Major Nerve Resections in Extremity Soft Tissue Sarcomas-Functional and Oncological Outcomes.

Soft tissue sarcomas form 1% of all cancers and are rare. The lower limb is one of the commonest sites of sarcoma, with the thigh accounting for the majority of these tumors. Large tumors abut the neurovascular bundles both anteriorly and in the hamstring compartment. Nerve involvement, especially the major nerves such as the femoral and the sciatic, by these tumors, was considered to be an absolute contraindication for limb salvage procedures. We present our data of major nerve resection without amputation, in an attempt to demonstrate the possibility of equivalent functional and oncological outcomes in these rare tumors. A total of 86 cases of extremity soft tissue sarcomas were operated on during the period September 2019 to September 2022, of which there were 12 cases of major nerve resections of the lower extremity. These patients were followed up and their clinicopathological data collected and analyzed. The functional outcome was recorded at different intervals. Of the 12 patients who underwent nerve resection along with the tumor, only 1 patient developed a local recurrence. Two patients developed multiple lung metastases, and the other 9 patients are alive and free of disease, with a median follow-up of 26 months. The MSTS score was assessed at 1 month post-surgery, 3 months, 6 months, and 1 year post-surgery. Except for one patient where the score was 20%, all the other patients had scores of 80% or more. Major nerve involvement by soft tissue sarcomas is not an indication for amputation. Limb salvage can be performed with no effect on the oncological outcomes.

Novel oncogenic transcriptional targets of mutant p53 in esophageal squamous cell carcinoma.

Missense mutations in the DNA binding domain of p53 are observed frequently in esophageal squamous cell carcinoma (ESCC). Recent studies have revealed the potentially oncogenic transcriptional networks regulated by mutant p53 proteins. However, majority of these studies have focused on common "hotspot" p53 mutations while rarer mutations are poorly characterized. In this study, we report the characterization of rare, "non-hotspot" p53 mutations from ESCC. In vitro tumorigenic assays performed following ectopic-expression of certain "non-hotspot" mutant p53 proteins caused enhancement of oncogenic properties in squamous carcinoma cell lines. Genome-wide transcript profiling of ESCC tumor samples stratified for p53 status, revealed several genes exhibiting elevated transcript levels in tumors harboring mutant p53. Of these, ARF6, C1QBP, and TRIM23 were studied further. Reverse transcription-quantitative PCR (RT-qPCR) performed on RNA isolated from ESCC tumors revealed significant correlation of TP53 transcript levels with those of the three target genes. Ectopic expression of wild-type and several mutant p53 forms followed by RT-qPCR, chromatin affinity-purification (ChAP), and promoter-luciferase assays indicated the exclusive recruitment of p53 mutants-P190T and P278L, to the target genes leading to the activation of expression. Several functional assays following knockdown of the target genes revealed a significant suppression of tumorigenicity in squamous carcinoma cell lines. Rescue experiments confirmed the specificity of the knockdown. The tumorigenic effects of the genes were confirmed in nude mice xenograft assays. This study has therefore identified novel oncogenic targets of "non-hotspot" mutant p53 proteins relevant for ESCC besides validating the functional heterogeneity of the spectrum of tumor-specific p53 mutations.

A Comprehensive Correlation of Clinicopathologic Prognostic Factors in Malignant Adult Renal Tumors: A Single Institutional Study.

