Hidehiro Takei

Smoking and atherosclerosis in youth

Coronary heart disease is the most common cause of death in the US. Studies have demonstrated that smoking is a major risk factor for coronary heart disease and that a positive relationship occurs between smoking and aortic and coronary atherosclerosis in adults. In 1985, a multicenter cooperative study, Pathobiological Determinants of Atherosclerosis in Youth (PDAY), was organized to study atherosclerosis in trauma victims 15-34 years of age. Reports from this study have demonstrated that smoking is strongly associated with the prevalence and extent of grossly visible raised lesions in the abdominal aorta but only weakly associated with similar lesions in the right coronary artery. Coronary arteries from 50 smokers and 50 non-smokers were classified microscopically using a system developed by the American Heart Association in order to determine the stage at which smoking affects atherosclerosis. Smokers had over twice as many advanced lesions, types IV and V, as non-smokers (32 vs 14%) and fewer early lesions, types I, II, III, as non-smokers (38 vs 62%). The prevalence of advanced or types IV and V lesions (32%) was over twice that of intermediate or type III lesions (14%) in smokers. The opposite relationship was observed in non-smokers (14 vs 26%). This observation suggest that intermediate lesions progress rapidly into advanced lesions in smokers and that intima formerly having early lesions is replaced by intima with raised lesions.

Immunolocalization of apolipoproteins in aortic atherosclerosis in American youths and young adults: findings from the PDAY study.

The immunohistochemical distribution of apolipoproteins in the abdominal aortas of 142 men, 15-34 years of age, collected in a cooperative multicenter study group (Pathobiological Determinants of Atherosclerosis in Youth) was examined in relationship to serum VLDL+LDL+HDL cholesterol levels. ApoB deposits were limited to the intima of specimens with intimal fibro cellular thickening or atherosclerotic lesions. Apo A-I, E and J were observed in both the intima and media of the aortas with intimal lesions. The pattern of apoJ distribution was similar to that of apoA-I and E. The distribution patterns of these apolipoproteins in these young adults were very similar to those in adults and old men seen in an earlier study. The extent of apolipoprotein distribution in the intima and media increased with age and the stage of atherosclerosis development, but was not correlated significantly with serum VLDL+LDL or HDL cholesterol levels. The infiltration of lipoprotein particles into the aortic wall seems to be more strongly associated with the progression of intimal lesions rather than with serum cholesterol levels.

Cervicovaginal Flora Comparison of Conventional Pap Smears and a Liquid-Based Thin-Layer Preparation

We compared the effectiveness of SurePath (TriPath Imaging, Burlington, NC) with that of conventional Papanicolaou smears (CP) to demonstrate microorganisms in cervicovaginal smears. Samples from 904 randomly selected cases were examined at the Medical Center of Louisiana clinics for 2 years—the year before and the year after the implementation of SurePath. One observer reviewed the CP and SurePath preparations for detection of microorganisms. Comparison of the 2 systems was made, taking into account patient age, ethnicity, and previous hysterectomy and seasonal variation in prevalence. A seasonal variation was observed in the prevalence of candidiasis. Trichomonas and a shift in bacterial flora were detected more often with CP than with SurePath (13.4% vs 8.3% and 38.7% vs 30.2%, respectively). In contrast, candidiasis was detected more frequently with SurePath than with CP (13.7% vs 7.7%). At the Medical Center of Louisiana clinics, CP was more effective for detecting trichomoniasis and bacterial vaginosis; SurePath was more effective for detecting candidiasis.

The Presence of Anti-HLA Donor-Specific Antibodies in Lung Allograft Recipients Does Not Correlate With C4d Immunofluorescence in Transbronchial Biopsy Specimens

CONTEXTnC4d immunofluorescence (IF) is a surrogate for development of donor-specific antibodies (DSAs) against human leukocyte antigen (HLA) class I and II antigens in kidney and heart biopsy specimens for monitoring of antibody-mediated (humoral) allograft rejection (AMR). Use of C4d IF in monitoring of lung allografts has shown conflicting results.nnnOBJECTIVEnTo determine if C4d IF can be used as a reliable marker for AMR and if it correlates with the presence of DSAs and histologic findings on biopsy.nnnDESIGNnAll transbronchial biopsies in lung allograft recipients, performed at our institution in a 3-year period, were reviewed. A cohort of 92 patients with 110 corresponding biopsies met the inclusion criteria of (1) having a resulted DSA within 2 weeks of biopsy and (2) having C4d immunofluorescence studies performed and confirmed.nnnRESULTSnTwenty-nine patients (31.5%) were positive for DSAs and 63 patients (68.5%) did not develop DSAs. Positive C4d capillary IF was seen in 18 of 110 total biopsy specimens (16.4%). Eight of these biopsy samples were from patients positive for DSAs and 10 were from patients negative for DSAs. The correlation coefficient between the presence of DSAs and C4d IF was 0.1628 (P = .09).nnnCONCLUSIONSnA significant proportion of DSA-positive patients had negative C4d IF results and frequently have no histologic changes on biopsy specimens. DSA-negative patients can be positive for C4d and may show the same histologic changes as reported for DSA-positive patients. Diagnosis of AMR in lung may require a collaborative approach combining clinical data, DSA status, and histology.

