Diagnostic utility of immunohistochemical marker prostein for evaluation of primary and metastatic prostatic carcinomas

Context: The diagnosis of prostatic adenocarcinoma on histopathology depends on architectural and cytomorphological features supported by immunohistochemistry (IHC). Though all the prostate markers show excellent specificity, the sensitivity and percentage positivity vary. Aims: In this study, we aim to study the expression of prostein in normal, benign, and malignant (primary and metastatic) lesions with particular emphasis on its utility in the differential diagnosis of poorly differentiated and metastatic prostatic adenocarcinoma along with a standard panel of IHC markers. Settings and Design: This was both a prospective and retrospective as well as descriptive and observational study. Subjects and Methods: All samples from patients with clinically suspected carcinoma prostate from both primary and metastatic sites from June 2015 to May 2016 were included in the study. Samples with difficulty in diagnosis on hematoxylin and eosin staining were subjected to a panel of IHC markers along with prostein. Statistical Analysis Used: Receiver operating curve analysis and Chi-square test. Results: Prostein showed a 100% sensitivity and specificity to identify normal prostatic epithelium, benign and premalignant lesions, and prostatic adenocarcinoma. Prostein showed a specificity of 100% in differentiating prostatic carcinoma from poorly differentiated urothelial carcinoma and in differentiating metastatic prostatic carcinoma from adenocarcinoma of nonprostatic origin. Conclusions: Prostein is a new and promising prostate-specific marker that showed slightly more sensitivity and specificity than prostate-specific antigen. Thus, adding prostein to the IHC panel will greatly improve the detection of poorly differentiated primary and metastatic lesions of the prostate.

Impact of sand organic carbon and climatic changes on the population density and morphometric characters of Emerita asiatica in the East Coast of Southern India

A population density of Emerita asiatica in relation to sand organic carbon in the Nemmeli beach, East coast, Kanchipuram District of Tamil Nadu was studied. Specimens were collected once in a fortnight from April 2017 to March 2018 by hand picking method in the intertidal region of Nemmeli beach. The total sand organic carbon level was recorded once in a fortnight. The population presented a smaller incidence of males in relation to females (48.66:51.34); however, in May 2017 an inverse pattern occurred (73:27). Ovigerous females were present in all samples with greater frequencies in October and November 2017 whereas, the highest juveniles were present in May and September 2017. The variation noted in a population of Emerita asiatica showed there is a relationship to sand organic carbon fluctuations; it can be determined that the sand organic carbon fluctuations have an influence on the population density of this species in Nemmeli beach. Hence, the rather stable sand organic carbon throughout the year and moderate changes in the sand may well be conducive to population biology of Emerita asiatica

Noninvasive follicular thyroid neoplasm with papillary-like nuclear features: A distinct clinicopathologic entity

Objective: The objective of this study is to retrospectively evaluate follicular variant of papillary thyroid carcinoma (FVPTC) and reclassify encapsulated FVPTC as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) according to the criteria proposed by The Endocrine Pathology Society working group in 2015 to correlate with outcome. Materials and Methods: Retrospective review of case records of all patients diagnosed as carcinoma of thyroid between 2015 and 2016 was done for the histologic subtype. Gross and microscopic features on resected specimens of FVPTC were reviewed and subtyped as invasive and encapsulated based on capsular/vascular invasion; the encapsulated forms were further studied for size, number, follicular architecture, nuclear features, presence of psammoma bodies, stromal fibrosis, necrosis, mitoses, and lymph node status. Results: Out of the 383 patients with thyroid carcinomas in the study period, 349 were PTC which included 106 FVPTC. Thirty-three patients fulfilled the criteria to be labeled as NIFTP. Total thyroidectomy was performed in 8 patients and hemithyroidectomy in 25 patients. Lymph node dissection along with total thyroidectomy was done in 3 and completion thyroidectomy following hemithyroidectomy was done in 9. There were 29 single and 4 multiple lesions with size varying from 0.2 to 7 cm including 5 lesions measuring <1 cm. The involvement was confined to one lobe in 31 and both lobes in 2 specimens. Patients are on follow-up with no recurrence till date. Conclusion: Thyroid carcinomas currently diagnosed as FVPTC should be evaluated for criteria of NIFTP to avoid overtreatment as they have an indolent behavior.

