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We report 3 cases of an unusual tumor, that is, the giant cell tumor of the tendon sheath. The patients consulted due to the appearance of a well-defined, painless, soft tissue mass with mild-to-moderate inflammation located in the thumbs or toes. These clinical data, together with the bone scan findings, oriented the diagnostic suspicion that was confirmed by a pathology study of the tumor after resection. This work has aimed to review the characteristics of the bone scan (BS) image of this tumor and its correlation with the conventional X-ray imaging and magnetic resonance imaging (MRI).

Tenosynovial giant cell tumors arise from synovium of joints, bursae, or tendon sheaths, and are classified into localized and diffuse types based on the growth pattern and clinical behavior. The mononuclear component of these tumors includes small histiocytoid cells and large mononuclear cells, which are positive for desmin in about 50% of cases. This study seeks to further characterize the immunophenotype of these tumors, and investigates the utility of clusterin as a diagnostic marker. Immunostaining for clusterin was performed on 40 cases of tenosynovial giant cell tumor (11 localized and 29 diffuse). Most cases were also stained for desmin, CD163, CD21, and CD35. Four cases were stained for podoplanin/D2-40 and CXCL13. Clusterin staining was diffuse and strong in the large mononuclear cells in all cases. Desmin positivity in the large cells was identified in 24 out of 34 cases (71%), but was seen in only a subset of cells (<5% to 80%), with 19 out of 24 cases (79%) showing positivity in 10% or less. The large cells were positive for podoplanin in 4 out of 4 cases, but negative for CD163, CD21, CD35, and CXCL13. The smaller histiocytoid cells were positive for CD163 and negative for all other markers. When present, non-neoplastic synoviocytes were positive for clusterin and podoplanin, and focally positive for desmin. Clusterin is a highly sensitive marker for tenosynovial giant cell tumors, which has diagnostic utility in challenging cases. The observed staining patterns provide evidence linking the large mononuclear cells with normal synoviocytes and support that tenosynovial giant cell tumors are neoplasms showing synovial differentiation.

Giant cell tumor of tendon sheath (GCTTS) and Wegener's granulomatosis (WG) are rare conditions both characterized by polyclonal cellular proliferation and multinucleated giant cells formation. Here, we report the case of a 27-year-old Caucasian woman affected by WG who experienced the metachrone appearance of two different GCTTSs at the right hand within a time of 3 years. To our knowledge, the combination of GCTT with WG is exceptional and this could probably be the first case reported. The subsequent appearance of two rare diseases both characterized by giant cell formation apparently points to similarities in their pathogenesis. However, at present no pathogenic relationship between GCTTS and WG is demonstrable and their simultaneous occurrence has to be considered coincidental. Actually, an emerging opinion is to consider GCTTS as a mixed lesion in which both tumoral and non-tumoral inflammatory cells play a central pathogenic action. On this view, the proposed case could support the evidence about the crucial role of a chronic inflammatory injury in enhancing GCTTS appearance.

Pleomorphic lipomas are benign tumors that most commonly present as subcutaneous masses in the head and neck, shoulder, or back region of middle-aged to elderly men. They are related to spindle cell lipomas based on shared cytogenetic aberrations and histologic features. When little or no fat is present, the diagnosis can be challenging. A review of 38 pleomorphic lipomas seen in consultation revealed 7 cases in which fat was present in reduced (<5%) amounts (n = 5) or absent (n = 2). Six of 7 cases were from men with a mean age of 59 years. Excluding 1 case where the site was not specified, they all presented as solitary well-circumscribed subcutaneous masses in the head and neck (n = 3) or shoulder (n = 2) region. The seventh case was an intradermal tumor from the nose of a 48-year-old woman. All displayed pleomorphic and multinucleated floret cells interspersed among bland spindle cells and ropey collagen. They were diffusely immunoreactive for CD34. Referring diagnoses, when provided, included myxofibrosarcoma, giant cell fibroblastoma, and granulomatous rosacea for the tumor from the nose; none considered pleomorphic lipomas. When fat is absent or present in reduced amounts, clinical context and identification of classic nonlipogenic components are essential for the diagnosis of pleomorphic lipomas.

Subependymal giant cell tumors (SGCTs) are observed in 5-20% of patients with tuberous sclerosis complex (TSC) but account for approximately 25% of neurological morbidity. The authors report the case of a 7-year-old girl with TSC and multiple cortical tubers who presented with worsening seizures in the context of the rapid growth of a cystic, calcified, extraventricular SGCT in the right frontal lobe, initially thought to represent a cortical tuber. The tumor and surrounding tubers were excised, and clinical seizures resolved. This is the first report of an extraventricular SGCT in a child with TSC outside the neonatal period.

Primary giant-cell tumour of soft tissue arising in the ligamentum teres has not been previously described. We report a case of such a tumour in a 46-year-old woman. The lesion was only detected at the time of hip arthroscopy despite pre-operative MRI being performed. It was successfully excised arthroscopically with resolution of the symptoms.

