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Multicentric reticulohistiocytosis, also called as lipoid dermato-arthritis is a rare form of non-Langerhans cell histiocytosis characterised by nodular and papular skin lesions containing characteristic bizarre multinucleate giant cells with ground glass cytoplasm. The disease commonly involves the skin, mucosa, synovium, and internal organs with cutaneous nodules and progressive erosive arthritis being the most common presenting features. We report a case of a 61-year-old male presenting with multiple swellings over distal part of fingers for 6 years without involvement of joints. A diagnosis of multicentric histiocytosis was made based on typical histopathological features of sheets of histiocytes and multinucleate giant cells with ground glass eosinophilic cytoplasm. The disease has a low incidence and about 300 cases have been reported so far in literature. The present case is being reported as it is uncommon for the disease to present in absence of arthritis.

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.

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.

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.

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.

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.

Subsets of high-grade gliomas, including glioblastoma (GBM), are known to utilize the alternative lengthening of telomeres (ALT) pathway for telomere length maintenance. However, the telomere maintenance profile of one subtype of GBM-giant cell GBM-has not been extensively studied. Here, we investigated the prevalence of ALT, as well as ATRX and SMARCAL1 protein loss, in a cohort of classic giant cell GBM and GBM with giant cell features. To determine the presence of ALT, a telomere-specific fluorescence in situ hybridization assay was performed on 15 cases of classic giant cell GBM, 28 additional GBMs found to have giant cell features, and 1 anaplastic astrocytoma with giant cell features. ATRX, SMARCAL1, and IDH1 protein status were assessed in a proportion of cases by immunohistochemistry and were compared to clinical-pathologic and molecular characteristics. In the overall cohort of 44 cases, 19 (43%) showed evidence of ALT. Intriguingly, of the ALT-positive cases, only 9 (47.4%) displayed loss of the ALT suppressor ATRX by immunohistochemistry. Since inactivating mutations in SMARCAL1 have been identified in ATRX wild-type ALT-positive gliomas, we developed an immunohistochemistry assay for SMARCAL1 protein expression using genetically validated controls. Of the 19 ALT-positive cases, 6 (31.5%) showed loss or mis-localization of SMARCAL1 by immunohistochemistry. Of these cases, four retained ATRX protein expression, while two cases also displayed ATRX loss. Additionally, we assessed five cases from which multiple temporal samples were available and ALT status was concordant between both tumor biopsies. In summary, we have identified a subset of giant cell GBM that utilize the ALT telomere maintenance mechanism. Importantly, in addition to ATRX loss, ALT-positive tumors harboring SMARCAL1 alterations are prevalent in giant cell GBM.

Part 2 of this series on granulomatous diseases focuses on skin biopsy findings. Whereas the first part treated noninfectious conditions (metabolic disorders and tumors, among other conditions), this part mainly deals with various types of infectious disease along with other conditions seen fairly often by clinical dermatologists.

This series of 2 articles on dermatopathologic diagnoses reviews conditions in which granulomas form. Part 1 clarifies concepts, discusses the presentation of different types of granulomas and giant cells, and considers a large variety of noninfectious diseases. Some granulomatous diseases have a metabolic origin, as in necrobiosis lipoidica. Others, such as granulomatous mycosis fungoides, are related to lymphomas. Still others, such as rosacea, are so common that dermatologists see them nearly daily in clinical practice.

Giant cell tumors of soft tissue (GCT-ST) are rare low-grade neoplasms that were at one time thought to represent the soft tissue counterparts of GCT of bone (GCT-B) but are now known to lack the H3F3 mutations characteristic of osseous GCT. We present six distinctive giant cell-rich soft tissue neoplasms that expressed keratins and carried a recurrent HMGA2-NCOR2 gene fusion. Patients were five females and one male aged 14–60 years (median, 29). All presented with superficial (subcutaneous) masses that were removed by conservative marginal (3) or wide (2) local excision. The tumors originated in the upper extremity (2), lower extremity (2), head/neck (1), and trunk (1). Five patients with follow-up (median, 21 months; range, 14–168) remained disease-free. Grossly, all tumors were well-demarcated but not encapsulated with variable lobulation. Histologically, they were composed of bland plump epithelioid or ovoid to spindled mononuclear cells admixed with evenly distributed multinucleated osteoclast-type giant cells. Foci of stromal hemorrhage and hemosiderin were seen in all cases. The mitotic activity ranged from 2 to 14/10 high power fields (median: 10). Foci of necrosis and vascular invasion were seen in one case each. The mononuclear cells were immunoreactive with the AE1/AE3 keratin cocktail and less frequently/less diffusely for K7 and K19 but lacked expression of other lineage-associated markers. RNA-based next-generation sequencing revealed an HMGA2-NCOR2 fusion in all tumors. None of the keratin-negative conventional GCT-ST showed the HMGA2-NCOR2 fusion (0/7). Metaplastic bone (4/9) and SATB2 expression (3/4) were frequent in keratin-negative conventional GCT-ST but were lacking in keratin-positive HMGA2-NCOR2 fusion-positive tumors. The distinctive immunophenotype and genotype of these tumors strongly suggest that they represent a discrete entity, differing from conventional GCT-ST and other osteoclast-rich morphologic mimics. Their natural history appears favorable, although a study of additional cases and longer follow-up are warranted.

Involvement of toe phalanges by giant cell tumor (GCT) is extremely rare; tumors in these locations tend to be aggressive. Whereas aggressive GCTs of the distal phalanx may be managed successfully by en-bloc resection without reconstruction or amputation, management of these lesions, when they involve the proximal phalanx, can be challenging. We present a Campannaci grade III GCT of the hallucal proximal phalanx in a 14-year old girl that had breached into the dorsal soft tissues and the metatarso-phalangeal joint. Wide local resection of the proximal phalanx along with reconstruction arthrodesis with an autologous, non-vascularized fibular strut graft was performed. There was no recurrence at 3 years of follow-up. The patient had an excellent functional outcome. To the best of our knowledge, this is the first case reporting the outcomes of fibular strut arthrodesis for salvage of GCT of the hallucal proximal phalanx.

