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  Volume 95
Numero 4
luglio-agosto 2009 		I documenti sono in formato PDF, consultabili utilizzando Acrobat Reader
 
Perianal granular cell tumor: report of a case and review of the literature

Massimiliano Mistrangelo, Paola Cassoni, Gitana Scozzari, Isabella Castellano, Giorgia Gavello, Franco Corno, Mario Morino
1Department of Surgery and Center of Minimal Invasive Surgery, University of Turin,
and 2Department of Biomedical Sciences and Human Oncology, University of Turin, Italy

Key words: granular cell tumor, Abrikossoff’s tumor, anal neoplasms.

abstract

Introduction. Granular cell tumor was first described by Abrikossoff in 1926. Over the years several cases of this neoplasm have been reported, with a variety of localizations. We here report a case of perianal granular cell tumor and discuss its histogenesis and its relevance to clinical practice.
Methods. The clinical course and histopathology of the case are reviewed, and a literature search for other reported cases has been performed.
Results. A 46-year-old woman presented with a perianal nodular lesion. Pathological examination revealed a granular cell tumor. A literature search produced only 25 other cases of anal and perianal granular cell tumors.
Conclusions. Granular cell tumors are rarely observed in the perianal region. Their existence must always be borne in mind in the differential diagnosis of perianal neoplasms. In most cases surgical excision is curative, but potential malignant transformation must be considered during therapeutic procedures and follow-up.

Introduction
Granular cell tumor (GCT) is a rare neoplasm occurring primarily in the skin, soft tissues and mucosa of the upper aerodigestive tract, particularly the tongue and vocal cords1. GCTs are mostly benign and often solitary. First described by Abrikossoff in 19262, they have been observed in many different locations throughout the body. The gastrointestinal tract is one of the most uncommon locations, and anorectal involvement is rare. GCT generally presents as a sole firm lesion, although multiple lesions may appear synchronously or metachronously at more than one site (10-15% of cases). In rare cases malignant degeneration occurs. The differential diagnosis between benign and malignant lesions is sometimes difficult because of their similar histological appearance. In some cases only the occurrence of distant metastases allows the diagnosis of malignancy. Recent studies have demonstrated a Schwann cell origin for GCT. This has been confirmed by ultrastructural features and immunohistochemical reactivity with S-100 protein, neuron-specific enolase and myelin-specific protein 3. GCTs are often asymptomatic, but when they are located in the anorectal region, perianal discomfort and bleeding are common. When a suspicious lesion is observed, surgical excision is mandatory for diagnosis and treatment of anorectal GCT. Considering the potential for malignancy, the possibility of metachronous metastases, and the risk of recurrence, careful follow-up is mandatory in all patients.
Twenty-five cases of perianal GCT have been reported to date and here we present a new case.

Case report
A 45-year-old woman presented to us with anal pain related to the presence of a perianal mass which had arisen 3 months earlier and the volume of which was progressively increasing. Physical examination showed a perianal soft mass adhering to the external sphincter and extending to the right circumference of the anus. The mass was 1.5 cm in diameter, smooth, and movable on superficial tissues. The differential diagnosis was between a tumor, a quiescent perianal abscess, and a granuloma.
By common consent we decided to perform a surgical excision of the mass in the interest of a correct diagnosis. The mass was removed under local anesthesia; it presented as white and smooth and seemed to infiltrate the external sphincter. The excision included a small peripheral part of the sphincter.
The postoperative period was uneventful. The patient was followed up every 3 months and after 2 years she was still alive and there had been no recurrences. Follow-up consisted of clinical examination with anoscopy. Perianal endosonography at 1 and 2 years proved negative for recurrences.

Pathology
The final histological examination revealed a GCT. At histology, the lesion was characterized by uniform, large eosinophilic cells with a granular cytoplasm. At immunohistochemistry, the cells were intensively stained with an anti-S-100 antibody, definitely directing the diagnosis towards a GCT (Figure 1). The surgical margins were free of disease and the skin overlaying the tumor was normal. The mitotic index was very low: less than 1 per 10 high power fields. The Ki67 proliferative index was expressed in less than 1% of tumor cells. Vimentin and CD68 were assayed as requested in an automated immunostainer (Ventana BenchMark AutoStainer, Ventana Medical Systems, Tucson, AZ, USA). They strongly marked the tumor cells.




