A comparative analysis of immunohistochemistry and fluorescent in situ hybridization assay to detect anaplastic lymphoma kinase status in lung adenocarcinoma cases: A search for a testing algorithm.

INTRODUCTION: Testing for echinoderm microtubule-associated protein-like 4 (EML4) anaplastic lymphoma kinase (ALK) translocation by fluorescence in situ hybridization (FISH) is well established whereas the Food and Drug Administration (FDA) ALK immunohistochemical (IHC) test is relatively new. AIMS AND OBJECTIVE: The aim of this study is to compare FDA-approved ALK IHC test (D5F3 clone) with the standard ALK FISH test. MATERIALS AND METHODS: A validation and a test arm with 100 and 200 cases of Formalin-Fixed, Paraffin-embedded blocks of lung adenocarcinoma, respectively, comprised the material. All cases had ALK IHC test on automated Ventana Benchmark XT IHC slide stainer using anti-ALK D5F3 rabbit monoclonal primary antibody; when positive tumor cells (any percentage) showed strong granular cytoplasmic staining. For the FISH test, Vysis ALK Dual Color Break Apart Rearrangement Probe (Abbott Molecular Inc.,) was used to detect ALK gene 2p23 rearrangements; when positive the red and green signals were split two signal diameter apart and/or isolated 3'red signal were detected in more than 15% tumor cells. The ALK FISH results were available in all 100 validation cases and 64-test arm cases which formed the basis of this analysis. RESULTS: The ALK IHC test was positive in 16% cases; four discordant cases were ALK IHC positive but ALK FISH negative, but no case was ALK IHC negative and ALK FISH positive. There was 100% sensitivity, 90.5% specificity, and 93.75% accuracy. CONCLUSION: A negative ALK IHC result obviates the need for a FISH test barring those with a strong clinical profile, and a positive ALK IHC result is sufficient basis for the initiation of treatment.

Histopathologic review of 400 biopsies and resection specimens of trunk and extremity-based soft tissue tumors.

AIMS: To review various pathologic parameters in diagnosed cases of trunk and extremity-based soft tissue tumors (STTs), in order to identify concordance rate between initial biopsy and resection specimen and discrepancies between initial and review diagnosis, by a specialist pathologist. MATERIALS AND METHODS: Over a 2-year-period, 400 retrospectively diagnosed STTs (553 specimens) including referral and "in-house" cases were studied. The reviewing specialist pathologist was blinded to the initial diagnoses. Discordances including discrepancies and deficiencies were defined as major and minor. Major discrepancies included those that could lead to significant treatment changes. True discrepancies were those related to sampling issues between the biopsies and resection specimens. Deficiencies relating to tumor subtyping, sarcoma grading, documentation of tumor size, and marginal status (in resections) were subdivided as major and minor. RESULTS: Most cases (328, 82%) were sarcomas (most common, synovial sarcoma; most common Stage, III), followed by benign tumors (36, 9%) (most common, schwannoma) and intermediate malignancies (32, 8%) (most common, fibromatosis). Within STTs, liposarcomas, neural tumors, and undifferentiated pleomorphic sarcomas were relatively more frequently associated with discrepancies. Percentage of cases with major discordances between the referral reports (100 cases) and review diagnosis was 60%. Percentage of cases with major discordances between the specialist and other oncopathologists was 11%. True discrepancies were observed in 20 (5%) cases. The association of type of specimen with the rate of discordance was not significant (P = 0.114). CONCLUSIONS: Diagnoses of STTs are fraught with errors mostly from general pathologists, followed by nonspecialist oncopathologists. These findings reinforce the need for reporting of STTs, especially sarcomas, by specialist pathologists.

A clinicopathologic analysis of 88 lung resections of suspected metastatic carcinomas with proven primaries.

