Epithelioid sarcoma: clinical, MR imaging and pathologic findings.

OBJECTIVE: To report and describe the MR imaging features of eight new cases of this rare soft tissue sarcoma and correlate them with the clinical and histologic findings. DESIGN AND PATIENTS. Retrospective analysis was carried out for the MR imaging characteristics and histologic findings of eight patients with pathologically proven epithelioid sarcoma and the literature was reviewed. Findings were correlated in each case with the patient's clinical presentation and eventual outcome. RESULTS: The patients, whose primary tumors ranged from 2.5 cm to 19 cm in maximum dimension, were 1 to 90 years of age. Tumors involved the extremities ( n=5), the scalp ( n=2) and the paraspinal muscles ( n=1). Five tumors presented as well-defined, frequently painful, deeply situated masses and three as subcutaneous nodules or cutaneous ulcers with no palpable mass. Four patients had associated regional lymphadenopathy and one had distant metastases at diagnosis. MR imaging showed tumor infiltration of adjacent tissues in seven patients. Signal characteristics reflected varying degrees of cellularity, and the presence of necrosis, hemorrhage, fibrosis, hyalinization and inflammation. Bone marrow involvement was demonstrated in one patient. Clinical outcomes were generally poor. CONCLUSIONS: Epithelioid sarcoma is an aggressive soft tissue sarcoma with a varied clinical presentation, growth pattern, MR signal characteristics and histologic picture. The tumor favors the distal extremities and is commonly infiltrative and accompanied by enlarged regional lymph nodes. This neoplasm may present as an intramuscular mass but should also be suspected in patients with ulcerating cutaneous nodules with or without regional lymphadenopathy.

Progressively developed myocardial apoptotic cell death during late phase of reperfusion.

Myocardial apoptosis is primarily triggered during reperfusion (R). The aim of this study was to test the hypothesis that R-induced apoptosis develops progressively during the late phase of R, and that R-induced apoptosis is associated with changes in expression of anti- and pro-apoptotic proteins and infiltrated inflammatory cells. Thirty-one dogs were subjected to 60 min of left anterior descending coronary occlusion followed by 6, 24, 48, and 72 h R, respectively. There was no group difference in collateral blood flow, measured by colored microspheres during ischemia. Necrotic cell death (TTC staining) was significantly increased during R, starting at 27 +/- 2% at 6 h R and increasing to 41 +/- 2% at 24 h R. There was no further change at 48 (37 +/- 3%) and 72 (36 +/- 6%) h R, respectively. TUNEL positive cells (% total normal nuclei) in the peri-necrotic zone progressively increased from 6 (26 +/- 2) to 24 (38 +/- 1), 48 (48 +/- 3) and 72 (59 +/- 4) h R, respectively. The number of detected TUNEL positive cells at these time points was consistent with an increased intensity of DNA ladders, identified by agarose gel electrophoresis. Compared with normal tissue, western blot analysis showed persistent reduction in expression of anti-apoptotic protein Bcl-2 from 6 (16 +/- 0.8%) to 72 h R (78 +/- 2%), and increase in expression of pro-apoptotic proteins including Bax from 6 (30 +/- 3%) to 72 h R (66 +/- 3%), and p53 from 6 (12 +/- 1%) to 72 h R (91 +/- 2%), respectively. Immunohistochemical staining revealed that infiltrated neutrophils (mm(2) myocardium) were significantly correlated with development of necrotic and apoptotic cell death from 6 to 24 h R, respectively (P < 0.05), while large macrophage infiltration seen during 48 to 72 h R were correlated with apoptotic cell death (P < 0.05). These results indicate that 1) necrosis peaked at 24 h R when apoptosis was still progressively developing during later R; 2) changes in Bcl-2 family and p53 proteins may participate in R-induced myocardial apoptosis; 3) inflammatory cells may play a role in triggering cell death during R. P < 0.05 vs. normal nuclei and tissue; P < 0.01 vs. 6 h R.

Dynamic progression of contractile and endothelial dysfunction and infarct extension in the late phase of reperfusion.

