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Introduction: Metaplastic breast carcinoma is an uncommon malignancy that constitutes < 5% of all breast cancers. There are 5 subtypes which are spindle cell, squamous cell, carcinosarcoma, matrix-producing and metaplastic with osteoclastic giant cells. Spindle cell carcinoma represents approximately Case report: An elderly lady presented with an enlarging painful left breast lump for one year. Palpable left breast lump was found on clinical examination. Mammography demonstrated a high density, oval lesion with a partially indistinct margin. Corresponding ultrasound showed a large irregular heterogeneous lesion with solid-cystic areas. Histopathology showed atypical spindle-shaped cells that stained positive for cytokeratins and negative for hormone and human epidermal growth factor receptors, which favoured spindle cell metaplastic carcinoma. Left mastectomy and axillary dissection were performed, and the final diagnosis was consistent with metaplastic spindle cell carcinoma. Conclusion: Spindle cell carcinoma of the breast is a rare and aggressive histological type of carcinoma, which may present with benign features on imaging. Tissue diagnosis is essential for prompt diagnosis with multidisciplinary team discussion to guide management and improve patient’s outcomes.

PURPOSE To describe a hitherto unreported late ocular surface complication of retinal detachment surgery around a radial segment explant. METHODS A single case report of a 72 year-old white Caucasian male, with a previous history of right scleral buckling surgery for retinal detachment surgery 25 years ago, presented with right-sided ptosis of 6 months duration. RESULTS Ocular surface examination showed a prominent right supero-nasal quadrant radial segment explant, around which there was bulky pink conjunctival mass, extending from the supero-medial fornix down to the medial canthal area and inferior medial fornix with similar changes seen on the upper medial tarsal conjunctiva. The clinical differential diagnosis was either inflammation from an exposed radial explant or lymphoma. Biopsies of the conjunctival mass showed perivascular and interstitial solid eosinophilic deposits of amyloid, with scattered giant cells; the amyloid was of AL type. There was no morphological or immunohistochemical evidence of lymphoma or a plasma cell neoplasm in the specimen. CONCLUSION This is the first report of localised conjunctival amyloid deposition, secondary to a retinal detachment radial explant. It is proposed that the localised amyloid deposit arose from the ocular surface irritative effects of the radial explant.

Evaporation of phosphate species during thermal treatment (> 400 °C) of calcium phosphates leads to the formation of an alkaline layer on their surface. The aim of this study was to evaluate the hypothesis that the biological response of thermally treated calcium phosphates is modified by the presence of such an alkaline layer on their surface. For this purpose, 0.125-0.180 mm α- and β-tricalcium phosphate (TCP) granules were obtained by crushing and size classification, with some being subjected to thermal treatment at 500 °C. The four types of granules (α-TCP, β-TCP, α-TCP-500 °C, and β-TCP-500 °C) were implanted subcutaneously and orthotopically in rats. Sham operations served as control. Subcutaneously, α-TCP and β-TCP induced significantly more multinucleated giant cells (MNGCs) than calcined granules. Most of the induced MNGCs were TRAP-negative, CD-68 positive and cathepsin K-negative, reflecting a typical indication of a reaction with a foreign body. The vessel density was significantly higher in the α-TCP and β-TCP groups than it was in the α-TCP-500 °C and β-TCP-500 °C groups. In the femur model, β-TCP-500 °C induced significantly more new bone formation than that induced by β-TCP. The granule size was also significantly larger in the β-TCP-500 °C group, making it more resistant to degradation than β-TCP. The MNGC density was higher in the α-TCP and β-TCP groups than in the α-TCP-500 °C and β-TCP-500 °C groups, including cathepsin-positive, CD-68 positive, TRAP-positive and TRAP-negative MNGCs. In conclusion, this study confirms that the biological response of calcium phosphates was affected by the presence of an alkaline layer on their surface. Thermally-treated α-TCP and β-TCP granules produced significantly fewer MNGCs and were significantly less degraded than non-thermally-treated α-TCP and β-TCP granules. Thermally treating α-TCP and β-TCP granules shifts the reaction from a foreign body reaction towards a physiological reaction by downregulating the number of induced MNGCs and enhancing degradation resistance.