Background: This study was performed to evaluate the usefulness of high-resolution grayscale and color Doppler ultrasound to distinguish benign from malignant soft-tissue masses on the basis of ultrasonographic patterns., Methods: We enrolled 398 female and 420 male patients aged 1-104 years (mean, 49.8 years). All presented with a palpable nodule or mass located superficially in the body. Each lesion was examined by grayscale and color Doppler ultrasonography to assess its echogenicity, margin, shape, composition, acoustic transmission, size and other patterns. Spectral Doppler was applied in lesions with positive color flow signals. The nature of all masses was confirmed by aspiration cytology, biopsy, surgical pathology or long-term clinical follow-up., Results: There were a total of 693 benign and 125 malignant masses. Five malignant and 14 benign histologies (including 6 types with inflammation-related, hematoma or pseudoaneurysm) occurred that had more than 10 subjects with each histology. Eight benign histopathologies included cysts, neoplasms, vascular and miscellaneous. Five malignant histologies included metastases, osteogenic sarcomas, lymphomas, malignant fibrous histiocytomas and liposarcomas. There were significant differences (p < 0.05) between the benign and malignant soft-tissue tumors in terms of parameters including tumor margin, shape and size. Benign lesions did not have infiltrated margins or a scalloped shape and malignant tumors tended to be large. However, there was no significant difference (p > 0.05) between the benign and malignant soft-tissue tumors in terms of echogenicity, composition and color Doppler features., Conclusion: Ultrasonography with color Doppler imaging is a good modality for characterizing most soft-tissue masses, and tumor size > 5 cm and having infiltrated margin highly suggests malignancy.

Conventional urothelial carcinoma accounts for most carcinomas of the urinary tract lining. However, neoplastic urothelium has the capacity to demonstrate enormous plasticity. A variety of unusual architectural patterns of urothelial carcinoma, such as the nested, microcystic and inverted variants, can be mistaken for reactive processes or benign tumours. Others such as the micropapillary, plasmacytoid and discohesive variants, can mimic metastatic tumour from other sites. The micropapillary variant in particular is more aggressive. In addition, urothelial carcinoma has a propensity to demonstrate divergent differentiation with glandular, squamous, small cell neuroendocrine, lymphoepithelioma-like, sarcomatoid or other elements. Pure squamous carcinoma or adenocarcinoma (the latter in particular) can be difficult to distinguish from contiguous or metastatic spread. Some variants have prognostic and potential therapeutic implications. Molecular genetic evidence has emerged recently supporting a close relationship between urothelial carcinoma and various divergent elements. Sarcomatoid carcinoma and its differential diagnosis with other spindle cell lesions of urinary tract will be covered in a separate review.

Giant cell tumour (GCT) of bone is an uncommon primary bone neoplasm typically occurring at the epiphyses of long bones in young adults. They are osteolytic neoplasms with approximate local recurrence rates of 25%, and 2% of patients develop pulmonary metastases. These tumours appear very rarely in the skull, with those few reported cases arising predominantly in the sphenoid and occasionally the temporal bones. They demonstrate benign histological features, but are locally aggressive and surgical excision is the treatment of choice. It is widely believed that giant cell tumours should be distinguished from other giant cell lesions, importantly central giant cell reparative granulomata (CGCG) which are thought to have a lower recurrence rate and for which no cases of malignant transformation or metastases have been reported. Investigators have noted that giant cell lesions in the skull bones may be unique and that GCT and CGCG may be part of a spectrum of a single disease process. We present a case of a giant cell tumour of the temporal bone which illustrates and re-emphasises this concept and review the literature on these lesions.

Giant cell tumor of the salivary gland is extremely rare, with only 15 cases published in the English literature. The tumor characteristically contains a mixture of multinucleated giant cells, resembling osteoclasts of bone, and neoplastic mononuclear cells. In about half of the reported cases, there is an associated carcinomatous component. We are reporting an additional case of giant cell tumor of the parotid gland that was initially misinterpreted as an extraosseous osteosarcoma in the biopsy specimen. The histologic and immunohistochemical findings as well as a review of the literature with discussion of the histogenesis of this unusual neoplasm are presented.

Fifty-nine cases of lesions presenting in the patella were identified after review of the databases of four European bone tumour registries. Of the 59 cases, 46% were non neoplastic, 39% were benign and 15% were malignant. The commonest benign neoplasm was giant cell tumour (GCT) (11 cases). Younger patients were more likely to have a benign neoplasm. Lesions in patients less than 40 years of age included giant cell tumour, chondroblastoma, aneurysmal bone cyst (ABC), osteomyelitis, osteoid osteoma and solitary bone cyst. In patients older than 40 years, the following were common lesions: intra-osseous gout, metastasis and intra-osseous ganglion. Expansion of the patella with thinning of cortex was seen more commonly in GCT and brown tumour in hyperparathyroidism. There was associated soft tissue extension in gout and malignant lesions.