BACKGROUND: Myocardial injury during early reperfusion (R) has been well documented. However, the extent and time course of myocardial injury during late R are still unclear. The purpose of this study was to determine the extent of regional contractile and endothelial dysfunction and myocardial blood flow (MBF) defect as well as extension of infarction in association with neutrophil (PMN) actions during R. MATERIALS AND METHODS: A total of 29 dogs underwent a protocol of 1 h LAD ischemia followed by 6, 24, 48, and 72 h of R, respectively. Regional contractile function (sonomicrometry), MBF (colored microspheres), infarct size (triphenyltetrazolium chloride staining), and PMN localization (immunohistochemistry) were determined. RESULTS: Percentage segmental shortening at 6, 24, 48, and 72 h of R was significantly blunted (-1.8 +/- 1.2,* - 0.37 +/- 0. 6,* 0.04 +/- 0.2,* and 5.9 +/- 1.2* vs baseline 17.7 +/- 0.8). MBF (ml/min/g) was attenuated at 24 (0.27 +/- 0.03*), 48 (0.46 +/- 0. 07*), and 72 h of R (0.48 +/- 0.06*) vs 6 h of R (0.65 +/- 0.06). Infarct size increased from 6 (27 +/- 2%) to 24 h of R (41 +/- 2%*) with no further increase at 48 and 72 h of R, consistent with a peak of creatine kinase activity. PMN adherence (mm(2) endothelium) to left anterior descending coronary artery (LAD) segments was increased after 6 h of R (63 +/- 3*) vs nonischemic left circumflex coronary artery (LCX) segments (42 +/- 2) with a peak at 48 h of R (111 +/- 5*). Endothelium-dependent vascular relaxation in the LAD was also blunted at 6, 24, and 48 h of R. Immunostaining revealed CD18-positive PMNs were mainly accumulated in intravascular space during 6 h of R with an increase in migration of PMNs seen at 24 h of R, consistent with a peak of myeloperoxidase release. Myeloperoxidase activity in a given area at risk sample was significantly correlated with infarct extension during the first 24 h of R. CONCLUSIONS: These results provide pathologic evidence for myocardial injury during the extended R and a basis for exploration of interventions designed to limit myocardial injury after ischemia. (*P < 0.05 vs Baseline, 6 h of R and LCX segments.)

Genitourinary tuberculosis in patients with HIV infection: clinical features in an inner-city hospital population.

BACKGROUND: There has been a resurgence of tuberculosis (TB) in the United States, largely because of the HIV epidemic. The impact of this epidemic on the incidence and clinical presentation of genitourinary TB is largely unknown. We describe the clinical findings and outcomes of genitourinary TB in patients infected with HIV and compare them with those in patients not infected with HIV. METHODS: We retrospectively studied the case records of 16 patients infected with HIV and genitourinary TB and compared them with those of 8 patients without HIV infection diagnosed with genitourinary TB between January 1, 1991, and December 31, 1997, at a large, urban, inner-city, tertiary hospital. Data abstracted from records include demographics, symptoms, signs, laboratory and radiologic findings, and in-hospital mortality. RESULTS: Of 1282 patients with tuberculosis, 24 patients had positive urine cultures for Mycobacterium tuberculosis. HIV infection was present in 16 patients (75%). Patients infected with HIV were younger (mean age, 39.1 +/- 6.2 versus 53.9 +/- 17.2, P = 0.047) but did not differ significantly in clinical presentation from patients who did not have HIV infection. The combined mortality rate was 16.7%. Advanced age was the strongest predictor of poor outcome (P = 0.03). CONCLUSIONS: HIV infection was present in 66.7% of patients with genitourinary TB seen an inner-city hospital. Increasing age was associated with poor survival. No significant differences in clinical presentation nor in-hospital mortality were observed between those with HIV infection and those without HIV infection.

Cocaine and the kidney: a synthesis of pathophysiologic and clinical perspectives.

Cocaine abuse has reached epidemic proportions in the United States, and several forms of renal disease have been associated with this widespread use. The hemodynamic actions of cocaine, as well as its effects on matrix synthesis, glomerular inflammation, and glomerulosclerosis, may contribute to renal injury. Cocaine abuse has been associated with various forms of acute renal failure and acid-base and/or electrolyte disorders and may also have a role in the progression of chronic renal failure to end-stage renal disease. In utero exposure to cocaine has been associated with urogenital tract anomalies. Medical management of a hypertensive emergency caused by acute cocaine toxicity requires a multisystem approach, with close monitoring of cardiac, neurological, and renal functions.

Prevalence of non-diabetic renal disease among African-American patients with type II diabetes mellitus.