OBJECTIVE: To study the clinicopathologic prognostic parameters of malignant adult renal tumors as these have poor over-all survival (OS) and show frequent metastasis. MATERIAL AND METHODS: This was a retrospective analysis of the clinical and pathologic features of malignant renal tumors in adult patients from January 2011 to December 2020. All the tumors were studied with respect to age, clinical presentation, tumor type/subtype, histologic grade (WHO/ISUP grading system), TNM stage and presence of necrosis. Correlation of histopathologic features and survival analysis was done using Kaplan-Meier survival curves and Cox-regression analysis. RESULTS: A total of 257 cases were included in the study period including 253 renal cell tumors of which clear cell renal cell carcinoma accounted for 69.3%. The age of the patients ranged from 20 to 87 years (median-52 years). The overall survival significantly reduced with increasing histologic grade, stage, and presence of necrosis. The comparison between the histological subtypes was not statistically significant. Univariate Cox-regression analysis found significant hazard ratio with increasing age, size, histologic grade (G4 vs G1), stage, and presence of necrosis. The correlation of OS with histological subtypes was not significant. Multivariate analysis also showed increased hazard ratio with increasing age, size, grade, and stage. However, the P-value was significant only for age. CONCLUSION: Clear cell renal cell carcinoma was the commonest type of adult renal tumor. Older age at presentation, larger tumor size, presence of necrosis, and higher histologic grade and stage were associated with poor prognosis in these patients.

A Clinical and Immunopathological Analysis of Carcinoma of the Ovary with an Emphasis on Post-chemotherapy Histopathologic Changes.

Ovarian cancers are a heterogeneous group of malignant tumors that differ with respect to pathogenesis, morphology, molecular features, and behavior. Pathologists and clinicians need to be aware of the advances in diagnosis and the changes which occur after chemotherapy to offer the optimal treatment to each patient. The present work aims to study the morphologic and immunohistochemical (IHC) profile of primary ovarian cancers with an assessment of post-chemotherapy changes. A total of 51 cases were included in the study from June 2017 to June 2019 (prospective and retrospective). The demographic and clinical details of the patients were collected. The gross and microscopic features of the tumors were studied, and the post-chemotherapy changes were evaluated. A chi-square test was used to determine the association of tumor morphology, the chemotherapy response score (CRS), and stage of the tumor with survival (PFS and OS). The mean patient age was 47.5 years, and high-grade serous carcinoma (66.6%) (HGSC) was the most common subtype followed by mucinous carcinoma and endometrioid carcinoma. Immunohistochemical analysis with WT1 and p53 helped in the diagnosis of HGSC. The CRS was 1 and 2 in most of the cases. The follow-up for patients of HGSC was available for a period of 1-27 months with a mean survival for primary resection of 24 months and for post-NACT resection was 17 months. This difference was not statistically significant (p = 0.38). High-grade serous carcinoma was the most common ovarian cancer in our series, and immunohistochemistry played an important role in the diagnosis. We could not demonstrate any survival benefit of preoperative chemotherapy in our series.

Distinct NOD2 mutations reported in three families with Blau syndrome (BS) from a single center in India - Case series and review of literature.

OBJECTIVE: Blau syndrome (BS), considered a rare pediatric autoinflammatory disease, is characterised by a triad of granulomatous arthritis, dermatitis and uveitis. Here we present a tale of three families visited in our outpatient department in the last two years (2020-2022) where more than one member was affected with either skin, ophthalmological and joint involvement with either biopsy-proven granuloma or genetic mutation at NOD2 gene suggesting the diagnosis of BS. CASE SERIES: The first family had three affected members where the mother and her two children had skin changes, polyarthritis and a pathogenic mutation in NOD2 gene (exon 4, c.1000C > T, p.Arg334Trp) suggesting BS. The second family had two affected members where both mother and her son had uveitis, skin changes with NOD2 mutation at exon 4 with c.1147G > A (p Glu 383 Lys) variant. The son also had polyarthritis and his skin biopsy was suggestive of granulomatous inflammation. In the third family with two affected members, we found a mutation in NOD2 on exon 4 (c 1324C > T, p.Lys 442 Phe) which was described as pathogenic with only one report published till date. CONCLUSION: These three cases presented to us within the last two years and led to a diagnosis of BS in three other family members with discrete mutations (commonest to rarest) on the NOD2 gene in the three families.

Hepatocellular carcinoma: A clinicopathological and immunohistochemical study of 116 cases from a tertiary care hospital in Southern India.

