Bogdan Czerniak

Morphologic diversity of long bone adamantinoma. The concept of differentiated (regressing) adamantinoma and its relationship to osteofibrous dysplasia

A review of the clinical, radiologic, and histologic features of 25 cases of long bone adamantinoma is presented. To answer some questions concerning the nature of these tumors, relevant tissue markers were analyzed in seven cases using immunohistochemical assays. This study confirmed the epithelial nature of long bone adamantinomas irrespective of their wide‐ranging morphologic patterns that can mimic tumors of various origin. On the basis of distinct radiologic, histologic, and immunohistochemical patterns, a new type of adamantinoma termed “differentiated adamantinoma” could be distinguished from the classic long bone adamantinomas. The diagnostic features characteristic of the differentiated adamantinoma include: patient age (first two decades), intracortical location of the entire lesion, uniform predominance of an osteofibrous dysplasia‐like pattern, and scattered positivity of epithelial elements for cytokeratin. We postulate that the predominance of an osteofibrous dysplasia‐like pattern in differentiated adamantinoma is the result of a secondary reparative process overgrowing matured and regressing tumor tissue. It is possible that this process may lead to the total elimination of recognizable tumor cells from the lesion. Therefore, osteofibrous dysplasia (ossifying fibroma) of long bones, which has a similar anatomic location, age distribution, and radiologic appearance as differentiated adamantinoma, may, in some cases, represent the evolution of an underlying adamantinoma. Our analysis suggests that long bone adamantinoma could be another member of the unique family of tumors that may regress spontaneously.

Concurrent mutations of coding and regulatory sequences of the Ha-ras gene in urinary bladder carcinomas☆

This report concerns the study of Ha-ras gene mutations and ras p21 expression in primary tumors of the urinary bladder. Polymerase chain reaction-based techniques and computerized image analysis were used. The data obtained were related to tumor grade, DNA ploidy, and tumor invasion. A point mutation (G-->T) at Ha-ras codon 12 was found in 30 of 67 tumors. The mutation frequency was greater in grade III (65%) than in grade II (44%) tumors; no mutations were observed in grade I tumors. The mutation was observed more often in aneuploid (58%) than in diploid (28%) tumors. No other substitution at codon 12 was seen and no codon 61 mutation was detected. The tumors were also tested for the A-->G mutation at position 2719 of Ha-ras intron D. Concurrent codon 12 and intron D mutations were identified in seven high-grade aneuploid tumors; six were invasive. The levels of the ras gene product p21 were approximately 10 times higher in tumors with intron D mutation than in those without. These findings confirm on human bladder tumors the observations of the effect of synchronous exon-intron mutations reported on the bladder cancer cell line T24. Our results are the first demonstration of Ha-ras intron D alterations in human tumor tissues and suggest that concurrent mutations at codon 12 and intron D of this gene within the same tumor may contribute to the aggressive behavior of human bladder carcinomas.

Ha-ras gene codon 12 mutation and DNA ploidy in urinary bladder carcinoma

ImagesFigure 1

Expression of ras oncogene p21 protein in early gastric carcinoma and adjacent gastric epithelia

The expression of the ras gene product p21 in normal gastric mucosa, early gastric carcinoma of diffuse (gastric) and intestinal types, and in adjacent mucosal abnormalities is reported. The analysis was performed on paraffin sections by an immunohistochemical assay using the mouse monoclonal antibody RAP‐5 and the rat monoclonal antibody Y13–259. Expression of ras p21 was assessed by staining intensity and percentage of positively stained cells. In comparison to normal gastric mucosa of non‐cancer patients, p21 was overexpressed in nearly all early carcinomas of both types and in the dysplastic and/or metaplastic mucosal alterations accompanying intestinal type of gastric cancer. Increased p21 expression was also observed in the normal‐appearing mucosa adjacent to early carcinomas of diffuse type, but not in the morphologically normal gastric epithelium adjacent to the intestinal type. The results of this investigation suggest that ras p21 overexpression may be related to early events of human gastric carcinogenesis. The study supports the notion of different pathways in the development of diffuse (gastric) and intestinal types of gastric carcinomas.

