Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Sites | Pathophysiology | Etiology | Clinical features | Diagnostic criteria | Case reports | Treatment | Clinical images | Gross description | Gross images | Microscopic (histologic) description | Microscopic (histologic) images | Positive stains | Negative stains | Electron microscopy description | Electron microscopy images | Molecular / cytogenetics description | Differential diagnosis | Board review question #1 | Board review answer #1 | Board review question #2 | Board review answer #2Cite this page: Cohen J, LeBoit P. Granular cell tumor. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/skintumornonmelanocyticgct.html. Accessed December 8th, 2019.
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
- Also known as Abrikossoff's tumor and granular cell schwannoma (Arch Otolaryngol 1968;88:174)
- Originally described as granular cell myoblastoma, given its resemblance to skeletal muscle myocytes (Am J Pathol 1947;23:721)
ICD coding
- D23.9: other benign neoplasm of skin, unspecified
Epidemiology
- Slightly higher incidence in women (Cancer 1987;60:220)
- Mainly adults but has wide age range of presentation (J Surg Oncol 1980;13:301)
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
- Harboring multiple tumors has been associated with Noonan syndrome (Eur J Pediatr Surg 2013;23:257) and LEOPARD syndrome (Clin Genet 2009;75:185)
Clinical features
- Slowly growing papule or nodule; rarely ulcerates (Adv Anat Pathol 1999;6:186)
- Rare cases can exhibit multiple lesions (Cutis 2002;69:343)
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
- 48 year old woman with upper back nodule (Indian J Dermatol 2015;60:322)
- 51 year old woman with left posterior chest wall mass and lymph node metastases (Am J Dermatopathol 2015;37:334)
- 53 year old woman with an enlarging left lower abdominal nodule (Am J Dermatopathol 2010;32:370)
- 54 year old patient with toe lesion (Dermatol Res Pract 2010;2010:184125)
- 69 year old woman with a rapidly enlarging firm neck mass (Am J Dermatopathol 2017;39:e50)
Treatment
- Benign and malignant tumors are typically treated with wide local excision (J Surg Oncol 1980;13:301)
- MOHS micrographic surgery is an option in anatomic sites in which conservative re-excision is desired (Case Rep Oncol Med 2012;2012:453569)
Clinical images
Gross description
- Greyish-white to pale yellow
- Oftentimes not well circumscribed
Gross images
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.
Positive stains
Negative stains
Electron microscopy description
- Membrane bound cytoplasmic granules containing lysosomes of varying sizes (J Cutan Pathol 1981;8:277, Oral Surg Oral Med Oral Pathol 1977;44:227, Ultrastruct Pathol 2018;42:304)
- Larger secondary lysosomes can be seen
- Some membrane bound granules contain aggregates of virus-like particles
- Some lesional cells contain long spacing collagens (Luse bodies)
- Variably abundant basal lamina material may be seen
Electron microscopy images
Molecular / cytogenetics description
- A subset of nonneural granular cell tumors harbor ALK gene fusions (Am J Surg Pathol 2018;42:1133)
Differential diagnosis
- Melanocytic neoplasms (J Am Acad Dermatol 2004;50:765)
- Leiomyosarcoma (Am J Dermatopathol 1988;10:234, Am J Dermatopathol 1999;21:307)
- Positive for desmin and alpha smooth muscle type, negative for S100 and SOX10
- Atypical fibroxanthoma (AFX) (J Cutan Pathol 2005;32:314, J Cutan Pathol 2010;37:380)
- Dermatofibroma (benign fibrous histiocytoma) (Dermatology 1999;199:54)
- Xanthoma
- Reticulohistiocytoma
- Adult-type rhabdomyoma
- Can be composed of sheets of polygonal cells with abundant eosinophilic, variably granular cytoplasm
- Usually demonstrate cross striations
- Positive for desmin, actin - muscle specific and myogenin, negative for S100
- Alveolar soft part sarcoma
Board review question #1
- 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?
- The abundant granular cytoplasm is indicative of numerous membrane bound cytoplasmic granules containing aggregates of lysosomes.
- An S100 or SOX10 stain is positive in most tumors and is reflective of Schwannian differentiation.
- Perineural accentuation of cellularity is a feature of malignancy.
- 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.
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?
- A subset are negative for S100 and other neural markers and can have a polypoid appearance.
- Atypical features include necrosis, increased mitotic activity and nuclear pleomorphism.
- NF1 is commonly mutated in conventional granular cell tumors.
- 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.
Comment Here
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.
Comment Here
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