College of American Pathologists
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  Anatomic Abstracts





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June 2003

Molecular determinations in gynecologic patients with multiple tumors
The prognosis and treatment of patients with multiple tumors may depend on knowing whether the tumors represent multiple primary tumors, recurrent tumors, or metastatic disease. The authors investigated whether detecting molecular aberrations in multiple gynecologic tumors in individual patients provided clinically useful information. Between 1999 and 2001, molecular analyses were performed on tissue from 15 gynecologic patients, all of whom had multiple tumors. The molecular analyses included loss of heterozygosity determinations at eight DNA loci and mutation analyses of p53 exons 5-8 using the single-strand conformation polymorphism method. Molecular results were obtained from all tumors from the 15 patients. The DNA alterations that were detected provided evidence that two patients had second primary tumors, nine had a single tumor with metastases, and four had two independent primary tumors and metastatic disease. The results provided additional diagnostic information and contributed to clinical decisionmaking. The authors demonstrated that by comparing DNA alterations in multiple tumors within a patient they can obtain evidence about correlations between tumors. These investigations can be performed on routinely processed tissue. The results may be of clinical importance in helping to determine the management or prognosis of patients with gynecologic malignancies.

Dinjens WN, van der Burg ME, Chadha S, et al. Clinical importance of molecular determinations in gynecologic patients with multiple tumors. Cancer. 2003;97:1766–1774.

Reprints: Dr. Winand N.M. Dinjens, Dept. of Pathology, Josephine Nefkens Institute, Erasmus Medical Center, P.O. Box 1738, 3000 DR Rotterdam, Netherlands;

Significance of finding multiple papillomas in a breast biopsy
The authors performed a retrospective clinicopathologic study of 28 patients with breast lesions characterized by at least five papillomas in at least two nonconsecutive blocks. All histologic sections were assessed for coexisting fibrocystic lesions, including atypical hyperplasia (atypical ductal hyperplasia [ADH] or atypical lobular hyperplasia [ALH]), lobular carcinoma in situ (LCIS), and papillary atypia (defined as nuclear hyperchromatism, stratification, and architectural complexity of a lesser degree than in papillary carcinoma). All of the lesions were compared with a set of cases in which ductal carcinoma in situ (DCIS) (n=20) or invasive carcinoma (n=13) was accompanied by multiple papillomas. The multiple papilloma cases had a characteristic morphologic appearance, typically presenting as a mass comprising multiple adjacent ducts filled by papillomas, accompanied by dense fibrosis and intermingled with various proliferative fibrocystic lesions, particularly florid adenosis. Atypical hyperplasia was a frequent finding (12 of 28 cases), particularly in cases with atypical papillomas (seven of 11 cases). Although contralateral lesions occurred in four of 28 patients (three multiple papillomas and one invasive carcinoma), only one patient developed ipsilateral breast carcinoma (mean followup, 47 months). DCIS associated with multiple papillomas typically was low grade (17 of 20 cases) and arose from areas within or immediately adjacent to pre-existing benign lesions. None recurred (mean followup, 41 months), although one patient had contralateral multiple papillomas and three patients developed carcinomas in the opposite breast. Invasive carcinomas developing in a background of (ipsilateral) multiple papillomas were mostly small (eight of 11 smaller than 2.0 cm), node negative (seven of 10), and estrogen receptor positive (eight of eight). Only one of 13 patients died from disease (mean followup, 59 months), but five developed contralateral breast lesions (one multiple papilloma, one multiple papilloma DCIS, one CDIS, one LCIS, and one invasive carcinoma). The authors concluded that the frequent associations with ADH, ALH/LCIS, malignant lesions, and bilaterality imply that multiple papillomas may represent a marker of constitutionally increased breast cancer risk. Because carcinomas arose within or close to areas involved by pre-existing benign multiple papilloma lesions, it may also be appropriate to excise segments of tissue involved by multiple papillomas, particularly cases with atypia, and closely monitor for contralateral disease.

Ali-Fehmi R, Carolin K, Wallis T, et al. Clinicopathologic analysis of breast lesions associated with multiple papillomas. Hum Pathol. 2003;34:234–239.

Reprints: Dr. Daniel W. Visshcher, Dept. of Laboratory Medicine and Pathology, Mayo Clinic, 200 First St. SW, Rochester, MN 55905.

False-negative core needle biopsies of the breast: an analysis of study findings
A benign diagnosis in a core needle biopsy (CNBx) of the breast performed for a clinically or radiologically suspicious abnormality, or both, is often due to a nonrepresentative sample. The discordance may not be recognized, however, resulting in a logistic delay in diagnosis. Twenty-seven false-negative CNBxs were identified in 952 consecutive CNBxs of the breast (653 benign, 266 malignant, and 33 atypical) performed during a one-year period. Biopsies were analyzed with respect to clinical and radiologic findings, biopsy type, type of malignancy, and interval between the original CNBx and final diagnosis. Four hundred and thirty-eight (67 percent) of the patients with a benign CNBx diagnosis underwent excision or had a minimum of one-year followup (mean, 35.6 months; median, 36 months). The cancers missed on CNBx included six ductal carcinomas in situ, 17 invasive ductal carcinomas, three invasive lobular carcinomas, and one non-Hodgkin lymphoma. The overall false-negative rate was 9.1 percent. For palpable lesions, ultrasound-guided CNBx had a lower rate of missed cancer (3.6 percent) compared with CNBx without image guidance (13.3 percent). The false-negative rate for vacuum-assisted CNBx biopsy was 7.6 percent (3.3 percent for the 11-gauge needle; 22.2 percent for the 14-gauge needle; 5.6 percent for nonpalpable mass lesions; 8.2 percent for microcalcifications). In the seven false-negative CNBxs performed by radiologists, the discordance between the radiologic and pathologic findings was promptly recognized due to their standard followup protocol. The discordance between the degree of clinical suspicion, radiologic impression, and pathologic findings, however, was not immediately recognized in five of 20 false-negative CNBxs performed by surgeons (four without radiologic guidance and one with ultrasound guidance), resulting in a delay in diagnosis ranging from 112 to 336 days. The authors concluded that a false-negative diagnosis of breast carcinoma was more common in CNBx performed without image guidance but occurred to a lesser degree in image-guided biopsies. A delay in diagnosis can be avoided by establishing a standard post-CNBx followup protocol.

Shah VI, Raju U, Chitale D, et al. False-negative core needle biopsies of the breast: an analysis of clinical, radiologic, and pathologic findings in 27 consecutive cases of missed breast cancer. Cancer. 2003;97: 1824–1831.

Reprints: Dr. Usha Raju, Dept. of Pathology, Henry Ford Hospital, 2799 W. Grand Blvd., Detroit, MI 48202;

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.