Giant cell tumour of bone (GCTB) typically occurs in young adults from 20-40 years old. Although the majority of lesions are located in the epi-metaphyses of the long bones, approximately one third of tumours are located in the axial skeleton, of which only 4% in the sacrum. Sacral tumours tend to be large at the time of presentation, and they present with aggressive features such as marked cortical destruction and an associated soft tissue component. The 2020 World Health Organisation classification of Soft Tissue and Bone Tumours describes GCTB as a neoplasm which is locally aggressive and rarely metastasizing. The tumour contains three different cell types: neoplastic mononuclear stromal cells, macrophages and osteoclast-like giant cells. Two tumour subtypes were defined: conventional GCTB and malignant GCTB. Only 1-4% of GCTB is malignant. In this review article, we will discuss imaging findings at the time of diagnosis to guide the musculoskeletal radiologist in reporting these tumours. In addition, imaging for response evaluation after various treatment options will be addressed, such as surgery, radiotherapy, embolization and denosumab. Specific findings will be presented per imaging modality and illustrated by cases from our tertiary sarcoma referral center. Common postoperative and post-radiotherapy findings in GCTB of the sacrum on MRI will be discussed.

Background Pulmonary cryptococcosis is an opportunistic aggressive mycosis in immunocompromised patients, but it can be increasingly seen in immunocompetent patients. It is still challenging to make a rapid and accurate diagnosis due to the various clinical manifestations and limitations in the diagnostic tools. Method A 54-year-old man presented with intermittent productive cough and fever for 1 week. A chest X-ray demonstrated multiple consolidations in both lungs. Blood biochemistry indicated elevated immunoglobulin G levels. Including sputum cultures, polymerase chain reaction (PCR) tests for severe acute respiratory syndrome coronavirus 2, influenza A and B virus were all negative. Computed tomography of the chest showed ground-glass opacities with a nodular pattern. The serum cryptococcal antigen test was positive; however, the cerebral spinal fluid was negative. The diagnosis of pulmonary cryptococcal infection was made. An initial bronchoscopy was performed unsuccessfully and the patient received intravenous fluconazole therapy for 2 weeks. Due to poor improvement of clinical condition, he then underwent a surgical lung biopsy. The pathology revealed several encapsulated yeast cells, diffuse pulmonary interstitial fibrosis, noncaseating granulomas surrounded by T lymphocytes and multinucleated giant cells with intracellular inclusions, confirming pulmonary yeast infection associated with hypersensitivity pneumonitis. Ultimately, fungal cultures of the pathology samples revealed Cryptococcus neoformans. Subsequently antifungal therapy combined with oral steroid treatment, his general condition improved. After a total of 6 months of antifungal therapy, the patient recovered completely. Conclusions Applicable laboratory diagnosis can help facilitate the accurate and rapid diagnosis of pulmonary cryptococcosis. This report elected to provide an update on the topic of laboratory diagnosis, clinical manifestation, and management of pulmonary cryptococcosis.

Ameloblastoma is a locally aggressive, benign epithelial odontogenic neoplasm currently classified to include conventional, unicystic, and extraosseous/peripheral subtypes. Giant cells have been reported in various malignancies but rarely in odontogenic neoplasms. To date, only a single case of unicystic ameloblastoma with stromal giant cells has been reported in the literature. We report two new cases with histologic features compatible with unicystic ameloblastoma with stromal giant cells. CD68 immunohistochemical staining of the giant cells supported a histiocytic origin. Further research is needed to better understand the origin and nature of these giant cells.

We present a patient with bone abnormalities and a myriad of lesions secondary to his redeveloping renal failure and neurofibromatosis type 1 (NF1). A 21-year-old male renal transplant recipient with NF1 presented with painless masses and large, irregular radiolucent lesions in the maxilla and mandible. After histologic examination, the lesion was diagnosed as a central odontogenic fibroma (COdF) in association with a central giant cell lesion, most consistent with brown tumor of hyperparathyroidism. The bone changes were interpreted to be highly suggestive of renal osteodystrophy. Around 30 cases of hybrid central giant cell granuloma-like lesion in association with central odontogenic fibroma have been reported. This, to our knowledge, is the first reported case of brown tumor in association with COdF. Our case provides further evidence of the giant cell component as the initiating entity in these hybrid lesions.

