Pseudobasophilia as a Screening Tool in Dengue: A Single Center Study.

Objectives Proper serological testing for the definite diagnosis of dengue is costly and may not be easily available in a resource-limited setting. Hematological parameters can help in the early identification of dengue cases. This study aims to evaluate the occurrence and utility of pseudobasophilia in identifying dengue-affected patients. Materials and Methods This retrospective cross-sectional study included 1,304 dengue cases confirmed by serology and 1,044 dengue serology negative acute febrile illness cases as controls. Complete blood count (CBC) values of the first EDTA (ethylenediamine tetraacetic acid) blood sample from automated hematology analyzers were reviewed. The hematological parameters in the dengue and control groups were compared and the variation of these parameters with the day of fever was also analyzed. Statistical Analysis Mann-Whitney's test, Kruskal-Wallis test, and Fisher's exact test were used for statistical analysis. A p -value < 0.05 was considered statistically significant for all tests. Results There was a statistically significant variation between dengue cases and controls for hematocrit, platelet count, mean platelet volume, total white blood cell count, and absolute basophil count. The dengue group had a higher hematocrit from day 2 to day 10, platelet count ≤ 100,000/µL from day 4 to day 9, higher mean platelet volume from day 2 to day 7, leucopenia from day 3 to day 5, and higher absolute basophil count from day 2 to day 10. Interestingly, pseudobasophilia was seen in 533 (40.87%) of dengue cases and only 3 (0.28%) of the controls. Pseudobasophilia was also observed to have an increasing trend to the day of fever. Conclusion Pseudobasophilia along with other CBC parameters is useful and cost effective for the early identification of dengue. This can prompt early investigations and supportive treatment leading to improved clinical outcomes.

Histopathological changes in the right atrial appendages triggering atrial fibrillation: A tertiary care center study.

BACKGROUND: Atrial fibrillation(AF) is as an abnormal irregular rhythm with chaotic generation of electrical signals in the atria of the heart. Various studies in the West have proved that atrial substrates, like isolated atrial amyloidosis can trigger the development of atrial fibrillation. In India, these structural changes have been analyzed on autopsied hearts. AIM: To determine the role of Atrial Amyloid as a substrate for Atrial fibrillation in ante mortem hearts. METHODS AND RESULTS: Atrial appendages were obtained from seventy five patients undergoing open heart surgery at a tertiary care hospital in south India. They were stained with Hematoxylin &Eosin, Masson's Trichrome and Congo red stains and were examined for myocarditis, fibrosis and amyloidosis, respectively. 30 (40%) patients were in AF. Amyloid deposits were seen in 3 cases. All the three were in AF and had undergone mitral valve replacement (MVR) (P<0.05). 2 out of the 3 amyloid-positive cases showed active myocarditis and severe scarring but there was no statistically significant correlation between these factors. CONCLUSION: Amyloid and myocarditis, independently act as an arrythmogenic substrates in the development of atrial fibrillation and are also increasingly associated with female gender and MVR. We hypothesize that the amyloid deposits are due to isolated atrial amyloidosis as they were seen only in young individuals. Some patients in sinus rhythm (SR) had large left atria and myocarditis and probably are at a higher risk for developing AF. Hence, follow-up of these patients is required for prevention of severe organ damage and timely therapeutic intervention.

Diagnostic utility of bone marrow examination in evaluation of fever: a descriptive study on 98 immunocompetent adults from a tertiary care institute in south India.

Five-year clinico-laboratory data from 99 (one HIV seropositive) adults (mean age = 41.3 ± 20.4 years) who underwent bone marrow examination for fever persisting for ≥ 1 week were analysed and correlated with microbiological characteristics. Infections, reactive marrow changes and haematolymphoid malignancies were most commonly associated with fever. A high concordance rate of 71% was noted between aspiration and trephine biopsies. Bone marrow granulomas (BMG) were seen exclusively on sections and were most commonly of tubercular and typhoidal in origin (two Salmonella Typhi, one Salmonella Paratyphi A). The common aetiologies associated with fever and cytopenia(s) were BMG, acute leukaemia and haemophagocytic lymphohistiocytosis (HLH; n = 3). The yield from bone marrow culture was inferior compared to other body fluids. In conclusion, bone marrow histology is superior to smears in the evaluation of prolonged fever. Marrow culture may not be useful in immunocompetent individuals other than if Salmonellosis is suspected.

