Faculty Bibliography

Resveratrol is a bioactive molecule used in dietary supplements and herbal medicines and consumed worldwide. Numerous investigations by our group and others have indicated cardioprotective and anti-inflammatory properties of resveratrol. The present study explored potential atheroprotective actions of resveratrol on cholesterol efflux in cultured human macrophages exposed to plasma from systemic lupus erythematosus (SLE) patients. These results were confirmed in ApoE(-/-)Fas(-/-) double knockout mice, displaying a lupus profile with accelerated atherosclerosis. Resveratrol treatment attenuated atherosclerosis in these mice. THP-1 human macrophages were exposed to 10% pooled or individual plasma from patients who met diagnostic criteria for SLE. Expression of multiple proteins involved in reverse cholesterol transport (ABCA1, ABCG1, SR-B1, and cytochrome P450 27-hydroxylase) was assessed using QRT-PCR and Western blotting techniques. Ten-week-old ApoE(-/-)Fas(-/-) double knockout mice (n = 30) were randomly divided into two equal groups of 15, one of which received 0.01% resveratrol for 10 consecutive weeks. Atherosclerosis progression was evaluated in murine aortas. Bone marrow-derived macrophages (BMDM) were cultured and expression of cholesterol efflux proteins was analyzed in each group of mice. Our data indicate that inhibition of cholesterol efflux by lupus plasma in THP-1 human macrophages is rescued by resveratrol. Similarly, administration of resveratrol in a lupus-like murine model reduces plaque formation in vivo and augments cholesterol efflux in BMDM. This study presents evidence for a beneficial role of resveratrol in atherosclerosis in the specific setting of SLE. Therefore, resveratrol may merit investigation as an additional resource available to reduce lipid deposition and atherosclerosis in humans, especially in such vulnerable populations as lupus patients.

PURPOSE/OBJECTIVE:To clarify the histopathology of acute osteomyelitis, chronic osteomyelitis, primary vasculitis, and secondary-type vasculitis. TARGET AUDIENCE/BACKGROUND:This continuing education activity is intended for physicians and nurses with an interest in skin and wound care. OBJECTIVES/OUTCOMES/UNASSIGNED:After participating in this educational activity, the participant should be better able to:1. Describe the parameters and significance of this study.2. Identify chronic wound diagnosis and treatment.3. Differentiate the histopathology of osteomyelitis and vasculitis. ABSTRACT/UNASSIGNED/: OBJECTIVE:The presence of a chronic wound can result in significant morbidity/mortality. Understanding the pathological alterations of wound tissue that are refractory to standard wound therapy is essential for effective wound management and healing. The authors describe 4 wound etiologies, specifically, acute osteomyelitis, chronic osteomyelitis, primary vasculitis, and secondary-type vasculitis. SETTING/METHODS:A tertiary care hospital. DESIGN/METHODS:A retrospective review of 1392 wound operations performed during a 24-month period at a tertiary care hospital was conducted. Tissue specimens reviewed included soft tissue infections of the lower extremity, sacrum, hip/pelvis, trunk, perineum, and buttocks. MAIN RESULTS/RESULTS:Acute osteomyelitis is defined as bone tissue with a predominance of polymorphonuclear leukocytes, evidence of osteoclast bone resorption with scalloping of the cortical bone edges, and bone detritus. Chronic osteomyelitis is defined as bone tissue with a significant amount of fibrosis surrounding devitalized tissue and heavy infiltration of lymphocytes and plasma cells. Primary-type vasculitis is defined primarily as inflammation and necrosis of blood vessel walls. In cutaneous lesions of granulomatosis with polyangiitis, ulceration with numerous inflammatory granulomas is seen in the papillary dermis. Secondary vasculitis is defined by vessel wall infiltration by inflammatory cells and fibrinoid necrosis of the small vessel wall. CONCLUSIONS:Pathologies of these 4 types of wounds can complicate standard algorithms designed for diagnosis and treatment, and accurate diagnosis through histopathologic analysis can help tailor targeted treatment.

Myxoid degeneration of the appendix wall without accompanying acute appendicitis (AA) is rare. We report two cases of myxoid degeneration of appendix associated with appendiceal adhesions. Both the cases showed marked splitting and disruption of smooth muscle fibers of muscularis propria by abundant myxoid ground substance and dispersed degenerated hypereosinophilic myofibers with pyknotic nuclei. Scattered degenerated myocytes with vacuolated cytoplasm were also identified. Focal serosal fibrosis was observed in both cases. We reviewed other pathologic processes that involve the appendix such as fibrous obliteration, AA, and appendiceal mucinous neoplasm (AMN) and conclude that the constellations of pathologic findings described herein are unique. Nonneoplastic dissecting myxoid degeneration of the appendix muscularis propria has not been reported in the pathology literature to date. The pathologic nature of appendiceal mucinous stromal change remains unclear; however, we hypothesize that the lesion occurs as a consequence of traction related injury to the appendix.

