College of American Pathologists
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  Anatomic Abstracts





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February 2003

Scarring as a prognostic indicator in small peripheral lung adenocarcinomas
Several studies have demonstrated the prognostic value of desmoplasia for lung adenocarcinomas. The authors evaluated the density and extent of desmoplasia by modifying the scar grade and the prognostic impact on patient survival. Modified scar grade was defined as: grade 1, no desmoplasia; grade 2, sparse desmoplastic reaction; grade 3, dense desmoplastic reaction with diameter of 10 mm or less; grade 4, dense desmoplastic reaction with diameter of more than 10 mm. In addition, the prognostic impact of conventional histologic factors and modified scar grade was analyzed in 239 cases of small peripheral lung adenocarcinoma (maximum dimension, < 30 mm) for which long-term followup data were available. The five- and 10-year survival rates according to the modified scar grade were, respectively, 100 percent and 100 percent for grade 1 lung adenocarcinoma (n=29); 91.7 percent and 83.7 percent for grade 2 (n=61); 67.6 percent and 52.7 percent for grade 3 (n=78); and 50 percent and 37.5 percent for grade 4 (n=71). A significant difference in patient survival was found between grade 1 or 2 versus grade 3 or 4 (P<0.0001 by log rank test). Multivariate analysis showed that modified scar grade was an independent prognostic factor (P=0.0176), as were pathologic stage (P=0.0293), lymph node metastasis (P=0.0191), lymphatic permeation (P=0.0022), and pleural involvement (P=0.0452). Modified scar grade also had a significant impact on survival in various subsets of patients, including those with pathologic stage IA disease, patients with tumors of 20 mm or less diameter, or patients with mixed subtype tumors with a bronchioloalveolar component. The authors concluded that the modified scar grade is a useful prognostic factor in patients with small lung adenocarcinoma. Tumors with a sparse fibroblastic reaction (modified scar grade 2) may represent early invasive cancers or invasive cancers with low malignant potential, which should be distinguished from frankly invasive cancers (modified scar grade 3 or 4).

Maeshima AM, Niki T, Maeshima A, et al. Modified scar grade: a prognostic indicator in small peripheral lung adenocarcinoma. Cancer. 2002;95:2546-2554.

Reprints: Dr. Yoshihiro Matsuno, Clinical Laboratory Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan;

Imprint cytology in evaluation of sentinel lymph nodes in breast cancer
An upswing in lymphatic mapping techniques for breast carcinoma has increased the attractiveness of intraoperative evaluation of sentinel lymph nodes. Axillary lymph node dissection can be performed during initial surgery if the sentinel lymph node is positive, potentially avoiding a second operative procedure. An optimal technique for rapidly assessing sentinel lymph nodes has not been determined. Many institutions use frozen sectioning and intraoperative imprint cytology for rapid intraoperative sentinel lymph node evaluation. The authors performed a study of imprint cytology for intraoperative evaluation of sentinel lymph nodes in patients with breast cancer. They conducted a retrospective review of the intraoperative imprint cytology results of 678 sentinel lymph node mappings for breast carcinoma. Sentinel nodes were evaluated intraoperatively by bisecting or slicing them into 4-mm sections. Imprints were made of each cut surface and stained with hematoxylin and eosin or Diff-Quik, or both. Permanent sections were evaluated with up to four H&E stained levels and cytokeratin immunohistochemistry. Intraoperative imprint cytology results were compared with final histologic results. Imprint cytology had a sensitivity of 53 percent, specificity of 98 percent, positive predictive value of 94 percent, negative predictive value of 82 percent, and accuracy of 84 percent. The sensitivity for detecting macrometastases (>2 mm) was significantly better than for detecting micrometastases (<2 mm) at 81 percent versus 21 percent, respectively (P<00001). The authors concluded that the sensitivity and specificity of imprint cytology are similar to that of intraoperative frozen section evaluation. Imprint cytology is, therefore, a viable alternative to frozen sectioning when intraoperative evaluation is required. If sentinel lymph node micrometastasis is used to determine whether further lymphadenectomy is needed, then more sensitive intraoperative methods will be necessary to avoid a second operation.

Creager, AJ, Geisinger KR, Shiver SA, et al. Intraoperative evaluation of sentinel lymph nodes for metastatic breast carcinoma by imprint cytology. Mod Pathol. 2002;15(11):1140-1147.

Reprints: Dr. Andrew J. Creager, Dept. of Pathology, Duke University Medical Center, DUMC 3712, Durham, NC 27710;

Role of histology in predicting behavior of some neuroendocrine tumors
Metastasized neuroendocrine tumors of the gastrointestinal tract and of unknown origin have a highly variable clinical course. Within this group, low-grade and high-grade malignant tumors can be recognized based on the revised classification of neuroendocrine tumors of the lung, pancreas, and gut (Capella, et al, 1995). The authors investigated whether it is possible to fine-tune the prediction of prognosis by dividing the group of low-grade malignant tumors of the midgut and of unknown origin into typical and atypical carcinoids by grading them according to the World Health Organization classification criteria for neuroendocrine tumors of the lung. They also evaluated the prognostic value of immunohistochemical stainings and clinical parameters. The study group comprised patients diagnosed between 1983 and 1999 with liver metastases of a neuroendocrine tumor of the midgut (n=40) or of unknown origin (n=16). Tumors of the midgut and of unknown origin were evaluated together because they were clinically similar. As a control for consistency of grading, the authors also evaluated 10 patients with metastasized neuroendocrine tumors of the lung. They performed immunohistochemical staining for several antigens, and the findings were correlated with clinical parameters. In this group of 56 patients, the Capella and the WHO classification systems recognized the high-grade malignant tumors with a bad prognosis. When the low-grade malignant tumors (Capella) were divided into typical and atypical carcinoids (WHO), the authors did not note a difference in survival, but when the dichotomy into typical and atypical was based on mitotic count alone, the difference became borderline significant (P=.072). Of the immunohistochemical stains used, synaptophysin, cytokeratin 8, and ki67 had limited prognostic value. Age of more than 60 years was the only clinical parameter of unfavorable prognostic significance. The authors concluded that high-grade malignant neuroendocrine tumors of the midgut and of unknown origin are recognized by the Capella classification and the WHO classification of neuroendocrine tumors of the lung. Further subdividing low-grade malignant tumors at this location appears to be of less value than in the lung, but assessing the mitotic activity of these tumors might be of prognostic value.

Van Eeden S, Quaedvlieg PF, Taal BG, et al. Classification of low-grade neuroendocrine tumors of midgut and unknown origin. Hum Pathol. 2002;33:1126-1132.

Reprints: Marie-Louise Van Velthuysen, Dept. of Pathology, The Netherlands Cancer Institute, Plesmanlaan 121 1066 CX, Amsterdam, Netherlands.