Granular Cell Tumor

Synonyms: Granular Cell Myoblastoma

Definition

Slow-growing, usually benign tumor, of debatable histogeneses, that often involves the skin, mucosa, or connective tissue, composed of large cells with highly granular cytoplasm due to accumulation of lysosomes.

Clinical Features

Location:
- classically:
  - tongue
- also many other locations e.g.:
  - skin
  - vulva
  - breast
  - larynx
  - bronchus
  - esophagus
  - stomach
  - appendix
  - rectum
  - anus
  - bile ducts
  - pancreas
  - urinary bladder
  - uterus
  - brain
  - pituitary gland
  - soft tissue1–10
May be multiple:
- particularly if black patient 8,11
Occasionally congenital:
- most in gingiva 12–14
- some with systemic involvement 15
Usually benign clinical course
Few cases with distant metastases16–21

Pathogenesis

Histogenesis controversial:22
- most favor Schwann's cell origin23–26 (Fig. 1
  Fig. 1: Granular cell tumor growing concentrically within and around a nerve cut transversally.
  )
  - but sometimes no evidence of Schwann's cell participation27
- indistinguishable changes in neoplastic and non-neoplastic smooth muscle cells and in tumoral ameloblasts28–30
  - may therefore be expression of a degenerative change resulting in cytoplasmic accumulation of lysosomes in a variety of cell types whether:
    - part of a benign or a malignant neoplasm such as:
      - angiosarcoma 31–34

Gross Pathology

Usually small
- up to 5 cm diameter
Hard consistency
Ill-defined margins (Fig. 2
Fig. 2: Granular cell tumor of skin. There is an ill-defined permeation of the dermis by whitish tissue.
)
Sometimes ulcerate if larger and cutaneous
- can look like a malignant neoplasm
Rarely polypoid27

Histopathology

Cells:
- large
- cytoplasm:
  - highly granular (Fig. 3
    Fig. 3: Granular cell tumor. The cells contain innumerable fine cytoplasmic granules as well as scattered larger eosinophilic globules.
    )
- granules:
  - most:
    - small
    - regular
  - alternate with larger round droplets with:
    - homogeneous eosinophilic appearance
    - stronger PAS positivity
- stroma:
  - often elastosis35
Secondary epithelial hyperplasia:
- if near an epithelial surface in sites such as:
  - skin
  - vulva
  - larynx
- may be incorrectly diagnosed as carcinoma36 (Fig. 4
  Fig. 4: Pseudoepitheliomatous hyperplasia in squamous epithelium overlying granular cell tumor.
  )
Ultrastructurally:
- cytoplasmic granules have appearance of lysosomes
- second cell population with ‘angulated bodies’ resulting in Gaucher cell-like appearance27
- replicated basal lamina material around granular cells:
  - suggesting repeated cycles of cellular injury and repair37

Special Stains and Immunohistochemistry

Cytoplasmic granules:
- contain large amounts of hydrolytic enzymes such as acid phosphatase
- consistently positive for Luxol fast blue38
At least some lesions positive for:
- S-100 protein
- laminin
- calretinin
- α subunit of inhibin
- HLA-DR:
  - thought to be related not to cell of origin but common immunologic pathogenesis39
- myelin basic protein:
  - presence controversial40
- CEA:34,40–46
  - presence controversial 40
  - may result from cross-reacting antigen14,47

Diagnosis

Best to:
- make diagnosis only when entire lesion granular
- designate other cases according to basic component, noting presence of focal granular changes

Differential Diagnosis

Select up to 2 differential diagnoses to compare with Granular Cell Tumor

Prognosis

Features favoring malignancy (especially in combination):
- necrosis
- high mitotic activity
- spindling of tumor cells
- vesicular nuclei with large nucleoli
- high MIB-148

References

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2 Copas P, Dyer M, Hall DJ, Diddle AW. Granular cell myoblastoma of the uterine cervix. Diagn Gynecol Obstet. 1981;3:251–254.

3 Demay RM, Kay S. Granular cell tumor of the breast. Pathol Annu. 1984;19(Pt 2):121–148.

4 Garancis JC, Komorowski RA, Kuzma JF. Granular cell myoblastoma. Cancer. 1970;25:542–550.

5 Johnston J, Helwig EB. Granular cell tumours of the gastrointestinal tract and perianal region. A study of 74 cases. Dig Dis Sci. 1981;26:807–816.

6 Lack EE, Worsham GF, Callihan MD, Crawford BE, Klappenbach S, Rowden G, et al. Granular cell tumor. A clinicopathologic study of 110 patients. J Surg Oncol. 1980;13:301–316.

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9 Sakurama N, Matsukado Y, Marubayashi T, Kodama T. Granular cell tumour of the brain and its cellular identity. Acta Neurochir (Wien). 1981;56:81–94.

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Last updated: 24 Feb 2006