Humanities in medicine: experience at Pondicherry Institute of Medical Sciences, India.

A few institutes in India have started a programme of Humanities in Medicine (HiM) on a small scale. In 2014, the Pondicherry Institute of Medical Sciences (PIMS) decided to begin an HiM programme for undergraduate students and this has been conducted successfully for the last three years. The major strengths of the programme have been its formal integration within the curriculum and the contributions of a large number of enthusiastic, talented and motivated faculty. In this report, we wish to trace the evolution and implementation of the HiM programme in our institution.

Validating Micronucleus Score in Effusion Fluids.

BACKGROUND: Identifying malignant cells in effusion fluid is vital in staging and management of cancers. Differentiating reactive mesothelial cells from malignant cells in effusion fluid is a challenging task and there is an ongoing need for simpler and cost effective tool to aid the diagnosis. Micronucleus is an additional smaller nucleus in the cytoplasm, formed by chromosomes or chromosomal fragments formed during cell division. AIMS: The aim of this study was to assess the significance of micronucleated cell in effusion fluids to distinguish adenocarcinomatous from reactive mesothelial effusions. MATERIALS AND METHODS: Thirty cases of unequivocal malignant effusion fluids and 30 benign cases with reactive mesothelial cells as control were studied. Number of microucleated cells present per1000 well-preserved cells in Leishman-stained smears were counted. RESULTS: Mean (±SD) micronucleated score in malignant and benign effusions were 15.77 ± 9.78 and 1.87 ± 1.78, respectively. The median scores were 13 and 2, respectively. Mann-Whitney test showed that this difference was statistically significant (P < 0.001). This study revealed that there was a significant difference in micronucleus scoring between benign and malignant effusions. CONCLUSIONS: Micronucleus score can be used as an additional biomarker in the interpretation of routinely stained cytosmears.

Cutaneous Hyperpigmentation in Megaloblastic Anemia: a Five Year Retrospective Review.

BACKGROUND: Cutaneous hyperpigmentation is an often overlooked clinical sign in megaloblastic anemia (MA) which has been sporadically reported in the literature. METHODS: We describe the bone marrow (BM) changes and clinicolaboratory characteristics of 25 of 198 adult cases (>16 years) with cutaneous hyperpigmentation who underwent BM evaluation for cytopenia (s). RESULTS: Twenty-one of 25 cases (84%) had MA, while MA without hyperpigmentation occurred only in 12 of remainder 173 cases (P<0.001). Knuckle pad hyperpigmentation (KP) was noted in 16 (64%) cases; whereas 9 (36%) had diffuse brownish black discoloration (DP) of the palms and/or soles. Eighteen of 25 (72%) cases had pancytopenia (13 with KP) and 7 of 25 (28%) had bicytopenia (3 with KP). In addition, five cases (20%) presented with pyrexia. Of the 17 cases where data available, eleven were B12 deficient [<190 pg/ml; eight had severe deficiency (<100 pg/ml); ref.; 190-800pg/ml], while 4 had pure folate deficiency (< 4.0 ng/ml; ref.; 4-20ng/ml); and remainder 2 had combined B12 and folate deficiency. Compared to those with diffuse pigmentation; KP group had lower Hb (69.6 ± 24.2 vs. 86.3 ± 33.9 g/L), higher MCV (106.1 ±12.6 vs. 99.2 ± 7.6 fL), lower platelet count (50.9 ± 29.3 vs. 69.6 ± 36.5 × 10(9)/L), and lower median B12 [100.0 (30.0 - 822.0) vs. 316.0 (142.0 - 1617.3) pg/ml] (P>0.05). In six cases where follow-up data were available, there was a significant reversal of hyperpigmentation at 12 weeks following parenteral cobalamin therapy. In all five cases with pyrexia, fever subsided after 24 to 72 hours following administration of parenteral cobalamin therapy. CONCLUSION: Cutaneous hyperpigmentation and cytopenia (s) are strongly associated with megaloblastic anemia. Knuckle pad hyperpigmentation is much more frequent than diffuse pigmentation of the palms and/or soles in such patents. A nonsignificant trend towards a greater degree of MA was found in cases with pigmentation of the knuckles.

