Cryo-transbronchial lung biopsy in the diagnosis of IgG4-related lung disease.

IgG4-related lung disease is a diagnostic challenge as the presenting patterns can mimic other commonly seen pulmonary diseases like infections, interstitial pneumonia, malignancy, etc. The diagnosis of IgG4-related disease requires a correlation of clinical, radiological, biochemical, and histopathological features. Especially, an adequate tissue sample is necessary to diagnose this disease confidently. Conventionally surgical lung biopsy was needed for histopathology. But with the availability of the new less invasive technique-transbronchial cryo lung biopsy, adequate tissue can be obtained to clinch the diagnosis via bronchoscopy, thereby avoiding surgery. We report a case of IgG4-related interstitial lung disease diagnosed with the help of this technique in a tertiary care center in South India. Clinicoradiological features were inconclusive. Transbronchial cryo-lung biopsy helped to achieve the diagnosis.

Potential clinical implications of an incidental renomedullary interstitial cell tumor in renal allograft biopsy.

Renomedullary interstitial cell tumors (RMICTs) are often incidentally detected lesions at autopsy or resection of the kidney for other reasons. The RMICTs have not been reported in renal allograft biopsy. Overall, given the clinical implications of the differential diagnosis considered, such as morphologically similar neoplasms, interstitial fibrosis and tubular atrophy (IFTA), amyloidosis, and oxalosis, it is prudent to exclude these by an appropriate workup. Once excluded, the patients can be reassured. However, regular follow-up is recommended due to the propensity of RMICT to increase in size with age.

Unique characteristics of leukocyte volume, conductivity and scatter in chronic myeloid leukemia.

BACKGROUND: Modern automated hematology analyzers provide quantitative data on leukocyte size and structure that may be useful to distinguish reactive from neoplastic cellular proliferations. We compared leukocyte volume, conductivity and scatter (VCS) characteristics of chronic myeloid leukemia (CML), bcr-abl1-positive patients with those of non-neoplastic neutrophilia. MATERIALS AND METHODS: Complete blood counts and VCS data (LH750 hematology analyzers, Beckman Coulter) from 38 newly-diagnosed CML patients, 65 CML on imatinib mesylate therapy, 58 patients with elevated age-specific neutrophil counts due to varied causes, 100 pregnant women and 99 healthy controls were collated and compared. Receiver-operating-characteristic curves, logistic regression models and classification trees were studied for their abilities to distinguish various groups. RESULTS: Untreated CML had higher mean neutrophil volume and mean monocyte volume (MNV and MMV), mean lymphocyte scatter (MLS) and higher standard deviations of the mean neutrophil volume and conductivity (MNV-SD and MNC-SD) over all other groups (p < 0.0001 for all). MNV, MNC-SD and MLS distinguished CML from reactive neutrophilia + pregnancy groups (sensitivities 89.5%, 94.7%, 94.7% and specificities 90.6%, 95.6% and 94.0% respectively). Combination of MNV>163.0 AND MNC-SD>12.69 was 89.5% sensitive and 100% specific for CML. Two algorithmic classification-tree approaches using VCS parameters alone (i.e. without the aid of blood count parameters) correctly separated 100% cases of untreated CML from all others. CONCLUSION: Successful distinction of untreated but not post-imatinib CML patients from subjects who were either normal, pregnant or had reactive neutrophilia by automated analyzer-derived cell-population data opens possibilities for their applications in diagnosing and understanding the pathogenesis of CML.

Clathrin-mediated endocytic uptake of PUFA enriched self-nanoemulsifying lipidic systems (SNELS) of an anticancer drug against triple negative cancer and DMBA induced preclinical tumor model.

The current studies envisage unravelling the underlying cellular internalisation mechanism of the systematically developed docetaxel (DTH) polyunsaturated fatty acid (PUFA) enriched self-nanoemulsifying lipidic micellar systems (SNELS). The concentration-, time- and cytotoxicity-related effects of DTH-SNELS on triple negative breast cancer (TNBC) MDA-MB-231 and non-TNBC MCF-7 cell lines were assessed through Presto-blue assay. Subsequently, rhodamine-123 (Rh-123) loaded SNELS were employed for evaluating their internalisation through flow cytometry and fluorescence microscopy, establishing it to be "clathrin-mediated" endocytic pathway. Apoptosis assay (65% cell death) and cell cycle distribution (47% inhibition at G2/M phase) further corroborated the cytotoxicity of DTH-SNELS towards cancerous cells. Biodistribution, histopathology and haematology studies indicated insignificant toxicity of the optimized formulation on vital organs. Preclinical anticancer efficacy studies using 7,12-dimethylbenzantracene (DMBA)-induced model construed significant reduction in breast tumor-volume. Overall, extensive in vitro and in vivo studies indicated the intracellular localization and cytotoxicity, suggesting DTH-SNELS as promising delivery systems for breast tumor therapeutics including TNBC.