BACKGROUND: The lung is the most common site for metastatic carcinomas. Very few studies have comprehensively analyzed all pulmonary resections for metastatic carcinomas. AIMS AND OBJECTIVES: To analyze all lung resections for suspected metastatic carcinomas accrued over 10 years to evaluate: (i). The most frequent primary site,(ii). The interval between primary tumor diagnosis and lung metastases, and (iii). The proportion of inadvertently resected benign lesions, clinicoradiologically mistaken for metastatic deposits. MATERIALS AND METHODS: Between 2002 and 2011, 88 pulmonary metastasectomies were done for suspected metastatic carcinomas, which form the basis of this study. RESULTS: In 81 of 88 cases (92%) the diagnosis of metastatic carcinoma was histologically confirmed, whereas 7 cases (8%) were non-neoplastic. The mean interval between primary tumor and metastases was 2.5 years. The primary sites were colorectum (30; 37%), kidney and breast (14; 17.3% each), cervix (9; 10%), salivary gland carcinoma (3), thyroid carcinoma (2), squamous carcinoma (2, one each of mandible and larynx), papillary urothelial carcinoma (2), hepatocellular carcinoma (1), endometrioid adenocarcinoma (1), carcinosarcoma of endometrium (1), adrenocortical carcinoma (1), and neuroendocrine carcinoma (1). The 7 non-neoplastic lesions (8%) histologically revealed tuberculosis (4), bronchopneumonia (2), and aspergillosis (1). CONCLUSIONS: Almost three fourths (71.6%) of the metastatic pulmonary resections comprised primaries from colorectum, breast and kidney. The interval between primary tumor and metastases ranged from zero months to 10 years (mean 2.5 years). Tuberculosis was the most common histologic diagnosis among the 8% of the non-neoplastic lesions, which were mistaken for metastatic carcinoma on clinical evaluation.

A year of anaplastic large cell kinase testing for lung carcinoma: pathological and technical perspectives.

BACKGROUND: An in-frame fusion protein between echinoderm microtubule-associated protein-like 4 (EML4) and anaplastic large cell kinase (ALK) genes is seen in some non-small cell lung cancer (NSCLC). EML4-ALK demonstrates constitutive kinase activity. These ALK-positive lung carcinomas have been shown to respond to ALK kinase inhibitors. ALK gene rearrangement is commonly detected using fluorescent in situ hybridization (FISH). AIMS: To study the pathological features of ALK positive and negative NSCLC and evaluate the causes of uninterpretable FISH results. MATERIALS AND METHODS: This is a retrospective, observational study. The molecular pathology records of patients on whom test for ALK had been performed in a period of 1 year (February 2012 to February 2013) were accessioned. A total 224 cases were identified. Histological features were reviewed. The in situ hybridization was performed using Vysis ALK Dual Color Break Apart Rearrangement Probe (Abbott Molecular Inc.). Signal interpretation under the fluorescent microscope was performed in accordance with College of American Pathologists guidelines. RESULTS: Five patients showed ALK gene rearrangement, 182 were negative and 37 cases were uninterpretable. Five patients with ALK gene rearrangement had a mean age of 48 years and the male to female ratio was 2:3. In the ALK negative cases, the mean age was 54 years and male to female ratio was 3.2:1. Histologically, amongst the rearranged cases, three showed solid pattern, one showed acinar and one showed acinar with signet ring cells on histology. CONCLUSION: The percentage of ALK gene rearrangement was 2.7% (excluding the uninterpretable cases). These ALK positive patients were relatively younger than ALK negative patients. Solid pattern on histology was associated with ALK positivity. In a quarter of the uninterpretable results, the material submitted was fixed and processed outside.

Iatrogenic implantation of giant cell tumor at bone graft donor site and clinical recommendations to prevent "a rare avoidable complication".

The treatment of giant cell tumor of bone is directed toward local control without sacrificing joint function. This is achieved by intralesional curettage. When autograft is used for the reconstruction of the curetted cavity, there is always a theoretical risk of contamination of graft donor site. We report a case of iatrogenic implantation of giant cell tumor at the bone graft donor site after intralesional curettage and bone grafting of giant cell tumor of distal femur. Patient was treated with repeat intralesional curettage and excision of implantation lesion at bone graft donor site. We recommend precautionary measures to prevent this avoidable complication.

Critical histopathological analysis of 25 dedifferentiated liposarcomas, including uncommon variants, reviewed at a Tertiary Cancer Referral Center.

