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  Anatomic Abstracts





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February 2007

Michael Cibull, MD
Melissa Kesler, MD

Ductal carcinoma in situ with basal-like phenotype
Significance of micrometastases on survival of women with T1 breast cancer
Therapeutic role of lymph node resection in endometrioid corpus cancer
Hyalinizing trabecular adenoma of the thyroid revisited

bullet Ductal carcinoma in situ with basal-like phenotype

Basal-like carcinomas have been identified in gene expression profiling studies as a subtype of invasive breast cancer. These lesions are estrogen receptor-negative, progesterone receptor-negative, and HER2-negative (triple negative) and typically express basal cytokeratins, epidermal growth factor receptor (EGFR), and/or c-kit. As poorly differentiated invasive ductal carcinomas, they presumably have a ductal carcinoma in situ (DCIS) precursor with similar cytologic and immunophenotypic features. However, the frequency, and even the existence, of a DCIS lesion with an immunophenotype analogous to that of invasive basal-like carcinomas has not been previously evaluated. The authors studied 66 cases of high nuclear grade DCIS using antibodies to estrogen receptor, progesterone receptor, HER2, three basal cytokeratins, EGFR, and c-kit to determine the frequency of the triple-negative phenotype and the relationship between the triple-negative phenotype and expression of basal cytokeratins and other biomarkers characteristically expressed by invasive basal-like carcinomas. Four cases (six percent) exhibited the triple-negative phenotype; the remaining cases showed other combinations of estrogen receptor, progesterone receptor, and HER2 expression (nontriple negative). Basal cytokeratins, EGFR, or both, were expressed by all four triple-negative lesions, but by only 21 of 51 (42 percent) nontriple-negative cases (P=0.04). The authors concluded that a small pro-portion of high-grade ductal carcinomas in situ exhibit a triple-negative phenotype, and these lesions more commonly show expression of basal cytokeratins or EGFR, or both, than nontriple-negative high-grade DCIS. Given that invasive breast cancers typically share immunophenotypic features with the ductal carcinoma in situ from which they arise, the authors’ findings raise the possibility that the triple-negative, basal cytokeratin or EGFR-positive DCIS lesions they identified represent a precursor lesion to invasive basal-like carcinoma.

Bryan BB, Schnitt SJ, Collins LC. Ductal carcinoma in situ with basal-like phenotype: a possible precursor to invasive basal-like breast cancer. Mod Pathol. 2006;19:617–621.

Reprints: Dr. L.C. Collins, Dept. of Pathology, Beth Israel Deaconess Medical Center, 330 Brookline Ave., Boston, MA 02215;

bullet Significance of micrometastases on survival of women with T1 breast cancer

The most important factor in predicting survival among women with newly diagnosed breast cancer is the status of the axillary lymph nodes. Although straightforward to define, it is not completely clear how micrometastases impact survival. The authors reviewed data from the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute using 43,921 cases diagnosed from January 1988 through December 2001. Among women with invasive breast carcinoma of 2 cm or less who were undergoing a resection of the primary malignancy and an axillary lymph node dissection, there were 42,197 cases without lymph node metastases and 1,724 cases with micrometastases. The authors evaluated and reported on the survival differences of these two groups. They found that survival at 12 years was modestly affected by the presence of solitary (5.0 percent) or multiple lymph nodes (3.6 percent) with micrometastases when compared with lymph node-negative cases. In subgroup analyses, the decreased survival associated with micrometastases was inconsistent. The most significant survival disadvantage associated with micrometastases was found in cases with grade 3 carcinomas. The authors concluded that the modest and variable impact of micrometastases on long-term survival indicates that micrometastases are an important, but not a dominant, prognostic indicator.

Maibenco DC, Dombi GW, Kau TY, et al. Significance of micrometastases on survival of women with T1 breast cancer. Cancer. 2006;107:1234–1239.

Reprints: Dr. Douglas Maibenco, Surgical Specialists of Decatur, 1750 E. Lake Shore Drive, Suite 200, Decatur, IL 62521;

