Anatomic Abstracts
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June 2008 Editor:
EBV viral load in tumor tissue as a prognostic indicator for nasal NK/T-cell lymphoma
The authors retrospectively studied 19 cases of nasal NK/T-cell lymphoma for various potential prognostic factors and performed real-time quantitative polymerase chain reaction for Epstein-Barr virus (EBV) viral load in tumor tissue. They found that patients with a low EBV viral load (less than one copy per cell) more frequently survived for more than two years compared with patients with a high EBV viral load (one copy or more per cell) (seven of seven versus three of nine; P=.014; Fisher exact test). Furthermore, the patients with low EBV viral loads had a better overall survival rate than patients with high viral loads (50% accumulative survival, not reached versus four to five months; Kaplan-Meier survival analysis; P=.049). In contrast, the overall survival rate of the patients did not correlate with the extent of lesion, age, stage, necrosis, histologic subtypes, CD56 expression, or angiocentric or angiodestructive growth pattern. The findings suggest that EBV viral load in tumor tissue is a useful indicator for predicting outcome of nasal NK/T-cell lymphoma. Hsieh PP, Tung CL, Chan AB, et al. EBV viral load in tumor tissue is an important prognostic indicator for nasal NK/T-cell lymphoma. Am J Clin Pathol. 2007; 128: 579– 584. Reprints: Dr. C. C. Chang, Dept. of Pathology and Laboratory Medicine, Methodist Hospital, 6565 Fannin St., MS205, Houston, TX 77030
The WHO classification for well-differentiated pancreatic endocrine neoplasms incorporates stage and grade. The authors compared the prognostic value of a simplified staging and grading system with the WHO system in a large single-institution study. A prospective database for the years 1982 to 2005 identified 183 patients who underwent operative treatment for pancreatic endocrine neoplasms (PENs). Tumors were staged (less than 2 cm primary, 2 cm or greater primary, or metastases) and graded (low grade, no necrosis and fewer than two mitoses per 50 high-powered fields [HPF]; or intermediate grade, necrosis and/or two or more mitoses per 50 HPF) with a simplified schema. Influence of stage and grade on recurrence and disease-specific survival (DSS) was determined. Prognostic strength was assessed with the concordance index. Median age of the 183 patients was 56 years, and 53 percent were women. Median followup was 44 months (range, one to 226 months). Classification identified 28 patients (15%) with WHO 1.1 disease, 74 (41%) with 1.2 disease, and 81 (44%) with 2.0 disease. Classification by stage identified 35 patients (19%) with tumors of less than 2 cm, 96 (52%) with tumors of 2 cm or greater, and 52 (29%) with nodal or distant metastases. Tumors were low grade in 102 patients (56%). Earlier stage tumors were more likely to be low grade (less than 2 cm, 83%; 2 cm or greater, 61%; metastases, 28%; P<.001). The WHO classification, tumor stage, and grade were associated with five-year DSS (P<.001). Tumors of 2 cm or greater or metastases are stratified by grade (five-year DSS rate for low versus intermediate grade, 2 cm or greater, 97 versus 80%, respectively; P<.001; metastases, 93 versus 62%, respectively; P=.05). The concordance index was 0.72 for WHO, 0.71 for stage, 0.66 for grade, and 0.76 for stage combined with grade. The authors concluded that accurate prognostic information can be obtained by combining tumor size and metastases with simple grading information based on necrosis and mitotic rate. Ferrone CR, Tang LH, Tomlinson J, et al. Determining prognosis in patients with pancreatic endocrine neoplasms: Can the WHO classification system be simplified? J Clin Oncol. 2007;25:5609–5615. Reprints: Dr. Peter J. Allen, Dept. of Surgery, Memorial Sloan-Kettering Cancer Center, Howard 1223, 1275 York Ave., New York, NY 10021; allenp@mskcc.org
The International Society of Urologic Pathology consensus conference recommended in 2005 that men with biopsy Gleason scores 3 + 4 or 4 + 3 prostate cancer and tertiary pattern 5 have their cancer classified as Gleason score 8 or 9, respectively. Yet the management of men with Gleason score 7 versus 8 or 9 prostate cancer differs. The authors conducted a study to compare the prognostic significance of Gleason score 7 with tertiary grade 5 to other Gleason scores with respect to time to prostate-specific antigen (PSA) failure in men with prostate cancer. The study included 2,370 men, seen from 1989 to 2005, who had clinical tumor category 1c to 3b, node-negative, and nonmetastatic prostate cancer and who underwent definitive therapy with surgery or radiation therapy with or without hormonal therapy. A pathologist with expertise in genitourinary cancers assigned Gleason scores to the prostate needle biopsy specimens. Cox regression was used to assess whether a significant association existed between the presence of tertiary grade 5 in men with Gleason score 7 disease and time to recurrence compared with men with Gleason score 7 without tertiary grade 5, Gleason score 5 to 6, or 8 to 10 disease, adjusting for known prognostic factors and treatment. The study found that men with Gleason score 7 and tertiary grade 5 disease had a significantly shorter time to PSA failure than men with Gleason score 7 without tertiary grade 5 (median time, 5.0 versus 6.7 years, respectively; adjusted hazard ratio [HR], 0.56; 95% confidence interval [CI], 0.32–0.97; P=.04) or score of 6 or less (median time, 15.4 years; adjusted HR, 0.24; 95% CI, 0.13–0.43; P<.001). However, a significant difference was not observed when these men were compared with men with Gleason score 8 to 10 disease (median time, 5.1 years; adjusted HR, 0.96; 95% CI, 0.54–1.71; P=.90). The authors concluded that in this study population, men with prostate cancer having biopsy Gleason score 7 and tertiary grade 5 had a higher risk of PSA failure when compared with men with Gleason score 7 without tertiary grade 5 and had a comparable risk with men with Gleason score 8 to 10. Patel AA, Chen MH, Renshaw AA, et al. PSA failure following definitive treatment of prostate cancer having biopsy Gleason score 7 with tertiary grade 5. JAMA. 2007; 298: 1533– 1538. Reprint information not available.
