Pseudoinvasion with high-grade dysplasia in a colonic adenoma. Distinction from adenocarcinoma.

High-grade dysplasia was found to extend to an area of pseudoinvasion in the submucosa of a colonic adenoma mimicking invasive carcinoma. The presence of both benign and cytologically malignant epithelium and residual foci of lamina propria among the submucosal glands distinguishes this entity from adenocarcinoma arising in an adenomatous polyp.

Major histocompatibility complex class I and class II expression by myocytes in cardiac biopsies posttransplantation.

A total of 85 cardiac biopsies from patients 23-265 days posttransplant were studied for the correlation of the rejection grade score with the level of major histocompatibility complex (MHC) class I and class II expression on cardiac myocytes and endothelial cells, the quantitative level of leukocytic infiltrate, and the immunophenotype of the leukocytes. Results indicate a lack of absolute correlation between rejection grade scores and levels of MHC antigen expression. Further, a lack of absolute correlation was also seen with quantitation of leukocytic infiltrates and relative levels of MHC antigen expression. Of great interest was our preliminary finding that as early as 4 weeks prior to a rejection episode scored by routine histological criteria as grade 4, cardiac biopsy from the patient demonstrated high levels of MHC class I and class II expression. Similar increases of MHC antigen expression prior to an increase in histological rejection score grades were also noted in serial biopsies of 2 other patients. These data suggest that it may be quite useful to examine levels of MHC antigens on cardiac biopsies posttransplantation as an additional parameter for monitoring of cardiac rejection episodes.

Hypersensitivity myocarditis in heart transplant candidates.

Hypersensitivity myocarditis is a rare event; however, routine histologic examination of all (193) explanted hearts for heart transplantation in our institutions revealed hypersensitivity myocarditis in 15 patients (7%). This is a previously unreported finding in heart transplant recipients. None of the cases was detected clinically, although all manifested peripheral eosinophilia at some point during the 2 weeks before transplantation. Only one patient exhibited a skin rash interpreted as allergic. The severity of the interstitial infiltrate varied from grade I to grade IV (semiquantitative). This group of pretransplantation patients was receiving a multiplicity of drugs, some of which could have potentially triggered the hypersensitivity myocarditis, although in only one case was a definite association between a hypersensitivity reaction and a drug made. The unusually high rate (10.3% for the Emory cases) of drug-induced myocarditis in this group of patients, contrasted with the general autopsy population, probably reflects that these patients received more vigorous than usual drug treatment, particularly antibiotics, to sustain them until a suitable donor was found.

Ovarian granulosa cell tumors--immunohistochemical localization of estradiol and ultrastructure, with functional correlations.

The authors studied immunohistochemical localization of estradiol and ultrastructure in 11 ovarian granulosa cell tumors in an effort to establish the cellular source of increased estrogen in patients with granulosa cell tumors. Estradiol was identified by the immunoperoxidase method in 10 tumors, and staining was confined to scattered groups of granulosa cells or isolated granulosa cells. The majority of tumor cells in all 5 cases examined by electron microscopy were undifferentiated cells, but in 2 cases, a small percentage of tumor cells contained mitochondria with tubular cristae and well-developed smooth endoplasmic reticulum. Interpreted in conjunction with in vitro studies of granulosa cells, the results suggest that neoplastic granulosa cells may resemble ovarian follicular granulosa cells of all stages of maturation and are capable of estrogen production.

Surgical options, hematologic evaluation, and pathologic changes in Budd-Chiari syndrome.

This article presents a scheme of management for Budd-Chiari syndrome based on experience with 33 patients. Therapy in acute Budd-Chiari syndrome is dictated by the liver biopsy, with hepatocyte necrosis indicating the need for placement of a decompressive shunt. The type of shunt was determined by intrahepatic vena cava obstruction; a higher morbidity rate was associated with the mesoatrial shunt in 11 patients than with a portacaval shunt in 10 patients. Successful shunt placement allowed stabilization of the liver biopsy and maintenance of good hepatocyte function [galactose elimination capacity (preoperative: 349 +/- 40 mg/minute; 20 months: 344 +/- 60 mg/minute)]. Severe fibrosis and reduced galactose elimination capacity (264 +/- 43 mg/minute) indicated advanced disease--chronic Budd-Chiari syndrome--and were indications for liver transplant. Hematologic evaluation documented a myeloproliferative disorder in 8 of the last 13 patients evaluated; perioperative and late anticoagulation and/or chemotherapy reduced recurrent thrombosis. We conclude that the Budd-Chiari syndrome requires different therapies depending on the stage of disease. If no hepatocyte injury is present on biopsy, therapy may not be needed. Acute, reversible injury can be managed by placement of a decompressive shunt. Irreversible damage requires transplantation. Selection of the right therapy requires a complete evaluation.

