Ki-67 immunoexpression and radiological assessment of necrosis improves accuracy of conventional and modified core biopsy systems in predicting the final grade assigned to adult-soft tissue sarcomas. An international collaborative study.

Based on the French Federation Nationale des Centers de Lutte Contre le Cancer (FNCLCC) grading system, this study assesses the accuracy of conventional and modified core biopsy (CB) systems in predicting the final grade (low vs high) assigned to the resected specimen. Substituting Ki-67 immunoexpression for mitotic count, and radiological for histological assessment of necrosis, we used two modified FNCLCC CB grading systems: (1) Ki-67 immunoexpression alone, and (2) Ki-67 plus radiological assessment of necrosis. We graded 199 soft tissue sarcomas (STS) from nine centers, and compared the results for the conventional (obtained from local histopathology reports) and modified CB systems with the final FNCLCC grading of the corresponding resected specimens. Due to insufficient sample quality or lack of available radiologic data, five cases were not evaluated for Ki67 or radiological assessment of necrosis. The conventional FNCLCC CB grading system accurately identified 109 of the 130 high-grade cases (83.8%). The CB grading matched the final FNCLCC grading (low vs high) in 175 (87.9%) of the 199 resected tumors; overestimating the final grade in three cases and underestimating in 21 cases. Modified system 1 (Ki-67) accurately identified 117 of the 130 high-grade cases (90.0%). The CB grading matched the final FNCLCC grading (low vs high) in 175 (89.7%) of the 195 evaluated cases; overestimating seven and underestimating 13 cases. Modified system 2 (Ki-67 plus radiological necrosis) accurately identified 120 of the 130 high-grade cases (92.3%). This last matched the final FNCLCC grading (low vs high) in 177 (91.2%) of the 194 evaluated cases; overestimating seven and underestimating 10 cases. Modified system 2 obtained highest area under ROC curves, although not statistically significant. Underestimated CB grades did not correlate with histological subtypes, although many of the discrepant cases were myxoid tumors (myxofibrosarcomas or myxoid liposarcomas), leiomyosarcomas or undifferentiated pleomorphic/spindle cell sarcomas. Using modified FNCLCC CB grading systems to replace conventional mitotic count and histologic assessment of necrosis may improve the distinction between low and high-grade STS on CB. Our study confirms that classifying grade 1 as low grade and grades 2 and 3 as high grade improves correlation between CB and final grade by up to 21%, irrespective of CB system used. A higher than expected Ki-67 score in a low-grade sarcoma diagnosed on CB should raise concern that a higher-grade component may not have been sampled. Furthermore, correlation of all clinicopathological and radiological findings at multidisciplinary meetings is essential to assess the histological grade on CB as accurately as possible.

Effectiveness of contrast-enhanced ultrasound for characterisation of intestinal inflammation in Crohn's disease: a comparison with surgical histopathology analysis.

BACKGROUND: Differentiation between predominantly inflammatory versus fibrous-predominant lesions is particularly important in order to decide the optimal therapy in patients with refractory symptoms in Crohn's disease (CD). OBJECTIVE: The purpose of this investigation was to evaluate the accuracy of several US parameters, especially of contrast-enhanced US, for evaluation of mural inflammation in CD, with histopathology as the reference. MATERIALS AND METHODS: Preoperative ultrasound examination, including contrast-enhanced ultrasound (CEUS) was performed in 25 consecutive patients with Crohn's disease undergoing elective bowel resection. Ultrasound variables, such as wall thickness, transmural complications, colour Doppler grade, quantitative analysis of the enhancement and the presence and severity of strictures, were prospectively evaluated and compared with the histopathology results. Histopathology grading of acute inflammation using the acute inflammatory score and the degree of fibrostenosis was performed in each segment and the results were compared with all the US variables as well as with a previously defined ultrasound score system for inflammatory and fibrostenotic changes. RESULTS: 28 segments were analysed. In pathology analysis there were 12 predominantly inflammatory segments, 9 predominantly fibrostenotic and 7 compound lesions. When the pathology score was dichotomised into two groups (inflammatory and fibrostenotic) the number of stenoses correctly classified by US was 23 out 28, with a substantial agreement (kappa=0.632). There was a good correlation between the sonographic and pathology scores, both inflammation (Spearman's, r=0.53) and fibrostenosis (Spearman's, r=0.50). Transmural complications, colour Doppler grade and percentage of increase in contrast enhancement were significantly associated with the pathology inflammatory score (p=0.018, p=0.036 and p=0.005, respectively). There was a significantly negative association between the colour Doppler grade and the pathologic fibrostenotic score. CONCLUSIONS: Ultrasound, including CEUS, can be a useful tool for distinguishing inflammatory from fibrostenotic lesions in CD. This information can be useful in the management of CD.

Presence of human papillomavirus DNA in testicular biopsies from nonobstructive azoospermic men.

CONTEXT: Human papillomavirus (HPV) plays a major role in the etiology of many malignancies of diverse localization, such as uterine cervical carcinoma and its precursors. Human papillomavirus sequences have been detected throughout the male lower genitourinary tract, but the role of men as transmitters remains unclear. OBJECTIVE: To investigate the relationship between azoospermia and the presence of HPV DNA in testicular cells. DESIGN: One hundred eighty-five patients with azoospermia undergoing testicular biopsy were studied. Histologic study was done on formalin-fixed, paraffin-embedded samples from testicular biopsies, stained with hematoxylin-eosin. Molecular study to detect HPV sequences was performed on genomic DNA isolated from paraffin sections by standard protocols. Seven cases containing HPV sequences were studied after microdissection with PALM microlaser technology in order to determine the presence of HPV DNA sequences in different cells, as well as from seminal tubules or stromal (Leydig) cells. RESULTS: Human papillomavirus DNA sequences were detected in testicular biopsies of 12 patients (6.48%). Human papillomavirus type 16 was the most common genotype encountered. Among the 92 patients who underwent bilateral testicular biopsy, HPV sequences were detected in 9 patients (9.78%), all of whom showed only unilateral testicular affection, more often in the left testicle (ratio, 2: 1). After microdissection, HPV DNA sequences were seen in Leydig and Sertoli cells; the presence of HPV in germinal cells could not be ruled out. CONCLUSIONS: Leydig cells, Sertoli cells, and probably germinal cells (cases 2, 3, and 4) harbored HPV DNA sequences. Such findings have not been previously described in testicular tissue.