Giant-cell tumor (GCT) is locally aggressive bone neoplasm, with an unpredictable pattern of biological aggressiveness. The optimal treatment had to achieve a negligible local recurrence rate while maximizing musculoskeletal function. Numerous options for reconstruction are available, but in the literature there is a lack of salvage surgery data. We present a case of a 67-year-old woman who underwent complete wrist arthrodesis with vascularized fibular graft as salvage procedure for allograft necrosis, after excision of a distal radius GCT. The patient did not complain of any impairment in daily use, and the functional score was 22 points (73%) at latest follow-up of 14 months. Despite joint salvage remains the most favorable treatment with regard to functional outcome for aggressive tumors of the distal radius, vascularized fibular grafts is a valuable alternative especially in salvage procedures, where the use of another allograft could lead to higher complications rate. Keywords: Vascularized fibular graft, Wrist arthrodesis, Giant-Cell Tumor, Fibula free flap.

Giant cell tumour (GCT), also known as osteoclastoma, is an osteolytic tumour. It involves the epiphyseal and metaphyseal regions of long bones in adults. Rarely these may occur in pediatric patients as well as involve uncommon locations such as sternum, pelvis and occasionally, rib bones. We present a rare case of GCT arising from a rib in a child, diagnosed on fine needle aspiration.

An understanding of the biochemistry of the giant cell tumour of bone (GCTB) provides an opportunity for the development of prognostic markers and identification of therapeutic targets. Based on metabolomic analysis, we proposed glycerophospholipid metabolism as the altered pathway in GCTB., The objective of this study was to identify these altered metabolites. Using phosphorus-31 nuclear magnetic resonance spectroscopy (31P-NMR), sphingomyelin was determined to be the most dysregulated phospholipid in tissue samples from six patients with GCTB. Enzymes related to its biosynthesis and hydrolysis were examined using immunodetection techniques. High expression of sphingomyelin synthases 1 and 2, but low expression of neutral sphingomyelinase 2 (nSMase2) was found in GCTB tissues compared to non-neoplastic bone tissues. Sphingomyelin/ceramide biosynthesis is dysregulated in GCTB due to alterations in the expression of SMS1, SMS2, and nSMase2.

The term giant cell-rich tumors of bone refers to a shared morphologic pattern in a group of different osseous lesions, that is, the abundance of osteoclastlike giant cells. Fitting with a broad spectrum of clinical presentations and biological behavior, the recent detection of characteristic molecular alterations in giant cell tumor of bone (H3-3), nonossifying fibroma (KRAS, FGFR1), giant cell granuloma of the jaws (KRAS, FGFR1, TRPV4), and aneurysmal bone cyst (USP6) have contributed significantly to the biological understanding of these morphologically related but clinically distinct lesions and their systematic classification, highlighting differences and pathogenic relationships.

Clear cell sarcoma-like tumour of the gastrointestinal tract (CCSLGT) is a rare entity which has been recently described as late as 2003. Only around 70 cases have been reported in the English literature till date. CCSLGT is mostly seen in young adults in the late 20 s and early 30 s. CCSLGT are aggressive tumours. They are similar to the clear cell sarcoma of the soft tissue but lack melanocytic differentiation, retain neuroendocrine differentiation, and have osteoclastic giant cells. EWSR1-CREB1 fusion is characteristic of these tumours. Complete surgical excision is the best treatment option available. They have a high recurrence rate and poor prognosis. Currently, effective chemotherapy or a targeted agent is not available for the management of these tumours. Here, we describe a case of clear cell sarcoma-like tumour of jejunum encountered by us in a young man. The immunohistochemical and genetic profiling of these tumours are also discussed.

