Showing papers on "Fibrinoid necrosis published in 2011"

Pathogenesis of Kawasaki disease.

Abstract: Kawasaki disease (KD) most frequently affects infants and young children under 5 years of age. This disease is considered a kind of systemic vasculitis syndrome, and primarily invades the medium-sized muscular arteries, including coronary arteries. Diagnosis of KD is based on characteristic clinical signs and symptoms, which are classified as principal clinical findings and other clinical and laboratory findings. Even though the aetiology of KD is unknown, epidemiological data suggest that some kinds of infectious agents are involved in the onset of KD. In addition, the data indicate that host genetics underlie the disease's pathogenesis. Histologically, coronary arteritis begins 6-8 days after the onset of KD, and leads immediately to inflammation of all layers of the artery. The inflammation spreads completely around the artery; as a result, structural components of the artery undergo intense damage; the artery then begins to dilate. Inflammatory cell infiltration continues until about the 25th day of the disease, after which the inflammatory cells gradually decrease in number. KD arteritis is characterized by granulomatous inflammation that consists of severe accumulation of monocytes/macrophages. Aberrant activation of monocytes/macrophages is thought to be involved in the formation of vascular lesions. The lesions in all the arteries are relatively synchronous as they evolve from acute to chronic injury. There is no fibrinoid necrosis nor any mixture of acute inflammatory lesions and scarring lesions, which are characteristics in polyarteritis nodosa in KD.

Spectrum of changes in placenta in toxemia of pregnancy.

Abstract: Background: Toxemia of pregnancy is the leading cause of maternal mortality and is an important factor in fetal wastage. The incidence is high in developing countries with malnutrition, hypoproteinemia, and poor obstetric facilities. Objectives: The present study was undertaken to analyze placental changes in the preeclampsia-eclampsia syndrome with a view to assess the significance of villous abnormalities by histopathological methods because these changes serve as a guide to the duration and severity of disease. Gross abnormalities noted were the placental infarcts, retroplacental hematoma, and calcification. Results: The striking villous abnormalities observed in the study group were cytotrophoblastic proliferation (86%), thickening of the villous basement membranes (95.23%), increase in syncytial knots (90.4%), villous stromal fibrosis (92%), fibrinoid necrosis (97.82%), endarteritis obliterans (53.96%), decreased villous vascularity, and paucity of vasculosyncytial membranes (93.65%). Conclusions: The gross abnormalities and villous lesions in the preeclampsia (P < 0.001) and eclampsia syndrome (P < 0.05) were significant.

Review: role of cerebral vessels in ischaemic injury of the brain.

Abstract: This review discusses the pathological changes in the heart and vessels underlying brain ischaemic injury, with a major focus on atherosclerotic disease of the brain induced by lesions of the extracranial cervical and major intracranial arteries and small-vessel disease of the brain. The carotid bifurcation is the primary site for atherosclerotic changes, for which extensive clinical trials and pathological analyses on carotid endarterectomy specimens have been performed. Plaque rupture and erosion give rise to thrombus formation, which leads to brain ischaemic injury. These changes have much in common with atherosclerotic lesions of the subepicardial coronary arteries. Emboli of various types of particles are characteristics of brain ischaemic injury. Thrombi rich in fibrin and red blood cells (red thrombi) that develop in the cardiac chambers are common sources of cerebral emboli. Small-vessel disease of the brain induces fibrinoid necrosis, microaneurysm, fibrohyalinosis, lipohyalinosis and microatheroma, changes commonly associated with hypertension. The acute hypertensive small-vessel changes organize to create segmental arterial disorganization and deep small infarcts when they escape from rupture. Some specific vascular diseases responsible for brain ischaemic injury are briefly reviewed also.

Two subtypes of Churg-Strauss syndrome with neuropathy: the roles of eosinophils and ANCA.

Abstract: The aim of this study was to clarify the differences in the pathogenesis of neuropathy between myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA)-positive and -negative patients with Churg–Strauss syndrome (CSS). Eight MPO-ANCA-positive and 14 MPO-ANCA-negative patients were included. In addition to the standard histology, nerve biopsies were examined, employing immunohistochemistry for eosinophil major basic protein and electron microscopy. The groups did not differ significantly in clinical profiles, including the peak disability score and number of blood eosinophils. In nerve biopsies, necrotizing vasculitis was found in 63% (5/8) of the ANCA-positive and 21% (3/14) of the ANCA-negative patients. Fibrinoid necrosis of vessel walls was noted in 4 ANCA-positive patients (50%), and in one ANCA-negative patient (p = 0039). In contrast, a large number of eosinophilic infiltrations in the epineurium was shown in 36% (5/14) of the ANCA-negative patients, with no eosinophilic infiltrations shown in ANCA-positive patients. In 3 ANCA-negative patients, endoneurial eosinophils were seen where focal axonal loss and capillary dilatation were occasionally noted. There may be 2 pathogenetic mechanisms of neuropathy with CSS: ANCA-related vascular fibrinoid necrosis, and a toxic eosinophilic effect on nerve fibers which is independent of ANCA. Therapy targeting activated eosinophils may be a possible treatment for intractable neuropathy of CSS.

