Pre-operative simultaneous stereotactic core biopsy and fine-needle aspiration biopsy in the diagnosis of invasive lobular breast carcinoma.

PURPOSE: To determine the diagnostic value of stereotactic core needle biopsy (SCNB) in comparison to stereotactic fine-needle aspiration biopsy (SFNAB) in patients with invasive lobular carcinoma (ILC). MATERIAL AND METHODS: Twenty-two patients with clinical or mammographic findings suspicious of malignancy underwent surgery where postoperative histopathology showed ILC. Pre-operative attempts of diagnosis were made using SFNAB and SCNB. SFNAB was done with a spinal needle 0.7- or 0.9-mm and SCNB was simultaneously performed with an automated 2.1-mm biopsy gun in all patients. RESULTS: SFNAB was diagnostic of carcinoma in 9 women, showed "probable carcinoma" in 5 and "atypia" in 3. In the remaining 5 women, SFNAB showed no atypia. SCNB diagnosed ILC in 20 patients and showed ILC as well as invasive ductal carcinoma (IDC) in 1. Ductal carcinoma in situ was suggested in the remaining patient. CONCLUSION: SCNB was superior to SFNAB in diagnosing ILC and did not miss any carcinoma, whereas SFNAB was non-diagnostic in 8 cases. SCNB is thus recommended in patients with suspicion of ILC of the breast.

Prognostic factors in thin cutaneous malignant melanoma.

BACKGROUND: Thin melanomas can metastasize and be lethal. The predictive importance of tumor thickness in thin melanomas and the specific features identifying the patients at risk have not been investigated fully. METHODS: Prognostic factors were analyzed in 585 patients with clinical Stage I invasive cutaneous malignant melanoma with a thickness of less than or equal to 0.8 mm. The patients were included in a population-based cancer registry in Stockholm county during 1976-1987. They constituted about 64% of all patients with thin melanomas who were diagnosed in the region during the study period. Information was available on age, sex, anatomic site of the tumor, histologic type of melanoma, level of invasion, tumor thickness, and tumor regression. In a Cox regression analysis, the prognostic importance of each factor was studied. By a case-control technique with individual matching for the identified independent predictors of recurrence, the additional prognostic information given by type and grade of inflammatory response, presence of vertical growth phase, mitotic rate/mm2, and histologic ulceration of the tumor was assessed. RESULTS: After a median follow-up time of 50 months, recurrent disease developed in 26 patients (4%). There was no difference in recurrence rate between patients treated with narrow (1-2 cm) or wide (5 cm) excision. Anatomic site, tumor thickness, level of invasion, and tumor regression were found to be independent prognostic factors in the multivariate analysis. In the case-control study, only grade of inflammatory reaction added significant prognostic information. No subgroup could be identified that was without risk of recurrent disease. CONCLUSIONS: Thin melanomas do not seem to constitute a separate form of melanoma, but compose one end of a continuous spectrum of biologic behavior.

Nuclear DNA analyses in archival material from primary malignant melanoma. A pilot study.

In 28 cases of malignant melanoma, paraffin-embedded specimens were analyzed in order to determine the reliability of ploidy results. The material consisted of thin and thick melanomas. The results indicate that useful prognostic information may be obtained in this kind of material by means of DNA measurements, provided that the analysis is performed on morphologically identified tumor cells. The value of DNA measurements in malignant melanomas may, however, not be as clear as has been reported for several other tumors.

Comparison of nuclear DNA content in primary and metastatic malignant melanoma.

The DNA patterns obtained from 23 primary malignant melanomas and 35 corresponding metastases were compared and found to differ in many cases. In eight cases the primary tumors and their metastases had a ploidy type I ("euploid") DNA pattern. One case had a type I primary tumor and both type I and type II metastases. Five cases had type I primary tumors and ploidy type II ("aneuploid") DNA pattern metastases. In five cases the primary tumors and corresponding metastases were type II, and in another four cases the primary tumors were type II, whereas the metastases were type I. We interpret these data as indicating that malignant melanomas (more often than adenocarcinomas) are composed of genetically heterogeneous tumor sublines that frequently give rise to heterogeneously composed metastases. Since we sometimes observed a change in the DNA content in malignant melanomas, it seems to be more difficult to obtain prognostic information from DNA analysis in malignant melanoma as compared to the more stable adenocarcinomas.