A 34-year-old, previously healthy female presented with severe acute upper quadrant abdominal pain and an 11-cm cystic mass in the tail of the pancreas. The patient underwent distal pancreatectomy with total gross excision of the mass. Grossly, the mass consisted of a multiloculated cystic lesion measuring 11.7 cm in its greatest dimension. An irregular solid lobulation at the lateral aspect of the cyst was visible, measuring 3 cm in the largest dimension. Histologically, there were two distinct components: a mucinous, neoplastic epithelial cyst with few foci of moderate atypia, and nodular spindle cell areas containing multinucleated tumor giant cells. Immunohistochemically, the multinucleated giant cells were positive for vimentin, CD68 and CD45, and negative for cytokeratin and epithelial membrane antigen (EMA). The spindle cells of hypercellular stroma were stained for vimentin, but not for EMA or carcinoembryonic antigen (CEA). Neuron-specific enolase (NSE), S100 and Ki-67 showed no reactivity. The histological diagnosis "osteoclast-like giant cell tumor of the pancreas associated with borderline mucinous cystic neoplasm" was made. The patient recovered and is free of disease 4 years after the diagnosis.

A retrospective analysis of all bone tumors accessioned at a large referral center (Instituto Nacional de Rehabilitacion) in Mexico City between 2000 and 2005 is presented. A total of 6216 biopsies and surgical resection specimens were reviewed during this period, of which 566 corresponded to bone tumors. Benign bone tumors accounted for 71.6% of cases and malignant bone tumors for 28.4%. The tumors affected men in 53.7% of cases and women in 46.3% of cases, with an average age at presentation of 25 years. The femur was the most common location of the tumors (39.9%), followed by the tibia (17.7%) and humerus (11.8%). The commonest malignant bone tumors were osteosarcoma (46.6%) and chondrosarcoma (8.7%). Of malignant bone tumors, 18.6% corresponded to metastases of carcinomas from internal organs and 8.1% were multiple myeloma. The most common benign bone tumor was osteochondroma (43.7%) followed by giant cell tumor of bone (14.6%) and enchondroma (10.1%). The age distribution showed a peak in children and adolescents comprised predominantly of benign lesions and a second peak in young adults that corresponded to malignant bone tumors (principally osteosarcoma). Malignant bone tumors most often involved the femur, vertebra, and tibia. Our results parallel the findings previously reported in the world literature and show a similar distribution and epidemiology as in other developed and underdeveloped countries. Geographic location does not appear to represent a risk factor for any particular type of bone tumor and does not affect the age distribution, location, or histopathologic type of the lesions.

Introduction: Osteoclastic and pleomorphic giant cell tumors of the pancreas are rare entities that have been typically described only in single case reports. We report on our experience with a series of 5 patients with pancreatic giant cell tumors seen at our institution., Methods: This was a retrospective study involving a search of the study institution's medical records from 2001 to 2007 for patients diagnosed with giant cell-containing neoplasms of the pancreas., Results: Five patients (2 women, 3 men) were identified. Age range was 59 to 81 years, with a mean of 70.2 years. None were current or former smokers. None had a history of alcohol abuse or preexisting pancreatitis of any kind. On EUS, tumors tended to be large, with a mean diameter of 47 mm (range 20-70 mm). All tumors had a heterogeneous echotexture and a distinct appearance when compared with the typical appearance of adenocarcinoma when viewed via EUS. The diagnosis of giant cell tumor of the pancreas, as well as the subtype, was made via EUS-guided FNA of the pancreatic lesion. Patients with pleomorphic giant cell tumors of the pancreas had a poor clinical course with a rapid decline, whereas those with mixed or osteoclastic giant cell tumors tended to have a better outcome, with a greater long-term survival. One patient is still alive more than 18 months after diagnosis., Limitation: Retrospective study., Conclusions: Giant cell tumors of the pancreas have unique clinical, endoscopic, and cytologic features. The risk factors for these lesions may be different from those associated with pancreatic adenocarcinoma. Some giant cell tumor subtypes may carry a more favorable prognosis than pancreatic adenocarcinoma, and awareness and recognition of these differences can affect patient care.

The giant cell tumor of the tendon sheath is regarded as one of the most common neoplasms of the hand. This tumor usually manifests itself as a localized, solitary, painless and palpable subcutaneous nodule on the palmar aspect of a digit. A multifocal origin of the tumor has rarely been reported in the literature before. In this article we present a case of a giant cell tumor of the tendon sheath, in which two separate lesions developed simultaneously on the same tendon (flexor digitorum superficialis) of the little finger of the right hand together with a literature review about multifocal cases.

Giant cell tumour of soft part is a very rare neoplasm. The majority of these tumours are located superficially (in subcutaneous tissue) and occur in the proximal parts of the extremities. The deep-situated giant cell tumours of the neck are extremely rare. That is why we report a case of primary giant cell tumour of soft part localized in the trapezius muscle of a 19-year-old woman. We present both cytological and histological picture of the neoplasm. The cytological image of the smear is so representative that the proper diagnosis can be settled basing on the fine-needle aspiration cytology.

Extraosseous manifestations of osteoclast-like giant cell tumors (OGCTs) in soft tissue are unusual, especially in the breast. However, multinucleated osteoclast-like giant cells have been described in association with epithelial malignancy, as a variant of breast carcinoma. We report a case of OGCT of the soft tissue of the breast, not associated with epithelial elements. To the best of our knowledge, this is only the second such case reported.