Crescentic glomerulonephritis: a clinical and histomorphological analysis of 46 cases.

Abstract: Background: Crescentic glomerulonephritis (CrGN), defined as crescents involving more than 50% of the glomeruli, includes pauci-immune, immune complex-mediated and anti-glomerular basement membrane disease. Objectives: The present study was aimed at evaluating the various clinical, biochemical and histological parameters in CrGN with respect to these categories and clinical outcome. Materials and Methods: Renal biopsies diagnosed as CrGN between Jan 2008 and Feb 2010 were included. Clinical and laboratory parameters were retrieved along with the therapeutic approach and clinical outcome, wherever available. Renal biopsy slides were evaluated for various glomerular, tubulo-interstitial and arteriolar features. Appropriate statistical tests were applied for significance. Results: A total of 46 cases of CrGN were included; majority (71.7%) of cases were pauci-immune (PI) while 28.3% were immune complex-mediated (IC). Among clinical features, gender ratio was significantly different between PI and IC groups (P = 0.006). The various histological parameters, including proportion of cellular crescents, tuft necrosis and Bowman's capsule rupture, were similar in both the groups. Four unusual associations, including idiopathic membranoproliferative glomerulonephritis (MPGN), multibacillary leprosy, acute lymphoblastic leukemia and C1q nephropathy were detected. Adequate follow-up information was available in 21 (46%) of the patients. Of these, 11 (52.4%) were dialysis-dependent at the last follow-up. Adult patients required renal replacement therapy more frequently than pediatric cases (P = 0.05). Presence of arteriolar fibrinoid necrosis also showed association with poor clinical outcome (P = 0.05). Conclusions: Crescentic glomerulonephritis remains one of the main causes of acute renal failure with histological diagnosis. Immunohistologic examination is essential for accurate classification into one of the three categories. This condition should be considered in rare causal associations like leprosy or MPGN with renal failure, to allow for timely performed renal biopsy and appropriate aggressive therapy.

A second case of Marburg’s variant of multiple sclerosis with vasculitis and extensive demyelination

Abstract: Marburg's variant of multiple sclerosis is a rapidly progressive and malignant form of multiple sclerosis (MS) that usually leads to severe disability or death within weeks to months without remission. Few cases have been described in the literature since the original description by Marburg. The classic pathological findings usually include highly destructive zones of extensive demyelination, necrosis with dense cellular infiltrate, and giant reactive astrocytes. We report a case of a 31-year-old woman with Marburg's variant of MS who, over a period of eight months, became totally disabled, blind, and quadriplegic, with vocal cord paralysis, requiring a tracheostomy. The patient underwent diagnostic stereotactic brain biopsy. Clinical findings, magnetic resonance imaging (MRI), serologic and cerebrospinal fluid (CSF) findings, and neuropathology are discussed. MRI showed extensive white matter involvement in the brain and spinal cord that continuously progressed over time. A diagnostic stereotactic brain biopsy revealed extensive active demyelination with unexpected finding of active vasculitis and fibrinoid necrosis with a vascular inflammatory cell infiltrate, including polymorphonuclear neutrophils and rare eosinophils. Serologic work-up for vasculitis and neuromyelitis optica was unremarkable and the CSF showed only one oligoclonal band (OCB) not present in serum. This is the second case of Marburg's variant of MS that demonstrated both demyelination and vasculitis. In our case these features were demonstrated simultaneously, even though the demyelination was the predominant pathological finding. Since vasculitis is not a feature of classic MS, these findings pose the question as to whether Marburg's variant of MS is a true variant or different entity altogether.

Histopathological analysis of the placental lesions in pregnancies complicated with IUGR and stillbirths in comparison with noncomplicated pregnancies.

Abstract: OBJECTIVE Placental factors and hypoxemia are the keys to intrauterine growth restriction (IUGR) and stillbirth. The aim of the study is to analyze histological changes in placentas of IUGR fetuses in pregnancies with no apparent etiologic factor and unexplained intrauterine fetal deaths. MATERIAL AND METHODS A total of 110 placentas were collected; 26 placentas of IUGR fetuses with no apparent cause, 58 placentas from unexplained intrauterine deaths over 20 weeks of gestation, and 26 placentas from uncomplicated pregnancies who delivered a healthy live baby. Microscopic examinations of placentas were performed for histopathological analyzes. RESULTS Gestational age at delivery was 33.67±4.37 weeks, 29.15±8.36 weeks, and 39.0±1.52 weeks in women in group I, group II and group III, respectively (p<0.01). Infarction and intervillous thrombosis are significantly more frequent in placentas of Group I and group II. Chronic villitis occurred in 69%, 63% and 30% of group I, group II, and group III, respectively. Placental intravascular thrombi (Group I, 31% and group II, 26%), perivillous fibrin deposition and fibrinoid necrosis (65% in Group I and 53% in group II), infarction, intervillous thrombosis, chronic villitis, hemorrhagic endovasculitis, placental intravascular thrombi, perivillous fibrin deposition, fibrinoid necrosis, erythroblastosis and villous edema were found in the study group. CONCLUSION The results reported here indicate that a relationship exists between morphological changes in the placentas of IUGR and intrauterine fetal deaths.

