Osteoclastic Giant Cells Research Articles

Malignant Phyllodes Tumour with Heterologous Osteosarcomatous differentiation and Osteoclast-like giant cells: Case Report of an uncommon neoplasm

Background: Phyllodes tumour (PT), an uncommon fibroepithelial neoplasm accounts for less than 1% of all primary tumours of the breast. MPT with osseous differentiation often gets misdiagnosed on imaging as benign giant calcifications resulting in treatment delay. We describe a rare case of MPT with heterologous osteosarcomatous differentiation and osteoclast-like giant cells and review the literature to discuss clinical-radiological findings, differential diagnosis and treatment options. Case Presentation: A 34-year-old female presented with a right breast lump. Mammography showed a high-density irregular mass with amorphous dense calcification, suggesting neoplastic aetiology. Preoperative core needle biopsy raised the possibility of a phyllodes tumour versus giant cell tumour. Wide local excision was performed to confirm the diagnosis which revealed the presence of a biphasic tumour with osteoid-like matrix and numerous osteoclastic giant cells. Immunohistochemistry was used to rule out metaplastic carcinoma or carcinosarcoma. The stromal cells were negative for panCK and P63 and positive for vimentin, CD10 and BCL-2. The osseous component was positive for Osteonectin and SATB2. Thus, a final diagnosis of malignant phyllodes tumour with heterologous osteosarcomatous differentiation and osteoclast-like giant cells was made. Conclusion: MPT with osteosarcomatous differentiation is a rare and challenging entity associated with a poor clinical outcome. Accurate diagnosis requires a multidisciplinary approach involving breast surgeons, pathologists and radiologists with careful histopathological examination. Wide local excision with close surveillance is crucial for timely detection of tumour recurrence and metastasis.

A314 UNDIFFERENTIATED PANCREATIC CARCINOMA WITH OSTEOCLAST-LIKE GIANT CELLS: A CASE REPORT

Abstract Background Pancreatic undifferentiated carcinoma with osteoclast-like giant cells (UCOGC) is a rare form of pancreatic cancer representing under 1% of cases. UCOGC is hypothesized to be a variant of pancreatic adenocarcinoma and while the pathophysiology is incompletely defined, it is felt to be an undifferentiated sarcomatoid carcinoma variant with chemotaxis of osteoclastic giant cells. Clinical, radiographic, or biochemical features do not reliably differentiate this from other tumors. Definitive diagnosis is made by histologic examination demonstrating non-neoplastic multinucleated osteoclastic giant cells (CD68 positive), mononuclear histiocytes, and neoplastic mononuclear cells. Aims To describe the case of a patient with UCOGC, highlighting key clinicopathologic features and management. Methods Case report and literature review. Results A 79-year-old man with atrial fibrillation on Xarelto presented with 4 months of abdominal pain, nausea, vomiting, and weight loss (22 kg). An MRI revealed a dilated main pancreatic duct and side branches with abrupt cutoff in the neck due to an ill-defined lesion. Endoscopic ultrasound confirmed a 36 mm hypoechoic ill-defined mass in the pancreatic neck. Biopsy performed with a 22-gauge needle with dry suction showed tissue fragments consistent with UCOGC (Figure 1). Unfortunately, the patient presented to hospital with worsened abdominal pain and nausea and was found to have new portal, superior mesenteric, and splenic vein thrombosis. His anticoagulant was changed to Dalteparin. A multidisciplinary cancer conference was held including input from experts in Toronto, and due to surrounding inflammation and new thrombosis he was not considered a surgical candidate at the time and neoadjuvant treatment with standard adenocarcinoma chemotherapy was planned. Unfortunately, the patient continued to decline and he was treated with palliative intent FOLFIRINOX for 2 cycles before opting for a medical assistance in dying procedure. Conclusions Treatment for UCOGC has not been well studied due to its rarity. Surgery is first-line therapy if appropriate based on patient status and cancer stage. The efficacy of chemotherapy and radiation is unclear but as a suspected adenocarcinoma variant, standard chemotherapy regimens are often used. Research is ongoing with an area of interest being PD-L1 inhibition due to high tumor PD-L1 positivity rates. Recognition of this rare entity is crucial due to its distinct diagnostic and therapeutic characteristics with more research needed to establish optimal therapy. Figure 1: Pathologic examination with HPS and CD68 stains demonstrating UCOGC Funding Agencies None