Case report: fulminant Kaposi's sarcoma after orthotopic liver transplantation.

Fulminant multicentric Kaposi's sarcoma developed in an American-born HIV-negative patient 8 months after orthotopic liver transplantation. Despite its rarity in liver transplantation, Kaposi's sarcoma should be considered in the differential diagnosis in hepatic allograft recipients presenting with rapidly growing cutaneous or polylymphadenopathic lesions.

The surgical pathologist's role in liver transplantation.

Liver transplantation has become an option in treating a wide variety of diseases. The surgical pathologist, as a member of the transplantation team, is increasingly involved in the evaluation of allograft dysfunction. Interpretation of the liver allograft biopsy specimen requires integration of clinical history, biochemical data, and histologic patterns of a wide variety of lesions, including harvesting injury, vascular thrombosis, rejection, infection, and recurrent disease. This article reviews the varied histologic appearances of the more common forms of liver allograft injury, the contexts in which they arise, and their distinction from one another.

Primary non-Hodgkin's lymphoma of the heart in two patients with the acquired immunodeficiency syndrome.

We report two cases of primary cardiac lymphoma that developed in patients suffering from the acquired immunodeficiency syndrome. Both cases of lymphoma were histologically aggressive as generally observed in patients with the acquired immunodeficiency syndrome. The lymphoma cells in the center of a tumor nodule obtained from one patient were monoclonal B-cells, whereas those at the periphery showed a polyclonal pattern of staining. It is postulated that this represents a monoclonal lymphoma evolving from a polyclonal B-cell lymphoproliferation analogous to those reported in some cases of lymphoma in immunosuppressed patients infected with Epstein-Barr virus. The lymphoma cells in the other case failed to stain for cytoplasmic immunoglobulins. The possible underlying basis for the increase in incidence of lymphoma in immunodeficiency and the reasons for prevalence of extranodal sites are discussed.

Hypertrophic cardiomyopathy evolving into a hypokinetic and dilated left ventricle: coronary embolization as a probable pathogenetic mechanism.

A long-term follow-up (9 years) in a patient with hypertrophic cardiomyopathy revealed an evolution to a hypokinetic and dilated left ventricle. The patient underwent heart transplantation, and therefore the native heart was available for morphologic studies. Gross and microscopic stigmata of hypertrophic cardiomyopathy were present, as well as evidence of left ventricular dilatation. Multiple myocardial scars in both ventricles indicated past ischemic episodes, most probably due to coronary embolization from left ventricular mural thrombi. Other possible pathogenetic mechanisms for the progression of hypertrophic cardiomyopathy to a dilated one are discussed.

Diagnosis of pulmonary toxoplasmosis by bronchoalveolar lavage in cardiac transplant recipients.

We report two cases of fatal, clinically unsuspected disseminated toxoplasmosis that developed following orthotopic cardiac transplantation. Toxoplasma gondii trophozoites, pseudocysts, and cysts were best visualized on hematoxylin and eosin and Giemsa-stained cytospin preparations of bronchoalveolar lavage fluid. Post-mortem examination in both cases revealed disseminated toxoplasmosis with extensive involvement of the lungs and heart. The patients, who were seronegative for antibody to T. gondii prior to transplantation, received organs from donors whose serology status was unknown. Demonstration of anti-toxoplasma antibodies post-transplantation occurred in both cases. Bronchoalveolar lavage may be useful in diagnosis of pulmonary toxoplasmosis. Clinicians, pathologists, and cytopathologists must consider T. gondii in the differential diagnosis of pneumonia in the immunocompromised patient, especially cardiac transplant patients.

Optimal beef cattle diets formulated by nonlinear programming.

A beef diet model based on National Research Council recommendations is significantly nonlinear for feed ingredients, daily gain and weight of cattle. Solving a diet model has been difficult, but advances in nonlinear programming now allow solutions that are quick and easy. This study developed a nonlinear programming method for optimally planning a feeding program by choosing feeds, daily gains and selling weight. Two types of diets are important for this purpose:optimal-return diets and least-cost-gain diets. For a given weight of cattle, an optimal-return diet chooses feeds and daily gain to maximize returns above feed costs. A least-cost-gain diet chooses feeds and daily gain to minimize feed plus yardage costs per kilogram of gain. In an optimal feeding program, a sequence of optimal-return diets is fed to increasing weights of cattle. Feed costs plus yardage per kilogram of gain rise to equal the actual selling price at the optimal selling weight, and the cattle are sold. Cattle feeders and researchers with access to a microcomputer can maximize net returns from a feeding program.