Study of Gross and Histological Features of Placenta in Intrauterine Growth Retardation

Abstract: Fetal growth retardation is most commonly caused by failure of the placenta to meet the increasing demands for oxygen and substrate of the developing fetus. Intra uterine growth retardation is common occurrence in Indian setup. Recent literature suggests that placental causes are more common than the maternal causes in intrauterine growth retardation. Gross and histological study of placenta can help us to understand the pathophysiology of placental involvement. This is warranted specially in those cases of intrauterine growth retardation which are not confounded by maternal causes. Fifty five placentae [30 from cases of intrauterine growth retardation and 25 from normal (control)] were utilized for the study. Fetal weights, placental weights and placental dimensions were measured. Tissue for histological examination was obtained from: i) Umbilical cord ii) membranes and iii) three zones in placenta. The tissues were processed and stained with Haematoxlyin and Eosin. Tissues were microscopically studied for villous and intervillous lesions utilizing various criteria. Microscopic findings were: i) increased fibrinoid necrosis (46.7%), increased perivillous fibrinoid deposition (16.7%), increased syncytial knots (60%) and increased placental infarction (1.8%). Macroscopically there was significant decrease in placental weight, fetal weight, diameter and thickness of placenta. The findings of the present study document comparatively higher incidence of fibrinoid necrosis and perivillous fibrinoid deposition. These findings underscore the predominant role of placental causes in cases of idiopathic intrauterine growth retardation.

Annular leukocytoclastic vasculitis in a patient with ulcerative colitis.

Abstract: Leukocytoclastic vasculitis (LV) is characterized by neutrophilic invasion and fibrinoid necrosis along with endothelial enlargement in postcapillary venules. Annular appearance of LV (ALV) is rare, but it can be accompanied by several systemic diseases. One of these systemic diseases is ulcerative colitis (UC), a subgroup of inflammatory bowel disease. Only one case was previously reported in which ALV was associated with UC, and herein we present one more case. A 66-year-old woman presented with painful polycyclic erythema on both palms, which had been present for 4 days. She had suffered from UC for 5 years. The patient had no fever or other systemic symptoms, and histological examination demonstrated typical LV. 200 mg of oral dapsone was taken daily to rapidly reduce her symptoms and signs, and after 1 week all lesions resolved completely without any adverse events. ALV is not a distinct condition and it can appear in a broad range of small vessel vasculitides. Although ALV in patients with UC is a very rare combination, clinicians need to be aware of this possible association.

Atypical pseudotumour after metal-on-polyethylene total hip arthroplasty causing deep venous thrombosis.

Abstract: We describe a patient who developed a mass extending into the pelvis, five years after a metal-on-polyethylene total hip arthroplasty (THA). The histological pattern of perivascular lymphocytic infiltrate and fibrinoid necrosis was more in keeping with a metal-on-metal bearing failure. The pseudotumour compressed the femoral vein causing a deep venous thrombosis.

Gastrointestinal Manifestations of Churg-Strauss Syndrome

Abstract: Background and Aims: The diagnosis of Churg-Strauss syndrome (CSS), an allergic granulomatosis involving small- and medium-sized vessels, requires the presence of at least four of six criteria including asthma, peripheral eosinophilia, and systemic vasculitis. The gastrointestinal manifestations have never been reviewed. Methods: The 75 articles in the English literature found by electronic searches from 1960 to 2011 were examined. Results: Ischemia from vasculitis causes ulcerations, perforation, annular stenosis, and/or intestinal occlusions usually involving the small bowel, presenting as an acute abdomen or intestinal angina. Colonoscopy characteristically shows shallow ulcers with erythematous halos. Endoscopic biopsies usually do not reveal vasculitis as this requires sampling of the submucosa. Intestinal resections reveal eosinophilic infiltrates, vasculitis, fibrinoid necrosis, and/ or granulomas. Unusual complications include acalculous cholecystitis and eosinophilic ascites from involvement of the peritoneum. Most patients respond to corticosteroids although mesenteric ischemia is associated with a poor outcome. Conclusion: CSS, while rare, has characteristic GI involvement.

An autopsy-proven case of myeloperoxidase-antineutrophil cytoplasmic antibody-positive polyarteritis nodosa with acute renal failure and alveolar hemorrhage.

Abstract: An 80-year-old woman positive for myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA) was admitted with a 3-month history of fever, general malaise, and weight loss, after unsuccessful treatment with antibiotics. Upon admission, her fever persisted, and there was concomitant deterioration of renal function without active urine sediments. Furthermore, she developed hemoptysis, and chest computed tomography (CT) scan revealed bilateral diffuse alveolar hemorrhage. Although a renal biopsy was not performed because of her dementia, we initially suspected microscopic polyangiitis (MPA) on the basis of her clinical course. Because of her poor general condition, she was administered a low dose of prednisolone. Although her fever subsided, she suffered from intractable alveolar hemorrhage and eventually died from respiratory failure. During the autopsy, fibrinoid necrosis was restricted to medium-sized arteries, including the arcuate arteries of the kidneys and the bronchial arteries, without necrotizing crescentic glomerulonephritis and alveolar capillaritis. Therefore, polyarteritis nodosa (PAN) was diagnosed. It is important to distinguish between MPA and PAN because they can lead to life-threatening complications, and their treatment strategies and prognosis are different. When a patient presents with MPO-ANCA, alveolar hemorrhage, and acute renal failure with little evidence of glomerulonephritis, a differential diagnosis of PAN should be made; however, it is difficult to do so without pathological findings. Therefore, pathological examination should be carried out whenever possible.