BACKGROUND:The most common categories causing fevers of unknown origin (FUOs) include infective rheumatic/inflammatory disorders and malignancies. Among neoplastic causes of FUOs, lymphomas, hepatomas, renal hypo-nephromas, and hepatomas are the most common. Other malignancies rarely present with FUOs (eg, multiple myeloma). CASE REPORT/METHODS:We describe a 58-year-old man who presented with an FUO accompanied by night sweats, weight loss, and a groin mass. A biopsy of the groin mass (ie, his lymph node) was negative for infectious diseases, rheumatic or inflammatory diseases, and malignancies. Histochemical and immunological studies of the lymph node showed it to contain a plasmacytoma expressing immunoglobulin A (IgA). An immunohistochemical study of the plasma-cell infiltrate demonstrated strong CD138 staining. A bone marrow biopsy was negative for multiple myeloma. CONCLUSION/CONCLUSIONS:We believe this is the first reported rare case of an indolent, lymphoproliferative disorder attributable to an IgA-secreting plasmacytoma presenting as an FUO.

BACKGROUND:EUS-guided liver biopsy by Trucut yields variable specimen adequacy at high cost, limiting its utility. A modified EUS-guided technique with reliable adequacy could be a viable alternative to standard techniques in cost-effective clinical settings. OBJECTIVE:To describe our experience with EUS-guided liver biopsy by 19-gauge FNA, non-Trucut, needle in a cost-effective setting: patients with abnormal liver test results of unclear etiology referred for EUS to exclude biliary obstruction in whom an unrevealing EUS would have prompted a next-step liver biopsy by the referring physician. DESIGN/METHODS:Prospective case series. SETTING/METHODS:Tertiary-care teaching hospital. PATIENTS/METHODS:Consecutive patients with abnormal liver tests referred for EUS. INTERVENTIONS/METHODS:EUS-guided liver biopsy by 19-gauge FNA needle (non-Trucut). MAIN OUTCOME MEASUREMENTS/METHODS:Diagnostic yield, specimen adequacy, and complications. An adequate specimen was defined as a length of 15 mm or longer and 6 or more complete portal tracts (CPTs). RESULTS:Between July 2008 and July 2011, 22 of 31 consecutive patients meeting inclusion criteria underwent unrevealing EUS with same-session EUS-guided liver biopsy by 19-gauge FNA needle. A median of 2 FNA passes (range 1-3) yielded a median specimen length of 36.9 mm (range 2-184.6 mm) with a median of 9 CPTs (range 1-73 CPTs). EUS-guided liver biopsies yielded a histologic diagnosis and adequate specimens in 20 of 22 patients (91%). Expanded experience led to improved specimen adequacy. There were no complications. LIMITATION/CONCLUSIONS:Small study size. CONCLUSIONS:EUS-guided liver biopsy by using a 19-gauge FNA needle appears to be feasible and safe and provides excellent diagnostic yield and specimen adequacy.

OBJECTIVE:To investigate the occurrence, clinical correlates, and immunohistochemical phenotype of temporal small-vessel inflammation (TSVI) in temporal artery biopsies from patients presenting with clinical features of giant cell arteritis (GCA). METHODS:We retrospectively reviewed 41 temporal artery biopsy specimens for the presence of inflammatory infiltrates in small vessels external to the temporal artery adventitia (TSVI); 33 had sufficient clinical and pathological data for detailed analysis. Clinical and laboratory features at presentation and corticosteroid treatment patterns of patients with isolated TSVI were compared to those of patients with positive and negative biopsies. The cellular composition of the infiltrates was further characterized by immunohistochemistry. RESULTS:Twenty-three (70%) specimens had evidence of TSVI including 10 with concurrent GCA and 13 (39%) with isolated TSVI. TSVI was found in all positive temporal artery biopsies. The proportion of macrophages and of lymphocyte subpopulations differed between infiltrates observed in TSVI and those of the main temporal artery wall. Initial erythrocyte sedimentation rate (ESR) was similar in the TSVI and positive biopsy groups and was significantly higher than in the negative biopsy group. Patients with isolated TSVI more often had symptoms of polymyalgia rheumatica compared to the positive biopsy group. Patients with TSVI received corticosteroid doses that were intermediate between patients with positive and those with negative biopsies. CONCLUSION/CONCLUSIONS:A significant number of patients with clinical features of GCA demonstrated isolated TSVI. Differences in the clinical presentation and cellular composition suggest that TSVI may represent a subset of GCA and should be considered in the interpretation of temporal artery biopsies and treatment decisions.

Background. To our knowledge, the hormone receptor status of noncontiguous ductal carcinoma in situ (DCIS) occurring concurrently in ER/PgR-negative invasive cancer has not been studied. The current study was undertaken to investigate the ER/PgR receptor status of DCIS of the breast in patients with ER/PgR-negative invasive breast cancer. Methods. We reviewed the immunohistochemical (IHC) staining for ER and PgR of 187 consecutive cases of ER/PgR-negative invasive breast cancers, collected from 1995 to 2002. To meet the criteria for the study, we evaluated ER/PgR expression of DCIS cancer outside of the invasive breast cancer. Results. A total of 37 cases of DCIS meeting the above criteria were identified. Of these, 16 cases (43.2%) showed positive staining for ER, PgR, or both. Conclusions. In our study of ER/PgR-negative invasive breast cancer we found that in 8% of cases noncontiguous ER/PR-positive DCIS was present. In light of this finding, it may be important for pathologists to evaluate the ER/PgR status of DCIS occurring in the presence of ER/PgR-negative invasive cancer, as this subgroup could be considered for chemoprevention.