College of American Pathologists
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  Anatomic Abstracts






April 2004

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, and Melissa Kesler, MD, hematopathology fellow, University of Texas Southwestern Medical Center at Dallas.

Diagnostic methods of HER2/neu detection in breast cancer with regard to real-time PCR

The authors compared different diagnostic methods for measuring HER2/neu gene amplification in breast cancer with a particular focus on real-time polymerase chain reaction (PCR). Fifty breast cancer specimens were analyzed, and the use of laser-assisted microdissection prior to PCR was investigated. Thirty-eight of 50 cases showed HER2/neu overexpression in immunohistochemistry. In the 2+ scored group, two of 23 cases were amplified after fluorescence in situ hybridization (FISH) analysis, and 14 of 15 cases in the 3+ group were amplified. Of the 16 amplified cases, three initially were measured as nonamplified by real-time PCR but showed amplification after laser-capture microdissection. One case showed amplification by PCR but turned out to have only one copy of chromosome 17 by FISH. All 0 or 1+ scored cases were measured as nonamplified by FISH and PCR. The initial concordance rate between FISH and PCR was 92 percent and could be increased to 98 percent using laser-assisted microdissection. FISH and PCR show high diagnostic accuracy and concordance, while immunohistochemistry overestimates amplification in the 2+ scored group. The authors concluded that FISH or PCR should be applied in cases scored 2+ by immunohistochemistry. The diagnostic accuracy of PCR can be increased using laser-assisted microdissection.

Merkelbach-Bruse S, Wardelmann E, Behrens P, et al. Current diagnostic methods of HER2/neu detection in breast cancer with special regard to real-time PCR. Am J Surg Pathol. 2003;27:1565–1570.

Reprints: Dr. Sabine Merkelbach-Bruse, Institute of Pathology, University of Bonn, Sigmund-Freud-Strasse 25, 53105 Bonn, Germany;

Are there recognizable preneoplastic ovarian changes?

The tumorigenesis of ovarian carcinoma is poorly understood. The authors studied morphologic features and immunohistochemical expression patterns of neoplasia-associated markers in ovaries removed prophylactically, normal ovaries, and papillary serous ovarian carcinomas to identify possible preneoplastic changes in ovarian surface epithelium. Morphologic features and immunohistochemical expression patterns of CA-125, Ki-67, p53, E-cadherin, and Bcl-2 were evaluated in 21 normal ovaries, 31 ovaries that were removed prophylactically because of increased carcinoma risk, and seven ovarian papillary serous carcinomas. Representative slides from formalin-fixed, paraffin-embedded tissue blocks were submitted for immunohistochemical staining and were evaluated independently by three gynecologic pathologists. Immunohistochemical staining results were correlated with morphologic findings. The authors found progressive increases in reactivity, with the lowest expression in normal ovarian epithelium, stronger expression in epithelium from ovaries removed prophylactically, and the highest expression in carcinomas for Ki-67 and p53. A similar trend was observed for CA-125. Positivity for Ki-67 and p53 was seen predominantly in the epithelium of inclusion cysts and deep invaginations, including those areas that had been identified as hyperplastic or dysplastic on routine hematoxylin and eosin-stained sections. The authors concluded that the results suggest biologic/molecular evidence for the existence of preneoplastic changes in ovarian surface epithelium and support the previously proposed concept of ovarian dysplasia. Subtle morphologic alterations of the ovarian epithelium may be biologically significant.

Schlosshauer PW, Cohen CJ, Penault-Llorca F, et al. Prophylactic oophorectomy: a morphologic and immunohistochemical study. Cancer. 2003;98:2599–2606.