BACKGROUND: De-differentiated liposarcomas (DDLSs) are uncommon tumors with a wide histopathological spectrum. MATERIALS AND METHODS: Over an 8-year period (2003-2011), 25 DDLSs, after review, were critically analyzed for histopathological features. RESULTS: Twenty-five tumors, in 14 men and 11 women (M: F = 1.2:1), with age range of 22-88 years (mean, 53.9), occurred in retroperitoneum (14) (56%), thigh (3) (12%), paratesticular region (3) (12%), chest wall (2) (8%), leg (1) (4%), shoulder (1) (4%), and groin (1) (4%). Tumor size (21 tumors) varied from 7.5 to 25 cm (mean, 17.5). Histopathologically, DD component was high grade in 19 (76%) and low grade in 6 (24%) tumors. Whereas the most common WD component was adipocytic type; the most common DD component was pleomorphic sarcomatous (13) (52%), followed by myxofibrosarcomatous (MFS)-type (6) (24%). Low-grade DD components included MFS (2), fibrosarcoma (2), myogenic/myofibroblastic type (1), and IMFT-type (1). Three tumors displayed meningothelial-like whorls and metaplastic bone formation. Heterologous elements, noted in 11 (44%) tumors, included bone (8) and rhabdomyoblastic differentiation (2). Two tumors displayed homologous differentiation, reinforced with MDM2 staining. S100-P was diffusely positive in WD components (5/7) and focally in DD components (2/9). All patients were treated with surgery, including 10, who underwent adjuvant radiotherapy. Outcomes (16 patients, 64%), over 1-48 months included 10 patients free of disease, 4 died of disease, and 2 patients alive with disease. CONCLUSIONS: This study forms the largest documentation of DDLSs, including its wide histopathological spectrum, from our country. Rare cases overlap with pleomorphic liposarcoma. S100-P and MDM2 are useful in substantiating adipocytic differentiation, especially in selected cases. Analysis of adequate tumor sections is vital for correct identification of a DDLS. Surgical excision with adjuvant RT forms optimal treatment.

Results of surgical resection in pelvic Ewing's sarcoma.

OBJECTIVE: To evaluate the results of patients with non-metastatic Ewing's sarcoma of the pelvis treated with surgical resection as part of their multimodality treatment METHODS: Twenty-six patients treated between September 2000 and September 2009 were evaluated. Thirteen resections included the acetabulum and 13 did not. Thirteen resections excluding the acetabulum had no reconstruction. Arthrodesis was done in two, extracorporeal radiation and reimplantation in two, and pseudarthrosis in nine patients. RESULTS: Three patients had involved margins. Seventeen patients had good response to chemotherapy and nine were poor responders. Twenty-one patients were available for follow-up. The follow-up ranged from 4 to 129 months (mean 36 months). Thirteen patients are currently alive. There was one local recurrence. On Kaplan-Meier analysis the overall survival was 72% at 5 years. The 3-year survival in good responders to chemotherapy was 94% compared to 30% in poor responders. The Musculoskeletal Tumor Society Score ranged from 23 to 29, with patients in whom the acetabulum was retained having better function compared to patients in whom acetabulum was resected. CONCLUSION: Surgery provides good local control and oncologic outcomes with acceptable function in these patients.

A clinico-morphological study of 95 cases of sarcomas with metastases to the lungs.

BACKGROUND: Metastasis of soft tissue sarcoma most commonly occurs to the lungs. There are very few studies on histology of pulmonary metastatectomy and hardly any wherein the histology of the primary tumor has been compared with the metastasis. AIMS AND OBJECTIVES: To review histologically all metastatic sarcomas to lung and compare with the primary where available. MATERIALS AND METHODS: Ninety-five patients with pulmonary metastases from sarcoma were analyzed histologically for type of sarcoma, chemotherapy-related changes, and changes in adjacent lung. Various clinical parameters like laterality, multiplicity, and interval between primary and metastasis were also studied. RESULTS: Osteosarcoma constituted half of the metastatic sarcomas (48 cases, 50.5%) followed by synovial sarcoma (16 cases, 16.8%) and high grade spindle cell sarcoma-NOS (10 cases, 10.5%). The histology of primary and the metastases was similar in 60% of cases of osteosarcoma. CONCLUSIONS: Osteosarcoma is the commonest metastatic sarcoma to the lung. There is often a change to fibroblastic histology in patients of conventional osteosarcoma treated with chemotherapy.

Primary leiomyosarcoma of bone--a clinicopathologic study of 8 uncommon cases with immunohistochemical analysis and clinical outcomes.

