Malignant lymphoma in northern Iraq: a retrospective analysis of 270 cases according to the World Health Organization classification.

BACKGROUND: Based on the World Health Organization (WHO) classification, the distribution of various subtypes of malignant lymphoma (ML) appears to differ by geographical region. AIMS AND DESIGN: studying the patterns of ML retrospectively in a previously uncharted country (Iraq) and to compare it with patterns observed regionally and worldwide. MATERIALS AND METHODS: Two hundred and seventy lymphoma patients referred to two major histopathology referral centers in Northern Iraq, were categorized according to the WHO classification, using morphology and appropriate immunohistochemistry. RESULTS: There were 205 (76%) non-Hodgkin lymphomas (NHL) and 65 (24%) Hodgkin lymphomas (HL). Of the NHL, 91% were B-cell and 9% T-cell. The most common NHL was Diffuse large B-cell lymphoma (DLBCL) which comprised 52.2% of NHL, followed by Burkitt's lymphoma (BL) at 14.6%. The latter were mostly intestinal primaries. While follicular lymphomas (FL) were infrequent constituting 2.9 % of NHL. Extranodal primaries were found in 48.3% of NHL. Hodgkin's lymphoma (HL) included 48% nodular sclerosis (NS) and 37% mixed cellularity (MC). All HL were nodal primaries. CONCLUSIONS: Among NHL, the high frequencies of DLBCL, extra nodal primaries and intestinal BL, and the infrequency of FL in northern Iraq, is similar to reports from nearby countries but differs considerably from the West and Far East, indicating a shared regional Middle East influence on non-Hodgkin lymphoma patterns. In contrast to earlier Iraqi and regional studies on HL, NS has surpassed MC as the most frequent histological subtype in Northern Iraq. This trend probably reflects the increasing urbanization that has taken place in this region.

Distribution of volumes of individual glomeruli in kidneys at autopsy: association with age, nephron number, birth weight and body mass index.

BACKGROUND: Glomerular hypertrophy occurs in a number of normal and pathological states. Glomerular volume in kidneys at autopsy is usually indirectly derived from estimates of total glomerular mass and nephron number, and provides only a single value per kidney, with no indication of the range of volumes of glomeruli within the kidney of any given subject. We review findings of the distribution of volumes of different glomeruli within subjects without kidney disease, and their correlations with age, nephron number, birth weight and body mass index (BMI). METHODS: The study describes findings from autopsy kidneys of selected adult white males from the Southeast USA who had unexpected deaths, and who did not have renal scarring or renal disease. Total glomerular (nephron) number and total glomerular volume were estimated using the disector/fractionator combination, and mean glomerular volume (Vglom) was derived. The volumes of 30 individual glomeruli (IGV) in each subject were determined using the disector/Cavalieri method. IGV values were compared by categories of age, nephron number, birth weight and BMI. RESULTS: There was substantial variation in IGV within subjects. Older age, lower nephron number, lower birth weight and gross obesity were associated with higher mean IGV and with greater IGV heterogeneity. High Vglom and high IGVs were associated with more glomerulosclerosis. However, amongst the generally modest numbers of sclerosed glomeruli, the pattern was uniformly of ischemic collapse of the glomerular tuft. There was no detectable focal segmental glomerular tuft injury. DISCUSSION: In this series of people without overt renal disease, greater age, nephron deficit, lower birth weight and obesity were marked by glomerular enlargement and greater glomerular volume heterogeneity within individuals.

Interactions between oxidative stress and inflammation in salt-sensitive hypertension.

The goal of this study was to test the hypothesis that increases in oxidative stress in Dahl S rats on a high-salt diet help to stimulate renal nuclear factor-kappaB (NF-kappaB), renal proinflammatory cytokines, and chemokines, thus contributing to hypertension, renal damage, and dysfunction. We specifically studied whether antioxidant treatment of Dahl S rats on high Na intake would decrease renal inflammation and thus attenuate the hypertensive and adverse renal responses. Sixty-four 7- to 8-wk-old Dahl S or R/Rapp strain rats were maintained for 5 wk on high Na (8%) or high Na + vitamins C (1 g/l in drinking water) and E (5,000 IU/kg in food). Arterial and venous catheters were implanted at day 21. By day 35 in the high-Na S rats, antioxidant treatment significantly increased the renal reduced-to-oxidized glutathione ratio and decreased renal cortical H(2)O(2) and O(2)(*-) release and renal NF-kappaB. Antioxidant treatment with vitamins C and E in high-Na S rats also decreased renal monocytes/macrophages in the glomeruli, cortex, and medulla, decreased tumor necrosis factor-alpha by 39%, and decreased monocyte chemoattractant protein-1 by 38%. Vitamin-treated, high-Na S rats also experienced decreases in arterial pressure, urinary protein excretion, renal tubulointerstitial damage, and glomerular necrosis and increases in glomerular filtration rate and renal plasma flow. In conclusion, antioxidant treatment of high-Na Dahl S rats decreased renal inflammatory cytokines and chemokines, renal immune cells, NF-kappaB, and arterial pressure and improved renal function and damage.

