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.

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.

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.

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.

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.

Vasculitic Neuropathy: A Retrospective Analysis of Nerve Biopsies and Clinical Features from a Single Tertiary Care Center.

OBJECTIVE: Vasculitic neuropathy can be either restricted to the peripheral nerves or associated with systemic involvement of other organs. The objective of this study was to analyze the nerve biopsies reported as "vasculitic neuropathy" with clinical features. MATERIALS AND METHODS: All cases diagnosed with vasculitic neuropathy were retrospectively analyzed and categorized as systemic vasculitis and nonsystemic vasculitic neuropathy based on the clinical features. The histological features were further evaluated and classified according to the Peripheral Nerve Society Guidelines. RESULTS: Of the 126 cases, there were 65 nonsystemic vasculitis, 45 secondary systemic vasculitis, and 16 primary systemic vasculitis. Definite vasculitis was more common in the systemic vasculitis group. The epineurial vessels were predominantly involved with chronic axonal changes. CONCLUSION: The sensitivity of definite vasculitis on nerve biopsy was 54.76%. The sensitivity increases when the diagnostic criteria of definite and probable vasculitis were applied taking into account perivascular inflammation accompanied by vascular changes and axonopathy.

Juvenile idiopathic inflammatory myopathies: A clinicopathological study with emphasis on muscle histology.

BACKGROUND: Juvenile idiopathic inflammatory myopathies (JIIM) are rare and heterogeneous. Subtype identification is important for treatment. MATERIALS AND METHODS: Patients below 18 years diagnosed as idiopathic inflammatory myopathy (IIM) according to the Bohan and Peter criteria between January 2010 and May 2015 were evaluated with muscle biopsy in the four domains: muscle fiber, inflammation, connective tissue, and vascular, with basic panel of histochemical stains as per recommendations of the European Neuromuscular center (ENMC) workshop 2015. Immunohistochemistry with CD 31 was done to assess capillary density. RESULTS: JIIM constituted 15.25% of IIM with juvenile dermatomyositis (JDM) being the most common subgroup (24/27) followed by juvenile overlap myositis (JOM) (3/27) in association with systemic lupus erythematosus (2) and systemic sclerosis (1). Muscle biopsy in JDM was characterized by perifascicular atrophy, necrosis, degeneration, and regeneration in all and the other features included perivascular inflammation (21), lymphoid aggregates (2), mitochondrial abnormalities (9), sarcoplasmic vacuoles (6), capillary dropout (5), capillary dilatation (6), and perimysial fibrosis (14). JOM was characterized by auto-antibodies and perivascular inflammation. CONCLUSION: JIIMs were rare and JDM was the most common subtype. Muscle biopsy evaluation as per ENMC criteria characterized the subgroups.

Pericardial mesothelioma presenting as chronic constrictive pericarditis. A series of three cases from a single institution.

Pericardial mesotheliomas are rare tumors which often present with features of constrictive pericarditis. We present clinical, imaging, histological, and immunohistochemical findings of three cases presenting with chronic constrictive pericarditis. Two of these cases were initially treated as tuberculous pericarditis. Histologically, all the three cases were of an epithelioid type and showed positivity for more than one mesothelial markers. Two patients had a fatal outcome, and one was lost to follow-up.

Histological transformation of adenocarcinoma to small cell carcinoma lung as a rare mechanism of resistance to epidermal growth factor receptor-tyrosine kinase inhibitors: Report of a case with review of literature.

A subset of non-small cell lung carcinoma (NSCC) harbor active mutations of epidermal growth factor receptor (EGFR). In these, EGFR tyrosine kinase inhibitors (EGFR-TKIs) are recommended as the first-line treatment. Though drug resistance is inevitable, histological transformation to small cell lung carcinoma (SCLC) is a rare mechanism for acquired resistance. Here we report one such rare case of histological transformation of pulmonary adenocarcinoma to small cell lung carcinoma in 46 year old male treated with Gefitinib.

Malignant mesothelioma: A histomorphological and immunohistochemical study of 24 cases from a tertiary care hospital in Southern India.

