Anatomic Abstracts
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December 2010 Editors:
Sclerosing adenosis of the prostate is a benign, small, acinar proliferation in dense spindle cell stroma with a distinct immunohistochemical profile. It is incidentally found in about two percent of transurethral resection specimens. The authors sought to describe cases with significant cytological atypia mimicking cancer, which have not been previously reported. They described five cases of sclerosing adenosis with significant cytological atypia, referred to as atypical sclerosing adenosis (ASA), which were initially considered suspicious or diagnostic of adenocarcinoma. They used seven cases of typical sclerosing adenosis as controls. The authors determined that all cases of typical and atypical sclerosing adenosis displayed an intact basal cell layer, which was immunoreactive for high-molecular–weight keratin, S100 protein, smooth muscle actin, and prostate-specific antigen, with no differences between ASA cases and the control group. Alpha-methylacyl-coenzyme A racemase was negative. Three of four cases of ASA showed aneuploid DNA content on digital image analysis. All cases of typical sclerosing adenosis were diploid. During a mean followup of 33 months (range, five to 73 months), no subjects developed recurrence or prostatic cancer. The authors concluded that ASA is an unusual, small, acinar proliferation of the prostate that may be mistaken for adenocarcinoma and should be distinguished from other mimics, including atypical adenomatous hyperplasia, mesonephric remnant hyperplasia, and post-atrophic hyperplasia. Atypical sclerosing adenosis is a benign lesion, and aggressive treatment is unwarranted. Cheng L, Bostwick DG. Atypical sclerosing adenosis of the prostate: a rare mimic of adenocarcinoma. Histopathol. 2010;56:627–631. Correspondence: Dr. L. Cheng at liang_cheng@yahoo.com
The authors conducted a phase III, multicenter, randomized, placebo-controlled trial to assess the efficacy and safety of sorafenib, an oral multikinase inhibitor, in combination with carboplatin and paclitaxel, in chemotherapynaïve patients with unresectable stage IIIB or IV non-small–cell lung cancer. They randomly assigned 926 patients to receive up to six 21-day cycles of carboplatin area under the curve 6 and paclitaxel 200 mg/m2 (CP) on day one, followed by sorafenib at 400 mg twice a day (n=464, arm A) or a placebo on days two to 19 (n=462, arm B). The maintenance phase after CP consisted of sorafenib at 400 mg or a placebo twice a day. The primary end point was overall survival. Secondary end points included progression-free survival and tumor response. The authors found that overall demographics were balanced between the two groups, and 223 patients (24 percent) had squa-mous cell histology. On the basis of a planned interim analysis, median overall survival was 10.7 months for the arm A group and 10.6 months for the arm B group (hazard ratio, 1.15; 95 percent confidence interval [CI], 0.94–1.41). The study was terminated after the interim analysis concluded that it was highly unlikely to meet its primary end point. A prespecified exploratory analysis revealed that patients with squamous cell histology had greater mortality if they were in the arm A group (hazard ratio, 1.85; 95 percent CI, 1.22–2.81). The primary grade 3 or 4 sorafenib-related toxicities included rash (8.4 percent), hand-foot skin reaction (7.8 percent), and diarrhea (3.5 per-cent). The authors concluded that no clinical benefit was observed by adding sorafenib to CP chemotherapy as a first-line treatment for non-small–cell lung cancer. Scagliotti G, Novello S, von Pawel J, et al. Phase III study of carboplatin and paclitaxel alone or with sorafenib in advanced non-small–cell lung cancer. J Clin Oncol. 2010;28(11):1835–1842. Correspondence: Dr. Giorgio Scagliotti at scagliotti@ihnet.it
The authors sought to establish an objective histologic grading system for venous invasion. They retrospectively analyzed 229 patients with pT3 and pT4 colorectal cancer who underwent curative surgery with lymph node dissection. Potential prognosis-related characteristics of venous invasion, including the number of venous invasions, morphologic type of venous invasion, maximum size of veins invaded, and location of venous vessel involved, were evaluated on elastica van Gieson stained sections. The authors found that the relapse-free survival curves between the venous-invasion–positive group and the negative group differed significantly (five-year survival rates were 73.4 percent and 92.2 percent, respectively; P=0.001). When patients were divided into three groups according to the average number