Nodular lymphoid hyperplasia of the lung: a clinicopathologic study of 14 cases

Nodular lymphoid hyperplasia is a controversial entity in which its existence in the lung has been doubted. The current opinion is that most, if not all, such cases represent extranodal marginal zone B-cell lymphomas masquerading as reactive lesions. We found 14 cases of nodular lymphoid hyperplasia in the files of the Pulmonary Department at the Armed Forces Institute of Pathology from 1974 through 1998. All had clinical histories and hematoxylin-eosin slides. In 12 of 14 with paraffin blocks, we applied immunohistochemical antibodies for CD20, CD3, CD43, CD5, bcl-2, bcl-1, CD45RA, and kappa and lambda immunoglobulin light chains. Molecular genetic analysis was performed on paraffin sections in 10 of 14 by the polymerase chain reaction for rearrangements of the immunoglobulin heavy chain gene and the minor and major break-point regions of the chromosomal translocation t (14;18). There were eight women and six men ranging in age from 19 to 80 years (median, 65 yrs). Most lesions (71%) were incidental findings on routine chest x-rays. Most patients (64%) had a single lesion by chest x-ray whereas the remainder had two to three lesions, except for one patient who had "multiple" lesions. There was associated regional lymphadenopathy in five of 14 cases (36%) which, on biopsy, proved to be reactive follicular hyperplasia. The only treatment was surgical excision. Of the seven patients with follow-up information from 8 months to 6 years (mean, 30 mos), none had clinical recurrence and no patient died of disease. The histology and immunophenotype of the lesions were strikingly similar, including abundant reactive germinal centers, intense interfollicular polyclonal plasmacytosis, and a variable degree of interfollicular fibrosis. No case showed a molecular rearrangement of the immunoglobulin heavy chain gene or the minor or major break-point region of the t (14;18). We conclude that nodular lymphoid hyperplasia of the lung, although rare, does exist and deserves its place in the spectrum of reactive pulmonary lesions that ranges from follicular hyperplasia to diffuse hyperplasia of the bronchus-associated lymphoid tissue (lymphoid interstitial pneumonitis).     

Infants born to narcotic dependent mothers: Physical growth patterns in the first 12 months of life

Objectives: To describe the physical growth patterns of infants born to narcotic dependent mothers (INDM) over a 12 months period and, if possible, to relate the growth to drug taking patterns during pregnancy.
Methodology: The growth of a cohort of 43 INDM was measured during the first 12 months of life. Weight and length measurements were compared with percentile charts and converted to Z scores. Questionnaire data about drug taking practices, demographic variables and the neonatal period (including withdrawal scores) were obtained.
Results: Twenty-four (55.8%) of INDM had evidence of neonatal drug withdrawal requiring treatment with phenobarbitone. At birth, Z scores for weight and length indicated relative intrauterine growth retardation. By 12 months, there had been some catch up growth, but Z scores for weight and length were still below zero. Persistent weight retardation at 12 months was correlated with methadone dosage during pregnancy, but not the need for phenobarbitone therapy.
Conclusions: The growth patterns of INDM in the first 12 months of life indicated that at birth there was evidence of intrauterine growth retardation, but by 12 months the growth was little different from the rest of the community. There appears to be some influence of narcotic agents taken while pregnant on subsequent growth of INDM.     

Identification of differentially expressed genes in aflatoxin B1- treated cultured primary rat hepatocytes and Fischer 344 rats

Aflatoxin B1 (AFB1), a mutagen and hepatocarcinogen in rats and humans, is a contaminant of the human food supply, particularly in parts of Africa and Asia. AFB1-induced changes in gene expression may play a part in the development of the toxic, immunosuppressive and carcinogenic properties of this fungal metabolite. An understanding of the-role of AFB1 in modulating gene regulation should provide insight regarding mechanisms of AFB1-induced carcinogenesis. We used three PCR- based subtractive techniques to identify AFB1-responsive genes in cultured primary rat hepatocyte RNA: differential display PCR (DD-PCR), representational difference analysis (RDA) and suppression subtractive hybridization (SSH). Each of the three techniques identified AFB1- responsive genes, although no individual cDNA was isolated by more than one technique. Nine cDNAs isolated using DD-PCR, RDA or SSH were found to represent eight genes that are differentially expressed as a result of AFB1 exposure. Genes whose mRNA levels were increased in cultured primary rat hepatocytes after AFB1 treatment were corticosteroid binding globulin (CBG), cytochrome P450 4F1 (CYP4F1), alpha-2 microglobulin, C4b-binding protein (C4BP), serum amyloid A-2 and glutathione S-transferase Yb2 (GST). Transferrin and a small CYP3A-like cDNA had reduced mRNA levels after AFB1 exposure. Full-length CYP3A mRNA levels were increased. When liver RNA from AFB1-treated male F344 rats was evaluated for transferrin, CBG, GST, CYP3A and CYP4F1 expression, a decrease in transferrin mRNA and an increase in CBG, GST, CYP3A and CYP4F1 mRNA levels was also seen. Analysis of the potential function of these genes in maintaining cellular homeostasis suggests that their differential expression could contribute to the toxicity associated with AFB1 exposure.      

The impact of calcineurin inhibitors on graft survival

The discovery of the first calcineurin inhibitor (CNI), cyclosporine, represents a watershed event in the history of immunosuppression, as it was the first drug shown to reversibly inhibit T-lymphocyte function, therefore allowing for one of the major breakthroughs in modern medicine, that of organ transplantation.Calcineurin inhibitors remain the most effective and widely used immunosuppressive agents in organ transplantation today. The 2010 OPTN/SRTR Annual Report showed that 96% of renal transplant recipients were on CNI at the time of discharge from hospital.The prolonged use of CNI, however, may result in renal toxicity, renal dysfunction and eventual renal failure in both recipients of renal and other solid organ transplants, as well as in patients treated with these agents for autoimmune diseases.This brief review, while acknowledging that CNI toxicity does indeed exist, will focus on the successful use of CNI in renal transplant recipients, highlighting recent observations that provide alternative explanations for some of the adverse outcomes that have been attributed to CNI nephrotoxicity in the past.     

BRCA1‐associated protein (BAP1)‐inactivated melanocytic tumors

Although discussed using variable terminology, cutaneous BRCA1‐associated protein (BAP1)‐inactivated melanocytic tumor (BIMT) has been considered a discrete diagnostic entity since 2011. Here, we review the initial genomic studies that identified these distinct melanocytic tumors and the clinical and histopathological features that define these tumors. These epithelioid, predominantly dermal, and melanocytic tumors present as erythematous nodules and histopathologically have features that may overlap with Spitz nevi and nevoid melanoma. There is no sex predilection, and cutaneous BIMTs can appear at any age; however, in most familial (germline mutant) cases patients have multiple cutaneous tumors with a first diagnosis in the second or third decade of life; ocular melanoma and other tumors are increasingly identified in these kindreds with germline BAP1 mutation. These tumors have been described with a myriad of terms including: Wiesner nevus, nevoid melanoma‐like melanocytic proliferation (NEMMP), BAP1 mutant Spitz nevus, BAP1 mutant nevoid melanoma, cutaneous BAPoma, and most recently cutaneous BIMT.