Primary mucinous adenocarcinoma of the thymus: a case report and review of the literature

Primary thymic mucinous adenocarcinoma is extremely rare; to our knowledge, only 2 cases have been reported to date. We describe a third case of primary mucinous adenocarcinoma of the thymus in a 41-year-old man who presented with an anterior mediastinal mass with subsequent metastasis to the lung. The initial diagnosis was of metastatic mucinous adenocarcinoma, but extensive clinical workup of the patient failed to reveal a primary tumor elsewhere in the body. The specific identification of mucinous adenocarcinoma as a primary thymic neoplasm can be difficult or impossible. Morphologic and immunophenotypic similarities to mucinous adenocarcinomas of the gastrointestinal tract can pose diagnostic challenges for surgical pathologists, especially in small biopsy specimens.     

Sensitivity and specificity of human brain glutathione concentrations measured using short‐TE 1H MRS at 7 T

Although the MR editing techniques that have traditionally been used for the measurement of glutathione (GSH) concentrations in vivo address the problem of spectral overlap, they suffer detriments associated with inherently long TEs. The purpose of this study was to characterize the sensitivity and specificity for the quantification of GSH concentrations without editing at short TE. The approach was to measure synthetically generated changes in GSH concentrations from in vivo stimulated echo acquisition mode (STEAM) spectra after in vitro GSH spectra had been added to or subtracted from them. Spectra from five test subjects were synthetically altered to mimic changes in the GSH signal. To account for different background noise between measurements, retest spectra (from the same individuals as used to generate the altered data) and spectra from five other individuals were compared with the synthetically altered spectra to investigate the reliability of the quantification of GSH concentration. Using STEAM spectroscopy at 7 T, GSH concentration differences on the order of 20% were detected between test and retest studies, as well as between differing populations in a small sample (n = 5) with high accuracy (R² > 0.99) and certainty (p ≤ 0.01). Both increases and decreases in GSH concentration were reliably quantified with small impact on the quantification of ascorbate and γ‐aminobutyric acid. These results show the feasibility of using short‐TE ¹H MRS to measure biologically relevant changes and differences in human brain GSH concentration. Although these outcomes are specific to the experimental approach used and the spectral quality achieved, this study serves as a template for the analogous scrutiny of quantification reliability for other compounds, methodologies and spectral qualities. Copyright © 2016 John Wiley & Sons, Ltd.     

BRCA1 and BRCA2 in Indian breast cancer patients

Incidence of breast cancer in Indian women is not as high as in Western countries, nonetheless age-adjusted incidence rates (AAR) have risen from 17.9 to 24.9 per 100,000 from 1965 to 1985. Although these rates are still approximately one quarter to one third of incidence rates in North America and Europe, respectively, due to the large population of women at risk, nearly 80,000 new cases were diagnosed in India in 2000. Although identification of BRCA1 and BRCA2 has greatly increased our understanding of breast cancer genetics in populations of Western European descent, the role of these genes in Indian populations remains unexplored. Analysis of a series of 20 breast cancer patients from North India with either family history of breast and/or ovarian cancer (2 or more affected first degree relatives) or early age of onset (<35 years) led to identification of two novel splice variants (331+1G>T; 4476+2T>C) in BRCA1 (10%). In addition, two BRCA2 missense variants were each identified in more than one patient (two unrelated individuals each) and likely represent population-specific polymorphisms.     

Diagnostic role of fine-needle aspiration of bone lesions in patients with a previous history of malignancy

At the present time fine-needle aspiration (FNA) is considered a routine diagnostic procedure in evaluating neoplastic vs. nonneoplastic lesions in many organs, with high sensitivity and specificity. The purpose of this study was to assess the utility of FNA in areas of diagnostic difficulty and its limitations in evaluating bone lesions in patients with a previous history of malignancy. From 1989 to 2000, 249 CT-guided FNAs of bone lesion were performed at our institutions; 187/249 (75.1%) patients had a previous history of malignancy. Aspirated material was air-dried for Diff-Quik stain or fixed in ethanol for Papanicolaou staining. Subsequent surgical tissue was available in 69/187 (36.9%) of the cases. There were 114 males and 73 females, ages 14-86 yr (mean, 64 yr). The primary tumor site was lung 49, genitourinary 46, breast 31, gastrointestinal 28, hematopoietic 26, soft tissue/skin 5, and thyroid 2. There were 125 FNAs of the vertebral spine, 19 from the pelvis, 11 from the ribs, 9 from the sternum, 5 from the femur, and 18 from miscellaneous bone sites. Out of 187, 166 (88.7%) were malignant aspirates confirming the patients' primary malignancies. The most common malignancy encountered was adenocarcinoma, 126/187 (67.4%). Surgical tissue was available for review in 69 patients and the results were in agreement with the FNAs diagnosis in all cases. Nine out of 187 (4.8%) cases were diagnosed as marrow elements on cytological material. These patients have been followed for 1-9 yr and have failed to reveal signs or symptoms of clinical recurrence. Three out of 187 (1.6%) cases showed osteomyelitis. Nine out of 187 (4.8%) were unsatisfactory specimens, with biopsy follow-up available in four cases, showing three metastatic tumors and one case of osteomyelitis. FNA of metastatic bone lesions is a major step in pretreatment diagnosis. On satisfactory specimens, the cytological diagnosis viewed in the clinical-radiological context proves to be similar to surgical diagnosis. FNA is an excellent technique with a high accuracy rate in assessing metastatic bone lesions.     