This report reviews the management of a case of Giant Cell Myocarditis (GCM) that presented with cardiogenic shock. This case highlights the importance of a multi-disciplinary approach to the care of these patients including the use of a mechanical circulatory support (MCS) device.

This is a retrospective analysis of 145 cases of lateral intraventricular tumors that were larger than 4 cm in their maximum dimension. The aim of surgery was radical tumor resection. During the period January 2000 to December 2019, 145 cases of lateral intraventricular tumors were treated by surgery by an interhemispheric approach. There were 101 males and 44 females. The ages of the patients ranged from 2 months to 77 years (average 29 years). Histological examination of tumors identified 73 central neurocytomas, 20 choroid plexus papillomas, 23 subependymal giant cell astrocytomas (SEGA), 5 ependymomas, 21 gliomas, 2 primitive neuroectodermal tumors (PNET/embryonal tumors) and 1 atypical teratoid rhabdoid tumor (ATRT). Nineteen patients had mild to severe hemiparesis in the immediate post-operative period. Eight patients died in the postoperative period. At a follow up of 1 year 137 patients were leading active and symptom free lives. Twenty seven patients received adjuvant radiation treatment. At a follow-up of more than 3 years, 8 additional patients died of their disease. Tumor recurrence or re-growth was observed in 13 patients and 2 patients needed reoperation. Surgery on large lateral intraventricular tumors can be associated with significant postoperative morbidity and mortality. Majority of tumors in this location are relatively ‘low-grade’ malignant tumors and when successfully treated, the long term outcome can be gratifying.

A metastatic giant cell–rich osteosarcoma (GCRO) to the jaws is an exceedingly rare neoplasm. To date, fewer than 10 cases have been reported in the English language literature. In this article, we describe an additional case of a metastatic GCRO that presented the diagnostic challenge of a painless mass in the posterior mandible of a 19-year-old girl who exhibited rapid and aggressive local growth. The lesion was confirmed radiologically as an ill-defined expansive osteolytic mass showing cortical perforation. Microscopically, the presence of osteoclast-like giant cells permeated with atypical oval and rounded mesenchymal cells in a fibrovascular stroma, cellular atypia, and scarce osteoid formation were observed. Immunohistochemistry revealed the Ki-67 proliferative index in 50% of positive cells, positivity for vimentin and CD68, as well as scarce positivity for CDK4. The patient's medical history involved a GCRO in the proximal ulna. This report highlights the aggressive behavior of GCRO and its high capacity for metastasis to different parts of the body. Clinicians, pathologists, and surgeons should be aware of the giant cell–rich variant of osteosarcoma of the jaws, an imminent “wolf in a sheep's skin”, because its indolent but unrelenting growth and dissemination, with radiographic and histologic characteristics that may represent a diagnostic pitfall regarding aggressive central giant cell lesions of the jaws.

Giant cell granulomas are a type of giant cell lesions and classified as follows: central giant cell granulomas occurring in the mandible and peripheral giant cell granulomas occurring in the gingiva. Central giant cell granulomas are less frequent than peripheral giant cell granulomas, and it rarely occurs in the mandibular condyle. Mandibular condylectomy is a widely used treatment strategy for lesions in the mandibular condylar region. A commonly indicated treated for mandibular condylectomy is the preauricular approach or the Al-Kayat Bramley method; however, we used the high cervical transmasseteric anteroparotid (HC-TMAP) approach. In recent years, the use of this approach has been reported for open reduction and internal fixation for mandibular condylar fracture cases. In this case report, we describe a technique using the high cervical transmasseteric anteroparotid approach for resecting a mandibular condyle in which a central giant cell granuloma had developed.

Objective The aim of this study was to report the clinicopathologic features of 62 cases of central odontogenic fibroma (COdF). Study Design Clinical and radiographic data were collected from the records of 13 oral pathology laboratories. All cases were microscopically reviewed, considering the current World Health Organization classification of tumors and were classified according to histopathologic features. Results There were 43 females and 19 males (average age 33.9 years; range 8–63 years). Clinically, COdF lesions appeared as asymptomatic swellings, occurring similarly in the maxilla (n = 33) and the mandible (n = 29); 9 cases exhibited palatal depression. Imaging revealed well-defined, interradicular unilocular (n = 27), and multilocular (n = 12) radiolucencies, with displacement of contiguous teeth (55%) and root resorption (46.4%). Microscopically, classic features of epithelial-rich (n = 33), amyloid (n = 10), associated giant cell lesion (n = 7), ossifying (n = 6), epithelial-poor (n = 3), and granular cell (n = 3) variants were seen. Langerhans cells were highlighted by CD1a staining in 17 cases. Most patients underwent conservative surgical treatments, with 1 patient experiencing recurrence. Conclusions To the best of our knowledge, this study represents the largest clinicopathologic study of COdF. Most cases appeared as locally aggressive lesions located in tooth-bearing areas in middle-aged women. Inactive-appearing odontogenic epithelium is usually observed within a fibrous/fibromyxoid stroma, occasionally exhibiting amyloid deposits, multinucleated giant cells, or granular cells.

Next-generation sequencing of pediatric gliomas has revealed the importance of molecular genetic characterization in understanding the biology underlying these tumors and a breadth of potential therapeutic targets. Promising targeted therapies include mTOR inhibitors for subependymal giant cell astrocytomas in tuberous sclerosis, BRAF and MEK inhibitors mainly for low-grade gliomas, and MEK inhibitors for NF1-deficient BRAF:KIAA fusion tumors. Challenges in developing targeted molecular therapies include significant intratumoral and intertumoral heterogeneity, highly varied mechanisms of treatment resistance and immune escape, adequacy of tumor penetrance, and sensitivity of brain to treatment-related toxicities.

