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Background: Expression of the colony-stimulating factor 1 (CSF1) gene is elevated in most tenosynovial giant-cell tumors. This observation has led to the discovery and clinical development of therapy targeting the CSF1 receptor (CSF1R)., Methods: Using x-ray co-crystallography to guide our drug-discovery research, we generated a potent, selective CSF1R inhibitor, PLX3397, that traps the kinase in the autoinhibited conformation. We then conducted a multicenter, phase 1 trial in two parts to analyze this compound. In the first part, we evaluated escalations in the dose of PLX3397 that was administered orally in patients with solid tumors (dose-escalation study). In the second part, we evaluated PLX3397 at the chosen phase 2 dose in an extension cohort of patients with tenosynovial giant-cell tumors (extension study). Pharmacokinetic and tumor responses in the enrolled patients were assessed, and CSF1 in situ hybridization was performed to confirm the mechanism of action of PLX3397 and that the pattern of CSF1 expression was consistent with the pathological features of tenosynovial giant-cell tumor., Results: A total of 41 patients were enrolled in the dose-escalation study, and an additional 23 patients were enrolled in the extension study. The chosen phase 2 dose of PLX3397 was 1000 mg per day. In the extension study, 12 patients with tenosynovial giant-cell tumors had a partial response and 7 patients had stable disease. Responses usually occurred within the first 4 months of treatment, and the median duration of response exceeded 8 months. The most common adverse events included fatigue, change in hair color, nausea, dysgeusia, and periorbital edema; adverse events rarely led to discontinuation of treatment., Conclusions: Treatment of tenosynovial giant-cell tumors with PLX3397 resulted in a prolonged regression in tumor volume in most patients. (Funded by Plexxikon; ClinicalTrials.gov number, NCT01004861.).

Giant cell tumors, a well-recognized neoplasm of bone, can rarely be found in the uterus. Such tumors are characterized by a dual population of mononuclear and osteoclast-like giant cells that lack epithelial and specific mesenchymal differentiation. In this study, the clinicopathologic features of 3 giant cell tumors of the uterus were reviewed. Immunohistochemistry for CD68, CD163, h-caldesmon, desmin, SMA, AE1/AE3, CD10, ER, PR, cyclin D1, CD1a, CD34, CD30, S100, myogenin/myoglobin, and Ki-67 was performed in all tumors, along with ultrastructural analysis in one. The patients were 47, 57, and 59 yr and the tumors measured 2.5, 7.5, and 16.0 cm. One neoplasm was confined to the endometrium, whereas the other 2 were myometrial. All 3 tumors showed a nodular growth comprised of mononuclear and osteoclast-like giant cells. The endometrial-confined tumor consisted of histologically benign mononuclear cells, whereas the others exhibited marked atypia. Mitotic activity was up to 5/10 HPF in the benign tumor and up to 22/10 HPF in the malignant. No cytologic atypia or mitoses were observed in the giant cells. CD68 and CD10 were strongly and diffusely expressed in both components of 3 and 2 neoplasms, respectively. Cyclin D1 was focal in the mononuclear cells and focal to diffuse in the giant cells. CD163 was diffuse in the mononuclear cells, but absent to focal in the giant cells. Ultrastructural analysis lacked diagnostic features of epithelial or specific mesenchymal differentiation. Both malignant tumors demonstrated an aggressive behavior. In summary, although rare, giant cell tumor of the uterus should be included in the differential diagnosis of benign or malignant tumors containing osteoclast-like giant cells.

The syndrome of nonislet cell tumor induced hypoglycemia (NICTH) represent extreme cases of excessive expression and production of incompletely processed high-molecular-mass pro-IGF-II forms (big IGF-II) by an often large tumor. Tumor-derived big IGF-II is responsible for enhanced insulin-like effects in the body through complicated mechanisms, leading to hypoglycemia. Case studies on NICTH usually focus on measurements of diagnostic parameters in the circulation of patients. Some studies have also reported on qualitative immunohistochemical analysis of tumor tissue, in particular with respect to the expression of IGF-II at the mRNA or protein level. However, quantitative data on the concentrations of IGFs and IGFBPs in tumor specimen causing NICTH, in relation to their corresponding plasma levels are lacking. Such an analysis would provide an estimate of the total potential of (big) IGF-II retained by the tumor and more insight in the relative levels of different IGFBPs and their origin in the circulation, that is, systemically induced by tumor related factors or directly tumor-derived. Here we investigated quantitatively the levels of IGFs and IGFBPs in a large, 1.76 kg weighing, solitary fibrous tumor from a typical case of NICTH using highly specific immunometric assays. Besides a high level of big IGF-II, patient's plasma also contained increased levels of both IGFBP-2 and -6 which declined after removal of the tumor. These IGFBPs have a higher affinity for (pro-) IGF-II than IGF-I and exhibit intrinsic IGF-independent bioactivities. Tumor tissue contained high amounts of big IGF-II and IGFBP-6, exceeding that in patient's circulation many-fold. A relatively low tumor content of IGFBP-2 was found suggesting that the preoperative high levels in plasma were attributable to systemic mechanisms. The background literature and possible implications of these findings are briefly discussed. Based on the present results we postulate that tumor tissue is not the source of the elevated levels of IGFBP-2 often seen in NICTH patients. Large tumors that cause NICTH can produce IGFBP-6 leading to enhanced levels of this IGFBP in the circulation. Hence, the measurement of IGFBP-6 in plasma may serve as an additional marker of this disease pattern., (© 2015 International Union of Biochemistry and Molecular Biology.)