Discussion
GCT is a rare soft tissue neoplasm that generally presents as a solitary small nodule. It may be sessile or pedunculated, and is usually benign4,5. It develops between the second and sixth decades of life, more frequently in women. The nosological entity was first described by Abrikossoff in 19262 and numerous cases occurring at different sites throughout the body have been reported since. The most frequent localizations were the oral mucosa, especially the tongue, and the skin6. Rare case reports described GCTs in the breast, respiratory tract, biliary tree, nervous system, and gastrointestinal tract. The latter localization, in particular the esophagus, accounts for about 5-10% of all CGTs4. Due to its low incidence, the literature on GCT consists mainly of single reports; Johnston and Helwig reported the largest series of gastrointestinal GCTs (74 cases) in 19814,17. GCTs of the anal and perianal region are extremely rare, and only 25 cases have been described so far4-17, including some malignancies10,15. GCTs are often small and painless and may be clinically mistaken for a quiescent abscess or an early neoplasm. In fact, Johnston and colleagues misdiagnosed a GCT as a squamous cell carcinoma on the basis of its appearance, featuring pseudoepitheliomatous hyperplasia of the overlying epithelium4. Of the GCTs reported by Johnston as occurring in the perianal region, nearly all presented as painless lumps.
Regardless of its location within the body, the histological, histochemical, and electron microscopic appearance of this neoplasm is similar. The histogenesis, however, has been the subject of much controversy and more than 20 designations related to different histogenetic theories have been coined over the years4. These theories suggested a variable origin from smooth or striated muscle cells, mesenchymal cells, or neural cells. Today the neural origin, first proposed by Feyrter in 1935, is considered the most likely18. In 1962, immunohistochemical and ultrastructural studies carried out by Fisher and Wechsler demonstrated a Schwann cell derivation19. However, at the present time, most authorities regard the lesion as a benign neoplastic process.
GCTs usually present as yellow-tan submucosal or subcutaneous nodules, generally less than 3 cm in diameter; the largest tumor described was in the stomach and measured 4 cm. GCTs, however, cannot be diagnosed by gross appearance alone and require histological examination.
The histological picture shows large polyhedral cells with a small central nucleus and eosinophilic granular cytoplasm. A PAS-positive reaction of intracytoplasmic granules is observed. Immunohistochemically, S-100, vimentin and the lysosomal marker CD68 are stained in the nucleus and cytoplasm. S-100 protein is characteristic of Schwann cells and points to the probable neural origin of these tumors20,21. As described by Ciulla et al., cells also contain cytoplasmic vacuoles, a packet of parallel microtubules better known as angulate bodies, and are generally surrounded by incomplete basal lamina and may show poorly-formed cell junctions7. Other pathological entities, however, may show similar features and the histological differential diagnosis may therefore be difficult. GCT can be confused with a well differentiated squamous cell carcinoma because both tumors may display overlying acanthosis and pseudoepitheliomatous hyperplasia. Immunohistochemical analysis of 21 benign GCTs by Melo et al.5 demonstrated that the tumors have a characteristic immunophenotype: neural markers, including S-100 protein and vimentin, are uniformly expressed4,5. The cells are negative for keratin, desmin, and muscle-specific actin.
In Parfitt’s series of 11 cases of GCT of the gastrointestinal tract, nestin, an intermediate filament protein expressed in undifferentiated cells during central nervous system and skeletal muscle development, was always expressed, proving to be a useful immunohistochemical marker for identifying these tumors. The results of previous studies suggest that GCTs may arise from a common multipotential stem cell in the gastrointestinal tract, which has the ability to differentiate among both interstitial cells of Cajal and peripheral nerve cell lines 14.
Gastrointestinal tract GCTs are usually asymptomatic and are often detected incidentally. The majority of GCTs show a benign behavior and malignancies are rare, accounting for 1-2% of all GCTs. A malignant GCT may histologically seem identical to a benign GCT and only the appearance of metastases (generally after local recurrence) will lead to a subsequent diagnosis of malignancy. In fact, 31 tumors that were thought to be benign and were treated by local excision ended up being malignant, with the occurrence of metastases in the long-term follow-up 15. It is not clear if malignant lesions result from the transformation of benign lesions or start out as malignant. Considering these observations, excision is mandatory in order to avoid local recurrence, lymphatic spread, and hematogenous dissemination in malignant cases. Adequate local excision is an effective treatment for GCT of the anorectal region. Complete and accurate follow-up, including repeated endoscopy, should be considered after local tumor excision, even if malignancies are rare.

References
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