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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; jepstein@jhmi.edu
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
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