Primary leiomyosarcoma of bone is a rare and a diagnostically challenging tumor entity. Over a 7-year period, we identified 8 such cases that fulfilled the diagnostic criteria in 6 men and 2 women, with age ranging from 25 to 59 years (mean, 42.7 years). All cases were noted in the lower limbs, including femur and tibia as the commonly involved bones in 4 and 3 cases, respectively. On radiography, the most consistent feature was a solitary osteolytic lesion with cortical destruction, unassociated with matrix formation. On histopathology, all cases showed spindly sarcomatous cells, mostly arranged in fascicles and whorls. Of 8 cases, 6 (75%) were of high grade. Prominent vasculature was noted in 5 cases. Two cases displayed focal mineralization, including calcification and heterotropic woven bone formation in 1 case each, but lacked malignant osteoid or chondroid matrix. One case showed osteoclast-like giant cells. On immunohistochemistry, smooth muscle actin was diffusely positive in all cases (100%), desmin was positive in 6 (75%) of 8 cases, and h-caldesmon was positive in 5 (83.3%) of 6 cases. Five cases underwent surgery, including 3 amputations and 2 wide excisions. One case underwent chemotherapy. On follow-up, 5 cases developed metastasis, including 1 case with another, who died within 17 and 5 months. Leiomyosarcoma of bone is uncommon and diagnostically challenging. An index of suspicion is necessary for this diagnosis, especially in cases of lytic, destructive bone lesions, unassociated with matrix production, that show spindly sarcomatous cells on histopathology. Immunohistochemical analysis, including an optimum panel formed by smooth muscle actin (diffuse positivity), desmin, and h-caldesmon, is necessary for substantiating this diagnosis. Surgery forms the treatment mainstay. The prognosis appears to be dismal.

Synchronous squamous cell carcinoma of tongue and unicentric cervical Castleman's disease clinically mimicking a stage IV disease: a rare association or coincidence?

Malignancy in a setting of hyaline vascular type of Castleman's disease (HVCD) is an exceptional occurrence. Herein, we report an extremely rare case of synchronous unicentric cervical HVCD and squamous cell carcinoma (SCC) of tongue mimicking stage IV disease. A 32-year-old gentleman presented with an ulcerated mass on the right tongue border and ipsilateral cervical nodal mass. As the clinical stage was IVB (T(1)N(3)M(0)), an anterior two-third glossectomy with bilateral modified neck dissection was performed. On gross examination, an ulcerated mass on the right lateral border was identified. In addition, an 8 cm large nodal mass at right level III-V was seen. Microscopy from the ulcerated growth in the tongue revealed an invasive well differentiated squamous cell carcinoma. However, the right cervical nodal mass yielded surprise histology of Castleman's disease, hyaline-vascular type. Final tumor pathological staging was revised to pT1N0M0 . This case reveals that HVCD can rarely be associated with an epithelial malignancy wherein it can clinically mimic nodal metastasis. Whether such a phenomenon occurs due to underlying immune aberrations or is a rare co-incidence remains unclear.

A t (11; 22) (p13; q12) EWS-WT 1 positive desmoplastic small round cell tumor of the maxilla: an unusual case indicating the role of molecular diagnosis in round cell sarcomas.

A desmoplastic small round cell tumor (DSRCT) is an uncommon tumor characterized by polyphenotypic expression and a specific reciprocal translocation t (11; 22) (p13; q12). It has been rarely identified in the head and neck region. Herein, we describe a DSRCT in the maxilla of a young man, who was initially diagnosed with a primitive neuroectodermal tumor (PNET), based on histopathological appearance of a round cell tumor, with MIC2 and -FLI-1 positivity, on immunohistochemistry (IHC). Diagnosis of a DSRCT was confirmed on molecular analysis with positive -RT-PCR and sequencing results for EWS-WT1 transcript and negativity for EWS-FL1. The case is presented to highlight the value of molecular diagnosis in round cell sarcomas at uncommon sites, especially when similar IHC markers can be expressed in a PNET and a DSRCT. An exact diagnosis of a round cell sarcoma has a therapeutic relevance.

Metastatic giant cell tumor of bone: are there associated factors and best treatment modalities?