Ovarian Leiomyoma Along with Uterine Leiomyomata: A Common Tumour at an Uncommon Site.

Ovarian leiomyoma is one of the rarest benign tumours of the ovary, mostly seen in women of reproductive age group. Here we report a case of ovarian leiomyoma as an incidental finding in a patient of 38-year-old woman with uterine leiomyomata. Peroperatively, her left ovary appeared bulky & she underwent total abdominal hysterectomy with left salpingo-oophorectomy. Macroscopically, in addition to uterine leiomyomata, a grey-white solid mass was seen entirely within the ovary without any capsular breach. Microscopically, the ovarian mass resembled its uterine counterpart without any evidence of atypia or necrosis. Masson trichrome stain & immunohistochemistry for desmin positivity confirmed the smooth muscle origin of the tumour cells. Despite its rarity, ovarian leiomyoma has to be considered as one of the differential diagnosis of ovarian spindle cell tumours. In difficult cases, immunohistochemistry aids the diagnosis.

Hemophagocytic lymphohistiocytosis: An unusual complication in disseminated Mycobacterium tuberculosis.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is an uncommon, potentially fatal, hyperinflammatory syndrome that may rarely complicate the clinical course of disseminated Mycobacterium tuberculosis (MTB). The clinical course of tuberculosis-associated HLH (TB-HLH) has been reported to be unpredictable. MATERIALS AND METHODS: Here we describe the clinicopathological features, laboratory parameters, management, and outcome data of a patient who satisfied the 2004 diagnostic criteria for HLH secondary to disseminated MTB; we also do a systematic review of the international literature on TB-HLH. The literature review (January 1975-March 2014) found that HLH complicated the clinical course of 63 tuberculosis patients (41 males, 22 females, mean age = 45 ± 23.5 years) with a high mortality rate of 49% (31/63 died). The mean serum ferritin level (n = 44/63) was 5963 ng/mL (range 500-38,539 ng/mL); and a higher proportion (54.2%) of patients had pancytopenia at presentation. On univariate analysis (n = 53/63), age >30 years [hazard ratio (HR): 2.79, 95% confidence interval (CI):1.03-7.56, P = 0.03], presence of comorbidities (HR 4.59, CI: 1.08-19.52, P = 0.04), marked hemophagocytosis in bone marrow (HR: 2.65, CI: 1.16-6.05, P = 0.02), and nonusage/delayed usage of antitubercular therapy (ATT) (HR: 3.44, CI: 1.51-7.87, P = 0.003) were associated with decreased survival, though none of these parameters attained statistical significance (P > 0.05) in multivariate analysis. Usage of corticosteroids and/or immunomodulator drugs (HR 1.00, CI: 0.66-3.22, P = 0.35) did not alter the outcome in these patients. CONCLUSION: HLH should be considered as a differential diagnosis in patients with tuberculosis who present with cytopenias, organomegaly, and coagulopathy. Strong clinical suspicion and early usage of ATT might be useful in reducing the morbidity and mortality. The utility of immunosuppressive/immunomodulator therapy lacks general concensus among treating physicians, and warrants further studies.

Subcutaneous Fungal Cyst Masquerading as Benign Lesions - A Series of Eight Cases.

