granular cell tumor ( gct ) , also known as abrikossoff 's tumor , is a rare benign soft tissue neoplasm that most often arises in the tongue , and also occurs in other anatomic locations , including the vulva . gct was originally described by abrikossoff in 1926 in a patient with a tongue lesion and because of the apparent association between granular tumor cells and skeletal muscle the term " granular cell myoblastoma " was proposed in the original description . however , it is now commonly accepted that gct is of neural origin and most likely derived from schwann cells , a pathogenesis suggested by immunohistochemical and ultrastructural studies , although some authors believe that gct is not a specific entity , but rather a degenerative change that can occur not only in schwann cells , but also in a variety of other neoplastic cells . gct usually occurs as a single tumor , frequently in the head and neck region especially in the tongue , nevertheless multiple lesions occur in 729% of cases . multiple gcts most often appear in black women , frequently including intraoral gct , having either a synchronous appearance or presenting as a sequential development over time . in the present study we report a case of a gct involving the tongue of a 14-year  old girl , with no other abnormalities and with a metachronous occurrence of a second gct in vulva , after a period of 10 years . both tumors were analyzed by optical microscopy and immunohistochemistry and several observations were made regarding their presentation and immunohistochemical profile . in november 2001 , a 14-year - old caucasian girl presented with a painless lingual swelling , incidentally discovered 4 months earlier . there was no previous clinical history of interest , the patient referred a healthy lifestyle , had no family history of tumors and all laboratory data were normal . oral examination revealed a single , firm nodule about 2 cm in size on the left side of the dorsum of the tongue , with a smooth surface and a slight yellowish color . the lesion was apparently indolent and not ulcerated ; there were no palpable lateral cervical lymph nodes . excisional biopsy was performed , which revealed histopathological features consistent with a gct associated with pseudoepitheliomatous hyperplasia ( peh ) of lingual epithelium [ figure 1 and 2 ] . the deep resected margin was affected by the tumor ; therefore , a clinical follow - up was planned at 1 , 6 , 12 , 24 and 36 months after surgical excision . photomicrograph of the lingual lesion showing overlying surface epithelium with cellular underlying connective tissue ( h&e stain , x10 ) the surface epithelium of lingual gct shows pseudoepitheliomatous hyperplasia ( peh ) ( h&e stain , 100 ) ten years later , in september 2010 , at 24 years of age , the patient was seen again by the gynecology service for a single vulvar nodule , slightly painful on palpation , associated with pruritus . at this time gynecological examination was unremarkable , except for the finding of a subcutaneous 1.5 cm mobile nodule in the skin of the left labium minus , which was preoperatively interpreted as a vulvar sebaceous cyst . in lithotomy position , the vulvar nodule was resected via a longitudinal incision with decapsulation of the nodule together with a small portion of vulvar skin . histopathological examination revealed the presence of a gct [ figure 3 ] without peh in the overlying vulvar mucosa and with no cytologic features of atypia or malignancy . at present the patient remains free of vulvar tumor recurrence after 15 postoperative months.a prolonged clinical follow - up is planned for the patient . photomicrograph of the vulvar lesion diagnosed with an interval of 10 years showing a cellular tumor ( h&e stain , x10 ) histologically , both lingual and vulvar lesions were composed of cells with large eosinophilic and granular cytoplasm , presenting small central nuclei and intracytoplasmic pas - positive granules [ figure 4 ] . no atypical mitoses , pleomorphism or necrosis were observed in either lesion and both showed involvement of the deep resected edge . in the lingual lesion , the tumor cells were intermingled in the deep areas with bundles of striated muscle [ figure 5 ] and arranged in nests and sheets of variable size . these characteristics were absent in the vulvar tumor that showed a nodular growth pattern with expansive outline . tumor cells showed a periodic acid schiff ( pas ) positive 
 granular cytoplasm ( pas stain , x400 ) deep areas of lingual granular cell tumor ( gct ) showing tumor cells intermingled with bundles of striated muscles ( h&e stain , x200 ) the immunohistochemical study revealed strong positivity ( + + + ) of the tumor cells of both lesions for s-100 protein ( cytoplasmic and nuclear staining ; polyclonal rabbit antibody , ready to use ( rtu ) ; dako , glostrup , denmark ) [ figure 6 ] , vimentin ( predominantly membranous pattern ; v9 clone , rtu ; dako ) [ figure 7 ] and cd57 ( leu7;tb01 clone , rtu ; dako ) ; and a mild positivity ( + + ) for enolase ( ens ; bbs / nc / vi - h14 clone , rtu ; dako ) , cd68 ( kp1 clone , rtu ; dako ) and -inhibin ( r1 clone , rtu ; dako ) ; the latter marking about 10% of tumor cells ; whereas , pan - cytokeratin ( clone ae1/ae3 , rtu ; dako ) , desmin ( d33 clone , rtu ; dako ) , smooth muscle actin ( 1a4 clone , rtu ; dako ) , -estrogen receptor ( -er ; 1d5 clone , rtu ; dako ) , progesterone receptor ( pgr 636 clone , rtu ; dako ) and androgen receptor ( ar-441 clone , dilution 1:50 ; dako ) were all negative . the tumor cells were intensely immunoreactive for s-100 protein ( ihc stain , x400 ) the tumor cells showing intense positivity for vimentin ( ihc stain , x400 ) in addition , we found only weak positivity ( + ) for calretinin antibody ( polyclonal antibody , dilution 1:30 , biogenex ) in the vulvar tumor . however , calretinin was more pronounced ( + + ) in the lingual tumor , particularly in tumor cells located in the vicinity of the overlying peh figure 8 that showed a clear calretinin over expression . interestingly , tumor vasculature situated close to peh showed marked cd105 ( endoglin ; sn6h clone , rtu ; dako ) reactivity figure 9 , while all remaining vessels were negative for endoglin , as was found in all vulvar tumor vessels . moreover , in both tumors ki-67 antigen ( mib-1 clone , ready to use ; dako ) showed a very low percentage ( 12% ) of labeled tumor cell nuclei , nuclear expression of p53 ( do-7 clone , rtu ; dako ) being completely negative . in the lingual tumor , areas with peh showed marked ki-67 positivity in overlying epithelia [ figure 10 ] , with strong nuclear ki67 staining in 2030% of basal and parabasal cells . gct in close contact with peh displayed overexpression of calretinin protein ( ihc stain , x250 ) the tumor cells close to the epithelium of lingual tumor were associated with a cd 105 positivity in the vascular network unlike the remaining vessels that were negative for endoglin ie cd 105 ( ihc stain , x400 ) isolated tumor cells were positive for ki67 whereas the overlying peh epithelium of the lingual tumor showed marked ki67 activity ( ihc stain , x250 ) although it most frequently involves the head and neck region , especially the tongue which represents approximately 30% of lesions , it has been found throughout the body . gct is seen almost invariably as a benign tumor , usually solitary , although very uncommon malignant gcts have also been described and multiple benign gct lesions can occur in up to approximately 25% of cases , suggesting that a patient with gct should undergo a complete physical examination , given that the presence of another tumor is quite possible and certainly more common than is generally thought . multiple gcts are most often located in the intradermal or subcutaneous tissue , although oral mucosa , gastrointestinal and genital tract can also be involved , with a synchronous or metachronus occurrence , as was presented by our patient with an interval of 10 years between the two tumors . nevertheless , the cases of concurrent presentation seem to be more frequently reported in the literature . clinically , our patient presented no other abnormality and had no family history of gct , all exploratory data being completely normal after a full medical checkup . this is important since in the last decade multiple gct have been described in association with syndromes , such as leopard syndrome and noonan syndrome , as well as with neurofibromatosis type i. curiously , in all these processes there is an aberrant signaling in the ras / map pathway , which promotes cellular differentiation , proliferation and oncogenesis , with a special vulnerability in schwann cells , the putative origin of gct . given these associations , it has been suggested that a diagnosis of multiple gct , especially in young patients as in this case warrants a complete physical examination , for systemic manifestations of underlying genetic or somatic defects . so the take - home message , given these data and the potential multicentricity of gct , would be that in the presence of a diagnosis of gct in a young patient a complete physical examination in search of other possible tumors or coexisting abnormalities is obligatory , as well as planning a prolonged clinical follow - up , as highlighted by the present case is also necessary . in our patient both gct were studied with a broad panel of antibodies and our immunohistochemical findings being generally in agreement with those reported in the literature . in our opinion , the strong positivity found for s-100 , vimentin and cd57 point to a possible schwannian / neural origin as the most plausible for these tumors . the low proliferation index with ki67 and p53 negativity confirm the benign nature of the two cgts in our patient , which curiously has not recurred despite involvement of the deep rim , an aspect previously reported by others , indicating that these are slow - growing tumors with a low and late recurrence rate , even with positive margins and regardless of the pattern of invasion . absence of hormone receptors ( -er , pgr and ar ) in both tumors in principle excludes the existence of any hormonal influence on their appearance , data that can not explain the increased incidence of multiple gct in women . finally with regard to peh , this morphological change can appear in the overlying epithelium of approximately 50% of gct , mimicking squamous cell carcinoma and sometimes posing a challenge for diagnosis . in addition , the cellular component of gct close to the peh showed a clear over expression of calretinin , a primarily neuronal protein , in comparison to the deep portions of tumor , suggesting that calretinin overexpression in some way influenced the appearance of peh , as already noted by others . we also found that peh is located in proximity to a localized network of vessels immunoreactive to endoglin , this previously undescribed data suggests , in our opinion , an interaction between peh cells and underlying stroma since gct lacks cd105 + vessels . however , a full understanding of the role of cd105 in the interaction between gct and hyperplastic squamous epithelium requires further study in a wide series of gct analyzing what factors trigger the development of peh in gct . our study emphasizes that patients with gct , especially young patients , should be followed for a long - term , looking for multiple tumors or other abnormalities suggestive of a systemic syndrome , given the associations described in multiple gct .
granular cell tumor ( gct ) usually occurs as a single tumor , although sometimes multiple lesions can occur . in present report 
 we analyze the clinicopathological and immunohistochemical features of a multiple gct involving the tongue of a 14-year - old girl , with no other abnormalities , with a metachronous occurrence of a second gct in vulva , after a period of 10 years . 
 both tumors revealed s-100 , vimentin and cd57 positivity . 
 in addition , over expression of calretinin was observed in tumor cells located in the vicinity of pseudoepitheliomatous hyperplasia ( peh ) of the tongue . 
 tumor vasculature situated close to the peh showed marked cd105 reactivity , data not described so far , suggesting an interaction between peh cells and underlying stroma , since gct completely lacks cd105 vessels . 
 our study emphasizes that patients with gct , especially young patients , should be followed long - term , looking for multiple tumors or other abnormalities suggestive of a systemic syndrome , given the associations described in multiple gct .