We present a case of metastatic malignant melanoma in a patient initially diagnosed with glioblastoma multiforme, giant cell variant. A forty year old female presented to our institution for a re-resection of a recurrent right parietal lobe mass, presumed to be recurrent glioblastoma multiforme. PET scan during preoperative evaluation revealed a 3 cm left lower lobe lung mass. Metastatic glioblastoma to lung was considered in the differential diagnosis. Resection of the brain mass revealed a highly pleomorphic giant and spindle cell lesion with an immunophenotype strongly supportive of melanoma. Immunostains for melanocytic markers were subsequently performed on the lung biopsy specimen, and demonstrated diffuse staining of the atypical cells, supporting the diagnosis of malignant melanoma in the lung. This case demonstrates the importance of considering melanoma in the differential in any tumor with high grade features.

Background: Multinucleated giant cells (MNCs) form an integral part of numerous bone and soft tissue tumors, tumor-like lesions and are often associated with granulomas of immunological and nonimmunological origin. The presence of various types of giant cells depends on the lesions in which they are present which are difficult to be diagnosed under routine histological techniques. Immunohistochemistry can be used for a better diagnosis and understanding of the origin of various giant cells using various markers of immune response like human leukocyte antigen-DR (HLA-DR) and those expressed on monocytes and macrophages like CD 68 and leukocyte common antigen (LCA)., Materials and Methods: The study group consisted of 10 cases of giant cell tumor (GCT) of long bones, tuberculous granuloma, and giant cell granuloma to evaluate and analyze the expression pattern of LCA, CD 68, and HLA-DR in various giant cell lesions., Results: Strong expression of CD 68 was observed in 80% of the lesions, strong and moderate expression of CD 45 observed in 70% of the lesions among and within the groups. In contrast, HLA-DR demonstrated negative expression in 80% of cases except for tuberculous granuloma where all the 10 cases showed moderate to strong immunoreactivity., Conclusion: CD 68 and CD 45 expression was found in central giant cell granuloma, peripheral giant cell granuloma and GCT, suggesting the origin from mononuclear phagocyte system and considering their clinical behavior of osteoclast type. High expressivity of HLA-DR in tuberculous granulomas which is an essential factor for presentation of the microbial antigen to CD 4 helper cells thus reassuring the fact that they are up-regulated in response to infection.

Dermatofibromas are slow-growing solitary nodules, composed mostly of a dermal proliferation of spindle cells and epithelioid cells. Some dermatofibromas present with multinucleated giant cells, such as Touton, foreign body, and osteoclast-like cells. We report a case of dermatofibroma containing both Touton giant cells and floret-type cells. A 12-year-old boy presented with a 6-mm, firm, nontender, dusky-red to greyish dermal nodule on his left popliteal fossa. As suggested clinically by the central opening, perforation of the epidermis with partial extrusion of the dermal components, including macrophages and vertically oriented collagen bundles, via transepidermal elimination, were detected. In the upper dermis, collagen trapping and mostly epithelioid cells with many giant cells were seen, while the lower part contained mainly spindle cells in a storiform pattern. Multinucleated giant cells scattered in the upper dermis were mainly floret-type multinucleated giant cells with star-shaped cytoplasmic projections, associated with some Touton giant cells. To our knowledge, this is the first report of a perforating dermatofibroma with floret-type multinucleated giant cells., (© 2014 British Association of Dermatologists.)

Competing Interests: The authors have no conflict of interest.

