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.

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.

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.

Outcomes in Adult Acute Promyelocytic Leukemia: A Decade Experience.

BACKGROUND: Acute promyelocytic leukemia (APL), a distinct variant of acute myeloid leukemia (AML), accounts for 10% of AML cases. Over the past decade, APL has emerged from a highly fatal disease to a highly curable one. The published data on outcomes of APL from India are scant. The present study was designed to analyze the clinicopathologic features and outcomes in adult APL. MATERIALS AND METHODS: The present report is a single institutional, observational, retrospective study, and data of patients diagnosed with APL from 2006 to 2018 were analyzed. All patients with APL, diagnosed by morphology and confirmed by reverse transcriptase polymerase chain reaction (promyelocytic leukemia/retinoic acid receptor alpha) and over 18 years of age, were included in this study. SPSS software v25.1 was used for statistical analysis. RESULTS: A total of 1396 patients with AML were seen between January 2005 and June 2018, of which 190 (13.6%) had APL. Of these, 111 patients met the inclusion criteria and were analyzed. The median age at presentation was 33 years (range, 19-60 years). The median duration of symptoms before presentation was 15 days (range, 3-180 days). High risk, intermediate risk, and low risk were seen in 43.3%, 41.4%, and 15.3% of patients, respectively. At the end of induction chemotherapy, 88 (79%) patients achieved complete hematologic remission, and 23 (21%) succumbed during induction. The median time to attain complete hematologic remission was 30 days (range, 19-47 days). At a median follow-up of 34 months, the event-free survival and overall survival were 69.3% and 74.7%, respectively. On univariate analysis, bcr3 variant and high-risk category at presentation had significant impact on event-free survival (P = .029 and P = .003, respectively) and overall survival (P ≤ .001 and P = .007, respectively). On multivariate analysis, only high risk at presentation was significant for event-free survival (P = .04) and overall survival (P = .02). CONCLUSION: APL constituted one-tenth of patients with AML. The majority of patients were high risk at presentation. Sanz high risk category and bcr3 variant at presentation had significant impact on outcomes in APL.

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.

Clinicopathological Features and Outcomes in Primary Central Nervous System Lymphoma: A 10-year Experience.

CONTEXT: Primary central nervous system lymphoma (PCNSL) is a variant of extranodal lymphoma, accounting for 4% of primary central nervous system tumors. PCNSL was more common in immunocompetent individuals. International Extranodal Lymphoma Study Group (IELSG) scoring was used for prognostication. High-dose methotrexate regimens along with radiotherapy improved outcomes in PCNSL. AIMS: The aim of this study is to analyze the clinical and pathological features, progression-free survival (PFS), and overall survival (OS) in patients with PCNSL. MATERIALS AND METHODS: Data of patients with PCNSL between 2005 and 2016 were retrospectively analyzed. Outcome was analyzed in patients who received chemotherapy. GraphPad Prism software for Windows Version 6 was used to plot the Kaplan-Meier curves for PFS and OS. Log-rank test was used to calculate P values. P < 0.05 was considered as statistically significant. RESULTS: A total of 42 patients were available for analysis. Of these, 34 patients who received chemotherapy were evaluable for outcome parameters. The median age at presentation was 46 years (range, 10-75) with male-to-female ratio of 2.2:1. Only 2 (4.7%) patients were HIV positive. Diffuse large B-cell lymphoma (DLBCL) was the most common histology seen in 41 (97.6%) patients. Using IELSG risk scoring, scores of 8 (19%), 19 (45.2%), and 15 (35.8%) were stratified into low, intermediate, and high risk. The median PFS and OS were 11 months (range, 2-72) and 15.9 months (2.4-80.4), respectively. The median OS was 36.2 months (range, 8.8-72), 15.6 months (2-36), and 6.1 months (2.6-12.7) in low-, intermediate-, and high-risk groups, respectively, which was statistically significant (P = 0.0002). CONCLUSIONS: Immunocompetent patients with PCNSL outnumber immunocompromised patients. DLBCL was the most common histology, and IELSG risk stratification significantly predicts the outcome in PCNSL.

Cytomorphology and Histology Correlation of Rosai-Dorfman Disease: A 15-Year Study from a Tertiary Referral Centre in South India.