Granulomatous interstitial nephritis (NIG) is a rare form of interstitial nephritis that can be related to acute or chronic clinical presentation. NIG is characterized by granulomas located to the renal interstitium and composed of either epithelioid histiocytes with giant cells and/or of foreign body reaction. The symptoms are unspecific and associate varying degrees of renal failure with abnormal urinanalysis. Extra-renal signs may point to systemic disease. Pathological examination from kidney percutaneous biopsy or surgical resection is required to assert NIG diagnosis and to guide the etiological research. The main causes of NIG are sarcoidosis, drug reactions, mycobacterial infections and crystalline nephropathies. Sarcoidosis is characterized by non-necrotic and well-formed giant cell epithelioid interstitial granulomas. Drug reactions have less well-defined granulomas with inconstant eosinophils. The presence of caseous necrosis within giant cell and epithelioid granulomas leads to infectious NIG diagnosis (tuberculosis and fungal infection). Identification of crystals within foreign body reaction can be improved by polarized light study. Xanthogranulomatous pyelonephritis and malakoplakia are rarer causes of NIG characterized by patches of histiocytes associated with inconstant giant cells. Differential diagnoses of NIG are represented by granulomatous reactions centered on glomeruli and vessels (vasculitis and emboli of cholesterol crystals). Less than 10% of NIG are idiopathic. The prognosis and the treatment vary according to the cause. The factors of poor renal prognosis are chronic irreversible tubulo-interstitial injury (tubular atrophy and interstitial fibrosis).

In view of controversy about the source of placental multinuclear giant cells, we have re-examined the literature which clearly shows they are derived from trophoblastic elements that have populated the decidua. Archival material for electron microscopy from 17 to 18 week placentae demonstrates they can be found connected via desmosomes to the outer extravillous cytotrophoblast cells of anchoring columns, thus identifying a primary source. We suggest their formation is a terminal differentiation step occurring at all stages of invasion from the cell column to the myometrium, progressively reducing the invasive population.

Background and Aims ORISE Gel is a recently introduced, FDA-approved submucosal lifting agent used in endoscopic resection of GI lesions. Histologically evident gel deposits in resected specimens may pose a potential diagnostic pitfall. In order to aid in recognition of this procedure-related artifact, we report the largest histologic series of ORISE Gel in endoscopic and surgical resection specimens to date. Methods Included were 58 endoscopic mucosal resection (EMR)/endoscopic submucosal dissection (ESD) specimens with ORISE Gel injection, and 5 interval surgical resection specimens with previous ORISE Gel injection. Patient demographics and endoscopy reports were obtained. Histologic slides from all cases were reviewed. Histochemical stains were performed on select cases. Results Fifty-one EMR and 7 ESD specimens were identified. In 51 out of 58 (88%) endoscopic resection specimens, amorphous, pale blue-gray, finely granular material was evident in the submucosa, as well as focally within the mucosa in 4 cases. Most cases showed homogenous near-complete filling of the submucosa with this material, whereas a few demonstrated areas of condensation and retraction. Mucicarmine and PAS stains were negative for mucin. Interval surgical resection specimens revealed extensive deposition of dense, eosinophilic material with associated multinucleated giant cells in the submucosa in all cases, with transmural extension in 3 cases. Conclusion ORISE Gel injection during endoscopic resection of gastrointestinal lesions results in deposition of amorphous, blue-gray material seen in histologic sections, whereas interval surgical resection specimens demonstrate dense, eosinophilic material with an associated giant cell reaction. Awareness of these artifacts will help avoid misinterpretation of their presence as pathologic findings.

Inflammatory cardiomyopathies, also known as "myocarditis" are inflammatory pathologies affecting the myocardium and characterized by vast etiological and clinical heterogeneity. They can be asymptomatic, particularly in viral forms, or be responsible for sudden death, particularly in subjects under 35 years olds. Due to insufficient sensitivity and specificity of imaging and biology, the gold standard is histopathological and is performed on an endomyocardial biopsy or on explanted heart samples in a transplant context. Their classification has considerably evolved and is now based on the identification of a predominant cell pattern such as lymphocytic, neutrophilic or eosinophilic polynuclear, giant cell or granulomatous myocarditis. These different patterns will guide the etiological diagnosis, prognosis and the therapies to be implemented. Due to the importance of viral etiologies, this morphological analysis must be complemented by a virological analysis based on PCR with viral load quantification. In addition, some authors have been able to demonstrate the occurrence of myocarditis in patients with arrhythmogenic cardiomyopathy of genetic origin. The aim of this chapter is to review the current state of knowledge on inflammatory cardiomyopathies and their management.

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.

Highlights • This article aims to present a rare tumor due to its nature and location. Which will allow professionals a rapid recognition and adequate management of this type of tumor. • It also presents the peculiarities of histological diagnosis. • Our work talks about the specificity of the management of fibular head tumors. • Finally it deals with the stability of the knee post-surgery., Introduction Primary bone liposarcoma are extremely rare tumors and their location in the fibular head is exceptional. Case report A 19 year-old patient with a pain on the lateral of the proximal leg. The X-ray found an osteolytic lesion; MRI of the knee revealed a proximal epiphyseal-metaphyseal lesion process of the right fibula contours with cortical lysis and local medullary damage. The pathological study, follow by the immunohistochemical exam and the FISH concluded in an amplification of MDM2 (Murine double minute 2) confirming the presence of a liposarcoma. Discussion The primary bone localization of liposarcomas remains rare. Their localization at the level of the fibular head is exceptional. The proximal fibula is mainly affected by benign tumors, in particular giant cell. Malignant tumors localized to the head of the fibula as well as aggressive benign tumors most often require en bloc resection. Conclusion Although rare, primary liposarcomas can localize to the head of the fibula. It is necessary to establish a clinical, radiological and histological diagnosis for adequate management.

