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.

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.

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.

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.

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.

Serum Human Epididymis Protein-4 (HE4) - A novel Approach to Differentiate Malignant Frombenign Breast Tumors.

BACKGROUND: The lack of sensitivity and specificity of existing diagnostic markers like Carbohydrate Antigen 15-3(CA15-3) and Carcinoembryonic antigen (CEA) in breast cancer stimulates the search for new biomarkers to improve diagnostic sensitivity especially in differentiating benign and malignant breast tumors. Expression of Human epididymal protein 4 (HE4) has been demonstrated in ductal carcinoma of the breast tissue. So we tried to evaluate serum HE4 levels as diagnostic marker in breast cancer patients and to comparatively assess serum HE4, CEA and CA15-3 in breast tumor patients both benign and malignant. METHODS: Total 90 female subjects were included in the study. We selected 30 breast cancer cases (Malignant group) and 30 benign breast lump cases (Benign group) based on histopathology report. And other 30 were age matched apparently healthy controls (Control group). HE4, CEA and CA15-3 were analysed in serum samples of all subjects by Electrochemiluminiscence immunoassay method. RESULTS: A significant difference in the median (IQR) of HE4 (pmol/l) was identified among malignant, benign and control groups {62.4(52.6-73.7) vs 49.3(39.8-57.4) vs 52.3(50.6-63.3) P=0.0009} respectively. The cutoff value for prediction of breast cancer was determined at >54.5 pmol/l for HE4, with a sensitivity of 73.3%, specificity of 65.3%, whereas cutoff value of CA 15-3 was >21.24 (U/ml) with a sensitivity of 56.7%, specificity of 74.5%. For CEA at cutoff value >0.99 (ng/ml) the sensitivity and specificity were 96.7 % and 62.7% respectively. AUC for HE4, CA15-3 and CEA were 0.725, 0.644 and 0.857 respectively. CONCLUSION: Our study demonstrated that serum levels of HE4 were significantly higher in malignant group compared to benign and control groups. There is no significant difference between HE4 levels between benign and control groups. These results indicate that HE4 appears as a useful and highly specific biomarker for breast cancer, which can differentiate between malignant and benign tumors.

Tissue microarray based immunohistochemical study of TLE1 in synovial sarcoma and its histologic mimics.

BACKGROUND AND AIMS: Molecular analysis is gold standard for diagnosis of synovial sarcoma (SS) but use of these ancillary techniques is limited by many practical issues like cost and limited resources. Several studies analyzed TLE1 as a diagnostic immunohistochemical marker for synovial sarcoma and few studies disagreed. The objective of the study was to evaluate immunohistochemical expression of TLE1 in synovial sarcoma and its histological mimics. METHODS: The study included a total of 63 cases; of which 28 were synovial sarcomas (SS) and 35 its histologic mimics. A tissue microarray was constructed from these cases and subjected to TLE immunostaining. Nuclear immunoreactivity of TLE1 was graded as 0, 1+, 2+ and 3+ based on intensity and percentage of cells. RESULTS: All SS except one (27/28; 96.4%) were positive for TLE 1. These included 18 of monophasic spindle cell type (94.7%), 5 biphasic type (100%), followed by two each (100%) of poorly differentiated and calcifying type of SS. Of the other tumours 2 GISTs (50%), 2 haemangiopericytoma (66.7%), 2 schwannomas (50%) and one mesenchymal chondrosarcoma (33.3%) were positive for TLE1. CONCLUSION: TLE 1 is a highly sensitive marker with reasonable specificity for synovial sarcoma. Awareness of TLE1 expression in other tumours, is important to avoid misdiagnosis.

Clinicopathological and immunohistochemical study of pulmonary neuroendocrine tumors - A single-institute experience.