A Case of Aneurysmal Bone Cyst of Fourth Metacarpal Bone: A Rare Entity at Unusual Location

An Aneurysmal Bone Cyst (ABC) is a locally aggressive, rapidly growing, rare benign bone tumour that typically occurs in children and early adulthood. It usually occurs in the first and second decades of life, with a female predominance. The long bones of the lower extremities and spine are common sites for ABC, with rare involvement of the small bones of the hand. An 18-year-old female presented to the hospital with progressive swelling over her left hand for 4 to 5 months, associated with pain. Local examination elicits pain and tenderness over the 4th metacarpal bone with restricted movement at the Metacarpophalangeal (MCP) joint. A histopathological diagnosis of ABC was made due to the presence of osteoclastic giant cells lining a cyst, along with areas showing a pool of haemorrhage and stromal cells. The postoperative period remained uneventful, with no complaints of pain and good healing of the operation site noted during follow-up. Metacarpal bones are rare sites for ABCs.

Brown Tumor, a Deceptive and Rare Entity: A Case Report

A case of 27 years old male from Jhapa district, who presented to Oral and Maxillofacial department of B&C hospital with firm, non-tender swelling over buccal vestibule for 2 months. Computed tomography (CT) revealed an expansile lytic bony lesion with soft tissue component at the right hemimandible with cortical destruction. Provisional diagnosis of ameloblastoma was made. Incisional biopsy done and specimen was sent to the Pathology department. Haematoxylin and Eosin- stained slides revealed disorderly, fascicular architecture exhibiting clustered distribution of osteoclastic giant cells, surrounded by fibroblastic stromal cells along with reactive new bone formation. The differentials considered were CGCG (Central giant cell granuloma), GCT (Giant Cell tumor), ABC (Aneurysmal Bone Cyst) and Brown tumor. Serum Calcium and Serum PTH (Parathyroid hormone) were advised to ruleout brown tumor in histopathology report and for rest of the differentials excisional biopsy was suggested. Serum calcium and serum PTH were found to be raised. On further probing, the patient has been having right lower back pain and thin urine stream on and off for few months. USG abdomen was done for the same which revealed bilateral nephrolithiasis with left sided PUJ calculus causing gross hydronephrosis along with bilateral medullary nephrocalcinosis. DJ stenting was thus advised by the nephrologist. On identifying the primary cause, hemithyroidectomy with parathyroid removal was done. The decrease in parathyroid hormone level was drastic after the surgery. His urine stream was normal during his post –op stay at the hospital. The patient was advised for regular follow up.

Giant cell tumor of bone-an update

In the past few years, numerous new insights have been gained in the field of giant cell tumor of bone (GCTB). On the one hand, the detection of the highly characteristic histone mutation in the H3F3A gene in GCTB is becoming increasingly important in diagnostics in differentiating GCTB from other giant cell-rich lesions of bone as well as for defining rare variants of GCTB without osteoclastic giant cells. On the other hand, the effects of the H3F3A mutation were shown to have an impact on the epigenetic profile of tumor-driving stromal cells, providing new insights into tumorigenesis of GCTB.

Cytomorphologic panorama of giant cell tumour of tendon sheath.

