Soft tissue
Peripheral nerve - other benign
Granular cell tumor


Topic Completed: 12 June 2019

Revised: 25 November 2019

Copyright: 2002-2019, PathologyOutlines.com, Inc.

PubMed search: Granular cell tumor[TI] soft tissue full text[sb]

Farres Obeidin, M.D.
Borislav Alexiev, M.D.
Page views in 2018: 16,330
Page views in 2019 to date: 18,753
Cite this page: Obeidin F, Alexiev B. Granular cell tumor. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/softtissuegranularcell.html. Accessed December 13th, 2019.
Definition / general
  • Soft tissue tumor with neuroectodermal differentiation composed of large cells with eosinophilic, granular cytoplasm
Essential features
  • Very rare, predominantly benign soft tissue tumor involving a wide variety of sites
  • Shows neural differentiation
  • Histology: large cells with eosinophilic, granular cytoplasm; may show pseudoepitheliomatous hyperplasia
  • Immunohistochemistry: S100+, SOX10+, CD68+
Terminology
ICD coding
  • ICD-10: D21.9 - benign neoplasm of connective and other soft tissue, unspecified
  • ICD-10: C49.9 - malignant neoplasm of connective and soft tissue, unspecified
Epidemiology
Sites
  • Wide variety of sites
    • Peripheral soft tissues (38%)
    • Trunk (36%)
    • Head and neck (20%)
      • Predilection for the tongue
    • Internal (16%)
      • Esophagus most common
  • 5 - 15% have multiple lesions
Pathophysiology / etiology
Clinical features
  • Majority are benign (only 0.5 - 2% are malignant)
  • Most are asymptomatic, typically 1 - 2 cm in greatest dimension
  • Slow, indolent growth
Radiology description
  • Mostly nonspecific
  • MRI:
    • Isointense or brighter than muscle on T1
    • High peripheral signal and centrally isointense to muscle on T2
    • May be affected by the amount of stromal component in the tumor
    • Malignant variants show characteristics seen in other aggressive neoplasms (Skeletal Radiol 2005;34:625)
Prognostic factors
  • Majority are benign with excellent outcome after surgical resection
  • Some propensity for local recurrence if incompletely excised (J Surg Oncol 1980;13:301)
  • Malignant granular cell tumors behave similarly to malignant peripheral nerve sheath tumors and have a 50% rate of metastasis
  • Adverse prognostic factors include local recurrence, metastasis, larger tumor size, older patient age, histologic classification as malignant, presence of necrosis, increased mitotic activity, spindling of tumor cells, vesicular nuclei with large nucleoli and Ki67 ≥ 10% (Am J Surg Pathol 1998;22:779)
  • Another study showed size > 5 cm and distant metastases were the factors most negatively affecting survival (J Surg Oncol 2018;118:891)
Case reports
Treatment
  • Benign lesions treated with surgical excision have excellent prognosis
  • Malignant tumors require wider surgical resection
    • Lymph node dissection not recommended unless metastasis is biopsy proven
    • Benefit of adjuvant radiotherapy / chemotherapy is debatable but may be helpful in controlling progression in advanced disease (J Surg Oncol 2018;118:891)
    • Pazopanib showed activity in a single case report (Case Rep Med 2014;2014:794648)
Clinical images

Contributed by Mark R. Wick, M.D.

Arm



Images hosted on other servers:

Esophagus

Cecum

Gross description
  • Uninodular firm mass
  • In the skin, overlying epidermal hyperplasia can be seen
  • Cut surface is yellow with finely granular texture
Gross images

Contributed by Farres Obeidin, M.D.