BACKGROUND: Subcutaneous fungal infections are caused by penetration of the causative fungi into the subcutaneous layer and are usually localised. We present a series of eight cases with subcutaneous fungal cystic lesions masquerading as benign lesions. MATERIALS AND METHODS: A retrospective study was conducted on subcutaneous fungal infections seen between January 2007 to July 2014 in the Department of Pathology. Eight patients with biopsy proven subcutaneous fungal infection were included. We collected and analysed their demographic, clinical and histopathological details. RESULTS: Among eight patients, six were male and two were female. The mean age was 47 years (Range: 21-70). All the eight patients presented with non-tender cystic swelling. The size of the swellings varied from a minimum of 3x3 cm to maximum of 10x4 cm. Out of eight, hand was involved in three, forearm in one, elbow in two, leg in one and foot in one. On H&E staining, all the cases showed fibro collagenous cyst wall, lined by histiocytes, granulomatous reaction, foreign body type of giant cells with acute and chronic inflammatory infiltrate containing fungal elements. Six were identified as hyalohyphomycosis and two were identified as phaeohyphomycotic cysts based on pigmentation of hyphae. CONCLUSION: Fungal infection should be suspected in all subcutaneous cystic lesions. Excised tissue should always be sent for culture and histopathology.

Pulmonary alveolar microlithiasis: an interesting case report with systematic review of Indian literature.

Pulmonary alveolar microlithiasis is a rare disease characterized by intra-alveolar presence of microliths. This study reports an interesting case of pulmonary alveolar microlithiasis and provides a systematic review of cases reported from India. A 23-year-old female presented with a history of cough, wheeze, chest pain, and episodic wheeze for five months. Pulmonary function tests demonstrated an obstructive pattern, and chest Xray showed fine micronodular opacities predominantly involving the middle and lower zones of both lungs. Transbronchial lung biopsy revealed the diagnosis. She responded well to inhaled steroid therapy. A systematic review of literature was performed and identified 73 cases of pulmonary alveolar microlithiasis reported from India. The mean (SD) age of the patients was 28.8 (14.9) years, with an almost equal male:female ratio. Many patients were asymptomatic at presentation. Breathlessness and cough were the most common symptoms, and the disease progressed into respiratory failure associated with cor pulmonale. About one-third of the cases were initially misdiagnosed and treated as pulmonary tuberculosis. Extra-pulmonary manifestations and comorbidities were also evident in our series. This systematic review helps to determine epidemiological and clinical characteristics of pulmonary alveolar microlithiasis. Further research is needed to elucidate the etiopathogenesis, diagnosis, and therapeutic options, which are beneficial in developing and identifying cost-effective treatment for pulmonary alveolar microlithiasis.

Jejunal diverticulosis with perforation - a challenging differential diagnosis of acute abdomen: case report.

Multiple diverticulosis of the jejunum represents a very rare entity. Jejunal diverticula are found to be the rarest of all small bowel diverticula. The disease is usually asymptomatic and often becomes clinically relevant when complicated. This rarity makes it a difficult differential diagnosis. Related complications such as diverticulitis, perforation, and bleeding and/or intestinal obstruction appear in about 10-30% of the patients which increase the morbidity and mortality rates in such individuals. Here, we present a case of jejunal diverticulosis with perforation who presented with symptoms of acute abdominal pain, vomiting and fever along with a brief review of literature.

Clinicopathological profile of salmonella typhi and paratyphi infections presenting as Fever of unknown origin in a tropical country.

BACKGROUND: Enteric fever, a common infection in the tropics and endemic to India, often manifests as an acute febrile illness. However, presentation as fever of unknown origin (FUO) is not uncommon in tropical countries. METHODS: We aim to describe the clinical, laboratory and pathological features of patients hospitalized with fever of unknown origin and diagnosed as enteric fever. All culture proven cases of enteric fever were analyzed retrospectively over a period of three years from January 2011 to December 2013. RESULTS: Seven of 88 (8%) cases with enteric fever presented as FUO. Abdominal pain was the most common symptom besides fever. Relative bradycardia and splenomegaly were uncommon. Thrombocytopenia was the most common haematological abnormality while leucopenia was rare. Transaminase elevation was almost universal. S. Typhi and S. Paratyphi A were isolated from six cases and one case respectively. Yield of organisms from blood culture was superior to that of bone marrow aspirate. Multiple granulomas were identified in 4 out of 6 (67%) of the bone marrows studied, including that due to S. Paratyphi A and histiocytic hemophagocytosis was noted in two cases. CONCLUSION: FUO is a relatively common manifestation of enteric fever in the tropics. Clinical and laboratory features may be atypical in such cases, including absence of relative bradycardia, leucopenia, and presence of thrombocytopenia, bicytopenia or pancytopenia. In addition, in endemic countries, enteric fever should be considered as a differential diagnosis, next to tuberculosis, in the evaluation of bone marrow granulomas in cases with FUO and culture correlation should be mandatory.