Facial skin complaints and work at visual display units. A histopathological study.

Facial punch biopsies from 83 patients with skin complaints with or without skin lesions and supposedly associated with work at visual display units (VDUs) were compared to biopsies from 51 subjects with no VDU exposure with or without skin lesions. Coded slides were assessed by three independent observers regarding hyperplasia of sebaceous glands, occurrence of telangiectases, intensity of inflammatory infiltrate, degree of hydropic degeneration of basal cells, occurrence of demodex folliculorum, number of mast cells and degree of degenerative changes in elastic fibers. No parameter was significantly more common in exposed subjects than in non-exposed persons with equivalent skin signs. The controls without skin lesions also showed various degrees of histologic changes. Hyperplasia of sebaceous glands was more common in men and in young persons. Degenerative changes in elastic fibers increased with age, but were also obvious in some persons under 35 years of age. In this study no characteristic histologic changes in facial skin were found in individuals with skin symptoms claimed to be associated with exposure to VDUs.

Nuclear DNA content and nuclear atypia. Relation to survival in patients with breast adenocarcinoma and serious ovarian tumors.

The grade of nuclear atypia (low, medium, or high) was compared with DNA content in 122 tumors comprising 73 serous ovarian tumors and 49 mammary carcinomas of ductal type. The study was performed on two consecutive histologic sections 4 mu in thickness, one of which was stained with hematoxylin-eosin for estimation of nuclear atypia, and the other with Feulgen for measurements of DNA. In both tumor groups there was a significant correlation between nuclear atypia and nuclear DNA content. The results suggest that DNA analysis is of significant additional prognostic value even when the grade of nuclear atypia is known.

Analysis of DNA distribution in Kaposi's sarcoma in patients with and without the acquired immune deficiency syndrome.

While Kaposi's sarcoma in patients with the acquired immune deficiency syndrome (AIDS) may present as a multicentric disease with progressive organ involvement, the classic form of Kaposi's sarcoma is an indolent tumor seldom affecting extracutaneous areas and almost never responsible for the patient's demise. An attempt was made to correlate these clinical differences with the nuclear DNA content of tumor cells in histologic sections from 15 patients (9 with AIDS and 6 without AIDS). All tumors showed a similar DNA distribution pattern, with most cells appearing diploid, indicative of a low malignant potential. These findings indicate that Kaposi's sarcoma of both AIDS and non-AIDS patients is a tumor of intrinsically low malignancy and that lack of immune surveillance is most probably responsible for its aggressive biologic behavior in many AIDS patients.

Does successful interferon treatment of tumor patients require life-long treatment?

Case histories of 5 tumor patients treated with natural leukocyte interferon-alpha (IFN-alpha) are presented. One patient with juvenile laryngeal papillomatosis responded well to interferon treatment, but the disease recurred when therapy was withdrawn. Upon reinstitution of treatment, the patient once again responded well. Another patient with myelomatosis also responded well to interferon therapy and in this case, too, the tumor recurred when interferon treatment was withdrawn. Reinstitution of interferon therapy was, however, unsuccessful. One patient with generalized giant cell tumor of bone responded with regression after more than 5 years of interferon treatment. Another patient with pulmonary osteosarcoma metastases, having received irradiation and interferon combination therapy followed by sole interferon treatment, responded well with a lasting stationary radiogram after 6 years of interferon treatment. One patient with malignant glioma, showing signs of tumor growth during the first few months of interferon therapy, eventually responded, and became disease-free after 6 years. The latter 3 patients are continuously receiving interferon therapy although more than 5 years have elapsed since their interferon therapy was initiated. It is suggested that interferon therapy for malignant tumors be given for life (or to progression of disease) in responding patients. Such a concept entails biological implications for interferon therapy in general and for antitumor action of interferons in particular. Other possible clinical schedules should only be constructed within the framework of controlled clinical trials.

Nuclear DNA content in squamous cell carcinoma, small cell carcinoma, and bronchiolo-alveolar carcinoma of the lung.