Background: Diagnosis of hepatocellular carcinoma (HCC) is difficult on morphology alone in poorly differentiated tumors and metastatic carcinomas. Appropriate immunohistochemical markers are required for definite diagnosis. In this article, we have analyzed the histopathological and immunohistochemical features of HCC and elucidate the best possible immunohistochemistry (IHC) marker combination by comparing the sensitivity of various markers in different grades of tumor. Methods: A total of 116 consecutive cases were analyzed retrospectively. The hematoxylin and eosin stained sections were reviewed in all the cases. IHC was done using hepatocellular specific antigen (HSA), arginase-1, glypican-3, and polyclonal carcinoembryonic antigen (pCEA). The sensitivity of various immunohistochemical markers individually as well as in combination for different tumor grades was determined. Results: Histologically, the predominant subtype comprised of classic variant (109,93.9%) followed by combined hepatocellular and cholangiocarcinoma (4,3.4%) and fibrolamellar variant (3,2.6%). Trabecular pattern was the most common histological pattern. On grading, 65,56.03% were moderately differentiated, 34,29.31% well differentiated, and17, 14.65% poorly differentiated. HSA and polyclonal-CEA showed higher sensitivity than arginase-1 and glypican-3 in well and moderately differentiated tumors. In contrast arginase-1 and glypican-3 showed better sensitivity in poorly differentiated HCC. The overall sensitivity increased to greater than 90% if HSA/polyclonal-CEA is combined with either arginase-1/glypican-3 irrespective of tumor grade. Conclusion: Majority of the tumors were classic variants and moderately differentiated. HSA along with either arginase-1 or glypican-3 is the best combination of immunomarker for identification of hepatocellular differentiation irrespective of tumor grade.

H3F3A mutation as a marker of malignant giant cell tumor of the bone: A case report and review of literature.

Giant cell tumor of the bone (GCTB) is a locally aggressive lesion, which characteristically arises from the epimetaphyseal region of long bones. They occur commonly in the third or fourth decade of life with a slight female preponderance. Various lesions such as chondroblastoma, aneurysmal bone cysts, and nonossifying fibromas can mimic the radiologic appearance of giant cell tumors. However, the greatest challenge is to differentiate between a conventional GCTB, a malignancy arising in a giant cell tumor, and osteoclast-rich osteosarcomas. The presence of a histone gene mutation, H3F3A, involving the substitution of glycine 34 has been reported in more than 95% of GCTB. Immunohistochemical (IHC) analysis of the biopsy specimens for H3.3pG34W expression is a surrogate for gene analysis and can be used to establish the presence of GCTB. Our report is the first in Indian literature to report the use of H3.3pG34W IHC in establishing the diagnosis of a primary malignant GCTB.

An Audit of Breast Conservation Surgery for Breast Cancer - a 7-Year Experience from Southern India.

To audit the use of breast conservation surgery for breast cancer treatment in a tertiary care centre over a 7-year period, and also to chart the clinical, demographic and pathological characteristics of breast cancer patients treated in the setting of a referral centre in a middle income (MDI) group country. A retrospective analysis of the case records of all patients of invasive breast cancer treated at our institute between January 2014 and December 2020 was done after obtaining approval from the Institute Ethics Committee (IEC). The number of patients seen, age, parity, menopausal status, family history of cancer, laterality, site of tumour in the breast, the symptomatology, clinical stage and presence or absence of metastases was the clinical parameters examined. The pathological stage and grade of the tumour, receptor status, treatment offered according to stage and the patterns of failure with respect to the surgery performed were recorded. Statistical analysis was a direct head to head comparison of the percentage proportions of the different variables. A total of 685 patients of breast cancer were treated between January 2014 and December 2020. A total of 53% of the cohort was more than 45 years old and 56.7% were post menopausal. A total of 58.8% of the patients presented with a cancer in the left breast and in the upper outer quadrant. Nearly 41% of the tumours were more than 4 cm in size. The most common receptor profile in our patient population was ER positive, PR positive and HER 2 negative. A total of 27.7% of the patients were offered neo-adjuvant chemotherapy and 63.06% underwent upfront surgery. A total of 19.7% of all surgeries performed (overall) were breast conservation surgeries (BCS). The use of BCS showed an increasing trend over the 7 years studied rising from 16.79 to 25% (annually). The local failure rate for BCS was 11.8% but the incidence of distant metastases was not significantly different compared to the patients who underwent a mastectomy. Breast conservation is safe and feasible in a referral setting even in a middle income nation with multi-disciplinary treatment planning and needs to be adopted widely to preserve the body image and self esteem of patients with breast cancer.

Impact of macroscopic on-site evaluation on the diagnostic outcomes of endoscopic ultrasound-guided fine-needle aspiration.

BACKGROUND: Endoscopic ultrasound (EUS)-guided tissue acquisition is the preferred modality for diagnosing pancreatic lesions and mediastinal and abdominal lymph nodes. Rapid on-site cytologic evaluation improves the diagnostic outcome of EUS-guided fine-needle aspiration (FNA) but is unavailable at many centers. Alternatively, macroscopic on-site evaluation (MOSE) may improve the diagnostic outcome of EUS-FNA, but data are limited. Hence, the present study was conducted to assess the efficacy of MOSE in improving adequacy and accuracy. METHODS: We retrospectively analyzed data of consecutive patients with pancreatic or lymph nodal lesions undergoing EUS-guided FNA at a tertiary care center from December 2020 to December 2022. The study's primary outcomes were adequacy and diagnostic accuracy of the EUS-guided tissue acquisition, with secondary analysis of predictors of adequacy and accuracy. RESULTS: Data from 124 patients (44.4% male, median age: 54 years) who underwent EUS-FNA were included in the present analysis. The presence of macroscopic visible core (MVC) on MOSE was reported in 93/124 (75%) cases. An adequate sample for histopathological or cytological examination was obtained in 110/124 (88.7%) cases, while the diagnostic accuracy was 85.5%. On multivariate analysis, the absence of MVC on MOSE was found to be the independent negative predictor of both adequacy (OR 0.092, 95% CI: 0.024-0.349) and accuracy (OR 0.175, 95% CI: 0.057-0.536). CONCLUSION: The presence of MVC on MOSE can be an indicator of specimen adequacy and can improve the diagnostic yield of EUS-FNA.

Evaluation of Serum Mammaglobin as an Alternative Biomarker in the Diagnosis of Breast Tumors.

Introduction Breast cancer is the most common cancer in women in India and accounts for 14% of all cancers in women. Rise in mortality is due to lack of awareness and proper screening. Mammography and presently available serum biomarkers have low sensitivity and specificity. In our quest to identify a better biomarker, we studied mammaglobin (MAM) in patients with breast cancer and benign breast tumors. Aim To evaluate serum mammaglobin in breast cancer patients and compare it with benign breast tumor patients and healthy controls. To compare it with existing biomarkers serum carcinoembryonic antigen (CEA) and cancer antigen 15-3 (CA 15-3). Materials and methods: This is a cross-sectional, case-control study of 77 subjects, of which 27 were breast cancer patients, 20 benign breast tumor patients, and 30 healthy controls. Serum CEA and CA15-3 were estimated by electrochemiluminescence immunoassay (ECLIA) and mammaglobin (MAM) by enzyme-linked immunosorbent assay (ELISA). Results Mammaglobin and CEA levels were elevated in breast cancer patients, followed by benign breast tumors when compared with controls ( P < 0.000001). Mammaglobin showed 81.5% sensitivity, 100% specificity, 100% positive predictive value (PPV), and 88.9% negative predictive value (NPV). CEA showed 88.9% sensitivity, 82.5% specificity, 77.4% PPV, and 91.7% NPV. The area under the curve was the highest for MAM (0.892), followed by CEA (0.889) and CA 15-3 (0.555). CA15-3 showed poor diagnostic efficacy. Combined receiver operating characteristic (ROC) curve of the biomarkers MAM and CEA had an AUC of 0.913. Conclusion Mammaglobin proved to be an efficacious biomarker in diagnosing breast cancer.