UNLABELLED: Giant cell tumors of bone are sometimes locally aggressive and may metastasize, although uncommonly. We attempted to identify associations of clinical and histopathologic parameters with metastasis, the long-term outcome with metastases, and the best treatment. We identified distant metastases in 24 of 470 patients with giant cell tumors during a 20-year period. The median age of these 24 patients at presentation was 26 years (range, 16-76 years), and the male:female ratio was 1.6:1, with no predilection for primary site. Metastasis occurred at a mean of 2 years (range, 4 months-11 years) after initial diagnosis. Sites for distant metastases were the lung (21 of 24 patients), scalp, calf muscle, and regional lymph nodes. The 24 patients had a mean followup of 3.5 years (range, 0-16 years). Thirteen of the 24 patients has local recurrence before or at the time of metastasis. Two patients refused treatment, eight underwent metastasectomy, and 14 were inoperable (four had chemotherapy, 10 were treated symptomatically). We observed disease progression with hemoptysis in one of 14 patients. None of the patients died of their metastatic disease. None of the risk factors we studied was associated with metastasis in giant cell tumors. Although the overall outcome was favorable, metastasectomy is recommended where feasible. LEVEL OF EVIDENCE: Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

The use of p63 as an effective immunomarker in the diagnosis of pulmonary squamous cell carcinomas on de-stained bronchial lavage cytological smears.

OBJECTIVES: A diagnosis in pulmonary onco-cytopathology primarily necessitates distinguishing small cell carcinoma (SCLC) from non-small cell carcinoma (NSCLC), which includes squamous cell carcinoma and adenocarcinoma. Lately, p63 antibody has been used for distinguishing squamous cell carcinoma from SCLC and adenocarcinoma. We present an analysis of p63 expression in cytological smears from 100 bronchial lavage specimens comprising 51 cases of SCLC and 49 cases of NSCLC. METHODS: A single Papanicolaou-stained conventional smear was de-stained and re-fixed with cold acetone and methanol for immunocytochemical staining with p63 antibody. Staining results were graded as 0 (nil), 1+ (focal), 2+ (moderate, diffuse) and 3+ (strong, diffuse). RESULTS: Out of 100 cases, 21 were cytologically diagnosed as squamous cell carcinoma. Twenty of these showed 2+ or 3+ p63 positivity, whereas one, which was adenocarcinoma on histology, showed 1+ staining. Of seven cases cytologically diagnosed as adenocarcinoma, six showed no p63 staining, whereas one, which was squamous cell carcinoma on histology, showed 1+ staining. All 48 cases cytologically diagnosed as SCLC were confirmed as such on histology and showed no p63 staining. Four cases were cytologically designated as poorly differentiated carcinomas, of which three showed no p63 staining and one showed 3+ staining. The former three were found to be SCLC on histology while the latter was squamous cell carcinoma. The remaining 20 cases were cytologically designated as NSCLC. Of these, eight showed no p63 staining, whereas 10 showed 1+ and two showed 2+ staining. The former eight were adenocarcinoma on histology and the latter two were squamous cell carcinoma. The 10 cases that showed 1+ p63 staining were adenocarcinomas (n = 5), squamous cell carcinoma (n = 4) and NSCLC, not otherwise specified (n = 1). Positive staining was seen in normal basal cells, which acted as an internal control. Overall sensitivity of p63 for squamous cell carcinoma was 100% and specificity was 90.4%. CONCLUSIONS: p63 immunostaining on processed cytology smears can be used to help identify squamous cell carcinoma. Its diffuse expression was specific for squamous cell carcinoma while focal staining was also seen in adenocarcinoma.

Clinicopathologic profile of 470 giant cell tumors of bone from a cancer hospital in western India.

Over 20 years, 470 cases of giant cell tumor of bone diagnosed at a tertiary cancer hospital were analyzed. Male predominance (57%), predilection for bones around the knee joint (42%), and occurence in the 21- to 30-year-old age group (49.1%) with 6% being in the immature skeleton are well known facts. Accurate diagnosis was possible in 66% and 88% of cases on radiology and biopsy, respectively. Tumors measured 6 to 20 cm and, in 402 cases, showed "usual" histology comprising uniformly scattered multinucleate giant cells amidst mononuclear stromal cells, together imparting a syncitium-like appearance. Presence of osteoid, hemorrhage, and aneurysmal bone cyst-like areas; spindle cells in sheets (devoid of giant cells); or storiform pattern and intravascular osteoclasts were less common. The less common histologic features posed diagnostic difficulty in the setting of a small biopsy. Treatment included intralesional curettage (33.19%), marginal excision (4.2%), wide excision (31%), or radical surgeries (14.25%). Recurrences seen in 170 cases were multiple in 47 cases. Metastases largely to the lung were recorded in 24 cases. The histology of all the tumors, namely, primary, recurrent, or metastatic was identical. Statistical analysis using the computer software SPSS (SPSS Inc, Chicago, Ill)was performed with particular reference to the unusual histologic features vs recurrence and metastasis by chi(2) test. The only statistically significant factors were occurrence in the axial skeleton vs appendicular skeleton (P = .001) and primary treatment elsewhere vs at this hospital (P = .045), each of these being associated with increased frequency for local recurrence but not metastasis.