Giant Cell Tumour of Tendon Sheath (GCTTS) is a slow growing benign soft tissue tumour arising from synovium of tendon sheath or joint. These tumours occur more frequently in upper limbs, especially hands. In the present study, we aimed to evaluate the cytomorphological spectrum of GCTTS. This retrospective study includes a total of 56 cases of GCTTS diagnosed over a period of 8 years. The clinical and radiological details of these cases were retrieved from the cytopathology records and detailed cytomorphological features were studied and analysed. Histopathological correlation was done in 16/56 cases, where follow-up was available. The mean age of patients at the time of presentation was 32 years and were predominantly females (68%). The most common site of GCTTS was fingers (76%), followed by foot, wrist and toes. The most consistent finding on cytology was stromal cells (100%) of polygonal, spindle and plasmacytoid morphology with interspersed multinucleated osteoclastic giant cells (100%), followed by binucleated stromal cells (75%), xanthoma cells (61%) and hemosiderin laden macrophages (52%). Presence of proteinaceous fluid background was also observed in 50% of the cases. GCTTS can be diagnosed with certainty on FNAC based on characteristic cytomorphological features in an appropriate clinical and radiological setting. FNAC plays a pivotal role in diagnosing GCTTS and differentiating it from other giant cell rich lesions, thus obviating the need of tissue biopsy for diagnosis, which in turn helps the clinician in timely and adequate management of the patient.

Histomorphometric Analysis of 38 Giant Cell Tumors of Bone after Recurrence as Compared to Changes Following Denosumab Treatment.

Giant cell tumor of bone (GCTB) is an osteolytic tumor driven by an H3F3A-mutated mononuclear cell with the accumulation of osteoclastic giant cells. We analyzed tissue from 13 patients with recurrence and 25 patients with denosumab therapy, including two cases of malignant transformation. We found a decrease in the total number of cells (p = 0.03), but not in the individual cell populations when comparing primary and recurrence. The patients treated with denosumab showed induction of osteoid formation increasing during therapy. The total number of cells was reduced (p < 0.0001) and the number of H3F3A-mutated tumor cells decreased (p = 0.0001), while the H3F3A wild-type population remained stable. The KI-67 proliferation rate dropped from 10% to 1% and Runx2- and SATB2-positive cells were reduced. The two cases of malignant transformation revealed a loss of the H3F3A-mutated cells, while the KI-67 rate increased. Changes in RUNX2 and SATB2 expression were higher in one sarcoma, while in the other RUNX2 was decreased and SATB2-positive cells were completely lost. We conclude that denosumab has a strong impact on the morphology of GCTB. KI-67, RUNX2 and SATB2 expression differed depending on the benign or malignant course of the tumor under denosumab therapy.

Aneurysmal bone cyst of dorsal spine presenting with paraparesis in a pediatric patient: a case report

Introduction: Aneurysmal bone cyst (ABC) are rare benign tumours of spine. They most commonly presents with backache. However neurological deficit in spinal ABCs are not uncommon. Magnetic resonance imaging of ABC may sometimes be confused with osteosarcoma or Giant cell tumours. Treatment options are varied but complete excision of tumour with spine stabilisation should be the goal. Clinical case: Here we presented the case of a 13 year old girl presenting with spastic paraparesis and bladder incontinence with MRI dorsal spine suggestive of an expansile lesion of D5 body. She underwent subtotal corpectomy with fixation of spine . Biopsy was suggestive of aneurysmal bone cyst. Post operative neurological outcome was excellent and followup scans over 2 year period suggest complete remission. Discussion: ABC are non neoplastic expansile bone lesion consisting of blood filled spaces separated by connective tissue septa of bony trabeculation and osteoclastic giant cells. Similar to our case it is seen more commonly in young females. Lumbar spine has higher incidence of ABC as compared to dorsal and cervical spine. Most common presentation is backache. Surgical options for ABC include intralesional curettage, en bloc resection followed by fixation. Vertebroplasty is also a treatment option to reinforce spinal stability. Post operative radiotherapy also can be considered in partially resected cases. Although ABC have high recurrence rate of 10-44% which has been reported with 2 years following surgery. However our patients continue to have no radiological evidence of recurrence on 2 year follow up. Conclusion: ABCs are benign tumour which may present with neurological deficit. Although treatment of ABC remains controversial but early surgery with complete removal of tumour in patients with neurological deficit provides excellent recovery. However due to high recurrence rate regular follow up is necessary.

A single-institution analysis of a rare variant of pancreatic neoplasm-osteoclastic giant cell tumor.

e16315 Background: Pancreatic osteoclastic giant cell tumor (OGCT) is a rare variant (&lt;1% cases) of pancreatic neoplasm. Due to its rarity, prospective studies on management are limited. The prognosis and molecular characteristics may differ from pancreatic adenocarcinoma. Methods: We analyzed demographics, clinical features, treatment modalities, and outcomes of overall survival (OS) and progression-free survival (PFS) in patients with pancreatic OGCT at our institution from 2005-2022. Results: We identified 8 OGCT patients with a median age of 67, of whom 7 had locoregional disease (resectable- 5, borderline resectable- 1, locally advanced-1), and 1 had denovo metastatic disease at diagnosis. The borderline resectable and locally advanced patients eventually developed metastatic disease. The majority of patients were male (n=5), Caucasian (n=7), former smokers (n=5), had no significant alcohol use (n=8) and had no pre-existing pancreatitis (n=8). 4 of the 5 resectable patients had surgery, and 2 received adjuvant chemotherapy. The median OS was 54 months for locoregional disease (n=5) vs.16 months for metastatic disease (denovo metastatic and progression to metastatic disease, n=3). The median OS was 54 months for surgical resection (n=4) vs. 25 months for those without surgical resection (n=4) based on quartile computations from the Kaplan-Meier survival curve. Conclusions: Our patients had a longer OS than the previously reported OS of less than 12 months for all stages of pancreatic OGCT. There was no progression in resectable patients, indicating an indolent disease with an overall good prognosis. Patients with locoregional disease or those who underwent surgical resection had longer OS, but due to the small sample size and censored patient survival times (i.e., patients still alive), the statistical significance of this trend could not be calculated. Studies are required to understand tumor biology and determine the optimal multidisciplinary treatment. [Table: see text]

Histopathological response to denosumab in giant cell tumours of bone - A review of 11 cases.

Giant cell tumor (GCT) of the bone is a locally aggressive primary bone tumor, that can rarely metastasize. Arising mostly in epiphysis of the long bones in young adults, the tumor is composed of mononuclear cells that are admixed with osteoclastic giant cells(OLGCs), which express RANK ligand and RANK respectively. Denosumab a monoclonal antibody against RANK ligand has been shown to reduce the tumor by causing bone lysis by inhibiting RANKL. Histological changes in 11 patients of GCT who were treated with denosumab are presented here. Clinical records and slides of 11 patients of GCT who had been administered neoadjuvant denosumab were included in the study. Evaluation of pre and post therapy GCT specimens was performed by two pathologists (RK and VM). There were 4 males and 7 females. Their mean age was 30 years. All the patients received 120 mg denosumab subcutaneously every week with additional 120 mg on days 8 and 15 of therapy. The histological slides were reviewed and following points noted: 1) degree of ossification,2) fibrosis,3) loss of osteoclastic giant cells,4) proliferation of mononuclear cells,5) atypia,6) Permeation of osteoid by malignant cells. Out of 11 cases, 2 cases did not show any significant histological improvement. 7 cases showed reduction in giant cells, increased fibrosis, enhanced mononuclear cell proliferation and ossification consistent with a pathological response. Atypia and osteoid permeation were noted in 2 cases which showed transformation to osteosarcoma. Denosumab treated giant cell tumor show dramatic histological changes. The post therapy lesions may bear no resemblance to pretherapy lesion. There may be complete resolution or may be confused with benign or malignant lesions Rarely they may show sarcomatous transformation. It is imperative that the pathologist is aware of these changes to prevent diagnostic pitfalls as it poses therapeutic and prognostic implications.

Expression of SATB2, RUNX2, and SOX9 and possible osteoblastic and chondroblastic differentiation in chondroblastoma.

Chondroblastoma (CB) is histologically characterized by oval to polygonal-shaped mononuclear neoplastic cells, multinucleated osteoclastic giant cells, and eosinophilic matrix with occasional calcification. Genetically, the majority of CBs harbor H3F3B p.K36M mutation. Despite the historical nomenclature, it has been reported that the matrix of CB is similar to osteoid rather than true cartilage; however, it remains unclear whether neoplastic cells in CB have the potential for osteoblastic differentiation. To clarify this issue, we immunohistochemically examined the expression of osteogenic and chondrogenic markers (SATB2, RUNX2, p63, and SOX9) as well as H3K36M mutant protein in 33 cases of CB. All 33 cases of CB were positive for H3K36M, while SATB2, RUNX2, p63, and SOX9 were expressed in 30/33 (91%), 33/33 (100%), 29/33 (88%), and 31/32 (97%) CB cases, respectively. Our immunohistochemical results suggest that neoplastic cells in CB frequently express both osteogenic and chondrogenic markers and may have an intermediate feature of osteoblastic and chondroblastic nature.

