College of American Pathologists
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  Anatomic Abstracts





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November 2001

Tumor grade as a predictor of metastasis in adult soft
tissue sarcomas

While completeness of excision has been identified as the major predictor for local recurrence of soft tissue sarcomas, histologic grade has been identified in several studies as an important predictor of metastasis and overall survival. The authors of this study used a database of 1,240 patients with nonmetastatic cancer to address the importance of tumor grade for the various common subtypes of adult STS. Of the large number of variables addressed, the following were found to be independent predictors of subsequent metastasis: tumor grade, tumor size, neurovascular or bone involvement (NBI), and tumor depth for the overall group; grade and NBI for malignant fibrous histiocytomas; tumor size, histologic subtype, and grade for liposarcomas; NBI, grade, and tumor size for leiomyosarcomas; and grade and NBI for synovial sarcomas. Grade was predictive for unclassified sarcomas and sarcomas of other types. None of the parameters studied were predictive for malignant schwannoma or rhabdomyosarcoma. The authors employed the French Federation of Cancer Centers grading system, which is based on tumor differentiation, mitotic count, and necrosis. They concluded that histologic grade appeared to be an independent predictor of metastasis development in the primary histologic types of STS, except in cases of malignant schwannoma and rhabdomyosarcoma.

Coindre JM, Terrier P, Guillou L, et al. Predictive value of grade for metastasis development in the main histologic types of adult soft tissue sarcomas: a study of 1,240 patients from the French Federation of Cancer Centers Sarcoma Group. Cancer. 2001;91:1914-1926.

Reprints: Jean-Michel Coindre, MD, Institut Bergonie, 180 rue de Saint-Genes, 33076 Bordeaux, France;

An update on TNM staging for malignant melanoma
The American Joint Committee on Cancer has approved the final version of the revised tumor-node-metastasis staging system for cutaneous melanoma. This version will become official with the publication of the sixth edition of the AJCC Cancer Staging Manual in 2002. The major changes include: revising the thickness thresholds to 1, 2, and 4 mms; using level of invasion only for T1 melanomas; using ulceration in T and N staging; combining satellitosis with in-transit metastases and using it as a determinate in the N category; moving melanomas greater than 4 mms in thickness from stage III to stage II; including the number of nodes involved by tumor as the primary determinate of N staging and using tumor burden (clinically occult versus clinically apparent nodal metastases) in lieu of the dimensions of nodal metastases as a determinate in the N category; separating lung metastases from other visceral metastases because of its more favorable prognosis; and incorporating sentinel lymph node results into the N category. It is necessary to address these modifications in the staging system and the accompanying large data set when constructing pathology reports for melanoma specimens.

Balch CM, Buzaid AC, Soong SJ, et al. Final version of the American Joint Committee on Cancer staging system for cutaneous melanoma. J Clin Oncol. 2001;19:3635-3648.

Balch CM, Soong SJ, Gershenwald JE, et al. Prognostic factors analysis of 17,600 melanoma patients: validation of the American Joint Committee on Cancer Melanoma Staging System. J Clin Oncol. 2001;19:3622-3634.

Reprints: Dr. Charles M. Balch, American Society of Clinical Oncology, 1900 Duke St., Ste. 200, Alexandria, VA 22314;

Epithelial membrane antigen overexpression: an independent predictor of recurrent endometrial carcinoma
Identifying independent predictors of recurrence in endometrial carcinoma helps in selecting management options. The authors studied 178 paraffin-embedded specimens (including 105 endometrial carcinomas, 40 endometrial hyperplasias, and 33 benign endometrial tissues) for epithelial membrane antigen overexpression using immunohistochemistry (clone GP1.4, Sigma-Aldrich Chemical Co.). They also correlated EMA overexpression with traditional prognostic factors (FIGO stage, histologic subtype, depth of myometrial invasion, and tumor grade). EMA overexpression (intense apical cell membrane staining) was associated with a significant decrease in progression-free survival. On multivariate analysis, EMA overexpression and FIGO stage were independent prognostic factors for five-year survival. Statistically significant differences were also noted in EMA overexpression and the type of endometrial lesion (adenocarcinoma: 63/105, hyperplasia: 6/40, benign endometrium: 3/33). EMA overexpression also correlated with the nonendometrioid carcinoma subtypes studied (clear cell, papillary serous, adenosquamous) but was noted in benign endometrium only in association with secretory changes. Of 19 patients with hyperplasia not subjected to hysterectomy, two patients progressed to carcinoma in less than two years. These two were the only cases associated with EMA overexpression in this group.

Coronado PJ, Fasero M, Vidart JA, et al. A comparison of epithelial membrane antigen overexpression in benign and malignant endometrium. Gynecol Oncol. 2001;82:483-488.

Reprint information unavailable.

Analysis of carcinoma ex pleomorphic adenoma
The authors conducted a study to define predictive pathological features for carcinoma ex pleomorphic adenoma arising in major salivary glands. They studied 73 cases identified from the Mayo Clinic files between 1960 and 1994. In addition to analyzing tumor grade, stage, size, histologic subtype, proportion of carcinoma, and invasion, the authors addressed a variety of antigens by employing immunohistochemistry on paraffin-embedded material. Data regarding DNA content and proliferation index were obtained using digital image analysis of Feulgen- and MIB-1-stained sections, respectively. The carcinoma component was predominant in 82 percent of the tumors and consisted of adenocarcinoma not otherwise specified in 44 percent, salivary duct carcinoma in 34 percent, and a variety of other carcinoma types in a minority of cases. Eighty-five percent of the carcinomas were high grade. Pathological features that were statistically significant with regard to overall survival included pathological stage, tumor size, proportion of tumor, extent of invasion, and proliferation index. All four patients whose tumors were confined within the capsule of the pre-existing pleomorphic adenoma had a favorable outcome. Apart from proliferation index, this study found that none of the immunohistochemical stains studied added predictive information beyond that available from gross and microscopic examination.

Lewis JE, Olsen KD, Sebo TJ. Carcinoma ex pleomorphic adenoma: pathologic analysis of 73 cases. Hum Pathol. 2001;32:596-604.

Reprints: Dr. Jean E. Lewis, Division of Anatomic Pathology, Mayo Clinic, 200 First St. SW, Rochester, MN 55905