The distribution of oxidatively-modified lysine in the human vasculature.

Fifty-seven sections of human vessels, collected in the Pathobiological Determinants of Atherosclerosis in Youth study from individuals aged 25-34, were stained with two monoclonal antibodies to oxidatively-modified lysine. Intensity and extent of immunoreactivity were graded by three pathologists. Aorta from a Watanabe heritable hyperlipidemic (WHHL) rabbit was stained as a positive control. Intimal immunoreactivity in the rabbit was predominantly localized to lesions. Although immunoreactivity in humans was somewhat more intense in atherosclerotic plaques, substantial staining was present in intima with diffuse intimal thickening and coronary veins. Localization of oxidatively-modified lysine in humans did not correlate with localization or severity of atherosclerosis. Localization of immunoreactivity for oxidatively-modified lysine to intimal lesions in the WHHL rabbit may be due to absence of diffuse intimal thickening, which prevents retention of epitopes throughout the intima.

Intravascular carcinomatosis of central nervous system due to metastatic inflammatory breast cancer

Central nervous system (CNS) involvement by metastatic cancer is well‐recognized and typically presents with multifocal solid tumors within the brain parenchyma or leptomeningeal dissemination. We describe herein a histologically very rare case of CNS metastasis in a 52‐year‐old woman who presented with mental status changes. Post mortem examination revealed extensive CNS involvement by metastatic inflammatory breast carcinoma, characterized by the presence of single tumor cells diffusely present within capillaries without parenchymal or perivascular invasion, and acute ischemic changes/infarcts bilaterally involving multiple areas. The cancer cells were found predominantly in the cerebral cortices and deep gray matter structures. Pre‐mortem magnetic resonance and CT imaging of the brain did not identify metastatic cancer; however, widespread ischemic changes (i.e. brain infarcts) were identified. Inflammatory breast carcinoma is well‐known to have a predilection for spread through lymphovascular spaces. Post mortem examination revealed tumor involvement of bilateral lungs, heart and bladder, with sinusoidal spread in the liver and lymph nodes and prominent involvement of the splenic red pulp in addition to extensive vascular involvement of the brain and spinal cord without a discrete mass, despite the presence of widely metastatic disease. The tumor cells in the CNS were strongly immunoreactive for pancytokeratin, E‐cadherin, cytokeratin‐7, epithelial membrane antigen and CAM 5.2. This unique histologic pattern of tumor spread is considered to represent “intravascular carcinomatosis” in the CNS, and most likely the cause of the patients widespread ischemic injuries.

A New Ever-Evolving Paradigm

Cancer biomarker testing is now a mainstay of 21st century pathology practice, embracing the pathologist’s role in patient selection for specific targeted therapies. Pathologists, oncologists, and others require direction in adapting to this new ever-evolving paradigm. The Department of Pathology and Genomic Medicine at Houston Methodist Hospital in Texas hosted the Cancer Biomarker Conference (CBC) on March 22, 2014, at the Houston Methodist Research Institute in association with the department’s Houston Methodist Diagnostic Laboratories. The CBC was inspired by the work of the Cancer Biomarker Reporting Committee (CBRC) of the College of American Pathologists (CAP), which cosponsored the conference. The conference covered a range of issues from how to provide a cancer biomarker service and testing/ interpretation/reporting/reimbursement issues for biomarker testing, to tissue management and biomarker testing/ interpretation for specific solid cancers. Speakers included members of the CBRC, as well as other renowned experts who serve on related CAP committees, and presidents of the CAP, Texas Society of Pathologists (TSP), and the American Society of Clinical Oncology (ASCO). The articles in this first part of a 2-part special section are derived from lectures at the CBC, as well as contributions from other members of the CBRC and faculty at Houston Methodist Hospital. Other cosponsors of the CBC included the Texas Society of Pathologists, Association for Molecular Pathology, American Society for Investigative Pathology, Chinese American Pathologists Association, Florida Society of Pathologists, Oklahoma State Association of Pathologists, The University of Texas MD Anderson Cancer Center, The University of Texas MD Anderson Cancer Center Department of Translational Molecular Pathology, The University of Texas Health Science Center San Antonio, The University of Texas Medical Branch Galveston, The University of Texas Southwestern Medical Center Dallas, University of Arkansas for the Medical Sciences, The University of Oklahoma Health Sciences Center, and Baylor Scott & White Healthcare-Central. We would specifically like to recognize the following individuals: Primary Sponsors: