Bench to bedside: recent advances in lung cancer pathological research with implications for diagnostic clinical practice

After decades of relative stagnation lung cancer is emerging as a disease type where rapid progress is being made in diagnosis and therapy, as well as in our understanding of disease biology. Much of this progress is of immediate impact to diagnosticians, and more is likely to affect diagnostic practice in the near future. In this review we seek to briefly summarize several key areas of active research of immediate or probable imminent value to trainee and consultant pulmonary pathologists alike. We cover some major changes in tumour classification, grading, and patient stratification, as well as considering the state of the art in machine-assisted interpretation of lung cancer histology, and the use of genetically modified lung cancer models.     

Pathological variables determining the prognosis of non-Hodgkin''s lymphomas

The aim of the study was to assess the role of pathological grade, cell proliferation, ploidy, immunophenotype and site in determining the prognosis of non-Hodgkin's lymphomas. Of particular interest was the relative value of grades derived from the Kiel classification as opposed to the National Cancer Institute (NCI) working formulation. The study consisted of 181 cases, treated in a relatively uniform way over an 18-month period spanning 1986. Using life table analysis, both NCI working formulation grade and Kiel grade correlated strongly with survival. However, the differences between grades were entirely due to an excess of early deaths in the high-grade and intermediate-grade categories. In patients surviving greater than 0.1 years (37 days), phenotype, site, ploidy and cell proliferation had no effect on survival. There was no evidence that intermediate-grade tumours, when subdivided into Kiel low- and high-grade types, differed in survival from tumours graded as low- or high-grade by both methods. However, NCI working, formulation high-grade tumours, especially those with a high proliferation rate, formed a group with a very high likelihood of death within 0.1 years.     

Grading static versus dynamic images of contact lens complications

Background: This study was conducted to investigate grading performance when estimating the severity of static versus dynamic images of contact lens‐related ocular pathology. Methods: Thirty‐eight subjects used the Efron Grading Scales for Contact Lens Complications to grade the severity of ocular pathological changes depicted in static and dynamic (movie clip) computer‐displayed images of each of the following contact lens complications: bulbar conjunctival redness, limbal redness, papillary conjunctivitis, corneal staining, corneal infiltrates and meibomian gland dysfunction. The viewing of static and dynamic images was separated by seven weeks. Results: Grades assigned to dynamic images were 0.6 and 0.7 grading scale units higher than those assigned to static images for limbal redness and papillary conjunctivitis, respectively (p < 0.0001 for both). No difference was observed for the other four complications. There was an apparent trend for grading variability to be reduced (that is, observers grading in closer agreement) when grading dynamic versus static images. Conclusions: Absolute grades based on an assessment of signs of pathology represented in static images may, in some instances, underestimate the true severity of the condition.     

图像分析DNA含量对判断膀胱移行细胞癌分级和预后的意义

采用IBAS图像分析系统检测37例膀胱移行细胞癌病人的肿瘤细胞DNA含量，其中35例随访18个月至7年（平均5l个月），结果显示DNA含量和AN出现率增加与肿瘤的恶性程度有关（P＜0.01和P＜0.05）；肿瘤复发亦与非整倍体细胞（AN）出现率密切相关，AN出现率小于10％无复发，＜30％5例复发，＞30％9例复发。研究资料表明，图像分析技术测定细胞核的DNA含量对判断膀胱移行细胞癌病人的分级和预后有重要意义。     

近年火车创伤中关节损伤变化的特点

目的 探讨与分析快速列车所致火车创伤中关节损伤的变化特点。方法 集1997～2000年火车提速后10214例火车创伤中1279例关节损伤病例，分析在特定条件下的致伤因素、损伤严重程度、损伤类型特点，经AIS-ISS评分证实与预后的关系。结果 提速后关节损伤发生率由提速前33.54％上升到34.12％，死亡率由28.88％上升到30.33％，多关节离断伤由19.84％上升到34.13％，开放性关节损伤由31.71％上升到63.65％，关节离断伤的死亡率由21.19％上升到49.07％。结论 火车创伤无疑是十分严重的损伤，多发伤率远高于其他损伤，治疗棘手，多器官功能不全综合征(MODS)是致死的主要因素。     

汗腺癌病理分级的预后意义

目的：探讨汗腺癌不同病理组织学分级对复发和转移及预后的影响。方法：参照Ｂｌｏｏｍ－Ｒｉｃｈａｒｄｓｏｎ乳腺癌分级标准对１０５例汗腺癌进行分级，并探讨其与复发、转移和预后间的关系。结果：在１０５例汗腺癌中，属分化型者４２例，属低分化型者６３例，两者复发率、多次复发率、区域淋巴结转移率和远处转移率及死亡率比较，提示在多次复发、远处转移方面差异有显著性，在预后方面差异非常显著。结论：将汗腺癌按腺管形成多少、核的多形性和核分裂数进行病理组织学分级，对选择治疗、估计预后具有很大的指导意义     

