College of American Pathologists
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  Anatomic Abstracts





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June 2004

Michael Cibull, MD, professor of pathology and laboratory medicine and director of surgical pathology, University of Kentucky Medical Center, Lexington
Subodh Lele, MD assistant professor of pathology and laboratory medicine, University of Kentucky Medical Center
Melissa Kesler, MD, hematopathology fellow, University of Texas Southwestern Medical Center at Dallas

CMV in steroid-refractory ulcerative colitis: a case-control study
Antibody cocktail to identify melanoma micrometastases in sentinel lymph nodes
Pathologic features linked to fibrosis in nonalcoholic fatty liver disease

CMV in steroid-refractory ulcerative colitis: a case-control study

Cytomegalovirus infection is reported to be a cause of steroid-refractory ulcerative colitis, but the strength of this association has not been tested in a case-control study. Controlled studies also have not been performed to determine the sensitivity of available immunohistochemical techniques to detect cytomegalovirus (CMV) in this setting. The authors searched the pathology database at Stanford Hospital for ulcerative colitis patients with a diagnosis of severe colitis between 1992 and 2002 and reviewed the medical records. Forty patients were identified with refractory ulcerative colitis, defined as poor response to high-dose systemic steroids for more than two weeks. Another group of 40 patients with severe but nonrefractory ulcerative colitis was case-matched for age and year of biopsy. A series of 40 patients who underwent colectomy for reasons other than inflammatory bowel disease with representative sections of normal colon were selected as noncolitis controls. CMV inclusions were detected on hematoxylin and eosin (H&E) staining in two of 40 patients with refractory ulcerative colitis but not in other patients. Immunohistochemistry (IHC) detected CMV in 10 of 40 (25 percent) patients with refractory ulcerative colitis and one of 40 (2.5 percent) patients with nonrefractory ulcerative colitis (P=0.007). The CMV-positive cases initially identified on IHC but not on H&E were re-reviewed for viral inclusions on H&E: three had rare but typical inclusions, three had atypical inclusions, and three had no inclusions. CMV was not detected by H&E or IHC in 40 noncolitis controls. Of 10 steroid-refractory ulcerative colitis patients in whom CMV was detected, seven were refractory to cyclosporine or 6-mercaptopurine/azathioprine (70 percent) and six had undergone proctocolectomy (60 percent) prior to detection of CMV. Two patients with recognized CMV infection who were treated with gancyclovir improved and were able to taper off steroids and avoid proctocolectomy. This study provides evidence that unrecognized and therefore untreated CMV infection is significantly associated with steroid-refractory ulcerative colitis. Moreover, IHC is more sensitive than H&E for detecting CMV and should be considered part of the routine evaluation of steroid-refractory ulcerative colitis patients before proceeding with other medical or surgical therapy that may be unnecessary once the CMV is treated.

Kambham N, Vij R, Cartwright CA, et al. Cytomegalovirus infection in steroid-refractory ulcerative colitis: a case-control study. Am J Surg Pathol. 2004;28:365-373.

Reprints: Dr. Teri Longacre, Dept. of Pathology, Stanford University School of Medicine, Room L235, 300 Pasteur Drive, Stanford, CA 94305;

Antibody cocktail to identify melanoma micrometastases in sentinel lymph nodes

Immunohistochemistry is often used as an adjunct in the diagnosis of melanoma micrometastases in sentinel lymph nodes. The antibodies may, however, have varying sensitivity, and some may stain normal lymph node elements, limiting their usefulness when used alone. The use of more than one antibody in different immunohistochemical preparations for each lymph node leads to added costs. A cocktail of monoclonal antibodies recognizing different epitopes may have greater sensitivity in detecting the target than if the antibodies were used singly. This was shown to be true in a study where antibodies to epitopes recognized by MART-1, Melan-A, and tyrosinase were used as a cocktail in the immunostaining procedure to identify melanoma micrometastases. The mixture enabled identification of micrometastases in four additional sections (from two lymph nodes of two cases) as compared to MART-1 and Melan-A used singly. There were no false-positives in 81 sections from axillary lymph nodes in cases of mammary carcinoma. However, the cocktail also stained benign capsular melanocytic nevi (cohesive bland spindle cells in the lymph node capsule) in nine of 188 sections from nonaxillary sentinel lymph nodes in cases with melanoma. The authors concluded that the cocktail appears to be a useful adjunct in the diagnosis of melanoma micrometastases.

Shidham VB, Qi D, Rao R, et al. Improved immunohistochemical evaluation of micrometastases in sentinel lymph nodes of cutaneous melanoma with 'MCW melanoma cocktail'-a mixture of monoclonal antibodies to MART-1, Melan-A, and tyrosinase. BMC Cancer. 2003;3:15.

Reprints: Dr. Vinod B. Shidham, Dept. of Pathology, Medical College of Wisconsin, 9200 W. Wisconsin Ave., Milwaukee, WI 53226;

Pathologic features linked to fibrosis in nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease represents a spectrum of clinicopathologic conditions ranging from steatosis to nonalcoholic steatohepatitis, with a varying degree of risk for progression to cirrhosis. Although steatosis alone seems to be nonprogressive, some patients with nonalcoholic steatohepatitis (NASH) can progress. This study focuses on the clinical and pathological characteristics of patients with nonalcoholic fatty liver disease (NAFLD) associated with the development of histological fibrosis. Patients with an established diagnosis of nonalcoholic fatty liver were identified through a NAFLD database containing extensive clinical, demographic, and laboratory data. Liver biopsy specimens were read blindly by one hepatopathologist using a 19-item pathological protocol and by another hepatopathologist using a second pathological protocol. Clinical and pathological data were matched to the presence of different types of histological fibrosis. Univariate and multivariate analyses helped determine all of the variables independently associated with histological fibrosis. Of 132 NAFLD patients, 21.2 percent had advanced fibrosis (septal/bridging fibrosis or well-established cirrhosis). Sinusoidal fibrosis was present in 20.3 percent of patients, and perivenular fibrosis was seen in 17.2 percent. Ballooning degeneration and Mallory bodies were independently associated with sinusoidal fibrosis and perivenular fibrosis. Aspartate aminotransferase/alanine aminotransferase ratio and ballooning degeneration were also independently associated with periportal-portal fibrosis. The authors concluded that hepatocyte injury in NAFLD is associated with fibrosis. These pathological features can be used to establish the pathological criteria for diagnosing the progressive form of NAFLD or NASH.

Gramlich T, Kleiner DE, McCullough AJ, et al. Pathologic features associated with fibrosis in nonalcoholic fatty liver disease. Hum Pathol. 2004;35:196-199.

Reprints: Dr. Zobair M. Younossi, Inova Fairfax Hospital, Center for Liver Diseases, Dept. of Medicine, 3300 Gallows Rd., Falls Church, VA 22042