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Anatomic Pathology Selected Abstracts, 11/14

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Anatomic pathology abstracts editors: Michael Cibull, MD, professor of pathology, University of Kentucky, 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.

Final trial report of sentinel-node biopsy versus nodal observation in melanoma

Sentinel-node biopsy, a minimally invasive procedure for regional melanoma staging, was evaluated in a phase three trial. The authors evaluated outcomes in 2,001 patients with primary cutaneous melanomas who were randomly assigned to undergo wide excision and nodal observation, with lymphadenectomy for nodal relapse (observational group), or wide excision and sentinel-node biopsy, with immediate lymphadenectomy for nodal metastases detected on biopsy (biopsy group). They found no significant treatment-related difference in the 10-year melanoma-specific survival rate in the overall study population (20.8 percent with nodal metastases and 79.2 percent without such metastases). Mean 10-year disease-free survival rates were significantly improved in the biopsy group compared with the observation group among patients with intermediate-thickness melanomas, defined as 1.2 to 3.5 mm (71.3±1.8 percent versus 64.7±2.3 percent; hazard ratio for recurrence or metastasis, 0.76; P=0.01), and those with thick melanomas, defined as greater than 3.5 mm (50.7±4.0 percent versus 40.5±4.7 percent; hazard ratio, 0.70; P=0.03). Among patients with intermediate-thickness melanomas, the 10-year melanoma-specific survival rate was 62.1±4.8 percent among those with metastasis versus 85.1±1.5 percent for those without metastasis (hazard ratio for death from melanoma, 3.09; P<0.001). Among patients with thick melanomas, the respective rates were 48.0±7.0 percent and 64.6±4.9 percent (hazard ratio, 1.75; P=0.03). Biopsy-based management improved the 10-year rate of distant disease-free survival (hazard ratio for distant metastasis, 0.62; P=0.02) and the 10-year rate of melanoma-specific survival (hazard ratio for death from melanoma, 0.56; P=0.006) for patients with intermediate-thickness melanomas and nodal metastases. Accelerated-failure-time latent-subgroup analysis was performed to account for the fact that nodal status was initially known only in the biopsy group, and a significant treatment benefit persisted. The authors concluded that biopsy-based staging of intermediate-thickness or thick primary melanomas provides important prognostic information and identifies patients with nodal metastases who may benefit from immediate complete lymphadenectomy. Biopsy-based management prolongs disease-free survival for all patients and prolongs distant disease-free survival and melanoma-specific survival for patients with nodal metastases from intermediate-thickness melanomas.

Morton DL, Thompson JF, Cochran AJ, et al. Final trial report of sentinel-node biopsy versus nodal observation in melanoma. N Engl J Med. 2014;370:599–609.

Correspondence email not provided.

Surgical pathology report defects: a CAP Q-Probes study of 73 institutions

The rate of surgical pathology report defects is an indicator of quality and affects clinician satisfaction. The College of American Pathologists conducted a study to establish benchmarks for defect rates and defect fractions through a large, multi-institutional prospective application of standard taxonomy. Participants in this 2011 CAP Q-Probes study prospectively reviewed all surgical pathology reports that underwent changes to correct defects and reported details regarding the defects. The 73 institutions that submitted data for the study reported 1,688 report defects discovered in 360,218 accessioned cases, for an aggregate defect rate of 4.7 per 1,000 cases. The median institutional defect rate was 5.7 per 1,000 (10th to 90th percentile range, 13.5–0.9). Defect rates were higher in institutions with a pathology training program (8.5 versus 5.0 per 1,000; P=0.01) and when a set percentage of cases were reviewed after sign-out (median, 6.7 versus 3.8 per 1,000; P=0.10). Of the defects, 14.6 percent were misinterpretations, 13.3 percent misidentifications, 13.7 percent specimen defects, and 58.4 percent other report defects. Overall, defects were most often detected by pathologists (47.4 percent), followed by clinicians (22 percent). Misinterpretations and specimen defects were most often detected by pathologists (73.5 percent and 82.7 percent, respectively; P<0.001), while misidentifications were most often discovered by clinicians (44.6 percent; P<0.001). Misidentification rates were lower when all malignancies were reviewed by a second pathologist before sign-out (zero versus 0.6 per 1,000; P<0.001), and specimen defect rates were lower when intradepartmental review of difficult cases was conducted after sign-out (zero versus 0.4 per 1,000; P=0.02). The authors concluded that this study provides benchmarking data on report defects and defect fractions using standardized taxonomy.

