Microscopic correlation of radiographically disparate appearing well differentiated osteosarcoma.

Well differentiated (low grade) osteosarcomas are often unrecognized and inadequately treated. We report on a patient with a well differentiated osteosarcoma of the tibia that radiographically presented with two strikingly dissimilar appearing juxtaposed lesions. Proximally, the lesion was sclerotic, and distally, osteolytic. The distal lytic half of the lesion showed focal cortical disruption on MR imaging. Microscopic correlation of the resected specimen suggested that the sclerotic component of the lesion had more fibrous dysplasia-like tissue with fewer features of well differentiated osteosarcoma, and the lytic component, features suggestive of well differentiated osteosarcoma. We believe this microscopic interpretation explains the disparate radiographic appearance as all belonging to well differentiated osteosarcoma with varying amounts of fibrous dysplasia-like tissue rather than the development of well differentiated osteosarcoma in fibrous dysplasia.

Acral synovial chondrosarcoma.

Acral chondrosarcoma is rare. Synovial chondrosarcoma is even rarer. Synovial chondrosarcoma arising without evidence of pre-existing or concurrent synovial chondromatosis is exceedingly rare. We present a case of acral synovial chondrosarcoma involving both sides of the metacarpophalangeal joint of the thumb in a 69-year-old man. Radiographically, the lesion mimicked gout. On MR imaging, the lobulated contours of the soft tissue mass suggested synovial chondromatosis. Histological examination revealed a chondrosarcoma, which on the basis of imaging findings we present as having arisen from the synovium. The tumor invaded a portion of the cartilage of the metacarpophalangeal joint and equally destroyed the bones of the distal metacarpal and base of the proximal phalanx of the thumb, while sparing the bony joint surfaces.

Histological evaluation of iron in liver biopsies: relationship to HFE mutations.

OBJECTIVE: Hepatic iron overload is observed in many forms of chronic liver disease. Hereditary hemochromatosis (HH) results in hepatic iron overload and is associated with 2 missense mutations in the HFE gene. The aim of this study was to define the usefulness of the histological pattern of iron deposition in determining the probability of an iron-loaded patient having HFE-related iron overload. METHODS: This study assessed liver biopsies containing stainable iron from 103 patients with various liver diseases; clinical information included hepatic iron concentration and HFE genotype (C282Y, H63D). The biopsies were evaluated using a reproducible histological scoring system for iron deposition. Three separate components of histological iron deposition were recorded: 1) pattern (primarily hepatocellular with a zonal gradient, or reticuloendothelial without an obvious zonal gradient), 2) pattern score to denote the extent of iron within the acinus, and 3) quantitation grade of iron granules within affected hepatocytes. RESULTS: The predominantly hepatocellular pattern (HH pattern) was observed in 72 biopsies of which only 42 were from patients homozygous for the C282Y mutation, indicating that this pattern alone cannot be used as a surrogate marker for HH genotype. The predominantly reticuloendothelial pattern (non-HH pattern) was observed in the remaining 31 patients, none of whom was compound heterozygous or homozygous for the C282Y mutation (negative predictive value: 100%). Thus, the non-HH, reticuloendothelial pattern reliably predicts the absence of homozygosity for the C282Y mutation. CONCLUSIONS: The use of histological evaluation for iron deposition is simple, assists in expanding information communicated from histopathologic observations, and may be clinically useful in determining the necessity of further evaluation of HFE genotype in subjects with histological evidence of hepatic iron overload.

Repetitive self-limited acute pancreatitis induces pancreatic fibrogenesis in the mouse.

The role of repetitive acute injury in the pathogenesis of chronic pancreatitis remains unknown. To determine if repetitive injury induced by pancreatic hyperstimulation would reproduce the characteristic features of human chronic pancreatitis, acute reversible pancreatic injury was induced in mice by twice weekly cerulein treatment, 50 microg/kg/hr x 6 hr, for 10 weeks. Procollagen alpha1(I) mRNA was markedly increased by week 2. Sirius red staining of interstitial collagen demonstrated progressive accumulation of extracellular matrix surrounding acinar units and in interlobular spaces. Atrophy, transdifferentiation of acinar units to ductlike tubular complexes, and dilatation of intraacinar lumina also developed. Electron microscopy demonstrated the presence of stromal cells in areas of fibrosis with morphologic characteristics of pancreatic stellate cells. These findings demonstrate that, in a murine model, repetitive acute injury to the pancreas by hyperstimulation can reproduce the major morphological characteristics of human chronic pancreatitis.

Nonalcoholic steatohepatitis: a proposal for grading and staging the histological lesions.