Introduction: The aim of this retrospective study was to study the clinical presentation, investigations, histopathological findings, and the best ways of treatment of the giant cell tumour of the tendon sheath (GCTTS)., Methods: The medical records of all patients diagnosed to have GCTTS during the period 1994-2001 were reviewed, and follow-up was for three to ten years., Results: The total number of patients was 52, of whom 36 were females, and the mean age was 32.4 years. All the tumours except one were located in the hand and wrist area, with the thumb being the most affected finger. Painless swelling was the most common presentation. All of them were treated surgically and the recurrence rate was 24 percent., Conclusion: After reviewing the literature and comparing with our results, we conclude that GCTTS is a true benign tumour with local aggressive behaviour in some cases, and the best way of treatment is wide local excision.

Objectives: To retrospectively study on malignant giant cell tumor of tendon sheath (MGCTTS) in the hand, and to evaluate its clinical, histologic, immunohistochemical features and biologic evolution., Methods: Between January 1991 and December 2001, 10 patients with histologically proven MGCTTS were treated. The clinical material, radiographs and hematoxylin and eosin-stained sections were reviewed. Immunohistochemical studies and nuclear suspensions for flow cytometry were done on paraffin embedded tissue. All patients were followed up., Results: Three of 10 patients in which the diagnosis of MGCTTS was originally considered were excluded after the slides reviewed and immunohistochemical examination performed. In the other 7 patients, one showed malignant and aggressive nature: the lesion recurred several times and the patient eventually died with pulmonary metastases. The immunohistochemical profile of the patient was similar to that reported in benign GCTTS, and the flow cytometry DNA analysis detected aneuploidy. Six cases presented histologic features of malignancy, 4 of them undertook the immunohistochemical examination and their profiles were similar to that reported in benign GCTTS. An aneuploidy DNA pattern was detected in one case on flow cytometry evaluation, diploidy DNA pattern was detected in 3 cases, and their S-phase fraction was 4.5%, 11.6% and 2.6% respectively. All of them had a benign clinical features, they were alive and without evidence of disease from 1.5 to 7.5 years (averagely, 4.5 years) after complete surgical excision or resections with wide surgical margins. None of them had received chemotherapy or radiation therapy., Conclusions: Malignant giant cell tumor of tendon sheath is an extremely rare malignant tumor, some cases have a poor outcome, the others, despite the histologically malignant features, have a good prognosis if wide surgical excision ablates the tumor completely.

Objective: To report on multinucleated giant cells (MNGCs) in salivary fine needle aspiration (FNA)., Study Design: The cytologic reports of salivary gland region FNA during a 10-year period was searched using the keyword giant cell in the final diagnosis or microscopic description. Cases with foreign body-type giant cells secondary to previous biopsy or FNA were excluded. Histologic correlations and immunohistochemical staining for CD68, CK, EMA, S100, HMB45 and CD1a were performed on selected cases., Results: Twenty-six aspiration smears containing MNGCs were identified from 1040 salivary gland FNAs (2.5%). MNGCs were seen in some reactive or inflammatory conditions, benign neoplasms and malignant neoplasms. By type of MNGC, the salivary lesions were categorized in 3 groups: those with foreign body type, osteoclast type and tumor giant cells., Conclusion: MNGCs can be seen in a wide spectrum of salivary gland lesions ranging from reactive to benign and malignant. They are of nonepithelial origin or can be of true neoplastic nature in metastatic lesions.

We report the case of a giant cell tumor with diffuse interstitial hemorrhaging and unusually prominent cystic components in the soft tissue of the thigh which has not been reported previously. Magnetic resonance image (MRI), showed signal intensity typical of a giant cell tumor. However, because of its conspicuous large well-circumscribed cystic components, the differential diagnoses, based on the image findings from an ultrasonography (US) and MRI, were complicated epidermoid cyst, cystic change of a neurogenic tumor, and a parasitic cyst.

We report here a previously undescribed tumor in a 72-year-old patient who had a nasal cutaneous sarcomatoid carcinoma. The epithelial component resembles a skin adnexal tumor, and the sarcomatous component resembles a giant cell tumor of soft parts.

According to most authors, dermatofibrosarcoma protuberans (DFSP) and giant cell fibroblastoma (GCF) represent the adult and juvenile forms, respectively, of the same disease entity, as evidenced by similar morphology, an identical chromosomal translocation, and CD34 positivity. It has been shown that DFSP and nuchal-type fibroma (NTF) (which is also CD34-positive) are related lesions, and that there might possibly be a continuum between the two. In addition, NTF exhibits CD99 positivity. It was therefore, hypothesized that both DFSP and GCF would show similar immunopositivity for CD99. Archives of pathology at several institutions were searched for DFSP and GCF tissue blocks. A total of 29 DFSP and 5 GCF were analyzed by immunohistochemistry for expression of CD99. Twenty-three of 29 DFSP (79%) and 2 of 5 GCP (40%) expressed CD99. Comparison of CD99 and CD34 showed that the non-tumoral periphery of DFSP was less probable to be CD99 positive, but this finding was not statistically significant.