OBJECTIVES: Rosai-Dorfman disease (RDD) is an uncommon, benign histiocytic disorder of unknown etiology, typically presenting in young adulthood. We highlight the cytomorphology of RDD and correlate it with the histopathology. STUDY DESIGN: All cases diagnosed as RDD on fine-needle aspiration cytology between January 2001 and June 2015 were included. Clinical details were obtained from medical records. The cytology smears were reviewed along with the histopathology and immunohistochemistry, wherever available. RESULTS: The study included 10 cases ranging in age from 11 to 68 years (median 29). There was a male predominance with a male:female ratio of 1.5:1. The patients commonly presented with bilateral cervical lymphadenopathy. Extranodal involvement was seen in 2 cases in the nose and mandible, respectively. Of these 10 cases, 8 were later biopsied. The cytological features included numerous crescentic histiocytes, emperipolesis, reactive lymphocytes and plasma cells. A histological diagnosis of RDD was made in 7 out of 8 cases, and 1 was diagnosed as Hodgkin lymphoma. CONCLUSION: FNA represents an efficient, minimally invasive, cost-effective and reliable technique for the diagnosis of RDD and may obviate the need for further biopsy. However, the disease has close differential diagnoses, including Langerhans cell histiocytosis, granulomatous lesions, and Hodgkin lymphoma. Hence, it must be remembered that there can be pitfalls when the diagnosis is made by cytology alone.

Mucoepidermoid Carcinoma in Carcinosarcoma of the Lung - A Rare Combination.

Carcinosarcomas of the lung are uncommon neoplasms and are presently categorized along with sarcomatoid carcinomas in the WHO 2004 classification. Morphological recognition of individual components in a surgical specimen is usually straightforward. The respiratory epithelium is also a rare site for salivary gland type tumors. A 72-year-old lady who was investigated for an episode of hemoptysis was found to have a well circumscribed intraluminal tumor. The histo-morphological features were unique and composed of mucoepidermoid carcinoma and undifferentiated sarcoma. To the best of our knowledge, this unusual morphological combination has never been reported in literature.

Hodgkin lymphoma: A clinicopathological and immunophenotypic study.

INTRODUCTION: The diagnosis of Hodgkin lymphoma (HL) is defined in terms of its microscopic appearance (histology) and the expression of cell surface markers (immunophenotype). AIMS AND OBJECTIVES: This study aims to analyze the clinical features, histomorphology, and immunoprofile of over 200 patients of HL diagnosed over a period of 4 years at our institute and to determine relative frequency of various histological subtypes (based on WHO classification) in relation to age and sex distribution in this part of the country. MATERIALS AND METHODS: All HL cases diagnosed between January 2006 and December 2009 were retrieved from hospital records. The histopathology of both lymph node and bone marrow biopsy (where ever available) along with immunohistochemistry (CD15, CD30, CD20, and ALK) were reviewed. RESULTS: There was a bimodal age distribution. HL affected people a decade earlier than in the western population. The most common presenting complaint was cervical lymphadenopathy. Mixed cellularity was the most frequent subtype (67%), followed by nodular sclerosing subtype (23.5%). Group A (CD15+, CD30+, CD20-), which represents the archetypical immunophenotype of classical HL (CHL) was the most common type (60.6%). The number of CD15 negative CHL was 35.8% and CD20 positive CHL was 17.5%. CD15 negativity with CD20 positivity was seen in 5% CHL. One out of seven CD20 positive CHL patients showed relapse. CONCLUSION: In this paper, we have discussed in detail about various clinical and histopathological parameters of HL and their relative frequency in various histological subtypes. This paper is being presented as it is a rather large study from India taking into consideration the clinical, pathologic, and immunophenotypic profile of the patients.

Solid-pseudopapillary neoplasm of the pancreas: a clinicopathological and immunohistochemical study of 33 cases from a single institution in Southern India.

