Electron Microscopy in Pathology Articles: A Retrospective Appraisal

Electron microscopy (EM) is a valuable standard tool in basic research and teaching. However, its use in diagnosis is limited, either for strategic reasons or budgetary constraints. This means that its many potential applications are more often neglected, either as an ancillary tool, quality control method, or gold standard, to complement, support, or confirm results of pathological studies. To evaluate the use of EM in this setting, the authors analyzed all articles (n = 2,531) in the three top indexed diagnostic pathology journals for a period of 60 months from July 1993 to June 1998. A total of 448 articles in which the use of EM was indicated, according to standard surgical pathology textbooks, were selected. Both the actual and the potential EM content of each article were scored, as follows: zero, illustrative, supportive, gold standard (for confirmation of research results), extensive, and predominant. Of the total number of articles in which EM was indicated, 77% made use of the technique. EM support was lacking most frequently in articles on serosal neoplasms and on new diagnostic strategies (p <. 00005). There was no definite trend toward an increase or decrease in the use of EM during the period analyzed. The authors conclude that EM is used in most reports on diagnostic pathology, when it is indicated. However, a small but non-negligible percentage of articles (23%) could benefit from including EM as an ancillary, control, or gold standard method to complement, support, or confirm their results.     

人肺癌中多药抗性基因的表达

临床上肿瘤细胞的抗药性常与编码Ｐ－糖蛋白的多药抗性基因有关，为测定肿瘤中多药抗生基因的表达，我们用地高辛标记的ｃＤＮＡ探针通过原位杂交检测了２５例肺癌组织中多药抗性基因的表达，发现在１２例中多药性基因过度表达。结果提示临床上这些肿瘤对化疗水敏感可以用Ｐ－糖蛋白介导的药物外流来解释。     

Fibrous histiocytoma of the orbit. A clinicopathologic study of 150 cases

This is a clinicopathologic study of 150 cases of fibrous histiocytoma of the orbit. The tumors occurred in adults (median age, 43 years). The upper and nasal portions of the orbit were the most common sites of involvement. The most common signs and symptoms were proptosis (60 per cent), mass (46 per cent), and decreased vision (25 per cent). Based on the histopathologic features, the tumors were classified in three groups: benign (94 cases), locally aggressive (39 cases), and malignant (17 cases). The biological behavior correlated well with the duration of symptoms, the size and margins of the mass, and the histologic classification. The rate of recurrence was 31 per cent for the benign tumors, 57 per cent for the locally aggressive tumors, and 64 per cent for the malignant tumors. Follow-up data were obtained for 123 patients, with a mean duration of seven years. The ten-year survival of patients with benign, locally aggressive, and malignant fibrous histiocytoma was 100 per cent, 92 per cent, and 23 per cent, respectively. Nine patients died as a result of the tumor, six from local invasion of adjacent structures and three from metastatic disease. Fibrous histiocytoma is the most common primary mesenchymal orbital tumor of adults. The origin of the neoplasm is probably a primitive mesenchymal cell. Complete surgical excision appears to be the treatment of choice.     

Carcinoid tumors of the eye and orbit: a clinicopathologic study of 15 cases, with histochemical and electron microscopic observations

This clinicopathologic study includes 15 cases of carcinoid tumors of the eye and orbit. The patients ranged in age from 14 to 86 years (median, 53). No prediction for either gender was found. Seven tumors involved the orbit, seven the choroid, and one the iris. The primary site of origin of the carcinoid tumor was known in 12 cases: seven in the bronchus, one in the trachea, and four in the ileum. In three cases an orbital tumor was present but no other known primary neoplasm was clinically apparent. The postoperative follow-up period ranged from 0 to 4 years. The urinary levels of 5-hydroxyindoleacetic acid (5-HIAA) were elevated in four of ten patients tested, each of whom had a known primary tumor and two of whom had clinical evidence of the carcinoid syndrome. Four main histologic patterns were recognized: pattern A (solid lobules or masses), pattern B (trabecular or cord-like), pattern C (tubular or rosette-like) and pattern D (mixed). The apparently primary carcinoid tumors and the orbital or ocular metastases were closely related by their histologic patterns, histochemical staining characteristics, and ultrastructural features.     

Hepatobiliary carcinoma associated with primary sclerosing cholangitis and chronic ulcerative colitis

Hepatobiliary carcinomas were found in eight patients with chronic ulcerative colitis (CUC) and primary sclerosing cholangitis (large-duct PSC; five cases) or "pericholangitis" (small-duct PSC; three cases). The tumors were extrahepatic in five cases and intrahepatic in two; in one case the neoplasm affected both liver and gallbladder. The tumors in seven patients were glandular and, sometimes, cystic and papillary; in the remaining patient a combined hepatocellular carcinoma and cholangiocarcinoma was found. The latter tumor seemed to arise from regenerative nodules in secondary biliary cirrhosis complicating PSC. The presence of carcinoma in situ in areas of fibrous cholangitis, the multicentric origin of the tumor, the presence of tumor-free large-duct PSC or small-duct PSC (pericholangitis) at a distance from the carcinomatous areas, and the documentation, in some cases, of long-standing inflammatory hepatobiliary disease prior to the discovery of the tumors would seem to confirm the clinical impression that carcinomas may develop in pre-existing PSC. The appearance of hepatobiliary carcinomas in patients with classic PSC and in patients with pericholangitis supports previous evidence indicating that cholangiographically diagnosed large-duct PSC and histologically diagnosed small-duct PSC (pericholangitis) are manifestations of a shared condition that could be named PSC syndrome. The findings of the present study indicate that the PSC syndrome predisposes patients for the development of bile duct carcinoma. Most patients with CUC and bile duct carcinoma seem to have PSC prior to the development of the hepatobiliary tumor.     

