Hepatitis C virus infection in non-Hodgkin's lymphoma.

Hepatitis C virus (HCV) infection is associated with immune-complex mediated disorders, including Type II mixed cryoglobulinaemia. Mixed cryoglobulinaemia is itself a low-grade B-cell lymphoproliferative disorder which may progress to non-Hodgkin's lymphoma (NHL). Studies from Europe and Asia have found a prevalence of hepatitis C virus infection in non-Hodgkin's lymphoma patients as high as 34%. Other viral infections are also associated with non-Hodgkin's lymphoma. We speculated that non-Hodgkin's lymphoma patients in the midwestern USA would have an increased prevalence of hepatitis C infection. We tested 73 patients with NHL and 20 controls with Hodgkin's disease for anti-HCV antibodies by EIA-2. Only 1/73 patients and no control subject was positive for anti-HCV. The anti-HCV positive patient had no identifiable risk factors for hepatitis C, and ALT was persistently normal. HCV-RNA testing by RT-PCR was negative. Thus, none of 73 non-Hodgkin's lymphoma patients could be confirmed to have hepatitis C infection. In a second part of the study, of 438 patients with HCV infection followed an average of 28.1 months, only one patient developed non-Hodgkin's lymphoma. We conclude that in our population, non-Hodgkin's lymphoma is not associated with hepatitis C virus infection. Based on these results and review of the literature, there are marked regional differences in the prevalence of hepatitis C infection in Non-Hodgkin's lymphoma.

Chronic, unexplained diarrhea: are biopsies necessary if colonoscopy is normal?

OBJECTIVE: We sought to determine the frequency of clinically important histological abnormalities in patients with chronic, unexplained diarrhea who had macroscopically normal colonic endoscopies. METHODS: Of 855 consecutive patients undergoing colonoscopy (595 cases) or flexible proctosigmoidoscopy (260 cases) by one endoscopist, biopsies were taken in 111 cases of unexplained diarrhea of at least 4-6 weeks duration in which the colorectal mucosa appeared grossly normal. All biopsies were blindly reviewed by one pathologist. RESULTS: In this group of patients with macroscopically normal colons, we identified no cases of Crohn's disease or ulcerative colitis or any definite cases of collagenous colitis (CC) or lymphocytic colitis (LC). There was one case classified as "possible CC" and 13 cases classified as "some features of LC". There were five cases of melanosis coli, one case of cytomegalovirus colitis (in an immunosuppressed patient), and one case of radiation injury. Ninety-one cases were classified as no pathological diagnosis or minimal histological change. Patients with abnormal histology were contacted to see if they had persistence or resolution of diarrhea. For the cases of "possible CC" and "some features of LC," diarrhea had resolved spontaneously in the majority. Interesting to note, only one of the five melanosis coli patients admitted to laxative use, raising the question of surreptitious abuse. CONCLUSIONS: We conclude that the yield of biopsies in diarrhea patients with macroscopically normal colons at endoscopy is low. It may be reasonable to obtain biopsies in patients with relatively severe or debilitating symptoms, with diarrhea that sounds "organic" (e.g., nocturnal stools, frequent watery stools, weight loss, elevated sedimentation rate), or in patients who are immunosuppressed. When biopsies are taken at colonoscopy, we suggest taking about six from throughout the colon and placing them into just one specimen container to help minimize costs.

Chronic mineralocorticoid excess and cardiovascular remodeling.

Chronic mineralocorticoid (MC) excess, whether due to elevated plasma aldosterone (ALDO) or deoxycorticosterone (DOC), is associated with a perivascular fibrosis of systemic and coronary arterioles. This remodeling of resistance vessels contributes to the appearance of hypertension. Chronic MC excess is also accompanied by cardiac myocyte necrosis, secondary to myocardial potassium depletion, and a subsequent reparative fibrosis that appears in the normotensive, nonhypertrophied right and hypertensive, hypertrophied left ventricles. Fibrosis contributes to the appearance of ventricular arrhythmias and dysfunction. Herein, clinical and experimental evidence linking chronic, inappropriate (relative to dietary sodium) elevations in circulating ALDO and DOC with these reactive and reparative forms of fibrous tissue formation in the heart and other tissues is presented.