Pancreatic transplants: CT-guided biopsy.

With use of computed tomographic (CT) guidance, 10 biopsies of pancreatic allografts were performed in four patients to determine the cause of pancreatic dysfunction. All biopsies were performed with an 18-gauge biopsy needle and with use of a biopsy gun. On four occasions, simultaneous biopsies of the pancreatic head and tail were performed. In nine of the 10 biopsies, specimens obtained were adequate for diagnosis. In two of the four simultaneous procedures, important histologic differences were noted between specimens from the head and those from the tail of the allograft. No complications occurred. These findings demonstrate the ease, accuracy, and safety of CT-guided biopsies of pancreatic transplants with a biopsy gun. Simultaneous sampling of the pancreatic head and tail may provide important clinical information that may not be available when the usual cystoscopically guided biopsy of the pancreatic head is used.

Effect of distal splenorenal shunt on survival of patients with primary biliary cirrhosis.

Distal splenorenal shunt is known to effectively control bleeding from esophageal and gastric varices; however, the effect of this selective shunt on liver function is less well understood. We examined retrospectively the effect of distal splenorenal shunt on the survival of 19 patients with primary biliary cirrhosis subjected to surgery for bleeding varices over a 20-yr period and had been followed for at least 1 yr. Actual Kaplan-Meier survival curve was compared with predicted survival curve based on the Mayo Clinic model using clinical data collected at the time of surgery. The patients median length of follow-up was 65.9 mo. Ten of the 19 patients died or underwent orthotopic liver transplantation during the period of observation. The actual Kaplan-Meier and predicted Mayo Clinic model survival curves were similar and did not differ significantly. Survival was best in patients with good liver function (i.e., low Mayo risk scores). Distal splenorenal shunt, therefore, did not appear to have an adverse effect on the survival of patients with primary biliary cirrhosis. We conclude that variceal bleeding in primary biliary cirrhosis patients with good liver function should not be considered an indication for liver transplantation. Instead, if treatment with sclerotherapy or beta-blockers fails then distal splenorenal shunt will prevent recurrent bleeding in 90% of patients and leave them with an excellent prognosis.

Endoscopic variceal sclerosis does not increase the risk of portal venous thrombosis.

In this study the risk of thrombosis in the portal venous system was assessed in patients with chronic variceal bleeding undergoing sclerotherapy. Twenty-two patients with cirrhosis were prospectively studied with angiography before initiation of sclerotherapy and at mean (+/- SD) 26 +/- 17-month (range, 8-63 months) follow-up. Sclerotherapy consisted of flexible endoscopy, intravariceal and paravariceal, using sodium morrhuate (1.5%-2%) and sodium tetradecyl sulfate (0.5%-1.5%), to obliteration. The mean number of sessions was 6.5 +/- 2.2 (range, 3-11), with a mean total amount of sclerosant of 62 +/- 25 mL (range, 25-112 mL). No patient developed splenic or portal vein thrombosis as shown by arteriography. The flow patterns of portal perfusion, vessel size, and coronary vein visualization showed no significant change. Only one patient had spontaneous reversal of portal flow. Splenic vein histology, examined in five patients in whom sclerotherapy failed and who required shunt surgery, was not significantly different from that in eight patients who had no prior sclerotherapy. It is concluded that under the conditions of the current study, chronic sclerotherapy did not increase the risk of thrombosis in the portal venous system and did not significantly alter the histology of the portal hypertensive splenic vein.

The role of continued drinking in loss of portal perfusion after distal splenorenal shunt.

Fifty percent of patients with alcoholic cirrhosis who undergo distal splenorenal shunting for variceal bleeding lose portal perfusion within 1 year. Although it was previously considered that this loss of portal flow was irrevocable, the present study shows that with resolution of alcoholic hepatitis, portal perfusion can be restored. A 34-year-old patient with alcoholic liver disease and a distal splenorenal shunt lost portal perfusion 1 year after the operation. He had continued to drink alcohol and had high sinusoidal pressure. Following forced abstinence over the next 2 years, his sinusoidal pressure fell, liver volume decreased, results of liver biopsy improved, and portal perfusion was restored. Shunt patency was documented, and the same collaterals from the portal vein to the shunt could still be visualized as had been seen when portal flow was absent. Restoration of portal perfusion was attributed to decreased intrahepatic resistance secondary to abstinence from alcohol. A return to drinking in the next 9 months led to alcoholic hepatitis and once again loss of portal perfusion. This study places emphasis on increased intrahepatic resistance rather than the development of portal-to-shunt collaterals as important in the loss of portal flow in such patients.

Glomus cell tumor of the eyelid.

