Preneoplastic and preinvasive lesions of the esophagus and stomach

Although it is possible to classify gastrointestinal tract mucosal changes by numerous classifications that have been published over the last 20 years, none has been accepted worldwide for the daily diagnosis of biopsies. With respect of routine surgical specimen diagnosis, it is argued in the article that the intraepithelial neoplasia (IEN) level be based on the terms of benign (precursor) lesions. In addition, esophageal and gastric IENs classifications are proposed as well as the question of whether it is possible to extend this classification to the colon and rectum.     

Preneoplastic and neoplastic lesions in the pancreas of rats fed choline-devoid or choline-supplemented diets

Groups of male Fischer 344 rats were chronically fed semipurified choline-devoid or choline-supplemented diets, high in fat (15%), and containing or not containing 0.06% phenobarbital. Atypical acinar cell nodules were observed in the pancreas of the rats, irrespective of the diet fed, with incidences varying from 38% to 100% in the various groups. No consistent differential effects of the dietary treatments on the incidence and growth of the nodules were evident, even though the diameter of the nodules tended to be greater in some of the groups fed the basal choline-devoid diet. The vast majority of the nodules were of the acidophilic type. More advanced pancreatic acinar cell lesions were observed in a few of the rats. Since the rats were not exposed to a chemical carcinogen(s), development of the nodules and of the more advanced lesions, even in rats fed the control diets, was most likely due to evolution of endogenous (spontaneous) initiated pancreatic cells, promoted primarily by the feeding of semipurified diets with a high fat content.     

Iatrogenic pulmonary lesions

Treatment of patients often includes the administration of medications and sometimes radiation. While the intent is to treat an underlying condition, in some cases, adverse effects occur due to these agents. Most of these adverse effects are mild, however, some can be severe and life-threatening. Furthermore, while these effects are often reversible upon cessation of exposure, especially if the inciting agent is recognized and withdrawn early, others might be permanent or even progressing.Most common histopathologic findings in drug-induced interstitial lung disease include nonspecific interstitial pneumonia (cellular and/or fibrotic), organizing pneumonia with or without bronchiolitis, eosinophilic pneumonia, pulmonary edema, diffuse alveolar damage, hypersensitivity pneumonitis, granulomatous interstitial lung disease, chronic bronchiolitis, and pulmonary hemorrhage. Pulmonary vascular changes or constrictive bronchiolitis can also occur. Drugs that are more commonly associated with lung toxicity include nitrofurantoin, amiodarone, and chemotherapeutic agents such as bleomycin and methotrexate. More recently introduced immune modulating agents including rituximab and immune checkpoint inhibitors such as anti-CTLA4, anti-PD-1 and anti-PD-L1 agents have also been associated with adverse effects in the lung.Radiation therapy to the chest can trigger acute or chronic lung toxicity. While newer radiation techniques are aimed to decrease and minimize side effects other risk factors such as additional chemotherapy, oxygen, and older age may be rising.Foreign substances such as talc, hydrogel, and medical devices such as hydrophilic polymer coated catheter may rarely also lead to pulmonary complications.It is important that clinicians and pathologists are aware of these potential adverse effects of drugs, radiation and medical devices and raise the possibility of drug-induced lung toxicity after exclusion of other differential diagnoses. It is the role of the clinician to provide the pathologist with an appropriate drug history. Early intervention to a drug-induced lung toxicity might prevent progression of side effects and permanent changes.     

Preneoplastic non-papillary lesions and conditions of the urinary bladder: an update based on the Ancona International Consultation

BACKGROUND AND AIMS: This paper summarizes the work done by the members of the Committee no. 2 at the International Consultation on the Diagnosis of Non-Invasive Urothelial Neoplasms held in Ancona, Italy (11-12 May 2001). The committee members discussed and reached consensus regarding the optimal contemporary diagnosis and classification of the preneoplastic non-papillary lesions of the urothelium. An important objective was to promote a precise terminology and to use it consistently in daily practice in pathology and urology. RESULTS AND CONCLUSIONS: The result of the meeting is represented by a refined classification of the non-papillary intraepithelial lesions and conditions of the urothelium. This classification includes epithelial abnormalities (reactive urothelial atypia and flat urothelial hyperplasia), presumed preneoplastic lesions and conditions (keratinizing squamous and glandular metaplasia, and malignancy-associated cellular changes), as well as preneoplastic (dysplasia) and neoplastic non-invasive (carcinoma in situ) lesions. Each of these lesions is defined with strict morphological criteria in order to provide more accurate information to urologists in managing patients.     