Reactive hemophagocytic syndrome simulating acute hepatitis. A case due to hepatic peripheral T-cell lymphoma.

The reactive hemophagocytic syndrome may mimic acute hepatitis, as we report here. It should be considered when hepatitis is accompanied by high fever, progressive cytopenias, and weight loss, with or without adenopathy and striking lactate dehydrogenase elevation. Bone marrow, lymph node, or liver biopsy are necessary to confirm the diagnosis. Recognition is important, because the syndrome has multiple potential causes amenable to therapy. Preliminary reports suggest that high-dose corticosteroid therapy is useful in suppressing cytokine-stimulated fever and hemophagocytosis, whatever the underlying cause.

Cardiac angiotensin converting enzyme and myocardial fibrosis in the rat.

OBJECTIVE: The aim was to test the hypothesis that cardiac angiotensin converting enzyme (ACE) is related to the accumulation of fibrous tissue in the heart. METHODS: A model of tissue repair (pericardiotomy with left coronary artery ligation) was used, together with the following: quantitative in vitro autoradiography (125I-351A) to determine ACE binding density; immunohistochemistry (monoclonal ACE antibody, 9B9) to identify cells expressing ACE; and in situ hybridisation to localise cells expressing type I collagen mRNA. Age and sex matched rats receiving this operative procedure without subsequent infarction (sham operated) served as controls to those with left ventricular myocardial infarction. Serial heart sections obtained from each group at 3 days and at 1, 2, 4, and 8 weeks following operation were examined for morphological evidence of injury and inflammatory cells (haematoxylin/eosin) and fibrillar collagen (picrosirius red). RESULTS: Following myocardial infarction: (a) on day 3, neutrophils and macrophages were present at the site of infarction, while fibrillar collagen and ACE binding were not increased compared with control; (b) at week 1, fibrillar collagen and ACE binding were present at the site of infarction and became progressively more advanced at 2, 4, and 8 weeks; (c) at week 2, there was increased ACE binding in the right ventricle and interventricular septum, when perivascular fibrosis of intramural coronary arteries and microscopic scars appeared, together with endomyocardial fibrosis of the septum; (d) there was marked ACE binding in the fibrosed visceral pericardium two weeks after operation in both myocardial infarction and sham operated groups; (e) there was type I collagen mRNA expression on postoperative week 1, localised within fibroblasts or fibroblast-like cells found at infarct and fibrous tissue sites in the right ventricle, septum, and pericardium; and (f) ACE-labelled cells included fibroblast-like cells, as well as macrophages and endothelial cells. CONCLUSIONS: Thus in this model of tissue repair, marked ACE binding density is associated with fibrillar collagen formation that appears within and remote to the site of myocardial infarction, including the pericardium. Cardiac ACE, originating from type I collagen producing cells, therefore represents an integral component of fibrous tissue formation in this rat model of tissue injury.

Angiotensin-converting enzyme, bradykinin, and angiotensin II receptor binding in rat skin, tendon, and heart valves: an in vitro, quantitative autoradiographic study.

Angiotensin converting enzyme (ACE), an ectoenzyme bound to vascular endothelial cells, is also found at tissue sites (TACE) normally composed of fibrillar collagen and fibroblasts. For example, TACE is present in the adventitia of intramural coronary arteries and matrix of heart valves, as well as the fibrous tissue that follows the chronic administration of angiotensin II (AII) or aldosterone. At these sites bradykinin (BK) receptor but not AII receptor binding has been observed, suggesting that in fibrous tissue TACE uses BK as substrate. Dermis, subcutaneous tissue, and skeletal muscle tendon likewise are sites that are rich in fibrillar collagen but are different in their cellularity. Accordingly, we tested the hypothesis that TACE is normally present at sites of fibrous tissue and that BK--not AIK--receptor binding is anatomically coincident with TACE in keeping with its role as a kininase II. TACE and receptors for BK and AII were localized by quantitative in vitro autoradiography with [125I]351A, 125I[Tyr8]BK, and 125I[Sar1, Ile8]AII, respectively. Skin morphology was examined in serial full thickness sections obtained from the dorsum of Sprague-Dawley rats. We found the following: (1) high TACE binding occurred in subcutaneous connective tissue and heart valves that was displaced by lisinopril or 351A in a dose-dependent manner; (2) BK receptor binding and low density AII receptor binding were seen at these sites, where AII receptor binding was totally displaced by a type 1 (DuP753) but not a type 2 (PD123177) receptor antagonist; (3) ACE, BK, and AII receptor binding was not evident in epidermis, dermis, skeletal muscle, or tendon.(ABSTRACT TRUNCATED AT 250 WORDS)