BACKGROUND: Malignant mesotheliomas are histologically heterogeneous neoplasms. Definite diagnosis requires a varied panel of immunohistochemical (IHC) markers to differentiate these from histological mimics. Only a few case series have been reported in the Indian literature where mesotheliomas have been analyzed on routine histology and IHC. AIM: To evaluate the histological features of malignant mesothelioma and to elucidate the best possible immunomarker combination useful in different scenarios. MATERIALS AND METHODS: A total of 24 cases of malignant mesotheliomas of different sites encountered over a 6-year period were retrospectively analyzed with regard to their histomorphology and IHC findings. RESULTS: The pleura was the most common site of involvement (16 cases) followed by peritoneum (5 cases) and pericardium (3 cases). Epithelioid mesothelioma was the most common histological type (15 cases, 62.5%) followed by sarcomatoid (5 cases, 20.84%), deciduoid (2 cases, 8.34%), and 1 case each of desmoplastic and biphasic mesothelioma. Among the mesothelial markers, WT1 was positive in 17 of 20 (85%) cases and calretinin was positive in 20 of 21 (95.23%) cases. D2-40 and CK5/6 were positive in all cases where they were studied. Adenocarcinoma markers TTF-1, napsin A, and CEA had very high negative predictive value in ruling out mesothelioma. CONCLUSION: The differential diagnosis of mesotheliomas varies with histological type and tumor location. Judicious use of various combinations of IHC markers in different situation has been highlighted in this article.

Clinicopathologic study of neuroendocrine tumors of gastroenteropancreatic tract: a single institutional experience.

BACKGROUND: The gastroenteropancreatic neuroendocrine tumors (GEPNET) have a characteristic histologic appearance unrelated of the exact site of origin. However the behavior of these tumors are different in each of these sites. In this article we study the clinicopathological features of GEPNET. These tumors were classified and graded according to WHO 2010 criteria. The immunohistochemical (IHC) features were evaluated and the grade of the tumor was correlated with Ki67. METHODS: A total of 40 cases of GEPNET diagnosed on biopsies as well as resected specimens were analyzed from January 2012 to June 2015. RESULTS: There were 28 resected specimens and 12 biopsies. Majority of the gastric neuroendocrine tumors (NET) showed classic morphology of cells arranged in islands. There were 3 cases each of grade 1 and grade 2 and one was diagnosed as mixed adenoneuroendocrine carcinoma (MANEC). All the duodenal NET were well differentiated (grade 1). There were 8 cases in colon and rectum, of which 4 cases were grade 3 and 3 cases were grade 2. Majority of the pancreatic tumors were grade 1. The mean mitotic count along with ki67 had good correlation in NET of stomach, duodenum colon and rectum. CONCLUSIONS: The most common site was small intestine followed by pancreas. Majority of the tumors were NET G1. Tumors from colorectal region were mostly NEC G3. There was a strong correlation by spearman correlation analysis between Ki67 and mitotic count and moderate correlation between ki67 and tumor grade as well as mitotic rate and tumor grade. Ki67 was helpful in grading these tumors.

Pure neuritic leprosy: Resolving diagnostic issues in acid fast bacilli (AFB)-negative nerve biopsies: A single centre experience from South India.

BACKGROUND AND PURPOSE: Demonstration of lepra bacilli is essential for definite or unequivocal diagnosis of pure neuritic leprosy (PNL) on nerve biopsy. However, nerves always do not show bacilli owing to the changes of previous therapy or due to low bacillary load in tuberculoid forms. In absence of granuloma or lepra bacilli, other morphologic changes in endoneurium and perineurium can be of help in making a probable diagnosis of PNL and treating the patient with multidrug therapy. MATERIALS AND METHODS: Forty-six biopsies of PNL were retrospectively reviewed and histologic findings were compared with 25 biopsies of non leprosy neuropathies (NLN) including vasculitic neuropathy and chronic inflammatory demyelinating polyneuropathy (CIDP). The distribution of endoneurial infiltrate and fibrosis, perineurial thickening, and myelin abnormalities were compared between PNL and NLN biopsies and analyzed by Chi-square test. RESULTS: Out of 46 PNL casses, 24 (52.17 %) biopsies were negative for acid fast bacilli (AFB). In these cases, the features which favor a diagnosis of AFB-negative PNL were endoneurial infiltrate (51.1%), endoneurial fibrosis (54.2%), perineurial thickening (70.8%), and reduced number of myelinated nerve fibers (75%). INTERPRETATION AND CONCLUSION: Nerve biopsy is an efficient tool to diagnose PNL and differentiate it from other causes of NLN. In absence of AFB, the diagnosis of PNL is challenging. In this article, we have satisfactorily evaluated the various hisopthological features and found that endoneurial inflammation, dense fibrosis, and reduction in the number of myelinated nerve fibers are strong supportive indicators of PNL regardless of AFB positivity.