[Atypical location of Wegener's granulomatosis with breast involvement: case report].

Abstract: INTRODUCTION Wegener's granulomatosis is a disease of unknown etiology associated with the presence of serum antibodies against proteinase 3 in most cases. It is characterized by formation of inflammatory infiltrates presenting as granulomas with fibrinoid necrosis, as well as by ulceration and inflammation of small and medium-sized vessels with the involvement of upper and lower airways and kidneys. The process may also occur in other less typical locations, such as the gastrointestinal tract, heart, and nervous system. There are some reports on the location of lesions in the breast. CASE REPORT We report a case of a 57-year-old female with Wegener's granulomatosis. In this patient, lesions in the skin, kidneys, upper airways, and lungs were accompanied by a breast tumor revealing the distinctive pattern of an inflammatory granuloma. The disease began in December 2002. The patient experienced painful and swollen joints, fever, mucous-purulent-bloody nasal discharge, and subcutaneous nodules with a tendency to ulceration. Histologically, the nodules had a texture typical for inflammatory granuloma. Renal symptoms included mild proteinuria, abnormalities in the sediment (fresh and leached erythrocytes), and slightly elevated serum creatinine. HRCT of the lungs revealed bilateral pulmonary nodules. The presence of antineutrophil cytoplasmic antibodies in serum with the cytoplasmic fluorescence pattern (c-ANCA/PR-3) was confirmed. The disease progressed with perforation of the nasal septum and extensive destructive changes within the bony structures of the paranasal sinuses. The patient underwent thoracic surgery in 2008 due to an inflammatory tumor in the upper lobe of the right lung. Two years later a tumor in the right breast was detected. Histopathology of the lung and breast tumors showed high similarity of both processes corresponding to lesions typical for Wegener's granulomatosis. The patient was treated with prednisone, methylprednisolone, methotrexate, cyclophosphamide, and azathioprine. CONCLUSIONS This case provides evidence that Wegener's granulomatosis is a systemic disease with a wide spectrum of organ involvement which should be taken into account during differential diagnosis of breast tumors.

A case of MPO-ANCA-positive polyarteritis nodosa complicated by exudative otitis media, mononeuritis multiplex, and acute renal failure

Abstract: In December 2008, a 69-year-old Japanese woman was admitted to the Department of Otorhinolaryngology because of hearing impairment due to bilateral exudative otitis media, and was discharged without complete recovery despite conventional treatment. Two weeks later, she was readmitted for worsened deafness, numbness, gait disturbance, and general fatigue. She was referred to our department for general investigation. On admission, laboratory examination revealed severe inflammatory signs and active nephritic urinary sediments. Cranial computed tomography (CT) revealed progressive exudative otitis media and sinusitis. Initially, Wegener’s granulomatosis was suspected. Nasal cavity biopsy, however, showed no granuloma formation or vasculitis. Serology revealed high titer of myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA), suggestive of microscopic polyangitis (MPA). However, contrast CT identified stenosis of a celiac artery, and renal biopsy showed tubulointerstitial changes with minor glomerular abnormalities. Therefore, polyarteritis nodosa (PAN) was suspected and treatment with intravenous methylprednisolone was initiated. However, a lacunar infarct developed followed by cerebral hemorrhage, and the patient died 19 days after readmission. Autopsy revealed fibrinoid necrosis, neutrophilic infiltration, and giant cell reaction in small to medium-sized arteries in multiple organs. These findings led to diagnosis of systemic vasculitis anatomically compatible with PAN. This was a rare case of a patient with MPO-ANCA-positive PAN who may have developed bilateral exudative otitis media and hearing loss as the initial manifestation of PAN.

Malignant catarrhal fever in a calf in Espírito Santo State, Brazil: report of the first case

Abstract: A case of malignant catarrhal fever (MCF) is described in a 9-month-old, male, mixed breed calf from Espirito Santo State, southeastern Brazil. MCF had not yet been described in this region. The clinical course was 5 days and clinical signs included proprioceptive deficits, depression, dyspnea, coughing, nasal discharge, and erosive-ulcerative lesions in the oral cavity. Necropsy findings included erosive-ulcerative lesions in the alimentary tract and bronchopneumonia. Histopathological exam revealed widespread lymphoplasmacytic vasculitis associated with fibrinoid necrosis of vessel walls, mainly in the vessels of carotid rete mirabile. The diagnosis of MCF was made based on clinical, necropsy and histological findings.