Giant cell tumor of the tendon sheath is a slowly growing benign tumor. It usually arises from the tendon sheath and periarticular soft tissue of small joints. However, it may infrequently involve the large joints emerging around the knee, elbow, and hip joints. Giant cell tumor of the tibialis tendon sheath is rarely reported in the foot and ankle joint. Here, we report the first case in the medical literature of bilateral mirror-symmetrical giant cell tumor of the tendon sheath in the foot and ankle. A 12-year-old male presented with a bilateral and mirror-image mass on his ankles extending to the foot. It was painless but affected his gait and footwear. Staged complete resection was done first on the right then on the left side, with no recurrence after 1 year. The role of genes can be argued for this presentation and giant cell tumor's etiology, owing to the bilateralism and mirror-image presentation. Studies are needed to explore this genetic aspect and its role in management.

Summary Background In giant cell arteritis, temporal artery biopsies often show vasculitis with giant cell formation, but optimal biopsy length for diagnosis is debated. We reviewed temporal artery biopsies from a 10-year period in the province of Alberta, Canada, to identify an ideal biopsy length in the diagnostic process for giant cell arteritis. Methods We retrospectively reviewed electronic medical records of patients who had undergone a temporal artery biopsy procedure in Alberta between Jan 1, 2008, and Jan 1, 2018, as reported in the Data Integration and Management Repository of Alberta Health Services. We extracted data on baseline demographic characteristics (sex and age), inflammatory markers (erythrocyte sedimentation rate [ESR] and C-reactive protein [CRP]), temporal artery biopsy characteristics (side of biopsy and postfixation length), and final pathological diagnoses. All positive biopsies were reviewed by a single pathologist to ensure uniformity of pathological interpretation, with subsequent discordant results removed from analysis. Predictors of positive pathological diagnosis of giant cell arteritis were modeled by logistic regression, and the Akaike information criterion was used to compare logistic regression models with varying biopsy length cutoffs (0·5, 1·0, 1·5, 2·0, and 2·5 cm) to determine a change point for diagnostic sensitivity in postfixation length. Findings We extracted data on 1203 temporal artery biopsies; after removal of 13 discordant biopsies, 1190 biopsies from 1163 patients were reviewed. The mean age of patients was 72·0 years (SD 10·3) and 799 (68·7%) patients were women. 222 (18·7%) temporal artery biopsies were positive for giant cell arteritis. In univariable analysis, increases in age (71·3 years [SD 10·6] in negative biopsies vs 75·3 years [8·3] in positive biopsies; odds ratio [OR] 1·04 [95% CI 1·02–1·06]; p Interpretation Accounting for postfixation shrinkage, our findings suggest a 1·5–2·0 cm prefixation length as the optimal biopsy length to diagnose patients with giant cell arteritis, with greater lengths unlikely to provide significant additional diagnostic yield to justify risks associated with surgery. Funding None.

A 90-year-old man with an uroseptic shock was admitted to the intensive care unit with endotracheal tube insertion and immunocompromised status for months. He developed progressive, blistering eruptions on the upper left side of the chest for 4 days. There was no preceding fever, pneumonia, or orogenital ulcer, and the contact history was negative. On examination, 2 noncontiguous groups of vesicles and bullae were linearly distributed on the left T1 and T7 dermatomes (Fig 1). Tzanck smear cytology revealed multinucleated giant cells from the blisters of both the dermatomes (Fig 2). Open in a separate window Fig 1 Open in a separate window Fig 2 Question 1: What is the most likely diagnosis? A. Allergic contact dermatitis (ACD) B. Linear IgA bullous dermatosis C. Herpes zoster duplex unilateralis D. Bullous impetigo E. Bullous erysipelas Answers: A. ACD – Incorrect. ACD is a type IV delayed hypersensitivity response to an antigen that contacts a sensitized individual's skin. Acute ACD characteristically presents as erythematous, eczematous, or vesiculobullous dermatitis. It may be localized to the contact region and can progress to a more generalized pattern. The clinical manifestation and lack of a contact allergen make ACD less likely in this patient. B. Linear IgA bullous dermatosis – Incorrect. Linear IgA bullous dermatosis is an autoimmune blistering disease with annular rings of vesicles involving the skin and mucosa membranes and is commonly referred to as a “crown of jewels.” On direct immunofluorescence, it is characterized by a linear band of IgA deposition at the dermoepidermal junction. This patient had neither mucosal lesions nor disseminated blistering. C. Herpes zoster duplex unilateralis – Correct. Herpes zoster is a viral infection that occurs due to the reactivation of the latent varicella zoster virus and classically presents as grouped vesicles or bullae on an erythematous base, involving a single or adjacent dermatome unilaterally. The Tzanck examination demonstrating multinucleated giant cells is diagnostic. When 2 noncontiguous dermatomes are simultaneously involved unilaterally, it is called herpes zoster duplex unilateralis. Noncontiguous herpes zoster is very rare (7 days) E. All of the above are correct Answers: A. Patients with this condition have a worse prognosis than classic herpes zoster – Incorrect. Patients with herpes zoster duplex have demonstrated prognosis similar to classic herpes zoster.4 B. Patients with this condition have prognosis similar to classic herpes zoster – Correct. Patients with herpes zoster duplex have demonstrated prognosis similar to classic herpes zoster.4 C. Patients with this condition have a higher tendency to develop postherpetic neuralgia than classic herpes zoster – Incorrect. Herpes zoster duplex has not been shown to increase the risk of postherpetic neuralgia.4 D. Patients with herpes zoster duplex require prolonged treatment (>7 days) – Incorrect. The antiviral dosing and pain control in the management of herpes zoster duplex remain the same as that of classic herpes zoster.4 E. All of the above are correct – Incorrect.