Bone marrow granuloma in typhoid Fever: a morphological approach and literature review.

Typhoid fever is one of the few bacterial infections in humans where bone marrow evaluation is routinely recommended. However, the morphological aspect of typhoid fever in bone marrow has been rarely described in the literature. We describe a 25-year-old male patient who presented with prolonged fever suspected to be of tubercular etiology. Bone marrow examination showed well-formed histiocytic and epithelioid granulomas and erythrophagocytosis; and the bone marrow aspirate culture grew Salmonella typhi A. In view of potential clinical implications, typhoid fever should be considered as a differential diagnosis to tuberculosis in the evaluation of prolonged fever; especially in high prevalent areas. We suggest that erythrophagocytosis may serve as a morphological marker in typhoid granulomas in the bone marrow; and bone marrow culture should be submitted in every suspected case for appropriate patient management.

Hemophagocytic Lymphohistiocytosis: an Unusual Complication of Orientia tsutsugamushi Disease (Scrub Typhus).

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is an uncommon, potentially fatal, hyperinflammatory syndrome that may rarely complicate the clinical course of Orientia tsutsugamushi disease (scrub typhus). METHODS: Here we describe the clinicopathological features, laboratory parameters, management, and outcome of three adult patients (1 female, 2 males) with scrub typhus associated HLH from a tertiary center. A brief and concise review of international literature on the topic was also added. RESULTS: All three patients satisfied the HLH-2004 diagnostic criteria; one had multi-organ dysfunction with very high ferritin level (>30,000 ng/ml), and all had a dramatic recovery following doxycyclin therapy. Literature review from January 1990 to March 2014 revealed that scrub typhus associated HLH were reported in 21 patients, mostly from the scrub endemic countries of the world. These included 11 females and 10 males with a mean age of 35 years (range; 8 months to 81 years). Fifteen of 17 patients (where data were available) had a favorable outcome following early serological diagnosis and initiation of definitive antibiotic therapy with (N=6) or without (N=9) immunosuppressive/immunomodulator therapy. Mutation analysis for primary HLH was performed in one patient only, and HLH-2004 protocol was used in two patients. CONCLUSION: We suggest that HLH should be considered in severe cases of scrub typhus especially if associated with cytopenia (s), liver dysfunction, and coagulation abnormalities. Further studies are required to understand whether an immunosuppressive and/or immunomodulator therapy could be beneficial in those patients who remain unresponsive to definitive antibiotic therapy.

Plasmablastic multiple myeloma following clear cell renal cell carcinoma.

We aim to describe the clinicohaematological profile of an elderly male with plasmablastic multiple myeloma (MM) (IgG λ, International System Stage II) with an unfavourable outcome following chemotherapy. The serum interleukin-6 level was found to be markedly elevated (2464 pg/mL, reference; <50 pg/mL). Thirty-six months prior to MM diagnosis, he underwent left radical nephrectomy for a stage III (pT3N0M0) clear cell renal cell carcinoma (RCC, Fuhrman grade 2). The unique MM-RCC association, shared risk factors, myeloma pathobiology and clinical implications are discussed with a brief literature review.

Endoscopic (video) demonstration of hookworm infestation of the stomach.

Hookworm infestation is common in southern India. The adult worms normally reside in the duodenum, graze the intestinal mucosa with their large buccal cavities and ingest the intestinal epithelial cells and blood. Depending on the number of worms the infection may be either asymptomatic or can cause iron deficiency anaemia due to chronic blood loss. Adult worms live in the small intestine and are not usually seen in the stomach. There are only very few case reports in the literature reporting hookworm infestation of the stomach. In this case report we present an endoscopic (video) demonstration of hookworm infestation of the stomach in a woman who presented with chronic anaemia.

Sertoli-leydig cell tumor of ovary- a diagnostic dilemma.