Nuclear DNA content in individual, morphologically identified tumor cells from 33 squamous lung carcinomas, 20 small cell lung carcinomas, and 10 bronchiolo-alveolar carcinomas were analyzed by means of cytophotometry on Feulgen-stained histologic and cytologic specimens. Twenty-eight of the squamous cell carcinomas and 17 of the small cell carcinomas had high and scattered DNA values, indicative of high malignancy potentials. None of the bronchiolo-alveolar carcinomas showed such high DNA values. These results are in line with clinical experience that squamous cell and small cell carcinoma are associated with rapid progression and death in patients, whereas bronchiolo-alveolar carcinomas have a more indolent course.

Prognostic significance of clinical stage, histologic grade, and nuclear DNA content in squamous-cell carcinoma of the anus.

Specimens from 47 cases of anal squamous-cell carcinoma were examined in Stockholm county (1978 to 1981) with respect to clinical stage (43 cases), histologic grade (41 cases), and DNA content of the tumor cells (31 cases). Follow-up ranged from four to seven years (median, 5.5 years). The increased mortality in advanced stage and high-grade lesions was significant. Analysis of DNA content showed that most tumors were aneuploid. No statistically significant effect of DNA content on survival could be demonstrated. Thus, histologic grade and clinical stage seem to be the best predictors of patient outcome in squamous-cell carcinoma of the anus.

Mammary carcinoma. Comparison of nuclear DNA content from in situ and infiltrative components.

Twenty-eight mammary carcinomas were analyzed with respect to their nuclear DNA content. Ten of the carcinomas were entirely in situ (noninfiltrative) while 18 showed areas of both infiltrative and noninfiltrative growth. The DNA content of individual tumor cells was measured in sections from the original paraffin-embedded specimens. In the tumors that had noninfiltrative as well as infiltrative zones, DNA analyses were performed in both areas. Comparison between the DNA patterns obtained from these different areas of the same tumor showed very close agreement. Both groups of tumors (those with and those without areas of invasion) contained some cases that showed a euploid DNA pattern and some cases that showed an aneuploid pattern. Furthermore, analysis of the DNA content of regional lymph node metastases in seven of the invasive cases did not show an increased aneuploidy in the metastases. The results suggest that, in mammary carcinomas, invasive and noninvasive tumors cannot be distinguished by DNA analysis and that tumor progression does not seem to be associated with a significant alteration of the nuclear DNA content.

Comparison between slide and flow cytophotometric DNA measurements in breast tumors.

Nuclear DNA analysis was performed in 37 human mammary adenocarcinomas in order to elucidate the difficulties and pitfalls connected with the interpretation of DNA histograms obtained using different methodologic approaches. For each tumor, DNA profiles were obtained by means of slide microspectrophotometry on a fine needle aspirate, slide cytophotometry on a 4-micron histologic section and flow cytometry on a suspension prepared from a cube of fresh tissue. When the DNA histograms were interpreted according to criteria usually applied to discriminate low-grade malignant tumors from high-grade malignant tumors, some tumors classified as euploid by one method were classified as aneuploid by another method. The main reasons for this weak correlation seem to be in specimen preparation and in tumor cell representation within the specimen between the methods. Another reason is that slide and flow techniques exhibit different sensitivities for malignancy-associated nuclear DNA changes: minor alterations of the DNA content of the tumor stemlines seem to be more exactly reported by means of the flow technique whereas structural alterations of the nuclear chromatin seem to be more sensitively recorded by means of the slide technique. It is suggested that thorough control of each step of the various DNA analysis procedures and the use of information obtainable by slide and flow techniques taken together may significantly improve the prognostic value of DNA measurements.

Affinity of human carcinoma cell nuclei for polyinosinic acid demonstrated by monoclonal antibodies.

The anti-nuclear cross reactivity of the monoclonal anti-actin antibodies M 372/809 was studied in some detail. The reactivity against a number of nuclear constituents was examined in the ELISA test and the capacities of these constituents to block the M 372/809 anti-nuclear and anti-actin reactions were evaluated in indirect immunofluorescence tests against tissue sections and monolayer cultures of fibroblasts and Vero cells. The repetitive polynucleotides polyinosinic and polyguanylic acid and their deoxyanalogues, actin and vimentin, were found to have the antigenic epitope. The epitope was covered or otherwise inactivated in the presence of polycytidylic acid. Using the M 372/809 antibodies as a reagent, carcinoma cell nuclei were found commonly to have an affinity for polyinosinic and polyguanylic acid. This was seldom noted with non-neoplastic cells.

