Major Histopathologic Diagnoses of Chronic Wounds.

PURPOSE: To clarify the histopathology of acute osteomyelitis, chronic osteomyelitis, primary vasculitis, and secondary-type vasculitis. TARGET AUDIENCE: This continuing education activity is intended for physicians and nurses with an interest in skin and wound care. OBJECTIVES/OUTCOMES: 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. 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: A tertiary care hospital. DESIGN: 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: 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.

Massive Hemorrhage Following Spontaneous Mediastinal Inflammatory Myofibroblastic Tumor Rupture: A Case Report.

A 45-year-old male in a hypertensive emergency was admitted with complaints of frontal headache, progressive chest discomfort, shortness of breath, dysphagia, and right upper quadrant abdominal pain radiating across the epigastrium and to the back that increases in intensity with deep inspiration. He denied any history of abdominal pain, vomiting, dyspnea, nausea, and weight loss. A computed tomography (CT) scan of the chest showed a posterior mediastinal mass between the esophagus and descending aorta. A magnetic resonance imaging (MRI) scan revealed a non-enhancing posterior mediastinal mass possibly compressing both the esophagus and the airway. A 30-degree thoracoscope was inserted in the chest cavity revealing a large hemothorax from a possibly ruptured inflammatory myofibroblastic tumor (IMT) encompassing nearly the entire pleural space with both fresh and clotted blood. Two liters of fresh blood was removed via a right thoracotomy procedure. Once removed, a large fibrinous clot-filled mass was resected entirely and sent to pathology. Postoperative recovery was uneventful; dysphagia and shortness of breath resolved. The patient gradually resumed his regular diet.

High yield of same-session EUS-guided liver biopsy by 19-gauge FNA needle in patients undergoing EUS to exclude biliary obstruction.

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: Prospective case series. SETTING: Tertiary-care teaching hospital. PATIENTS: Consecutive patients with abnormal liver tests referred for EUS. INTERVENTIONS: EUS-guided liver biopsy by 19-gauge FNA needle (non-Trucut). MAIN OUTCOME MEASUREMENTS: 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: 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.

Radiology-Pathology Conference: Colonic schwannoma.

We report the radiology and pathology findings on a patient with colonic schwannoma, and review the literature on this very rare tumor.

Radiology-Pathology Conference: rhabdoid tumor of the kidney.

Rhabdoid tumor of the kidney (RTK) is a rare pediatric malignancy. Its imaging features by ultrasound and CT have been well described; however, to our knowledge, there are only a handful of case reports that describe the MR appearance of rhabdoid tumor. We report the MR appearance of a RTK in an 18-month-old boy, review the literature on its imaging features, and discuss the differential diagnosis of solid renal tumors in children.

Radiology-pathology conference: sclerosing hemangioma of the lung.

Sclerosing hemangioma (SH) is a relatively rare, benign neoplasm of the lung. Although there are relatively characteristic imaging findings, biopsy remains the definitive diagnostic test. We report the radiology and pathology of a patient with a SH, with emphasis on the computed tomographic and (18)F-fluorodeoxyglucose positron emission tomography findings, and review the literature on this unusual tumor.

Resveratrol counters systemic lupus erythematosus-associated atherogenicity by normalizing cholesterol efflux.

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.

Myxoid degeneration of appendix wall: An entity in search of identity: Report of two cases.

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.

Fever of unknown origin (FUO) attributable to indolent lymphoproliferative disorder due to a plasmacytoma expressing immunoglobulin A.

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: 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: We believe this is the first reported rare case of an indolent, lymphoproliferative disorder attributable to an IgA-secreting plasmacytoma presenting as an FUO.

Temporal small-vessel inflammation in patients with giant cell arteritis: clinical course and preliminary immunohistopathologic characterization.

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: 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.

Study of Estrogen Receptor and Progesterone Receptor Expression in Breast Ductal Carcinoma In Situ by Immunohistochemical Staining in ER/PgR-Negative Invasive Breast Cancer.

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.

Mucinous tubular and spindle cell carcinoma of the kidney with sarcomatoid change.

Sarcomatoid change has been well documented in the various subtypes of renal cell carcinoma (RCC) and its presence is known to portend a worse prognosis in RCC. Mucinous tubular and spindle cell carcinoma is a RCC subtype, which is defined as polymorphous histology wherein the spindled epithelial cell is an inherent carcinomatous component. Many of these putatively low-grade tumors have been previously misdiagnosed as unclassified or sarcomatoid papillary RCC. We present 2 examples of hitherto undescribed sarcomatoid change in mucinous tubular and spindle cell carcinoma in a 71-year-old woman and an 80-year-old man who both underwent a radical nephrectomy procedure. In addition to the classic mucinous tubular and spindle cell carcinoma morphology, both cases had a sarcomatoid component characterized by predominantly high-grade spindle cells, solid pleomorphic epithelioid cells, and malignant fibrous histiocytoma-like storiform patterns. Sarcomatoid change comprised 60% and 20% of the tumors, respectively. Unlike the spindle sarcomatoid cells, the inherent spindle cell elements of mucinous tubular and spindle cell carcinoma had distinctively low-grade cytology and occasionally blended with tubular structures and variable mucinous stroma. The sarcomatoid cells were associated with significant necrosis, marked nuclear pleomorphism, mitoses of up to 5/10 high power field, higher proliferation fraction (MIB1), and loss of alpha-methylacyl-CoA racemase or cytokeratin 7 expression. Cytogenetic analysis in 1 tumor showed loss of chromosomes 14 and 15 and gains of chromosomes 2, 5, 7, 9, 10, 12, 17, 19, 20, 22, and X. Widespread metastasis to lymph nodes, bones and lungs occurred in one patient who succumbed 9 months after nephrectomy. Helpful features in distinguishing spindle cells of sarcomatoid component versus that of the native tumor include the presence of high-grade cytology, expansile growth with loss of typical imperceptible blending with the tubulo-papillary component, extensive necrosis, high mitotic activity, high proliferation fraction, and loss of expression of alpha-methylacyl-CoA racemase that contrasted the classic areas. Distinction of the sarcomatoid histology from inherent spindle cell component of mucinous tubular and spindle cell carcinoma is important because of its unfavorable prognostic implication.

Sulfhydryl oxidases: emerging catalysts of protein disulfide bond formation in eukaryotes.

Members of the Quiescin-sulfhydryl oxidase (QSOX) family utilize a thioredoxin domain and a small FAD-binding domain homologous to the yeast ERV1p protein to oxidize sulfhydryl groups to disulfides with the reduction of oxygen to hydrogen peroxide. QSOX enzymes are found in all multicellular organisms for which complete genomes exist and in Trypanosoma brucei, but are not found in yeast. The avian QSOX is the best understood enzymatically: its preferred substrates are peptides and proteins, not monothiols such as glutathione. Mixtures of avian QSOX and protein disulfide isomerase catalyze the rapid insertion of the correct disulfide pairings in reduced RNase. Immunohistochemical studies of human tissues show a marked and highly localized concentration of QSOX in cell types associated with heavy secretory loads. Consistent with this role in the formation of disulfide bonds, QSOX is typically found in the cell in the endoplasmic reticulum and Golgi and outside the cell. In sum, this review suggests that QSOX enzymes play a significant role in oxidative folding of a large variety of proteins in a wide range of multicellular organisms.