Improving the biopharmaceutical attributes of mangiferin using vitamin E-TPGS co-loaded self-assembled phosholipidic nano-mixed micellar systems.

The current research work encompasses the development, characterization, and evaluation of self-assembled phospholipidic nano-mixed miceller system (SPNMS) of a poorly soluble BCS Class IV xanthone bioactive, mangiferin (Mgf) functionalized with co-delivery of vitamin E TPGS. Systematic optimization using I-optimal design yielded self-assembled phospholipidic nano-micelles with a particle size of < 60 nm and > 80% of drug release in 15 min. The cytotoxicity and cellular uptake studies performed using MCF-7 and MDA-MB-231 cell lines demonstrated greater kill and faster cellular uptake. The ex vivo intestinal permeability revealed higher lymphatic uptake, while in situ perfusion and in vivo pharmacokinetic studies indicated nearly 6.6- and 3.0-folds augmentation in permeability and bioavailability of Mgf. In a nutshell, vitamin E functionalized SPNMS of Mgf improved the biopharmaceutical performance of Mgf in rats for enhanced anticancer potency.

Primary giant cell tumor of the female breast: a diagnostic red herring with therapeutic implications.

Primary giant cell tumor of the female breast is extremely rare. Major diagnostic difficulty is encountered not only by the surgeon but also by the radiologist and pathologist. Pathologically, it is similar to the bone and soft tissue counterparts. However, this is not always true. We describe a patient presenting clinically as cystosarcoma phyllodes and histopathological examination revealed a primary giant cell tumor which was confirmed by immunohistochemistry and electron microscopy. Interestingly, an intimate relationship between the mononuclear component of the tumor cells with eosinophils and mast cells was observed electron microscopically.

Pathogenic Sarcina in urine.

Sarcina is a Gram-positive anaerobic coccus that has been consistently reported in the upper gastrointestinal tract biopsies of patients with evidence of gastric stasis. The pathogenic role of Sarcina in humans is not entirely known. We describe an infant who was surgically treated for posterior urethral valve and the urine showed pathogenic Sarcina.

Aspergillus pseudomembranous tracheobronchitis in an immunocompetent individual: A diagnostic conundrum with therapeutic challenge.

Aspergillus tracheobronchitis is an extremely uncommon manifestation of Aspergillus infection. Most of the cases described in the literature are in the immunosuppressed individuals and is almost uniformly fatal. Immunocompetent individuals do manifest the disease, but the disease if diagnosed early can be appropriately treated and thus can be life-saving. Here, we describe a similar case which was diagnosed only at autopsy.

The Diagnostic Dilemma of Neurolymphomatosis.

Neurolymphomatosis (NL) defined as infiltration of the central nervous system or the peripheral nervous system (PNS) by malignant lymphoma cells is a rare clinical entity. However, the increasing use of fluorodeoxyglucose positron-emission tomography (FDG-PET) and magnetic resonance imaging in evaluating PNS disorders is resulting in; this condition being recognized more frequently. Here; we report five NL patients and review the current literature. We report five patients with non-Hodgkin's lymphoma (NHL) and NL, all of whom were men aged 47-69 years. The clinical presentation varied from symmetrical peripheral neuropathy to mononeuropathy. Peripheral neuropathy was the presenting manifestation of a systemic lymphoma in two patients (40%). Neuroimaging as well as whole-body FDG-PET helped in determining the correct diagnosis in all of the patients. NL is an unusual presentation of NHL resulting from infiltration of the PNS by malignant lymphomatous cells. While evaluating peripheral neuropathy, a high degree of suspicion of NL is required since the presenting symptoms vary, conventional radiology has only modest sensitivity, and a pathological diagnosis is often difficult. FDG-PET helps in the early diagnosis and treatment of this condition.