Osteoclast-like Multinucleated Cells Research Articles

Giant Cell Tumor of Soft Tissue: An Updated Review.

Giant cell tumor of soft tissue (GCTST) is a locally aggressive mesenchymal neoplasm of intermediate malignancy that predominantly occurs in the superficial soft tissue of the extremities. It is histologically similar to a giant cell tumor of bone (GCTB) and shows a mixture of round to oval mononuclear cells and osteoclast-like multinucleated giant cells. Currently, immunohistochemistry plays a very limited role in the diagnosis of GCTST. Primary or secondary malignant GCTST has recently been described and tumors exhibiting high-grade histological features demonstrate higher rates of distant metastasis. GCTST lacks the H3-3A gene mutations that are identified in the vast majority of GCTBs, suggesting a different pathogenesis. Surgery is the standard treatment for localized GCTST. Incomplete surgical resection is usually followed by local recurrence. Radiation therapy may be considered when the close proximity of critical structures prevents microscopically negative surgical margins. The systemic treatment options for advanced or metastatic disease are very limited. This review provides an updated overview of the clinicoradiological features, pathogenesis, histopathology, and treatment for GCTST. In addition, we will discuss the differential diagnosis of this peculiar neoplasm.

Recurrent USP6 rearrangement in a subset of atypical myofibroblastic tumours of the soft tissues: low-grade myofibroblastic sarcoma or atypical/malignant nodular fasciitis?

Low-grade myofibroblastic sarcoma (LGMS) is a rarely metastasizing myofibroblastic tumour mostly affecting extremities and the head and neck of adults. Histologically, it shows long infiltrative fascicles of spindle cells with moderate nuclear atypia. By immunohistochemistry, it stains positive for smooth muscle actin (SMA) and sometimes for desmin. To date, no recurrent genetic abnormalities have been described. Ubiquitin-specific peptidase 6 (USP6) gene rearrangement is typically found in some benign bone and soft-tissue tumours including nodular fasciitis (NF), among others. Nevertheless, rare cases of USP6-rearranged tumours resembling NF with atypical features have been reported. One index case of LGMS of the deltoid in a 56-year-old man presented the THBS2::USP6 translocation by RNA sequencing (Archer FusionPlex Sarcoma v2 panel). Further screening of 11 cases of LGMS using fluorescent in situ hybridization (FISH) analysis with a USP6 break-apart probe identified two additional cases. These cases were investigated with RNA-sequencing, and a RRBP1::USP6 translocation was detected in one. The other case was not assessable because of low-quality RNA. Noteworthy, rearranged LGMSs presented distinctive features including variable multinodular/plexiform architecture, prominent vasculature with occasional wall thickening, scattered osteoclast-like multinucleated giant cells, and peripheral lymphoid aggregates. Our findings support the notion that among soft-tissue neoplasms with fibroblastic/myofibroblastic phenotype, USP6 rearrangement is not limited to benign tumours, and warrants further investigation of genetic changes in myofibroblastic sarcomas.

Pharmacological inhibition of endoplasmic reticulum stress mitigates osteoporosis in a mouse model of hindlimb suspension

Hindlimb suspension (HLS) mice exhibit osteoporosis of the hindlimb bones and may be an excellent model to test pharmacological interventions. We investigated the effects of inhibiting endoplasmic reticulum (ER) stress with 4-phenyl butyrate (4-PBA) on the morphology, physicochemical properties, and bone turnover markers of hindlimbs in HLS mice. We randomly divided 21 male C57BL/6J mice into three groups, ground-based controls, untreated HLS group and 4-PBA treated group (HLS+4PBA) (100mg/kg/day, intraperitoneal) for 21 days. We investigated histopathology, micro-CT imaging, Raman spectroscopic analysis, and gene expression. Untreated HLS mice exhibited reduced osteocyte density, multinucleated osteoclast-like cells, adipocyte infiltration, and reduced trabecular striations on micro-CT than the control group. Raman spectroscopy revealed higher levels of ER stress, hydroxyproline, non-collagenous proteins, phenylalanine, tyrosine, and CH2Wag as well as a reduction in proteoglycans and adenine. Furthermore, bone alkaline phosphatase and osteocalcin were downregulated, while Cathepsin K, TRAP, and sclerostin were upregulated. Treatment with 4-PBA partially restored normal bone histology, increased collagen crosslinking, and mineralization, promoted anti-inflammatory markers, and downregulated bone resorption markers. Our findings suggest that mitigating ER stress with 4-PBA could be a therapeutic intervention to offset osteoporosis in conditions mimicking hindlimb suspension.