Background. The standard treatment for giant-cell tumors of the bone includes radical surgery. However, specific anatomical location of the tumor and/or its spread may hinder its complete excision or result in poor functional outcomes. Currently, combination treatment that includes preoperative denosumab and surgery is preferable. It saves patients’ lives and improves their quality of life. Reduction of local recurrence rate by combination therapy for giant-cell tumors of the bone is being actively studied now.Objective – to analyze treatment outcomes of patients with giant-cell tumors of the bone, including those who received combination treatment that included preoperative therapy with denosumab followed by surgery.Materials and methods. This study included 277 patients with giant-cell tumors treated in N.N. Blokhin National Cancer Research Center between 2005 and 2020. The mean duration of follow-up was 56 months. Study participants were divided into two groups. Group 1 included patients who received surgical treatment alone (n = 212), whereas Group 2 comprised patients who received combination treatment (n = 65). Neoadjuvant therapy included subcutaneous denosumab 120 mg on days 1, 8, 15, and 28, then every 4 weeks until stable effect. There were two variants of surgical treatment: radical (removal by a single block or segmental resection with defect replacement, with or without fixation) and non-radical (excochleation or marginal resection with defect replacement, with or without fixation).Results. During treatment, patients in Group 2 had a significantly milder pain syndrome (assessed both using the visual analog scale for pain and Watkins scale) compared to Group 1. In case of radical surgery, the incidence of local recurrence was 12 % and 0 % in Groups 1 and 2, respectively; the difference was significant (р Conclusion. Combination treatment for giant-cell tumors that includes neoadjuvant therapy with denosumab reduces the risk of recurrence, duration of surgery, blood loss, and the risk of postoperative complications. However, it is important to consider tumor location and the volume of surgery. Since the disease is quite rare, further study of long-term efficacy and safety of combination treatment for giant-cell tumors, including rare ones and those with challenging anatomical location, is necessary.

Background Extended curettage has increasingly become the preferred treatment for giant cell tumour of bone (GCTB), but the high recurrence rate after curettage poses a major challenge for orthopaedic surgeons. Computed tomography (CT) is valuable in the evaluation of GCTB. Our aim was to identify specific features of GCTB around the knee in pre-operative CT images that might have prognostic value for local recurrence. Methods We retrospectively analyzed data from 124 patients with primary GCTB around the knee who underwent extended curettage from 2010 through 2019. We collected demographic, clinical, and therapeutic data along with several CT-derived tumour characteristics. CT-derived tumor characteristics included tumour size, the distance between the tumour edge and articular surface (DTA), and destruction of posterior cortical bone (DPC). Akaike information criterion (AIC) was used to select which variables to enter into multivariate logistic regression models and to determine significant factors affecting recurrence. Results The total recurrence rate was 21.0% (26/124), and the average follow-up time was 69.5 ± 31.2 months (24–127 months). Age, DTA ( Conclusion Identifying certain features of GCTB around the knee on CT has prognostic value for patients treated with extended curettage. A three-factor model predicts tumour recurrence well after extended curettage.

Undifferentiated carcinoma with osteoclastic giant cells is a distinctive rare neoplasm involving pancreas and rarely bile ducts. This neoplasm shows characteristic histologic features with variable admixture of mononuclear histiocytic cells, non- neoplastic osteoclastic giant cells and neoplastic mononuclear cell component. Though, this tumor has been shown to share genetic alterations with pancreatic ductal adenocarcinoma, clinically, it behaves unpredictably with a substantial proportion of patient showing prolonged survival period. We present a case of this rare pancreatic tumour with brief literature review discussing the key pathologic features, immunophenotype, genetic profile and clinical behavior. Key Message: Undifferentiated carcinoma with osteoclastic giant cells is a rare neoplasm in pancreas which is believed to be of epithelial origin and shares genetic aberrations with ductal adenocarcinoma. Despite this, these tumours have better prognosis with prolonged survival period. Keywords: Undifferentiated carcinoma, Osteoclastic giant cells

