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CAP Home > CAP Reference Resources and Publications > CAP TODAY > CAP TODAY 2006 Archive > Anatomic Abstracts
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  Anatomic Abstracts

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cap today

 

 

August 2006

Editor:
Michael Cibull, MD
Subodh Lele, MD
Melissa Kesler, MD

Criteria for additional treatment after endoscopic mucosal resection for esophageal cancer
Poorly differentiated thyroid carcinomas defined on the basis of mitosis and necrosis
Ki67 immunohistochemistry: a valuable marker in prognostication but with a risk of misclassification

Criteria for additional treatment after endoscopic mucosal resection for esophageal cancer

No previous reports on lymph node metastasis from superficial squamous cell carcinoma of the esophagus have proposed definite criteria for additional treatment after endoscopic mucosal resection. The authors investigated the association between histopathological factors and lymph node metastasis (LNM) in 464 consecutive patients with superficial squamous cell carcinoma of the esophagus who had undergone a radical esophagectomy with lymph node dissection (14 M1 lesions, intraepithelial tumors; 36 M2 lesions, tumors invading the lamina propria; 50 M3 lesions, tumors in contact with or invading the muscularis mucosa; 32 SM1 lesions, tumors invading the most superficial one-third of the submucosa; and 332 SM2/3 lesions, tumors invading deeper than SM1 level). Histopathological factors, including invasion depth, size, lymphatic invasion, venous invasion, tumor differentiation, growth pattern, degree of nuclear atypia, and histological grade,  were assessed for their association with LNM in 82 M3 or SM1 lesions to determine which patients need additional treatment after endoscopic mucosal resection. LNM was found in zero, 5.6, 18, 53.1, and 53.9 percent of the M1, M2, M3, SM1, and SM2/3 lesions, respectively. Univariate analysis showed that each of the following histopathological factors had a significant influence on LNM: invasion depth (M3 versus SM1), lymphatic invasion, venous invasion, and histological grade. Invasion depth and lymphatic invasion were significantly associated with LNM in a multivariate analysis. Four of 38 patients (10.3 percent) with M3 lesions without lymphatic invasion had LNM, whereas five of 12 patients (41.7 percent) with M3 lesions and lymphatic invasion had LNM. Only patients with M1/2 lesions are good candidates for endoscopic mucosal resection. Invading the muscularis mucosa (M3) is a high risk condition for LNM, the same as submucosal invasion, but M3 lesions without lymphatic invasion can be followed up after endoscopic mucosal resection without additional treatment.

Eguchi T, Nakanishi Y, Shimoda T, et al. Histopathological criteria for additional treatment after endoscopic mucosal resection for esophageal cancer: analysis of 464 surgically resected cases. Mod Pathol. 2006;19:475–480.

Reprints: Dr. Y. Nakanishi, Pathology Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan; yknakani@gan2.ncc.go.jp

bullet Poorly differentiated thyroid carcinomas defined on the basis of mitosis and necrosis

Poorly differentiated thyroid carcinomas occupy an intermediate position at the prognostic level on the spectrum of thyroid carcinoma progression. However, their histologic definition is controversial. The authors conducted a study to assess the prognostic significance of poorly differentiated thyroid carcinoma (PDTC) defined on the basis of mitosis and necrosis and searched for prognostic markers within this group of tumors that are predictive of overall survival and progression-free survival. PDTC was defined as thyroid carcinoma with follicular cell differentiation at the histologic or immunohistochemical levels, or both, and displaying tumor necrosis or five or more mitoses per 10 high-power fields (¥400), or both. Retrospective chart review and microscopic examination identified 58 patients with primary tumors meeting the above criteria and seen at the Memorial Sloan-Kettering Cancer Center between 1992 and 2004. These 58 patients were analyzed for various histologic, clinical, and imaging parameters. Each parameter was correlated with overall survival and progression-free survival. Of the 58 patients studied, 22 (38 percent) patients died of disease, with a five-year overall survival rate of 60 percent. Forty-three of the 58 patients (74 percent) developed disease recurrence or disease progression, with a five-year progression-free survival rate of 25 percent. The median followup for the entire patient population was 42.6 months (range, 4–205 months). Tumor size greater than 4 cm was found to be correlated with decreased progression-free survival time (P<0.001). Those tumors with a capsule demonstrated significantly improved overall survival compared with unencapsulated tumors (P=0.001). The extent of capsular invasion was found to be a significant adverse factor for progression-free survival (P=0.05). The presence of extrathyroid extension into perithyroid soft tissue was found to be correlated with decreased overall survival (P=0.001) and progression-free survival (P=0.004). Of 27 patients with distant metastasis, 19 (70 percent) had concentrated radioactive iodine at their metastatic sites. On multivariate analysis, extrathyroid extension and tumor size emerged as the only significant variables in predicting progression-free survival (P=0.04 and P=0.01, respectively), whereas extrathyroid extension was found to be the sole independent prognostic factor for overall survival (P=0.01). Growth pattern and cell type did not appear to influence outcome. The authors concluded that PDTC defined on the basis of mitosis and necrosis constitutes a group of tumors that is more aggressive and homogeneous than PDTC defined by growth pattern. Within this group of patients, microstaging (tumor size, extent of capsular invasion, and, especially, extrathyroid extension), and not growth pattern or cell type, is able to stratify patients into different prognostic categories. Radioactive iodine uptake occurs in a significant number of patients with PDTC.

Hiltzik D, Carlson DL, Tuttle RM, et al. Poorly differentiated thyroid carcinomas defined on the basis of mitosis and necrosis. Cancer. 2006;106:1286–1295.

Reprints: Dr. Ronald A. Ghossein, Dept. of Pathology, Memorial Sloan-Kettering Cancer Center, 1275 York Ave., New York, NY 10021; ghosseir@mskc.org

bullet Ki67 immunohistochemistry: a valuable marker in prognostication but with a risk of misclassification

Counting mitotic figures is considered to be a reliable prognosticator, but evaluating Ki67 immunohistochemistry has become more popular in evaluating proliferation. The authors conducted a study to investigate their earlier findings that suggested an occasional discrepancy between mitotic figures and Ki67 fraction and to analyze the associations between bcl-2 and p53 expression and proliferation. For the study, they immunostained 265 infiltrating breast carcinomas for Ki67, p53, and bcl-2. They then determined the standardized mitotic index (SMI). Four proliferation groups were based on Ki67 positivity fraction and SMI at optimal cut-off points. Cox’s multivariate model was used to test the power of the prognosticators. SMI and nodal status were the most powerful individual prognosticators. Ki67 was an independent prognosticator if nodal status, tumor size, and histological grade were included in the analysis but not if analyzed with SMI. The group with low SMI and low Ki67 fraction had the best prognosis. Groups with high SMI had the poorest prognosis. The group with low SMI and high Ki67 fraction had a favorable prognosis. Bcl-2 negativity and p53 positivity correlated with proliferation. The authors concluded that they found a “wrong positive” Ki67 group with favorable prognosis and that Ki67 cannot replace SMI because of the danger of misclassifying some patients.

Jalava P, Kuopio T, Juntti-Patinen L, et al. Ki67 immunohistochemistry: a valuable marker in prognostication but with a risk of misclassification: proliferation subgroups formed based on Ki67 immunoreactivity and standardized mitotic index. Histopathology. 2006;48:674–682.

Reprints: Dr. Päivi Jalava, Dept. of Pathology, University of Turku, FIN-20520, Turku, Finland; paivi.jalava@utu.fi


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