Gene expression profiles in granuloma tissue reveal novel diagnostic markers in sarcoidosis

Sarcoidosis is an immune-mediated multisystem disease characterized by the formation of non-caseating granulomas. The pathogenesis of sarcoidosis is unclear, with proposed infectious or environmental antigens triggering an aberrant immune response in susceptible hosts. Multiple pro-inflammatory signaling pathways have been implicated in mediating macrophage activation and granuloma formation in sarcoidosis, including IFN-γ/STAT-1, IL-6/STAT-3, and NF-κB. It is difficult to distinguish sarcoidosis from other granulomatous diseases or assess disease severity and treatment response with histopathology alone. Therefore, development of improved diagnostic tools is imperative. Herein, we describe an efficient and reliable technique to classify granulomatous disease through selected gene expression and identify novel genes and cytokine pathways contributing to the pathogenesis of sarcoidosis. We quantified the expression of twenty selected mRNAs extracted from formalin-fixed paraffin embedded (FFPE) tissue (n = 38) of normal lung, suture granulomas, sarcoid granulomas, and fungal granulomas. Utilizing quantitative real-time RT-PCR we analyzed the expression of several genes, including IL-6, COX-2, MCP-1, IFN-γ, T-bet, IRF-1, Nox2, IL-33, and eotaxin-1 and revealed differential regulation between suture, sarcoidosis, and fungal granulomas. This is the first study demonstrating that quantification of target gene expression in FFPE tissue biopsies is a potentially effective diagnostic and research tool in sarcoidosis.     

人甲胎蛋白基因顺式作用元件的重新组合

本研究采用ＤＮＡ重组技术及ＰＣＲ方法对人甲胎蛋白（ＡＦＰ）基因顺式调控元件＋２９ｂｐ至－５．１ｋｂ区进行改造，将改建的ＤＮＡ片段分别克隆到荧光素酶报告基因载体ｐＧＬ２－Ｂａｓｉｃ中，构建了６种含有ＡＦＰ基因增强子和／或沉寂子不同组合的载体。以期筛选出对人肝癌细胞特异的，具有强启动活民生的ＡＦＰ顺序调控元件组合，为进一步实行肝癌基因治疗提供依据。     

Follicular bronchitis/bronchiolitis

Nineteen open lung biopsies demonstrating follicular bronchitis/bronchiolitis were reviewed with special attention to clinical manifestations. Morphologically, follicular bronchitis/bronchiolitis was represented by coalescent reactive germinal centers adjacent to airways in the absence of clinical or pathologic evidence of chronic obstructive pulmonary disease or bronchiectasis. Three clinicopathologic groups were identified: 1) patients with collagen vascular diseases, especially rheumatoid arthritis and Sj?gren's syndrome; 2) patients with a familial form of the disease or with immunodeficiency syndromes; and 3) a heterogeneous group of patients with frequent peripheral blood eosinophilia, suggesting a hypersensitivity reaction. Prognosis was related to age at the time of biopsy and, to some extent, to the clinical group. Steroid therapy had inconsistent effects in all groups identified. The differential diagnosis of lymphoid lesions in the lung is also discussed.     

DMD基因缺失和重复及其在基因诊断中的应用

本文应用DMD基因位点的cDM02b—3和8探针对正常中国人及20例无亲嫁关系的DMD患者的基因组DNA进行了分析。结果显示,20例病例中有10例可检测到DMD基因缺失,缺失率为50％,缺失的部位、大小不同,呈现遗传异质性。采用双波长薄层扫描仪(CS—910),还发现了两例基因重复的病例,重复率为1％。此外,在两例有缺失的病例中各发现一个大小异常的联接片段。本文讨论了cDNA探针在DMD基因诊断、携带者检出以及产前基因诊断中的应用和价值。     

Characterization of papillomaviruses isolated from cutaneous fibromas of white-tailed deer and mule deer

Deer fibromavirus (DFV), a member of the papillomavirus genus, was isolated from cases of fibromatosis in white-tailed deer (Odocoileus virginianus) and mule deer (Odocoileus hemionus). SDS-polyacrylamide gel electrophoresis analysis of virions indicated no molecular weight differences in the major structural protein. DFV agglutinated mouse erythrocytes and the reaction could be inhibited by both DFV-specific and BPV-1-specific antisera. Although analysis of restriction endonuclease digestion products indicated minor differences in cleavage patterns, the DFV DNAs were indistinguishable by liquid phase hybridization and restriction enzyme cleavage maps indicated most of the sites in common. Comparison of DFV DNA to BPV-1 and BPV-2 DNA under stringent liquid-phase hybridization conditions indicated that 3 to 9% DNA sequence homology could be detected between the genomes of these viruses. Blot-transfer hybridization revealed that DFV DNA reannealed to the same restriction fragments of BPV-2 DNA under stringent conditions that DNA from other papillomaviruses hybridize to under nonstringent conditions.