OBJECTIVE: Steatohepatitis is a morphological pattern of liver injury that may be seen in alcoholic or nonalcoholic liver disease. This pattern may occur with obesity, diabetes, the use of certain drugs, or the cause may be idiopathic. The well-recognized histopathological features of nonalcoholic steatohepatitis (NASH) include hepatocellular steatosis and ballooning, mixed acute and chronic lobular inflammation, and zone 3 perisinusoidal fibrosis. Currently, there are no systems for grading necroinflammatory activity or for staging fibrosis as exist for various other forms of chronic liver disease. The purpose of this study was to develop such a grading and staging system and was based on review of liver biopsies from 51 patients with nonalcoholic steatohepatitis from Saint Louis University Health Sciences Center. METHODS: For determination of grade, 10 histological variables of activity were initially analyzed; an overall impression of mild, moderate, and severe was made and the variables considered to be most significant were used to develop the necroinflammatory grade. RESULTS: The histological lesions considered to be significant were: steatosis, ballooning, and intra-acinar and portal inflammation. A staging score was developed to reflect both location and extent of fibrosis. The fibrosis score was derived from the extent of zone 3 perisinusoidal fibrosis with possible additional portal/periportal fibrosis and architectural remodeling. Fibrosis stages are as follows: Stage 1, zone 3 perisinusoidal fibrosis; Stage 2, as above with portal fibrosis; Stage 3, as above with bridging fibrosis; and Stage 4, cirrhosis. CONCLUSION: We propose a grading and staging system that reflects the unique histological features of nonalcoholic steatohepatitis.

Ber-H2 (CD30) immunohistochemical staining in malignant melanoma.

Malignant melanoma can be included in the differential diagnosis of Hodgkin's disease, anaplastic large cell lymphoma, or embryonal carcinoma These malignancies express CD30, a marker of diagnostic value. A retrospective immunohistochemical study was undertaken to determine the frequency of immunoreactivity of Ber-H2 (anti-CD30 monoclonal antibody) in malignant melanoma Archival paraffin-embedded tissue from 24 primary and metastatic lesions was used. No Ber-H2 labeling was observed in the majority of the studied cases. Variable weak cytoplasmic staining was present in only one case. The findings are compared with the previous reports claiming frequent CD30 expression in malignant melanoma. We discuss issues pertaining to the interpretation of the Ber-H2 IHC staining in formalin-fixed, paraffin-embedded tissue.

Diagnosis and management of appendiceal mucoceles.

Preoperative diagnosis of appendiceal mucoceles is rare. If untreated, one type of mucoceles may rupture producing a potentially fatal entity known as pseudomyxoma peritonei. The importance of diagnosing appendiceal mucoceles is highlighted through a case presentation of a woman who had an incidental finding of mucinous cystadenoma of the appendix during colonoscopic evaluation for occult gastrointestinal bleeding. A detailed review of the medical literature regarding appendiceal mucoceles is presented, with emphasis on the pathologic, clinical, radiologic, and evolving endoscopic features. Surgical options and prognosis are discussed.

Clinics in diagnostic imaging (21). Intraosseous lipoma of the calcaneum.

A 50-year-old woman presented with plantar foot pain. Radiographs and computed tomography demonstrated an intraosseous lipoma of the calcaneum. Curettage and packing were performed. The imaging features, including the magnetic resonance appearances, of intraosseous lipomas are described.

Testicular circulatory isolation: not a cause of immune-mediated testis injury in the rat.

BACKGROUND: Testicular circulatory isolation (TCI), a regional drug exclusion approach designed to prevent chemotherapy-induced male infertility, can reduce testicular drug exposure and preserve fertility. The immunological sequelae of this surgical procedure were investigated. METHODS: Forty Sprague-Dawley rats received unilateral TCI for 45 min and were killed at intervals of up to 43 days later. Testicular histology was evaluated qualitatively using hematoxylin and eosin stain, a direct immunofluorescent technique for detection of antigen-antibody complexes, and an indirect immunofluorescent technique to detect circulating antitestis antibodies. RESULTS: No immune-mediated injury was evident up to 43 days after TCI. CONCLUSION: The current work, taken together with previously published data, indicate that TCI produces no immunological damage in the rat testis. Because TCI is well tolerated in humans, this work also supports the institution of human clinical trials of this technique in men about to receive fertility-threatening chemotherapy.

Dynamic sequential 3D gadolinium-enhanced MRI of the whole breast.

Dynamic contrast-enhanced 2D MR imaging of the breast has shown high sensitivity and specificity for the detection and characterization of breast lesions. We investigated the ability of a dynamic fast 3D MR imaging technique that repeatedly scans the whole breast in 44-s intervals without an interscan delay time to obtain similar sensitivity and specificity as 2D imaging. Fifty-six patients scheduled for breast biopsy were entered into the study, and 83 lesions detected by 3D dynamic scanning were biopsied. Dynamic 3D contrast-enhanced breast imaging with subtraction detected and correctly classified all 23 cancers, and 44 of the 60 benign lesions yielding a sensitivity of 100%, a specificity of 73%, and a 100% predictive negative value. The enhancement profiles of metastatic lymph nodes were similar to those of primary cancer. This technique allowed detection of multifocal and multicentric lesions and did not require a prior knowledge of lesion location. These results indicate that dynamic contrast-enhanced 3D MRI of the whole breast is a useful and economically feasible method for staging breast cancer, providing a comprehensive noninvasive method for total evaluation of the breast and axilla in patients considering breast conservation surgery or lumpectomy.