Immune suppression prevents renal damage and dysfunction and reduces arterial pressure in salt-sensitive hypertension.

The goal of this study was to test the hypothesis that renal infiltration of immune cells in Dahl S rats on increased dietary sodium intake contributes to the progression of renal damage, decreases in renal hemodynamics, and development of hypertension. We specifically studied whether anti-immune therapy, using mycophenolate mofetil (MMF), could help prevent increases in renal NF-kappaB activation, renal infiltration of monocytes/macrophages, renal damage, decreases in glomerular filtration rate (GFR) and renal plasma flow, and increases in arterial pressure. Seventy-four 7-to 8-wk-old Dahl S, Rapp strain rats were maintained on an 8% Na, 8% Na + MMF (20 mg.kg(-1).day(-1)), 0.3% Na, or 0.3% Na + MMF diet for 5 wk. Arterial and venous catheters were implanted at day 21. By day 35, renal NF-kappaB in 8% Na rats was 47% higher than in 0.3% Na rats and renal NF-kappaB was 41% lower in 8% Na + MMF rats compared with the 8% Na group. MMF treatment significantly decreased renal monocyte/macrophage infiltration and renal damage and increased GFR and renal plasma flow. In high-NA Dahl S rats mean arterial pressure increased to 182 +/- 5 mmHg, and MMF reduced this arterial pressure to 124 +/- 3 mmHg. In summary, in Dahl S rats on high sodium intake, treatment with MMF decreases renal NF-kappaB and renal monocyte/macrophage infiltration and improves renal function, lessens renal injury, and decreases arterial pressure. This suggests that renal infiltration of immune cells is associated with increased arterial pressure and renal damage and decreasing GFR and renal plasma flow in Dahl salt-sensitive hypertension.

Reduced nephron number and glomerulomegaly in Australian Aborigines: a group at high risk for renal disease and hypertension.

Aborigines in remote areas of Australia have much higher rates of renal disease, as well as hypertension and cardiovascular disease, than non-Aboriginal Australians. We compared kidney findings in Aboriginal and non-Aboriginal people in one remote region. Glomerular number and mean glomerular volume were estimated with the disector/fractionator combination in the right kidney of 19 Aborigines and 24 non-Aboriginal people undergoing forensic autopsy for sudden or unexpected death in the Top End of the Northern Territory. Aborigines had 30% fewer glomeruli than non-Aborigines--202,000 fewer glomeruli per kidney, or an estimated 404,000 fewer per person (P=0.036). Their mean glomerular volume was 27% larger (P=0.016). Glomerular number was significantly correlated with adult height, inferring a relationship with birthweight, which, on average, is much lower in Aboriginal than non-Aboriginal people. Aboriginal people with a history of hypertension had 30% fewer glomeruli than those without--250,000 fewer per kidney (P=0.03), or 500,000 fewer per person, and their mean glomerular volume was about 25% larger. The lower nephron number in Aboriginal people is compatible with their susceptibility to renal failure. The additional nephron deficit associated with hypertension is compatible with other reports. Lower nephron numbers are probably due in part to reduced nephron endowment, which is related to a suboptimal intrauterine environment. Compensatory glomerular hypertrophy in people with fewer nephrons, while minimizing loss of total filtering surface area, might be exacerbating nephron loss. Optimization of fetal growth should ultimately reduce the florid epidemic of renal disease, hypertension, and cardiovascular disease.

Hypertension, glomerular number, and birth weight in African Americans and white subjects in the southeastern United States.