Anti-histone H3.3K36M Antibody is a Highly Sensitive and Specific Immunohistochemistry Marker for the Diagnosis of Chondroblastoma. A Validation Based on Study 136 Cases Comprising Chondroblastoma and its Mimics from Single a Centre in India.

Introduction. Chondroblastoma has a wide range of differential diagnosis encompassing various benign and malignant entities. The closest differential diagnosis is giant cell tumor of the bone due to overlapping radiological and histomorphological features. Extensive aneurysmal bone cyst like changes and lack of adequately sampled chondroid matrix often masquerades the primary bone lesion and amplifies the diagnostic difficulty in small biopsies with limited tissue. Immunohistochemistry is helpful in such instances to resolve the diagnostic dilemma. Objectives. To analyze the immunohistochemical expression of anti-histone H3F3K36M antibody inchondroblastoma and validate its utility in differentiating chondroblastoma from its histological mimics. Material and methods. Immunohistochemistry was performed using anti-histone antibody H3.3K36M in 44 histologically diagnosed chondroblastoma and 92 other histological mimickers. All chondroblastoma and giant cell tumor of the bone included in the study were also tested for anti-histone H3.3 G34W antibody. Of the 33 giant cell tumors of bone with classic morphology and imaging findings, 24 H3.3 G34W positive and 9 negative tumors were included intentionally to rule out the possibility of chondroblastoma. The sensitivity, specificity, positive and negative predictive value of marker with regard to chondroblastoma was calculated. Results. Immunohistochemistry revealed unequivocal nuclear positivity for H3.3K36M in the mononuclear cells in all the 44 chondroblastoma tested, denoting a sensitivity of 100% cases. Allthesetumors tested simultaneously for anti-histone H3.3G34W were negative. None of the histological mimickers were positive H3.3K36M indicating a specificity of 100%. The positive and negative predictive value was 100%. Conclusion. H3.3K36M mutant antibody is highly sensitive and specific IHC marker and can be used as a valuable adjunct to distinguish chondroblastoma from its histological mimics especially on small biopsies.

Fibrocartilaginous mesenchymoma of pelvis-a potential diagnostic pitfall.

Fibrocartilaginous mesenchymoma (FM) is a rare bone tumor mimicking other fibrocartilaginous lesions on imaging and histologically. Hence, it is difficult to diagnose this entity especially on small biopsies. In this article, we report a case of FM mimicking desmoplastic fibroma on biopsy. A 36-year-old male presented with pain in the left hip. Imaging showed a large expansile lytic lesion involving the acetabulum and pubis. The differential diagnosis was suggestive of giant cell tumor, aneurysmal bone cyst, intraosseous desmoplastic fibroma, and chondrosarcoma. Biopsy revealed a low-grade spindle cell lesion with no evidence of osteoid or chondroid matrix. The lack of cartilaginous nodules in the biopsy prompted a preoperative diagnosis of desmoplastic fibroma. The excised mass showed bland spindle cell proliferation, benign cartilage nodules, and epiphyseal plate-like enchondral ossification suggestive of fibrocartilaginous mesenchymoma. Negative immunostaining for SATB2, CDK4, and MDM2 ruled out low-grade central osteosarcoma. Though GNAS mutations were not performed in this case, rimming of the bony trabeculae at the periphery of the epiphyseal growth plate-like cartilaginous nodule ruled out fibrous dysplasia. The absence of cartilaginous component misleads the diagnosis preoperatively in small biopsies.

Utility of bone marrow examination (BME) in the diagnosis of pyrexia of unknown origin (PUO).