Purpose: To investigate whether MRI (RECIST 1.1, WHO criteria and the volumetric approach) or (18)F-FDG PET/CT (PERCIST 1.0) are able to predict long-term outcome in nonsurgical patients with giant cell tumour of the tendon sheath or of the diffuse type (GCT-TS/DT)., Methods: Fifteen "nonsurgical" patients with a histological diagnosis of GCT-TS/DT were divided into two groups: symptomatic patients receiving targeted therapy and asymptomatic untreated patients. All 15 patients were evaluated by MRI of whom 10 were treated, and a subgroup of 7 patients were evaluated by PET/CT of whom 4 were treated. Early evolution was assessed according to MRI and PET/CT scans at baseline and during follow-up. Cohen's kappa coefficient was used to evaluate the degree of agreement between PERCIST 1.0, RECIST 1.1, WHO criteria, volumetric approaches and the reference standard (long-term outcome, delay 505 ± 457 days). The response rate in symptomatic patients with GCT-TS/DT receiving targeted therapy was also assessed in a larger population that included additional patients obtained from a review of the literature., Results: The kappa coefficients for agreement between RECIST/WHO/volumetric criteria and outcome (15 patients) were respectively: 0.35 (p = 0.06), 0.26 (p = 0.17) and 0.26 (p = 0.17). In the PET/CT subgroup (7 patients), PERCIST was in perfect agreement with the late symptomatic evolution (kappa = 1, p < 0.05). In the treated symptomatic group including the additional patients from the literature the response rates to targeted therapies according to late symptomatic assessment, and PERCIST and RECIST criteria were: 65 % (22/34), 77 % (10/13) and 26 % (10/39)., Conclusion: (18)F-FDG PET/CT with PERCIST is a promising approach to the prediction of the long-term outcome in GCT-TS/DT and may avoid unnecessary treatments, toxicity and costs. On MRI, WHO and volumetric approaches are not more effective than RECIST using the current thresholds.

Intra- and extra-articular giant cell tumor of tendon sheath (GCTTS) and pigmented villonodular synovitis (PVNS) are histologically similar, usually benign tumors that can be characterized by synovial involvement (GCTTS) or overgrowth (PVNS). These tumors are most often found in the knee and digits of the hand. Although recurrence is a common feature of both conditions, multifocal lesions are rare. We present an unusual case of multifocal, recurrent, bilateral GCTTS/PVNS involving both upper and lower extremities. Recurrent right ankle and right index finger masses, in addition to masses on the right small finger and left thumb, were excised over a 14-year period., (Copyright © 2015 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

Background: Due to the complex anatomy of the upper cervical spinal column region and the variable aggressiveness of giant cell tumors (GCTs), there exists no standard treatment for GCTs of axial vertebra. To the best of our knowledge, there are only a few case reports in the literature and no large sum numbers of clinical trials about the treatment of, or research into, axial vertebra GCTs., Methods: Between 2009 and 2013, five patients pathologically diagnosed with axial vertebra GCTs were treated at our hospital. We performed intralesional excision and odontoid process reconstructive surgery to preserve the odontoid process, followed with adjuvant radiation therapy after surgery., Results: For those with an intact bone shell, part of the β-TCP (beta tricalcium phosphate) artificial bone could be seen clearly after surgery and became blurred three months after surgery, as seen on a radiograph. One year later, the part of β-TCP artificial bone was fused as a block. Subsequently, autogenous bone regenerated successfully and artificial bone degraded thoroughly. For those with a defective cortical bone, partial fusion of the odontoid process, autograft ilium and third vertebra body could be seen three months after surgery, and complete fusion was seen nine months later. The odontoid process was preserved successfully, and the upper cervical spine was reconstructed effectively, without implant failure or infection., Conclusions: In this study, the odontoid process and function of upper cervical vertebra was preserved successfully through lesion curettage, combined with reconstruction with bone grafting, and adjuvant radiation therapy after surgery. During the follow-up periods, no recurrence or complications was observed.

Giant cell tumor (GCT) is primarily a bone neoplasm. Rare origin of the tumor from soft tissues has been reported. Involvement of mediastinum by GCT is even rarer. We herein describe an interesting case of huge mediastinal tumor in a young man. Radiologically, no primary osseous lesion was present throughout the body. Morphologically, tumor resembles osseous GCT with increased mitotic activity. Hence, the case was diagnosed as soft tissue GCT of low malignant potential at the rare site of mediastinum. To the best of our knowledge, the present case is the fourth reported case. Pathologists and clinicians need to be aware of the rare diagnosis of GCT in mediastinum and should carefully evaluate the clinical and radiological findings., (© The Author(s) 2014.)

