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April 2002
Importance of tumor size in clear cell carcinoma of kidney
The authors studied the importance of tumor size in determining prognosis
for clear cell carcinoma of the kidney. They identified 135 cases
of organ-confined clear cell renal cell carcinoma, with a minimum
of five years’ followup, from the New South Wales Cancer Registry.
Tumor size was compared with survival using the Kaplan and Meier method
for tumor, nodes, metastases size categories, and proportional hazards
regression was used to assess size as a continuous variable. Proportional
hazard regression also was used for multivariable comparisons of size
and other prognostic parameters (Fuhrman grade, AgNOR score, and Ki-67
index) against survival. Of 116 cases for which tumor dimension was
recorded, 25 patients had died of cancer-related causes. Primary tumor
size ranged from 12 to 140 mm (mean, 57.3 mm). The association between
survival and size was significant irrespective of the TNM classification
and was also significant when size was modeled continuously (P=0.000125;
hazard of death increased by 3.51 times for each doubling of tumor
size). On univariate analysis, Fuhrman grade (P=0.04) and AgNOR
score (P=0.015) were associated with survival. On multivariate
analysis, however, only tumor size was still significant. Although
the cut point of T1 and T2 TNM categories and the proposed T1 subdivision
cut point correlate with survival, the finding that size is a continuous
variable indicates that as a prognostic parameter for clear cell renal
cell carcinoma, primary tumor size is relative rather than indicative.
Delahunt B, Kittelson JM, McCredie MRE, et al. Prognostic importance
of tumor size for localized conventional (clear cell) renal cell carcinoma.
Assessment of TNM T1 and T2 tumor categories and comparison with other
prognostic parameters. Cancer. 2002;94: 658-664.
Reprints: Brett Delahunt, Dept. of Pathology and Molecular Medicine, Wellington
School of Medicine, P.O. Box 7343, Wellington South, New Zealand; bd@wnmeds.ac.nz
Extracapsular spread and
squamous cell carcinoma of the tongue
The presence or absence of extracapsular extension of tumor in lymph
node metastases is not considered in the current American Joint Committee
on Cancer staging of tumors of the hypopharynx and tongue. The authors
documented its importance in a study of 266 patients with carcinoma
of the oral tongue treated at a single institution. One hundred and
forty-six patients (55 percent) were pathologically node-negative,
75 (28 percent) were node-positive without extracapsular extension
of tumor, and 45 (17 percent) were node-positive with extracapsular
extension of tumor. The overall recurrence rates were 19.8 percent,
34.2 percent, and 51.1 percent, respectively, with regional failure
rates of 11.5 percent, 19.2 percent, and 28.9 percent, respectively,
and distant metastases rates of 3.3 percent, 8.2 percent, and 24.4
percent, respectively. These data suggest that extracapsular extension
of tumor is the most significant predictor of regional recurrence
and distant metastases in these patients. This is reflected by the
five-year disease-specific survival rates of 88 percent, 65 percent,
and 48 percent for the three groups.
Myers JN, Greenber JS, Mo V, et al. Extracapsular spread. A significant
predictor of treatment failure in patients with squamous cell carcinoma
of the tongue. Cancer. 2001;92:3030-3036.
Reprints: Dr. Jeffrey N. Myers, Dept. of Head and Neck Surgery,
University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd.,
Box 441, Houston, TX 77030-4009; jmyers@notes.mdacc.tmc.edu
Cytokeratin-positive reticulum
cells in benign reactive lymph nodes
Cytokeratin immunostaining of sentinel lymph nodes is used to confirm
or exclude micrometastasis in managing patients with breast cancer.
Knowledge of the cytokeratin immunostaining pattern in benign reactive
lymph nodes is important to avoid misinterpreting positive staining
cells. In this study, the authors analyzed the cytokeratin staining
profile in paraffin of histologically benign cervical and axillary
lymph node specimens from 20 cases. Each case was immuno-stained with
a cytokeratin antibody preparation: AE1/ AE3, CAM 5.2, or a cocktail
prepared in-house that was composed of seven antibodies (three clones
of MAK-6, AE1/AE3, CAM 5.2, 34ßE12, and 35ßH11). The three
antibody preparations stained reticulum cells in varying proportions:
rare cells with AE1/AE3 (2/20); rare to 10 percent of cells with CAM
5.2 and the cytokeratin cocktail (85 percent of cases). The cytokeratin-positive
reticulum cells were also positive for calponin and negative for KP-1
(CD68) and MAC 387, which stained macrophages and sinus histiocytes.
