Rent-a-doc: pathology goes on the road.
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Biomedical subjects
Publications and source records attributed to L R Rubel.
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We describe the chronology of hepatic histopathologic alterations in 50 cases of fatal exertional heatstroke related to military training. Five patients who died in the field demonstrated the earliest alterations: fatty change (sometimes microvacuolar), amitotic hepatocellular regeneration, accumulation of hemosiderin, and congestion. In addition, the sinusoids contained polymorphonuclear leukocytes, immature erythroid and granulocytic cells, megakaryocytes, and lymphocytes. Fibrin was not evident. The other 45 patients, who survived up to 8 days following hospitalization, also demonstrated these findings. Microvacuolar fatty change was common in this group of patients, and degenerated hepatocytes resembled Councilman bodies. Coagulative degeneration and submassive necrosis were uncommon. Of those surviving over 12 h, more than half had bile stasis (sometimes ductal), frequently associated with acute cholangitis and ductular proliferation. Regeneration and pigmentary alterations have not been recognized as early hepatic findings in heatstroke, nor have intrasinusoidal bone marrow elements, ductal bile stasis, and acute cholangitis been described. Possible pathogenic factors, other than hyperthermia and sequellae of shock, include obesity, recent illnesses and immunizations, bacterial toxemia, hemolysis, and bone marrow injury.
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Six cases of Thorotrast-associated cholangiocarcinoma (TACC) are studied and compared with eight previously reported cases as well as with cases of non-TACC. TACC shares some epidemiologic features both with non-TACC as well as Thorotrast-associated angiosarcoma (TAAS) but appears to occur in younger patients than non-TACC. There is an apparent increased prevalence of both benign and malignant thyroid disease in the current group of patients with TACC; previous epidemiologic studies have not identified this phenomenon. Thorotrast-associated hepatic fibrosis was present in all 14 TACC cases; otherwise, both non-TACC and TACC are clinically and morphologically similar. Bile duct dysplasia and/or transition to adenocarcinoma, which occurred in all the AFIP cases, are seldom described in case reports of either TACC or non-TACC; in the current study they served to validate the intrahepatic origin of the tumors.
A pathogenetic relationship between hepatic manifestations of alpha 1-antitrypsin deficiency (AATD) and hepatocellular carcinoma has previously been suggested but not established. We encountered three patients with hepatocellular carcinoma (HCC) and nonneoplastic hepatocytes containing globules positive for alpha 1-antitrypsin by immunoperoxidase staining or immunofluorescence microscopy. The AATD was severe in one patient, mild in the second, and not evaluated in the third; any pathogenetic relationship between the deficiency and HCC must therefore remain speculative. Nonneoplastic hepatocytes of all three patients demonstrated copper storage and, in two patients who were not alcoholic, Mallory bodies. Simultaneous presence of copper storage and Mallory bodies has not been reported in liver disease associated with AATD. The pathogenetic mechanisms of these findings are unknown.
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Primary biliary cirrhosis is infrequently diagnosed in men, so that the clinical, biochemical and histopathological spectrum of this disease in men has not been evaluated. Therefore, we studied 30 men who had a histological diagnosis of primary biliary cirrhosis and had positive tests for antimitochondrial antibodies. Five patients had no hepatobiliary symptoms, and two of these patients had neither biochemical nor histological evidence of cholestasis. These 30 male patients' findings were compared with the findings in 30 age-matched women who also had primary biliary cirrhosis and antimitochondrial antibodies. Six of these patients were asymptomatic. Clinical findings and symptomatic status, in addition to biochemical and histopathological features, were generally similar in both male and female patients. The possible significance of higher serum alkaline phosphatase activities and lower frequency of occurrence of piecemeal necrosis in men with primary biliary cirrhosis, as compared with women, requires further study.
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The histopathology of hepatic injury associated with heatstroke is described, with particular attention being devoted to the chronology of histologic alterations. These alterations are discussed with respect to their pathogenesis. Some lesions appear to be a direct result of thermal injury to the liver, while others are secondary effects of clinical risk factors for heatstroke, such as obesity, or reflect systemic complications which include circulatory failure, hemolysis, and endothelial injury.