Patients with Paget's bone disease (PDB) have an increased risk of developing giant cell tumor (GCT). This study was performed to evaluate the clinical characteristics and evolution of GCT complicating PDB and to compare these clinical characteristics to those observed in two large PDB cohorts, the PDB Italian Registry and the United Kingdom's Multi-Centre Randomised Controlled Trial of Symptomatic Versus Intensive Bisphosphonate Therapy for Paget's Disease (PRISM) study. A systematic literature review identified 117 cases of PDB complicated by GCT (PDB-GCT), which involved the skeletal sites affected by PDB (110 patients) or the extraskeletal tissues adjacent to affected bones (7 patients). In contrast to what previously reported for GCT patients without GCT patients (83.2%) were white and one-fourth of them (24.8%) had multifocal GCTs. Compared to PDB patients without GCT, PDB-GCT patients showed a higher male/female ratio (2.1 versus 1.2) and more severe disease (age at PDB onset 52.1 ± 12.1 versus 63.3 ± 10.6 years; number of affected sites 6.1 ± 2.9 versus 2.34 ± 1.6; prevalence of polyostotic PDB 93.3% versus 60.6%). The mortality rate of PDB-GCT patients was higher than those occurring in GCT patients without PDB (about 50% versus 0% to 5% at 5 years) or in PDB patients without GCT (log rank = 29.002). Moreover, up to 98% of PDB-GCT cases had elevated total alkaline phosphatase levels at neoplasm diagnosis, suggestive of active PDB. Importantly, PDB-GCT patients from Southern Italy (45.6% of all GCT patients) showed a higher prevalence of multifocal GCT (51.7%) and of positive familial history for PDB (70.8%) and GCT (65.0%). Finally, indirect evidence suggests a decline in the incidence of GCT in PDB patients. The occurrence of GCT in PDB patients is associated with severe disease and reduced life expectancy of affected patients. The increased prevalence of familial diseases in PDB-GCT patients from Southern Italy suggests a founder effect. The observed changes over time in the incidence of GCT in PDB patients could be related to improved clinical management and/or living conditions of patients., (© 2014 American Society for Bone and Mineral Research.)

Giant cell tumor is an uncommon but most aggressive benign tumour of the spine with unpredictable outcome and challenging treatment. Spinal giant cell tumors located above the sacrum are rare and treatment recommendations are still unclear. We report a rare case of this lesion in an adult and discuss the management and outcome of such uncommon tumors. A 31-year-old woman presented with progressive motor weakness of both lower limbs with back pain during the past month, associated with sphincter disturbances for the past two days. She was diagnosed with a lytic heterogeneously enhancing mass depending mainly on the T6 posterior arch with small vertebral body involvement. The tumor extent reached surrounding soft tissue and the spinal canal with marked spinal cord compression. A posterior approach was realized as an emergency. Histological examination showed evidence of a giant cell tumor and a complementary irradiation was used. The patient improved well post operatively. There was no recurrence or metastasis over 5 years of follow-up.

Background: Tenosynovial giant cell tumour/pigmented villonodular synovitis (TGCT/PVNS) is a benign neoplasm of synovium and tendon sheath. We conducted a retrospective pooled analysis in three major referral centers., Methods: Patients treated between 1998 and 2008 were examined. Only patients presenting with primary disease or first relapse were included. 5-year local failure free survival (5-year-LFFS) was analysed., Results: 294 patients were included: 254 with new diagnosis and 40 in 1st local recurrence (171 F/123 M; median age: 36 years; tumour size ⩽2 cm in 27% of patients, >2 to ⩽5 cm in 41%, and >5 cm in 32%). A diffuse pattern was reported in 69%, localised in 31%. No metastases were documented. Local failure (LF) was reported in 28% of patients: 36% in diffuse pattern, 14% in localised (p = 0.002); median time to LF: 16 months. With a median follow-up of 4.4 years, 5-year-LFFS was 66%, with multiple (up to five) local recurrences in 40% of relapsed patients. Size <2 cm, macroscopically complete resection, female gender and new diagnosis were associated with a better local control. After multivariate analysis, a previous relapse was independently associated with local failure., Conclusions: This study underlines the propensity of TGCT/PVNS to multiple local recurrences. In absence of clinical factors, biological studies are needed to identify prognostic factors of local failure. After a first local recurrence, surgery does not seem to have a curative potential. In these high risk patients, studies addressing the role of target therapies are needed., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Iatrogenic spinal cord herniation is a rare complication following spinal stabilization surgery. The authors present a case of circumferential thoracic tumor decompression and fixation by anterior instrumentation complicated by delayed anterior spinal cord herniation. This complication resulted in progressive paraparesis 5 years after the original procedure. The patient underwent reexploration and repair of the dural defect, resulting in the reduction of the spinal cord to its normal position. The patient's paraparesis improved significantly after dural repair. Although progression of neurological deficit can be very slow, repair of the dural defect can restore normal spinal cord alignment and improve neurological deficit. To the best of the authors' knowledge, this is the first reported case of spinal cord herniation following an anterior thoracic vertebrectomy.

