Anatomic Abstracts

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May 2003

Atypical diagnosis rendered on breast needle core biopsy
The three recent papers referenced herein assess the problem of what to do with the patient for whom a diagnosis of atypical ductal hyperplasia or lobular intraepithelial neoplasia has been made on an image-guided needle core biopsy. Middleton et al, who addressed lobular lesions in their study, found little evidence to support excision unless there was also an associated radiographic mass. In their study, all six cases with invasive carcinoma on excision had this finding. The two studies that addressed atypical hyperplasia identified cytologic atypia as an important predictor of significant residual disease. The study by Bonnett et al also noted that atypical papillary pattern, number of atypical foci (>4), and larger span of microcalcifications (>2.0 cm) were associated with an increased risk of residual ductal carcinoma in situ. In addition to cytologic atypia, Yeh et al. added apoptosis/individual cell necrosis as a noteworthy feature in identifying a more serious lesion on excision. These three papers do not provide definitive answers by themselves. They do, however, provide ammunition in the struggle to develop meaningful clinical recommendations based on the pathologic findings observed in small specimens obtained from “minimally invasive” procedures.

Yeh IT, Dimitrov D, Otto P, et al. Pathologic review of atypical hyperplasia identified by image-guided breast needle core biopsy. Correlation with excision specimen. Arch Pathol Lab Med. 2003;127:49-54.

Reprints: Dr. I-Tien Yeh, Dept. of Pathology, University of Texas Health Science Center, San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229; yehi@uthscsa.Edu.

Middleton LP, Grant S, Stephens T, et al. Lobular carcinoma in situ diagnosed by core needle biopsy: When should it be excised? Mod Pathol. 2003;16(2):120-129.

Reprints: Dr. Lavinia P. Middleton, Dept. of Pathology, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd., Box 85, Houston, TX 77030; lpmiddleton@mdanderson.org.

Bonnett M, Wallis T, Rossmann M, et al. Histopathologic analysis of atypical lesions in image-guided core breast biopsies. Mod Pathol. 2003;16(2):154-160.

Reprints: Dr. Daniel Visscher, Dept. of Pathology, Mayo Clinic, 200 First St. SW, Rochester, MN 55905; visscher.daniel@mayo.edu.

Renal carcinomas associated with PRCC-TFE3 gene fusion
Molecular analysis of tumors may help identify neoplasms with unique clinicopathologic features and may also provide insight into treatment strategies. The authors described 11 renal carcinomas with a t(X;1)(p11.2;q21) or the resulting PRCC-TFE3 gene fusion, or both. A characteristic morphologic feature of these neoplasms is the immediate juxtaposition of cells with clear and eosinophilic cytoplasm with nested and papillary architecture. Such features may cause these neoplasms to be confused with conventional clear cell, papillary, or recently described ASPL-TFE3 renal carcinomas. Unlike conventional clear cell or papillary renal carcinomas, however, these neoplasms are negative or only focally positive for cytokeratin and epithelial membrane antigen and are positive for TFE3 protein (90 percent), RCC antigen (90 percent), and CD10 (100 percent). They may mimic ASPL-TFE3 renal carcinomas clinically and on histomorphology; however, unlike ASPL-TFE3 carcinomas, they show more consistent epithelial features on ultrastructural examination and appear to have a less invasive growth pattern. The authors noted that PRCC-TFE3 tumors are likely slow-growing indolent lesions, with some having a long interval to metastasis. The presence of a fibrous pseudocapsule that may be calcified appears to be a gross characteristic of these tumors.

Argani P, Antonescu CR, Couturier J, et al. PRCC-TFE3 renal carcinomas: morphologic, immunohistochemical, ultrastructural, and molecular analysis of an entity associated with the t(x;1)(p11.2;q21). Am J Surg Pathol. 2002;26:1553-1566.

Reprints: Dr. Pedram Argani, Johns Hopkins Hospital, Surgical Pathology, Weinberg Building, Room 2242, 401 N. Broadway, Baltimore, MD 21231-2410; pargani@jhmi.edu.

Clinical significance of gastrointestinal involvement in mantle cell lymphoma
The reported frequency of gastrointestinal tract involvement in patients with mantle cell lymphoma (MCL) is 15 to 30 percent. This figure, however, is most likely underestimated because most patients with MCL involving the GI tract that was previously reported were examined endoscopically only if they had GI tract symptoms. How endoscopic assessment influences the management of MCL patients is unknown. In this study, only 26 percent of patients presented with GI symptoms at the time of diagnosis. MCL was present histologically in the lower GI tract of 53 of 60 patients (88 percent) and in the upper GI tract of 28 of 58 patients (43 percent). Microscopic evidence of MCL was found in 84 percent of patients with normal visual (macroscopic) findings by lower endoscopy and in 45 percent of patients with macroscopically normal findings by upper endoscopy. Despite this high frequency of GI tract involvement, the use of upper and lower endoscopy with biopsies in this group of patients resulted in changes in clinical management in only three (four percent) patients. Gastrointestinal tract involvement was found in most patients with MCL, usually at a microscopic level involving macroscopically normal mucosa. Aggressive staging evaluation of the GI tract was found to have little impact on patient-management decisions in this study.

Romaguera JE, Mederios LJ, Hagemeister FB, et al. Frequency of gastrointestinal involvement and its clinical significance in mantle cell lymphoma. Cancer. 2003;97:586-591.

Reprints: Dr. Jorge E. Romaguera, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd., P.O. Box 429, Houston, TX 77030; jromague@mail.mdanderson.org.

Morphologic reappraisal of serrated colorectal polyps
The “hyperplastic polyp” is considered a benign lesion with no malignant potential, whereas “serrated adenoma” is a precursor of adenocarcinoma. The morphologic complexity of serrated adenoma varies from being clearly adenomatous to being difficult to distinguish from hyperplastic polyp. This creates a need for more detailed morphologic analysis of all serrated polyps. The authors evaluated 24 morphologic variables in 289 serrated polyps from the colon and rectum. They performed cluster analysis and discriminant analysis. A subset of polyps was immunostained for hMHL1 and hMSH2. Major differences were found between right-sided and left-sided polyps. A distinct group of serrated polyps with abnormal proliferation was identified throughout the colon and rectum. These polyps demonstrated decreased expression of hMHL1 and hMSH2 compared with polyps with normal proliferation. Left-sided serrated polyps with normal proliferation further clustered into three groups: vesicular cell-type, goblet cell-type, and mucin-poor-type. The authors recommend evaluating localization, size, and morphologic features when serrated polyps are included in colorectal carcinogenesis research. Polyps with abnormal proliferation are similar to the polyps in “hyperplastic polyposis” and, because of their decreased expression of hMLH1 and hMSH2, may be the subset of polyps associated with the development of colorectal carcinoma via the microsatellite instability pathway.

Torlakovic E, Skovlund E, Snover DC, et al. Morphologic reappraisal of serrated colorectal polyps. Am J Surg Pathol. 2003;27(1):65-81.

Reprints: Dr. Dale C. Snover, Dept. of Pathology, Fairview Southdale Hospital, 6401 France Ave. S., Edina, MN 55435; snoverd@umn.edu.

Anatomic pathology abstracts editors

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.