OBJECTIVE: This study aimed to characterize the prevalence of non-diabetic renal disease among African-Americans (AA) with type II diabetes mellitus based on a biopsy series. No previous study has investigated the nature of renal lesions in AA with type II DM. MATERIAL AND METHODS: Thirty AA patients with type II DM who were being managed at an inner-city hospital had kidney biopsies to evaluate suspected non-diabetic renal disease (NDRD) between 1994 and 1998. The demographic, clinical and histopathological data on these patients were analysed retrospectively. Kidney biopsies were reviewed by light microscopy, immunofluorescence and electron microscopy. RESULTS AND CONCLUSIONS: Three patterns of glomerular disease were observed. Diabetic nephropathy alone was seen in 13 patients (41.9%), diabetic nephropathy coexisted with glomerulonephritis in 12 patients (38.7%), while NDRD was seen in six patients (19.4%).

Vasculopathic changes of CADASIL can be focal in skin biopsies.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a newly described cause of vascular dementia. Pathologic examination shows multiple small infarcts in the deep cerebral white matter together with a nonatherosclerotic, nonamyloid angiopathy involving the media of small cerebral arteries. Ultrastructurally, characteristic granular material is present in the basal lamina of vascular smooth muscle cells in cerebral and extracerebral blood vessels. The ultrastructural changes have also been demonstrated in skin biopsies of affected patients; consequently, some investigators have recently recommended skin biopsies for the diagnosis of CADASIL. This study describes a 54-year-old male with a family history for strokes who had clinical and radiological features suggestive of CADASIL. A skin biopsy was performed to confirm the diagnosis. Initially, the characteristic vasculopathic changes of CADASIL were not identified within small blood vessel walls. However, multiple deeper sections in other areas showed electron-dense material associated with vascular smooth muscle cells, characteristic of CADASIL. Subsequent genetic testing demonstrated a single nucleotide substitution at position 659 on chromosome 19p13.1 causing an amino-acid change (Cys --> Phe), a finding indicative of CADASIL. The involvement of blood vessels within the dermis makes skin biopsy a useful adjunct in the diagnosis of CADASIL. However, as illustrated by this case, the findings may be focal, requiring a thorough evaluation of the entire biopsy specimen.

Ischemic preconditioning reduces neutrophil accumulation and myocardial apoptosis.

BACKGROUND: This study tested the hypothesis that ischemic preconditioning (IP) inhibits myocardial apoptosis after a short period of ischemia and reperfusion. METHODS: In 9 anesthetized dogs, the left anterior descending (LAD) coronary artery was occluded for 30 min and reperfused for 3 h (control), while in 9 others, LAD occlusion was preceded by 5 min of occlusion and 5 min of reperfusion (IP). DNA from frozen myocardial tissue samples was extracted, and apoptosis were identified as "ladders" by agarose gel electrophoresis or confirmed histologically using the terminal transferase UTP nick end-labeling (TUNEL) assay. Neutrophil accumulation was detected by measuring cardiac myeloperoxidase activity. RESULTS: Thirty minutes of LAD occlusion caused a significant decrease in blood flow (colored microspheres), which was comparable between groups. In the control group, DNA ladders occurred in the area at risk (AAR) in six out nine experiments. In contrast, DNA laddering in the AAR was not observed in any of the IP group. AAR in the control group showed a greater percentage of apoptotic cells than IP (6.7 +/- 0.9% vs 1.2 +/- 0.2%; p < 0.01). Cardiac myeloperoxidase activity (U/g tissue) was significantly reduced from 0.07 +/- 0.004 in control to 0.04 +/- 0.01 in IP group (p < 0.05). CONCLUSIONS: We conclude that ischemic preconditioning attenuates apoptosis and neutrophil accumulation in the AAR in a model of nonlethal acute ischemia and reperfusion.

An unusual cervical carcinoma showing exception to epitheliotropism of human papillomavirus.

Human papillomaviruses (HPV) infect epithelial tissues but have not been previously detected within mesenchymal cells. During a systematic investigation of FIGO stage Ib cervical cancers with colorimetric in situ hybridization, we detected HPV 16 DNA within the stromal compartment of an unusual undifferentiated carcinoma. The mesenchymal nature of the HPV-containing cells was confirmed by immunohistochemistry and electron microscopy. No viral particles were identified. Sequencing the majority of the HPV 16 genome identified few changes from the revised reference clone; all previously reported in other HPV 16 variants. These viral changes are unlikely to explain the exceptional mesenchymal localization of the HPV 16 DNA in this case.