of venous invasions observed in a glass slide (G0, none; G1, positive but fewer than four; and G2, four or more), a significant difference in the survival rate was noted among the three groups. Five-year survival rates were 92.2, 77.8, and 56.4 percent, respectively (P=0.008 for G0 versus G1; P=0.017 for G1 versus G2). The postoperative recurrence rate was 10.8 percent in G0 patients, 32.5 percent in G1 patients, and 51.7 percent in G2 patients (P=0.0007 for G0 versus G1; P=0.047 for G1 versus G2). Multivariate analysis showed that number of venous invasions (hazard ratio, 2.72; P=0.027), depth of invasion (hazard ratio, 2.26; P=0.014), and lymph node metastasis (hazard ratio, 2.43; P=0.008) were independent prognostic factors. The authors conclu-ded that the aforementioned three-category tumor grading system based on the number of venous invasions in a glass slide with elastica van Gieson staining could be an objective and important treatment index for colorectal cancer patients. Sato T, Ueno H, Mochizuki H, et al. Objective criteria for the grading of venous invasion in colorectal cancer. Am J Surg Pathol. 2010;34(4):454–462. Correspondence: Dr. Taichi Sato at taichiikota@yahoo.co.jp
The authors conducted a study to confirm that the grades of lymph vessel tumor emboli in biopsy specimens obtained before neoadjuvant therapy and in surgical specimens obtained after neoadjuvant therapy, according to a grading system they devised, are significant histological outcome predictors for invasive ductal carcinoma patients who received neoadjuvant therapy. The study focused on 318 consecutive invasive ductal carcinoma (IDC) patients who had received neoadjuvant therapy in the authors’ institution. The lymph vessel tumor embolus grades in the biopsy and surgical specimens were significantly associated with increases in the mean number of nodal metastases. Multivariate analyses with well-known prognostic factors and p53 expression in tumor-stromal fibroblasts clearly showed that the lymph vessel tumor embolus grade based on the biopsy and surgical specimens significantly increased the hazard rates for tumor recurrence and tumor-related death in all the IDC patients as a whole, in the IDC patients who did not have nodal metastasis, and in the IDC patients who had nodal metastasis. The analyses also showed that the outcome-predictive power of the lymph vessel tumor embolus grades based on the surgical specimens was superior to that of the lymph vessel tumor embolus grades based on the biopsy specimens. The grades in the grading system for lymph vessel tumor emboli were significantly associated with nodal metastasis. The authors concluded that the histological grading system is an excellent method for predicting the outcome of patients with IDC of the breast who have received neoadjuvant therapy. Hasebe T, Tamura N, Iwasaki M, et al. Grading system for lymph vessel tumor emboli: significant outcome predictor for patients with invasive ductal carcinoma of the breast who received neoadjuvant therapy. Mod Pathol. 2010;23:581–592. Correspondence: Dr. T. Hasebe at thasebe@ncc.go.jp
Two relatively unknown and recently described placental membrane hypoxic lesions—laminar necro-sis and microscopic chorionic pseudocysts—have never been compared with time-honored, focal (infarction), and diffuse hypoxic lesions of placental parenchyma. Therefore, the author conducted a study to compare the effect of placental membrane hypoxic lesions and chorionic disk hypoxic lesions (infarctions and global hypoxic pattern of placental injury) on placental diagnosis. They retrospectively compared 23 clinical (maternal and fetal) and 32 gross and microscopic placental features in 4,590 placentas from a placental database built during a 13-year period. Of the placentas in the database, 168 had at least one hypoxic disk lesion (infarct or global hypoxia) and at least one membrane lesion (microscopic chorionic pseudocysts or laminar necrosis [group one]); 750 had at least one hypoxic villous lesion but no membrane lesion (group two); 480 had at least one membrane lesion but no villous lesion (group three); and 3,192 had no hypoxic villous or membrane lesions (group four). The author found that several clinical and fetal conditions and placental features known to be associated with in utero hypoxia had a statistically significant correlation with the index hypoxic placental lesions, both villous and membranous. Of the placentas from patients who were linked with clinical conditions that put them at risk for hypoxia, 15 percent featured only hypoxic membrane lesions without a chorionic disk hypoxic lesion. The author concluded that recognizing placental membrane hypoxic lesions increases the sensitivity of placental examination in diagnosing placental hypoxia by at least 15 percent. The risk of in utero hypoxia increases when microscopic chorionic pseudocysts and laminar necrosis occur in conjunction with villous hypoxic lesions. Stanek J. Diagnosing placental membrane hypoxic lesions increases the sensitivity of placental examination. Arch Pathol Lab Med. 2010;134(7):989–995. Correspondence: Dr. Jerzy Stanek at jerzy.stanek@cchmc.org