Extraskeletal Osteosarcoma with Extensive Gastrointestinal Tract Involvement

Abstract Introduction/Objective Extraskeletal osteosarcoma (ESOS) is a rare aggressive mesenchymal tumor that originates from soft tissues or visceral organs, differentiating it from primary bone osteosarcoma. ESOS represents less than 5% of all osteosarcomas and less than 1% of soft tissue sarcomas. Primary ESOS in the gastrointestinal tract (GIT) is exceedingly uncommon, with a low incidence rate Methods/Case Report A 70 year-old-man with a history of hypertension, Myasthenia Gravis, hypothyroidism (status post total thyroidectomy), and skin cancer presented to the clinic with a chief complaint of abdominal fullness of 4 months duration. Primary work-up revealed anemia (Hemoglobin 7 g/dl) and peripheral blood smear was suggestive of bone marrow infiltration. Evaluation with upper gastrointestinal endoscopy and ultrasound demonstrated regular mucosal folds of the stomach with a solid-cystic lesion between the body of the pancreas and the posterior aspect of the stomach. The patient underwent a fine needle biopsy showing a spindle cell lesion with positive immunohistochemistry (IHC) for Smooth Muscle Actin (SMA), beta-Catenin, CD34, and negative for panCK, DOG-1, and CD117; suggestive of leiomyoma. The patient underwent a total gastrectomy, distal pancreatectomy, and splenectomy. Examination of the specimen confirmed a high-grade malignant spindle cell lesion with numerous associated osteoclast-like multinucleated giant cells, and focal areas consistent with osteoid changes. The IHC was requested and the cells were positive for WT1 and Muscle Specific Actin, SATB2, and Ki-67>90% whereas the cells were negative for SMA, Myo-D1, Myogenin, S100, SOX10, MART1, CD34, CD31, and Calretinin. Also, the genetic analysis for MDM2 was negative. These findings confirmed the diagnosis of ESOS with abdominal visceral involvement (stomach, pancreas, and omentum) Results (if a Case Study enter NA) NA Conclusion ESOS is an extremely rare condition that demands a comprehensive evaluation involving clinical, radiological, histopathological, and immunohistochemical analyses to establish an accurate diagnosis. Distinguishing ESOS from primary bone osteosarcoma is vital due to the different treatment strategies. Additionally, ESOS requires a unique therapeutic approach compared to more prevalent gastrointestinal sarcomas like GIST or leiomyosarcoma. The mainstay of ESOS treatment entails complete surgical resection of the tumor with clear margins, accompanied by adjuvant chemotherapy. Ensuring precise diagnosis is of utmost importance to provide suitable and effective treatment

Aggressive Osteoblastoma of Temporal Bone Causing Facial Palsy in a 9-year-old Child: A Case Report Based on 2020 WHO Classification of Bone Tumors

AbstractAggressive osteoblastoma (AO) is an uncommon bone tumor that represents a borderline lesion between osteoblastoma and osteosarcoma. The vertebral column, the sacrum, the pelvis, and jaw/craniofacial bones are primarily affected. Aggressive osteoblastoma does not metastasize and is treated by surgical resection. The authors report a case of AO in a 9-year-old female patient presenting with 5th and 7th cranial nerve palsy. Prior pathological history included resection of an expansile nodule in the left temporal bone. Conventional radiological examination and computed tomography (CT) of the skull revealed an osteoblastic lesion arising in the petrous portion of the left temporal bone, measuring 5.2 cm in the largest dimension. The patient was subjected to partial surgical resection of the process. Microscopy revealed a primary neoplastic bone composed of numerous epithelioid round osteoblasts disposed in solid sheets and with mild atypia, large eosinophilic cytoplasm, and an eccentric, ovoid nucleus. The process exhibited loose stroma, low mitotic index, osteoid formation, and a few osteoclast-like multinucleated giant cells. The diagnosis of AO was thus established. After 5 months of clinical follow-up, the patient is asymptomatic, without evidence of tumoral growth on CT scans.