A case of giant cell fibroblastoma in a 62-year-old male is described. The 2 x 1.5 x 1.5 cm tumor was excised from the right supraclavicular area. Histologically, it was typical with exceptions that the typical pseudovascular spaces were seen only focally and the neoplastic cells were closely spatially associated with lymphocytes and plasmocytes. This association was suggestive of emperipolesis. The unusual clinicopathologic features caused some diagnostic difficulty.

In horses, giant-cell tumors of soft parts are rare neoplasms, with the majority of reported cases occurring within the hind limb muscles and soft tissues in older horses. The following article documents 21 cases of equine giant-cell tumors of soft parts clinically examined within the state of Colorado from 2000 to 2007. The majority of cases occurred in male horses aged 10 years or older. Nine (43%) arose within the hind limbs. Key histologic features included numerous multinucleated giant cells and hemosiderin-laden macrophages admixed with a spindle-cell proliferation. The majority demonstrated liposarcomatous change, variable areas of necrosis and hemorrhage, and an intermediate number of mitotic figures. Immunohistochemical results demonstrated 2 distinct cell populations: vimentin-expressing neoplastic mesenchymal cells and CD18 (histiocytic marker) expressing multinucleated giant cells. These results suggest a mesenchymal origin of the neoplasm with possible recruitment of the secondary histiocytic population. Surgical excision was attempted in the majority of horses and was considered clinically complete. A recurrence of the neoplasm was documented in 1 horse and 1 mule. In 18 horses, surgical excision, regardless of margin integrity, appeared successful with no recurrence of disease documented. Unfortunately, 10 of 21 horses were lost to follow-up within approximately 3 months of surgery. Of the 11 remaining horses that were available for follow-up evaluation, there has been no evidence of metastasis. A larger case series with more controlled follow-up is necessary to evaluate malignant potential and the importance of complete surgical excision.

Primary giant cell tumor of soft tissue (GCTST) arising in a finger is a rare event. We report a case of a 54-year-old man with a primary finger giant cell tumor that appeared histologically identical to giant cell tumor of bone. The patient presented with a cystic mass of the finger. The magnetic resonance imaging showed no relation between the nodule and bone, tendons or synovial tissues. The distinction of this entity from other more common primary finger tumors with giant cell morphology is emphasized.

Purpose: To compare CD34 expression in both aggressive and nonaggressive giant cell lesions of the jaws and identify any associations between tumor vascular density and biologic behavior., Materials and Methods: This was a retrospective study of subjects treated for giant cell lesions of the jaws at Massachusetts General Hospital from 1992 to 2006. The primary predictor variable was tumor classification (aggressive or nonaggressive); tumors were considered aggressive if they were greater than 5 cm in size, recurred after treatment, or exhibited 3 of the following: presence of root resorption, tooth displacement, or cortical bone thinning or perforation. Secondary predictor variables, recorded for each patient, were demographic, anatomic, and clinical measures. The outcome variable was the average CD34 staining density of histologic specimens quantified in 2 different areas. Descriptive and bivariate statistics were computed to identify predictors associated with vascular density., Results: The study sample was composed of 32 subjects with a mean age of 24.4 +/- 19.77 years (range: 2-83); 23 subjects (71.8%) were female. Of the tumors included, 11 (34.4%) were located in the maxilla, 21 (65.6%) in the mandible. Twenty-six tumors (81.2%) were classified as aggressive; the remainder (18.8%) were nonaggressive. There were no statistically significant differences between subjects with aggressive versus nonaggressive tumors with regard to age, gender, or location. Subjects with aggressive tumors had a significantly higher CD34 staining density (P = .02). None of the secondary predictors was associated with vascular density., Conclusion: Vascular density of giant cell tumors of the jaws is significantly increased in aggressive tumors.

Hallux valgus is a lateral deviation of the proximal phalanx of the first metatarsophalangeal joint. It is a common disorder in adults. The etiologic factors include modern shoes, rheumatoid arthritis, pes planus, metatarsus primus varus, and trauma. Tumors causing hallux valgus deformities are unusual. We report a 50-year-old female with a hallux valgus deformity caused by a giant cell tumor of the second EDL tendon sheath. Surgical excision of the tumor and corrective osteotomy produced a permanent cure. This unusual cause of a hallux valgus deformity should increase awareness of tumors as a possible cause of foot deformities.

Dedifferentiated parosteal osteosarcoma is characterized histologically by the admixture of low-grade fibroblastic osteosarcoma and a high-grade component typically resembling conventional osteosarcoma or malignant fibrous histiocytoma. We report an unusual distal femoral dedifferentiated parosteal osteosarcoma in which the dedifferentiated component resembled a giant cell tumor of bone. This phenotype is rarely described in the dedifferentiated component of a dedifferentiated parosteal osteosarcoma. The clinical, radiographic, and pathologic features of this unusual tumor are described to further expand the histologic spectrum of dedifferentiated parosteal osteosarcoma.

