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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; sabine.merkelbach-bruse@ukb.uni-bonn.de
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@
mountsinai.org
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.
ucla.edu
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@
medctr.osu.edu
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@
emoryhealthcare.org
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
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