Double synchronous pulmonary lymphatic-related lesions

A wide range of pathologies may primarily affect the lymphatic vessels in the lungs. In this article, a unique case of pulmonary silicosis associated with a subtle lymphangitic carcinomatosis from an unknown prostate cancer is reported and discussed.     

Transthoracic aspiration cytology of pulmonary lesions

In a seven-year period (1974 to 1981), 1,390 patients had transthoracic aspiration biopsy for radiologically suspected pulmonary neoplasms. Of the 1,209 proven malignant neoplasms, 1,059 (88%) were cytologically diagnosed as malignant. There were only two (0.2%) false-positive diagnoses both due to florid bronchoalveolar hyperplasia associated with granulomatous disease. Cytologic and histologic correlations for primary lung cancers were 92% for adenocarcinoma, 87% for oat cell (small cell) carcinoma, and 83% for epidermoid carcinoma. Characteristic cytomorphology of pulmonary carcinomas, some metastatic neoplasms, and inflammatory lesions are described.     

结直肠锯齿状病变与癌

结直肠增生性息肉是一类具有典型“锯齿状”形态特征的病变,一直以来被认为是一种良性病变,不会恶变。随着内镜的广泛应用,病理学家发现了一系列相关病变,这些病变以具有锯齿状组织学形态为特征,呈一个连续的谱系,有明显的异质性,具有特殊的分子改变,其生物学行为既不同于经典的增生性息肉又不同于普通腺瘤,呈现一条与肠癌发生相关的所谓锯齿状通路（serrated neoplasia pathway）。为了能进一步认识这类病变的性质,本文就其形态学特征、分类以及分子发生机制作一概述。     

p53 gene alteration in atypical epithelial lesions and carcinoma in patients with idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is well known to be associated with lung cancer. Several atypical epithelial lesions are frequently observed in the fibrotic area in IPF patients, and they have been suspected to be related to lung carcinogenesis. Several studies have suggested that p53 protein accumulation and mutation occur in the early pathogenesis of squamous cell carcinoma of the lung, suggesting some abnormality of the p53 tumor-suppressor gene in interstitial lung diseases. To examine the cause of the high frequency of lung cancer in IPF, we examined the p53 changes in atypical epithelial lesions and carcinoma in patients with IPF by immunohistochemistry and mutational analysis. We examined 19 lung cancer patients with IPF who underwent surgical resection for lung cancer in our institute. Paraffin-embedded tissues were treated by microwave and stained with an anti-p53 antibody (RSP53) by the avidin-biotin-peroxidase complex method. Mutations in exons 5 through 8 of the p53 gene were also examined by polymerase chain reaction mediated single-strand conformation polymorphism (polymerase chain reaction-single-strand conformation polymorphism) analysis and DNA sequencing. p53 protein was immunohistochemically detected in 13 (62%) of 21 squamous cell carcinomas, 3 (60%) of 5 squamous metaplasia with atypia, 16 (54%) of 30 squamous metaplasia, and 1 (4%) of 26 other hyperplastic lesions. p53 mutation was detected in 12 (57%) of 21 squamous cell carcinomas, 2 (40%) of 5 squamous metaplasia with atypia, 7 (23%) of 30 squamous metaplasia, and 0 (0%) of 26 other hyperplastic lesions. In conclusion, there are frequent p53 gene alterations in squamous metaplasia, which is distributed in the peripheral zone of the fibrotic area in patients with IPF. The present findings might provide a clue to the molecular mechanisms underlying the high incidence of lung cancer, especially peripheral-type squamous cell carcinoma in IPF patients, and suggest that p53 gene alterations play an important role in the early stages of lung carcinogenesis in patients with IPF.     

The pulmonary vascular lesions of intravenous drug abuse

We examined microscopic sections of lungs from 70 autopsies on persons who abused drugs by intravenous injection in order to evaluate systematically the spectrum of pulmonary vascular lesions resulting from this practice. Angiothrombosis, the most frequent pulmonary vascular lesion, occurred in 13 instances. Morphologic subgroups of this category include weblike and eccentric intimai fibrous lesions, “plexiform-like” lesions, and aneurysmally dilated, tortuous small vessels. Thrombotic changes typically are induced by intravenous injections of solutions derived from tablets or capsules that ethically are intended for oral consumption, because oral pharmaceutical preparations usually contain insoluble microcry-stals such as talc, starch, or cellulose. Ordinary illicit heroin does not contain enough insoluble crystalline debris to induce extensive pulmonary angiothrombosis.We found only two specimens with vascular changes indicative of nonthrombotic pulmonary hypertension; one of these persons had concomitant cirrhosis of the liver, and the other had aortic and mitral valvular bacterial endocarditis. Morphometric studies of the muscular arteries in all other lung samples containing scant embolic foreign material did not show a significant difference between drug abusers and normal control subjects, a finding that fails to support the hypothesis that vasoconstriction or other nonthrombotic reactions to intravenous drug abuse cause pulmonary hypertension and cor pulmonale.     