Hepatitis C Related Vasculitides

Abstract: Vasculitides comprise a heterogeneous group of autoimmune diseases sharing the common histopathologic feature of inflammation and fibrinoid necrosis of the blood vessel walls. Vasculitis features a wide variety of clinical manifestations depending on the localization and the size of the vessels involved, type of inflammatory infiltrate, and associated conditions making the diagnosis of specific forms of vasculitis difficult. The classification of the vasculitis remains a matter of controversy. Some classification systems have focused on the size of the vessels, while others have been based on histologic findings, yet an overlap of vessels of various sizes may occur, also the type of inflammatory infiltrate may change over time. Epidemiologic factors including; age, gender and ethnic background, patterns of organ affection, histopathologic and serologic features represent potential considerations while establishing the diagnosis and classification of vasculitis. The etiologic factors associated with the triggering of vascular endothelial injury and inflammations are quite variable with an unrecognized clear etiology in almost 50% of the cases. (Pipitone and Salvarni, 2006) The interest in infection related vasculitides has been boosted for the last two decades by the development of new molecular techniques. Currently, a causal relationship between hepatitis C virus (HCV) and vasculitis has been established. (Falk and Hoffman, 2007) Chronic hepatitis C viremia has been known to provoke a plethora of autoimmune syndromes, as well as nonspecific rheumatologic manifestations referred to as extra-hepatic manifestations of HCV. Such extra-hepatic syndromes have been reported in as much as 4090% of the chronic HCV infected patients, with a variable clinicopathological and serological spectrum that ranges between nonspecific serological abnormalities to manifest clinical disease with subsequent affection of multiple organs and systems. Established associations include; mixed cryoglobulinaemia (MC), complete or incomplete MC syndrome, porphyria cutanea tarda, significant associations include; autoimmune hepatitis, B cell non Hodgkin’s lymphoma, monoclonal gammopathies, possible association include; chronic polyarthritis, sicca syndrome, lung fibrosis, polyarteritis nodosa, poly/dermatomyositis, thyroiditis/thyroid cancer, diabetes mellitus, lichen planus, mooren corneal ulcers. (Kattab et al., 2010, Mohammed et al., 2010)

Clinical and morphological aspects of sinovitis in early rheumatoid arthritis.

Abstract: The earliest joint changes in rheumatoid arthritis occur in the synovial membrane, leading to development of an unsuppurated proliferative synovitis. This study is based on 33 cases of early rheumatoid arthritis for which we have investigated a series of clinical and morphological parameters. For the examined cases we found that the disease incidence reached its maximum in fifth and sixth decades of life, predominantly in females, over half of cases being diagnosed in the first six months from the onset of the disease. Histopathological study of synovial membrane samples showed characteristic morphological changes but unspecific for the disease, represented by the synoviocytes proliferation, inflammatory infiltrates, fibrinoid necrosis, fibroblasts proliferation and vascular changes. Reaching composite histological score may be useful by providing some information on the severity of the disease.

Rheumatoid nodule and combined pulmonary carcinoma: topographic correlations; a case report and review of the literature.

Abstract: An association between rheumatoid arthritis (RA) and malignancies has been ascertained and patients with RA appear to be at higher risk of lymphoma and lung cancer. The higher risk of the latter malignancy may be related to rheumatoid interstitial lung disease and immunosuppressive therapies. Herein we illustrate the case of a 59-year-old male smoker affected by RA and treated with cortisone, methotrexate and TNF-? antagonists, who underwent right lower lobectomy for a nodular lesion. On microscopic examination, the lesion consisted of two distinct areas: a central area of fibrinoid necrosis, bordered by histiocytes in a palisaded arrangement, lymphocytes and a 0.4 cm thick peripheral area constituted by a combined small cell anaplastic carcinoma, adenocarcinoma and squamous cell carcinoma. The combination of three histotypes is very rare in such a small tumour. In our case, it may be hypothesized that synchronous, heterogeneous mutations occurred in different type of committed cells or in stem cells, due to the production of cytokines by RA nodule histiocytes and lymphocytes, which are contiguous to the carcinomatous area. Since few studies have evaluated the topographic correlation between tumors and rheumatoid lung lesions, further morphological and molecular studies are needed to clarify this association and the pathogenetic relationship between RA and cancer of the lung.

Histopathology and outcome of acute humoral rejection in renal allografts.

Abstract: Our purpose was to see if histopathologic features of acute antibody-mediated rejection (AMR) in renal allografts have prognostic value; and to compare two-year graft survival with and without additional therapy with plasmapheresis and intravenous immunoglobulin (IVIG). We reviewed renal allograft biopsies taken within the first 6 months after transplant from patients with C4d positive AMR, performed between January 2000 to December 2005 (n=57). We formed two groups: Group 1: biopsied between 2003 and 2005 (n=26), when C4d staining was routinely performed and option for plasmapheresis and IVIG was available; Group 2: biopsied between 2000 and 2002 (n=31), retrospectively found to be C4d positive. Patients whose biopsies showed cortical necrosis or arterial fibrinoid necrosis had early graft loss. Other histopathologic features did not statistically correlate with graft loss. Overall, additional plasmapheresis/IVIG treatment did not show convincing improvement in graft survival or function at 2 years post-transplant, but all six patients with thrombotic microangiopathy (TMA) who received plasmapheresis/IVIG had functioning grafts at two-year follow-up.