Sertoli Leydig Cell Tumours (SLCTs) are rare, unilateral, sex cord stromal tumours of ovary, which constitute less than 1% of all the ovarian neoplasms. These tumours can be functionally diverse and they may have heterologous elements. We aim to report a case of a 25-year- old woman who presented with suprapubic pain of 5 days duration, a unilateral adnexal mass, hypertestosteronism without virilization. Intraoperative frozen section of the unilateral salpingo-oophorectomy specimen was suggestive of granulosa cell tumour. Histopathological examination, supplemented with alpha-inhibin immunohistochemistry, was diagnostic of Meyer's type II SLCT. Clinical presentation, pathology and the diagnostic pitfalls in the present case have been presented with a brief review of literature.

Ellagic acid modulates sodium valproate induced reproductive toxicity in male Wistar rats.

This study evaluated the protective effect of ellagic acid on sodium valproate-induced sperm abnormalities in male Wistar rats. A total of 30 rats were grouped into five groups, each having 6 animals. Vehicle, sodium valproate (400 mg/kg) and ellagic acid (10, 25, 50 mg/kg) were given orally from day 1 to day 7, and ellagic acid was continued for 3 more days. On day fourteen, animals were sacrificed and the different parameters were recorded. There was a significant decrease in the sperm count and sperm motility after the exposure to sodium valproate. The percentage of abnormal sperms increased in a dose-dependent manner. The histopathological examination revealed that sodium valproate had caused degeneration and desquamation of germinal cells in the epithelium and also showed a decrease in the Johnsen's scoring. Ellagic acid provided partial protection at the doses of 10 and 25 mg/kg and complete protection at 50 mg/kg, against sodium valproate induced testicular and spermatozoal damage.

A rare presentation of gastric signet ring cells: signet ring cell lymphoma.

We herewith present a rare and interesting case of gastric signet ring cell lymphoma (SRCL) in a 40-year-old retroviral positive lady. SRCL is a rare morphological variant of nodal lymphomas.Biopsy from the suspected lesion in the stomach showed diffuse sheets of cells with a large central vacuole displacing the nucleus to the periphery of the cell, imparting signet ring cell morphology. Negative reaction to PAS (Periodic acid Schiff) stain and subsequent strong positivity for the immunohistochemical markers such as CD45 (Leucocyte commonantigen) and CD20, a B-cell marker helped us to arrive at a diagnosis of signet ring B- cell lymphoma.

Hemophagocytic lymphohistiocytosis: critical reappraisal of a potentially under-recognized condition.

Hemophagocytic lymphohistiocytosis (HLH) is an uncommon, potentially life threatening, hyper inflammatory syndrome of diverse etiologies. Cardinal signs include prolonged fever, organomegaly, and persistent unexplained cytopenias. In spite of the well known diagnostic criteria put forth by HLH society, this continues to pose great diagnostic challenge in both pediatric and adult intensive care settings. We describe 4 adult (2 males, 2 females, aged 19, 29, 40, and 17 years) and 3 pediatric (2 males, 1 female, aged 1 month, 6 months, and 12 years) patients with secondary HLH who satisfied the HLH-2004 diagnostic criteria. Definite evidence of hemophagocytosis was noted in 4 patients on initial bone marrow examination. The underlying etiologies were as follows: Rickettsia tsutsugamushi (case 1), autoimmune disorder (case 2), systemic onset juvenile idiopathic arthritis (sJIA) (case 3), unknown bite (possibly a venomous snake) (case 4), Plasmodium vivax (case 5), Cytomegalo virus (case 6), and Mycobacterium tuberculosis (case 7). In one patient, hemophagocytosis was presumed to have been exacerbated by administration of granulocyte monocyte colony stimulating factor (GMCSF) for severe neutropenia. Two patients died with disseminated intravascular coagulation (DIC) and multi organ failure within few days of HLH diagnosis. Immunosuppressive therapy was started in 3 patients, and etoposide was started in one patient only. Due to lack of specificity of diagnostic criteria, diagnosing and differentiating HLH from its closest mimickers like sepsis/septic shock may be quite challenging in critically ill patients. Therefore, increasing awareness among physicians is essential for early diagnosis and effective therapy to reduce the mortality.