The latter suggested that the cytokeratin immunoreactive lymph node
reticulum cells were a unique cell type and not of macrophage/histiocyte
derivation.
Linden MD, Zarbo RJ. Cytokeratin immunostaining patterns of benign,
reactive lymph nodes: applications for the evaluation of sentinel
lymph node specimen. Appl Immunohistochem Mol Morphol. 2001:9:297-301
Reprints: Dr. Michael D. Linden, Dept. of Pathology, W-605, Henry Ford Hospital,
2799 W. Grand Blvd., Detroit, MI 48202
Unexpected fallopian tube, ovarian, and -peritoneal neoplasms
in patients who may have BRCA-1 or -2 mutations
Few reports address the processing of specimens from patients having prophylactic
surgery for suspected or proven inheritable mutations. The authors described
five patients who had prophylactic total abdominal hysterectomy and sal-pingo-oophorectomy
for a known BRCA-1/BRCA-2 mutation or a family history of breast or ovarian
cancer, or both. Two additional patients had surgery for benign disease (ovarian
serous cystadenoma in one and uterine leiomyomata in another) and a family history
of breast or ovarian carcinoma, or both. All were asymptomatic, except for the
patient with leiomyomata. The initial pathologic examination in one patient
did not reveal a malignancy, but because the peritoneal washings were positive
on cytology, the specimen was re-examined and revealed a 0.7-cm papillary serous
adenocarcinoma involving the fallopian tube and cells similar to the peritoneal
fluid in the fallopian tube lumen. In three cases, the situation was similar
to the first in that no definite lesions were noted grossly, yet fallopian tube
carcinomas were found on microscopic examination (0.2 to 0.8 cm) after complete
embedding in the fallopian tubes and ovaries. In one of these three cases, the
peritoneal washing was positive. Primary peritoneal serous carcinoma and a borderline
clear cell adenofibroma were identified in two cases, respectively. The authors
noted that to identify early neoplastic changes, it is necessary to perform
peritoneal fluid cytology and careful pathologic examination of specimens from
patients who undergo prophylactic surgery because they are suspected of having
these mutations or are known to have them. Interestingly, in one of the seven
cases, a diagnosis of fallopian tube carcinoma and significant family history
resulted in rigorous clinical followup and identification of a 1-cm node-negative
left breast carcinoma. This patient subsequently developed a carcinoma in the
opposite breast and is alive but has recurrent breast carcinoma.
Agoff SN, Mendelin JE, Grieco VS, et al. Unexpected gynecologic neoplasms
in patients with proven or suspected BRCA-1 or -2 mutations. Implications
for gross examination, cytology, and clinical follow-up. Am J Surg Pathol.
2002;26:171-178.
Reprints: Dr. S. Nicholas Agoff, University of Washington Medical Center,
Dept. of Anatomic Pathology, Box 356100, 1959 NE Pacific St., Seattle, WA
98195-6100; agoff@u.washington.edu
Prognosis of brain tumors—beyond histology
The authors conducted a study to assess whether mutations in the TP53 gene or
the degree of expression of p53 protein in high-grade gliomas is associated
with progression-free survival in children with such tumors. Paraffin-embedded
specimens of malignant gliomas from children treated in the Children’s Cancer
Group study CCG-945 were evaluated using mutational analysis of TP53 (121 specimens)
and immunohistochemical analysis of p53 (115 specimens). For mutational studies,
areas of tissue that contained malignant gliomas were isolated by microdissection,
and the DNA underwent polymerase chain-reaction-based amplification and sequencing
of TP53 exons 5, 6, 7, and 8. Immunohistochemical analysis was performed with
a microwave-enhanced antigen retrieval and an antibody that bound wild-type
and mutant p53. A significant association was noted between overexpression of
p53 and outcome. This association was independent of histologic features, age,
gender, extent of resection, and tumor location. The rate (±SE) of progression-free
survival at five years was 44±6 percent in the 74 patients whose tumors had
low levels of expression of p53 and 17±6 percent in the 41 patients whose tumors
had overexpression of p53 (P<0.001). A nonsignificant association was observed
between mutations in TP53 and outcome. Overexpression of p53 in malignant gliomas
during childhood is strongly associated with an adverse outcome that is independent
of clinical prognostic factors and histologic findings.
Pollack IF, Finkelstein SD, Woods J, et al. Expression of p53 and prognosis
in children with malignant gliomas. N Engl J Med. 2002;346:420-427.
Reprints: Dr. I. F. Pollack, Dept. of Neurosurgery, Children’s Hospital
of Pittsburgh, 3705 Fifth Ave., Pittsburgh, PA 15213; pollaci@chplink.chp.edu
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