Polyarteritis Nodosa Presenting with Bilateral Testicular Swelling and Complicated by Unilateral Facial Nerve Palsy

Abstract: Polyarteritis nodosa (PAN) is a systemic necrotizing vasculitis that is generally restricted to medium-sized vessels. Here we describe the first case of a patient in which a bilateral testicular mass was a presenting symptom and the diagnosis was made on the basis of testicular histopathology. A 53-year-old Asian man presented with a history of constitutional symptoms and testicular swelling. Scrotal ultrasound revealed two avascular, bilateral, intratesticular lesions. The bilateral testicular abscess was treated without improvement. The patient developed left seventh cranial nerve palsy during his admission. The clinical changes made vasculitis or a related disorder more likely and the patient underwent a right testicular biopsy. Histopathology demonstrated features of transmural inflammation and fibrinoid necrosis of medium-sized vessel walls, consistent with PAN. This case illustrates the difficulty in diagnosing polyarteritis nodosa with isolated bilateral testicular swelling and the delay in the diagnosis. After 9 months of follow-up, no relapse had occurred and the patient's testosterone level was on the lower side of normal.

Membranous glomerulonephritis with superimposed ANCA-associated vasculitis: another case report.

Abstract: Dear Sir, We report here another case of primitive membranous nephritis with superimposed anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, in addition to 10 cases recently reported by Nasr et al. [1]. This association has since been reported in relation with systemic lupus erythematosus, hepatitis B or C virus infection and treatment with penicillamine, hydralazine and propylthiouracil [2–5]. A 67-year-old Caucasian male was presented at the emergency department with anorexia, nausea and vomiting. Routine laboratory tests revealed severe renal failure and a consultation with a nephrologist was requested. Blood pressure was 170/100 mm Hg, and urine output over 24 h was 2.2 L. Medical history was remarkable for hypertension (in treatment with β-blockers) and possible upper respiratory infection about 4 weeks before admission (treated with amoxicillin 2 g/day orally). Urinalysis revealed haematuria (+++) and non-selective proteinuria (4.8 g/24 h), in front of seric albumin levels of 2.6 g/dL. Skin examination revealed no significant lesions. LAC, ANA, anti-DNA, ENA, HBsAg, anti-HCV, cryoglobulins, complement levels, ANCAs and serum protein electrophoresis were normal. Perinuclear ANCA was positive at 1:40. A renal biopsy was performed, and sampling for LM included 11 glomeruli, three of which were globally sclerotic. Light microscopy revealed the presence of extracapillary proliferation which compressed the glomerular tuft and vasculitis with fibrinoid necrosis of the arterial wall. Cellular crescents were present exclusively in three glomeruli. The crescents were accompanied by foci of fibrinoid necrosis with endocapillary and extracapillary fibrin. Tubular atrophy and interstitial fibrosis were absent. Interstitial inflammation was present, focal and accompanied by tubular degenerative changes. There was evidence of necrotizing vasculitis. IF revealed granular, segmental to global glomerular capillary wall positivity for IgG, kappa and lambda. Weaker staining for C3 was detected. Staining for fibrinogen highlighted areas of glomerular fibrinoid necrosis. Immunofluorescence shows intense staining of the arterial wall for IgG. The final diagnosis was ‘membranous glomerulonephritis with superimposed ANCA-associated vasculitis and extracapillary proliferation’. The patient started a 6-month course of methylprednisolone (1 g i.v.) for three consecutive days at months 1, 3 and 5, followed by methylprednisolone per os alternated with cyclophosphamide per os. The patient is in partial remission. Creatinine fell to 1.6 mg/dL while proteinuria reduced to 1.2 g/24 h. Treatment ended on September 2010. Conflict of interest statement. None declared.

Clinical and Morphologic Differences between Class IV-S and Class IV-G Lupus Nephritis

Abstract: Introduction. The new ISN/RPS classification of lupus nephritis (LN) divides diffuse proliferative LN into two subcategories with predominantly segmental proliferative lesions (class IV-S) and with predominantly global proliferative lesions (class IV-G). This paper explores the validity of this distinction and possible differences between the two types of lesions. Patients and Methods. A retrospective analysis of biopsy-proven cohort of 231 patients with LN was performed. Clinical and laboratory data were available on all patients selected. Results. The prevalence of Class IV was 27,27% (41 patients had class IV-S, 22-class IV-G). The serum creatinine levels, proteinuria, and diastolic blood pressure were significantly greater in the IV-G class, but haemoglobin was significantly lower. Histologically combined lesions with segmental endocapillary proliferation and fibrinoid necrosis were more frequent in the class IV-S. No significant difference was detected in outcomes in the two groups after followups of 145,2 ± 76,87 months. Conclusions. There are definite clinical and morphologic differences between class IV-S and IV-G lesions. Data suggest that class IV-G lesions behave as an immune complex disease; however, in class IV-S lesions, the presence of proportionally greater glomerular fibrinoid necroses suggests that these lesions may have a different pathogenesis.