Context: Soft tissue lesions have a wide spectrum which includes non- neoplastic, benign & malignant lesions. FNAC act as preliminary diagnostic tool providing a predictive diagnosis of a benign or malignant soft tissue neoplasm and thus helps for further intervention. Aims: This study discusses the spectrum of FNAC of soft tissue lesions in upper and lower limbs. Methods and Materials: All cytology smears of soft tissue lesions from both upper and lower limbs were included over a period of three years at tertiary care hospital. Results: The most common age group was 31 to 40 years with male to female ratio being 1.3:1. The spectrum included broadly neoplastic (65.7%) & non-neoplastic (34.3%) cases. The neoplasms were further divided as benign (42.8 %), malignant (18.6%) and suspicious for neoplasm (4.3%) whereas (34.3 %) were non-neoplastic lesions. The most common lesion was giant cell tumor (GCT) of tendon sheath. The most common site was hand (24%) followed by feet (22.5%). Conclusions: FNAC of soft tissue lesions is useful for differentiating various lesions and neoplasms in extremities so as to help patients in further management. Keywords: Soft tissue tumors of extremities, Sarcoma, Cytology of soft tissue tumors, Giant cell tumor, Fungal lesions involving extremities

BACKGROUND Primary soft tissue giant cell tumor (GCT-ST) is rare and has relatively low malignant potential. Most reports are pathological and clinical studies, while imaging studies have only been reported in cases of adjacent bone or with atypical cystic degeneration. With regard to the findings on magnetic resonance imaging (MRI) or ultrasonography, superficial masses can be further identified based on facial edema, skin thickening, skin contact, internal hemorrhage or necrosis and lobulation of the mass. Unlike deep-seated masses, MRI features do not always provide an accurate diagnosis for benign and malignant patients with superficial soft-tissue lesions. Thus, the application of diffusion-weighted imaging (DWI) to evaluate superficial soft tissue tumors is necessary. CASE SUMMARY A 36-year-old woman who had a suspected malignant tumor in the upper limb on ultrasound and computed tomography is reported. The signal intensity of the suspected tumor was heterogeneous on plain MRI; nodular and heterogeneous enhancement was observed in the tumor with irregular shapes and blurred margins on dynamic contrast-enhanced MRI. The lesion on DWI was hyperintense with a higher mean apparent diffusion coefficient (ADC) value. Finally, a GCT-ST was confirmed by pathology. This case suggests that GCT-ST should be distinguished as a benign soft tissue mass from giant cell-rich soft tissue neoplasms or malignant tumors. CONCLUSION The MRI features of the superficial GCT-ST in the upper limb included heterogeneous signal intensity within the lesion on T2-weighted image (T2WI) and T1-weighted fat-saturation spoiled gradient recalled echo (T1 FSPGR), nodular enhancement with blurred margins, irregular shapes, and a slow-increased enhancement. DWI could be used to differentiate a benign soft tissue mass from a malignant mass by the mean ADC value and provide more radiologic-pathologic information for the diagnosis of GCT-ST. Comprehensive imaging of primary GCT-ST could help complete tumor resection, and in turn likely prolong survival after surgery.

Loss of the morphological and immunophenotypic characteristics of a neoplasm is a well-known phenomenon in surgical pathology and occurs across different tumor types in almost all organs. This process may be either partial, characterized by transition from well differentiated to undifferentiated tumor component (=dedifferentiated carcinomas) or complete (=undifferentiated carcinomas). Diagnosis of undifferentiated carcinoma is significantly influenced by the extent of sampling. Although the concept of undifferentiated and dedifferentiated carcinoma has been well established for other organs (e.g. endometrium), it still has not been fully defined for urological carcinomas. Accordingly, undifferentiated/ dedifferentiated genitourinary carcinomas are typically lumped into the spectrum of poorly differentiated, sarcomatoid, or unclassified (NOS) carcinomas. In the kidney, dedifferentiation occurs across all subtypes of renal cell carcinoma (RCC), but certain genetically defined RCC types (SDH-, FH- and PBRM1- deficient RCC) seem to have inherent tendency to dedifferentiate. Histologically, the undifferentiated component displays variable combination of four patterns: spindle cells, pleomorphic giant cells, rhabdoid cells, and undifferentiated monomorphic cells with/without prominent osteoclastic giant cells. Any of these may occasionally be associated with heterologous mesenchymal component/s. Their immunophenotype is often simple with expression of vimentin and variably pankeratin or EMA. Precise subtyping of undifferentiated (urothelial versus RCC and the exact underlying RCC subtype) is best done by thorough sampling supplemented as necessary by immunohistochemistry (e.g. FH, SDHB, ALK) and/ or molecular studies. This review discusses the morphological and molecular genetic spectrum and the recent develoments on the topic of dedifferentiated and undifferentiated genitourinary carcinomas.

