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.

Molecular and Histopathological Characterization of Patients Presenting with the Duchenne Muscular Dystrophy Phenotype in a Tertiary Care Center in Southern India

Objective: To study the histopathological characteristics and mutation spectrum of patientspresenting with the Duchenne muscular dystrophy (DMD) phenotype. Methods: This wasa descriptive study conducted over a period of 8 years. Multiplex ligation-dependent probeamplification (MLPA) was done in patients presenting with the DMD phenotype. If MLPA wasnegative, patients were offered muscle biopsy for histopathological studies and/or nextgeneration sequencing (NGS) based multigene panel testing for muscular dystrophies.Results: Of the 510 patients included, mutation in the DMD gene was detected by MLPA in372 (72.9%), of whom 342 (67.1%) had exonic deletions and 30 (5.9%) had exonicduplications. Exons 45-55 were most commonly involved in large deletions and exons 1-10were the commonest exons involved in duplications. In the MLPA-negative cohort, 27proceeded for muscle biopsy. NGS was done in 14 patients, 10 of whom had pathogenicmutations in the DMD gene, 3 were non dystrophinopathies and no pathogenic variant couldbe identified in one patient. Conclusions: For patients presenting with the DMD phenotype,MLPA of the DMD gene has a high diagnostic rate of about 73%, and non-dystrophinopathies may constitute a small but significant proportion.

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, β-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 β-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 β-catenin and E-cadherin with nuclear positivity can be used confi rm the diagnosis of SPN.

Diagnostic accuracy of morphologic identification of filamentous fungi in paraffin embedded tissue sections: Correlation of histological and culture diagnosis.

Aims and Objectives: The aim was to investigate the correlation between histological and culture diagnosis of fi lamentous fungi. Materials and Methods: Tissue sections from biopsy samples stained with Hematoxylin and Eosin and special stains from samples of chronic invasive/noninvasive sinusitis and intracranial space occupying lesions during 2005-2011 diagnosed to have infection due to fi lamentous fungi were reviewed. The histopathology and culture diagnoses were analyzed for correlation and discrepancy. Results: There were 125 samples positive for fi lamentous fungi on biopsy. Of these 76 (60.8%) were submitted for culture and fungi grew in 30 (39.97%) samples. There was a positive correlation between histological and culture diagnosis in 25 (83.33%) samples that included Aspergillus species (16/19), Zygomycetes species (8/10) and dematiaceous fungi (1/1). The negative yield of fungi was more in Zygomycetes species (20/30) when compared to Aspergillus species (25/44). There was a discrepancy in diagnosis in 5/30 (16.67%) samples which included probable dual infection in two, and dematiaceous fungi being interpreted as Aspergillus species in three samples. Conclusion: Histopathology plays a major role in the diagnosis of infection due to fi lamentous fungi, especially when cultures are not submitted or negative. The discrepancy between histological and culture diagnosis was either due to dematiaceous fungi being interpreted as Aspergillus species or probable dual infection.

Clear cell papillary cholangiocarcinoma: A case report with review of literature.

Clear cell papillary cholangiocarcinoma is a rare variant of intrahepatic cholangiocarcinoma with only nine reported cases in the literature. This tumor needs to be differentiated from clear cell variant of hepatocellular carcinoma and other metastatic clear cell carcinomas. This tumor is known to have better prognosis compared to conventional intrahepatic cholangiocarcinoma. Hence, it is important to correctly diagnose this entity and differentiate it from other histologic mimics. We describe clinical, histopathological, and immunohistochemical fi ndings of one such rare case in a 66-year-old gentleman who was incidentally detected to have an intrahepatic tumor at routine ultrasound examination.A review of all the similar cases reported so far in the literature is also provided.

Isolated malakoplakia of inguinal lymph node: A rare case report.

Malakoplakia is rare chronic infl ammatory disorder which commonly affects urinary tract. Though it has been reported in several sites outside the urinary tract, isolated lympnode involvement is extremely uncommon. Herein we present a case of 20 year old male with right inguinal lymphnodal mass. Histological fi ndings including special stains and immunohistochemistry fi ndings were characteristic of malakoplakia. This case is being presented to create awareness for inclusion of this entity in the differential diagnosis of lymphadenopathy.

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 per-iodic 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.

Light chain immunofluorescence in various nephropathies.

