Granular Cell Tumors

Updated: Nov 12, 2020
  • Author: Vladimir O Osipov, MD; Chief Editor: E Jason Abel, MD  more...
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Overview

Practice Essentials

Granular cell tumors (GCTs), also known as Abrikossoff tumors, are rare soft-tissue neoplasms probably derived from Schwann cells. [1, 2]  

Most granular cell tumors are benign, although some may be locally aggressive. [3]  Less than 2% are malignant, but these are aggressive and associated with a poor prognosis. [4, 5]

Granularity of the cells in these tumors is due to the accumulation of secondary lysosomes in the cytoplasm. This change is rather nonspecific and can be observed in many non-neural tumors, including those arising from smooth muscle, connective tissue, neuroglia, endothelial, and epithelial cells.

This article describes neural granular cell tumors. Non-neural granular cell tumors are discussed only as differential diagnoses.

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Etiology and Pathophysiology

Granular cell tumors are typically solitary and smaller than 3 cm. They are usually located in the dermis or subcutis and less frequently in the submucosa, smooth muscle, or striated muscle. Granular cell tumors are also found in the internal organs, particularly in the upper aerodigestive tract. Benign and malignant counterparts are known; the latter are rare, comprising fewer than 2% of all granular cell tumors. [6]

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. [7]

Following whole-exome sequencing, RNA sequencing, and targeted sequencing of 51 GCT samples,Sekimizu and colleagues reported identified loss-of-function mutations in 7 additional genes encoding vacuolar H+ -ATPase (V-ATPase) components. 

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Epidemiology

Frequency

The lesion is uncommon. Exact figures are unavailable. Much of the literature on granular cell tumors consists of reports of single cases.

Granular cell tumors appear to be more common in black persons. Multiplicity of lesions is definitely more common in black persons. Up to 10% of granular cell tumors are multiple (ie, two to four lesions).

Race-, sex-, and age-related demographics

A slight female predominance exists. The female-to-male ratio is estimated at approximately 3:2. [6]

Granular cell tumors affect persons of varying ages, and the range is wide. Most patients are middle-aged, with a peak incidence in the fourth through sixth decades of life.

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Prognosis

Prognosis for patients with granular cell tumors is as follows [6] :

  • In benign lesions, recurrence rates are 2-8%, even when the resection margins are deemed free of tumor infiltration; they are around 20% when the margins are positive for tumor.

  • Malignant lesions are aggressive and difficult to eradicate with surgery. Local recurrences are as high as 32%, and metastases were reported in half of the patients. Metastases are usually detected within 2 years.

  • Of patients with malignant granular cell tumors, 39% die of the disease within 3 years after detection of the primary tumor.

  • Ki-67 immunoreactivity of 10% or more tumor cells is an adverse prognostic factor.

The main complication of benign lesions is recurrence. With malignant granular cell tumors, the main complications are recurrence, metastases, or both.

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