Cutaneous Atypical Fibroxanthoma With Osteoclast-Like Giant Cell: A Rare but Diagnostic Pitfall.

Atypical fibroxanthoma (AFX) is a dermal-based, low-grade neoplasm with no specific lineage of differentiation. The occurrence of AFX with osteoclast-like giant cells is exceptionally rare. Less than 20 cases have been reported in the literature. A 77-year-old man with a medical history of multiple basal and squamous cell carcinomas of the skin, presented with a progressively growing erythematous nodule on the sun-damaged right central parietal scalp. A shave biopsy showed a dermal spindle cell proliferation accompanied by numerous osteoclast-like multinucleated giant cells and predominant atypical mitotic figures. The immunohistochemical staining showed a diffuse positive staining for CD68 and SMA, patchy staining for CD10, and negative staining for SOX-10, pan-cytokeratin, CK5/6, S100, CD34, and desmin. The tumor was completely excised with negative margins. A subsequent follow-up over a period of 13 months showed no recurrence. Distinguishing AFX with osteoclast-like giant cells from both malignant and benign skin lesions with osteoclast-like giant cells is crucial. Although AFX tumors display worrisome malignant histologic features, most cases have a favorable prognosis with a local recurrence rate below 5% and exceedingly rare metastasis.

Osteogenesis and osteoclastogenesis on a chip: Engineering a self-assembling 3D coculture

Healthy bone is maintained by the process of bone remodeling. An unbalance in this process can lead to pathologies such as osteoporosis which are often studied with animal models. However, data from animals have limited power in predicting the results that will be obtained in human clinical trials. In search for alternatives to animal models, human in vitro models are emerging as they address the principle of reduction, refinement, and replacement of animal experiments (3Rs). At the moment, no complete in vitro model for bone-remodeling exists. Microfluidic chips offer great possibilities, particularly because of the dynamic culture options, which are crucial for in vitro bone formation. In this study, a scaffold free, fully human, 3D microfluidic coculture model of bone remodeling is presented. A bone-on-a-chip coculture system was developed in which human mesenchymal stromal cells differentiated into the osteoblastic lineage and self-assembled into scaffold free bone-like tissues with the shape and dimensions of human trabeculae. Human monocytes were able to attach to these tissues and to fuse into multinucleated osteoclast-like cells, establishing the coculture. Computational modeling was used to determine the fluid flow induced shear stress and strain in the formed tissue. Furthermore, a set-up was developed allowing for long-term (35 days) on-chip cell culture with benefits including continuous fluid-flow, low bubble formation risk, easy culture medium exchange inside the incubator and live cell imaging options. This on-chip coculture is a crucial advance towards developing in vitro bone remodeling models to facilitate drug testing.

Undifferentiated carcinoma with osteoclast-like giant cells – a case report

Undifferentiated carcinoma of the pancreas with osteoclast-like giant cells is an exceptionally rare malignancy, with fewer than 100 cases reported to date. While the histological features of this entity have been well described, cytological diagnosis can present a challenge. This case report describes the cytological features of a fine needle aspirate from a heterogenous pancreatic mass in a 75-year-old man. The smears revealed singularly dispersed and clustered cells with marked atypia in a background of histiocytes and osteoclast-like multinucleated giant cells.

Clinical manifestations and imaging and pathological features of giant cell angioblastoma: Report of four cases and literature review.