Histopathological analysis of the placental lesions in pregnancies complicated with IUGR and stillbirths in comparison with noncomplicated pregnancies İUGR ve ölü doğumlarla komplike olmuş gebeliklerde plasental lezyonlarin histopatolojik analizi ve nonkomplike gebeliklerle karşilaştirilmasi

Abstract: Objective: Placental factors and hypoxemia are the keys to intrauterine growth restriction (IUGR) and stillbirth. The aim of the study is to analyze histological changes in placentas of IUGR fetuses in pregnancies with no apparent etiologic factor and unexplained intrauterine fetal deaths. Material and Methods: A total of 110 placentas were collected; 26 placentas of IUGR fetuses with no apparent cause, 58 placentas from unexplained intrauterine deaths over 20 weeks of gestation, and 26 placentas from uncomplicated pregnancies who delivered a healthy live baby. Microscopic examinations of placentas were performed for histopathological analyzes. Results: Gestational age at delivery was 33.67±4.37 weeks, 29.15±8.36 weeks, and 39.0±1.52 weeks in women in group I, group II and group III, respectively (p<0.01). Infarction and intervillous thrombosis are significantly more frequent in placentas of Group I and group II. Chronic villitis occurred in 69%, 63% and 30% of group I, group II, and group III, respectively. Placental intravascular thrombi (Group I, 31% and group II, 26%), perivillous fibrin deposition and fibrinoid necrosis (65% in Group I and 53% in group II), infarction, intervillous thrombosis, chronic villitis, hemorrhagic endovasculitis, placental intravascular thrombi, perivillous fibrin deposition, fibrinoid necrosis, erythroblastosis and villous edema were found in the study group. Conclusion: The results reported here indicate that a relationship exists between morphological changes in the placentas of IUGR and intrauterine fetal deaths (J Turkish-German Gynecol Assoc 2011; 12: 75-9)

Pathology of the Cutaneous Vasculitides: A Comprehensive Review

Abstract: Vasculitis has historically been poorly defined and the histological and clinical manifestations are protean, further complicating the diagnostic process. The definitive diagnosis is made by evidence of histologic effacement of a vessel with associated transumural inflammatory infiltrate of that vessel. Vasculitis can be a primary process or secondary to disseminated intravascular coagulation, ulceration, arthropod assault, and/or suppurative infiltrates (for example pyoderma gangrenosum). Vasculitis must further be distinguished from vasculopathies, particularly livedoid vasculopathy and connective tissue diseases (namely scleroderma and systemic lupus erythematosus) in which the primary process is vascular fibrin thrombi of the upper dermal vessels. A necrotizing vasculitis resulting secondary to the thrombotic process can occur, blurring the lines between true vasculitis and vasculopathy. Very few vasculitic processes have pathognomonic histological findings. Often times the dermatopathologist and clinician must work in concert and combine clinical, histological, and laboratory data to determine what the primary process is. As previously stated, histological evidence of inflammatory infiltrate within the vessel wall must be seen in order to diagnose vasculitis. Associated findings include fibrinoid necrosis, endothelial swelling, and endothelial cell apoptosis (Carlson, et al., 2005). Other secondary changes including extravasation of red blood cells, necrosis, ulceration, and neovascularization suggest that there has been vascular damage (Carlson et al., 2005). Associated changes can also be seen in the sweat glands and include basal cell degeneration, necrosis, and basal cell hyperplasia (Akosa & Lampert, 1991). Changes in the adjacent tissue can aid the dermatopathologist in determining what the underlying etiology causing the vasculitis could be. Extravascular granulomas characterized by degenerating collagen bundles surrounded by eosinophils and flame figures (“red” granulomas) are seen in Churg Strauss Syndrome while extravascular granulomas characterized by degenerating collagen bundles surrounded by basophilic debris (“blue” granulomas) are seen in Wegener’s granulomatosis and rheumatoid vasculitis (Carlson, 2010). Dermal lamellar fibrosis can be seen in erythema elevatum diutinum and granulomas faciale (Carlson et al., 2005). Direct immunofluorescence adds another important diagnostic piece of information. Absence of immune complex deposition (pauci-immune vasculitis) is seen in Wegener’s granulomatosis, microscopic polyangiitis, and Churg Strauss syndrome (Carlson, 2010).

Mechanisms of tumor necrosis in photodynamic therapy with a chlorine photosensitizer: experimental studies

Abstract: A photodynamic therapy experiment on 118 inbred white mice with transplanted Ehrlich's tumor (mouse mammary gland adenocarcinoma) is performed to reveal mechanisms of necrosis formation. In 7-10 days the tumor of 1-1.5 cm diameter is formed under skin at the injection point, and PDT procedure is applied. There were used a chlorine type photosensitizer Radachlorine TM and 662 nm wavelength diode laser. The drug is injected by intravenously at the dose of 40 mg/kg; the irradiation is executed in 2-2.5 hours at the surface dose of about 200 J/cm 2 . Each of the mice had a photochemical reaction in form of destructive changes at the irradiation region with subsequent development of dry coagulation necrosis. After rejection of the necrosis there occurred epithelization of defect tissues in a tumor place. Histological investigations were conducted in different follow-up periods, in 5 and 30 min, 1, 3, 6, and 12 hours, 1, 3, 7 and 28 days after irradiation. They included optical microscopy, immune marker analysis, morphometry with measurements of volume density of epithelium, tumor stroma and necroses, vascular bed. The investigations showed that an important role in damaging mechanisms of photodynamic action belongs to hypoxic injuries of tumor mediated by micro vascular disorders and blood circulatory disturbances. The injuries are formed in a few stages: microcirculation angiospasm causing vessel paresis, irreversible stases in capillaries, diapedetic hemorrhages, thromboses, and thrombovasculitis. It is marked mucoid swelling and fibrinoid necrosis of vascular tissue. Progressive vasculitises result in total vessel obliteration and tumor necrosis.