Reprints: Dr. Peter W. Schlosshauer, Dept. of Pathology, Mount Sinai School of Medicine, 1 Gustave L. Levy Place, Box 1194, New York, NY 10029; peter. schlosshauer@

Comorbidity in dementia

There is a paucity of accurate postmortem data pertinent to comorbid medical conditions in patients with dementia, including Alzheimer’s disease. The authors conducted a study to examine general autopsy findings in patients with a dementia syndrome and to establish patterns of central nervous system comorbidity in these patients. This was accomplished through a review of autopsy reports and selected case material from 202 demented patients who had brain-only autopsies during a 17-year period from 1984 to 2000 and from 52 demented patients who had general autopsies during a six-year period from 1995 to 2000. The autopsies were performed at a large academic medical center that handled approximately 200 autopsies per year. Among the 52 patients who underwent complete autopsy, the most common cause of death was bronchopneumonia (46.1 percent). Other respiratory problems included emphysema (36.5 percent) and pulmonary thromboembolism (17.3 percent). In six cases, pulmonary thromboembolism was the proximate cause of death. Twenty-one (40.3 percent) of the 52 patients had evidence of a myocardial infarct (varying ages) and 38 (73.1 percent) had atherosclerotic cardiovascular disease—27 of a moderate to severe degree. Four clinically unsuspected malignancies were found: one each of glioblastoma multiforme, diffusely infiltrative central nervous system lymphoma, pancreatic adenocarcinoma, and adenocarcinoma of the lung. One patient with frontotemporal dementia and amyotrophic lateral sclerosis died of severe meningoencephalitis/ventriculitis, probably secondary to seeding of the central nervous system by an infected cardiac valve. Of the 202 demented patients who underwent brain-only autopsies, 129 (63.8 percent) showed changes indicative of severe Alzheimer’s disease, 21 (10.4 percent) showed combined neuropathologic abnormalities (Alzheimer’s disease plus another type of lesion, such as significant ischemic infarcts or diffuse Lewy body disease), 12 (5.9 percent) showed relatively pure ischemic vascular dementia, 13 (6.4 percent) showed diffuse Lewy body disease, and eight (4.0 percent) showed frontotemporal dementia. The remaining 19 (9.4 percent) patients showed miscellaneous neuropathologic diagnoses, including normal pressure hydrocephalus and progressive supranuclear palsy. Among the demented patients, 92 (45.5 percent) had cerebral atherosclerosis, which was moderate to severe in 65 patients (32.2 percent). Had some of the conditions found at autopsy been known antemortem, they likely would have affected clinical management of the patients. Autopsy findings may be used as a quality-of-care measure in patients who have been hospitalized in chronic care facilities for neurodegenerative disorders.

Fu C, Chute DJ, Farag ES, et al. Comorbidity in dementia: an autopsy study. Arch Pathol Lab Med. 2004;128:32–38.

Reprints: Dr. Dennis J. Chute, Section of Neuropathology, Dept. of Pathology and Laboratory Medicine, UCLA Medical Center, CHS Room 18-170, Westwood Plaza, Los Angeles, CA 90095-1732; dchute@mednet.

ER and PR immunohistochemistry for distinguishing metastatic breast carcinoma from other tumors

In surgical pathology practice, one may encounter a rather bland appearing urothelial papillary lesion and be confused regarding the proper terminology for it given the varying names used in the literature for the same entity. In this study, the authors detailed the clinicopathologic features of 26 cases of urothelial, or transitional cell, papilloma, 23 of which were de novo lesions and three of which arose in patients with a known history of bladder carcinoma. Of the 23 de novo cases, all except five occurred in patients younger than 50 years old, whereas the three secondary lesions occurred in older patients. The main morphologic features that distinguish papilloma from a low malignant potential neoplasm/grade 1 carcinoma include shorter papillae covered by nonhyperplastic urothelium, greater covering of umbrella cells, and an absence of urothelial hyperplasia at the base of the lesion. Mild cytologic atypia of a degenerative nature that was not associated with mitotic activity was noted in three cases and did not preclude their being designated papillomas. Rare mitotic figures (none atypical) were noted in two of 26 cases. One of the 14 de novo cases with follow-up data had a recurrent papilloma, and one immunosuppressed patient with a papilloma progressed to a higher grade and stage of disease. The morphologic features described in the article may help identify urothelial papillomas that appear to be distinct bladder neoplasms.

Nash JW, Morrison C, Frankel WL. The utility of estrogen receptor and progesterone receptor immunohistochemistry in the distinction of metastatic breast carcinoma from other tumors in the liver. Arch Pathol Lab Med. 2003;127:1591–1595.

