College of American Pathologists
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  Anatomic Abstracts





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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;

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;

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;

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;