Erythema induratum of Bazin (EIB) is a predominantly lobular panniculitis with or without vasculitis due to Mycobacterium tuberculosis (MTB) infection. Atrophic scars may remain after EIB was healed. Rare cases of EIB showing sharp skin depression may mimic deep morphea and lupus profundus. A rare case of EIB was reported in a 35-year-old female with slightly tender erythematous-violaceous nodules and hyperpigmented depressed scars on both lower legs, resulting in asymmetrical lower leg shape. Histopathological examination showed lobular panniculitis without vasculitis and granulomatous inflammation consisted of caseous necrosis, epithelioid cells, and multinucleated giant cells. Polymerase chain reaction (PCR) from skin biopsy revealed deoxyribonucleic acid (DNA) of MTB. Tuberculin skin test (TST) was positive with a 20-mm induration, and nuclear 99mTc-ethambutol scintigraphy was positive for tuberculosis infection in one-third distal portion of the left lower leg. Clinical improvements were shown after 6 months of antituberculosis therapy. EIB must be considered in patient with erythematous-violaceous nodules on lower leg, especially in endemic areas of tuberculosis infection since diagnosis can be difficult and occasionally, deceptive.

Background: The current classification system of invasive fungal sinusitis (IFS) includes acute (aIFS) and chronic (cIFS) phenotypes. Both phenotypes display histopathologic evidence of tissue necrosis, but differ by presence of angioinvasion, extent of necrosis, and disease progression. aIFS is defined by a rapid onset of symptoms, while cIFS slowly progresses over ≥12 weeks. However, a subset of IFS patients do not fit into the clinical presentation and histopathologic characteristics of either aIFS or cIFS. Objectives: To investigate the demographic, clinical, and histopathologic characteristics of a distinct subset of IFS. Methods: Retrospective review of patients with IFS from a single tertiary-care institution (2010-2020). Patients with symptoms for ≤4 weeks were classified as aIFS if they displayed endoscopic evidence of mucosal necrosis or fungal angioinvasion on pathology. Patients with slowly progressive IFS for ≥12 weeks were classified as cIFS. Patients with symptom duration between 4 and 12 weeks with evidence of invasive fungal disease were classified as a new entity and were further investigated. Results: Of the 8 patients identified, 50% were immunosuppressed at presentation. The mean symptom duration prior to presentation was 50.5 days (SD 16.8), and common symptoms included facial pain (100%), vision change (87.5%), and blindness (37.5%). Two patients (25%) died of their disease. Sites of fungal involvement confirmed by histopathology included sphenoid (62.5%) and ethmoid sinuses (12.5%), orbital apex (25%), optic nerve (12.5%), pterygopalatine fossa (12.5%), and clivus (12.5%). Fungal elements but without obvious angioinvasion, were identified in all specimens, and fungus balls (50%), granulomas (37.5%), and giant cells (25%) were also observed on histopathology. CT and MRI radiographic imaging showed findings consistent with orbital, intracranial, or skull base involvement in all patients. Conclusion: We propose intermediate IFS as a new subgroup of patients with IFS who do not fit into the standard classification of aIFS or cIFS.

Giant cell reparative granuloma (GCRG) is a rare benign tumor that develops in the first two decades of life. Data on the incidence of GCRGin children vary significantly depending on the number of observations and methods of statistical data processing. GCRG is more common inlong bones, but rare cases of damage to the bones of the facial skeleton, which account for only 2–12 %, have been described. The etiologicalfactors of GCRG are unknown, but genetic predisposition and intraosseous hemorrhages after an injury are the predisposing factors. Despiteits benign nature, the process can be locally aggressive. Rapid invasive growth, complex anatomy of the base of the skull in childhood makesurgical treatment in this place quite difficult. The clinical symptoms of ethmoid GCRG are nonspecific and depend on the site involved andthe degree of local destruction. Distinctive morphological features of this neoplasm are the presence of multinucleated giant cells, cellularfibrous tissue and hemorrhages. Diagnostics of this disease includes endoscopic examination of the nasal cavity and nasopharynx, magneticresonance and X-ray computed tomography of the skull base, paranasal sinuses with intravenous contrast, radioisotope research methods.We report a case of the development of GCRG in a 6-year-old child, along with the clinical picture, X-ray, scintigraphic and morphologicaldata. The method of choice for the treatment of GCRG was its complete surgical removal.