An unusual case of Plasmodium vivax malaria monoinfection associated with crescentic glomerulonephritis: a need for vigilance

Plasmodium vivax infection is increasingly a major public health burden and the second most frequent human malaria. Higher levels of clinical severity and chloroquine resistance are major factors responsible for such increases. Malarial glomerular injury is uncommon and mainly observed in Plasmodium malariae-infected patients. Occasionally, transient immune complex-mediated glomerulonephritis is associated with Plasmodium falciparum infection. Coexistent crescentic glomerulonephritis and vivax malaria have not previously been reported. We report a fatal case of P. vivax malaria, who presented with acute renal failure. P. vivax monoinfection status was diagnosed with peripheral blood smear and rapid antigen test. Further evaluation for renal failure related to systemic illness and immunological markers were inconclusive. He was treated with antimalarial drugs, hemodialysis, and supportive therapy. Renal biopsy performed for nonrecovering renal failure reveled crescentic glomerulonephritis. This case highlights the need to thoroughly search for malaria-associated crescentic glomerulonephritis using renal biopsy after nonrecovering renal failure.     

Changing Profile of Severe Malaria in North Indian Children

Objective  

To look for profile of severe malaria and contribution of vivax infection to malarial morbidity in North Indian children.     

Aerobic bacterial isolates from choledochal bile at a tertiary hospital

We studied the aerobic bacterial isolates from bile and their susceptibilty pattern in patients with biliary tract disease. Samples of bile collected during endoscopic retrograde cholangio pancreatography (ERCP) and surgery, were inoculated on standard media. Bacterial identification and susceptibility were done by standard techniques. A total of 209 samples were cultured, out of which 128 samples showed growth. Total number of isolates obtained was 221. Poly-microbial infection was detected in 67 patients. Predominant aerobic bacterial isolates obtained were Escherichia coli 30% (67), Klebsiella species 23.98% (53), Enterococcus species 12.21% (27). Multi-drug resistance was noted in 57%. Higher resistance rate was noted among Gram negative bacilli for ampicillin (92.4%), cephalexin (82.46%), ciprofloxacin (68.42%), piperacillin (64.33%). Sensitivity to meropenem was 90.64% and amikacin was 76.61%. Gram positive bacteria showed high resistance to gentamicin (39.53%). Sensitivity to ampicillin was 86.05% and penicillin was 81.4%. Vancomycin and teicoplanin showed 100% sensitivity. From our study we conclude that E. coli, Klebsiella species and Enterococcus species are common pathogens infecting biliary tract. Poly-microbial infection and multi-drug resistance warrants culture and sensitivity to guide antimicrobial therapy. We recommend combination of amikacin and ampicillin for empirical therapy at our institution.     

A recurrent de novo mutation in ACTG1 causes isolated ocular coloboma

Ocular coloboma (OC) is a defect in optic fissure closure and is a common cause of severe congenital visual impairment. Bilateral OC is primarily genetically determined and shows marked locus heterogeneity. Whole‐exome sequencing (WES) was used to analyze 12 trios (child affected with OC and both unaffected parents). This identified de novo mutations in 10 different genes in eight probands. Three of these genes encoded proteins associated with actin cytoskeleton dynamics: ACTG1, TWF1, and LCP1. Proband‐only WES identified a second unrelated individual with isolated OC carrying the same ACTG1 allele, encoding p.(Pro70Leu). Both individuals have normal neurodevelopment with no extra‐ocular signs of Baraitser–Winter syndrome. We found this mutant protein to be incapable of incorporation into F‐actin. The LCP1 and TWF1 variants each resulted in only minor disturbance of actin interactions, and no further plausibly causative variants were identified in these genes on resequencing 380 unrelated individuals with OC.