Immunostaining for Leu-7 in the diagnosis of thyroid carcinoma.

The morphologic distinction between benign and malignant thyroid lesions can be difficult. Immunostaining for the Leu-7 antigen has been reported to be useful in the diagnosis of thyroid carcinoma. To test the specificity of immunostaining for Leu-7 in the diagnosis of thyroid carcinoma, we studied formalin-fixed, paraffin-embedded tissue specimens obtained from 66 thyroid lesions using the HNK-1 monoclonal antibody to Leu-7 and an avidin-biotin-complex technique. Positive reactivity for Leu-7 was seen in 11 (33%) of 33 benign thyroid conditions and in 27 (82%) of 33 thyroid carcinomas. We conclude that immunostaining for Leu-7 is not specific in the diagnosis of thyroid carcinoma.

Peripheral T-cell lymphoma of the scrotum.

Primary lymphoma of the scrotum is rare. We report a case of primary immunoblastic lymphoma of the scrotum in a homosexual who was negative for antibodies to human immunodeficiency virus. Immunoperoxidase stains of paraffin-embedded tissue were consistent with a T-cell phenotype. Although complete remission was initially induced with surgical extirpation of the tumor and combination chemotherapy, isolated skin relapse developed which again responded to chemotherapy.

Utility of BER-EP4 in the diagnosis of adenocarcinoma in effusions: an immunocytochemical study of 232 cases.

The usefulness of a new commercially available monoclonal antibody (MoAb) BER-EP4 was evaluated. This MoAb is directed against a cell surface glycoprotein reported to be present in most epithelial cells and epithelial tumors but not in mesothelial cells. Cell block sections from 103 adenocarcinomatous and 129 benign effusions were studied. Positive staining was seen in 85 of the 103 (83%) malignant effusions. Immunoreactivity was seen in 73-93% of adenocarcinomas from the ovary, gastrointestinal tract, lung, and breast. Mesothelial cells from 3 of the 129 (2%) benign effusions showed positive staining. It is concluded that immunocytochemical staining with MoAb BER-EP4 is a sensitive and specific aid in distinguishing reactive mesothelial cells from adenocarcinoma cells in body fluids.

Prospective evaluation of optimal number of biopsy specimens and brush cytology in the diagnosis of cancer of the colorectum.

We prospectively studied the diagnostic accuracy of endoscopic biopsy and cytology in the diagnosis of colorectal cancer and sought to ascertain the optimal number of biopsy specimens that should be taken. Seventy consecutive patients with colorectal masses or polypoid lesions that could not be removed by endoscopic polypectomy and which were referred for surgery were studied. Lesions were first brushed for cytology. A series of 10 biopsies were then obtained from each lesion; the first four were placed into the first container, and two were placed into each of three other containers. Cytology and biopsies were read blindly by one pathologist. Findings were compared with the resection specimen results. Ten lesions were benign; all had negative biopsies and cytology. Sixty lesions were malignant: cytology was positive in 77.2% and biopsies in 78.3%. The yield was increased to 91.7% when both were done (cytology plus six biopsies). Cytology detected seven cancers that were missed by biopsy. Biopsy detected eight cancers not diagnosed by cytology. Five cancers were missed by both. Of the 47 cancers detected by biopsy, the first four biopsies made the diagnosis in 41 cases. Taking two more biopsies (six total) identified six more cancers. No additional cancers were identified by taking more biopsies (eight or 10 total). When six different biopsy-cytology strategies were examined: 1) cytology alone, 2) four biopsies (Bx), 3) six Bx, 4) 10 Bx, 5) cytology + four Bx, and 6) cytology + six Bx, the yield was 77.2%, 68.3%, 78.3%, 78.3%, 90.0%, and 91.7%, respectively. We conclude that biopsy and cytology are complementary in the diagnosis of colorectal cancer. The combination of cytology and four to six biopsies is recommended. There appears to be little additional yield to taking more than six biopsies. Even combined biopsy and cytology will miss 8-10% of cancers.