A transitional variant of Castleman's disease presenting as a chylous pleural effusion.

Castleman's disease is an uncommon clinicopathologic entity that results in unregulated growth of lymphoid tissue. It may present as benign involvement of one lymph node group or as multicentric disease with serious systemic symptoms. Pleural effusions are an uncommon manifestation of Castleman's disease. We present a patient with Castleman's disease who initially presented with a chylous pleural effusion.

Rapid progression to end-stage renal disease in young hypertensive African Americans with proteinuria.

Hypertensive nephrosclerosis (HN) remains the most common cause of end-stage renal disease (ESRD) in blacks. This study examined whether renal histology corresponds with clinical hypertension in proteinuric blacks. Nondiabetic hypertensive blacks who satisfied inclusion criteria were enrolled in this study. Four male patients, each with a family history of hypertension and mean age 41 years, consented to kidney biopsy. Their mean arterial pressure was 116.5 mm Hg, mean urine protein excretion was 7.7 +/- 3.5 g/day. All patients progressed to ESRD within a mean duration of 14 months; the mean rate of decline in glomerular filtration rate was 53 mL/min/y, with an ESRD incidence of 80%/y. The histologic findings were consistent with previously described features of HN. Prominent glomerulosclerosis involved 30% to 75% of the glomeruli and extensive arteriolosclerosis/arteriosclerosis, tubular atrophy, and interstitial fibrosis. There was no evidence of immune complex disease by either immunofluorescence, electron microscopy, or serologic studies. The mean arterial pressure showed a strong but nonsignificant correlation with progression to ESRD (r = 0.8) and arteriosclerosis/arteriolosclerosis (r = 0.8). Glomerular sclerosis correlated with the reciprocal of serum creatinine (r = 0.6), interstitial fibrosis (r = 0.8), and arteriosclerosis/arteriolosclerosis (r = 0.3). Urine protein excretion correlated weakly with progression to ESRD (r = 0.4). These results indicate a poor correlation between clinical findings and histologic features on renal biopsy in young hypertensive African Americans. Hypertension remains a major cause of ESRD among African Americans, and progression to ESRD may be rapid in patients with marked proteinuria. Early and aggressive intervention is warranted.

Acute renal failure in pregnancy: a review of clinical outcomes at an inner-city hospital from 1986-1996.

Acute renal failure is a serious complication of pregnancy. Over the past few decades, the overall incidence of acute renal failure in pregnancy has decreased in Western societies. In less developed countries, the incidence of acute renal failure in pregnancy has remained high. This retrospective study examined the incidence, morbidity, fetomaternal mortality, and renal prognosis among pregnant inner-city patients. Serum creatinine levels of all pregnant patients seen at an inner-city hospital from January 1986 to December 1996 were reviewed. Twenty-one consecutive cases of acute renal failure were identified for an incidence of 2 in 10,000 pregnancies. Maternal mortality was high (15.7%) as was morbidity, with a tendency toward a high rate of intrauterine fetal growth retardation. These results suggest that the outlook for acute renal failure in inner-city patients is dismal in sharp contrast to the prognosis for other patient groups with acute renal failure in pregnancy in Western societies. Preventive strategies should be aimed at this subpopulation with a view to improving early prenatal care as well as enhancing overall access to the health-care system.

Coinfection with Giardia lamblia and Enterocytozoon bieneusi in a patient with acquired immunodeficiency syndrome and chronic diarrhea.

Diarrhea is an important clinical problem in immunosuppressed patients with acquired immunodeficiency syndrome (AIDS). There are numerous classical as well as emerging enteric pathogens that can produce diarrhea; however, these agents can be missed when only one method, such as microbiological examination of stool, is used for diagnosis. The endoscopic biopsy is a sensitive method for diagnosis of many viral, fungal, and parasitic infections of the gastrointestinal tract. Although only one agent is often identified in mucosal biopsies from these immunosuppressed patients, coinfection with multiple microbial agents is being increasingly recognized. Giardia infection is not as prevalent as other pathogens in patients with AIDS, but it remains an important diarrheal agent that is potentially curable. However, there have been only rare reports of coinfections with giardiasis and other infectious agents. This report describes a patient with AIDS and chronic diarrhea who had repeated negative stool examinations for ova and parasites. Light and electron microscopic examination of subsequent endoscopically obtained small intestinal biopsies revealed coinfection with two parasites, Enterocytozoon bieneusi and Giardia lamblia. Following treatment with metronidazole for giardiasis, the diarrhea persisted, but was less severe. This report also describes the diagnostic features of Giardia and Enterocytozoon infections in biopsy tissues and emphasizes the importance of identifying enteric coinfections in patients with AIDS to ensure timely and specific modes of therapy.