Aggressive osteoblastoma (AO) is a rare variant of osteoblastoma characterized histologically by epithelioid osteoblasts and clinically by local recurrences if not excised completely. Aggressive osteoblastoma has been described in various unusual sites; however, based on our search of the literature, involvement of the tarsal navicular has not been previously described. Herein, we report what we believe to be the first case of aggressive osteoblastoma involving the tarsal navicular in a 35-year-old woman. The tumor showed osteoid surrounded by epithelioid cells along with numerous osteoclastic giant cells. Absence of necrosis, mitosis, and infiltration into the surrounding native bone helped rule out the possibility of low-grade osteosarcoma.

Background Blood platelets are anucleate cell fragments that prevent bleeding and minimize blood vessel injury. They are formed from the cytoplasm of megakaryocytes located in the bone marrow. For successful platelet production, megakaryocyte fragments must pass through the sinusoid endothelial barrier by a cell biology process unique to these giant cells as compared with erythrocytes and leukocytes. Currently, the mechanisms by which megakaryocytes interact and progress through the endothelial cells are not understood, resulting in a significant gap in our knowledge of platelet production. Objective The aim of this study was to investigate how megakaryocytes interact and progress through the endothelial cells of mouse bone marrow sinusoids. Methods We used a combination of fluorescence, electron, and three-dimensional microscopy to characterize the cellular events between megakaryocytes and endothelial cells. Results We identified protrusive, F-actin-based podosome-like structures, called in vivo-MK podosomes, which initiate the formation of pores through endothelial cells. These structures present a collective and spatial organization through their interconnection via a contractile network of actomyosin, essential to regulate the endothelial openings. This ensures proper passage of megakaryocyte-derived processes into the blood circulation to promote thrombopoiesis. Conclusion This study provides novel insight into the in vivo function of podosomes of megakaryocytes with critical importance to platelet production.

Giant cell-rich bone lesions comprize heterogeneous neoplastic and non-neoplastic disorders with diverse clinical, radiological and pathological presentations. They are characterized by the presence of conspicuous osteoclast-type giant cells as a component of the presenting entity. Correlation with imaging, age and location of the lesion is essential to render an accurate diagnosis. Pathological diagnosis ultimately dictates the behavior and direct the management of these lesions. Both benign and malignant tumors of bone can elaborate an osteoclast-rich giant cell response and the distribution of giant cells vary with the type and nature of the underlying biological process. In recent years genetic alterations have emerged as ancillary techniques and are being used routinely to increase diagnostic specificity. This review will focus on common and uncommon giant cell-rich bone lesions and emphasize important clinical, radiological, pathological and molecular features which are necessary for a precise diagnosis.

Glioblastoma (GBM) is the most common primary brain tumor and is highly aggressive with a median survival of 15 months. We have previously shown that residual cells of GBM form multinucleated giant cells (MNGCs) showing a senescent phenotype, but eventually escape from therapy induced senescence (TIS), resulting in GBM recurrence. Here we demonstrate the role of PARP-1 in TIS and its recovery. We show that genetic and pharmacological inhibition of PARP-1 has an anti-proliferative effect on GBM cell lines and primary cultures derived from patient samples. Furthermore, the PARP-1 inhibitor olaparib, in combination with radiation increased MNGCs formation and senescence as assessed by β-galactosidase activity, and macroH2A1 levels in residual cells. Additionally, we found that reduced PARP-1 activity and not protein levels in residual cells was crucial for MNGCs formation and their maintenance in the senescent state. PARP-1 activity was restored to higher levels in recurrent cells that escaped from TIS. Importantly, olaparib + radiation treatment significantly delayed recurrence in vitro as well in vivo in orthotopic GBM mouse models with a significant increase in overall survival of mice. Overall, this study demonstrates that sustained inhibition of PARP-1 activity during radiation treatment significantly delays GBM recurrence.

Epithelial marker expression and/or epithelial differentiation, as well as “anomalous” expression of keratins, are features of some soft tissue tumors. Recently, we have encountered an unusual mesenchymal tumor composed of bland, distinctly eosinophilic, keratin-positive epithelial cells, which were almost entirely obscured by xanthogranulomatous inflammation. Six cases were identified (5 F, 1 M; 16–62 years (median 21 years)) arising in soft tissue (n = 4) and bone (n = 2) and ranging in size from 2 to 7 cm. The tumors were generally circumscribed, with a fibrous capsule containing lymphoid aggregates, and consisted in large part of a sheet-like proliferation of foamy histiocytes, Touton-type and osteoclast-type giant cells, and chronic inflammatory cells. Closer inspection, however, disclosed a distinct population of uniform, cytologically bland mononuclear cells with brightly eosinophilic cytoplasm arranged singly and in small nests and cords. Overt squamous and/or glandular differentiation was absent. By immunohistochemistry, these cells were diffusely positive with the OSCAR and AE1/AE3 keratin antibodies, and focally positive for high-molecular weight keratins; endothelial and myoid markers were negative and SMARCB1 was retained. RNA-seq identified a PLEKHM1 variant of undetermined significance in one case, likely related to this patient’s underlying osteopetrosis. Follow-up to date has been benign. In summary, we have identified a novel tumor of soft tissue and bone with a predilection for young females, provisionally termed “xanthogranulomatous epithelial tumor”. These unusual lesions do not appear to arise from adnexa, or represent known keratin-positive soft tissue tumors, and the origin of their constituent epithelial cells is obscure. The natural history of this distinctive lesion appears indolent, although study of additional cases and longer term follow-up are needed.