Loss of heterozygosity detected in formalin-fixed, paraffin-embedded tissue of colorectal carcinoma using a microsatellite located within the deleted in colorectal carcinoma gene.

We determined loss of heterozygosity from formalin-fixed, paraffin-embedded tissue of colorectal carcinoma using microsatellite polymorphism. The polymorphism was assayed based on DNA amplification by the polymerase chain reaction (PCR). The PCR-analyzed microsatellite method was applied to assay degraded DNA extracted from paraffin-embedded blocks with adenocarcinoma of colon. The DNA from 26 tumors as well as their corresponding normal tissue samples were successfully amplified using a dinucleotide microsatellite located within an intron of the deleted in colorectal carcinoma gene. Allele losses on this marker were detected in 33% of informative colorectal carcinomas. This study demonstrates that microsatellites provide a powerful set of DNA markers for loss of heterozygosity on archival specimens.

Common benign cutaneous tumors and tumor-like lesions of the head and neck.

The otolaryngologist is confronted with a wide variety of benign and malignant skin neoplasms. In this article, common benign cutaneous, epithelial, and nonepithelial tumors and tumor-like lesions of the head and neck region are described. Clinical presentation, histopathology, and differential diagnosis are discussed where appropriate.

Fibrosis of the human heart and systemic organs in adrenal adenoma.

In experimental animals, chronic mineralocorticoid (MC) excess is associated with fibrosis of the myocardium and systemic organs, where both a reactive, i.e. interstitial and perivascular, and reparative, i.e. microscopic scarring following cardiac myocyte necrosis, fibrosis are found. We sought to determine if a similar fibrous tissue response was present in human myocardium and systemic organs in association with adrenal adenoma. Postmortem specimens of heart, adrenals, pancreas, lungs, kidney and liver were obtained from 5 patients (age 67 +/- 5 years) with autopsy-proven adrenal adenoma. Documented histologically normal tissue from age-matched patients was used for comparison. Tissue sections were stained with the collagen specific stain Sirius Red F3BA and analyzed using normal and polarized light. Reactive and/or reparative fibrosis was found in the heart, pancreas, adrenal glands and lungs, but not in the kidney or liver. These observations support a link between chronic MC excess and fibrosis of the heart and systemic organs in humans with adrenal adenoma.

Follicular carcinoma with clear cell change arising in lingual thyroid.

A case of follicular carcinoma arising in the lingual thyroid of a 23-year-old woman is added to the 22 previous reports. The embryology and the clinical and pathologic differential diagnoses are discussed. Histologic criteria useful in diagnosing follicular malignancy in this area include local and vascular invasiveness, hypercellularity, mitotic activity, and necrosis. The use of the immunohistochemical marker thyroglobulin and electron microscopy are described for the first time and confirm a thyroid follicular cell origin.

Nonspecificity of colon-specific antigen in adenocarcinomas. An immunohistochemical study of 422 cases.

To determine the specificity of colon-specific antigen in adenocarcinomas, routinely prepared paraffin-embedded tissue from 422 cases of adenocarcinoma were studied using a commercially available monoclonal antibody to colon-specific antigen and a standard avidin-biotin immunohistochemical technique. Positive reactivity for colon-specific antigen was very common (80% to 100%) in adenocarcinomas of the colon, distal esophagus/stomach, ovary, endocervix, endometrium, lung, pancreas, prostate, and bile ducts. Positive reactions were infrequent in adenocarcinomas of the breast (16%) and in hepatocellular carcinomas (23%). No immunoreactivity was seen in adenocarcinomas of the thyroid or in renal cell carcinomas. It is concluded that colon-specific antigen is not a colon-specific marker in adenocarcinomas. However, it may be useful in ruling out adenocarcinomas of renal or thyroid origin in certain clinical settings.