Classification of endoscopic ultrasound guided fine needle aspiration cytology of pancreatic space occupying lesionsby Papanicolaou Society of Cytopathology System: A five year study.

Majority of the pancreatic cancer patients present at an advanced stage and have poor 5year survival rate. Thus, there is a need for early detection of pancreatic cancer with the initiation of the therapy. This is a retrospective study including all the endoscopic ultrasound guided (EUS) guided pancreatic FNAs from 2016 to 2020. The aspirate smears were analyzed and classified according to The Papanicolaou Society of Cytopathology System for Reporting Pancreaticobiliary Cytology (PSCPC). A total of 245 EUS guided FNAs from pancreatic lesions were included. Cyto-histological correlation was done wherever available. Category I (non diagnostic) accounted for 40 cases (16%) cases, Category II (negative) comprised of 44 cases (18%); and Category III (Atypical) had 5 cases (2%). Category IV neoplastic-benign category included 3 cases of serous cystadenoma, while neoplastic-others category included pancreatic neuroendocrine tumors (n=21), solid pseudo-papillary neoplasms (SPEN) (n=12) and mucinous cystic neoplasms (n=4). A total of 7 cases (2.8%) were reported in Category V (Suspicious). A diagnosis of adenocarcinoma (Category VI) was rendered in 105 cases (42.8%) cases. Rarer types included non Hodgkins lymphoma (n=3) and one case of primary undifferentiated carcinoma with osteoclastic giant cells. Cyto-histological correlation in all categories was available in 58 cases with 8 false negative cases. Thus overall sensitivity of EUS guided FNAC was found to be 87.8% with a diagnostic yield of 83.6% while sensitivity in diagnosing adenocarcinoma was 96.9%. The present study highlights the spectrum of EUS guided FNA of pancreatic lesions in a subset of North Indian population and classified them according to PSCPC. EUS guided FNAC is a sensitive investigation which plays a crucial role in confirming the diagnosis of pancreatic space occupying lesions (SOLs)in advanced stage.

The Uncancerous Helix-Benign Fibrous Histiocytoma

Benign fibrous histiocytoma occurs as an exceptional, painless, subcutaneous, mesenchymal, fibrohistiocytic neoplasm devoid of dermal incrimination. Additionally designated as deep dermatofibroma, deep seated benign fibrous histiocytoma commonly emerges within subcutaneous tissue, deep seated soft tissue or parenchymal organs. Generally, benign fibrous histiocytoma arises in adult males &gt; 25 years and appears between 6 years to 84 years with a median age of disease emergence at 40 years. A male predominance is observed. Commonly, benign fibrous histiocytoma emerges within lower or upper extremities, head and neck or trunk. Neoplasms confined to deep soft tissue of retroperitoneum, mediastinum or pelvis are infrequently discerned [1,2]. Deep seated benign fibrous histiocytoma emerges as a painless, gradually progressive, well circumscribed or encapsulated tumefaction [1,2]. Grossly, firm, yellow to tan, well circumscribed tumefaction encompassed with a pseudo-capsule is discerned. Pseudo-capsule may be absent where tumefaction extends to the cutis [1,2]. Characteristically, tumour magnitude is ~ 4 centimetres and varies from 0.5 centimetres to 25 centimetres. Cut surface exhibits variable foci of haemorrhage [1,2]. Upon microscopy, neoplasm exhibits a prominent storiform pattern configured of uniform, spindle-shaped cells imbued with eosinophilic cytoplasm with ill defined cellular perimeter and bland, elongated or plump nuclei with vesicular chromatin and delicate nucleoli. Tumour nuclei are devoid of nuclear atypia [1,2]. tumefaction is admixed with disseminated lymphocytes, plasma cells multinucleated giant cells, osteoclastic giant cells or foamy macrophages [1,2]. Frequently, prominent vascular articulations may configure a hemangiopericytoma-like pattern. Mitotic figures appear ≤5 mitosis per 10 high power fields [1,2]. Intervening stroma is myxoid or hyaline. Focal necrosis or tumour infiltration of lymphatic and vascular configurations is exceptional. Tumour perimeter is non-infiltrative and peripheral entrapment of adipose tissue is absent. Focal entrapment of collagen fibres may occur [1,2].