Giant cell angioblastoma is a relatively rare vasogenic tumour. To date, studies on its clinical manifestations, imaging characteristics, pathological features, and prognosis are extremely limited and unknown, with only a few cases recorded. In this study, four cases of giant cell angioblastoma confirmed by pathological examination were reported to improve our understanding and deep exploration of the tumour spectrum. All cases in our study were male, including two adults and two boys. The lesions were located in the lower segment of the femur, medial condyle of the femur, knee joint, and popliteal fossa. Regarding the imaging characteristics, two patients with lesions in bone showed bone destruction, while the other two had lesions that invaded soft tissues, showing irregular, abnormal signal shadows and obvious enhancement. Histopathological analysis revealed that the nodular tumour tissue was mainly composed of oval and spindle cells, with varying numbers of osteoclast-like multinucleated giant cells, and the interstitial tissues were often filled with blood vessels of different sizes. The immunophenotype demonstrates that endothelial cells of small vessels in nodules expressed CD31, SMA, and ERG, while osteoclast-like multinucleated giant cells and histiocytes expressed CD68 and CD163, and the surrounding cells expressed SMA. All four patients were treated with surgical resection. One of them relapsed 1 month after surgery and received a second surgical resection. No distant metastasis or death occurred during the follow-up period. This study indicates that giant cell angioblastoma is a local invasive vascular tumour that can develop both in children and adults with skin, mucous membrane, soft tissue, and bone involvement. Imaging characteristics show bone destruction and irregular, abnormal signal shadows; in addition, obvious pathological morphological features can be observed. Currently, the treatment is mainly surgical resection, and interferons may be used as adjuvant chemotherapy.

OSTEOBLASTOMA OF THE MANDIBLE: A CASE REPORT

A 19-year-old White female patient presented with the chief complaint of pain in the left region of the mandible, without extra- or intraoral clinical alteration. Radiographic exams and cone beam computed tomography revealed a mixed-density lesion, with poorly defined borders, promoting dental displacement, and cortical expansion by lingual. Teeth 31 to 35 showed thickening of the periodontal ligament. The provisional diagnosis was osteoblastoma. An incisional biopsy revealed the presence of thin, anastomosed irregular bone trabeculae, lined by a rim of osteoblasts and occasional osteoclast-like multinucleated giant cells, permeated by fibrovascular stroma, confirming the clinical hypothesis of osteoblastoma. The lesion was surgically removed, and the final diagnosis was osteoblastoma. Osteoblastoma is a rare benign neoplasm in the jaw, and diagnosis is based on the correlation between clinicopathologic findings. Because of its varied clinical behavior, early diagnosis is an important strategy for the establishment of an effective treatment.

Https://doi.org/10.18019/1028-4427-2022-28-4-579-583 Гистологическая характеристика гигантоклеточной опухоли оболочек сухожилий, сочетанной с ладонным фасциальным фиброматозом (случай из практики)

Giant cell tumor of the tendon sheaths and palmar fascial fibromatosis are both fibrohistiocytic diseases. There is no information about their combination in the available literature. Aim To analyze the histological characteristics of a giant cell tumor of the tendon sheath associated with palmar fascial fibromatosis. Materials and methods Case history and pathomorphological examination of the surgical material of patient M with recurrent palmar fascial fibromatosis and Dupuytren's contracture of the 5th ray of the right hand in grade 3 and a neoplasm of the 2nd finger of the right hand Results A neoplasm with a thin fibrous capsule, permeated with blood vessels, many of them had abnormally thickened fibrous walls and completely obliterated lumens. The cellular composition of the tumor is mixed: fibroblast-like cells, small histiocytes, siderophages, osteoclast-like giant multinucleated cells, xanthoma and plasma cells. The frequency of mitoses is less than one per 10 fields of view, apoptotic bodies from zero to several per field of view. In the composition of fibromatous cords in the projection of the V beam, giant multinucleated cells (possibly cells of foreign bodies) were found. Conclusion For the first time, a clinical case of a giant cell tumor of the tendon sheaths, which developed against the background of a long-term recurrent palmar fascial fibromatosis, is presented. Taking into account the pathomorphological characteristics of the surgical material, the risk of its recurrence and malignancy in patient M. is low. However, the unpredictability of the histogenesis of this tumor known from the literature is an indication for active clinical observation.