Granulomatous interstitial nephritis and uveitis presenting as salt-losing nephropathy.

Salt-wasting nephropathy is a rare syndrome in which renal insufficiency is associated with extracellular volume depletion from marked natriuresis in the absence of adrenal insufficiency or diuretics. We report the clinical course of a 23-year-old woman with renal insufficiency, in association with orthostatic hypotension and salt wasting. A combination of daily infusion of saline, a high-salt diet and oral fludrocortisone did not compensate for her salt loses. Renal biopsy showed noncaseating granulomas and marked interstitial inflammation. Renal function and salt loss improved with prednisone therapy and 6 months after withdrawal of steroids, her renal function remains stable.

Ultrastructural distinction of basaloid-squamous carcinoma and adenoid cystic carcinoma.

Basaloid-squamous carcinoma is a unique and infrequent variant of squamous cell carcinoma with a predilection for occurring in the upper aerodigestive tract. The cardinal diagnostic criteria are the presence of basaloid cells arranged in lobules or cords and a squamous component. Another feature that distinguishes basaloid-squamous carcinoma from conventional squamous cell carcinoma is the development of multiple foci of amorphous, eosinophilic, or mucinous materials among the basaloid tumor cells. It is this feature in basaloid-squamous carcinoma that causes confusion with adenoid cystic carcinoma, especially the solid variant of adenoid cystic carcinoma. To clarify the distinctive features of these two types of tumors, the ultrastructural findings in three basaloid-squamous carcinomas from the head and neck region were compared with three adenoid cystic carcinomas, one from the head and neck region and one each from trachea and bronchus. Widened intercellular spaces, tonofilaments, and replicated basal lamina were present in both types of tumor. However, the ultrastructural features of glandular differentiation were present only in adenoid cystic carcinoma, whereas the ultrastructural features of squamous cell differentiation were present only in basaloid-squamous carcinoma. The distinction between basaloid-squamous carcinoma and adenoid cystic carcinoma is important since basaloid-squamous carcinoma is a clinically aggressive, high-grade form of squamous cell carcinoma, generally with a worse prognosis than adenoid cystic carcinoma.

Skin necrosis indicating antiphospholipid syndrome in patient with AIDS.

Although antiphospholipid antibodies have been detected in patients with human immunodeficiency virus (HIV) disease, the clinical manifestations of the antiphospholipid syndrome are extremely rare. We describe a woman with acquired immunodeficiency syndrome (AIDS) and elevated antiphospholipid antibodies who developed necrotic skin lesions and was subsequently shown to have antiphospholipid syndrome. This finding contradicts the general belief that such antibodies are not clinically significant in patients with HIV disease. We follow the report with a brief description of the antiphospholipid syndrome and its relation to AIDS.

The flexor digitorum longus: an anatomic and microscopic study for use as a tendon graft.

Recent experimental studies have shown that intrasynovial donor tendons have the capacity to heal with minimal alteration in the gliding surface when grafted to an intrasynovial location. In order to evaluate the flexor digitorum longus of the foot as a potential matched donor tendon for use in flexor tendon grafting, we dissected 15 feet (75 toes) and 10 hands (50 fingers) to determine the intrasynovial lengths of the flexor digitorum longus and flexor digitorum profundus and to determine a method of tendon graft harvest. Specimens were taken from the intrasynovial portion of each tendon for evaluation by light and electron microscopy. The intrasynovial tendons of the hand and foot were similar in vascularity, cellularity, gliding surface, and ultrastructure. The flexor digitorum longus tendon of the foot was a mean length of 12 cm to the area of tendon confluence in the midfoot, which will usually provide enough tendon length for grafting from the distal phalanx to the palm of the hand. Because of the difference in length of the synovial sheaths of the fingers and toes, some extrasynovial tendon will be transferred to the synovial space when a flexor digitorum longus tendon is used.