Context: Light chain immunofluoresence (IF) in renal biopsy is routinely used in the diagnosis of light chain deposition disease (LCDD), amyloidosis and cast nephropathy. Light chain predominance has also been reported in certain glomerulopathies like IgA nephropathy. However, pathogenesis of this pattern of deposition in various glomerulopathies is uncertain. Aim: To discuss the pathogenesis and utility of light chain IF in nephropathies. Setting and Design: Retrospective study. Materials and Methods: The pattern of light chain IF and light microscopic diagnosis in 306 cases of various nephropathies was reviewed. Direct IF was done in all these cases with commercial fluorescence (Fluoresciene Isothiocynate ) conjugated polyclonal rabbit anti-human antisera against IgM, IgG, IgA, C3, C1q, kappa and lambda light chains. Results: Light chain deposits were seen in 240 (78.43%) cases. In IgA nephropathy, lupus nephritis and post-infectious glomerulonephritis (PIGN), lambda positivity was more as compared to kappa. Light chain deposits in LCDD and membranous nephropathy were more kappa type. The IF pattern in amyloidosis was not consistent. Conclusion: The pathogenesis of light chain predominance in glomerulopathies is not clear and it depends on isoelectric point and size of the immune complex. Light chain IF should be performed routinely in all the renal biopsies.

Morphologic evaluation of renal function using semi-quantitative method in primary nonproliferative glomerular diseases.

Context: Fibrosis is universally accepted as a poor prognostic finding in renal pathology. Semi-quantitative assessment is widely used for prognostication in pathology. Aims: We propose a semi-quantitative method to prognosticate primary nonproliferative glomerular diseases. Settings and Design: A semi-quantitative method based on Banff schema, 97 classification has been modified to suit the requirements. Glomerular, tubulointerstitial, and vascular compartments were scored independently, and the scores were totaled to obtain total scores. Materials and Methods: Seventy-six renal biopsies were assessed by semi-quantitative scores and the individual compartmental and total scores were correlated with serum creatinine levels. Follow-up was available in 24 cases. Statistical Analysis: Pearson correlation coefficient, two-tailed t test, to determine the P value. Results: P values were significant for the total scores as well as individual compartments. There is a linear correlation between the scores and serum creatinine levels. A total score of ≥5 was significant. Conclusions: The semi-quantitative scoring system based on modified Banff schema, 1997 is useful in prognosticating renal biopsies in primary nonproliferative glomerular diseases.

Major histocompatibility complex class I expression can be used as a diagnostic tool to differentiate idiopathic inflammatory myopathies from dystrophies.

Aim: Utility of major histocompatibility complex (MHC) Class I antigen immunostaining was studied to differentiate idiopathic inflammatory myopathies from dystrophies. Materials and Methods: Forty muscle biopsies including seven dermatomyositis (DM), six polymyositis (PM), two sporadic inclusion body myositis (sIBM), 20 dystrophies (one Duchenne, three Becker's, four alpha, one gamma sarcoglycanopathy, nine limb girdle, one myotonic and one fascioscapulohumeral muscular dystrophy) and five controls were stained with antibody for MHC Class I antigen (Novocastra clone W6/32 HL 1:100 dilution). Results: Polymyositis and sIBM showed MHC class I antigen positivity along sarcolemma of single and small groups of muscle fibers. The regenerating fibers in the perifascicular area in DM showed intense cytoplasmic positivity of MHC class I antigen. Muscle fibers in all dystrophies except regenerating fibers and control normal muscle were negative for MHC. Capillaries and lymphocytes were positive controls. There were no false positives in the study. Conclusion: MHC Class I immunostaining can be used as a complementary diagnostic tool for the diagnosis of idiopathic inflammatory myopathies.

Lipid storage myopathies with unusual clinical manifestations.

We describe the clinical presentation, course and pathologic findings found in three adult patients with lipid storage myopathy. Excessive lipid storage was found in Type 1 fibers of muscle. Clinical improvement on oral levo-carnitine therapy suggests the possibility of carnitine deficiency as the most likely etiology in two of the patients and one had mitochondrial myopathy confirmed on genetic analysis.

Cerebral Aspergillus arteritis with bland infarcts: A report of two patients with poor outcome.

Two patients with cerebrovascular aspergillosis, in the form of arteritis, thrombosis and bland infarcts are reported. One patient had systemic lupus erythematosus with disseminated aspergillosis in lungs, kidneys and brain. The other patient was immunocompetent and had sphenoid sinusitis. Both the patients were diagnosed at autopsy only, despite extensive imaging and laboratory studies. High index of clinical suspicion and early aggressive antifungal therapy are required since definite diagnostic modalities are not available.

Leukemia as a second malignancy.

To study the occurrence of leukemia as a second malignancy following various primary solid and hematological malignancies. Total 11 cases of leukemia presenting as a second malignancy were studied over a period of 15 years from 1990 to 2005. The primary malignancies included carcinoma breast (4), multiple myeloma (3) and one each of Hodgkin's lymphoma, mediastinal germ cell tumor, papillary carcinoma thyroid and myxopapillary ependymoma. Ten patients had received chemotherapy with combination radiotherapy in six patients. The commonest type of leukemia was AML-M2. The cyogenetic test results were available in three cases. The secondary leukemia showed aggressive behaviour and all patients on follow-up died within a period of one month. The risk benefit ratio of chemotherapy and radiotherapy should be considered before starting the patients on treatment. A high degree of suspicion and follow up with hematological parameters is required for therapy related complications.