A clinicopathologic study of malignant melanoma based on cytomorphology.

CONTEXT: Melanoma accounts for 1‑3% of all malignancies. It is usually diagnosed as metastasis in the draining lymph nodes, that is inguinal lymph node. Due to paucity of cytological studies on melanoma in India, the present study was undertaken. AIM: To study the cytomorphology of malignant melanoma and to correlate the cytological diagnosis with histopathology and clinical details. SETTINGS AND DESIGN: Sixteen cytomorphological features were studied and analysed from the cases diagnosed as melanoma on cytology with histopathological correlation. MATERIALS AND METHODS: Thirty patients diagnosed with malignant melanoma on fine‑needle aspiration cytology (FNAC) were studied over a period of 10 years and compared by histopathology. Papanicolaou (Pap)‑ and May Grunwald Giemsa (MGG)‑stained smears were studied and analysed for the cytomorphological spectrum of melanoma. RESULTS: Among the 30 patients studied, males were 19 and females were 11 (M:F:1.7:1) with a mean age of 49.3 years. The commonest primary site was foot followed by maxilla and thigh. The most common site for metastasis was inguinal lymph node. All 30 cases had histopathological correlation. Pigmented melanophages (83%) was the predominant feature followed by presence of melanin pigment (77%) and pseudo‑inclusions (73%). Condensed chromatin was observed in the majority of the patients (53%). Smooth and irregular nuclear contours were seen in combination in 37% of the cases. A combination of nuclear placement, that is eccentric and central was observed as a predominant feature (53%). Spindle cell pattern was the predominant shape. Among cytoplasmic features, melanin granules and vacuoles were equally distributed (50%). Mixed pattern, that is singly scattered plasmacytoid cell pattern and cell clusters was the predominant cell architecture. CONCLUSION: A spectrum of cytomorphological features in correlation with clinical details leads to greater precision in diagnosis and helps to avoid pitfalls in diagnosing melanoma.

Spectrum of malignancies in human immunodeficiency virus – positive patients at a tertiary care centre in South India.

CONTEXT: India has a very large number of patients living with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome. Opportunistic infections in these patients are commonly encountered. However, malignancies in such patients also do occur. AIM: The aim was to study the spectrum of malignancies in HIV‑positive patients at a tertiary health care center. SETTINGS AND DESIGN: Retrospective study. MATERIALS AND METHODS: The cases were retrieved from pathology record files at our Institute from January 2003 to December 2008. The follow‑up was obtained from Medical oncology records. The morphology of each case was reviewed along with immunohistochemistry wherever done. RESULTS: There were 61 such cases (51 males, 10 females). The age range was 7–78 years with a median of 35 years. The clinical presentation varied according to the malignancy. The largest group was non‑Hodgkin lymphoma (18 nodal, 23 extra‑nodal). The others included carcinoma breast (4), chronic myeloid leukemia (3), Burkitt Leukemia (2), squamous cell carcinoma anal region (2), multiple myeloma (2) and one each of miscellaneous malignancies (7). CONCLUSION: Malignancies in HIV positive individual occurred in younger individuals. Non‑Hodgkin lymphomas, especially extra‑nodal lymphomas, were the most common malignancy. There were no cases of proven Kaposi’s sarcoma or invasive cervical carcinomas. There were two cases of multiple myeloma which are infrequently reported.

Correlation of p53 and KI-67 expression with grade and subtype of ependymoma.

