Mary Petrelli

Hepatic Veno-occlusive Disease Associated with Renal Transplantation and Azathioprine Therapy

Four patients with renal transplants developed hepatic veno-occlusive disease after immunosuppressive therapy with azathioprine. Severe progressive portal hypertension developed in all patients, with the clinical presentation varying from a mild viral-like syndrome to rapidly fulminant liver failure and death. The disease was associated with cytomegalovirus infection but not with the dose of azathioprine, the type or duration of transplant, or the type of underlying kidney disease. In view of the high mortality rate associated with veno-occlusive disease (a combined 55% in our four patients and in five reported in the literature) and wide spectrum of clinical presentation in patients with renal transplants, a high index of suspicion is required and aggressive intervention indicated.

Hindsight bias: An impediment to accurate probability estimation in clinicopathologic conferences

Although clinicopathologic conferences (CPCs) have been valued for teaching differential diagnosis, their instructional value may be compromised by hindsight bias. This bias occurs when those who know the actual diagnosis overestimate the likelihood that they would have been able to predict the correct diagnosis had they been asked to do so beforehand. Evidence for the presence of the hindsight bias was sought among 160 physicians and trainees attending four CPCs. Before the correct diagnosis was announced, half of the conference audience estimated the probability that each of five possible diagnoses was correct (foresight subjects). After the correct diagnosis was announced the remaining (hindsight) subjects estimated the probability they would have assigned to each of the five possible diagnoses had they been making the initial differential diagnosis. Only 30% of the foresight subjects ranked the correct diagnosis as first, versus 50% of the hindsight subjects (p < 0.02). Although less experienced physicians consistently demonstrated the hindsight bias, more experienced physicians succumbed only on easier cases. Key words: clinicopathologic conferences; hindsight bias; cognitive bias; debiasing techniques. (Med Decis Making 8:259-264, 1988)

Ductuloinsular tumors of the pancreas: A light, electron microscopic and immunohistochemical study

Most pancreatic tumors are of a single cell type and are identified ± as duct, acinar, or islet cell neoplasms. The authors report on three examples with both duct and endocrine characteristics as seen by light microscopy; two with further confirmation of endocrine differentiation by electron microscopy; and one by immunocytochemistry. Mixed differentiation of this sort can be understood by reference to the embryonic pancreas, which develops from the small intestine and forms ducts, intercalated ducts, acini, and islets, with their different cell types. The merging and intermingling of different cells prevents the identification of one specific cell of origin. It also suggests that the neoplastic process here may not be a clonal proliferation from a single cell mutation as this is generally understood. Alternative explanations are briefly mentioned.

Tissue and plasma carcinoembryonic antigen in early breast cancer. A prognostic factor.

A prospective study of plasma and tissue carcinoembryonic antigen (P‐CEA and T‐CEA) levels in 63 patients with early (Stage I and II) breast cancer was undertaken to determine if the presence of CEA in tissue and/or plasma at the time of primary surgery can be used as a prognostic factor. Thirty‐two Stage I and 31 Stage II patients were evaluable with a median follow‐up time of 26 months: 29/63 were T‐CEA and/or P‐CEA positive while 34/63 were T‐CEA and P‐CEA negative; 9/63 were both T‐CEA and P‐CEA positive; 13/63 were P‐CEA positive alone, while 25/63 were T‐CEA positive alone; 5/29 T‐CEA and/or P‐CEA positive showed disease progression with a mean DFI of 11.8 months, compared with 0/34 T‐CEA and P‐CEA negative patients (P < 0.02); 2/9 T‐CEA and P‐CEA positive compared with 0/34 negative patients progressed (P < 0.01). There was a significant difference (P < 0.05) between P‐CEA positive (3/13) patients with recurrence and P‐CEA negative (2/50). When T‐CEA positive patients (4/25) were compared with T‐CEA negative (1/38), the difference approaches significance. When the recurrences were analyzed with respect to CEA, estrogen receptor (ER) and nodal status, only in the CEA+ versus CEA– group was there a significant difference. The early data show that patients with positive T‐CEA and/or P‐CEA have a higher recurrence rate with probable poor prognosis. Prognosis correlates better with CEA status than with ER or nodal status.