Idiopathic giant cell myocarditis (GCM) is a rare rapidly progressing and usually fatal autoimmune disorder, which predominantly affects middle-aged people. It is usually associated with other autoimmune disorders, such as Crohn’s disease, rheumatoid arthritis, ulcerative colitis. We report an autopsy case of sudden death of a 38-year-old woman. At autopsy the heart was enlarged, with a motley appearance on sections. Microscopic examination showed abundant inflammatory infiltrates consisting of lymphocytes, leukocytes and multinucleated giant cells. Different staining methods and immunohistochemical examinations were performed for the diagnosis of GCM.

AimsA subset of patients with urothelial carcinoma (UCa) and lamina propria (LP) invasion in bladder biopsies/transurethral resections (TURs) are at significant risk for recurrence and have increased rates of progression to UCa with muscularis propria (MP) invasion. The clinicopathologic features of this patient population has not been well characterised in the Pathology literature.MethodsWe performed a search through our urologic pathology files and expert consult cases of the senior author for bladder biopsies/TURs of UCa with LP invasion and variant/divergent histology from 2014 to 2020. Patients with a prior diagnosis of UCa with MP invasion or upper tract UCa were excluded. Clinicopathologic data were obtained.ResultsNinety-five patients with at least one biopsy/TUR of UCa with LP invasion and variant/divergent histology were identified. Mean patient age was 72 years (range: 46–92 years) with a male predominance 2.3:1. Initial variant/divergent histologies identified were: glandular (35.8%), squamous (23.2%), micropapillary (20%), clear cell/lipid rich (12.6%), diffuse/signet ring/plasmacytoid (10.5%), nested (9.5%), sarcomatoid (6.3%), poorly differentiated/anaplastic (4.2%), small cell (2.1%), lymphoepithelioma-like (2.1%), osteoclast-like giant cells (1.1%) and tumour giant cells (1.1%). Two or more variant histologies were identified in 18.9% of these cases. The rate of micropapillary UCa was significantly higher in multifocal tumours compared with unifocal tumours (37% vs 7.1%).ConclusionsIn our cohort of patients undergoing early repeat biopsy/TUR, 75% of patients had persistent UCa. Additionally, almost 25% of patients had a prior diagnosis of UCa without a variant/divergent histology identified. Our findings highlight the critical role of repeat biopsy/TUR especially in a subset of patients who have variant/divergent histology, even in the absence of MP invasion.

Background The cytopathology of a giant cell tumor of soft tissue (GCT-ST), a fibrohistiocytic neoplasm distinct from other giant cell-rich soft tissue tumors, is rarely reported. The authors report their experience with a series of 4 GCT-ST fine-needle aspiration (FNA) biopsy cases and compare them with a set from giant cell tumors of bone (GCTBs). Methods The authors' cytopathology files were searched for GCT-ST examples with histopathologic confirmation. FNA biopsy smears were performed and examined with standard techniques. Results Four cases of GCT-ST presenting as a primary soft tissue mass from 4 patients (3 males and 1 female; age range, 28-75 years, mean age, 53 years) were retrieved. FNA sites included the anterior tibia, buttock, shoulder, and upper back. Three cases were interpreted as suspicious for sarcoma radiographically. The specific diagnoses were atypical giant cell tumor of tendon sheath, suspicious for GCT-ST, atypical myxoid lesion with giant cells, and benign with osteoclast-like giant cells (OLGCs). No case was interpreted as malignant. Aspirates consisted of mononuclear polygonal cells, spindled fibroblast cell clusters, and large OLGCs to the near exclusion of other cell types. OLGCs possessed 10 or more nuclei per cell. A comparison with GCTB aspirates and single case reports from the literature showed comparable cytomorphology. Conclusions GCT-ST FNA smears mimic those of GCTBs containing a limited population of uniform spindle cell clusters, single dispersed polygonal cells, and cytologically banal OLGCs. GCT-ST should be considered in the differential diagnosis of aspirates containing numerous osteoclast-like giant cells.