Central nervous system (CNS) germ cell tumors constitute a unique class of rare tumors that mainly affect children and adolescents. These tumors are believed to originate from displaced primordial germ cells. Recently, results of treatment of germ cell tumors have improved with use of radiotherapy and combination chemotherapy. However, some tumors have proven refractory to intensive treatment with surgery, radiation, and combination chemotherapy. Nestin is an intermediate filament protein expressed in undifferentiated cells during CNS development and in CNS tumors and is used as a marker of immature elements of tumors, including brain tumor stem cells. In this study, we examined for the first time nestin expression in 19 CNS germ cell tumors (nine pure germinomas, five germinomas with syncytiotrophoblastic giant cells, one yolk sac tumor, one choriocarcinoma, one embryonal carcinoma, and two mature teratomas). Nestin was expressed in 14 cases but was not expressed in three pure germinomas and two mature teratomas. Clinically, nestin-negative tumors did not exhibit dissemination, while all tumors that exhibited dissemination also strongly expressed nestin protein. These findings suggest that the detection of nestin expression could be useful in the management of CNS germ cell tumors, as an auxiliary predictor of dissemination and/or progression.

p63 contributes to skeletal development and tumor formation; however, little is known regarding its activity in the context of bone and soft tissue neoplasms. The purpose of this study was to investigate p63 expression in giant cell tumor of bone and to determine whether it can be used to discriminate between other giant cell-rich tumors. Seventeen cases of giant cell tumor of bone were examined to determine the cell type expressing p63 and identify the isoforms present. Total RNA or cell protein was extracted from mononuclear- or giant cell-enriched fractions or intact giant cell tumor of bone and examined by RT-PCR or western blot, respectively. Immunohistochemistry was used to evaluate p63 expression in paraffin embedded sections of giant cell tumor of bone and in tumors containing multinucleated giant cells, including: giant cell tumor of tendon sheath, pigmented villonodular synovitis, aneurysmal bone cyst, chondroblastoma, and central giant cell granuloma. The mononuclear cell component in all cases of giant cell tumor of bone was found to express all forms of TAp63 (alpha, beta, and gamma), whereas only low levels of the TAp63 alpha and beta isoforms were detected in multinucleated cells; DeltaNp63 was not detected in these tumors. Western blot analysis identified p63 protein as being predominately localized to mononuclear cells compared to giant cells. This was confirmed by immunohistochemical staining of paraffin-embedded tumor sections, with expression identified in all cases of giant cell tumor of bone. Only a proportion of cases of aneurysmal bone cyst and chondroblastoma showed p63 immunoreactivity whereas it was not detected in central giant cell granuloma, giant cell tumor of tendon sheath, or pigmented villonodular synovitis. The differential expression of p63 in giant cell tumor of bone and central giant cell granuloma suggest that these two tumors may have a different pathogenesis. Moreover, p63 may be a useful biomarker to differentiate giant cell tumor of bone from central giant cell granuloma and other giant cell-rich tumors, such as giant cell tumor of tendon sheath and pigmented villonodular synovitis.

Background: Malignant diffuse-type tenosynovial giant cell tumor (D-TSGCT), an unusual sarcoma with concurrent or previous benign D-TSGCTs, poses challenges to diagnosis and prognostication., Methods: We described the radiologic, clinicopathologic, and immunophenotypical findings of 5 primary and 2 metachronous malignant D-TSGCTs and reviewed published cases to better delineate their morphologic spectrum and behavior. Twenty-four benign D-TSGCTs were also statically compared to analyze the diagnostic values of various variables., Results: The 7 malignant cases affected 4 females and 3 males aged 45 to 78 (mean, 60.9) years, which included 1 intraarticular and 6 extra-articular lesions. These tumors were 5 to 17 cm (mean, 9.4) and located within or near the large joints of extremities. Magnetic resonance imaging revealed expansile or infiltrative masses with frequent lobulation and heterogeneous signals. Histologically, areas of benign D-TSGCTs blended abruptly or gradually with frank sarcomas composed of pleomorphic, spindle, or enlarged oval cells, forming malignant fibrous histiocytomalike (n = 4), fibrosarcomatous (n = 1), myxosarcomatous (n = 1), or giant cell tumorlike (n = 1) patterns. One patient experienced recurrences twice, and another 3 developed metastases to the lymph nodes (n = 2), lung (n = 1), or vertebrae (n = 1), with 1 dying from disseminated diseases. An older age (P = 0.003), a larger size (P = 0.036), tumor necrosis (P < 0.001), atypical mitoses (P < 0.001), and Ki-67 overexpression (P < 0.001) appeared preferentially in malignant lesions, but these parameters had overlap between few benign and malignant tumors., Conclusions: Malignant D-TSGCTs are a distinct sarcoma with considerable morphologic variability, metastatic propensity, and lethality. Altered architecture with anaplastic cells represents an important distinguishing feature, while abnormalities of other parameters should not be directly equated with malignancy.