Volmar KE, Idowu MO, Hunt JL, et al. Surgical pathology report defects: a College of American Pathologists Q-Probes study of 73 institutions. Arch Pathol Lab Med. 2014;138(5):602–612.

Correspondence: Dr. Keith E. Volmar at keith.volmar@rexhealth.com

Thyroid transcription factor-1 immunoreactivity relative to endometrioid adenocarcinoma of the uterine corpus

Thyroid transcription factor-1 is expressed in a small percentage of primary gynecological adenocarcinomas. Following the finding of TTF-1 positivity in a number of endometrioid adenocarcinomas of the uterine corpus that behaved aggressively, the authors performed immunohistochemical staining of a large series of endometrial adenocarcinomas of various types to investigate whether its expression is of prognostic significance. TTF-1 was performed on tissue microarrays containing 102 low-grade (grade one or two) endometrioid adenocarcinomas, 101 grade three endometrioid adenocarcinomas, 89 serous adenocarcinomas, and 29 clear cell carcinomas. All categories of endometrial adenocarcinoma exhibited TTF-1 staining in a small subset of cases (two percent low-grade endometrioid, 11 percent grade three endometrioid, nine percent serous, and seven percent clear cell). TTF-1 was less frequently expressed in low-grade endometrioid adenocarcinomas compared with other subtypes. Endometrioid adenocarcinomas that expressed TTF-1 had a statistically significantly worse prognosis with poorer disease-specific survival, and this was also statistically significant in the group of low-grade endometrioid adenocarcinomas. The authors concluded that TTF-1 is expressed in a small but not insignificant proportion of endometrial adenocarcinomas. TTF-1 positivity in low-grade endometrioid adenocarcinomas is an indicator of poorer prognosis.

Ervine A, Leung S, Gilks CB, et al. Thyroid transcription factor-1 (TTF-1) immunoreactivity is an adverse prognostic factor in endometrioid adenocarcinoma of the uterine corpus. Histopathol. 2014;64(6):840–846.

Correspondence: W. Glenn McCluggage at glenn.mccluggage@belfasttrust.hscni.net

Frequent expression of KIT in endometrial stromal sarcoma with YWHAE genetic rearrangement

Endometrial stromal sarcomas with the YWHAE-NUTM2A/B genetic fusion characteristically contain high-grade round to epithelioid cell component that is strongly and diffusely cyclin D1-positive and may show an associated low-grade fibroblastic/myxoid cell component. The sarcomas are clinically more aggressive than endometrial stromal sarcomas with the JAZF1-SUZ12 genetic fusion and frequently demonstrate extrauterine extension at initial clinical presentation. In this setting, the tumor may be misdiagnosed as gastrointestinal stromal tumor. The authors conducted a study in which they examined the expression of KIT and ANO1 in 14 YWHAE-NUTM2A/B tumors by immunohistochemistry. Staining localization was determined to be membranous or cytoplasmic, or both, and staining intensity was assessed as negative, weak, moderate, or strong. Of the 14 tumors, six contained only a high-grade round cell component, two only a low-grade fibroblastic component, and six both components in the slides evaluated. The high-grade round cell component displayed moderate to strong membranous/cytoplasmic KIT staining in all tumors. The low-grade fibroblastic cell component showed only weak cytoplasmic KIT staining in three of eight tumors. In contrast, ANO1 was negative in all 14 neoplasms, irrespective of the component evaluated. Sanger sequencing analysis (exons 9, 11, 13, and 17) and Ampliseq Cancer Panel mutation screen (Ion Torrent) demonstrated no KIT mutations in three KIT-positive YWHAE-NUTM2A/B tumors. The study shows that the high-grade round cell component of YWHAE-NUTM2A/B endometrial stromal sarcoma consistently expresses KIT but lacks KIT hotspot mutations. KIT expression may represent a potential diagnostic pitfall in the evaluation of YWHAE-NUTM2A/B endometrial stromal sarcoma presenting with pelvic/abdominal mass, particularly in situations where its uterine origin is not definitive. Therefore, a panel of antibodies that includes ANO1 and cyclin D1 is necessary.

Lee CH, Hoang LN, Yip S, et al. Frequent expression of KIT in endometrial stromal sarcoma with YWHAE genetic rearrangement. Mod Pathol. 2014;27:751–757.

Correspondence: Dr. E. Oliva at eoliva@partners.org

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