Low nephron number has been related to low birth weight and hypertension. In the southeastern United States, the estimated prevalence of chronic kidney disease due to hypertension is five times greater for African Americans than white subjects. This study investigates the relationships between total glomerular number (Nglom), blood pressure, and birth weight in southeastern African Americans and white subjects. Stereological estimates of Nglom were obtained using the physical disector/fractionator technique on autopsy kidneys from 62 African American and 60 white subjects 30-65 years of age. By medical history and recorded blood pressures, 41 African Americans, and 24 white subjects were identified as hypertensive and 21 African Americans and 36 white subjects as normotensive. Mean arterial blood pressure (MAP) was obtained on 81 and birth weights on 63 subjects. For African Americans, relationships between MAP, Nglom, and birth weight were not significant. For white subjects, they were as follows: MAP and Nglom (r=-0.4551, P=0.0047); Nglom and birth weight (r=0.5730, P=0.0022); MAP and birth weight (r=-0.4228, P=0.0377). For African Americans, average Nglom of 961 840+/-292 750 for normotensive and 867 358+/-341 958 for hypertensive patients were not significantly different (P=0.285). For white subjects, average Nglom of 923 377+/-256 391 for normotensive and 754 319+/-329 506 for hypertensive patients were significantly different (P=0.03). The data indicate that low nephron number and possibly low birth weight may play a role in the development of hypertension in white subjects but not African Americans.

Pulmonary thrombotic arteriopathy in patients with sickle cell disease.

BACKGROUND: Shortened life expectancy due to pulmonary hypertension (PH) is seen in 5% to 10% of patients with sickle cell disease. The principal factors suspected of causing PH are pulmonary thromboemboli (PE) and in situ arterial thrombosis. OBJECTIVE: To investigate the possible role that PE or in situ arterial thrombosis play in the development of PH in sickle cell disease. METHODS: Autopsies of 12 patients with sickle cell disease were correlated with clinical data from medical records. RESULTS: Right ventricular hypertrophy was present in 9 of 12 patients. Six patients with right ventricular hypertrophy had thrombi in large elastic pulmonary arteries. All patients with elastic artery thrombi had fresh or organized thrombi in small muscular pulmonary arteries. Hypertensive small arterial changes were present in 5 of these 6 patients. Six patients showed no thrombi in elastic arteries. Among these 6 patients, 3 had right ventricular hypertrophy and recent and organized thrombi, as well as hypertensive changes in small arteries. One of these 3 patients demonstrated plexiform-like lesions and fibrinoid necrosis of small arteries. Three patients without right ventricular hypertrophy had pneumonia or pulmonary edema with no identifiable pulmonary artery pathology. CONCLUSIONS: Arterial thrombosis with PH and cor pulmonale was regarded as the cause of death among most of these patients. Elastic artery thrombi are pulmonary thromboemboli, but pulmonary thromboemboli are always associated with widespread thrombosis of small arteries. Widespread thrombosis of small arteries alone was associated with PH in some cases. This finding suggests that pulmonary thromboemboli may be a late complication of PH and cor pulmonale and that an in situ thrombotic arteriopathy underlies the development of PH in most patients with sickle cell disease.

Alveolar hemorrhage and renal microangiopathy in systemic lupus erythematosus.

CONTEXT: Acute alveolar hemorrhage in systemic lupus erythematosus usually occurs as a pulmonary-renal syndrome. In most cases, the lungs show "bland" alveolar hemorrhage with little or no inflammation. Whether this alveolar injury is similar to the better-defined noninflammatory renal lupus vasculopathy is unresolved. OBJECTIVES: To investigate the relationships and the mechanisms of small vascular injury in the lung and kidney of 2 lupus patients who died of diffuse AH. METHODS: We investigated the relationship of AH to immune complex deposition in the lungs of 6 patients with systemic lupus erythematosus and correlated the findings with glomerular and vascular disease in the kidney. Lung and kidney were studied by light, immunofluorescence, and/or electron microscopy; apoptosis was investigated using in situ nick-end labeling. RESULTS: The clinical course of 2 patients was complicated by alveolar hemorrhage, and the lungs of these patients revealed alveolar wall immune complex deposits and bland alveolar hemorrhage. These 2 patients had World Health Organization class IV lupus nephritis and renal arterioles involved by a noninflammatory lupus vasculopathy. Apoptosis was identified in the lupus microangiopathy and in alveolar walls within areas of alveolar hemorrhage. Alveolar wall immune complex deposits were not found in 4 patients who had a lupus glomerulonephritis but did not have renal lupus vasculopathy. Apoptosis was not seen in renal arterioles or lungs of these 4 cases, except in areas of diffuse alveolar damage or herpesvirus pneumonia. CONCLUSIONS: Our findings indicate that alveolar hemorrhage in systemic lupus erythematosus, characterized by bland alveolar wall changes, is pathogenetically similar to the lupus microangiopathy of the kidney. In both lung and kidney, the pathogenesis of the microvascular injury appears to be related to immune complex deposition and the induction of apoptosis.