Nafcillin-associated hepatotoxicity. Report of a case and review of the literature.

Nafcillin is a semisynthetic penicillin that is generally well tolerated with few side effects. Hepatic complications are rare but have a potential for serious liver dysfunction. This unusual complication causes a predominantly cholestatic injury, which can persist for prolonged periods even after discontinuing the medication. The pathophysiology may include direct cytotoxicity or an immune-mediate hypersensitivity. Treatment is generally supportive, except for severely symptomatic patients who may require steroids. We report a case of nafcillin-associated hepatotoxicity and review the literature of this disorder.

Hepatic mitochondrial oxidative metabolism and lipid peroxidation in iron-loaded rats fed ethanol.

The aims of this study were to determine whether chronic ethanol consumption potentiates mitochondrial lipid peroxidation or impairment of mitochondrial oxidative metabolism in rats with chronic iron overload. Experimental iron overload was induced by feeding rats a chow diet supplemented with 2.5% carbonyl iron. After 8 to 12 weeks, half of the iron-loaded and control animals were changed to a liquid diet containing ethanol for 4 to 5 weeks. The remaining animals were fed an isocaloric amount of diet containing dextrin-maltose instead of ethanol for 4 to 5 weeks. Iron-supplemented animals had a 20-fold increase in hepatic iron concentration as compared with controls. Iron and ethanol independently increased plasma alanine aminotransferase (ALT) levels (p < 0.05) while the combination resulted in an additive increase in ALT levels (p < 0.01). Although iron overload increased the levels of mitochondrial conjugated dienes and significantly reduced the mitochondrial respiratory control ratio, ethanol administration did not affect these parameters in animals with or without iron overload. Livers from iron-loaded rats that received ethanol showed mild to moderate steatosis with scattered necroinflammatory foci. There was no significant increase in necroinflammatory foci in the livers of the iron plus ethanol group as compared with the iron group. In conclusion, we have demonstrated an additive increase in hepatocellular injury when ethanol is fed to iron-loaded rats, as evidenced by an increase in plasma ALT level. However, there were no additive or synergistic effects of iron and ethanol on either mitochondrial lipid peroxidation or mitochondrial oxidative metabolism.

Nonalcoholic steatohepatitis: an expanded clinical entity.

BACKGROUND/AIMS: In the past, nonalcoholic steatohepatitis has been described mostly in obese women with diabetes. The aim of this study was to describe a series of patients with nonalcoholic steatohepatitis with a different clinical profile. METHODS: The clinical, biochemical, and histological features of 33 patients with nonalcoholic steatohepatitis seen from July 1990 to June 1993 were analyzed. RESULTS: The mean age was 47 years. All patients were antibody to hepatitis C virus-negative. Nineteen of 33 (58%) were men, 20 of 33 (61%) were nonobese, 26 of 33 (79%) had normal glucose levels, and 26 of 33 (79%) had normal lipid levels. Fourteen of 33 (42%) had normal glucose and lipid levels and were not obese. Thirteen of 33 (39%) had pathological increases in fibrosis, 5 of whom had micronodular cirrhosis. Of these 13 with severe, progressive disease, 8 (62%) were women, 8 (62%) were obese, 4 (31%) were diabetic or had an elevated glucose level, and 3 (23%) had hyperlipidemia. Although serum iron studies (transferrin saturation and ferritin) were abnormal in 18 of 31 (58%), no patient had hemochromatosis. CONCLUSIONS: Nonalcoholic steatohepatitis can be a severe, progressive liver disease leading to the development of cirrhosis. It should no longer be considered a disease predominantly seen in obese women with diabetes.

Cerulein-induced pancreatic cysteine depletion: prevention does not diminish acute pancreatitis in the mouse.