INTRODUCTION: Bone marrow examination (BME) is a useful tool in the diagnosis of haematological and non-haematological diseases. It plays an important role in early diagnosis of the underlying cause of pyrexia of unknown origin (PUO) and can influence the management of patients. Bone marrow aspiration (BMA) plays a very important role in establishing a definitive diagnosis in cases of PUO. The aim of this study was to review the indications and usefulness of bone marrow aspirates sent for microbiological evaluation as a diagnostic tool with histopathological correlation. METHODOLOGY: A prospective study was conducted from 1 January 2017 to 30 September 2019 in the Department of Microbiology and Pathology on the bone marrow aspirates of patients of all groups. RESULTS: A total of 148 bone marrow aspirates were included. The cases were categorized as classical PUO (n = 81/148, 54.7%), nosocomial PUO (n = 4 /148, 2.7%), neutropenic PUO (n = 18/148, 12.1%), and immunocompromised PUO (n = 45/148, 30.4%), among which were systemic lupus erythematosus cases n = 8/45 (22.2%), human immunodeficiency virus positive cases n = 10/45 (17.7%), and renal transplant cases n = 27/45 (60%). A total of 28 BMAs were positive for microorganisms, out of which bacterial pathogens were n = 12 (42.8%), mycobacterial n = 12, 42.8%, fungal (n = 3, 10.7 %), and viruses (n = 1, 3.5%). CONCLUSIONS: This study helped in highlighting the role of bone marrow examination as an important diagnostic method in the diagnosis of infectious diseases.

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.

Context: 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. Objectives: 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. Design: 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. Results: 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%. Conclusion: 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.

Hepatic epithelioid hemangioendothelioma-report of three cases of a puzzling tumor.

Hepatic epithelioid hemangioendothelioma (EHE) is a rare malignant vascular neoplasm with unpredictable clinical behavior. These lesions are frequently misdiagnosed owing to its non-specific symptomatology, ambiguous radiological features, and overlapping histomorphology. We report three cases of hepatic EHE, of which one was male and two were female patients. While all three patients presented with abdominal pain, the male patient gave an additional history of weight loss and was jaundiced. The radioimaging showed multiple nodules in the liver and two of the patients also had pulmonary metastasis. The biopsies of the liver nodules revealed a tumor composed of spindle, epithelioid, and stellate tumor cells, some with characteristic intracytoplasmic vacuolations/lumina surrounded by myxohyaline stroma. Some of these intracytoplasmic vacuoles/lumina showed erythrocytes, suggesting its vascular origin which was confirmed by CD31 and CD34 positivity. The article highlights the importance of histopathology and IHC in the precise diagnosis of EHE.

Bone Marrow Metastasis of Solid Tumors: A Study of 174 Cases Over 2 Decades from a Single Institution in India.

To analyze the pathological findings in patients with marrow metastasis from solid tumors and to compare the accuracy of the bone marrow aspirate, trephine imprint and trephine biopsy in detecting metastasis. A total number of 174 cases diagnosed on bone marrow aspiration and/or bone marrow biopsy from January 2000 to December 2018 were included in the study. In addition to clinical and demographic data, we evaluated peripheral blood findings, and pattern as well as morphology of the tumor cells in bone marrow aspirate, imprint cytology and biopsy. The changes in the bony trabeculae were classified according to the classification of carcinomatous osteodysplasia. The most common laboratory findings included cytopenias and leucoerythroblastic blood picture. Trephine biopsy was found to be the most sensitive technique for detection of marrow metastases with a sensitivity of 99.4%. Trephine imprint cytology (89.9%) showed a significantly better detection rate than bone marrow aspiration (58.5%). Metastatic adenocarcinomas and undifferentiated carcinomas were more common than non-epithelial tumors. Metastatic carcinomas with known primary were mostly from breast, prostate and lung. Ewings/PNET and neuroblastoma were the commonest among metastatic non-epithelial tumors. Fibrosis (53.4%) was the most frequent stromal change and abnormalities in bony trabeculae were noted in 61.2% cases. Trephine biopsy has the highest sensitivity in detection of marrow metastasis followed by trephine imprint cytology. Immunohistochemistry on trephine section will help in confirming and or suggesting the primary tumor in unknown cases.

