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.     

Influence of differences in tumor vascularity upon the effects of hyperthermia

Summary Utilizing two types of human renal carcinoma heterotransplanted in nude mice, we investigated the variations in hyperthermic effects (42.5°C for 30 min) caused by differences in tumor type with special reference to variations in tumor vascularity. In the hypovascular JRC1 strain, sporadic vascular dilation was observed throughout the tumors after heating. Destruction of tumor cells was observed mainly in the region of dilation. In the hypervascular JRC11 strain, homogenous vascular dilation was observed immediately after heating, mainly at the periphery of tumors. There was a decrease in the viability of cells in the center of the tumor. Therefore, the hypervascular tumors showed greater destruction mainly at the center where blood circulation was reduced. The range of necrosis was also greatly affected by the extent of vascular dilation caused by heating in hypovascular tumors.     

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。     

The relationship between histopathological findings in oral squamous cell carcinoma and FDG uptake on PET

Objectives It is known that, in fluorine-18 fluorodeoxyglucose Positron Emission Tomography (FDG PET) for the diagnosis of oral cancer, FDG uptake may vary even among different cases of the same squamous cell carcinoma. However, the details of this phenomenon have not yet been elucidated. In this study, we analyzed the relationship between histopathological findings in oral squamous cell cancer and PET findings on FDG uptake. Methods We examined 45 patients with oral squamous cell carcinoma who had undergone FDG PET before treatment. FDG uptake was assessed by a standardized uptake value (SUV) calculated according to the PET-measured tissue concentration of FDG, the administered dose of radionuclide, and the body weight of the patient. The relationship between the mean SUV and each of the following parameters was examined: histological grade of malignancy, degree of cell differentiation, size and/or local extent of the primary lesion, and cell density of the tumor. Results The mean SUV of FDG uptake did not depend on the histological grade of malignancy or on the degree of cell differentiation, but tended to be greater the larger the primary lesion. SUV also depended on cell density, increasing with the percentage of tumor parenchyma. Conclusions It is concluded that cancer cell density greatly influences the SUV of FDG, in that a tumor with fewer cellular elements in cancer tissue tends to become a false negative.     

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。     

Autologous implantation of chondrocytes on a solid collagen scaffold: clinical and histological outcomes after two years of follow-up

Abstract From our overall experience in 56 patients, we here report the treatment with matrix-induced autologous chondrocyte implantation (MACI) of 35 patients suffering from knee cartilage defects measuring about 4 cm², and followed for a minimum of 6 months. A total of 36 knees were treated (1 patient on both knees) and clinically observed for 22 months (in some cases for over 39 months), in accordance with a standardised protocol. Subjective parameters (pain, well-being, functional state, symptoms during specific activity) and objective outcomes (IKDC score and Lysholm and Tegner scores) were recorded. One or 2 years after implantation, some biopsies of the regenerated cartilage were histologically evaluated. The subjective parameters (VAS pain score, 2.80±1.49, p<0.0001; change vs. basal score, 2.72) promptly normalized after 1 month, as did the objective ones (IKDC score after 6 months, 1.53±0.59, p<0.0001; change vs. basal score, 1.78). Similar results were observed after the treatment of a femoropatellar kissing lesion. The three cartilage biopsies that were analysed from different patients showed a tissue positivity to immunohistochemical markers of hyaline cartilage. The conclusions of this preliminary analysis are that the clinical outcome and histological evaluation suggest that MACI is able to relieve pain and restore the functionality of the knee, and that the treatment appears capable of regenerating hyaline cartilage.     

Stereotactic brain biopsy in AIDS

Summary In the hope of finding a treatable condition, the need for rapid diagnosis in HIV-seropositive patients with brain lesions is apparent. In order to evaluate the efficacy of stereotactic brain biopsy in AIDS patients, we retrospectively studied 25 HIV-infected patients undergoing stereotactic biopsy. Brain lesions were identified with gadolinium-enhanced MRI and/or contrastCT. Brain biopsy was performed using the system of Riechert. From 8 up to 15 small tissue samples from one or two targets were obtained in every patient. The biopsy material was examined cytologically, histologically (including electron microscopy), immunohistochemically and, in part, by animal test and polymerase chain reaction (PCR). A definite diagnosis was achieved in 92%. Diagnosis included primary central nervous system lymphoma (PCNSL) (10), toxoplasmosis (10), progressive multifocal leukoencephalopathy (2) and one case of co-existing toxoplasmosis and cytomegalovirus infection. Two biopsies were non-diagnostic. All PCNSLs showed polymorphic B-cell populations of high malignancy; accurate classification according to the Kiel classification was not possible. In 3 lymphomas Epstein-Barr nuclear antigen (EBNA) 2-mRNA could be detected by PCR and confirmed immunohistochemically by EBNA 2 expression. In 6 cases autopsy confirmed the biopsy diagnosis. Conventional histology was not sufficiently decisive for toxoplasmosis and progressive multifocal leukoencephalopathy, so that immunohistochemistry and animal tests became very important for a final diagnosis. With the help of different morphological and molecular biological techniques stereotactic brain biopsy appears to be an effective method in the diagnosis of HIV-associated brain lesions. In view of the marked radio- and chemosensitivity of PCNSLs it is mandatory to establish an early and accurate histological diagnosis for adequate treatment.     

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