Coexisting high-grade glandular and squamous cervical lesions and human papillomavirus infections.

The frequency of high-risk human papillomavirus (hr-HPV) genotypes in patients with adenocarcinoma in situ (ACIS) with coexisting cervical intraepithelial neoplasia (CIN), ACIS without coexisting CIN, and high-grade CIN (CIN II/III) was studied, in order to gain more insight into the relation between hr-HPV infections and the development of coexisting squamous and glandular lesions. The SPF(10) LiPA PCR was used to detect simultaneously 25 different HPV genotypes in biopsies obtained from 90 patients with CIN II/III, 47 patients with ACIS without coexisting CIN, and 49 patients with ACIS and coexisting CIN. hr-HPV was detected in 84 patients (93%) with CIN II/III, 38 patients (81%) with ACIS without CIN, and in 47 patients (96%) with ACIS and coexisting CIN. A total of 13 different hr-HPV genotypes were detected in patients with CIN II/III, and only five in patients with ACIS with/without coexisting CIN. HPV 31, multiple hr-HPV genotypes, and HPV genotypes other than 16, 18, and 45 were significantly more often detected in patients with CIN II/III, while HPV 18 was significantly more often detected in patients with ACIS with/without CIN. There were no significant differences in the frequency of specific hr-HPV genotypes between patients with ACIS with or without coexisting CIN. In conclusion, the frequency of specific hr-HPV genotypes is similar for patients with ACIS without CIN and patients with ACIS and coexisting CIN, but is significantly different for patients with CIN II/III without ACIS. These findings suggest that squamous lesions, coexisting with high-grade glandular lesions, are aetiologically different from squamous lesions without coexisting glandular lesions.

Late pulmonary metastases from chondroblastoma of the distal femur. A case report.

A patient treated with curettage and bone grafting for a chondroblastoma of the distal femur sustained a pathologic fracture after a local recurrence. He then underwent a local, radical resection and an arthrodesis of the knee. Ten years after the first operation, pulmonary metastases were found, for which he underwent a metastasectomy (thoracotomy). At the latest follow-up, 1 year later there were no signs of tumor.

Cytokeratin expression in chondroblastomas.

The present study is based on the histopathological and immunohistochemical examination of seven chondroblastomas, including one lung metastasis occurring 9 years after treatment. Chondroblastomas were shown to co-express vimentin, S-100 protein, neuron-specific enolase, and the epithelial markers recognized by CAM 5.2, EMA and a polyclonal cytokeratin antibody. The cytokeratins present in the tumour cells of the lung metastasis were characterized as cytokeratins 8, 18, 19 and, to a lesser extent, cytokeratin 7. The results suggest aberrant cytokeratin expression in chrondroblastomas.

Image and flow DNA cytometry of small cell carcinoma of the lung.

Both image and flow DNA cytometry were performed in isolated nuclei from paraffin-embedded tumor tissue of patients with small cell carcinoma of the lung (SCCL). In 14 patients tissue was obtained by surgery from the primary tumor. From 14 patients tissue was taken by autopsy. From two patients tissue obtained by both surgery and later autopsy were available. From the autopsy patients tissue was taken only from the primary tumor (n = 6), from a metastasis (n = 1) and from the primary tumor and distant metastases (n = 7). Twelve of the tumors obtained by surgery were diploid, and two multiploid (two stem lines present). This was found both with image and flow cytometry. The group of patients could clearly be subdivided in short survivors (less than 9 months, n = 6) and long survivors (greater than 16 months, n = 8); since in both groups one multiploid and the remainder diploid cases were present, ploidy did not seem to be a good prognosticator for survival. In most (n = 26) of the tissues measured from the autopsy patients, again, a good correlation between image and flow DNA cytometry was obtained, the histograms being either (near) diploid or multiploid. In six cases, however, flow cytometry showed multiploidy whereas image showed aneuploidy (one single peak clearly deviating from diploidy). This discrepancy is caused because normal diploid (nonneoplastic) cells in the preparations could not be discarded from the flow cytometry measurements. Using the image cytometry data of the primary tumors, five diploid, three aneuploid, and four multiploid tumors were found. In five of the seven patients of whom tissue was obtained from the primary tumor and multiple metastases, differences between the histograms were found, mostly showing two malignant cell populations in one tissue and only one of them in another. Of one of the two patients of whom tissue was obtained by surgery and later autopsy, a change in histogram pattern was observed. It is concluded that although there is a high similarity between image and flow DNA cytometry, for an optimal interpretation of the histogram pattern, image measurements are more reliable. Ploidy determination does not seem to be of use in prediction of survival, and care should be taken in interpreting DNA histograms of metastases in SCCL patients because of the variability in histogram pattern.

Immunocytochemical detection of human lung cancer heterogeneity using antibodies to epithelial, neuronal, and neuroendocrine antigens.

Lung cancers were investigated for their heterogeneity as expressed by their immunoreactivity for cytokeratins and neurofilament proteins, as well as for the neuroendocrine differentiation antigen MOC-1. Using broadly cross-reacting antibodies, cytokeratins were detected in nearly all cases of lung carcinomas. Keratinization could be detected only in cases of moderately to well-differentiated squamous cell carcinoma (SQC) using a monoclonal antibody to cytokeratin 10, while a monoclonal antibody reactive with cytokeratin 18, and specific for glandular epithelia, reacted with adenocarcinomas, small cell lung carcinomas (SCLC), and lung carcinoids. In SQC this antibody could detect non-squamous cell differentiation, showing increasing numbers of positive cells with decrease of histologically detectable SQC differentiation. Cells positive for neurofilaments were demonstrated in some of the poorly differentiated SQCs and in some of the cases of SCLC, possibly representing the variant type of SCLC. Also in some of the lung carcinoids neurofilament proteins were present, colocalizing with cytokeratins. MOC-1 was present in all SCLC and lung carcinoids. This antibody could also detect neuroendocrine differentiation in all combined small cell carcinomas, in one poorly differentiated adenocarcinoma, and in about 30% of the poorly differentiated SQCs. Therefore, lung cancer heterogeneity can be detected using a panel of well-defined antibodies to intermediate filaments in combination with the MOC-1 antibody. The use of these antibodies in diagnosis can have prognostic significance and can lead to a more selective therapeutic approach.