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granular cell tumor

Tuesday 16 June 2009

Abrikossoff tumor, Granular cell myoblastoma, Granular cell nerve sheath tumor, Granular cell schwannoma

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.

Images

- Granular cell tumor and mastocytosis

- Esophageal granular cell tumor with pseudoepitheliomatous hyperplasia (differential : squamous cell carcinomas )

Digital slides

- HPC:73 (HPC:73) : Mammary granular cell tumor
- HPC:63 (HPC:63) : Gingival granular cell tumor (Neonatal epulis)
- HPC:369 : Tracheal invasive granular cell tumor
- UI:340 - Granular cell tumor
- pathxchange.org #3106 : Esophageal granular cell tumor
- JRC:5333 : Mammary granular cell tumor

Granular cell tumor is a tumor that can develop on any skin or mucosal surface, but occurs on the tongue 40% of the time.

The formation of a granular cell tumor is a neoplastic process and the lesions formed are of neural derivation, as supported by immunophenotypic and ultrastructural evidence.

The usual presentation is of slow growing behavior, forming a polygonal accumulation of secondary lysosomes in the cytoplasm.

Granular cell tumors are typically solitary and are rarely larger than three centimeters.

Localization

The neoplasm can affect all parts of the body, however, the head and neck areas are affected 45% to 65% of the time.

Of the head and neck cases, 70% of lesions are located intra-orally (tongue, oral mucosa, hard palate). The next most common location that lesions are found in the head and neck area is the larynx (10%).

Granular cell tumors are also found in the internal organs, particularly in the upper aerodigestive tract.

- tongue
- skin
- vulva
- breast
- larynx
- bronchus
- esophagus
- stomach
- appendix
- rectum
- anus
-  bile ducts
- pancreas
- urinary bladder
- uterus
- brain
- pituitary gland
- soft tissue

Epidemiology

- May be multiple (particularly if black patient)
- Occasionally congenital (most in gingiva: neonatal epulis)
- some with systemic involvement
- Usually benign clinical course
- Few cases with distant metastases

Macroscopy

- Usually small

  • up to 5 cm diameter

- Hard consistency
- Ill-defined margins
- Sometimes ulcerate if larger and cutaneous
- can look like a malignant neoplasm
- Rarely polypoid

Microscopy

- large cells:
- large cytoplasm
- highly granular cytoplasm (granular cell tumors)
- The cells contain innumerable fine cytoplasmic granules as well as scattered larger eosinophilic globules.
- granules

  • mostly small and regular
  • alternate with larger round droplets with homogeneous eosinophilic appearance and stronger PAS positivity

- stroma

  • often elastosis

- Secondary epithelial hyperplasia:

  • if near an epithelial surface in sites such as skin, vulva, larynx
  • may be incorrectly diagnosed as carcinoma

Special Stains

Immunohistochemistry

- Cytoplasmic granules: contain large amounts of hydrolytic enzymes such as acid phosphatase, consistently positive for Luxol fast blue

- At least some lesions positive for:

  • S-100 protein
  • laminin
  • calretinin
  • α subunit of inhibin
  • HLA-DR:
  • myelin basic protein:
  • CEA

Differential diagnosis

- schwannoma
- neurofibroma
- alveolar soft part sarcoma
- make diagnosis only when entire lesion granular
- designate other cases according to basic component, noting presence of focal granular changes

Ultrastructure

- cytoplasmic granules have appearance of lysosomes
- second cell population with ‘angulated bodies’ resulting in Gaucher cell-like appearance
- replicated basal lamina material around granular cells, suggesting repeated cycles of cellular injury and repair

Management

The primary method for treatment is surgical, not medical.

Radiation and chemotherapy are not needed for benign lesions and are not effective for malignant lesions.

Prognosis

This type of tumor has been found to be both benign and malignant, although malignancy is rare and comprises only 2% of all granular cell tumors.

Benign granular cell tumors have a recurrence rate of 2% to 8% when resection margins are deemed clear of tumor infiltration.

When the resection margins of a benign granular cell tumor are positive for tumor infiltration the recurrence rate is increased to 20%.

Malignant lesions are aggressive and difficult to eradicate with surgery and have a recurrence rate of 32%.

Pathogenesis

- Histogenesis controversial
- most favor Schwann’s cell origin
- but sometimes no evidence of Schwann’s cell participation
- indistinguishable changes in neoplastic and non-neoplastic smooth muscle cells and in tumoral ameloblasts
- may therefore be expression of a degenerative change resulting in cytoplasmic accumulation of lysosomes in a variety of cell types whether:

  • previously normal
  • part of a benign or a malignant neoplasm such as:
    • MPNST
    • leiomyosarcoma
    • angiosarcoma

See also

- Tumors

References

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

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

- Garancis JC, Komorowski RA, Kuzma JF. Granular cell myoblastoma. Cancer. 1970;25:542–550.McSwain GR, Colpitts R, Kreutner A, O’Brien PH, Spicer S. Granular cell myoblastoma. Surg Gynecol Obstet. 1980;150:703–710.