Introduction: The morphological criteria for grading ependymomas were always felt subjective. Recently some studies have showed that Ki-67 and p53 immunolabeling are important prognostic markers in ependymomas. Materials and Methods: All the cases of ependymomas diagnosed from 2005 to 2010 were graded according to WHO classification for central nervous system (CNS) tumors 2007. Two tissue microarray (TMA) blocks were prepared. Immunohistochemical analysis with glial fibrillary acidic protein (GFAP), epithelial membrane antigen (EMA), Ki-67 and p53 was performed. The difference in expression of p53 and Ki-67 in various tumor grades and subtypes was evaluated using Student's t test. Results: There were 54 cases with a M: F ratio of 1.34 : 1, age ranging from 7 years to 65 years (mean 29.35 years). There were 33 intracranial and 21 spinal cases. There were 9 grade I ependymomas, 32 grade II ependymomas and 13 grade III ependymomas. GFAP immunopositivity was seen in all the cases and EMA was positive in 49% cases. The mean p53 indices were higher in grade III and grade II tumors (26.26% and 26.08%) as compared to subependymomas (7.25%). But these values did not show statistical significance (P = 0.2). The Ki-67 labeling index increased from grade I to grade III tumors. The difference was highly significant between grade II and grade III (0.5% vs. 2.75, P = 0.016). Conclusion: Ki-67 labeling index correlates with grade of ependymoma (P = 0.016). There is no correlation between p53 expression and grade of ependymomas.

Musa Paradisiaca flower extract improves carbohydrate metabolism in hepatic tissues of streptozotocin-induced experimental diabetes in rats

Objective: Musa Paradisiaca, commonly known as plantains have been traditionally used for various medicinal purposes. In the absence of an ideal drug to alleviate the primary and secondary complications of diabetes mellitus, search for novel drugs without side effects, preferably from plant origin continues. Recently, we have reported the presence of biologically active phytochemicals as well as the hypoglycemic activity of Musa paradisiaca tepals extract in STZ induced experimental diabetes in rats. The present study was aimed to evaluate the role of tepals, an integrated part of Musa paradisiaca flowers on carbohydrate metabolism in hepatic tissues of experimental diabetic rats. Methods: Streptozotocin-induced diabetic rats were treated with ethanolic extract of tepals at a concentration of 200mg/kg body weight/day for 30 days. The levels of fasting blood glucose, plasma insulin and glycosylated hemoglobin were estimated. The activities of key enzymes in carbohydrate metabolism such as glucokinase, pyruvate kinase, glucose-6-phosphatase, fructose-1, 6-bisphosphatase, glucose-6-phosphate dehydrogenase, glycogen synthase and glycogen phosphorylase in hepatic tissues were assayed. The levels of glycogen in hepatic tissues were also estimated. Results: Oral administration ofMusa paradisiaca tepals extract significantly improved the altered levels of blood glucose, plasma insulin, glycosylated hemoglobin and modulated the activities of carbohydrate metabolizing enzymes. The glycogen content in hepatic tissues was significantly increased in diabetic rats treated with tepals extract. Conclusions: The results of the present study clearly indicate that the tepals extract plays pivotal role to maintain normoglycemia in diabetes by modulating the activities of carbohydrate metabolic enzymes.

Heart rate variability during meditation in pranic healers.

