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January 2003

IBD-like morphologic features in collagenous and lymphocytic colitis
Collagenous colitis (CC) and lymphocytic colitis (LC) are clinical syndromes characterized by chronic watery diarrhea, few or no endoscopic abnormalities and biopsies that typically show normal crypt architecture, increased mononuclear inflammation in the lamina propria, absence of neutrophils, and increased intraepithelial lymphocytes. Patients with collagenous colitis also have a thickened subepithelial collagen layer. The authors have noted, anecdotally, that biopsy specimens from some patients with collagenous or lymphocytic colitis contain certain histologic features, such as Paneth cell metaplasia, that are normally seen in inflammatory bowel disease (IBD) or other types of healed colitis and thus may cause diagnostic difficulty. The purpose of this study was to evaluate the prevalence and significance of IBD-like morphologic features in colonic mucosal biopsies from patients with collagenous or lymphocytic colitis. Five hundred and thirty-one routinely processed hematoxylin-and-eosin-stained colonic mucosal biopsies from 150 patients with clinically, endoscopically, and histologically confirmed collagenous colitis (79 patients; male:female ratio, 14/65; mean age, 60 years) or lymphocytic colitis (71 patients; male:female ratio, 13/58; mean age, 55 years) were evaluated in a blinded fashion for a variety of histologic features. The results were compared between collagenous and lymphocytic colitis and correlated with the clinical and endoscopic data. None of the patients had or developed IBD during the study period. Active crypt inflammation was a common finding in both groups and was seen in 24 of 79 collagenous colitis patients (30 percent) and 27 of 71 lymphocytic colitis patients (38 percent). Surface ulceration was not seen in any of the lymphocytic colitis biopsies but was present in two of 79 (2.5 percent) of the collagenous colitis patients. Paneth cell metaplasia was frequent in both groups but was more common in collagenous colitis patients. Forty-four percent of collagenous colitis patients but only nine of 63 (14 percent) lymphocytic colitis patients had Paneth cell metaplasia (P<0.001). Crypt architectural irregularity was present in six of 79 patients with collagenous colitis (7.6 percent) and three of 71 (4.2 percent) patients with lymphocytic colitis. In patients with collagenous colitis, Paneth cell metaplasia was associated with more severe disease characterized by the presence of abdominal pain (P<0.001) and a higher frequency of bowel movements (more than three bowel movements/day; P=0.06). Also, active crypt inflammation correlated with antibiotic use at the time of clinical presentation (P=0.04) and was present in the only two patients who had positive stool cultures (one each for Campylobacter jejuni and Salmonella). None of the other histologic findings correlated with any of the other clinical or endoscopic features. Pathologists should be aware that some histologic features normally associated with IBD, such as crypt irregularity and neutrophilic cryptitis and crypt abscesses, are not uncommon in patients with collagenous or lymphocytic colitis. The presence of one or more of these features should not necessarily be interpreted as evidence against either diagnosis.

Ayata G, Ithamukkala S, Sapp H, et al. Prevalence and significance of inflammatory bowel disease-like morphologic features in collagenous and lymphocytic colitis. Am J Surg Pathol. 2002;26(11):1414-1423.

Reprints: Dr. Robert D. Odze, Gastrointestinal Pathology Service, Dept. of Pathology, Brigham and Women's Hospital, 75 Francis St., Boston, MA 02115; rodze@partners.org

Repeating IHC on patient materials referred elsewhere
Immunohistochemistry is an important adjunctive test in diagnostic surgical pathology. The authors studied the clinical significance and outcomes of performing IHC on patients with a previous diagnosis of cancer who were coming to the Fox Chase Cancer Center (FCCC), a National Cancer Institute-designated national comprehensive cancer center (NCCC), for treatment or second opinion, or both. The authors assessed all outside surgical pathology slide review cases seen at the FCCC during 1998 and 1999 in which IHC was performed. Cases were divided into confirmation of outside diagnosis with and without prior IHC performed by the outside institution (groups A and B, respectively) and cases with a significant change in diagnosis with and without prior IHC performed by the outside institution (groups C and D, respectively). During 1998 and 1999, 6,678 slide review cases were reviewed at the FCCC, with an overall significant change in diagnosis in 213 cases (3.2 percent). IHC was performed on 186 of 6,678 (2.7 percent) slide review cases, with confirmation of the outside diagnosis in 152 (81.7 percent) cases and a significant change in diagnosis in 34 (18.3 percent) cases. Patient followup was obtained in 32 of 34 cases with a significant change in diagnosis (groups C and D), which confirmed the diagnosis in 26 of 27 cases. (Followup was inconclusive in five cases.) The authors repeated the identical antibodies performed by the outside institutions in group D (37 antibodies) and group B (133 antibodies) with different results in 48.6 percent and 13.5 percent, respectively (overall nonconcordance rate, 21.2 percent). In group D, additional antibody tests beyond that performed by the outside institution were needed in 88.8 percent of cases to make a change in diagnosis. The authors concluded that in the setting of a NCCC, reperforming or performing IHC on cases with a previous diagnosis of cancer is not a duplication of effort or misuse of resources. Repeating or performing IHC in this setting is important in caring for and managing cancer patients.