Synthetic studies for destruxins and biological evaluation for osteoclast-like multinucleated cells: a review.

Synthesis of various destruxin analogs was accomplished using Shiina's macrolactonization as a key reaction. Combinatorial synthesis of cyclization precursors using solid-phase peptide synthesis and macrolactonization in solution were successful. In the synthesis of destruxin E and its analogs, the hydroxyacid-proline (HA1-Pro2) dipeptide with an acetonide-protected diol moiety was synthesized in an asymmetric manner, and the protected diol was converted to an epoxide after macrocyclization. Destruxin E was synthesized on a gram scale using solution-phase synthesis. The structure-activity relationships of destruxins were elucidated through biological evaluation of synthetic destruxins A, B, and E and their analogs for morphological changes in osteoclast-like multinucleated cells.

Primary Giant Cell Tumor of Soft Tissue in The Female Breast

A giant cell tumor of soft tissue (GCT-ST) is a rare tumor composed of mononuclear and osteoclast-like multinucleated giant cells. It is a low-grade malignant potential tumor morphologically analog to a giant cell tumor of bone. The superficial and deep soft tissue of extremities is the most frequent site of this tumor which is cured by complete or radical resection. GCT-ST as a primary tumor in the female Breast is exceedingly rare. Presentation of osteoclast-like multinucleated giant cells in the breast tumor has been described in association with the variant of breast carcinoma. We report a case of primary GCT-ST arising in the female Breast without a relationship with the epithelial component. To the best of our knowledge, this is the fifth such case report, and only the second one occurred in a female under 50 years.

Giant Cell Tumor of Bone Versus Tenosynovial Giant Cell Tumor - Similarities and Differences.

Giant cell tumor of bone (GCTB) and tenosynovial giant cell tumor (TGCT) share misleadingly similar names, soft texture and brown color macroscopically, osteoclast-like multinucleated giant cells microscopically and localisation in the musculoskeletal system. However, these two tumor types are biologically and clinically two distinct entities with different natural courses of progression and considerably different modes of surgical and medical treatment. In this article, we provide a detailed update on the similarities and the differences between both tumor types.GCTB is a locally aggressive osteolytic bone tumor, commonly seen in patients in their third decade of life. It usually occurs as a solitary lesion in the meta-epiphyseal region of long bones. It can be diagnosed using plain radiographic imaging, CT radiography or MRI to estimate the tumor extent, soft tissue and joint involvement. GCTB is usually treated with intralesional excision by curettage. Systemically, it can be treated with bisphosphonates and denosumab or radiotherapy.TGCT is a rare, slowly progressing tumor of synovial tissue, affecting the joint, tendon sheath or bursa, mostly seen in middle-aged patients. TGCT is usually not visible on radiographs and MRI is mostly used to enable assessment of potential bone involvement and distinguishing between two TGCT types. Localised TGCT is mostly treated with marginal surgical resection, while diffuse TGCT is optimally treated with total synovectomy and is more difficult to remove. Additionally, radiotherapy, intraarticular injection of radioactive isotopes, anti-TNF-α antibodies and targeted medications may be used.

In vitro and in vivo detection of tunneling nanotubes in normal and pathological osteoclastogenesis involving osteoclast fusion

AbstractOsteoclasts are multinucleated cells formed through specific recognition and fusion of mononuclear osteoclast precursors derived from hematopoietic stem cells. Detailed cellular events concerning cell fusion in osteoclast differentiation remain ambiguous. Tunneling nanotubes (TNTs), actin-based membrane structures, play an important role in intercellular communication between cells. We have previously reported the presence of TNTs in the fusion process of osteoclastogenesis. Here we analyzed morphological details of TNTs using scanning electron microscopy. The osteoclast precursor cell line RAW-D was stimulated to form osteoclast-like cells, and morphological details in the appearance of TNTs were extensively analyzed. Osteoclast-like cells could be classified into three types; early osteoclast precursors, late osteoclast precursors, and multinucleated osteoclast-like cells based on the morphological characteristics. TNTs were frequently observed among these three types of cells. TNTs could be classified into thin, medium, and thick TNTs based on the diameter and length. The shapes of TNTs were dynamically changed from thin to thick. Among them, medium TNTs were often observed between two remote cells, in which side branches attached to the culture substrates and beaded bulge-like structures were often observed. Cell-cell interaction through TNTs contributed to cell migration and rapid transport of information between cells. TNTs were shown to be involved in cell-cell fusion between osteoclast precursors and multinucleated osteoclast-like cells, in which movement of membrane vesicles and nuclei was observed. Formation of TNTs was also confirmed in primary cultures of osteoclasts. Furthermore, we have successfully detected TNTs formed between osteoclasts observed in the bone destruction sites of arthritic rats. Thus, formation of TNTs may be important for the differentiation of osteoclasts both in vitro and in vivo. TNTs could be one target cellular structure for the regulation of osteoclast differentiation and function in bone diseases.