"Malignant Mesenchymoma" Revisited: A Clinicopathologic Study of Leiomyosarcomas With Osteosarcomatous Differentiation.

Leiomyosarcoma (LMS) is the most common sarcoma in adults. Rarely, LMS dedifferentiates into an undifferentiated sarcoma. Very few cases of LMS with heterologous osteosarcomatous differentiation (OS) have been reported. The purpose of this study was to evaluate the clinicopathologic features of LMS with OS. Of 5570 LMS cases diagnosed from 2006 to 2022, 15 cases (0.2%) of LMS with OS were identified, affecting 13 females and 2 males; ages ranged from 32 to 66 years (median: 53y). Ten tumors arose in the uterus, 2 in the retroperitoneum, and 1 each in the mesentery, mediastinum, and rectum. Primary tumors ranged from 7 to 20cm (mean: 16cm). The LMS components showed conventional spindle cell morphology in most cases; 3 cases showed marked pleomorphism; 3 cases contained an epithelioid component; and 1 case showed myxoid features. In 5 cases OS was identified in the primary tumor, whereas in 10 cases OS was first detected in metastases. One metastatic and 2 primary LMS showed both OS and chondrosarcomatous differentiation. Prominent osteoclastic giant cells were seen in the OS components in 11 cases. Mitotic activity ranged from 17 to 61/10HPF with tumor necrosis in 10 cases. Twelve patients developed metastases; sites included lungs, diaphragm, kidney, adrenal glands, colon, small intestine, liver, bone, and pancreas. At last follow-up, 8 patients had died of disease, and 4 patients were alive with metastases. The interval between OS and death ranged from 3 weeks to 18 months (median: 6.5mo). Development of OS in LMS is exceptionally rare. This form of heterologous differentiation may occur in both primary tumors and metastases. LMS with OS is highly aggressive with poor outcomes. Awareness of this phenomenon is important to avoid misdiagnosis as osteosarcoma.

Epigenetic lockdown of CDKN1A (p21) and CDKN2A (p16) characterises the neoplastic spindle cell component of giant cell tumours of bone.

Giant cell tumour of bone (GCTB) comprises the eponymous osteoclastic multinucleated giant cells eliciting bone lysis, an H3F3A-mutated neoplastic mononucleated fibroblast-like cell population, and H3F3A wild-type mononucleated stromal cells. In this study, we characterised four new cell lines from GCTB. Furthermore, we compared the genome-wide DNA methylation profile of 13 such tumours and three further cell lines with giant cell-rich lesions comprising three H3F3B-mutated chondroblastomas, three USP6-rearranged aneurysmal bone cysts, three non-ossifying fibromas, two hyperparathyroidism-associated brown tumours as well as mesenchymal stem cells, osteoblasts, and osteoclasts. In an unsupervised analysis, we delineated GCTB and chondroblastomas from the other analysed tumour entities. Using comparative methylation analysis, we demonstrated that the methylation pattern of the cell lines approximately equals that of H3F3A-mutated stromal cells in tissue. These patterns more resemble that of osteoblasts than that of mesenchymal stem cells, which argues for the osteoblast as the cell of origin of giant cell tumours of bone. Using enrichment analysis, we detected distinct hypermethylated clusters containing histone and collagen genes as well as target genes of the tumour suppressor p53. We found that the promotor regions of CDKN1A, CDKN2A, and IGFBP3 are methylated more strongly in GCTB than in the other giant cell-containing lesions, mesenchymal stem cells, osteoblasts, and osteoclasts (p < 0.001). This hypermethylation correlates with the lower gene expression at the mRNA level for these three genes in the cell lines, the lack of p16 and p21 in these cell lines, and the lower expression of p16 and p21 in GCTB. Overall, our analysis reveals characteristic DNA methylation patterns of giant cell tumours of bone and chondroblastomas and shows that cell lines of giant cell tumours of bone are a valid model for further analysis of H3F3A-mutated tumour cells. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Giant cell-containing tumors of bone and differential diagnoses