Immunostaining for P-glycoprotein in the diagnosis of thyroid carcinomas.

The morphologic distinction between thyroid carcinoma and certain benign thyroid conditions can be difficult in selected cases. P-glycoprotein (Pgp), a glycoprotein associated with tumor multidrug resistance, has been reported to be expressed in thyroid carcinoma but not in benign thyroid conditions. To determine the specificity of immunostaining for Pgp in the diagnosis of thyroid carcinoma, we studied formalin-fixed, paraffin-embedded tissue from 69 cases of various thyroid lesions using a commercially available monoclonal antibody to Pgp (C219, Centocor, Malvern, PA) and an avidin-biotin-peroxidase complex technique. Positive reactivity was seen in 15 of 37 (41%) benign thyroid conditions and in 23 of 32 (72%) thyroid carcinomas. We conclude that immunostaining for Pgp is not specific in the diagnosis of thyroid carcinoma.

Squamous cell carcinoma of the pancreas. Report of an unusual case and review of the literature.

Squamous cell carcinoma is an uncommon form of cancer of the pancreas, comprising 0.5-3.5% of cases. We report an unusual case that occurred in a very young woman and showed cystic characteristics. Interesting radiographic features included extensive pancreatic calcifications and pancreatic duct communication to the mass. A literature review of this rare form of pancreatic cancer is also provided.

Lack of specificity of monoclonal antibody B72.3 in distinguishing chronic pancreatitis from pancreatic adenocarcinoma.

Making the morphologic distinction between chronic pancreatitis and pancreatic adenocarcinoma is a diagnostic challenge in small biopsy specimens and fine-needle aspiration samples. It has been suggested that immunohistochemical evaluation for the tumor-associated glycoprotein-72 antigen recognized by the monoclonal antibody B72.3 may be helpful in this setting. Formalin-fixed, routinely processed, paraffin-embedded tissue from 29 known cases of chronic pancreatitis and 31 cases of pancreatic adenocarcinoma were evaluated for reactivity with monoclonal antibody B72.3 using a standard avidin-biotin complex technique. Positive staining was seen in 26 of 31 adenocarcinomas (84%) and in 6 of 29 cases (21%) of chronic pancreatitis. Although monoclonal antibody B72.3 is more commonly reactive with pancreatic adenocarcinoma than with chronic pancreatitis, too many cases of chronic pancreatitis are reactive with this antibody for it to be useful as a diagnostic adjunct.

Distribution of BCA-225 in adenocarcinomas. An immunohistochemical study of 446 cases.

BCA-225 is a glycoprotein identified in human breast carcinoma cells that has been reported to show a restricted distribution in other human tissues. To further define the presence of BCA-225 in human carcinomas, the authors performed an immunohistochemical study, applying a commercially available monoclonal antibody to BCA-225 to formalin-fixed, paraffin-embedded sections of 446 adenocarcinomas from a variety of sites. BCA-225 expression was found to be common in adenocarcinomas of the breast (98%), kidney (94%), ovary (80%), and lung (74%) but was infrequent in adenocarcinomas of the gastrointestinal tract (10-16%). Adenocarcinomas of the prostate, bile ducts, thyroid, endometrium, endocervix, and pancreas showed an intermediate frequency of BCA-225 expression (36-68%). Although rare tumor cells in three hepatocellular carcinomas showed reactivity for BCA-225, staining of more than 10% of the tumor cells was not seen in any of the 23 hepatocellular carcinomas that were studied. The authors conclude that BCA-225 is expressed commonly in human adenocarcinomas and that it is not a breast-specific antigen. Antibodies to BCA-225 may have utility in helping one to exclude hepatocellular carcinoma in certain clinical settings.