College of American Pathologists
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  Anatomic Abstracts





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December 2002

Basal cells in prostatic adenocarcinoma
Determining that there is an absence of basal cells in the presence of features typical of prostatic adenocarcinoma is the conventional means of diagnosing carcinoma of the prostate. The authors conducted a study in which they noted the presence of basal cells in 36 of 3,198 consult prostate needle biopsies. The basal cells were identified by immunostaining for high-molecular-weight cytokeratin using antibody clone 34βE12 in all and confirmed by p63 immunostaining in some cases. Outpouching of high-grade prostatic intraepithelial neoplasia (HGPIN) may not explain this finding due to the presence of a large ratio of small atypical glands to HGPIN glands and absence of HGPIN in some cases. The authors consider this finding to represent early invasive carcinoma that may retain basal cells. Diagnosing carcinoma in the presence of basal cells requires solely relying on the features noted on the hematoxylin-and-eosin stain. In such cases, the authors said, caution is warranted and a consensus opinion is helpful.

Oliai BR, Kahane H, Epstein JI. Can basal cells be seen in adenocarcinoma of the prostate? An immunohistochemical study using high molecular weight cytokeratin (clone 34betaE12) antibody. Am J Surg Pathol. 2002; 26:1151-1160.

Reprints: Dr. J.I. Epstein, Dept. of Pathology, Johns Hopkins Hospital, 600 N. Wolfe St., Baltimore, MD 21287;

Tumor-suppressor gene loss in small-cell neuroendocrine carcinoma
Small-cell neuroendocrine carcinoma (SCNC) is a well-characterized malignancy with distinctive cellular morphology and aggressive biologic behavior. It is most often encountered in the lung but also originates from other sites. The basis for this difference in incidence and impact of primary site location on the molecular pathogenesis of the neoplasm is not well understood. To address this issue and identify reliable molecular markers of potential diagnostic value for primary site localization of this tumor, the authors compared the genetic profile of cancer-related gene damage of SCNC arising from a variety of organ sites. The analysis involved microdissected, paraffin-embedded, formalin-fixed specimens of SCNC. Tumors were organized into three groups: lung (n=18), head and neck region (n=5), and gastrointestinal tract (n=5). Genotyping evaluated allelic imbalance (loss of heterozygosity) involving genomic regions containing p53 (17p13), L-myc (1p34), OGG1 (3p26), MCC/APC (5q21), p16 (9p21), PTEN (10q23), and point mutational change in K-ras-2 (12p12) using polymerase chain reaction-based microsatellite analysis and DNA sequencing. Distinct genotypic profiles of allelic imbalance using this panel was seen for each group of SCNC, enabling primary site determination to be suggested based on genotypic profiling of microdissected tissue samples. Despite similarities in histologic appearance, the authors' study suggests that SCNC has a unique pattern of acquired allelic damage that is determined in part by the primary site of tumor development. These attributes can be used for primary localization of metastatic SCNC, thereby helping to diagnose and classify this neoplasm.

Dacic S, Finkelstein SD, Baksh FK, et al. Small-cell neuroendocrine carcinoma displays unique profiles of tumor-suppressor gene loss in relationship to the primary site of formation. Hum Pathol. 2002;33:927-932.

Reprints: Dr. Sanja Dacic, Dept. of Pathology, Room A160, University of Pittsburgh Medical Center, Presbyterian University Hospital, 200 Lothrop St., Pittsburgh, PA 15213

Immunohistochemical assessment of Ki-67 labeling index
Proliferative activity of tumor cells, as assessed by the Ki-67 labeling index, has been suggested as a potential prognostic indicator in many neoplastic diseases. To meaningfully apply the immunohistochemically determined tumor cell growth fraction in clinical decision-making requires obtaining information about its inter-laboratory reproducibility. To assess the reproducibility of Ki-67-determined growth fraction, the authors performed a multi-center immunohistochemical trial involving 172 laboratories, each testing 30 different tissue samples. The authors evaluated 5,160 Ki-67 labeling indices with a newly developed tissue microarray and found good inter-observer reproducibility but high inter-laboratory variability. Reassessment of all stainings revealed considerable inter-laboratory differences in the intensity and frequency of labeled nuclei, suggesting that antigen-retrieval or staining techniques are predominantly responsible for the inter-laboratory variability found in this trial. Consequently, cut-off levels for Ki-67, suggested to distinguish prognostic subgroups in tumors, appear to have limited reproducibility in a multi-center approach. The authors concluded that there is a need to standardize the immunohistochemical determination of the Ki-67 labeling index when it is used as a prognostic indicator in surgical pathology.

Mengel M, Wasielewski RV, Wiese B, et al. Interlaboratory and inter-observer reproducibility of immunohistochemical assessment of the Ki-67 labelling index in a large multi-centre trial. JPathol. 2002;198:292-299.

Reprints: Dr. Hans Kreipe, Institut für Pathologie, Medizinische Hochschule Hannover, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany

Hemangiopericytoma: modern analysis of outcome
Hemangiopericytoma (HPC) is a rare vascular tumor that is difficult to distinguish from synovial sarcoma and solitary fibrous tumor because they share histologic features. The authors defined the clinical behavior and prognosis for patients with HPC. Sixty-two patients with a diagnosis of primary, recurrent, or metastatic HPC were identified from a prospectively maintained database between July 1982 and February 1998. The pathology of all cases for which material was available (57 cases) was re-reviewed for histologic confirmation of diagnosis of HPC. Using strict pathologic criteria, including immunohistochemistry and electron microscopy, tumors from 25 of 57 patients qualified for the diagnosis of conventional hemangiopericytoma, and those tumors formed the basis of the authors' report. Survival was determined using the Kaplan-Meier method. At initial presentation, 19 patients had primary tumors, three had locally recurrent disease, and three had metastatic disease. The most frequent anatomic sites for HPC were the extremities, pelvis, and head and neck, which accounted for 80 percent of total cases. The median followup (n=25) was 49 months (range, one to 160 months). The two- and five-year overall survival rates (n=25) were 93 percent and 86 percent, respectively. The disease-specific survival rate was 86 percent at last followup. Patients undergoing complete resection (n=16) showed a 100 percent median survival at 60 months. Based on their findings, the authors recommended complete tumor resection for patients with conventional HPC. Considering the favorable outcome in this disease, however, they caution against performing operations that may cause loss of function or threaten limbs.

Espat NJ, Lewis JJ, Leung D, et al. Conventional hemangiopericytoma: modern analysis of outcome. Cancer. 2002;95:1746-1751.

Reprints: Dr. N. Joseph Espat, Assistant Professor of Surgery, University of Illinois at Chicago, Dept. of Surgery M/C 958, 840 S. Wood St., Room 435E, Chicago, IL 60612; jespat@uic.edun