bullet Therapeutic role of lymph node resection in endometrioid corpus cancer

The authors conducted a study to determine the potential therapeutic role of lymphadenectomy in women with endometrioid corpus cancer. They obtained demographic and clinicopathologic information from the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute between 1988 and 2001. They analyzed data using Kaplan-Meier methods and Cox proportional hazards regression. In all, 12,333 women (median age, 64) underwent surgical staging with lymph node assessment, including 9,009, 1,211, 1,223, and 890 with stages I to IV disease, respectively. Over the time intervals of 1988 to 1992, 1993 to 1997, and 1998 to 2001, the percentage of patients undergoing lymph node staging increased from 22.6 percent, to 29.6 percent, to 40.9 percent (P<0.001). In the intermediate/high-risk patients (stage IB, grade 3; stage IC and II to IV, all grades), a more extensive lymph node resection (1, 2 to 5, 6 to 10, 11 to 20, and more than 20) was associated with improved five-year, disease-specific survival across all five groups at 75.3 percent, 81.5 percent, 84.1 percent, 85.3 percent, and 86.8 percent, respectively (P<0.001). For stages IIIC to IV patients with nodal disease, the extent of node resection significantly improved survival from 51 percent, 53 percent, 53 percent, and 60 percent, to 72 percent, (P<0.001). However, no significant benefit of lymph node resection in low-risk patients could be demonstrated (stage IA, all grades; stage IB, grades 1 and 2 disease; P=0.23). In multivariate analysis, a more extensive node resection remained a significant prognostic factor for improved survival in intermediate/high-risk patients after adjusting for other factors, including age, year of diagnosis, stage, grade, adjuvant radiotherapy, and presence of positive nodes (P<0.001). The authors concluded that their study suggests that the extent of lymph node resection improves the survival of women with intermediate/high-risk endometrioid uterine cancer.

Chan JK, Cheung MK, Huh WK, et al. Therapeutic role of lymph node resection in endometrioid corpus cancer: a study of 12,333 patients. Cancer. 2006;107:1823–1830.

Reprints: Dr. John K. Chan, Division of Gynecologic Oncology, Dept. of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford Cancer Center, 875 Blake Wilbur Drive, MC 5827, Stanford, CA 94305;

bullet Hyalinizing trabecular adenoma of the thyroid revisited

Hyalinizing trabecular adenoma of the thyroid is a controversial entity—some consider it a unique entity, while others consider it a variant of papillary carcinoma, and still others consider it a nonspecific pattern that may be seen with a variety of thyroid lesions. Complicating the matter, studies demonstrating metastases have shown entities that do not appear to be hyalinizing trabecular adenomas (HTAs) as originally described, and molecular studies showing changes of papillary carcinoma have used methods that are not specific. The authors conducted a study in which they reviewed their experience with thyroid lesions that showed at least some histologic features of HTA and presented the immunohistochemical findings for these lesions using antibodies for diagnosing papillary carcinoma. The authors reviewed their files for all thyroid resection reports describing lesions with hyalinized or sclerotic stroma and a trabecular architecture within the diagnosis or diagnostic comment. They then classified them as HTA or as different lesions based on histologic features. Immunohistochemistry with antibodies to HBME1, CK19, and p63 was performed with all lesions and a series of controls. The authors identified 18 thyroid lesions with prominent sclerosis or hyalinization and trabecular architecture. Only four of these lesions were found to completely match the histologic and cytologic descriptions of HTA by HE review. The remaining 14 cases showed histologic features more compatible with other diagnoses, including cellular adenomatoid module (five), follicular adenoma (four), follicular variant of PC (FVPC) (three), and epithelial neoplasm with features of FVPC (two). All HTAs lacked immunoreactivity for HBME1, CK19, and p63. All cases deemed to be adenomatoid nodules, follicular adenomas, and epithelial neoplasms showed no immunoreactivity for HBME1 and CK19 and, of these, only a single adenomatoid nodule showed immunoreactivity for p63. Cases deemed to be FVPCs showed diffuse immunoreactivity for HBME1 and CK19, and one reacted with antibodies to p63. Of control papillary carcinomas and other thyroid lesions, reactivity for HBME1, CK19, and p63 was observed in eight of eight, seven of seven, and seven of eight, and three of 27, seven of 27, and seven of 27 cases, respectively. The authors concluded that sclerotic or hyalinized stroma with a trabecular growth pattern may be seen in a number of different thyroid lesions and, when seen, is usually a focal feature of a lesion other than HTA. Immunohistochemistry may be of assistance since cases of FVPC with prominent hyalinization and trabeculation will show immunoreactivity for HBME1 and CK19, whereas HTAs and other thyroid lesions with hyalinization and trabeculation will not.

Galgano MT, Mills SE, Stelow EB. Hyalinizing trabecular adenoma of the thyroid revisited: a histologic and immunohistochemical study of thyroid lesions with prominent trabecular architecture and sclerosis. Am J Surg Pathol. 2006;30:1269–1273.

Reprints: Dr. Edward B. Stelow, Dept. of Pathology, University of Virginia Health Sciences, Box 800214, Charlottesville, VA 22908;

Dr. Cibull is professor of pathology and laboratory medicine and direct of surgical pathology, University of Kentucky Medical Center, Lexington. Dr. Kesler is hematopathology fellow, University of Texas Southwestern Medical Center at Dallas.