- Garancis JC, Komorowski RA, Kuzma JF. Granular cell myoblastoma. Cancer. 1970;25:542–550.Moscovic EA, Azar HA. Multiple granular cell tumors (“myoblastomas”). Case report with electron microscopic observations and review of the literature. Cancer. 1967;20:2032–2047.

Localization

- Chandrasoma P, Fitzgibbons P. Granular cell tumor of the intrapancreatic common bile duct. Cancer. 1984;53:2178–2182.

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

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

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

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

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

- Garancis JC, Komorowski RA, Kuzma JF. Granular cell myoblastoma. Cancer. 1970;25:542–550.McSwain GR, Colpitts R, Kreutner A, O’Brien PH, Spicer S. Granular cell myoblastoma. Surg Gynecol Obstet. 1980;150:703–710.

- Garancis JC, Komorowski RA, Kuzma JF. Granular cell myoblastoma. Cancer. 1970;25:542–550.Moscovic EA, Azar HA. Multiple granular cell tumors (“myoblastomas”). Case report with electron microscopic observations and review of the literature. Cancer. 1967;20:2032–2047.Vance SF, Hudson RP. Granular cell myoblastoma. Clinicopathologic study of 42 patients. Am J Clin Pathol. 1969;52:208–211.

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

- Garancis JC, Komorowski RA, Kuzma JF. Granular cell myoblastoma. Cancer. 1970;25:542–550.McSwain GR, Colpitts R, Kreutner A, O’Brien PH, Spicer S. Granular cell myoblastoma. Surg Gynecol Obstet. 1980;150:703–710.

- Garancis JC, Komorowski RA, Kuzma JF. Granular cell myoblastoma. Cancer. 1970;25:542–550.Moscovic EA, Azar HA. Multiple granular cell tumors (“myoblastomas”). Case report with electron microscopic observations and review of the literature. Cancer. 1967;20:2032–2047.Seo IS, Azzarelli B, Warner TF, Goheen MP, Senteney GE. Multiple visceral and cutaneous granular cell tumors. Ultrastructural and immunocytochemical evidence of Schwann cell origin. Cancer. 1984;53:2104–2110.

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

- Garancis JC, Komorowski RA, Kuzma JF. Granular cell myoblastoma. Cancer. 1970;25:542–550.McSwain GR, Colpitts R, Kreutner A, O’Brien PH, Spicer S. Granular cell myoblastoma. Surg Gynecol Obstet. 1980;150:703–710.

- Garancis JC, Komorowski RA, Kuzma JF. Granular cell myoblastoma. Cancer. 1970;25:542–550.Moscovic EA, Azar HA. Multiple granular cell tumors (“myoblastomas”). Case report with electron microscopic observations and review of the literature. Cancer. 1967;20:2032–2047.de la Monte SM, Radowsky M, Hood AF. Congenital granular-cell neoplasms. An unusual case report with ultrastructural findings and a review of the literature. Am J Dermatopathol. 1986;8:57–63.

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

- Garancis JC, Komorowski RA, Kuzma JF. Granular cell myoblastoma. Cancer. 1970;25:542–550.McSwain GR, Colpitts R, Kreutner A, O’Brien PH, Spicer S. Granular cell myoblastoma. Surg Gynecol Obstet. 1980;150:703–710.

- Garancis JC, Komorowski RA, Kuzma JF. Granular cell myoblastoma. Cancer. 1970;25:542–550.Moscovic EA, Azar HA. Multiple granular cell tumors (“myoblastomas”). Case report with electron microscopic observations and review of the literature. Cancer. 1967;20:2032–2047.Lack EE, Worsham GF, Callihan MD, Crawford BE, Vawter GF. Gingival granular cell tumors of the newborn (congenital “epulis”). A clinical and pathologic study of 21 patients. Am J Surg Pathol. 1981;5:37–46.

- Matthews JB, Mason GI. Granular cell myoblastoma. An immunoperoxidase study using a variety of antisera to human carcinoembryonic antigen. Histopathology. 1983;7:77–82.

- Al-Sarraf M, Loud AV, Vaitkevicius VK. Malignant granular cell tumor. Histochemical and electron microscopic study. Arch Pathol. 1971;91:550–558.

- Kindblom L-G, Olsson K-M. Malignant granular cell tumor. A clinicopathologic and ultrastructural study of a case. Pathol Res Pract. 1981;172:384–393.

- Robertson AJ, McIntosh W, Lamont P, Guthrie W. Malignant granular cell tumour (myoblastoma) of the vulva. Report of a case and review of the literature. Histopathology. 1981;5:69–79.