Primary giant-cell tumors rarely arise in the common bile duct. We herein report a case of primary giant-cell tumor of the common bile duct. The patient was an 81-year-old male who was diagnosed with a well-defined 1.2-cm mass projecting into the lumen of the middle common bile duct. Excision of the gallbladder and extrahepatic bile duct and a Roux-en-Y cholangiojejunostomy were performed. Histologically, the tumor had no association with carcinomas of epithelial origin and was similar to giant-cell tumors of the bone. The tumor consisted of a mixture of mononuclear and multinucleated osteoclast-like giant cells. The mononuclear cells showed no atypical features, and their nuclei were similar to those of the multinucleated giant cells. CD68 was expressed on the mononuclear and multinucleated osteoclast-like giant cells, whereas CD163 immunoreactivity was restricted to the mononuclear cells. Six months after the operation, the patient was still alive and had no recurrence. The interest of this case lies in the rarity of this entity, the difficulty of preoperative diagnosis, and this tumor's possible confusion with other malignant tumors.

Soft tissue giant cell tumor (GCT-ST) of low malignant potential, also called primary giant cell tumor of soft tissue, is usually located in the lower extremities and trunk, whereas it is extremely rare in the head and neck region. It is a rare neoplasm involving both superficial and deep soft tissues that mainly affects young to middle-aged adults, presenting as an asymptomatic, well-circumscribed multinodular mass covered by normal skin or with a fleshy red-brown surface when superficially located. The purpose of this article is to report a case of osteoclast-like giant cell tumors of the lip and to review the literature about GCT-STs involving the head and neck region., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Giant-cell tumor of the tendon sheath (GCTTS) and pigmented villonodular synovitis belong to the same type of benign proliferative lesions originating in the synovia that usually affect the joints, bursae, and tendon sheaths. They frequently involve the hands, knees, ankles, and feet. We report a case of GCTTS in the external auditory canal in a 53-year-old woman who presented with hearing loss, fullness, and a sessile lesion protruding from the anterior wall of her external ear canal. The 1.5-cm diameter mass was spherical, well encapsulated, firm, and covered with normal skin. The lesion was completely excised, and the patient's symptoms resolved. No recurrence was detected at 2 years of follow-up.

We report a morphologically rare type of tenosynovial giant cell tumor (TSGCT), localized type, occurring in a 49-year-old man. Imaging examination revealed multiple nodular lesions around the right knee joint. The largest one extended to both intra- and extra-osseous region of the right distal femur. Histologically, the tumor consisted of epithelioid mononuclear cells and they looked like to have abundant eosinophilic cytoplasm reminiscent of hepatic tissues. In some areas, however, typical histologic features of TSGCT were observed. Electron microscopy revealed that the eosinophilic cytoplasm-like substance was intercellular fibrinous material surrounding the mononuclear tumor cells. Immunohistochemically, mononuclear tumor cells and multinucleate giant cells were positive for CD68 (Kp1) and some of the mononuclear tumor cells were also positive for desmin. Finally, we made the diagnosis of hepatoid TSGCT., (Copyright © 2014 Elsevier GmbH. All rights reserved.)

Diffuse-type tenosynovial giant cell tumor (TSGCT) is a locally aggressive neoplasm that primarily affects the synovium and tendon sheath in young adults. Rearrangement of chromosome band 1p13 is now considered a characteristic genetic feature of TSGCT, with the most frequent chromosomal alteration t(1;2)(p13;q37). Here, we describe a unique cytogenetic finding of diffuse-type TSGCT arising in the ankle of an 18-year-old woman. Magnetic resonance imaging demonstrated an ill-defined juxta-articular mass with decreased signal intensity on both T1- and T2-weighted images. Contrast-enhanced T1-weighted images showed intense enhancement of the mass. Open complete resection was performed. Histologically, the tumor was composed of mononuclear cells admixed with multi-nucleated osteoclast-like giant cells, foam cells, siderophages and inflammatory cells. Cytogenetic analysis revealed a reciprocal translocation involving chromosomes 1 and 17, concomitant with a few other numerical and structural alterations. In addition, trisomy 5 as the sole anomaly was identified in two metaphase cells. To the best of our knowledge, this is the first report of this neoplasm with t(1;17)(p13;p13)., (Copyright © 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Parathyroid hormone-related protein (PTHrP) has been identified to play a crucial role in osteolysis formation and stromal cell (GCTSC) proliferation in giant cell tumor (GCT). MiR-126-5p is an intronic miRNA identified as tumor suppressor in many tumors, but its role in GCT is poorly understood. We found that miR-126-5p was decreased in GCT and could directly regulate PTHrP expression. Furthermore, miR-126-5p could control osteoclast (OC) differentiation, GCTSC proliferation and osteolysis formation in GCT through negative regulation of PTHrP. Thus, these results suggest that miR-126-5p could directly target PTHrP and have a tumor suppressor function in GCT., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Anaplastic giant cell ependymoma (AGCE) is a very rare neoplasm. Its cytological features, helpful for the intraoperative diagnosis, have been reported only once. AGCE is characterized by giant cells with intranuclear inclusions, besides other findings, observable in ependymal neoplasms, such as intracytoplasmic vacuoles, epithelial and glial features of the tumor cells and ependymal pseudorosettes. These findings can be detected also in intraoperative squash smear. Herein we describe a pineal AGCE, highlighting the cytological and histological correlations and underlining some useful diagnostic clues of this unusual entity.