Wetherington RW, et al. Clinical significance of performing immunohistochemistry on cases with a previous diagnosis of cancer coming to a national comprehensive cancer center for treatment or second opinion. Am J Surg Pathol. 2002;26(9):1222-1230.

Reprints: Dr. Harry S. Cooper, Dept. of Pathology, Fox Chase Cancer Center, 7701 Burholme Ave., Philadelphia, PA 19111; hs_cooper@fccc.edu

Observer variation in encapsulated follicular lesions of the thyroid gland
Diagnosing and classifying follicular lesions of the thyroid remains one of the more challenging areas in surgical pathology. Although histologic definition of follicular thyroid lesions is readily available, application of the diagnostic criteria and personal experience may lead to disagreement among pathologists. To investigate interobserver variation in the assessment of encapsulated follicular lesions, eight pathologists (four American and four Japanese) reviewed the same hematoxylin-and-eosin-stained slide of each of 21 cases of thyroid lesions showing encapsulation and follicular growth pattern. There was complete agreement in 10 percent of the cases. At least seven pathologists agreed on the diagnosis in 29 percent of the cases and at least six in 76 percent of the cases. American and Japanese pathologists agreed among themselves in 33 percent and 52 percent of cases, respectively. The frequency of diagnosis of adenomatous goiter among Japanese pathologists (31 percent) was considerably higher than among American pathologists (six percent). In contrast, the frequency of diagnosis of papillary carcinoma among American pathologists (25 percent) was considerably higher than among Japanese pathologists (four percent). The authors’ analysis revealed three primary factors affecting observer variation: interpretation of the significance of microfollicles intimately related to capillaries within the tumor capsule; evaluation of what constituted the type of nuclear clearing indicative of papillary carcinoma; and absence of clear morphologic criteria for separating adenomatous goiter and follicular adenoma. More explicit criteria for diagnosis are necessary to reduce observer variation in encapsulated follicular lesions.

Hirokawa M, et al. Observer variation of encapsulated follicular lesions of the thyroid gland. Am J Surg Pathol. 2002;26(11): 1508-1514.

Reprints: Dr. M. Hirokawa, Dept. of Pathology, University of Tokushima School of Medicine, 3-18-15 Kuramoto-cho, Tokushima, 770-8503, Japan; hirokawa@basic.med.tokushima-u.ac.jp

Robotic telepathology for frozen-section diagnosis
Telepathology is the practice of digitizing histological or macroscopic images for transmission along telecommunication pathways for diagnosis, consultation, or continuing medical education. The use of telepathology is attractive because it allows pathologists to obtain immediate consultation. Oftentimes, a solo pathologist is asked to provide diagnostic services without the support of immediate second or expert consultation during an intraoperative consultation. Previous studies have addressed static versus dynamic imaging of specimens using a variety of systems and communication pathways. The authors assessed the validity of a Web-based telepathology system for frozen section consultation within the Army Medical Department. The system studied provided real-time, dynamic remote control of a robotic microscope over standard Internet connections. For the study, 120 consecutive frozen section cases were diagnosed at a distance using the system. Intraobserver agreement between the telepathology diagnosis and glass slide diagnosis was observed. Diagnostic agreement was 100 percent for a variety of specimens. The study found that such Web-based telepathology systems help support pathologists located at distant sites.

Kaplan KJ, Burgess JR, Sandberg GD, et al. Use of robotic telepathology for frozen-section diagnosis: a retrospective trial of a telepathology system for intraoperative consultation. Mod Pathol. 2002;15:1197-1204.

Reprints: Dr. Keith J. Kaplan, Dept. of Pathology, Walter Reed Army Medical Center, 6900 Georgia Ave. NW, Washington, DC 20307-5001; keith.kaplan@na.amedd.army.mil