Incidental prostatic carcinoma: Morphometry correlated with histological grade

Summary The histological grades of prostatic carcinoma, as defined by Gleason, were correlated with three methods of morphometry in 254 step-sectioned prostates obtained at autopsy. The variables studied were 1) the number of tumours in each prostate; 2) bilaterality and 3) tumour volume. Each characteristic yielded a statistically significant correlation with histological grade. The strongest correlations were obtained using tumour volume. These autopsy studied help to explain the inconsistent results obtained from morphometric analyses of surgical material, and lend support to the Gleason system as a means of predicting tumour behavior.Supported in part by research contracts PH 64-10, NCI-72-3213, N01-CP-53521; Grant R01-CA-33644; and the Grant-in-Aid for Cancer Research (33) from the Ministry of Health and Welfare     

Histopathological grading of soft tissue tumours. Prognostic significance in a prospective study of 278 consecutive cases

A consecutive 10-year series of 278 soft tissue sarcomas was prospectively graded, using a system based on the number of mitoses and taking into account parameters such as cellularity, anaplasia, necrosis, and histogenetic type and subtype of tumour. Prognostic factors in relation to metastasis-free survival were studied by uni- and multivariate analysis. Fifty-seven (20.5 per cent) were low-grade tumours, 43 (15.5 per cent) were intermediate, and 178 (64 per cent) were high grade. High-grade tumours were divided into two groups; 80 (29 per cent) grade 3A (= 5-20 mitoses per 10 high power fields (HPF)) and 78 grade 3B (28 per cent) (= more than 20 mitoses/10 HPF); 10 HPF corresponds to 2.5 mm2. Twenty (7.2 per cent) high-grade tumours could not be further subdivided. Grading was found to be the prognostic factor associated with the strongest predictive value. Five-year survival in low-grade and intermediate tumours (95 and 86 percent, respectively) differed significantly (P less than 0.0001) from high grade (50 per cent) and (p = 0.0018) between grade 3A (64 per cent) and grade 3B (41 per cent). Other prognostic indicators of importance in high-grade tumours were age, local recurrence at presentation (primary operation outside the Centre), and localization (superficial vs. deep).     

p27(Kip1) expression and grading of breast cancer diagnosed on cytological samples

The progressive reduction in p27(Kip1) (p27) protein immunohistochemical staining with increasing histological grading is a well-established finding occurring in breast cancer, and its role as diagnostic complement and prognostic marker has been thoroughly evaluated. To clarify whether this test may be applied to breast cytopathology, we performed p27 immunostaining on fresh fine-needle cytology (FNC) samples from 10 benign and 40 malignant breast lesions. On average, p27 immunostaining was significantly lower in carcinomas than in benign lesions (P < 0.005). In particular, among carcinomas, p27 immunostaining progressively reduced from well-to poorly differentiated lesions (G1 vs. G2, P < 0.05; G1 vs. G3, P < 0.001; G2 vs. G3; P < 0.001). A similar trend was noted in a subgroup of 20 matched FNCs and histological samples of breast carcinomas, when p27 immunostaining on FNCs was stratified according to the histological grading (G1 vs. G2, P = 0.18; G1 vs. G3, P < 0.05; G2 vs. G3, P < 0.05). In addition, p27 immunostaining on FNCs showed a good positive correlation with that on histology (Spearman R = 0.58; P < 0.01), with a diagnostic concordance between samples of 85%, by using the standard 50% positive cell cutoff. Taken in concert, our data suggest that p27 immunostaining is a reliable marker of tumor cell differentiation in breast cytopathology as well as in histopathology. Accordingly, staining FNCs for p27 may be an useful complement in addition to cytological grading in the preoperative assessment of breast cancer.     

Web-based virtual microscopy in teaching and standardizing Gleason grading

Gleason grading forms the basis of prognostic and therapeutic assessment in prostatic carcinoma despite its subjective nature and substantial interobserver variation. The accuracy of Gleason grading can be improved by the use of educational tools such as reference images. However, conventional microscopy images are of limited educational value because it is neither possible to view the sample at different magnifications nor to navigate into different areas of the specimen. This limitation can be overcome by the use of virtual microscopy, which allows viewing entire digitized microscope slides. We created an interactive Web site ( www.webmicroscope.net/gleason ) featuring a comprehensive set of prostatic needle biopsies as virtual slides, which can be viewed with a standard Web browser (Internet Explorer or Netscape). To evaluate the validity of Web-based virtual microscopy for Gleason grading, an experienced uropathologist (TK) scored a series of 62 biopsies from the original glass slides and 6 weeks later from virtual slides on the Web site using an ordinary desktop computer. The intraobserver agreement was excellent, with identical Gleason scores found in 48 of the 62 cases ( kappa = 0.73). The 14 remaining scores differed only by 1 point on the Gleason scale (2-10). The virtual slides were viewed by 2 other uropathologists (PM and HH), with interobserver kappa coefficients ranging from 0.55 to 0.62, which is within the range of previously reported studies using glass slides. The 3 uropathologists' Gleason scores were included as reference scores on the Web site, which now serves as a publicly open platform for self-testing and learning of Gleason grading. We conclude that Web-based virtual microscopy is a promising new tool for teaching and standardizing Gleason grading.