肺癌的立体定向放射治疗

目的 利用立体定向放射治疗肺癌，开辟肺癌治疗新途径。方法 27例病人采用CT定位2mm层厚连续扫描并通过图像重建，计算出临床靶体积（CTV），计划靶体积（PTV）及受累器官体积的照射量-体积直方图。应用德国Leibinger的立体定向系统和Varian600c加速器进行治疗。结果 本组27例肺癌病人在接受立体定向放射治疗过程中无一例死亡，患者一般评分标准采用Karmofsky(KPS)标准。术前KPS评分20-80分，平均59分，术后KPS评分20-100分，平均87分，随访患者按实体瘤疗效标准。完全缓解（CR）4例，部分缓解（PR）17例，无变化（NC）2例，进展（PD）4例，肿瘤控制有效率85%。结论 立体定向放射治疗肺癌近期疗效良好，且随着临床经验的不断积累，立体定向放射治疗必将在肺癌的综合治疗中占有重要的地位。     

乙肝病毒相关原发性肝细胞癌的癌前标志物检测

探讨乙肝病毒（HBV）相关原发性肝细胞癌（HCC）癌前标志物的检测及其临床意义。在HBx基因转染的HepG2细胞系中,采用PCR选择性分离cDNA,进行差减杂交,得到5个HBxAg上调基因URG4、URG7、URG11、S15a、Sui1。建立特异ELISA方法,对中国居民及美国的韩国裔移民共1046例（其中慢性HBV感染400例,对照组646例）,检测5个HBxAg上调基因的相应抗体,定其为HBV相关HCC癌前标志物,简称癌前抗体。结果表明,慢性乙肝组、乙肝肝硬化组、HBV相关HCC组以及HCV相关HCC组检出癌前抗体的阳性率与正常人群相比均有显著差异（P〈0．01）,且差异随慢性乙肝-乙肝肝硬化-肝癌的发展而增大,而HBV携带组、其它肝炎组以及其他肿瘤组与正常人群相比均无显著差异（P〉0．05）。在5个癌前抗体中,HBV相关HCC组检出3个或3个以上癌前抗体的阳性率为52．6％（30／57）,乙肝肝硬化组为29．2％（35／120）,慢性乙肝组为19．0％（29／153）,而正常人群仅为0．8％（4／494）。在HBV感染各组病例中,慢性乙肝组癌前抗体阳性率为48．4％（74／153）,乙肝肝硬化组为66．7％（80／120）,HBV相关HCC组为82．5％（47／57）（P〈0．01）,平均癌前抗体阳性数分别为1．37、2．12和3．52（P〈0．01）。这5个癌前抗体在正常人群中检测不到,而在肝癌及其高危人群中高比例地出现,且阳性率随慢性乙肝-乙肝肝硬化-肝癌的发展而显著升高,反映了这些癌前抗体是肝癌发生的高危风险因子,在肿瘤的发展过程中逐步产生,可以作为癌前病变趋势的诊断依据。     

肺黏液表皮样癌的分子特征

目的:探讨肺黏液表皮样癌的分子特征.方法:回顾性对2013年7月至2016年12月13例病理确诊并接受治疗的肺黏液表皮样癌临床特征和分子特点进行分析.结果:EGFR基因突变率为15.38%(2/13),且2例均为L861Q点突变,EGFR基因状态与性别(P=1.000)、年龄(P=1.000)、吸烟史(P=0.848)及分期(P=1.000)均无相关性;MAML2融合基因阳性率为45.45%(5/11),MAML2融合基因状态与性别(P=0.521)、年龄(P=0.521)、吸烟史(P=1.000)及分期(P=0.924)均无相关性(P>0.05).结论:肺黏液表皮样癌中EGFR基因最常见的突变为L861Q,EGFR基因野生型患者中存在MALM2基因融合.     

Transthoracic needle biopsy in the diagnosis of pulmonary lesions

Transthoracic needle biopsy therefore proved to be a minor, inexpensive and safe procedure, which with simple technique permits a direct approach to all kinds of localized pulmonary lesions with a high degree of accuracy.