Giant cell tumour of bone (GCTB) is a benign bone tumour known for the unpredictable clinical behaviour of recurrences and, in rare instances, distant metastases. It consists of uniformly distributed osteoclastic giant cells in a background of mononuclear rounded and spindle-shaped cells. Cytogenetically, telomeric associations are the most common chromosomal aberrations, which, however, are normally almost exclusively found in high-grade malignancies. GCTB has often been regarded as a polyclonal tumour, but more recently a recurrent specific aberration was reported, which suggests a possible role for disturbed telomere maintenance. Here we further investigate telomere maintenance in GCTB using 19 samples from 19 patients. A combination of immunofluorescence and FISH was performed, applying antibodies directed against promyelocytic leukaemia body-related antigen and hTERT and using telomere peptide nucleic acid probes. The TRAP assay and telomere restriction fragment length analysis were performed for functional detection of telomerase activity and alternative telomere lengthening. Both osteoclastic giant cells and mononuclear cells showed positivity for hTERT and promyelocytic leukaemia body-related antigen. In most mononuclear cells, co-expression was present. The TRAP assay demonstrated heterogeneous telomerase activity, while telomere restriction fragment length analysis showed non-heterogeneous telomere lengths, indicating the absence of alternative telomere lengthening. Confocal microscopy showed stereometric co-localization of nucleolin with promyelocytic leukaemia body-related antigen in association with telomeres in the spindle-shaped cells. hTERT was more diffusely distributed throughout the nucleus. Our results show that GCTB demonstrates remarkable telomere maintenance of activated telomerase and inactivated alternative telomere lengthening in the presence of normal mean telomere restriction fragment lengths. These findings strongly suggest that these aggregates, while activating telomerase, are part of a structural telomere protective-capping mechanism rather than of a telomere-lengthening mechanism. Telomere maintenance could be considered an important key factor in the pathogenesis of GCTB., (Copyright (c) 2008 Pathological Society of Great Britain and Ireland)

Objective: To correlate the cytomorphologic spectrum of giant cell tumor of tendon sheath (GCTTS) with clinical and histologic findings and determine key features helpful in preoperative diagnosis., Study Design: Retrospective analysis was done on 48 cases diagnosed cytologically over 9 years. Cases were divided into 2 groups: in group 1 cytology and histology were available (12), and in group 2 cytology alone was available (36). Cytomorphologic features were correlated with clinical and histologic findings., Results: Patients ranged in age from 11 to 60 years, with more women. Small joint involvement was seen in all cases except 1, with upper limb involvement in most cases. Recurrence occurred in 3 cases. Aspiration smears in all cases showed high cellularity, multinucleated osteoclastic type of giant cells and stromal cells. Other features seen less frequently were cytoplasmic granules and vacuoles, nuclear grooves, inclusions, budding, focal mild pleomorphism, hemosiderin-laden macrophages and foam cells. Mitosis and necrosis were absent. Cytologic features were classified as constant when present in all cases and variable when present occasionally., Conclusion: The constant cytologic features when combined with clinical and radiologic details are sufficiently distinctive of GCTTS. Fine needle aspiration cytology can be used in early, accurate preoperative diagnosis.

Giant cell fibroblastoma (GCF) is a subcutaneous mesenchymal neoplasm characterized by the chromosomal t(17;22), which results in the formation of the fusion gene COL1A1-PDGFB. This same fusion gene is also seen in the supernumerary ring chromosome of dermatofibrosarcoma protuberans (DFSP). Several studies have addressed the molecular genetics of DFSP but molecular cytogenetic characterization of individual areas and cell components in pure GCF and GCF/DFSP hybrids have not been performed. Herein, we studied the frequency and genomic copy number of COL1A1-PDGFB in pure GCF and GCF/DFSP hybrids, and identified the molecular cytogenetic signatures in individual cells in each component. Four pure GCF and nine GCF/DFSP hybrids were studied. All tumors exhibited classical histological features and CD34 expression. COL1A1 and PDGFB rearrangements were evaluated by fluorescence in situ hybridization (FISH) using probes for COL1A1 and PDGFB on paraffin-embedded thin tissue sections. All GCF and GCF/DFSP hybrids showed unbalanced rearrangements of COL1A1-PDGFB at the molecular cytogenetic level. Genomic gains of COL1A1-PDGFB were found predominantly in the DFSP component of GCF/DFSP hybrids but in none of the pure GCF, suggesting that these gains are associated with the histologic evolution of GCF into DFSP. The molecular cytogenetic abnormalities were found not only in the spindle/stellated cells but also in individual nuclei of the multinucleated giant cells, suggesting that these cells may result from the fusion of individual neoplastic cells., ((c) 2007 Wiley-Liss, Inc.)

This report describes the case of a 26-year-old woman with a recurrent extraarticular diffuse-type tenosynovial giant cell tumor (D-TGCT) of the medial region of the knee affecting the pes anserinus and hamstring tendons. Presurgical MRI did not exclude infiltrative properties of the tumor. In the histological evaluation, the tumor showed an aggressive dispersion by infiltrating the collagenous tissue of the hamstring tendons. The treatment included a resection of the pes anserinus complex with distal semitendinosus and gracilis tendons. Regarding extraarticular D-TGCT a review of the literature showed a predominant affection of the medial region of the knee and thigh.