INTRODUCTION: Pulmonary neuroendocrine tumors (NETs) comprise a spectrum of tumors ranging from indolent to highly aggressive neoplasm. This study aims to study the clinicopathological and immunohistochemical features of NETs and assess the sensitivity of various IHC markers. MATERIALS AND METHODS: All consecutive cases of pulmonary NETs diagnosed from January 2016 to June 2019 were analyzed retrospectively. The routine hematoxylin- and eosin-stained sections along with immunohistochemistry (IHC) slides were reviewed. IHC was done using a panel of markers which included synaptophysin, chromogranin, CD56, thyroid transcription factor-1 (TTF-1), p-40, napsin-A, and ki67. RESULTS: Of total number of 53 patients, diagnosis was made on biopsy in 40 patients and resection specimen in 13 patients. Small cell lung carcinoma was the most common (31 cases), followed by 16 cases of typical carcinoid, 5 cases of atypical carcinoid, and 1 case of combined SCLC. Both synaptophysin and chromogranin were positive in all the cases of typical carcinoid. Synaptophysin had better sensitivity than chromogranin in atypical carcinoid and small cell carcinoma. CD56 was positive in 8 out of 9 cases done. TTF-1 was negative in all the cases of typical carcinoid. The sensitivity of TTF-1 in small cell carcinoma was 85.19%. The mean Ki67 labeling index was 1.4%, 6.6%, and 65.6% in typical, atypical carcinoid, and small cell carcinomas, respectively. CONCLUSION: Synaptophysin was more sensitive than chromogranin, especially in atypical carcinoid and small cell carcinoma. TTF-1 along with high Ki67 differentiates small cell carcinoma from carcinoid.

Percutaneous core needle biopsy in the diagnosis of lung lesions: An experience on 280 consecutive cases from a university hospital in southern India.

CONTEXT: Percutaneous needle biopsy of lung (PCNBL) is advantageous over bronchoscopic biopsies to obtain adequate sample for peripheral lung lesions. OBJECTIVE: The objective was to evaluate the diagnostic yield of image-guided PCNBL in the diagnosis of lung lesions and to classify lung carcinomas as per the recently proposed International Association for the Study of Lung Cancer (IASLC)/American Thoracic Society/European Respiratory Society classification for small biopsies modified and adopted by the World Health Organization, 2015. MATERIALS AND METHODS: A total of 280 image-guided PCNBL were analyzed. The radiological findings and routine hematoxylin and eosin (H&E)-stained sections along with immunohistochemistry (IHC) were analyzed in all the cases. Molecular testing was done depending on tissue diagnosis and availability. RESULTS: Majority (81%) were diagnosed as malignant lesions, with adenocarcinoma (ADC) being the most common. More than 70% were diagnosed on H&E morphology alone, with thirty cases requiring IHC to categorize as ADC. Nearly 60% were categorized as squamous cell carcinoma on morphology alone and the rest required IHC. Though TTF1 showed higher sensitivity than napsin A, the latter is more specific. Both p63 and p40 were found to be highly sensitive for squamous cell carcinoma, but p40 was more specific than p63. Epidermal growth factor receptor could be evaluated on 94.4% of ADC samples, indicating good yield for molecular testing. CONCLUSION: PCNBL yields adequate sampling for tissue diagnosis and ancillary testing with minimal complications. The use of IHC markers reduces the number of non-small-cell not otherwise specified cases significantly.

Fine-Needle Aspiration Cytology in Preoperative Diagnosis of Bone Lesions: A Three-Year Study in a Tertiary Care Hospital.

AIM: The aim is to study the utility of fine-needle aspiration cytology (FNAC) in preoperative diagnosis of bone lesions in correlation with radiological and histopathological findings and to determine the spectrum and morphological features of various bone lesions on FNAC. MATERIALS AND METHODS: A total of 275 cases of bone lesions were studied by FNAC over a period of 3 years. 196 procedures were performed by pathologists, and 107 procedures were guided. Cytology findings were correlated with that of histology on cellblocks or on subsequent surgical biopsies. Immunohistochemistry (IHC) was done wherever necessary. RESULTS: Of the 275 cases, 49 lesions were inflammatory/infectious (granulomatous inflammation-19, nonspecific osteomyelitis-26, and fungal etiology-4), 16 were tumors of undefined neoplastic nature (aneurysmal bone cysts-12, and Langerhans cell histiocytosis-4), 99 lesions were benign (osteoblastoma-6, enchondroma-3, chondroblastoma-14, chondromyxoid fibroma-2, and Giant cell tumor-74), and 111 lesions were malignant (Osteosarcoma-36, chondrosarcoma-7, Ewing's sarcoma-28, lymphomas-4, plasma cell neoplasm-6, adamantinoma of long bone-1, and metastasis-29). Male to female ratio was 2:1, and the age range was between 4 and 84 years. Correlation with histology/cellblock was available in 149 tumors. Metastasis and round cell tumors such as Ewing's sarcoma and lymphoma were differentiated by IHC. The accuracy rate in cytological diagnosis of all bone lesions was 87.9% and for neoplasms was 93%. The discordance in the rest of the cases was due to inadequate cell material, and there were no false positives. CONCLUSION: We conclude that FNAC is a simple and accurate preoperative diagnostic technique for assessment of bone tumors.