P53 gene status and protein alterations are associated with progression of bladder cancer. Substantial discordance between p53 protein and gene status is documented, yet no studies have examined the relationship between gene-protein status and clinical outcome. Consequently, the authors evaluated the clinical relationship between p53 gene and protein status. For the study, the complete coding region of the p53 gene was queried using DNA from paraffin-embedded tissues and employing a p53 gene-sequencing chip. The authors compared p53 gene status, mutation site, and protein status with time to recurrence. They found that the p53 gene and protein statuses showed significant concordance, yet 35 percent of cases showed discordance. Exon 5 mutations demonstrated a wild-type protein status in 18 of 22 samples. Both the p53 gene and protein status were significantly associated with stage and clinical outcome. Specific mutation sites were associated with clinical outcome; tumors with exon 5 mutations showed the same outcome as those with the wild-type gene. Combining p53 gene and protein statuses stratifies patients into distinct groups based on recurrence-free intervals: patients showing the best outcome (wild-type gene and unaltered protein), intermediate outcome (a mutated gene or an altered protein), and worst outcome (a mutated gene and an altered protein). The authors concluded that evaluating the p53 gene and protein statuses provides information for assessing risk of recurrence of bladder cancer and that the specific mutation site may be important in assessing risk of recurrence. These findings may markedly influence the assessment of p53 alterations and management of bladder cancer. George B, Datar RH, Wu L, et al. p53 gene and protein status: The role of p53 alterations in predicting outcome in patients with bladder cancer. J Clin Oncol. 2007; 25: 5352–5358. Reprints: Dr. Richard J. Cote, Dept. of Pathology and Urology, University of Southern California Keck School of Medicine, 1441 Eastlake Ave., NOR 2424, Los Angeles, CA 90033; cote_r@ccnt.usc.edu
Eosinophilic esophagitis is an increasingly recognized cause of dysphagia. The authors prospectively assessed the prevalence of eosinophilic esophagitis (EE) using mid-esophageal biopsies from patients presenting with no endoscopically evident cause of dysphagia. They also aimed to determine the clinical and endoscopic factors predictive of EE in outpatients undergoing endoscopy for dysphagia. The study involved 376 outpatients (18 to 60 years old) undergoing endoscopy for dysphagia at the Mayo Clinic between June 2005 and June 2006. Patients completed the validated Mayo Dysphagia Questionnaire (MDQ). Biopsies were obtained from the mid-esophagus if there was no endoscopically evident cause of dysphagia or there were endoscopic findings suggestive of EE. Eosinophilic esophagitis was defined as the presence of more than 20 eosinophils per high-power field. Logistic regression was performed to identify predictors of EE. Of the 376 patients enrolled in the study, 238 (63%) completed the MDQ; 222 (59%) had mid-esophageal biopsies; and 33 (15%) (95% confidence interval, 6%–12%) had EE by biopsy. Ten of 102 (9.8%) patients who appeared endoscopically normal had EE by biopsy, while eight of 21 (38%) patients with endoscopic changes suggestive of eosinophilic esophagitis had EE on biopsy. Predictors of EE were younger age, endoscopic features suggestive of EE, absence of use of proton pump inhibitors, and history of any food impaction for greater than five minutes. The authors concluded that mid-esophageal biopsies from normal-appearing mucosa should be obtained from all patients with unexplained solid food dysphagia, which may lead to diagnosis of EE in about one in 10 cases. Prasad GA, Talley NJ, Romero Y, et al. Prevalence and predictive factors of eosinophilic esophagitis in patients presenting with dysphagia: a prospective study. Am J Gastroenterol. 2007; 102: 2627– 2632. Reprints: G. A. Prasad, Alfred Main, GI Endoscopy Unit, St. Mary’s Hospital, 200 1st St. SW, Rochester, MN 55905
Ovarian cancer and second malignant neoplasms occur rather frequently in the same patient. It is important to have quantitative information on concurrent malignancies in the same year of diagnosis of the epithelial ovarian cancer. The authors conducted a population-based study of such malignancies for which they used data from the Netherlands’ nationwide histopathology and cytopathology network and archive, called PALGA, and Netherlands Cancer Registry (NCR). Data on the ovarian cancer as well as on previous or later cancers were obtained. Age-specific cancer rates from the NCR were used to calculate expected numbers of cancer. Between 1987 and 1993, histopathology reports were identified for 4,577 patients with primary epithelial malignant or primary borderline malignant ovarian cancers and their longitudinal data. Because the database may lack detailed information on histopathology, a sample of 789 patients diagnosed