An 87 year-old white female presented with a two-year history of intermittent discomfort in her left foot. PET-CT identified intense18F-fluorodeoxyglucose (FDG) uptake corresponding to the lesion. Histology of a fine needle aspiration and open biopsy were consistent with a benign giant cell tumor (GCT) of the bone. GCT of bone is an uncommon primary tumor typically presenting as a benign solitary lesion that arises in the end of the long bones. While GCT can occur throughout the axial and appendicular skeleton, it is exceedingly uncommon in the bone of the foot. While 18F-FDG has been established in detecting several malignant bone tumors, benign disease processes may also be identified. The degree of 18F-FDG activity in a benign GCT may be of an intensity that can be mistakenly interpreted as a malignant lesion. Therefore, GCT of the bone can be included in the differential diagnosis of an intensely 18F-FDG-avid neoplasm located within the tarsal bones.

Introduction: Osteoclast-type giant cell tumors of the salivary gland are extremely rare; only 23 cases have been reported. Two presentations were observed: isolated tumor or tumor associated with a carcinomatous contingent., Case Report: A 51-year-old female patient consulted for a painless left retro-angulo-mandibular swelling having appeared 2 years before. This was a 2 cm parotid mass without facial nerve palsy or cervical lymphadenopathy. The patient underwent a superficial parotidectomy to remove the nodule. The direct microscopic examination revealed an osteoclastic giant cell tumor without any carcinomatous contingent. At immunohistochemistry, mononuclear cells were diffusely and intensely stained by anti-pancytokeratin, while multinucleated cells were totally negative and CD68 positive. The patient was not given any complementary treatment. She was followed-up 23 months later and did not present any signs of recurrence or metastasis., Discussion: The histogenesis and nosology of osteoclastic giant cell are currently unknown. Although this entity was not integrated into the latest WHO classification, most authors consider it as a variant of carcinoma. Published data on the epithelial or histiocytic nature of multinucleated cells is not consensual. Our case presentation supports the hypothesis of a histiocytic differentiation of giant cells and epithelial mononuclear cells., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

A 6-year-old male neutered Australian Shepherd dog was presented for evaluation of a subcutaneous mass on the plantar aspect of the proximal left metatarsus. Fine-needle aspirate smears contained numerous plump spindle cells and large multinucleated cells amongst a considerable amount of pink extracellular matrix. Histopathologic diagnosis of the tissue obtained during initial biopsy and eventual surgical cytoreduction of the mass was a benign giant cell tumor of the tendon sheath (GCTTS). Immunohistochemically, the synovioblastic neoplastic cells were diffusely strongly positive for vimentin and S-100, were multifocally moderately positive for cytokeratin AE1/3, and were negative for CD18, muscle-specific actin (MSA), and melanoma-associated antigen (mutated) 1 (MUM-1). The dog recovered from surgery and underwent definitive radiation therapy to treat the local residual disease. Eight months later, the mass had not recurred. The diagnosis of GCTTS in this case supports previously published reports describing GCTTS as a relevant disease entity in dogs, and provides the first documentation of cytologic findings with this tumor. Further investigation is needed to correlate pathologic features with clinical behavior and response to therapy in dogs., (© 2014 American Society for Veterinary Clinical Pathology and European Society for Veterinary Clinical Pathology.)