Renal cell carcinoma of end-stage renal disease: an analysis of chromosome 3, 7, and 17 abnormalities by microsatellite amplification.

End-stage renal disease (ESRD) patients have an increased risk of carcinoma of the kidney, thought to result from development of a disproportionately high number of papillary renal cell carcinomas. This study was undertaken to discover whether these renal carcinomas have a deletion of the short arm of chromosome 3, which characterizes conventional (clear cell) carcinomas, or trisomies of chromosomes 7 and 17, which characterize the majority of sporadic papillary renal cell neoplasms. Archival specimens from 17 end-stage kidneys containing renal cell carcinomas were collected from 16 ESRD patients. DNA was extracted from paraffin blocks of tumor and nontumorous tissue. Microsatellites on the long and short arm of chromosomes 3, 7, and 17 were amplified in paired "normal" tumor samples. Heterozygous loci were analyzed for loss of heterozygosity, indicating a deletion, and for allele ratio differences, indicating a duplication. Successful microsatellite studies were obtained on 18 tumors (2 conventional carcinomas, 14 papillary carcinomas, 2 unclassified [solid, eosinophilic cell] carcinomas). Of the papillary carcinomas, none had a 3p deletion, five had trisomies of both chromosomes 7 and 17, six had no changes in chromosomes 7 and 17, and three had either trisomy 7 or trisomy 17 but not both. A 3p deletion was present in one of two conventional carcinomas. No chromosome 3, 7, or 17 changes were identified in the unclassified carcinomas. The genetic abnormalities in 6 of 18 ESRD tumors seemed to be the same as those found in sporadic papillary or conventional renal cell carcinomas. Nine of 14 papillary carcinomas did not show allelic duplications of chromosomes 7 and 17. This is uncharacteristic of the findings reported for most of the sporadic forms of the neoplasm and suggests that the genetic mechanism underlying the development of many papillary renal cell carcinomas in ESRD patients might be different than that of the general population.

Clear-cell and papillary carcinoma of the kidney: an analysis of chromosome 3, 7, and 17 abnormalities by microsatellite amplification, cytogenetics, and fluorescence in situ hybridization.

Clear-cell and papillary renal cell carcinomas (RCCs) have specific genetic changes that allow them to be classified on the basis of histopathology and on the basis of cytogenetic and molecular genetic findings. Clear-cell carcinomas are characterized by a deletion of gene sequences on the short arm of chromosome 3 (3p). Papillary RCCs do not have 3p deletions but have an increase in chromosomal number that usually includes trisomies of chromosomes 7 and 17. This study was undertaken to determine whether PCR-amplified DNA microsatellites can be used to detect numerical abnormalities of chromosomes 7 and 17 and whether the numerical abnormalities and 3p deletions that are detected by microsatellite analysis can be correlated with histopathologic tumor types. A series of histologically unambiguous RCCs consisting of three papillary and ten clear-cell RCCs were studied by cytogenetics and by fluorescence in situ hybridization (FISH) with chromosome 7 and 17 centromeric probes. Microsatellites on the long and short arms of chromosomes 3, 7, and 17 were amplified in paired normal tissue and tumor samples, and the reaction products were analyzed for differences between the normal and the tumor allele ratios. Clear-cell carcinomas showed loss of heterozygosity (LOH) of 3p but not 3q alleles in eight of ten cases. LOH of 3p and 3q was seen in one case of papillary RCC that cytogenetically had two normal chromosomes 3. This indicated a nondisjunction duplication that could be confused with monosomy 3 if only microsatellite studies were performed. Differences in microsatellite allele ratios between normal tissue and tumor correlated with the presence of trisomy 7 that was identified in clear-cell and papillary RCCs by cytogenetics and by FISH. Microsatellite analysis did not detect numerical chromosome 17 abnormalities in the papillary RCCs but did show an abnormality in one clear-cell carcinoma that was markedly aneusomic for chromosomes 7 and 17 by FISH. In this collection of cases, microsatellite amplification genetically distinguished only clear-cell RCCs showing 3p but not 3q LOH as a separate class of tumors. The method detected abnormalities in chromosome number that were found in both clear-cell and papillary RCCs.

