, unspecified
  • Common sites are trunk, upper limbs and head / neck
  • May also arise on feet, hands, anogenital region and breast
  • Dysregulation of endosomal pH due to inactivation of accessory proteins of the vacuolar H+ ATPase can give rise to conventional granular cell tumors (Nat Commun 2018;9:3533)
  • A subset of nonneural granular cell tumors (S100-) harbor ALK gene fusions (Am J Surg Pathol 2018;42:1133)
Clinical features
  • Fanberg-Smith et al. proposed diagnostic criteria for atypical and malignant tumors (Am J Surg Pathol 1998;22:779):
    • Increased N:C 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 diagnostic 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
Clinical images

Images hosted on other servers:

Pedunculated buttock lesion

Subcutaneous waist lesion

Soft tissue swelling on the back

Hyperchromic nodule on right cubital fossa

Gross description
  • Grayish white to pale yellow
  • Oftentimes, not well circumscribed
Gross images

Images hosted on other servers:

Rough surface, ulceration and necrosis

Lobulated, solid leg mass

Infiltrative paraspinal 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 macroinclusions (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

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


Deep dermal tumor

Tumor surrounds nerve

Granular pink cytoplasm

Nonneural granular cell tumor

Nonneural granular cell tumor

Atypical granular cell tumor

Positive stains
Negative stains
Electron microscopy description
Molecular / cytogenetics description

Granular cell tumor

Sample pathology report
  • Skin, left antecubital fossa, shave biopsy:
    • Granular cell tumor (granular cell schwannoma) (see comment)
    • Comment: The lesional cells are positive with an immunostain for SOX10 protein, a finding that is typical of this entity.

  • Skin, left thigh, shave biopsy:
    • Nonneural granular cell tumor (see comment)
    • Comment: The biopsy shows a polypoid mass of large, oval cells with ample pallid and both finely and coarsely granular cytoplasm, with some pustulo-ovoid bodies. The lesional cells are S100 negative, MITF negative and NKI-C3 strongly positive. An ALK immunostain shows moderate patchy positivity. A phosphohistone H3 shows that cells in mitosis are exceedingly rare, under 1/mm2. The histopathologic and immunohistochemical findings are consistent with nonneural granular cell tumor (also known as primitive polypoid granular cell tumor).
Differential diagnosis
Board review style question #1
Missing Image Missing Image

    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 true?

  1. The abundant granular cytoplasm is indicative of numerous membrane bound cytoplasmic granules containing aggregates of mitochondria
  2. An S100 or SOX10 stain is negative in most tumors
  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 style answer #1
D. These tumors can display infiltrative architecture and can sometimes involve the subcutaneous fat. This statement is true since granular cell tumors often show infiltrative borders and can occasionally involve the subcutis. No studies have demonstrated an increased aggressive behavior of granular cell tumors that exhibit these features.

Comment Here

Reference: Granular cell tumor
Board review style question #2
    Which of the following statements about granular cell tumors is true?

  1. A subset are negative for S100 and other neural markers and can have a polypoid appearance
  2. Atypical features include association with pseudocarcinomatous hyperplasia and accentuation around peripheral nerves
  3. NF1 is commonly mutated in conventional granular cell tumors
  4. Tumors never demonstrate metastatic potential
Board review style answer #2
A. A subset are negative for S100 and other neural markers and can have a polypoid appearance. These so called nonneural granular cells tumors are negative for neural markers (e.g., S100 and SOX10). In addition, a subset has been shown to harbor ALK gene fusions and are positive by ALK immunohistochemistry.

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Reference: Granular cell tumor
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