The authors conducted a study to develop a histology-specific nomogram to predict postoperative overall survival at five and 10 years in primary retroperitoneal soft tissue sarcoma. They used data registered in a prospective sarcoma database at the National Cancer Institute, Milan, Italy. The present study included patients with primary localized retroperitoneal soft tissue sarcoma resected with curative intent between 1985 and 2007. A parametric piecewise exponential survival multivariate model was used for nomogram development, and internal validation was performed with standard methodologies. Known prognostic variables, such as age, tumor burden, histologic variant (as reviewed by a sarcoma pathologist), grade, and surgical margins, were considered as putative predictors. The authors found that among the 192 patients analyzed within 10 years after surgery, 114 were alive, with a median followup time of 55 months (inter-quartile range, 25–104 months). Among the factors investigated, only histologic subtype did not reach significance at the 10 percent level. The relative hazard increased with increasing tumor size up to about 25 cm and decreased thereafter. The authors concluded that a histology-specific no-mogram for retroperitoneal soft tissue sarcoma is now available. It can be used to better assess the risk for a single patient and then to make individualized decisions within the specific subset of retroperitoneal sarcomas. Cross-check external validation should be performed. Ardoino I, Miceli R, Berselli M, et al. Histology-specific nomogram for primary retroperitoneal soft tissue sarcoma. Cancer. 2010;116:2429–2436. Correspondence: Dr. Alessandro Gronchi at alessandro.gronchi@istitutotumori.ml.it
Log odds of positive lymph nodes is defined as the log of the ratio between the probability of being a positive lymph node and the probability of being a negative lymph node when one lymph node is retrieved. The value of the LODDS staging system in prognostically assessing gastric cancer patients with R0 resection is still unclear. Therefore, the authors conducted a study in which they retrospectively evaluated the clinicopathologic and prognostic data for 2,547 gastric cancer patients who underwent D2 or D3 lymphadenectomy with R0 surgery. Multivariate analysis identified LODDS stage, but not pN classification or rN classification, as an independent prognostic factor. The scatter plots of the relationship between LODDS and the number, the ratio of nodes metastases, suggested that the LODDS stage could divide patients with the same number or ratio of nodes metastases into different groups. Significant differences in rates of survival were consistently observed for patients in each of the pN or rN classifications among patients in different LODDS stages. However, prognosis was highly homologous between those in different pN or rN classifications among patients in the same LODDS stage. A minimum number of 10, 15, 20, 25, and 10 nodes retrieved should be met for patients in the pN0, pN1, pN2, pN3, and rN0-3 classifications, respectively, unless the hazard risks of death would be underestimated or overestimated. However, LODDS stage could discriminate among five groups of patients with highly homologous prognosis, regardless of how many nodes were retrieved. The authors concluded that the LODDS system is more reliable than the Union Internationale Contre le Cancer and American Joint Committee on Cancer pN system and the rN system for prognostic assessment. Sun Z, Xu Y, De Ming L, et al. Log odds of positive lymph nodes: a novel prognostic indicator superior to the number-based and ratio-based N category for gastric cancer patients with R0 resection. Cancer. 2010;116(11):2571–2580. Correspondence: Dr. Hui Mian Xu at xuhuimian@126.com Anatomic pathology abstracts editors: Michael Cibull, MD, professor and vice chair, Department of Pathology and Laboratory Medicine, University of Kentucky College of Medicine, Lexington; Melissa Kesler, MD, and Rouzan Karabakhtsian, MD, assistant professors of pathology and laboratory medicine, University of Kentucky College of Medicine; and Megan Zhang, MD, visiting fellow, Division of Dermatopathology, University of California, San Francisco. |