BACKGROUND: The clinicopathological and immunohistochemical data of solid-pseudopapillary neoplasm (SPN) from India are limited. Our objectives were to evaluate various histopathological parameters and immunomarkers to elucidate the best possible immunomarker combination that can accurately diagnose these tumors. MATERIALS AND METHODS: Clinicopathological features of 33 consecutive cases of SPN were retrospectively analyzed. Immunohistochemistry (IHC) was performed on a tissue microarray of 31 of these cases with antibodies to pan-cytokeratin (CK), vimentin, CD 10, E-cadherin, ß-catenin, estrogen receptor (ER), progesterone receptor (PR), chromogranin. RESULTS: Totally, 32 of 33 patients were females with a mean age of 26 years (range 12-62 years). Majority presented with abdominal pain (93.93%) and/or abdominal mass (48.48%). Location in pancreas included tail (14), head (7), body and tail (6), body (5) and neck (1). The mean diameter of the tumor was 8.6 cm (range 0.5-16 cm). Surgical exploration was done in all cases. On IHC, tumor cells were consistently positive for vimentin and negative for chromogranin (100%). CK was positive in 12 cases (38.7%), CD 10 showed perinuclear dot positivity in 14 (45.16%) cases and cytoplasmic positivity in 05 (16.12%) cases. All cases showed loss of membranous staining for both ß-catenin and E-cadherin with nuclear positivity in 90.32% and 70.16% cases, respectively. PR was positive in 20 (64.51%) cases, while all of them were negative for ER. CONCLUSION: Solid-pseudopapillary neoplasm is a tumor commonly affecting young females. Loss of membrane expression of ß-catenin and E-cadherin with nuclear positivity can be used confirm the diagnosis of SPN.

Response to imatinib mesylate in childhood chronic myeloid leukemia in chronic phase.

INTRODUCTION: Childhood chronic myeloid leukemia (CML) accounts for less than 3% of all childhood leukemias, hence, data on imatinib (IM) in adult CML patients has been largely extrapolated to children. We have analyzed our data to add to the existing literature. AIMS: Primary objective is to assess the progression-free survival (PFS). Secondary objective are cytogenetic response, overall survival (OS), and toxicities. SETTINGS AND DESIGN: This is a retrospective analysis from the case records from a single institution. MATERIALS AND METHODS: Institutional ethics committee approval was obtained. All the children diagnosed CML in chronic phase (CML-CP) aged less than 18 years registered between 2000 and 2009 were enrolled. All the patients were started on IM at 260 mg/m(2). STATISTICAL ANALYSIS: Kaplan-Meier curves were used to calculate the PFS and OS. RESULTS: There were 64 children with median age of 13 years (range, 1-18) with male predominance (male:female (M: F) - 1.85:1). Sixty-one patients (95.4%) achieved complete hematological response (CHR) at median of 8 weeks. Thirty-seven (57.8%) patients had evaluation of cytogenetic response and were subjects for outcome analysis. The median time to best cytogenetic response evaluation was 13 months (range, 4-52). Twenty-nine patients (78.3%) achieved complete cytogenetic response (CCyR). At a median follow-up of 36 months (range 5-75), 21 (56.8%) remained progression free and 35 (94.5%) are alive. Adverse events were tolerable. CONCLUSIONS: PFS at a median follow-up of 36 months is 56.8% and OS 94.5%.

Hepatosplenic T cell lymphoma: a rare case report.

Hepatosplenic T cell lymphoma is a rare form of extra nodal and systemic neoplasm derived from cytotoxic T cells and represents less than 1 % of all non Hodgkins lymphoma. Here we present a case of hepatosplenic T cell lymphoma in a 30 year old male who presented with icterus, pancytopenia and hepatosplenomegaly, highlighting the diagnostic conundrum and pointers towards an accurate diagnosis. Histologically the sinusoids of liver and splenic red pulp were infiltration by CD 3 positive neoplastic lymphoid cells. The pattern of marrow involvement was very subtle and diagnosis was difficult to establish without the help of immunohistochemistry. This case highlights the importance of considering hepatosplenic T cell lymphoma as differential diagnosis in the clinical setting of pancytopenia with hepatosplenomegaly to allow timely diagnosis of these aggressive neoplasms.

Report of chronic myeloid leukemia in chronic phase from Dr. Senthil Rajappa, 2002-2009.

Nizam's Institute of Medical Science is a premier institute of Hyderabad, established in 1980. The Medical Oncology Unit is the 1(st) comprehensive cancer center established for the state of Andhra Pradesh. The department has presented a data of total 201 patients with the median age of 32 at diagnosis. Among these 66 (33%) patients belonged to low Hasford risk group. Complete hematologic response was seen in 195 (97%) of patients. The progression free survival (PFS) was 77% for all patients while those who achieved complete cytogenetic response, PFS was 88% at 29 months.