Stromal cells of giant cell tumor of bone show primary cilia in giant cell tumor of bone.

Giant cell tumor of bone (GCTB) is a locally aggressive primary bone neoplasm composed by tumoral stromal cells (SCs) and a reactive component that consists of monocytic/histiocytic cells that give rise by fusion to osteoclast-like multinucleated cells. Recently, specific Histone 3.3 mutations have been demonstrated in SCs of GCTB. Many of the pathways related to bone proliferation and regulation depend on the primary cilium, a microtubule-based organelle that protrudes outside the cell and acts as a sensorial antenna. In the present work, we aimed to study the presence and role of primary cilia in GCTB. Ultrastructural, immunohistochemical, and immunofluorescence studies were performed in order to demonstrate, for the first time, that the primary cilium is located in spindle-shaped SCs of GCTB. Moreover, we showed Hedgehog (Hh) signaling pathway activation in these cells. Hence, primary cilia may play a relevant role in GCTB tumorogenesis through Hh signaling activation in SCs. RESEARCH HIGHLIGHTS: Transmission electron microscopy allows describing and differentiating cellular subpopulations in giant cell tumor of bone (GCTB). The primary cilium is present in some tumoral stromal cells of GCTB. Hedgehog signalling is activated in these cells.

Serglycin induces osteoclastogenesis and promotes tumor growth in giant cell tumor of bone

Giant cell tumor of bone (GCTB) is an aggressive osteolytic bone tumor characterized by the within-tumor presence of osteoclast-like multinucleated giant cells (MGCs), which are induced by the neoplastic stromal cells and lead to extensive bone destruction. However, the underlying mechanism of the pathological process of osteoclastogenesis in GCTB is poorly understood. Here we show that the proteoglycan Serglycin (SRGN) secreted by neoplastic stromal cells plays a crucial role in the formation of MGCs and tumorigenesis in GCTB. Upregulated SRGN expression and secretion are observed in GCTB tumor cells and patients. Stromal-derived SRGN promotes osteoclast differentiation from monocytes. SRGN knockdown in stromal cells inhibits tumor growth and bone destruction in a patient-derived orthotopic xenograft model of mice. Mechanistically SRGN interacts with CD44 on the cell surface of monocytes and thus activates focal adhesion kinase (FAK), leading to osteoclast differentiation. Importantly, blocking CD44 with a neutralizing antibody reduces the number of MGCs and suppresses tumorigenesis in vivo. Overall, our data reveal a mechanism of MGC induction in GCTB and support CD44-targeting approaches for GCTB treatment.

Human osteoclastogenesis in Epstein-Barr virus-induced erosive arthritis in humanized NOD/Shi-scid/IL-2Rγnull mice.