The most common of age distribution ranges from second to fourth decade of life and patients with giant cell tumors (GCT) aged less than 18 years is more uncommon. We are aiming to reveal what the conservative nerve-sparing surgery values for adolescent patients with sacral GCT. We retrospectively reviewed 15 adolescent patients with sacral GCT agedeighteen years, who received the conservative nerve-sparing surgery at our center from 2007 to 2018. Four patients presented with tumor of Campanacci grade II and 11 patients with grade III. According to the location of tumor at the sacrum, we classified the surgical resection of sacral giant cell tumor into three types. In our adolescent cohort, nine had the aortic balloon occlusion and five received the selective arterial embolization. All patients were free of disease and no one had the pulmonary metastasis or died of disease. All five wound complications required the debridement. 6 out of 15 patients had the local recurrence that required surgery treatment. The average time to recurrence after initial surgery in the present adolescent cohort was 22.4 months. Two patients had the surgical site infection and three had the wound dehiscence. One had the femoral artery thrombosis due to the aortic balloon occlusion and received the surgical removal of thrombosis. With the help of preoperative selective embolization and intraoperative aortic balloon occlusion, adolescent patients undergoing conservative nerve-sparing surgery for giant cell tumor of sacrum based on the proposed surgical resection classification have an acceptable clinical outcome and neurologic function.

Brucellar spondylodiscitis (BS) is the most common form of musculoskeletal brucellosis. The isolation of Brucella spp from blood, other body fluids or tissue cultures is the gold standard for definitive diagnosis of BS. BS shows a large histopathological spectrum of lesions with non-specific and granulomatous forms, and its histopathological features are not widely reported. This case series study reported the histopathological features of a series of 21 BS. Ten cases revealed nonspecific forms of BS. Lymphocytes were the predominant inflammatory cells in this group. In one case neutrophils were predominant. The eleven remaining were granulomatous. The 11 exhibited histiocytic type granulomas. Ten were non-necrotizing. One case, taken from abscess wall, contained minimal deposition of caseous like necrotic material. This case and 2 others corresponding to abscess wall biopsies, showed histiocytic granulomas mixed with small aggregates of epithelioid cells without well-formed epithelioid granuloma nor giant cell. The histopathological diagnosis of BS is challenging. Nonspecific forms of BS, mimiking pyogenic spondylodiscitis, are observed in about half of the cases. Although nonspecific forms of BS are characterized by the predominance of lymphocytes and plasmocytes, BS forms with predominant neutrophil cell infiltration do exist. Histiocytic granuloma is highly suggestive of BS. Purely epithelioid forms of BS were not observed in the present series. Caseous like necrosis suggestive of tuberculosis is a possible feature of BS.

Background Locally aggressive vertebral body tumors of the axis must be treated with wide local excision for best outcome. Reconstruction of the load-bearing vertebra needs to be done after tumor resection in such a manner so as to give stable, long-term fusion in this young population. Methods We describe the management strategy of a 25-year-old acutely quadriplegic patient, with respiratory distress, with a C2 giant cell tumor. The use of a novel iliac crest graft modification used for C2 reconstruction along with a modified mesh cage used as an anterior plate has been reported. Results The patient had a good outcome at 18 months' follow-up, with neurologic improvement and a solid fusion. Conclusions Iliac crest autograft is inexpensive and easy to harvest and can be considered as a C2 prosthesis, especially in a resource-constrained setting. Modified iliac crest graft can be used for load transmission from C1 lateral mass to C3 body, and the mesh cage can be modified according to need as a plate with good results in an emergency.

Purpose Giant cell tumors (GCT) of the distal radius are thought to be more aggressive than in other locations. Therefore, the aim of this study was to investigate factors associated with recurrence of GCTs in the upper extremity. Methods We retrospectively identified 82 patients who underwent primary surgical treatment for an upper extremity GCT. Tumors were located in the radius (n = 47), humerus (n = 17), ulna (n = 9), and hand (n = 9). Treatment consisted of either wide resection or amputation or intralesional resection with or without adjuvants. A multivariable logistic regression was performed including tumor grade, type of surgery, and tumor location, from which the percentage of contribution to the model of each variable was calculated. Results The recurrence rate after intralesional resection was 48%; after wide resection or amputation, it was 12%. Two patients developed a pulmonary metastasis (2.4%). In multivariable analysis, intralesional resection was independently associated with recurrence. Intralesional resection had a 77% contribution to predict recurrence and the distal radius location had a 16% contribution in the predictive model. Conclusions As expected, intralesional resection was the strongest independent predictor of recurrence after surgical treatment for GCT. The distal radius location contributed to the prediction of giant cell tumor recurrence to a lesser extent. Type of study/level of evidence Prognostic IV.

Endoscopic resection techniques, such as endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD), are frequently aided by injection of submucosal lifting solutions that create a plane for dissection and protect deeper mural layers. ORISE™ gel is a recently approved synthetic lifting solution that produces a localized inflammatory reaction associated with retained gel at the injection site. We describe a series of six cases of ORISE™-associated inflammatory lesions in patients who underwent endoscopic resections. Deposits comprised pale fibrillary or hyalinized eosinophilic material, depending on their age. All cases were associated with an inflammatory reaction composed of foreign-body giant cells and scattered eosinophils. ORISE™ gel extended laterally and deeply beyond residual tumors in all cases. Histochemically, the material proved to be negative for Congo Red, and mucicarmine, faint blue with Alcian blue, but positive for PAS and PAS-D. It stained blue with trichrome. Such deposits were absent in cases, wherein other widely-available lifting solutions were used. We compared ORISE™ deposits to histologically similar extracellular deposits, namely amyloid and pulse granulomata. Unlike ORISE™ material, amyloid deposits appear as waxy, more densely eosinophilic material, and stain positive with Congo Red. Amyloid demonstrated prominent intramucosal and perivascular distributions, features not seen in this series of ORISE™ deposits. Hyalinized pulse granulomata showed strong overlap with ORISE™ deposits, since they also comprise eosinophilic material associated with giant cell reaction. On the other hand, they form ribbons of glassy material in circumscribed lobules, unlike the ill-defined ORISE™ deposits. In summary, we describe the pathologic findings at injection sites in patients who underwent endoscopic procedures aided by the recently approved lifting agent, ORISE™. Pathologists should be aware of its appearance and associated reaction to avoid confusion with other common extracellular deposits seen in the gastrointestinal tract.