A t(X; 18) SYT-SSX2 positive synovial sarcoma in the pelvis of a young adult male: a rare case report with review of literature.

Synovial sarcoma is uncommonly documented in the pelvis. Rarely, such cases have dealt with molecular analysis. A 19-year-old boy presented with pain and swelling in his left lower limb of two months duration. He developed acute urinary retention four days prior to his hospital admission, wherein radiological examination unraveled a large soft tissue mass, displacing his pelvic muscles, along with a lytic lesion involving his right pubic bone. Biopsy showed a cellular spindle cell sarcoma, exhibiting hemangiopericytoma-like vascular pattern with focal necrosis. Immunohistochemistry (IHC) showed positivity for vimentin, BCL-2, calponin and MIC 2. Cytokeratin (CK) and epithelial membrane antigen (EMA) were negative. MIB 1 count was 70% (high). P53 was positive. Diagnosis of a poorly differentiated synovial sarcoma was offered and confirmed with a positive t(X; 18) SYT-SSX2 translocation. This case highlights the value of molecular analysis in diagnosis of a synovial sarcoma at rare sites, especially when IHC results are equivocal and the biopsy material is limited.

Anaplastic large cell lymphoma (ALCL) presenting as primary bone and soft tissue sarcoma--a study of 12 cases.

This study highlights the rare presentation of anaplastic large cell lymphoma as primary bone and soft tissue tumour. Twelve cases were studied. Clinical impression was non Hodgkin's lymphoma in 4 cases, sarcoma in 6 (osteosarcoma-2, Ewing's/primitive neuroectodermal tumour-1, and sarcoma NOS-3), and tuberculosis of thoracic spine in 1 and the last case involving the rib had a differential diagnosis of tuberculosis and NHL. Histology revealed round cells with eosinophilic cytoplasm and pleomorphic nuclei. Immunohistochemically all tumours were CD30 positive and 8 of 9 cases (88.9%) showed ALK-1 positivity. The pleomorphic cytomorphology ofALCL leads to confusion with the more frequent bone and soft tissue sarcomas affecting the musculoskeletal system. A high index of suspicion is necessary to initiate the correct panel of immunohistochemical markers to first confirm the lymphomatous nature of this tumour and to subsequently subclassify. This alone will lead to an accurate recognition of ALCL and the appropriate chemotherapy.

Polyphenotypic peripheral neuroepithelioma occuring in the foot: a case report.

Peripheral neuroepithelioma of the soft tissues is an uncommon member of primitive neuroectodermal tumors. Divergent differentiation and polyphenotypia is known in peripheral neuroepithelioma. We report one such recurrent peripheral neuroepithelioma in an infant which was detected at one month of age, in the foot. Microscopically, it showed tumor cells in nests and lobules with abundant Homer-Wright rosettes. Immunohistochemically, tumor cells were immunoreactive for neural markers but also displayed an aberrant myoid phenotype. The prognostic implications of this anomalous phenotype are unclear as of now, but documentation of this is necessary for possible future references.

Diffuse-type giant cell tumor of the subcutaneous thigh.

Diffuse-type giant cell tumor is an extra-articular form of pigmented villonodular synovitis. The localized form of this lesion (tenosynovial giant cell tumor) is frequent, representing the most common subset arising from the synovium of a joint, bursa or tendon sheath, with 85% of cases occurring in the fingers. The less frequent diffuse-type giant cell tumors are commonly located in the periarticular soft tissues, but on rare occasions these lesions can be purely intramuscular or subcutaneous We report the case of a 26-year-old female with diffuse-type giant cell tumor of the subcutaneous thigh, remote from a joint, bursa or tendon sheath. A review of the literature did not reveal any similar description of a diffuse-type giant cell tumor completely within the subcutaneous thigh, remote from a joint, bursa or tendon sheath. These lesions were initially regarded as inflammatory or reactive processes, but since the identification of clonal abnormalities in these patients, and in view of their capacity for autonomous growth, they are now widely considered to represent benign neoplasms.