Background: There are many reports of en bloc resection for spinal tumors. However, no studies have evaluated the clinical outcomes with follow-up exceeding 10 years after surgery., Methods: We reviewed 82 patients who had undergone total en bloc spondylectomy (TES) before January 2002 and identified 29 (19 with primary tumors and 10 with metastatic tumors) who had survived for more than 10 years after surgery. We evaluated the clinical outcomes including patient-based outcomes using questionnaire. The questionnaire included subjective assessment of the results of TES and SF-36., Results: Overall, 33 % of patients with metastases from kidney cancer and 25 % of those with metastases from thyroid cancer survived for more than 10 years after TES for solitary spinal metastases. Four patients with metastatic tumors had no evidence of disease at the time of survey. There were no tumor recurrences in any of the 23 patients who underwent TES as the primary surgery. No revision surgeries have been required as a result of instrumentation failure in any of the 29 patients. About 90 % of the patients were satisfied or very satisfied with the results of TES. The SF-36 results demonstrated that the both physical and mental health of patients with primary tumors was equivalent to those of healthy individuals, and the mental health of patients with metastatic tumors was almost similar to them., Conclusions: This study showed the long-term clinical outcomes after TES to be favorable. TES played an important role in the treatment strategy for spinal tumors including metastases.

Tenosynovial giant cell tumors are a group of neoplastic disorders that involve synovium-lined tendon sheaths, synovial joints, and adjacent soft tissue. They are divided into localized and diffuse subtypes. TSGCTs have well-established clinical and histological diagnostic criteria; however, the subtypes and nomenclature can be confusing. They also pose diagnostic challenges when they occur in atypical locations or without multinucleated giant cells. With the possibility for systemic targeted therapy in relapsing pigmented villonodular tenosynovitis and diffuse-type giant cell tumor, accurate diagnosis and subtyping of TSGCTs is increasingly important. We report two cases of TSGCTs in order to elucidate the diagnostic nomenclature, clinicopathological features, differential diagnosis, and diagnostic pitfalls. Recent advancements in the pathogenesis and targeted therapy of TSGCTs are also discussed.

We report on a unique case of a young female patient with the Goltz-Gorlin syndrome who developed a giant cell tumor of bone in the distal phalanx of the thumb. This case is noteworthy because of the combination of some unusual features. Firstly, it is only the fifth case report on the association of giant cell tumor of bone and the Goltz-Gorlin syndrome. Also the localization of the lesion in the bones of the hand and the presentation at adolescent age is rarely seen.

Objective: To study the clinical features, tumor characteristics and outcomes of giant cell tumors (GCTs) in the skull base based on long-term follow-up. We also report the largest series of GCTs in the temporal bone and the lateral skull base., Materials and Methods: A retrospective study was conducted of all GCTs managed at the Gruppo Otologico, a quaternary referral skull base institute, in Italy from 1993 to 2013. The clinical features, investigations, surgical management and follow-up were recorded. The surgical approaches used were infratemporal fossa approach (ITFA) type B and D and middle cranial fossa (MCF) approaches., Results and Observations: A total of 7 patients with GCTs of the skull base were treated at our institution. The principal complaints were hearing loss reported in 6 (85.71%) patients, tinnitus in 5 (71.43%) and swelling in 3 (42.9%). Pure-tone audiometry showed conductive hearing loss in 5 (71.43%) patients. High-resolution CT scan and MRI with gadolinium enhancement were done in all patients. Radiology showed involvement of the ITF and middle ear in 6 (85.71%) patients each, temporomandibular joint in 4 (57.14%) patients, invasions of the squamous part of the temporal bone, mastoid, MCF and greater wing of sphenoid in 3 (42.9%) patients each and the petrous bone in 2 (28.6%) patients. ITFA type B was applied as an approach for tumor removal in 5 (71.43%) patients, including a case where an additional MCF approach was employed, and ITFA type D and the transmastoid approach were applied in 1 (14.3%) patient each. Total tumor removal and successful cure was achieved in 6 (85.71%) patients. Subtotal removal leading to recurrence and eventual mortality was the result in 1 (14.3%) patient., Conclusions: A thorough knowledge of the anatomy of the skull base and the various skull base approaches is necessary to tackle GCTs. ITFA type B and D combined with MCF approaches provide good exposure of the tumor with minimal postoperative sequelae and good locoregional control. Recurrence due to either subtotal removal or suboptimal treatment may have disastrous consequences for the patient.