with ovarian cancer from 1996 to 2003 was studied comprehensively as well. In the eventual data analysis of 5,366 patients, 244 (4.5%) cases of concurrent primary malignancy were reported in the same year that the malignant epithelial ovarian tumor had been diagnosed. The observed versus expected ratio was 4.8 (95% confidence interval, 4.3–5.5). For cancer of the uterus/ endometrium, the observed versus expected ratio was 62.3 (95% CI, 52.5–73.5). For skin, breast, colorectal, urinary bladder, renal, and cervical cancer, the ratio was also larger than unity. The elevated risk of concurrent cancer may lead to clinical screening protocols. The findings on endometrial cancer may prompt research on common etiologies and biomarkers. Van Niekerk CC, Vooijs GP, Bulten J, et al. Increased risk of concurrent primary malignancies in patients diagnosed with a primary malignant epithelial ovarian tumor. Mod Pathol. 2007;20:384–388. Reprints: Dr. C. C. van Niekerk, Dept. of Epidemiology and Biostatistics, Radboud University, Nijmegen Medical Centre, P.O. Box 9101, Nijmegen 6500 HB, Netherlands
The authors conducted a randomized trial to determine whether testing for DNA of oncogenic human papillomaviruses is superior to the Papanicolaou test for cervical cancer screening. They compared human papillomavirus (HPV) testing using an FDA-approved assay with conventional Pap testing as a screening method to identify high-grade cervical intraepithelial neoplasia in women ages 30 to 69 years, in Montreal and St. John’s, Canada. Women with abnormal Pap test results or a positive HPV test (at least 1 pg of high-risk HPV DNA per milliliter) underwent colposcopy and biopsy, as did a random sample of women with negative tests. Sensitivity and specificity estimates were corrected for verification bias. A total of 10,154 women were randomly assigned to testing. Both tests were performed on all women in a randomly assigned sequence at the same session. The sensitivity of HPV testing for cervical intraepithelial neoplasia of grade 2 or 3 was 94.6 percent (95% confidence interval, 84.2–100), whereas the sensitivity of Pap testing was 55.4 percent (95% CI, 33.6–77.2; P=.01). The specificity was 94.1 percent (95% CI, 93.4–94.8) for HPV testing and 96.8 percent (95% CI, 96.3–97.3; P<.001) for Pap testing. Performance was unaffected by the sequence of the tests. The sensitivity of both tests used together was 100 percent, and the specificity was 92.5 percent. Triage procedures for Pap or HPV testing resulted in fewer referrals for colposcopy than did either test alone but were less sensitive. No adverse events were reported. The authors concluded that, compared with Pap testing, HPV testing has greater sensitivity for detecting cervical intraepithelial neoplasia. Mayrand MH, Duarte-Franco E, Rodrigues I, et al. Human papillomavirus DNA versus Papanicolaou screening tests for cervical cancer. N Engl J Med. 2007;357:1579–1588 Reprint information not available.
An insular growth pattern may be observed focally in papillary and follicular thyroid carcinoma. The authors conducted a study to determine whether a greater extension of the insular component influences different clinical and histologic features at diagnosis, tumor aggressiveness in terms of frequency of occurrence of metastases, as well as survival. Thirty-three patients with histopathologic findings consistent with insular component were included in the study. Insular component was focal (less than 50% of the tumor area) in 16 patients and predominant (more than 50% of the tumor area) in 17 patients. These two groups were compared with a control group of 66 patients with differentiated thyroid carcinoma. At diagnosis, carcinomas with predominant insular component had a greater tumor size and higher frequency of extrathyroidal extension and distant metastases than those with focal insular component. Patient followup ranged from five to 188 months. The cumulative rate of distant metastases was significantly higher in patients with predominant insular component. At last followup, carcinomas with predominant insular component demonstrated a lesser frequency of disease-free outcome (P=.002) and a higher number of tumor-related deaths (P=.002), regardless of whether distant metastases were present (P=.03) or absent (P=.05) at diagnosis. The authors concluded that the presence of predominant insular component is associated with a poor prognosis in terms of ongoing disease or death. Predominant insular component should be considered a separate entity from not only the classical papillary or follicular carcinomas but also the focal insular component tumor. Rufini V, Salvatori M, Fadda G, et al. Thyroid carcinomas with a variable insular component: prognostic significance of histopathologic patterns. Cancer. 2007;110: 1209– 1217. Reprints: Dr. Vittoria Rufini, Istituto di Medicina Nucleare, Policlinico A Gemelli, Largo Gemelli, 8,00168 Rome, Italy; v.rufini@rm.unicatt.it 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. |