BACKGROUND/AIMS: Induction of acute necrotizing pancreatitis with cerulein causes profound pancreatic glutathione depletion in the mouse. Because cysteine availability can be rate-limiting for glutathione synthesis, the pancreatic content of cysteine during cerulein treatment was measured and the potential benefit of augmenting pancreatic cysteine was determined. METHODS: Female Swiss-Webster mice were treated with cerulein with and without simultaneous administration of the cysteine prodrug, L-2-oxothiazolidine 4-carboxylic acid. Pancreatic cysteine and glutathione content were measured, and serum amylase levels and pancreatic histology were assessed. RESULTS: Pancreatic cysteine content decreased to 42% of normal after 4 hours of cerulein treatment. L-2-oxothiazolidine 4-carboxylic acid more than doubled pancreatic cysteine content at 4 hours and prevented pancreatic cysteine depletion when administered with cerulein. Cerulein caused pancreatic glutathione depletion despite this normalization of cysteine. Moreover, the biochemical and histological evidence of cerulein-induced pancreatitis was unaltered by preventing cysteine depletion. CONCLUSIONS: Pancreatic cysteine is depleted during induction of acute pancreatitis with cerulein in parallel with depletion of pancreatic glutathione. Because preventing pancreatic cysteine depletion with L-2-oxothiazolidine 4-carboxylic acid did not prevent glutathione loss, causes of pancreatic glutathione depletion other than insufficiency of this critical precursor must also play an important role in cerulein-induced glutathione depletion.

Jejunized colon: a rare complication of carcinoid tumor.

A 23-yr-old female with a history of dyspnea, palpitation, productive cough, occasional hemoptysis, intermittent diarrhea, and abdominal pain was found to have metastatic carcinoid tumor and a "jejunized colon." Carcinoid tumors are relatively rare neoplasms found throughout the gastrointestinal tract, the ovaries, and the lungs. Barium enema showed a normal rectum and a pattern identical to jejunum in the proximal colon. Endoscopic biopsies confirmed the presence of small intestinal mucosa in the colon. Foreshortening of the colon was probably due to a desmoplastic reaction secondary to the carcinoid tumor. Histologic confirmation of these findings has never been described before.

A fast 3D-imaging technique for performing dynamic Gd-enhanced MRI of breast lesions.

The characterization of breast lesions by their Gd-enhancement profiles has been proposed as a method for differentiating benign from malignant breast lesions. The limitations of dynamic contrast enhanced 2D imaging of the breast are the low number of slices that can be acquired, and the need to know the location of the lesion a priori to correctly select the noncontiguous 2D slice locations. These problems are exacerbated when multi-focal disease is present but not anticipated. Standard fast 3D gradient-echo imaging has a variable delay between successive acquisitions. We have developed a fast 3D gradient-echo imaging technique for dynamic Gd-DTPA enhanced breast imaging which obtains multiple 3D image sets of 32 contiguous images at 44 s intervals without an interscan delay time. This rapid 3D imaging technique achieves good temporal resolution and reduces patient motion between pre- and postcontrast images while covering a much larger portion of the breast and eliminating the need for a priori knowledge concerning the location of the lesion(s) when performing Gd-enhanced dynamic MR imaging.

Testicular cytotoxicity of intravenous procarbazine in rats.

Although the testicular cytotoxicity of procarbazine has been evaluated in the rat, previous models have utilized routes other than the intravenous one, and have generally employed multiple-dose regimens. In this report, we describe testicular toxicity in the Sprague-Dawley rat following a single intravenous bolus of procarbazine (0-700 mg kg body weight), with necropsy 59 +/- 2 days later. Testicular toxicity was evaluated qualitatively by histology and quantitatively by testicular weight, sperm head count, repopulation index and epididymal index. Effects of procarbazine on heart, lung, liver and kidney histology were evaluated qualitatively. Progressive dose-dependent testicular atrophy and oligospermia occurred at low and intermediate dosages of procarbazine. Marked testicular atrophy, oligospermia and germinal hypoplasia were observed at high dosages (500 and 700 mg kg-1 body weight). LD50 at day 59 for procarbazine appears to be approximately 600 mg kg-1 body weight using this regimen. This model will facilitate the study of techniques to avoid drug-induced testicular damage.

A new case of IgE myeloma.

We report a case of IgE myeloma in a 78-year-old woman who presented with bone pain in the shoulder and hip and progressive weakness. Except for hypercalcemia, routine chemistry values were within normal limits. Hemoglobin was decreased and the leukocyte count slightly increased. Plasma cells were not observed in the peripheral blood. Serum protein electrophoresis showed a monoclonal protein in the beta-globulin fraction. Immunofixation confirmed the presence of an IgE kappa monoclonal protein. A bone marrow biopsy revealed an interstitial and nodular infiltration of abnormal plasma cells comprising 60% of nucleated cells present. Skeletal roentgenograms and bone scans of this patient showed osteolytic lesions and osteopenia of the thoracic and lumbar spine and osteolytic destruction of the right half of the sacrum. Flow-cytometric analysis of mononuclear cells isolated from peripheral blood showed that 15% of the lymphocytes bound IgE. Using cell-surface markers, we identified 45% of the IgE-positive cells as natural killer cells. Similar results have been found in other diseases marked by increased IgE. The clinical, radiological, and laboratory findings for this patient are compared with previously reported cases of IgE and other types of myeloma.