Reprints: Dr. Wendy L. Frankel, Dept. of Pathology, E-401 Doan Hall, 410 W. 10th Ave., Columbus, OH 43210-1228; frankel-1@

Assessing urothelial papilloma of the urinary bladder

The All Wales Lymphoma Panel is a central expert pathological review service that reviews all primary lymphoma diagnoses made by district general hospital pathologists. It also functions as a primary diagnostic service for cases in which the diagnosis is not known. In a previous report, the group documented a 20 percent discordance rate between initial and reviewed diagnoses over the two-year period following its inception. The current study attempts to determine whether changes in diagnosis affect patient management. Between January 1998 and August 2000, 125 of 745 (17 percent) cases received for review by the All Wales Lymphoma Panel had a consequent change in diagnosis. Changes included reclassification from one non-Hodgkin lymphoma category to another, revision of NHL to Hodgkin lymphoma or vice versa, and, in 42 cases (42 percent), reclassification from reactive lymphadenopathy to malignant lymphoma or vice versa. Complete case notes were recovered in 99 cases (79 percent). For these cases, a hypothetical management plan was generated based on the diagnosis submitted, clinical protocols, and patient clinical information, including history, presentation, and IPI score. This was compared with the treatment the patients received after the revised diagnosis. Forty-six of the 99 cases (46 percent) had a change in management as a result of expert review. Changes included treatment to no treatment, no treatment to treatment, and modification of treatment regimen. The authors concluded that expert pathologic review is important for accurate diagnosis and directly impacts patient management.

McKenney JK, Amin MB, Young RH. Urothelial (transitional cell) papilloma of the urinary bladder: a clinicopathologic study of 26 cases. Mod Pathol. 2003;16:623–629.

Reprints: Dr. Mahul B. Amin, Dept. of Pathology and Laboratory Medicine, Emory University Hospital, Room G-167, 1364 Clifton Rd., NE, Atlanta, GA 30322; mahul_amin@

Reliability of the histopathological diagnosis of follicular thyroid carcinoma

The authors evaluated interobserver and intraobserver reproducibility in the histopathology of follicular thyroid carcinoma. Forty-one anonymous follicular thyroid carcinoma (FTC) pathology slides were independently reviewed by five pathologists—31 of them were evaluated twice by the same pathologist. A final consensus diagnosis was made at the end of the study. Interobserver and intraobserver agreement were determined as the kappa statistic for qualitative data and intraclass correlation coefficient for quantitative data. The agreement between the five observers’ initial diagnoses and the final consensus diagnosis was 0.69, 0.41, 0.35, 0.28, and 0.11, respectively, strongly suggesting a leadership phenomenon. The final consensus diagnosis classified 30 cases as malignant, including 24 cases diagnosed as FTC. The observers reached unanimous agreement on 13 of the 24 FTCs. Diagnostic reproducibility was found to be acceptable for the nonminimally invasive FTC. Diagnostic discrepancies occurred in 57 percent of the seven cases classified as minimally invasive FTC by the final consensus diagnosis. That diagnosis excluded malignancy in 11 cases, including six atypical adenomas. Interobserver and intraobserver agreement for FTC diagnosis was 0.23 (standard error, 0.04) and 0.68, respectively. Interobserver and intraobserver agreement for the presence of vascular invasion was 0.20 (standard error, 0.04) and 0.51, respectively, contrasting with a moderate to substantial level of agreement when considering the number of vascular invasion. Interobserver and intraobserver agreement for nucleus optical clearing were slight and moderate, respectively. The study confirms that the diagnostic reproducibility of minimally invasive FTC is low and that this has clinical implications as well as implications for designing studies on the treatment and outcome of FTC.

Franc B, de la Salmonière P, Lange F, et al. Interobserver and intraobserver reproducibility in the histopathology of follicular thyroid carcinoma. Hum Pathol. 2003;34:1092–1100.

(See also the accompanying editorial: LiVolsi VA. Can we agree to disagree? Hum Pathol. 2003;23(11):1081–1082.)

Reprints: Brigitte Franc, Hôpital Ambroise Paré, 9 Avenue Charles de Gaulle, 92104, Boulogne Billancourt, France