Germline and somatic mutations in the tyrosine kinase domain of the MET proto-oncogene in papillary renal carcinomas.

Hereditary papillary renal carcinoma (HPRC) is a recently recognized form of inherited kidney cancer characterized by a predisposition to develop multiple, bilateral papillary renal tumours. The pattern of inheritance of HPRC is consistent with autosomal dominant transmission with reduced penetrance. HPRC is histologically and genetically distinct from two other causes of inherited renal carcinoma, von Hippel-Lindau disease (VHL) and the chromosome translocation (3;8). Malignant papillary renal carcinomas are characterized by trisomy of chromosomes 7, 16 and 17, and in men, by loss of the Y chromosome. Inherited and sporadic clear cell renal carcinomas are characterized by inactivation of both copies of the VHL gene by mutation, and/or by hypermethylation. We found that the HPRC gene was located at chromosome 7q31.1-34 in a 27-centimorgan (cM) interval between D7S496 and D7S1837. We identified missense mutations located in the tyrosine kinase domain of the MET gene in the germline of affected members of HPRC families and in a subset of sporadic papillary renal carcinomas. Three mutations in the MET gene are located in codons that are homologous to those in c-kit and RET, proto-oncogenes that are targets of naturally-occurring mutations. The results suggest that missense mutations located in the MET proto-oncogene lead to constitutive activation of the MET protein and papillary renal carcinomas.

Renal cell carcinoma of end-stage renal disease: a histopathologic and molecular genetic study.

Renal cell carcinomas (RCC) are responsible for the deaths of 3% to 4% of patients with ESRD. The clear cell carcinoma of the kidney, which comprises 80% of sporadic RCC within the general population, shows a deletion of gene sequences in the short arm of chromosome 3 (3p) in as many as 100% of cases. The von Hippel-Lindau tumor suppressor gene at 3p25-26 is found to be mutated in the nondeleted allele in 57% of these sporadic clear cell carcinomas. This study was undertaken to determine the histopathologic types of RCC occurring in ESRD patients in the United States and to investigate the frequency with which 3p genetic changes can be found in these ESRD tumors. Seventeen end-stage kidneys containing RCC were collected from 15 ESRD patients at ten US medical centers. The tumors were classified by Thoenes' histopathologic typing. DNA extracted from paraffin blocks of tumor and nontumorous tissue was analyzed by single-stranded conformational polymorphism analysis for von Hippel-Lindau mutations and by microsatellite amplification for deletion of 3p gene sequences. Twenty-one RCC were identified in the 18 kidneys. The 21 RCC were classified histopathologically as follows: clear cell, compact, three cases; chromophilic, tubulopapillary, 15 cases; chromophilic, compact, three cases. Among the three clear cell carcinomas, one showed 3p genetic loss. None of the chromophilic RCC showed a 3p deletion and none of 19 tumors studied by single-stranded conformational polymorphism analysis disclosed von Hippel-Lindau mutations. In contrast to the general population, clear cell RCC with 3p abnormalities represent only a small proportion of the renal carcinomas in this collection of ESRD tumors. The findings indicate that the genetic changes underlying the development of most ESRD tumors are different from those occurring in sporadic clear cell RCC and do not characteristically involve the inactivation of a 3p tumor suppressor gene.

Renal cell carcinoma in an end-stage kidney of a patient with a functional transplant: cytogenetic and molecular genetic findings.

Renal cell carcinomas (RCCs) occur at an increased rate and at a younger age in patients with end-stage renal disease (ESRD) than in the general population. A papillary RCC from a patient with ESRD treated by hemodialysis and then by renal transplantation was karyotyped and showed a 55,XY,+2,+4,+7,+10,+12,+16,+17,+17,+20 mainline. No loss of gene sequences in the short arm of chromosome 3 was identified by chromosomal or molecular genetic analysis. Together with one prior report of a cytogenetic study of a RCC in an end-stage kidney, the findings indicate that papillary RCCs that arise in ESRD patients have genetic changes that are similar to those found in sporadic tumors. The increased frequency of tumors and the younger age of the patients may be due to an increased rate at which abnormal mitoses occur in diseased renal tissues.