Osteoclastic giant cells represent acommon cellular component of lesions arising in bone. Highlighting this morphological finding, the current WHO classification of bone tumors defines adiagnostic group comprising aneurysmal bone cyst, giant cell tumor of bone and non-ossifying fibroma, which may display morphologic similarities while being distinct with regard to molecular and biological features. Starting with these tumors - putting afocus on lesions arising in bone - this article gives asurvey of other (chondrogenic and osteogenic) tumors that frequently contain osteoclastic giant cells, which may, particularly in small biopsies, enter differential diagnosis. Overlapping features with selected giant cell-containing soft tissue tumors, which may be of differential diagnostic relevance in daily routine, are discussed.

Anti-Histone H3.3 G34W antibody is a sensitive and highly specific immunohistochemistry marker for the diagnosis of Giant cell tumor of bone. A validation based on analysis of 198 cases from a single centre in India.

The diagnosis of giant cell tumor of bone (GCTB) is difficult in small biopsies with unusual age of presentation, location, and extensive secondary changes. Most of the GCTBs harbor H3F3A G34W mutations with a subset of cases showing alternate G34V, G34R, and G34L mutations. To analyze the expression of anti-histone H3.3G34W antibody in different cellular components of GCTB across different locations and presentations (including the unusual ones) and validate the utility of this antibody in the diagnosis of GCTB and differentiate it from the other osteoclast-like giant-cell-rich lesions. Immunohistochemistry was performed using anti-histone H3.3G34W antibody in the diagnosed cases of GCTB (136 cases of GCTB from 133 patients, including two malignant GCTBs) and other giant cell-containing lesions (62 cases). The presence of unequivocal crisp nuclear staining was considered positive. Immunohistochemistry revealed unequivocal nuclear positivity in the mononuclear cells in 87.3% of the cases of GCTB. Of these, most showed diffuse expression with moderate to strong intensity staining. The positive staining was restricted to the nuclei of mononuclear cells with the nuclei of osteoclastic giant cells being distinctly negative. In addition to conventional GCTBs, two cases each of multicentric and malignant GCTB showed positive staining. The other giant-cell containing lesions were distinctly negative. The present study showed a sensitivity of 87.3% with specificity and positive predictive value of 100%. The anti-histone G34W antibody is a highly sensitive and specific marker for the diagnosis of GCTB and differentiating it from its mimics. The positive staining is restricted to the mononuclear cell component of GCTB with sparing the osteoclastic giant cells further reiterating the fact that the mononuclear stromal cells are the true neoplastic component of GCTB.

Undifferentiated carcinoma with osteoclastic giant cells of pancreas: Case report and brief literature review

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. 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.

Undifferentiated and dedifferentiated urological carcinomas: lessons learned from the recent developments

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.

1594 Invasive Ductal Carcinoma with Osteoclast Giant Cells During Pregnancy: A Case Report and A Review of Literature

Abstract Mammary carcinoma with Osteoclast Giant Cells (OGCs) is a rare tumour. Although several cases were reported, the significance of this histological finding remains incompletely understood. OGCs may occur in several types of breast carcinoma with different epidemiological characteristics but, in association with pregnancy, OGCs has not been reported to date. Here we report a case 37-year-old presenting with a symptomatic breast lump in pregnancy that has been confirmed clinically and radiologically. Microscopic examination of biopsies and surgical specimens showed OGCs accompanying invasive ductal carcinoma with no evidence of axillary metastasis. Immunohistochemical analysis revealed tumour cells to be positive for oestrogen, and progesterone receptors, with human epidermal growth factor negative status (ER6, PR8, HER2 negative). This is the first case of OGCs during pregnancy to be reported, to our best of knowledge, following a search of the literature published in English language.