BACKGROUND/METHODS: Glomus cell tumor, a vascular neoplasm, has been rarely reported to occur in the eyelid. The authors examined the clinicopathologic features of two patients with glomus cell tumor of the eyelid. RESULTS: The tumors occurred as enlarging violaceous to bluish masses. One patient had a solitary eyelid tumor that contained sheets of individual glomus cells. The other patient had eyelid and wrist tumors and multiple family members with similar lesions. CONCLUSION: This report provides clinicopathologic evidence that glomus cell tumor can occur in the eyelid in two different settings; in one setting, the tumor is solitary and sporadic, and in the second setting, it is multiple and familial.

Liver transplant biopsies with a biopsy gun.

The authors evaluated the safety and efficacy of a biopsy gun for performance of image-guided percutaneous biopsy of hepatic allografts in liver transplant recipients. Two hundred fifty-two liver biopsies were performed in 58 transplant recipients over a 27-month period by using this instrument with an 18-gauge needle. Major complications occurred in two of the 252 biopsies (0.8%): One hemopneumothorax necessitated drainage with a chest tube, and one hemorrhage necessitated transfusion. No patient required surgical exploration because of a complication of the biopsy. Specimens were adequate for accurate histopathologic diagnosis in 248 of 252 procedures (98.4%). The authors conclude that image-guided percutaneous biopsy of hepatic allografts with use of the biopsy gun is a safe and accurate method of obtaining hepatic tissue from liver transplant recipients for histopathologic analysis.

Hepatic arterial resistive indices: correlation with the severity of cirrhosis.

Forty-three patients who were scheduled to undergo a percutaneous liver biopsy were evaluated with Doppler sonography to determine the hepatic arterial resistive index (RI). The histologic specimens were graded by a pathologist regarding cirrhosis and inflammation. The specimens demonstrated no cirrhosis in 12 of 43 (28%) patients, early cirrhosis in 10 of 43 (23%), and established cirrhosis in 21 of 43 (49%). Analysis also revealed that inflammation was absent in three of 43 (7%) patients, minimal in seven of 43 (16%), mild in 17 of 43 (40%), moderate in 13 of 43 (30%), and severe in three of 43 (7%). Hepatic artery RIs (without correction for heart rate) ranged from 0.64 +/- 0.06 in patients with early cirrhosis to 0.68 +/- 0.09 in patients with severe inflammation. There was no significant correlation between the degree of cirrhosis and/or inflammation and hepatic artery RI (with or without correction for heart rate). We conclude that Doppler determination of hepatic artery RIs is not a reliable method of predicting the severity of hepatic cirrhosis and/or inflammation.

Studies of major histocompatibility complex class I/II expression on sequential human heart biopsy specimens after transplantation.

Our previous data indicate that normal human cardiac myocytes do not express detectable levels of major histocompatibility complex (MHC) class II gene products and express only low levels of MHC class I gene products. Examination of heart biopsy samples after transplantation with immunoperoxidase techniques revealed that such myocytes are induced to express high levels of MHC class I/II gene products and that the expression of these gene products appeared to precede histologic evidence of rejection. In efforts to objectively quantitate the level of MHC antigen expression on sequential heart biopsy samples, a radioimmunoassay was set up. Monoclonal antisera was used against human monomorphic MHC class I and II determinants. In addition, to control for the variability in the quantity of biopsy sample, use was made of a monoclonal antisera against human cardiac myosin. A series of three to four sections (4 micron each) of the heart biopsy specimen was treated with each antisera, followed by affinity purified and absorbed iodine 125-labeled goat antimouse immunoglobulin. The mean counts per minute of MHC class I and II was divided by the mean counts per minute obtained with anti-myosin and an index of MHC class I/II derived. Data using such a radioimmunoassay indicate that MHC antigen expression on the heart biopsy specimens does not strictly correlate with histologic rejection grade scores, levels of leukocyte infiltrate, or the immunophenotype of the infiltrating mononuclear cells. Of interest was the finding that an increase in the level of MHC antigen expression occurred before histologic evidence of rejection grades of 3 or greater. In addition, MHC class I antigen expression appeared to increase in heart biopsy samples early during the post-transplant period, followed sequentially by an increase in the level of MHC class II antigen expression. Rejection episodes later during the posttransplant period, however, were accompanied by increased levels of MHC class II antigens. A kinetic analysis of the increase in the levels of MHC class I and II antigens on heart biopsy samples may not only provide a refinement of the histologic scoring of heart biopsy samples for rejection but may also suggest the use of different chemotherapeutic immunosuppressive drug regimens for the treatment of MHC class I as compared with MHC class II dependent rejection episodes.