Background: Heart rate variability (HRV) can be measured non-invasively in humans to study the physiological responses to various stimuli. The sympathetic branch increases heart rate and the parasympathetic branch decreases heart rate. HRV is an indicator of the dynamic interaction and balance between these two divisions of the Autonomic Nervous System. The pranic healers practice meditation which utilizes unification of body and mind. A reduced HRV is associated with increased risk of cardiac and overall mortality. Studies suggest a number of non-pharmacological techniques for the improvement of HRV. These techniques are believed to stabilize the ANS by modulating the parasympathetic nervous system and in turn improve HRV. The impact of these techniques on HRV and their effectiveness as therapeutic tools in patients with reduced HRV is to be determined.Methods: This study included 15 professional pranic healers as subjects in the age group 18-40 years. ECG was recorded during the phases, Series 1 (before meditation) and Series 3 (during meditation). HRV parameters were computed with the aid of suitable software and were analyzed. Results: The HRV parameters (Mean, Low frequency / LF, High frequency / HF, Total power, pNN50%) were compared. Power spectrum analysis showed distinctive change in frequency components. Low frequency component (LF; 0.04Hz to 0.15Hz), high frequency component (HF; 0.15Hz to 0.40Hz) and total power were significantly higher during the meditation phase (p = 0.05). pNN50% showed a trend towards decrease (though not significant) during the meditation phase (p = 0.066).Conclusions: The variance of the heart rate during meditation was significantly higher during meditation than before meditation for all subjects. These techniques are believed to stabilise the ANS by modulating the parasympathetic nervous system and in turn improve HRV.

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.

Salivary duct carcinoma: Correlation of morphologic features by fine needle aspiration cytology and histopathology.

Background: Salivary duct carcinoma (SDC) is a highly aggressive primary salivary gland neoplasm that resembles intraductal and infiltrating breast carcinoma. Objectives: To review cytomorphologic features of histology proven SDC and evaluate potential pitfalls in cytologic diagnosis. Materials and Methods: Fine needle aspiration cytology (FNAC) of five histologically proven SDCs were reviewed. Results: One patient was an elderly male (61 years), while the other four patients were younger, in their fourth decade (average age: 38 years). The initial cytologic diagnoses in two of the cases were poorly differentiated carcinoma with differential diagnosis of SDC and high grade mucoepidermoid carcinoma, while in the third case, a possibility of malignant mixed tumor was suggested. In fourth and fifth cases, the diagnosis was suggestive of pleomorphic adenoma with cystic change. The spectrum of cytologic changes included flat sheets and cohesive papillary and three-dimensional clusters. There was moderate to severe nuclear pleomorphism and atypia. Cribriform pattern and necrosis were occasionally identified. Prominent bright granular metachromatic stroma was seen in two of the cases interpreted as pleomorphic adenoma with cystic change and in the tumor reported as suggestive of malignant mixed tumor. The fifth case showed numerous cyst macrophages and apocrine cells with mild nuclear atypia. Conclusion: FNAC of SDC is difficult to interpret because of overlapping cytomorphologic features. Bland cytomorphologic features in some cases and several clinical pitfalls are demonstrated in our series.

Cerebral phaeohyphomycosis due to Cladophialophora bantiana.

Cladophialophora bantiana, a dematiaceous fungus and a member of the family Phaeohyphomycetes, is primarily a neurotropic fungus causing central nervous system (CNS) infection. We report a case of a well preserved, young adult male presenting with a capsuloganglionic abscess caused by C. bantiana, a rare entity. Diagnosis was made based on the mycology and histopathology findings of the aspirate from the abscess through a burr hole. The patient responded clinically to amphotericin B.

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.

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.

Pathobiology of fungal infections of the central nervous system with special reference to the Indian scenario.

Ubiquitously present fungi in the environment find a nidus in the human body and adopt its metabolic machinery to be in symbiosis or become pathogenic. Immunocompromised states like human immunodeficiency virus (HIV) / acquired immunodeficiency syndrome (AIDS), systemic neoplasia and organ transplantation have enhanced the frequency of fungal infections. High-risk behavior, IV drug abuse and air travel have led to the emergence of new fungal infections hitherto geographically localized. The pathology in the central nervous system (CNS) is dictated largely by the size of the fungus - the yeast forms, by virtue of their small size enter the microcirculation to cause meningitis and microabscesses, while hyphal forms invade the vasculature to manifest as large pale or hemorrhagic infarcts. The growth kinetics of fungi, the antigenic character of the capsule. the proteases secreted by the mycelial forms and the biochemical milieu in the host also determine clinical manifestations. A hospital-based analysis of the available information from India suggests that in the non-HIV patient population, hyphal forms like Aspergillosis and Zygomycosis are the most common pathogens, while yeast forms like Cryptococcus and Candida are the prime pathogens in cases of HIV/AIDS, the altered macrophage function acting in synergy with suppressed cell-mediated immunity. In Northeastern states, systemic infection by Penicillium marneffei is reported in association with HIV though CNS involvement is not recorded. Although fungal infections of the CNS are reported from various hospitals in India, studies are limited by non-availability of relevant microbiological studies and the reported prevalence data is biased by the surgical practices, availability of postmortem and microbiology and laboratory support. Detailed clinical and mycological investigations related to the interaction between the fungus and host environment is a fertile area of research to understand the basic pathogenetic mechanisms.