Analysis of 3p allelic loss in papillary and nonpapillary renal cell carcinomas. Correlation with tumor karyotypes.

Nonpapillary renal cell carcinomas (RCCs) are characterized by deletions of the short arm of chromosome 3 (3p) and papillary RCCs by increased numbers of selected chromosomes. Although recent molecular genetic studies have reported some papillary RCCs to show loss of heterozygosity (LOH) on 3p, a 3p deletion has not been demonstrated in a papillary RCC by karyotype analysis. To investigate this apparent discrepancy between molecular methods and chromosomal changes in the genetic evaluation of RCC, a series of 13 papillary and nonpapillary RCCs was investigated for 3p LOH by PCR-based restriction fragment length polymorphism (PCR-RFLP) analysis and for 3p and 3q LOH by microsatellite analysis. Karyotypes were obtained in six cases. Loss of 3p but not of 3q alleles was found in 8 of 10 nonpapillary RCCs. The region of overlapping deletion was 3p14--p21, and in six cases the deletion involved 3pter loci. One papillary RCC displayed 3p and 3q LOH, but the tumor had two morphologically normal chromosomes 3 and several trisomies. This indicated that nondisjunction of a chromosome from one parent compensated a whole chromosome loss from the other parent during tumor development. LOH in this papillary RCC constituted a reduction of chromosome 3 alleles to homozygosity, but the karyotype change, consisting of an increased number of whole chromosomes and an absence of a structural chromosome 3 abnormality, is regarded as being more characteristic of papillary than nonpapillary RCC.

Spectrum of vascular pathology affecting patients with the antiphospholipid syndrome.

A thrombotic microangiopathy that is identified in patients with the antiphospholipid syndrome (APS) represents only a part of the vascular pathology that can be associated with antiphospholipid antibodies (aPL). Tissues from two autopsies, four renal biopsies, two skin biopsies, and one amputated leg were obtained from six patients who met criteria for the diagnosis of APS. Three patients had systemic lupus erythematosus (SLE), one had lupus-like disease, and two had a primary APS. Five of the patients were hypertensive. Arteries of three patients disclosed fibrin thrombi along with widespread obstruction by recanalized intimal connective tissue. Small renal, leptomeningeal, and pulmonary arteries showed concentric cellular and fibrous intimal hyperplasia indistinguishable from hypertensive vascular disease. Glomerular capillary and afferent arteriolar thrombi were found in renal biopsies from two SLE patients. One of these SLE patients required a leg amputation in which the popliteal artery demonstrated thrombosis, intimal hyperplasia, and acute inflammation. The findings support clinical and experimental data that indicate aPLs cause thrombosis but suggest diversity in the pathogenetic mechanisms aPLs are capable of promoting. Inflammation seems to be rare and to accompany thrombosis. Intimal hyperplasia is particularly common. Its involvement of renal arteries may contribute to hypertension that develops in some APS patients.

Rochalimaea henselae infection in acquired immunodeficiency syndrome causing inflammatory disease without angiomatosis or peliosis. Demonstration by immunocytochemistry and corroboration by DNA amplification.

Rochalimaea henselae causes bacillary angiomatosis, bacillary peliosis, and persistent bacteremia. Difficult to cultivate, it is detectable in infected tissues by immunocytochemistry. This technique demonstrated R henselae in autopsy specimens obtained from three deceased patients who had acquired immunodeficiency syndrome, with pathologic tissue changes lacking neoangiogenic features. From the first patient, the cause of nodular collections of lymphocytes and nonepithelioid histiocytes in the liver, spleen, lymph nodes, bone marrow, and heart eluded detection until immunocytochemical identification of R henselae. In the second case, unexpected gross and microscopic necroinflammatory nodules in the liver and spleen contained Warthin-Starry-staining bacilli identified as R henselae immunocytochemically. The third patient was found to have pathologic changes in his liver and spleen comparable with those of the second case, as well as several other disseminated infections. In two cases, identification of R henselae was corroborated through sequencing polymerase chain reaction-amplified bacterial DNA recovered from tissue; in one case, DNA could not be amplified, possibly because of postmortem degradation. Application of the immunocytochemical technique thus has expanded the recognized spectrum of histopathologic findings associated with R henselae infection in acquired immunodeficiency syndrome, as well as proving to be potentially more sensitive than DNA amplification for this purpose when applied to autopsy tissues.