Uninodular subcutaneous mass

Tan-yellow, gritty nodule

Ill defined borders

Intervening fibrous septae

Sessile subcutaneous nodule

Microscopic (histologic) description
  • Architecture:
    • Poorly defined mass composed of sheets of cells or nests / ribbons separated by thin collagenous bands
  • Cytological features:
    • Cells are round and polygonal to slightly spindled; cell borders can be distinct or show a syncytial pattern
    • Nuclei: range from small and dense to large and vesicular; mild to moderate nuclear atypia can be seen
    • Abundant eosinophilic cytoplasm with coarse granules (representing phagolysosome aggregates)
  • Overlying squamous epithelium may show pseudoepitheliomatous hyperplasia
  • Malignant criteria still debated
    • Fanburg-Smith criteria:
      • Necrosis, tumor cell spindling, vesicular nuclei with large nucleoli, > 2 mitoses/10 high power fields, high nuclear to cytoplasmic ratio and pleomorphism
      • 0: benign; 1 - 2: atypical; ≥ 3: malignant (Am J Surg Pathol 1998;22:779)
    • Nasser-Ahmed-Kowalski criteria:
      • Necrosis and > 2 mitoses/10 high power fields
      • 0: benign; ≥ 1: granular cell tumor of uncertain malignant potential
      • Metastasis was the only criteria to diagnose malignant granular cell tumor (Pathol Res Pract 2011;207:164)
Microscopic (histologic) images

Contributed by Farres Obeidin, M.D.

Involving tongue musculature

Pseudoepitheliomatous
hyperplasia

Coarse granular cytoplasm

Sheets of cells with abundant cytoplasm

Interspersed chronic inflammation

Ovoid to spindled appearance


Large cytoplasmic inclusions

S100+

Desmin-

Gastrointestinal tract submucosal lesion

Focal nuclear atypia

Adnexal sparing


Spindled area

Pseudoepitheliomatous
hyperplasia

CD68+

S100+

Fibrotic stroma

Cytology images

Case of the Week #434

Papanicolaou

May-Grünwald-Giemsa

Positive stains
Electron microscopy description
  • Cells in small clusters separated by basement membrane material
  • Nuclei have irregular, invaginated contour with dense granulation
  • Cytoplasm is complex and filled with irregular osmophilic granules
  • Occasional unmyelinated axons can be seen among the clusters of granular cells (J Surg Oncol 1980;13:301)
Molecular / cytogenetics description
Sample pathology report
  • Tongue, mass, resection:
    • Granular cell tumor, 1.3 cm (see comment)
    • Surgical margins, negative for tumor
    • Comment: Microscopic sections show an ill defined proliferation of bland round to ovoid cells with prominent eosinophilic, granular cytoplasm. The overlying epithelium shows pseudoepitheliomatous hyperplasia. S100 and CD68 stains are positive, supporting the diagnosis.
Differential diagnosis
Board review question #1
A 45 year old man presents with a 1.2 cm mass on the right subcutaneous forearm. The mass is diffusely positive for S100 and CD68. Which of the following is true about this lesion?



  1. Cells are filled with PAS+, diastase resistant granules
  2. It's likely reactive in nature and will regress without treatment
  3. Lesion is associated with multifocal lymphadenopathy
  4. Overlying epithelium is usually ulcerated and thinned
Board review answer #1
A. Cells are filled with PAS+, diastase resistant granules. This is a granular cell tumor. The granules are composed of phagolysosomes and are PASD+. They are not reactive and typically need surgery for treatment. Granular cell tumors are not associated with lymphadenopathy and the overlying epithelium is typically hyperplastic, giving a pseudoepitheliomatous appearance.

Reference: Granular cell tumor

Comment Here
Board review question #2
Which of the following immunostaining profiles would you expect to see in a granular cell tumor?

  1. Desmin+, myogenin+, MyoD1+
  2. S100+, CD1a+, fascin+
  3. S100+, CD68+, TFE3+
  4. S100+, SOX10+, HMB45+, MelanA+
Board review answer #2
C. S100+, CD68+, TFE3+. Granular cell tumors stain with S100, CD68 and TFE3. HMB45 and MelanA positivity favors a melanoma. Desmin and more specific myogenic markers are seen in adult type rhabdomyoma. CD1a and fascin are characteristic for Langerhans cell histiocytosis.

Reference: Granular cell tumor

Comment Here
Back to top