Objective: To determine the rate of giant cell tumor (GCT) recurrence and evaluate the factors associated with its recurrence in patients who underwent surgery and submitted to only one adjuvant method., Methods: Forty-one patients (22 female, 19 male; mean age: 34.22 ± 9.70 years) with GCT, who underwent surgical and one adjuvant treatment, were evaluated after a mean follow-up period of 40.17 ± 22.08 months. The average tumor size was 8.51 ± 3.69 cm. The tumors in 18 patients (43.9%) were grade II and in 23 patients (56.1%) grade III, according to the system developed by Campanacci et al. The surgical margin was intralesional resection and curettage in 60.9% of the patients, and marginal or wide resection in 39.1%., Results: Nine (22%) of the 41 patients had recurrence. None of the gender (p=0.436), age (p=0.310), site of the tumor (p=0.940), surgical margins (p=0.400) and the type of the filling material (PMMA or autograft) (p=0.680) had an association with recurrence. However, Campanacci grade III (p=0.028) and the size of the tumor (p=0.034) was associated with the recurrence., Conclusion: Tumor size and tumor grade III according to the Campanacci system appear to be risk factors for local recurrence after the local resection of GCT.

Giant cell tumor of soft parts is a rare tumor that is clinically and histologically similar to giant cell tumor of the bone. We present a 53-year-old female with a giant cell tumor of low malignant potential arising from the neck. The clinicopathological features and the importance of immunohistochemistry in the differential diagnosis with other giant cell rich tumors was discussed.

Giant cell tumors (GCTs) are generally benign, locally aggressive lesions mostly located in the metaphysis of long bones. GCTs of the skull are rare and the majority of the cases have been presented as case reports. The authors retrospectively reported 18 patients with GCTs of the skull at a single institution from April 1994 to February 2012 and summarized the clinical, radiological, pathological characteristics and management of the disease. Meanwhile, a systematic review of 94 case reports of GCTs of the skull was performed. Headache and symptoms related to the involvement of intracranial nerves were the most common symptoms. Over 90 % of the tumors originated from sphenoid and temporal bones. On MRI, very low signal on T2-weighted images were found highly indicative of GCTs of the temporal bone. Univariate analysis revealed that extent of tumor resection and post-operative radiation therapy (RT) were prognostic factors significantly influencing the survival of the patients. We concluded that complete tumor resection is the optimal goal in treating this disease and adjuvant RT should be given once tumor residual is inevitable.

Background: Sarcomatoid carcinomas (SCs) are rare tumors that may arise in the lung, accounting for 0.4% of non-small-cell lung cancers; the prognosis is poor. Only few retrospective small-size series have studied the efficacy of chemotherapy (CT) for metastatic SC., Methods: Multicenter study of patients with advanced or metastatic SC who received first-line CT. Clinical characteristics at baseline, response to first-line CT (Response Evaluation Criteria in Solid Tumors version 1.1), progression-free survival (PFS), and overall survival (OS) were retrospectively collected., Results: Ninety-seven patients were included. Median age was 62 (54-72) years. The majority of patients were men (70%), white (84%), and smokers (84%). Overall, 73% of patients received first-line platinum-based CT. At first tumor evaluation, 69% of patients experienced progression, 31% had disease control, and 16.5% had partial response. Partial response was observed in 20% of patients receiving platinum-based CT, and in none of those receiving non-platinum-based CT (p = 0.018). Median PFS was 2.0 months (confidence interval [CI] 95%: 1.8-2.3). PFS was not statistically different between patients receiving or not receiving a platinum-based CT. Median OS was 6.3 months (CI 95%: 4.7-7.8). There was a trend toward better OS for patients treated with platinum-based CT (7.0 months [CI 95%: 4.9-9.0] versus 5.3 months [CI 95%: 2.8-7.6]; p = 0.096). In multivariate analysis, disease control at first evaluation (hazard ratio = 0.38 [CI 95%: 0.21-0.59]) and at platinum-based CT (hazard ratio = 0.92 [CI 95%: 0.85-0.99]) was associated with better OS., Conclusion: SC is associated with poor prognosis and high rate of resistance to conventional first-line CT. New therapeutic strategies are needed, based on better knowledge of the carcinogenesis of SC.

Giant cell tumors of the spine are uncommon. Usually they are benign and solitary, but locally very aggressive. Most of them occur at the sacral spine. There are only 26 reported cases in the literature involving this type of tumor in the lumbar spine, in particular exhibiting an intraperitoneal growth. We present the case of a woman with a primary tumor of the lumbar spine (giant cell tumor) with intraperitoneal growth, the outcome as well as a review of the literature. Furthermore, after reviewing all spinal cases in the literature above the sacral spine, we carefully suggest a management algorithm.

Custom-made endoprosthetic reconstruction for distal tibia tumors is a viable option of treatment in carefully selected patients. It maintains satisfactory function and provides good pain relief. We report four cases of giant cell tumors of the distal tibia successfully treated by endoprosthetic reconstruction. This is a feasible option in cases of this nature and offers a better function than the other available options., (© 2012 Wiley Publishing Asia Pty Ltd.)