Severe Intrahepatic Cholestasis Caused by Amiodarone Toxicity After Withdrawal of the Drug A Case Report and Review of the Literature

Cholestasis has been reported as a rare presentation among patients with severe liver injury secondary to amiodarone hepatic toxicity. We report an unusual case of amiodarone-induced cholestatic hepatotoxicity occurring after amiodarone had been discontinued and the initial abnormal liver function findings had improved. The patient, without jaundice at the initial presentation, developed severe jaundice about 4 months after withdrawal of amiodarone. Light and transmission electron microscopic examination of a specimen secured by computed tomographically guided liver biopsy was consistent with amiodarone hepatic toxicity as the cause of intrahepatic cholestasis. An abdominal ultrasound, endoscopic retrograde cholangiography, and dimethyl iminodiacetic acid and computed tomographic scans of the abdomen all failed to demonstrate any other causes for jaundice other than amiodarone toxicity. Thus, amiodarone hepatic toxicity may occur after drug withdrawal even if results of liver function tests improve. Histopathologic examination of a liver biopsy specimen is of value for diagnosis and prognosis. The liver biopsy findings, clinical course, and liver function test results are discussed, and the English-language literature on amiodarone cholestatic hepatotoxicity is reviewed.

Pleomorphic adenoma ("mixed" tumor) of human female breast mimicking carcinoma clinico-radiologically.

A case of pleomorphic adenoma („mixed”︁ tumor) of the breast is described Although rare, this is a distinctive primary neoplasm which can be mistaken for a malignant tumor both clinically and radiologically. Brief reviews of the pertinent literature and of the possible origin of this tumor are presented.

Diffuse cystic glandular malformation of the stomach associated with adenocarcinoma: Case report and review of the literature.

A 60‐year‐old man was found to have diffuse cystic glandular malformation and adenocarcinoma of the stomach. Review of the literature revealed one similar reported case and five others with diffuse heterotopic cystic malformation only. Clinically, the lesion is associated with gastrointestinal symptoms, and radiologically, it can mimic diffuse gastric carcinoma, lymphoma, or polyposis.

Stromal sarcoma of breast. A light and electron microscopic study

A case of stromal sarcoma of the breast was studied by light and electron microscopy. The tumor comprised of uniform, plump spindle cells with neither epithelial nor “metaplastic” mesenchymal elements. Ultrastructurally most of the tumor cells appeared immature, containing abundant free ribosomes, variable amounts of microfilaments and profiles of rough endoplasmic reticulum, with scant intercellular collagen and elastic fibers. The cells often showed prominent nesting as well as a variety of cell junctions, including desmosomes. We believe this tumor is a poorly differentiated, precursor mesenchymal sarcoma which belongs in the category of “stromal sarcoma of breast,” a term coined by Berg et al. in 1962.4 To our knowledge, this represents the first published electron microscopic study on this tumor. Despite a high mitotic figure count in the tumor, the patient has survived a simple mastectomy with no evidence of metastasis 30 months later.

Adenoacanthoma of the sigmoid colon

SummaryA case of adenoacanthoma of the sigmoid colon is described. Twelve other cases have been reported in the literature. This figure suggests that this histologic tumor differentiation in the colon is rare. The histologic appearance and theories of histogenesis are discussed and the literature reviewed.

The effect of trypan blue on the hepatotoxicity of carbon tetrachloride in the rat

Abstract Rats were given intravenous injections of either physiologic saline or trypan blue dye suspended in saline. After 24 hours, the livers of these animals were sampled for light and electron microscopic study. The livers of the saline treated rats showed no morphologic alterations. The livers of the trypan blue injected animals exhibited no structural abnormalities in the hepatic parenchymal cells, but their sinusoidal lining cells were hypertrophied, mainly due to the appearance of numerous phagosomes, increased quantities of rough endoplasmic reticulum, and prominent Golgi zones. Similarly prepared rats were given intraperitoneal injections of CCl 4 , 24 hours after the intravenous administration of saline or trypan blue. The livers of these animals were sampled, 24 and 48 hours after the toxic challenge. At both intervals, the livers of the rats treated with trypan blue and CCl 4 displayed far less necrosis and inflammatory reaction than was found in the animals given saline and CCl 4 . It was considered unlikely that this difference could be completely explained by changes in hepatic blood flow. It was also demonstrated that, at 24 hours after administration of trypan blue, there were no hepatocellular morphologic alterations that might account for the divergent response to CCl 4 . It was proposed, therefore, that the hypertrophied sinusoidal lining cells of the trypan blue treated rats might be related to the observed protection from CCl 4 hepatotoxicity.