Many human viruses, including Epstein-Barr virus (EBV), do not infect mice, which is challenging for biomedical research. We have previously reported that EBV infection induces erosive arthritis, which histologically resembles rheumatoid arthritis, in humanized NOD/Shi-scid/IL-2Rγnull (hu-NOG) mice; however, the underlying mechanisms are not known. Osteoclast-like multinucleated cells were observed during bone erosion in this mouse model, and therefore, we aimed to determine whether the human or mouse immune system activated bone erosion and analyzed the characteristics and origin of the multinucleated cells in hu-NOG mice. Sections of the mice knee joint tissues were immunostained with anti-human antibodies against certain osteoclast markers, including cathepsin K and matrix metalloproteinase-9 (MMP-9). Multinucleated cells observed during bone erosion stained positively for human cathepsin K and MMP-9. These results indicate that human osteoclasts primarily induce erosive arthritis during EBV infections. Human osteoclast development from hematopoietic stem cells transplanted in hu-NOG mice remains unclear. To confirm their differentiation potential into human osteoclasts, we cultured bone marrow cells of EBV-infected hu-NOG mice and analyzed their characteristics. Multinucleated cells cultured from the bone marrow cells stained positive for human cathepsin K and human MMP-9, indicating that bone marrow cells of hu-NOG mice could differentiate from human osteoclast progenitor cells into human osteoclasts. These results indicate that the human immune response to EBV infection may induce human osteoclast activation and cause erosive arthritis in this mouse model. Moreover, this study is the first, to our knowledge, to demonstrate human osteoclastogenesis in humanized mice. We consider that this model is useful for studying associations of EBV infections with rheumatoid arthritis and human bone metabolism.

Osteoclastic giant cell tumor of the pancreas with osteoid and bone formation: a case report

Background: Extraosseous giant cell tumors involving visceral organs (pancreas, kidneys, bladder, etc.) and soft tissues present similar histological features to those occurring in the bones. Rarely, they may affect pancreas and their origin remains still controversial, with some authors supporting the epithelial and some others the mesenchymal origin. Case Presentation: We report the case of a pancreatic giant cell tumor with osteoclast-like cells, negative for epithelial markers. A 64-year-old man presented with a 2-month history of progressively worsening abdominal pain, radiating to the lumbar region. He reported no other symptoms. The abdominal clinical examination was unremarkable and there was no associated jaundice. Liver function tests remained within normal limits. His past medical history had nil of note. He underwent an outpatient abdominal computed tomography which revealed a large cystic lesion at the body of the pancreas measuring 10 × 7 × 6.5 cm. We proceeded with a limited excision of the pancreatic mass alone, avoiding major dissections that would unnecessarily increase morbidity and mortality and the postoperative course was good. The histological morphological and immunohistochemical assessment revealed two tumor cell types: osteoclast-like multinucleated giant cells and pleomorphic mononuclear cells, with bone formation and without important cellular and nuclear atypia. Conclusion: Pancreatic giant cell tumors with osteoclast-like giant cells are rare tumors of the pancreas with various clinical characteristics and controversial origin. En bloc resection has prevailed as the only beneficial treatment so far.

Characterization of novel USP6 gene rearrangements in a subset of so-called cellular fibroma of tendon sheath

Fibroma of tendon sheath (FTS) is an uncommon benign fibroblastic/myofibroblastic neoplasm that typically arises in the tenosynovial tissue of the distal extremities. Histologically, it is a well-circumscribed proliferation of spindle cells within collagenous stroma with peripheral slit-like vessels. Most examples are relatively hypocellular and more densely collagenous than nodular fasciitis; however, a cellular variant has been described, which has considerable morphologic overlap with nodular fasciitis and has been shown to harbor USP6 translocations in a subset of cases. The incidence of these rearrangements and the identity of the USP6 fusion partners have not been described in detail. In this study we evaluate 13 cases of cellular fibroma of tendon sheath by anchored multiplex PCR/next generation sequencing in order to detect potential gene fusions. Nucleic acids of adequate quality were obtained in 11 cases, demonstrating gene fusions in 7/11 (64%), all of which involve USP6 with a variety of partners, including PKM, RCC1, ASPN, COL1A1, COL3A1, and MYH9. Some unusual histomorphologic findings were present in a subset of cases including palisading growth pattern, epithelioid cells, and osteoclast-like multinucleated giant cells, particularly in the tumors with PKM and ASPN gene partners. Overall, the findings support a biologic relationship between cellular fibroma of tendon sheath and other lesions within the spectrum of USP6-rearranged neoplasms, particularly nodular fasciitis.