Kinase domain mutations and responses to dose escalation in chronic myeloid leukemia resistant to standard dose imatinib mesylate.

Imatinib has shown unprecendeted success in the treatment of chronic myeloid leukemia (CML). However, over few years there have been reports regarding the primary and secondary resistance to Imatinib dampening the overall outcome in CML patients. In this study we have tried to assess the effect of dose escalation in patients resistant to standard dose of Imatinib and correlate it with presence of ABL kinase domain (KD) mutations. There were 90 patients resistant to imatinib, out which 29 patients were identified with KD mutations. The most common mutation was T315I , 9 out of 29 patients had it. 35 (38%) responded to dose escalation and had 67% event free survival (EFS) at estimated 2 years. Our results showed that dose escalation can over come resistance in some patients especially those in cytogenetic failure.

Primary extra nodal non Hodgkin lymphoma: a 5 year retrospective analysis.

BACKGROUND AND AIM: The incidence of extra nodal non Hodgkin lymphoma (ENL) is rising throughout the world. However, data regarding ENL as a group is limited. The aim was to study the epidemiological and histomorphological trends of primary ENL (pENL) in India. MATERIAL AND METHODS: The biopsy materials from sixty eight patients with pENL (45 male, 23 female, M:F= 1.9:1), diagnosed over a five year period (2005-2009), were analysed and pathologically reclassified according to the World Health Organization (WHO) classification, 2008 criteria. RESULTS: Primary extra nodal non Hodgkin lymphomas constituted 22.0% (68/308) of all non Hodgkin lymphomas (NHL). The mean age at presentation for pENL and primary nodal NHL was 43 years and 58 years, respectively with a male predilection (M: F=2:1). Central nervous system (CNS) constituted the most common extranodal site (20/68, 29.5%) followed by gastrointestinal tract (17/68, 25%), and nose/nasopharynx (8/68, 11.8%). Diffuse large B-cell lymphoma (DLBCL, not otherwise specified), extranodal marginal lymphoma of mucosa associated lymphoid tissue (MALT) type, and B cell NHL unclassified (U) were the three most common histological types observed. T-cell phenotype was rarely noted (4%). Follicular lymphomas and anaplastic large cell lymphoma, seen among nodal NHL, were absent at extra nodal sites. Majority (41/68, 60%) of the patients with pENL were immunocompetent and 55% were in stage I-II with favorable prognosis. CONCLUSION: Central nervous system was the most common site of ENL, followed by gastrointestinal tract. Majority of pENL occurred in immunocompetent hosts with a favorable prognosis.

Fungal infections as a contributing cause of death: an autopsy study.

CONTEXT: With the continuing rise in the number of immunocompromised patients, the incidence of invasive mycoses has increased. Various studies have reported the trends of fungal infections in autopsies. Because of limitations in antemortem clinical diagnosis owing to lack of sensitive diagnostic tools, information regarding frequency and pathogenesis of fungal infections is largely dependent on autopsy studies. AIM: To study the prevalence of fungal infections at autopsy spanning a period of 20 years and to document recent trends, prevalence of various fungi over decades along with underlying predisposing factors and pathological findings. SETTINGS AND DESIGN: Retrospective study. MATERIALS AND METHODS: All autopsies between 1988 and 2007 were reviewed and all cases showing fungal infections were analyzed. The clinical details and demographic data were retrieved from medical records. Representative sections from all organs were stained with hematoxylin and eosin stain and special stains including Gomori's silver methenamine (GMS) and periodic acid Schiff (PAS). Culture details were noted, wherever available. RESULTS: A total of 401 autopsies were performed during the study period. Fungal infections were identified in 35 (8.7%) of these cases. Leukemia was the commonest risk factor. The commonest pathogen in the present study was Aspergillus sp. The commonest single organ involved was brain (n = 18). Culture positivity was seen in 23.8% cases. CONCLUSION: The study highlights various predisposing factors and organisms in autopsy series. Existing diagnostic modalities are not sensitive to ensure antemortem diagnosis of fungal infections.