Thrombotic cerebral arteriopathy in patients with the antiphospholipid syndrome.

OBJECTIVE: A distinctive type of chronic cerebral vasculopathy was identified in the small leptomeningeal arteries of patients with high levels of serum antiphospholipid antibodies. This study characterizes the vascular lesions and investigates their pathogenesis. DESIGN: A comparative study of cerebrovascular disease in patients dying of systemic lupus erythematosus (SLE) and the antiphospholipid syndrome. PATIENTS: Cerebrovascular disease observed in autopsies on a patient with primary antiphospholipid syndrome and a patient with SLE and antiphospholipid syndrome was compared with findings on two SLE patients who did not have serum antiphospholipid antibodies and with findings on 15 patients having diseases in which pathological changes of meningeal arteries might be anticipated or are known to occur (six patients with hypertensive cerebrovascular disease, one patient with thrombotic thrombocytopenic purpura, seven patients with marantic or bacterial endocarditis, and one patient with a left ventricular mural thrombus). Multiple blocks of brain tissue were studied by serial histologic sections and histochemical and immunohistochemical methods. Immunofluorescent and electron microscopic (EM) studies were performed on kidneys and EM studies on brain and choroid plexus in each case of antiphospholipid syndrome. RESULTS: Leptomeningeal arteries of antiphospholipid syndrome patients disclosed fibrin thrombi and widespread obstruction by a proliferation of intimal fibrous tissue or myointimal cells. The fibrous and cellular segments of obstructed arteries frequently contained fibrin thrombi and displayed varying stages of recanalization. In late stages of organization, fibrous webs were formed across arterial lumens. Obstructed arteries were traced to small infarcts localized to an underlying column of cortical gray matter. None of the tissues from antiphospholipid syndrome patients showed evidence of an active or healed inflammatory vasculitis or of vascular immune complex deposits. Recanalized thrombi, fibrous and cellular occlusions, and fibrous webs were not found in the leptomeningeal arteries of patients who did not have the antiphospholipid syndrome. CONCLUSIONS: The cerebrovascular changes of the antiphospholipid syndrome are derived from a chronic thrombotic microangiopathy. The findings support the hypothesis that antiphospholipid antibodies can cause recurring episodes of intravascular thrombosis.

Nonpapillary and papillary renal cell carcinoma: a cytogenetic and phenotypic study.

Cytogenetic and molecular genetic studies allow the common renal cell neoplasms to be separated into two main types: (1) Nonpapillary renal cell carcinomas (RCC) which have a loss of 3p13-pter sequences and (2) Papillary renal cell tumors having tri- or tetrasomies of chromosome 7 and trisomy 17. To investigate renal proximal (PT) and distal (DT) tubular epithelial phenotype expression in these genetically distinct neoplasms, a panel of antibodies and lectins selectively reactive with normal adult PT and DT was applied to 10 nonpapillary and seven papillary RCC. All tumors except one papillary RCC demonstrated characteristic karyotypes. Phenotype expression varied depending upon changes in the histopathologic patterns within a tumor. Among tumors composed of only one cell type, columnar, eosinophilic cells showed only PT staining and small, basophilic cells showed only DT staining. One tumor revealed a transition from small, basophilic cells to columnar, eosinophilic cells. The basophilic cells stained for DT markers and the eosinophilic cells for PT markers. One tumor consisted of nests of clear cells between indistinct papillary structures. The clear cells stained for both PT and DT markers. All 10 nonpapillary RCC demonstrated PT staining; nine exhibited DT markers. Staining was most intense in areas of tumor showing higher nuclear grades, tubuloglandular differentiation or in granular, eosinophilic cells and was absent or weak in solid groups of low nuclear grade clear cells. Papillary and nonpapillary RCC demonstrated lectin-binding or antigens associated with both PT and DT indicating a capacity for multipotential metanephric differentiation in each type of neoplasm.(ABSTRACT TRUNCATED AT 250 WORDS)