Giant cell tumor (GCT) of bone is common type of osteolytic tumor being benign involving epiphyseal aspect of long bones like femur, tibia, humerus. In contrast, GCT of hand bones are relatively rare incidence of around 1-4%. Despite being benign in nature, they may be locally malignant with significant bone destruction, local recurrence. The diagnosis is based on the clinical, radiological, and histopathological findings with primary treatment being surgical. Each case should be assessed individually to ensure adequate treatment, aiming to prevent recurrences and functional limitations. Resection with reconstruction using iliac crest graft can be considered as alternate modality instead of ray amputation in terms of functionality and cosmesis.

Peroxisome proliferator-activated receptor (PPAR) γ1, a nuclear receptor, is abundant in the murine placenta during the late stage of pregnancy (E15-E16), although its functional roles remain unclear. PPARγ1 is encoded by two splicing isoforms, namely Pparγ1canonical and Pparγ1sv, and its embryonic loss leads to early (E10) embryonic lethality. Thus, we generated knockout (KO) mice that carried only one of the isoforms to obtain a milder phenotype. Pparγ1sv-KO mice were viable and fertile, whereas Pparγ1canonical-KO mice failed to recover around the weaning age. Pparγ1canonical-KO embryos developed normally up to 15.5 dpc, followed by growth delays after that. The junctional zone of Pparγ1canonical-KO placentas severely infiltrated the labyrinth, and maternal blood sinuses were dilated. In the wild-type, PPARγ1 was highly expressed in sinusoidal trophoblast giant cells (S-TGCs), peaking at 15.5 dpc. Pparγ1canonical-KO abolished PPARγ1 expression in S-TGCs. Notably, the S-TGCs had unusually enlarged nuclei and often occupied maternal vascular spaces, disturbing the organization of the fine labyrinth structure. Gene expression analyses of Pparγ1canonical-KO placentas indicated enhanced S-phase cell cycle signatures. EdU-positive S-TGCs in Pparγ1canonical-KO placentas were greater in number than those in wild-type placentas, suggesting that the cells continued to endoreplicate in the mutant placentas. These results indicate that PPARγ1, a known cell cycle arrest mediator, is involved in the transition of TGCs undergoing endocycling to the terminal differentiation stage in the placentas. Therefore, PPARγ1 deficiency, induced through genetic manipulation, leads to placental insufficiency.

Giant cell tumor (GCT) is a locally aggressive benign primary bone tumor accounting for 20% of all the benign primary bone tumors. Peak incidence is between 20 and 45 years with slight female predominance. Distal end of ulna is a rare site for any primary bone tumor, especially 2-4 for giant cell tumors with reported incidence of 0.45 to 3.2% in literature. Considering local aggressive nature and high recurrence, resection is the treatment recommended. In such cases, instability of the ulnar stump and ulnar translation of the carpals are known 3-6 complications causing reduced grip strength. Literature review states, reconstruction with iliac bone graft and stabilization of the ulnar stump with tenodesis using extensor carpi ulnaris. We report a 34 year old female with giant cell tumor of the distal ulna treated by en bloc resection and reconstruction of the distal radio-ulnar joint (DRUJ) and triangular fibrocartilage (TFCC) complex with proximal fibula, palmaris longus graft with augmentation by extensor carpi ulnaris tenodesis and stabilization of the proximal stump with dynamic compression plate. This newer technique of DRUJ and TFCC reconstruction with proximal fibula and palmaris longus graft following en bloc resection of the distal ulna had excellent functional results with no evidence of recurrence after seven months follow-up. This case is presented for its rarity and novelty of the technique used for the anatomical reconstruction.