The authors present a case of a 42-year-old female who developed a leiomyosarcoma of the right proximal tibia that appeared radiologically similar to a giant cell tumor Histology revealed spindle cells running in whorl-like fashion with focal atypia and low mitotic figures. The immuno-stains revealed positive reactivity for alpha-smooth muscle (SMA), muscle actin and cytokeratin (AE1/AE3). The authors rendered a diagnosis of low-grade leiomyosarcoma of bone. The lesion was considered a primary lesion since the patient did not have other leiomyomatous tumors. The MRI showed hypo- to iso- signal intensity on T1-weighted imaging and heterogeneous intensity on T2-weighted imaging. This was likely due to admixed fibrotic tissue in the lesion. The tumor cells were not positive for Ebstein-Barr virus by in-situ hybridization as seen in leiomyomatous tumors in immunodeficiency patients.

The final diagnosis of a bone tumour comes in many cases like the last piece of a puzzle which requires integration of clinical, imaging and pathological data. However there are situations in which a discrepancy exists between histology and imaging studies and where histology alone cannot be decisive. This paper reviews such situations.

This report presents a case of widespread intramedullary giant cell ependymoma arising from the central canal of the C4 segment of the spinal cord in a 28-year-old man admitted to hospital with tetraplegia and signs of increased intracranial pressure, eight months after surgical spinal cervical decompression without tetraplegia improvement. Magnetic resonance imaging and autopsy revealed a tumour extending from segment C3/C4 of the spinal cord to the lower half of the fourth ventricle with coexisting syringomyelia. This slow-growing ependymoma of low-grade malignancy exhibited unusual morphology as well as degenerative and ischaemic changes. All intramedullary and ventricular tumour segments featured coexistence of two forms of neoplastic cell, classic ependymomal and pleomorphic multinucleated giant cells. The morphological diagnostic criteria of unusual giant-cell variant of ependymoma and tumour-related syringomyelia in adults are discussed, based on the presented case and a review of the literature.

Although osteoclast giant-cell-like proliferations have been reported in a diverse range of human malignancies, to the best of our knowledge, they have never been described in cutaneous squamous cell carcinoma (SCC). Histologically, osteoclastic giant cell tumors within extraosseous malignancy resemble their bony and soft tissue counterparts, with round to spindle-shaped cells admixed with osteoclast-like multinucleate cells. These cells should be distinguished from sarcomatoid differentiation within a carcinoma; they have a benign morphology with a low nuclear to cytoplasmic ratio, minimal pleomorphism/mitoses and negative immunohistochemistry for cytokeratin. The authors report the rare occurrence of osteoclast-like giant cells (OGCs) and accompanying epithelioid histiocytes lacking overtly malignant features in association with a poorly differentiated SCC occurring on sun-damaged skin. Immunohistochemically, the area rich in OGCs was strongly positive for CD68 and completely negative for cytokeratin, whereas the poorly differentiated infiltrative area had the reverse immunophenotype and nuclear positivity for p63. The histological differential diagnosis and the origin of the proliferation are discussed in this article.

Primary giant-cell tumor of the salivary gland is a rare lesion with an incompletely characterized histogenesis. To the best of our knowledge, only 16 cases have been previously documented in the English-language literature. We report a new case, which occurred in a 75-year-old man who presented with a parotid mass and cervical lymphadenopathy. The patient underwent a left total parotidectomy and cervical lymph node dissection. As far as we know, ours is the only reported case of a primary giant-cell tumor of the salivary gland in which the patient presented with lymph node metastasis. Because so little is known about giant-cell tumor of the salivary gland, we use the occasion of this case report to describe the cytologic, histologic, and immunohistochemical characteristics that we observed.

Primary giant cell tumor of soft tissue (GCT-ST) arising in breast is exceedingly rare. We report a case of a 60-year-old woman with a primary breast giant cell tumor that appeared histologically identical to giant cell tumor of bone and had a clinically malignant course. The patient presented with a cystic mass of the breast, suspected on imaging to be an organizing hematoma, possibly related to previous injury. Histopathological evaluation revealed a neoplasm composed of mononuclear cells admixed with osteoclast-like giant cells resembling giant cell tumor of bone. Immunohistochemical staining was positive for CD68, smooth muscle actin, and vimentin, but was negative for a panel of epithelial and additional muscle markers. These features were most consistent with GCT-ST, an uncommon neoplasm of low malignant potential. Despite aggressive surgical treatment achieving clear surgical margins, the patient expired with pulmonary metastases within a year of her initial presentation. This case demonstrates the difficulty of predicting clinical behavior of GCT-ST of breast on the basis of histological features and depth of tumor alone. To our knowledge, this is the first case report of a GCT-ST arising in the breast associated with a fatal outcome. The distinction of this entity from other more common primary breast tumors with giant cell morphology is also emphasized.