The Role of Proteinase 3 and Neutrophils in ANCA-Associated Systemic Vasculitis

Abstract: Systemic vasculitides are a group of disorders characterized by vascular inflammation, leading to vessel occlusion and consequent necrosis or ischemia. Depending on site and extent of inflammation, vasculitis has a varied presentation and prognosis. The classification of systemic vasculitides is based on the dominant vessel involved. They are also classified as idiopathic, primary and secondary to connective tissue diseases (rheumatoid arthritis, systemic lupus erythematosis), infections (infective endocarditis) and drugs (Firestein GS, 2008; Watts R, 1995). AASV (ANCA-Associated Systemic Vasculitis) is the most common primary small-vessel vasculitis that occurs in adults, and recent data indicates that the incidence has shown an up-swing. As per recent reports, the annual incidence of AASV varies from 12.4 to 19.8 per million. In two recent studies by our group, we found an incidence for AASV of 20.9/million, with a point prevalence of 268/million inhabitants in southern Sweden (Knight, 2006; Mohammad, 2007; Mohammad, 2009). ANCA (anti neutrophil cytoplasmic antibodies)-associated Vasculitis is a term that refers to a group of disorders marked by multi-organ system involvement, small vessel vasculitis and the presence of ANCA. These include Wegener’s granulomatosis (WG), Churg-Strauss syndrome (CSS) and Microscopic polyangiitis (MPA). The two most important ANCA antigens are PR3 and MPO. The vast majority of anti-PR3 antibodies yield a c-ANCA (cytoplasmic) pattern on IIF, while most antiMPO antibodies produce a p-ANCA (perinuclear) pattern, with some exceptions (Segelmark, 1994). As per an international consensus document from 1999, anti-MPO and anti-PR3 antibodies are referred to as MPOANCA and PR3-ANCA. AASV is characterized histologically by leukocytoclasis, infiltration and accumulation of apoptotic and necrotic neutrophils in tissues, and fibrinoid necrosis of the vessel walls. The histological lesions in AASV are also termed pauci-immune, as only a few or no immunoglobulins/ complement components are detected in the vasculitic lesions. AASV is associated with significant morbidity and mortality (median survival of five months, in the absence of treatment), with almost all patients requiring long term and aggressive immunosuppressive treatment (Booth, 2003). The etiology of AASV remains largely unknown. Genetic predisposition (PIZ allele of ┙1AT, CTLA-4, PTPN22, HLA DR1-DQw1) and environmental factors including exposure to silica and asbestos, drugs (anti-thyroid medications), and various infections (bacterial endocarditis, hepatitis C virus) have been demonstrated to either predispose to, or correlate with ANCA and development of vasculitis (Beaudreuil, 2005; Choi, 2000; Elzouki, 1994;

Prognostic importance of condition of blood vessels in burn wounds

Abstract: Background: The pathophysiologic alterations involving the vascular system of the burn wounds are of crucial importance. They can thus be used to study and predict the clinical outcome of these patients. Aims and objectives: The study was conducted to ascertain the histopathological changes in blood vessels in and near the burn wounds and correlate these with morbidity and mortality of the patient including relation with burn wound infections Material and methods: The present study was conducted on 56 in-patients with burns involving 30% total body surface area (TBSA). Biopsies were taken from the burn wounds on first instance and subsequently according to relevant signs and symptoms. A total of 72 biopsies were performed. Histopathological examination with particular attention to blood vessels as well as microbiological cultures was performed on the biopsies. These findings were correlated. Observation: Out of the 72 biopsies observed, 39 (54.16%) showed congestion of the blood vessels. Thrombosis was seen in 9 (12.5%) biopsies, and this finding heralded the onset of disseminated intravascular coagulation and septicemia in the patients. Biopsies from cases with massive destruction of tissues showed unremarkable vessels (17 i.e. 23.61%). Other important finding was fibrinoid necrosis which was seen in 11 biopsies (15.27%) and this was associated with uncontrolled burn wound infection. Conclusion: The study showed that congestion of the vessel was the commonest finding in the biopsies while thrombi were associated with a poor prognosis. Other important finding was fibrinoid necrosis which correlated with uncontrolled wound infection.

Systemic Vasculitis: Anatomy and Histopathology

Abstract: Vasculitides are defined by inflammation of the blood vessel walls leading to vascular stenosis or occlusion, with various degrees of fibrinoid necrosis of the media and inflammatory infiltration, mainly neutrophilic and sometimes granulomatous. Systemic vasculitides are classified according to their clinical presentations, their precise histological features, and the size of the predominantly affected vessels. Some of them are necrotizing: there is fibrinoid necrosis of the media with endothelial inflammatory infiltration and an inflammatory reaction of the adventitia frequently associated with lumen thrombosis. Others are non-necrotizing, and show giant cell infiltration and destruction of the internal elastic lamina. Finally, there are leucocytoclasic vasculitides without giant cell infiltrate or fibrinoid necrosis.