- Troncoso P, Ordonez NG, Raymond AK, Mackay B. Malignant granular cell tumor. Immunocytochemical and ultrastructural observations. Ultrastruct Pathol. 1988;12:137–144.

- Usui M, Ishii S, Yamawaki S, Sasaki T, Minami A, Hizawa K. Malignant granular cell tumor of the radial nerve. Cancer. 1977;39:1547–1555.

- Uzoaru I, Firfer B, Ray V, Hubbard-Shepard M, Rhee H. Malignant granular cell tumor. Arch Pathol Lab Med. 1992;116:206–208.

- Ordonez NG, Mackay B. Granular cell tumor: a review of the pathology and histogenesis. Ultrastruct Pathol. 1999;23:207–222.

- Bedetti CD, Martinez AJ, Beckford NS, May M. Granular cell tumor arising in myelinated peripheral nerves. Light and electron microscopy and immunoperoxidase study. Virchows Arch [A]. 1983;402:175–183.

- Budzilovich GN. Granular cell “myoblastoma” of vagus nerve. Acta Neuropathol. 1968;10:162–169.

- Fisher ER, Wechsler H. Granular cell myoblastoma – a misnomer. Electron microscopic and histochemical evidence concerning its Schwann cell derivation and nature (granular cell schwannoma). Cancer. 1962;15:936–957.

- Shimamura K, Osamura RY, Ueyama Y, Hata J-I, Tamaoki N, Machida N, et al. Malignant granular cell tumor of the right sciatic nerve. Report of an autopsy case with electron microscopic, immunohistochemical, and enzyme histochemical studies. Cancer. 1984;53:524–529.

- Le Boit PE, Barr RJ, Burall S, Metcalf JS, Yen TS, Wick MR. Primitive polypoid granular-cell tumor and other cutaneous granular-cell neoplasms of apparent nonneural origin. Am J Surg Pathol. 1991;15:48–58.

- Christ ML, Ozzello L. Myogenous origin of a granular cell tumor of the urinary bladder. Am J Clin Pathol. 1971;56:736–749.

- Navarrette AR, Smith M. Ultrastructure of granular cell ameloblastoma. Cancer. 1971;27:948–955.

- Sobel JH, Marquet E, Schwarz R. Granular degeneration of appendiceal smooth muscle. Arch Pathol. 1971;92:427–432.

- Finkel G, Lane B. Granular cell variant of neurofibromatosis. Ultrastructure of benign and malignant tumors. Hum Pathol. 1982;13:959–963.

- McWilliam LJ, Harris M. Granular cell angiosarcoma of the skin. Histology, electron microscopy and immunohistochemistry of a newly recognized tumor. Histopathology. 1985;9:1205–1216.

- Miettinen M, Lehtonen E, Lehtola H, Ekblom P, Lehto V, Virtanen I. Histogenesis of granular cell tumor. An immunohistochemical and ultrastructural study. J Pathol. 1984;142:221–229.

- Nistal M, Paniagua R, Picazo ML, Cermenño deGiles F, Ramos Guerreira L. Granular changes in vascular leiomyosarcoma. Virchows Arch [A]. 1980;386:239–248.

- McMahon JN, Rigby HS, Davies JD. Elastosis in granular cell tumours. Prevalence and distribution. Histopathology. 1990;16:37–41.

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- Mittal KR, True LD. Origin of granules in granular cell tumor. Intracellular myelin formation with autodigestion. Arch Pathol Lab Med. 1988;112:302–303.

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- Clark HB, Minesky JJ, Agrawal D, Agrawal HC. Myelin basic protein and P2 protein are not immunohistochemical markers for Schwann cell neoplasms. A comparative study using antisera to S-100, P2, and myelin basic proteins. Am J Pathol. 1985;121:96–101.

- Fine SW, Li M. Expression of calretinin and the alpha-subunit of inhibin in granular cell tumors. Am J Clin Pathol. 2003;119:259–264.

- Mazur MT, Shultz JJ, Myers JL. Granular cell tumor. Immunohistochemical analysis of 21 benign tumors and one malignant tumor. Arch Pathol Lab Med. 1990;114:692–696.

- Mukai M. Immunohistochemical localization of S-100 protein and peripheral nerve myelin proteins (P2 protein, PO protein) in granular cell tumors. Am J Pathol. 1983;112:139–146.

- Nakazato Y, Ishizeki J, Takahashi K, Yamaguchi H. Immunohistochemical localization of S-100 protein in granular cell myoblastoma. Cancer. 1982;49:1624–1628.

- Nathrath WBJ, Remberger K. Immunohistochemical study of granular cell tumours. Demonstration of neurone specific enolase, S 100 protein, laminin and alpha-1-antichymotrypsin. Virchows Arch [A]. 1986;408:421–434.

- Penneys NS, Adachi K, Ziegels-Weissman J, Nadji M. Granular cell tumors of the skin contain myelin basic protein. Arch Pathol Lab Med. 1983;107:302–303.

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