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Anatomic Pathology Selected Abstracts, 8/15

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Editors: Michael Cibull, MD, professor emeritus, University of Kentucky College of Medicine, Lexington; Rouzan Karabakhtsian, MD, attending pathologist, Department of Pathology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY; Thomas Cibull, MD, dermatopathologist, Evanston Hospital, NorthShore University HealthSystem, Evanston, Ill.; and Rachel Stewart, DO, resident physician, Department of Pathology and Laboratory Medicine, University of Kentucky.

Quality of diagnostic staging in patients with bladder cancer: a process-outcomes link

Ability of peritumoral eosinophils to predict recurrence in colorectal cancer

Predicting locally advanced rectal cancer after neoadjuvant radiochemotherapy

Analysis and grading of disseminated appendiceal mucinous neoplasms

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Quality of diagnostic staging in patients with bladder cancer: a process-outcomes link

Muscle sampling is often used as a surrogate for staging quality in patients with bladder cancer. The association of staging quality at diagnosis and survival was examined among patients with bladder cancer. The clinical records of all individuals within the Los Angeles Surveillance, Epidemiology, and End Results registry with an incident diagnosis of nonmuscle-invasive bladder cancer in 2004–2005 were reviewed. Patient demographics, tumor characteristics, staging quality (presence of muscle in the specimen and mention of muscle in the pathology report), and vital status were recorded. The association of patient and tumor characteristics with staging quality and cancer-specific survival was quantified with mixed-effects and competing-risks regression analyses. The sample included 1,865 patients, 335 urologists, and 27 pathologists. Muscle was reported to be present in 972 (52.1 percent) and absent in 564 (30.2 percent) of the initial pathology reports; it was not mentioned in 329 (17.7 percent) of the initial pathology reports. The presence of muscle did not differ according to grade or depth of invasion. Mortality was associated with staging quality (P<0.05). Among patients with high-grade disease, the five-year cancer-specific mortality rates were 7.6 percent, 12.1 percent, and 18.8 percent when muscle was present, absent, and not mentioned, respectively. The authors concluded that the omission of muscle in the specimen or its mention in the pathology report in nearly half of all diagnostic resections was associated with increased mortality, particularly in patients with high-grade disease. Because urologists cannot reliably discern between high- and low-grade or Ta and T1 disease, it is contended that patients with bladder cancer should undergo adequate muscle sampling at the time of endoscopic resection.

Chamie K, Ballon-Landa E, Bassett JC, et al. Quality of diagnostic staging in patients with bladder cancer: a process-outcomes link. Cancer. 2015;121:379–385.

Correspondence: Dr. Karmin Chamie at kchamie@mednet.ucla.edu

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Ability of peritumoral eosinophils to predict recurrence in colorectal cancer

In colorectal cancer, the presence and extent of eosinophil granulocyte infiltration may render important prognostic information. However, it remains unclear whether an increasing number of eosinophils might simply be linked to the overall inflammatory cell reaction or represent a self-contained, antitumoral mechanism that needs to be documented and promoted therapeutically. The authors conducted a study in which peritumoral and intratumoral eosinophil counts were retrospectively assessed in 381 primary colorectal cancers from randomly selected patients. Twenty-one percent of the tumors were diagnosed as American Joint Committee on Cancer (AJCC)/Union Internationale Contre le Cancer (UICC) stage I, 32 percent as stage II, 33 percent as stage III, and 14 percent as stage IV. The presence and extent of eosinophils were related to various histopathological parameters and to patient outcome. Overall, peritumoral and intratumoral eosinophils were observed in 86 percent and 75 percent of cancer specimens, respectively. The peritumoral eosinophil count correlated strongly with the intratumoral eosinophil count (r=0.69; P<0.001) and intensity of the overall inflammatory cell reaction (r=0.318; P<0.001). Increasing peritumoral and intratumoral eosinophil counts were significantly associated with lower T and N classification, better tumor differentiation, absence of vascular invasion, as well as improved progression-free and cancer-specific survival. However, only peritumoral eosinophils were an independent prognosticator of favorable progression-free survival (hazard ratio [HR], 0.75; 95 percent confidence interval [CI], 0.58–0.98; P=0.04) and cancer-specific survival (HR, 0.7; 95 percent CI, 0.52–0.93; P=0.01), independent of the intensity of overall inflammatory cell reaction. This was also found for patients with AJCC/UICC stage II disease, wherein the presence of peritumoral eosinophils was significantly associated with favorable outcome. The authors concluded that the number of peritumoral eosinophils had a significant favorable impact on the prognosis of colorectal cancer patients independent of the overall tumor-associated inflammatory response. Evaluation of peritumoral eosinophils represents a promising, readily assessable tool and should, therefore, routinely be commented on in the pathology report.