Utility of P63 in Differentiating Giant Cell Tumor from Other Giant Cell-Containing Lesions.

OBJECTIVE: To assess P63 expression in giant cell-containing lesions of the bone (GCLB) and to determine its utility in differentiating giant cell tumor of the bone (GCTB) from other GCLBs. MATERIAL AND METHOD: Cases diagnosed as GCLB on histopathology were included in the study. P63 immunohistochemistry was performed in all the cases. The percentage of cells showing nuclear positivity was assessed in the non-giant cell component. Statistical analysis was performed using the Mann-Whitney U test. RESULTS: Of the total 53 cases studied, the majority were GCTBs (23), followed by 12 cases of chondroblastomas (CBL) and 18 other giant cell lesions (GCLs). All giant cell-containing lesions except one case of CBL and brown tumor of hyperparathyroidism (BTH) showed P63 staining in the non-giant cell component. However, the mean P63 labeling of GCT (52.6%) was higher compared to CBL (28.3%), aneurysmal bone cyst (ABC) (15.2%), non-ossifying fibroma (NOF) (24.5%), giant cell lesion of small bones (GCLSB) (11%), BTH (6.8%) and chondromyxoid fibroma (CMF) (12.3%), with a p-value of < 0.001. CONCLUSION: Although p63 was present in majority of the GCLBs, its percentage positivity was significantly higher in GCTB compared to the other GCLBs. The diagnosis of GCTB is likely if cut-off value of > 50% is applied.

Bone metastases: A compilation of 365 histologically verified cases spanning over two decades from a single center.

OBJECTIVE: To analyze the clinicopathological features of metastatic bone tumors over a period of two decades and identify the primary site of malignancy in metastasis of unknown origin. MATERIALS AND METHODS: A total number of 365 cases were included in the study. The clinical features and location of the tumors were noted. The histopathological features of all the cases were studied. Immunohistochemistry (IHC) was done either to categorize or confirm the primary diagnosis using organ specific/organ restricted markers. RESULTS: A total 712 bony sites were involved by metastasis in 365 patients, of which spine was the most commonly affected. Metastasis was the initial presentation in 69.5% patients. The primary site was known in 220 patients and almost half of them were detected after the diagnosis of metastasis. IHC was used as adjunct to suggest the possible origin in cases with unknown primary in 27.4%. Among the metastatic carcinoma, adenocarcinoma was the most common histological subtype with thyroid being the most frequent primary site of origin followed by lung and breast. CONCLUSION: More than two-third of cases in surgical pathology practice present as initial manifestations. Detection rate of primary depends on extent of metastatic work-up and IHC with organ specific/organ restricted markers to facilitate treatment with bone targeting agents.

Grossing and reporting of bone tumor specimens in surgical oncology: Rationale with current evidence and recent updates.

Primary bone tumors, including sarcomas, are rare tumors and require a multidisciplinary approach, including inputs from a radiologist, pathologist, medical oncologist, and surgical and radiation oncologist, for optimal management. Over the years, there has been a paradigm shift toward the treatment of bone sarcomas, from radical resections to conservative surgical procedures, to achieve improved clinical and functional outcomes. This has led to receiving and processing various types of specimens in orthopedic oncopathology. Grossing and reporting of bone tumors require expertise. This review focuses upon the types of biopsies, grossing techniques of various specimens in orthopedic oncology and reporting, with rationale and recommendations from pathologists, actively involved in reporting and pursuing a special interest in bone tumors, based on current evidence. Furthermore, there is a section on some of the updates in the diagnosis of bone tumors, based on the recent fifth edition of the World Health Organization classification of tumors of soft tissues and bone.