Pathogenesis and pathology of brain abscess.

Brain abscess continues to be a serious medical problem with increasing incidence despite advances in diagnostic and surgical methods, and advent of new antibiotics. This is due to increase in immune suppressed individuals, opportunistic pathogens and resistance to antibiotics. The morbidity, mortality and long term sequelae of brain abscess like cognitive impairment and poor neurological outcome are due to persistent release of proinflammatory mediators by activated microglia, astrocytes and infiltrating inflammatory cells, along with disruption of blood brain barrier. Anti-inflammatory drugs along with specific antimicrobial agents help in minimizing damage to the adjacent brain parenchyma. Identification of microorganisms in the aspirated material or the excised specimen help decide the optimal antimicrobial therapy. Prompt examination of smear and meticulous culture techniques to identify aerobes, anerobes, mycobacteria, actinomycetes, parasites and fungi are of utmost importance in choosing antibiotics. Histology complements culture and plays a key role especially in specific infections. Use of appropriate histochemical stains along with tissue reaction helps in diagnosis. The route of spread, the type and virulence of the organism, thickness of the capsule, location and number of abscesses in the brain, and immune status of the host are important determinants of outcome. Identification of microorganisms and insights into pathogenesis allow appropriate therapeutic interventions to improve outcome.

Infantile rhabdomyofibrosarcoma: a distinct variant or a missing link between fibrosarcoma and rhabdomyosarcoma?

Infantile rhabdomyofibrosarcoma (IRMFS) is a rare soft tissue tumour affecting infants and young children. It occupies an intermediate position between infantile fibrosarcoma and spindle cell rhabdomyosarcoma in its clinical presentation, behaviour, morphology, immunohistochemical and ultrastructural features. This case is reported here to reiterate its occurrence as tumour with distinct morphological immunohistochemical and clinical behavioral patterns.

Choriocarcinoma - a rare association with squamous cell carcinoma of esophagus.

Extragenital choriocarcinoma involving the gastrointestinal tract is rare. We report a 60-year-old woman with squamous cell carcinoma of esophagus with a choriocarcinomatous focus. She was palliated with chemotherapy and an endoprosthesis.

Extramedullary myeloid cell tumours--the NIMS experience.

Extramedullary myeloid cell tumours are rare clinical entities, which often pose diagnostic problems. From the pathology record files of Nizam's Institute of Medical Sciences, Hyderabad, 16 cases of EMCTs were traced, over a period of 14 years. The clinical details, follow-up were noted and morphology re-evaluated, and immunohistochemistry with LCA was performed. Of the 16 cases, the distribution was as follows--skin and subcutaneous nodules, lymph nodes, extradural masses presenting with cord compression and one case each with eyelid, orbital and breast masses. The problems in diagnosis are presented and a panel of immunohistochemical markers suggested for proper diagnosis and treatment.

Brain abscess due to Entamoeba histolytica.

A patient of cerebral amoebiasis due to Entamoeba histolytica with no evidence of disease elsewhere is described. He made a complete recovery after surgical excision of the abscess along with metronidazole therapy.

Medulloepithelioma: a case report.

Histological, immunohistochemical, and CT morphological features of medulloepithelioma, a rare embryonal tumor of primitive neuroepithelium, are described.