Multinucleate cell angiohistiocytoma is a rare, benign vascular proliferation of unknown etiology. It occurs mainly in middle-aged women and usually affects the acral regions; the lesions appear as discrete, grouped, and asymptomatic violaceous papules. Histopathology shows proliferation and dilated small vessels in the papillary dermis, fibrous stroma with thickened collagen bundles, and multinucleated giant cells. To date, there are approximately 140 cases described in the indexed literature. This report presents the case of a 62-year-old woman with a typical clinical condition, who chose not undergo treatment, considering the benign character of her illness. The clinical and immunohistological aspects of this unusual dermatological entity are emphasized.

The giant cell tumor of tendon sheath (GCTTS) or nodular tenosynovitis arises as discrete solitary nodule in the tendon sheath near joints of toes and fingers. Multifocal giant cell tumor of tendon sheath is a rare entity, of which the etiology is not yet fully understood and it is different from diffuse type of GCTTS. Diffuse type of GCTTS occurs around large joints having a main mass from which a small satellite nodule may arise. Multifocal GCTTS along a single tendon is a more rare entity. Herein, we describe a case of multifocal GCTTS along the tendon sheath of flexor digitorum profundus tendon of index finger. The patient was managed by surgical excision of the tumor swellings with no recurrence at two years follow up.

In patients with tuberous sclerosis complex (TSC) the upregulation of the mechanistic target of rapamycin (mTOR) pathway leads to the development and growth of subependymal giant cell tumors (SGCTs) and renal angiomyolipomas (AMLs). Drugs that inhibit the mTOR pathway, such as sirolimus, can reduce the size of both SGCTs and AMLs. Recent preclinical studies have suggested cannabidiol (CBD) may mediate the mTOR pathway, however, its exact effects are unclear. This study examines the volumes of SGCTs and renal AMLs in patients with TSC during treatment with purified CBD for refractory epilepsy. We retrospectively reviewed the medical records of patients with TSC with radiological evidence of AMLs and SGCTs who were being treated with plant-derived highly purified CBD in oral solution (Epidiolex®, GW Research Ltd) for refractory epilepsy at Massachusetts General Hospital. Patients who had surgical intervention for AMLs or SGCTS, and patients who had been treated with mTOR inhibitors were excluded. The volumes of SGCTs and dominant renal AML were measured before and after CBD initiation using abdominal and brain scans and compared. Patient demographics and CBD doses were collected from medical records. Six out of the seven dominant renal AMLs and three out of the three SGCTs increased in volume during CBD treatment. One AML had a decrease in volume after CBD initiation which was not considered significant. The results suggest that unlike mTOR inhibitors, CBD treatment does not decrease the volume of SGCTs or AMLs in TSC patients.

Histiocytic sarcoma (HS) is a haematopoietic tumour of histiocyte origin that has been sporadically reported in four-toed hedgehogs (Atelerix albiventris). The present study aimed to investigate clinical, gross, histopathological and immunohistochemical features of HS in eight hedgehogs. Histological and immunohistochemical features of normal histiocytes and Langerhans cells (LCs) of hedgehogs were also investigated. HLA-DR-, Iba-1- and E-cadherin-positive LCs were observed in the epidermis, while Iba-1- and CD204-positive histiocytes were detected in the lymph nodes and spleen of normal hedgehogs. Localized HS (six cases) developed in the skin and spleen, while disseminated HS (two cases) occurred in the intestine. Tumour cells of disseminated HS were also distributed within the mesenteric lymph nodes, liver, kidney, spleen, lung and adrenal glands. Tumour cells of both localized and disseminated HS were composed of histiocytic cells, spindle to pleomorphic cells, multinucleated giant cells and erythrophagocytic cells. Most tumour cells were immunopositive for Iba-1, CD204 and lysozyme. A small number of tumour cells were positive for E-cadherin and CD208, and the tumour cells in one case were positive for HLA-DR. These results suggest that the tumour cells have variable features of histiocyte origin, including dendritic cells, LCs and macrophages. The behaviour of HS in the hedgehog was very aggressive, and 50% of cases died within 90 days of resection. The present study also highlighted the tendency for local tumour recurrence in localized cutaneous HS cases, suggesting a requirement for a long-term follow-up after excision.

Chondroblastoma is a rare bone tumor, accounting for less than 2% of all bone tumors. Tumors arising in the temporal bone are extremely rare. A 66-year-old female was referred to the ENT department with hearing disturbance on the right side. Computed tomography showed a mass with a bony defect on the right squamous part of the temporal bone and glenoid fossa. T2-weighted magnetic imaging revealed a low signal mass in the right squamous part of the temporal bone. The pathological diagnosis from a biopsy specimen was chondroblastoma. Complete resection of the tumor and reconstructive surgery were performed by the surgical team, which included ENT, brain, oral maxillofacial, and plastic surgeons. Histopathological findings of the surgical specimen revealed that mononuclear cells and multinucleated giant cells proliferated with extensive hemosiderin deposition with a background of fibrous tissue and a cartilage-like myxoid matrix. Immunohistochemically, the nucleus and cytoplasm of mononuclear cells were positive for the anti-S-100 protein antibody. Therefore, the pathological diagnosis of chondroblastoma was confirmed. The patient has been followed up for 5 years and 7 months postoperatively without any severe clinical disturbance or sign of recurrence.

