Granular Cell Tumors Clinical Presentation

Updated: Dec 29, 2018
  • Author: Vladimir O Osipov, MD; Chief Editor: E Jason Abel, MD  more...
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Presentation

History

Benign lesions manifest as nonulcerated and usually painless nodules with an insidious onset and slow growth rate. They are rarely larger than 3 cm and usually have been noted for less than 6 months.

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Physical

Granular cell tumors may occur at any site, but easily noticed surface lesions (ie, head, neck, trunk, extremities) are far more common than visceral lesions. Other aspects of location are as follows:

  • The tongue is affected in approximately 25% of cases; breast involvement is also common

  • All together, parenchyma, subcutaneous tissue, and dermis account for approximately 15% of cases; a third of those are in the parenchyma

  • Origin in skeletal muscle is rare

  • The lesions usually involve small- to medium-sized cranial or spinal nerves, although neurologic deficit is rare

  • Visceral involvement is encountered as mucosal or submucosal nodules in the esophagus, [7, 8] stomach, small and large intestines, larynx, bronchi, gallbladder, and biliary tract

  • The gastrointestinal tract harbors approximately 5% of all granular cell tumors

  • Central nervous system granular cell tumors are extremely rare [9]

  • Lesions can be incidental findings, or they may give rise to obstructive or pressure symptoms when large enough and in a critical location

Nodules are usually solitary but may be multiple in up to 10% of cases (patients with 26 and 52 tumors are on record). Multiple granular cell tumors have been reported in patients with LEOPARD (lentigenes, electrocardiographic conduction anomalies, ocular hypertelorism, pulmonary stenosis, abnormalities of genitalia, retardation of growth, deafness) syndrome (Noonan syndrome), a rare autosomal dominant, disorder caused by a mutation in the protein tyrosine phosphatase, nonreceptor type 11 gene (PTPN11). [2, 10]

An association between multiple cutaneous granular cell tumors and neurofibromatosis has been suggested, but remains unproven. [11]

Malignant lesions

Malignant granular cell tumors are rare. By convention, granular cell tumors are classified as malignant when their constituent cells show cytologic features of malignancy or when a morphologically benign granular cell tumor metastasizes to regional lymph nodes or distant sites or otherwise causes death.

Malignancy is encountered more often in deep-seated lesions in adults, with a mean patient age of 50 years. Sex and race distribution of malignant tumors mirrors that of benign lesions. A history of long clinical duration and rapid recent growth has been observed in some cases, suggesting a possibility of malignant transformation from a preexisting benign granular cell tumor.

The lesions are usually larger (ie, 4-15 cm) and may be locally destructive, thus causing symptoms (eg, pressure, obstruction, hemorrhage, ulceration, secondary infection) depending on the site. Metastases to regional lymph nodes and/or distant organs (most common site is the lungs) and concomitant symptoms may be present.

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Causes

Pareja et al identified loss-of-function mutations in ATP6AP1 or ATP6AP2 in 72% of granular cell tumors. Silencing of these genes in vitro results in impaired vesicle acidification, redistribution of endosomal compartments, and accumulation of intracytoplasmic granules, which are cardinal phenotypic characteristics of granular cell tumors. [12]

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