Granular Cell Tumour

ICD-O:9580/0

Granular cell tumour (GCT) is an uncommon benign, slowly growing lesion and about half of the cases occur in the head and neck region [201, 205, 371]. Various histogenetic origins have been attributed to GCT, but recent prevailing opinion supports a relationship to Schwann cells. The tongue and subcutaneous tissue of the head and neck are the most common sites of the tumour, while laryngeal involvement is less frequent [162, 176, 187, 205, 286, 330, 371], and comprises about 10% of all cases [205]. These tumours most commonly appear in the posterior area of the true vocal cords and half of them extend into the subglottis as a smooth, polypoid and sessile lesion [205, 286, 371]. GCT typically appears between the fourth and fifth decades and the average age for laryngeal forms is 36 years [286]. The tumour rarely occurs in children [162]. Hoarseness, stridor and dysphagia are the most common complaints.

Histologically, the tumour is poorly circumscribed and consists of clusters and sheets of rounded and polygonal cells with indistinct cellular borders and small, bland-looking and central nuclei. A mild degree of nuclear pleomorphism may be present, but mitotic activity is low. Cytoplasm of tumourous cells is abundant, characteristically coarsely granular and eosinophilic.

Cytoplasmic granula are PAS-positive and resistant to digestion. Marked desmoplasia is often present in older lesions, thereby masking the presence of granular cells. In about 50-60% of cases, the covering epithelium shows pseudoepitheliomatous hyperplasia of the overlying squamous epithelium [190]. This curious histologi-cal feature mimicking infiltrative growth of islands of squamous epithelium may lead to the lesion being mistaken for a squamous cell carcinoma. However, the coexistence of GCT and true squamous cell laryngeal carcinoma has also been reported [206].

I mmunohisto chemical positivity for S-100 protein, vimentin, CD-68 and neuron-specific enolase, and negativity for keratin is in accordance with the proposed theory [49, 198, 232]. It is also confirmed by electron microscopic examination; the cytoplasmic granula were found to be lysosomal structures that contain infold-ings of cell membranes similar to those in Schwann cells [245].

Differential diagnosis should include benign lesions such as rhabdomyoma, paraganglioma or histiocytic proliferations. In contrast to GCT, rhabdomyoma does not show infiltrative growth, its cells are larger with well-defined cellular borders and evidence of cross-stri-ation. Paraganglioma typically shows an organoid pattern (i.e., Zellballen) and positivity for neuroendocrine markers. Proliferation of histiocytes is usually related to inflammatory reaction. Sheets of histiocytes are characteristically intermingled with inflammatory cells not commonly found in GCT. Covering pseudoepithelioma-tous hyperplasia of the GCT may lead to incorrect diagnosis of squamous cell carcinoma. An identification of the underlying granular cells may resolve this sometimes difficult diagnostic problem.

Complete surgical excision, with an attempt to preserve the normal structures, is the treatment of choice [371].

but the tumours may also be asymptomatic. Computerised tomography is a method of choice for radiological evaluation [324].

Histologically, chondromas show a characteristic well-defined lobular pattern with benign looking and evenly distributed chondrocytes that lack nuclear pleo-morphism and mitotic activity. The cellularity is judged to be low, when a given high power (x40) field is unlikely to contain more than 40 nuclei of chondrocytes [83, 209].

Pathologic diagnosis of laryngeal chondroma, especially from a small biopsy specimen, should be reported with due reservation. A misleading chondro-ma-like area may present in a well-differentiated case of a chondrosarcoma [26]. It has become apparent that many of the so-called chondromas from the past that recurred locally were actually misdiagnosed as low-grade chondrosarcomas [83]. It is obvious that the distinction between chondroma and low-grade chondro-sarcoma remains a very difficult task. Increased cellu-larity, nuclear pleomorphism and hyperchromasia, and the appearance of clusters of malignant-looking chon-drocytes in a single lacuna, are the most conspicuous histological features of chondrosarcoma. A thorough examination of the entire specimen is suggested, trying to avoid an incorrect diagnosis of a given tumour. Chondromas should also be distinguished from laryngeal chondrometaplasia, which appears as small nodules of the fibroelastic cartilage in the submucosal tissue of the glottic region [112].

Local conservative excision is preferred for treatment of laryngeal chondromas. Each recurrence of the lesion should be considered a low-grade chondrosarco-ma [358].

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