Harbaum L, Pollheimer MJ, Kornprat P, et al. Peritumoral eosinophils predict recurrence in colorectal cancer. Mod Pathol. 2015;28:403–413.

Correspondence: Dr. C. Langner at cord.langner@medunigraz.at

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Predicting locally advanced rectal cancer after neoadjuvant radiochemotherapy

Neoadjuvant radiochemotherapy followed by surgical resection is the treatment for locally advanced mid-rectal or low rectal cancer. The authors conducted a study to evaluate postoperative histological prognostic factors in a series of surgical specimens after neoadjuvant radiochemotherapy (RCT). The study included 113 patients. Macroscopic and microscopic examinations were performed according to CAP recommendations, with additional criteria, such as tumor budding, presence of calcifications, and response to neoadjuvant therapy, assessed according to Modified Rectal Cancer Regression Grade (m-RCRG). The three-year disease-free survival was 67.6 percent. In univariate analysis, the prognostic factors were ypTN stage, tumor budding, circumferential margin, invaded margin, and vascular and perineural invasion. In multivariate analysis, the presence of calcifications (P=0.04) and an involved circumferential margin (P=0.03) were the only independent factors for worse disease-free survival. M-RCRG was not correlated with disease-free survival. Among the 50 m-RCRG1 tumors, such survival was better in ypT0 patients than in other ypT stages (P=0.003). The authors concluded that calcifications in the tumor bed are a prognostic factor in rectal cancer. The prognostic value of budding was demonstrated in this study after neoadjuvant RCT. The ypT stage appears to be a more reliable predictor of oncological outcome than histological tumor regression grade, which needs to be standardized for better reproducibility.

Sannier A, Lefèvre JH, Panis Y, et al. Pathological prognostic factors in locally advanced rectal carcinoma after neoadjuvant radiochemotherapy: analysis of 113 cases. Histopathol. 2014;65:623–630.

Correspondence: A. Sannier at aureliesannier@free.fr

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Analysis and grading of disseminated appendiceal mucinous neoplasms

Previous studies have demonstrated that the prognosis for disseminated mucinous appendiceal neoplasms is highly dependent on tumor grade. Reflecting this, the seventh edition of the American Joint Committee on Cancer (AJCC) cancer staging system incorporates a three-tier grading system for prognostic staging of mucinous appendiceal tumors. However, the grading criteria are not well described. To address this issue, the authors evaluated the clinicopathologic and molecular features of 219 cases from 151 patients with widely disseminated appendiceal mucinous neoplasia treated at their institution between 2004 and 2012. They identified histologic features that were associated with worse overall survival on univariate analysis: destructive invasion, high cytologic grade, high tumor cellularity, angiolymphatic invasion, perineural invasion, and signet ring cell component (all P<0.0001). The authors used these morphologic characteristics to classify neoplasms into three grades: AJCC grade G1 lacked all adverse histologic features; AJCC grade G2 had at least one adverse histologic feature but no signet ring cell component; and AJCC grade G3 was defined by the presence of a signet ring cell component. Patients with AJCC grade G2 and grade G3 adenocarcinomas had a significantly worse prognosis compared with AJCC grade G1 (P

Davison JM, Choudry HA, Pingpank JF, et al. Clinicopathologic and molecular analysis of disseminated appendiceal mucinous neoplasms: identification of factors predicting survival and proposed criteria for a three-tiered assessment of tumor grade. Mod Pathol. 2014;27:1521–1539.

Correspondence: Dr. R. Pai at pair@upmc.edu

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