Diagnosis of orbital tumors by aspiration biopsy guided by computerized tomography

Thin‐needle aspiration biopsy (TNAB) was performed on 22 patients with orbital tumors. Nine patients were studied before the introduction of computed tomography (CT) and only two cytologic diagnoses could be established. Thirteen aspiration biopsies guided by CT were successful. The technique of the CT‐guided TNAB of orbital tumors is described. The cytologic features combined with the clinical data made it possible to diagnose precisely 10 malignant orbital tumors that were either metastatic or primary. Two meningiomas and one abscess were also identified. There were no complications. The TNAB of orbital tumors under CT guidance appears to offer several significant benefits to the patients.

ras oncogene p21 as a tumor marker in the cytodiagnosis of gastric and colonic carcinomas.

This study was undertaken to determine whether the expression of ras oncogene product p21 can be used as a tumor cell marker of gastric and colonic carcinoma in brush smears. To detect p21 an immunocytochemical assay with RAP‐5 monoclonal antibody was used. Benign epithelial gastric cells obtained from normal gastric mucosa or benign gastric lesions reacted negatively in 12 out of 13 cases. Similarly, benign epithelial colonic cells from normal colon or benign colonic lesions were negative for p21 in nine out of ten cases. Weakly positive reaction, confined to a few cell clusters only, was observed in one smear of a benign gastric ulcer and one smear of chronic ulcerative colitis. All 20 smears from colonic carcinoma and all 20 smears of gastric carcinoma contained cells that stained positively for p21, and the degree of tumor differentiation had no impact on the staining pattern. The results recorded in this study show that the immunocytochemical assay for the ras oncogene product may prove to represent a new tool for the cytodiagnosis of gastric and colonic carcinomas.

DNA distribution patterns in early gastric carcinomas. A feulgen cytometric study of gastric brush smears

DNA distribution patterns were studied by cytophotometry in 20 Feulgen‐stained brush smears of early gastric carcinomas. Two different DNA distribution patterns, classified as predominantly diploid and aneuploid, were correlated with histologic data. Six of seven carcinomas of diffuse type were predominantly diploid. By contrast, 11 of 13 intestinal type carcinomas were aneuploid and two were diploid. Since the DNA distribution patterns recorded in this study were previously observed in advanced gastric carcinomas, this would suggest that the basic genetic make‐up of the tumors does not change with tumor progression. Cancer 59:113–117, 1987.

Expression of ras oncogene p21 protein in relation to regional spread of human breast carcinomas.

The oncogenes most frequently detected in human tumors belong to the ras gene family (Ha‐ras, Ki‐ras, and N‐ras). These genes encode a group of closely related 21,000 dalton proteins termed p21. An immunohistochemical study of ras p21 expression was carried out on paraffin sections of 54 human breast carcinomas using monoclonal antibodies to p21. The control group consisted of ten cases of benign fibrocystic disease. The p21 expression was significantly higher in cancer cells than in epithelial cells of control specimens. No correlations, however, were observed between oncogene product expression and tumor size, histologic type, or grade. As a group, tumors with axillary lymph node metastases expressed higher levels of ras p21 than nonmetastasizing tumors. However, because of the significant overlap in individual p21 values, it is unlikely that the immunohistochemical assay for p21 could be used to predict the behavior of mammary carcinomas.

Expression of CA antigen on human urinary bladder tumors

Flow cytometric measurements of Ca antigen (Ca) visualized by immunofluorescence with Cal monoclonal antibody (Ca1) were performed on cells from 26 urinary bladder carcinomas of various histologic grades and DNA ploidy and on 6 samples of morphologically normal urothelium. In normal urothelium and in the 14 diploid tumors the proportion of positively staining cells was low and the differences were not statistically significant. A significant increase in the proportion of fluorescent cells was observed in all but one of the 12 aneuploid tumors. Among the 11 tumors with an increased proportion of positive cells, 7 were invasive. Data recorded in this study suggest that the quantitation of Ca1 fluorescence corresponding to the presence of Ca may prove to be helpful in the evaluation of clinical behavior of bladder tumors.

Flow cytometric identification of cancer cells in effusions with Ca1 monoclonal antibody.

The fluorescence of cells from 42 pleural and peritoneal effusions stained with Ca1 monoclonal antibody (Ca1MA) was studied by flow cytometry. In 14 of 17 malignant effusions a significantly higher intensity of fluorescence was observed in samples exposed to Ca1MA when compared with controls. There was no increase of fluorescence intensity in 25 benign effusions. The method failed in three malignant effusions: one due to endometrial carcinoma and two to malignant lymphoma. The sensitivity of the method was tested in experimental samples with a known percentage of malignant cells. The positive fluorescence with Ca1MA was detected in samples containing 0.1% of carcinoma cells. Flow cytometry with Ca1MA can be a relatively simple method of identification of malignant cells in effusions.