Giant cell tumor is a benign primary bone neoplasm which most often occurs in a periarticular location. Involvement of the bones of the foot and ankle is rare, and there have been a limited number of previous case reports involving the talus. Here we report a case of giant cell tumor of the talus, which was initially radiographically occult in a 43-year-old female, with emphasis on MRI imaging characteristics. The patient underwent surgical excision and curettage. Histological examination revealed the presence of spindle cells admixed with giant cells, confirming GCT. We further provide an overview of the radiological findings of GCT. Giant cell tumor is a benign bone neoplasm of mesenchymal origin, identified by multinucleated giant cells [1]. GCT is locally aggressive and can destroy adjacent bone and articulations. The most commonly affected bones are the distal femur, proximal tibia, and distal radius, with an epiphyseal predominance in 90% of cases [2]. Presentations are mostly mono-ostotic, however multicentricity may occur in younger patients [3]. Very few cases have been reported in the bones of the feet, an incidence of 1%-2% have been previously reported [4]. GCT is seen between ages 20 and 40 years, with a 56% predominance in females [3]. Although benign, 1%-9% cases may “metastasize” to the lungs. The initial treatment is surgical removal, either en bloc, or more commonly intralesional curettage and the use of adjuvants. Even after resection, GCT has a high recurrence rate [2]. The trigger for GCT is currently unknown. However, a majority of cases have cytogenetic abnormalities of telomeric associations (tas). Involvement of the RANK pathway is also believed to contribute to the pathogenesis of GCT [2].

Objectives This study aimed to evaluate and compare the immunohistochemical expression of OCT-4 and SOX-2 and to determine their use in differentiating giant cell tumor (GCT) from central giant cell granuloma (CGCG) and peripheral giant cell granuloma (PGCG). Study Design Formalin-fixed, paraffin-embedded tissue blocks of 10 histopathologically diagnosed cases of GCT, CGCG, or PGCG were examined for anti–OCT-4 and anti–SOX-2 antibodies. Nuclear staining of stromal mononuclear cells and multinucleated giant cells was considered positive for OCT-4 and SOX-2 expression. Results Nuclear immunoexpression of OCT-4 in stromal mononuclear cells was observed in 80% (8 of 10) of GCT cases, whereas none of the CGCG and PGCG cases showed OCT-4 immunoreactivity. SOX-2 immunoreactivity was negative in GCT, CGCG, and PGCG. Conclusions OCT-4 immunopositivity in GCT can be used as a cancer stem cell marker to differentiate GCT from CGCG and PGCG. The presence of OCT-4 in GCT versus its complete absence in CGCG and PGCG suggests that these three conditions are separate entities. The absence of stem cell marker OCT-4 and SOX-2 raises questions regarding their role in the pathogenesis of CGCG and PGCG.

Chondroblastoma is a rare, benign, cartilaginous-derived tumor accounting for ∼1% to 2% of all primary bone tumors and almost 9% of all benign bone tumors. In this case report, we describe a patient with chondroblastoma and a secondary aneurysmal bone cyst, with the adjacent talus being mildly affected. The initial diagnosis was giant cell tumor and was then confirmed after computed tomography-assisted biopsy. We performed a total calcanectomy via bilateral structural iliac bone autografting to relieve pain and reconstruct the loadbearing function because of the presence of extensive lesions. The patient was pain free and expressed satisfaction with postsurgical dorsiflexion and plantarflexion function at the 60-month follow-up visit. Radiographic images showed that the autografted iliac bone was completely healed, with no evidence of local recurrence.

Cherubism is a hereditary disease that generally presents during childhood and causes bilateral symmetrical enlargement of the jaws. It is a self-limiting disease that spontaneously remits or regresses after puberty, in most cases. Owing to the rarity of the disease, there have been few reports about patients with cherubism, who underwent tooth extraction due to dental caries and apical periodontitis. We present the case of an adult patient with cherubism, who underwent dental extraction due to chronic apical periodontitis, at a bony site that was involved with a lesion in the affected jaw. A 19-year-old woman with cherubism, exhibiting severe bilateral expansion of the lower jaw, had a decayed second molar present in a lesion of her affected mandible. Although she had reached adulthood, it was unclear if active growth of the lesion had been arrested. On removal, the tooth showed osseous ankyloses and required root separation. Postoperative healing was normal and without complications, such as wound infection and regrowth of the lesion. Histologically, the periapical lesion comprised granulation tissue accompanied by inflammatory cell infiltration and blood capillaries. The alveolar septum consisted of lamellar trabecular bone surrounded by fibrous tissue. Typical histological findings of cherubism, such as multinucleated giant cells and newly formed bone, were absent both within and near the extraction site. A case of cherubism with uneventful dental extraction, necessitated by chronic infection, has not been reported to date.

Cellular senescence has been associated with age-related diseases, wound healing, fibrosis, diabetes and cancer. Senescent cells lack the capacity to proliferate, but are known to aggravate tumorigenesis. The polyploid giant cells arise from the cancer cell population mainly due to genotoxic stress caused by chemotherapy and/or radiotherapy. They exhibit features of senescence and have been reported to secrete an array of cytokines, chemokines and growth factors. These small molecules can bind to their receptors located on the surface of neighboring cells and activate/deactivate relevant signaling pathways, thereby modulating the tumor microenvironment. Some of these signaling cascade(s) might play a role in imparting therapy resistance to the cancer cells. This review throws light on the incidence of senescence and how the senescent polyploid giant cells affect the tumor microenvironment. Their role in giving rise to chemoresistant cancer cell population as well as acquired chemoresistance in the neighboring cancer cells along with various potential and established therapeutic avenues have also been discussed.

VenaSeal (Medtronic, Minneapolis, Minn) is a cyanoacrylate polymer adhesive for the treatment of patients with chronic venous insufficiency. As an implanted device, questions remain about how long cyanoacrylate persists after closure. In this report, a 65-year-old man was examined 5.5 years after cyanoacrylate closure, and a segment of great saphenous vein was excised for histopathologic analysis. Findings were typical of a foreign body reaction. The vessel was occluded with collagenized mature fibrous tissue and polymer remnants, which were encapsulated by multinucleated giant cells. Focal areas of granulomatous inflammation were present in the vein wall extending to the adventitia.