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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; w.dinjens@erasmusmc.nl.
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; uraju1@hfhs.org.
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.
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