Prognostic significance of nuclear DNA analysis in histological sections in mammary carcinoma.

The nuclear DNA content in tumor cells from invasive ductal breast carcinomas was analyzed in 26 patients who survived more than 10 years and in 23 patients who died within 2 years after operation. The DNA content of individual tumor cells was measured in sections from the originally paraffin-embedded specimens. In short-term survivors, a large proportion of cells with very high DNA values was found in all tumors except one. Only two patients of the long-term survivors had tumors that exhibited such high DNA values. Prognostic information obtained by DNA analysis compared with histologic malignancy grading showed that the specificity using DNA analysis was distinctly higher. The data thus suggest that analysis of DNA content of tumor cells in breast adenocarcinomas can be a useful supplement to histologic malignancy grading to obtain prognostic guidance in individual patients.

Comparison between histologic type, estrogen receptor, and nuclear DNA content in mammary carcinoma.

Histological specimens from 80 invasive breast carcinomas comprising typical cases of 16 ductal, nine papillary, 14 comedo, 13 colloid (mucous), 15 lobular, and 13 medullary carcinomas were examined with respect to nuclear DNA and estrogen receptor content. In agreement with previous studies, ductal carcinomas were found to exhibit different types of nuclear DNA distribution patterns, i.e., tumors with DNA values in the normal diploid or tetraploid regions indicative of good prognosis (euploid tumors) or those with values exceeding the normal tetraploid region indicative of poor prognosis (aneuploid tumors). The majority of the papillary and colloid tumors were euploid, while comedocarcinomas in general had aneuploid profiles. These findings are in agreement with expected survival within these patient groups. In lobular breast carcinomas, the correlation between the DNA distribution patterns and expected patient survival was less obvious; and in medullary carcinomas where the vast majority of the tumors showed aneuploid DNA profiles, the correlation to expected patient survival was low. Thus, lobular carcinoma in general seems to have a worse prognosis than is expected from nuclear DNA analysis, whereas medullary carcinomas in general seem to carry a better prognosis than indicated from DNA measurements. In agreement with earlier reports there was a good correlation between nuclear DNA content of the tumor cells and cytosol estrogen receptor values, i.e., euploid tumors in general exhibited relatively high receptor levels, whereas aneuploid tumors had low or unmeasurable estrogen receptor levels.

Mammary carcinoma: DNA analysis in areas showing different histological features in the same tumor.

Specimens from 17 invasive primary breast adenocarcinomas that showed distinct areas of different histologic appearance were examined with respects to nuclear DNA content of the tumor cells. DNA in individual tumor cells was measured in sections from the original paraffin-embedded specimens. DNA distribution patterns obtained from the histologically different areas in the same tumor were compared. In 15 cases these patterns were very similar, whereas in two cases the patterns were found to be different. The results suggest that, in spite of histological variations, breast carcinoma often show similar nuclear DNA content throughout the entire tumor. Since nuclear DNA content in breast tumors has been shown to be correlated to prognosis, our observations suggest that the differences in structural pattern occasionally seen in mammary adenocarcinoma do not necessarily reflect a dedifferentiation towards more malignant tumor populations.

Patterns of DNA distribution and neurohormone immunoreactivity in the tumour cells: tools for the histopathological assessment of gastro-intestinal carcinoids.

Modern immunohistochemical and DNA cytochemical analyses of gastro-intestinal carcinoids have yielded results that have increased our knowledge of the biological properties and the histogenesis of these theoretically and practically so fascinating kinds of neoplasm. Carcinoids in different anatomical localisations were found to show marked differences with regard to their neurohormone peptide immunoreactivity pattern and their ability to evoke clinical signs and symptoms of hormone overproduction. This can be of great help to the practising pathologist when he tries to predict the anatomical site of an unknown primary tumour from the results of this histopathological assessment of a metastatic nodule of a carcinoid. The DNA distribution pattern in the nuclei of carcinoid tumour cells is a tool in the histopathological assessment of the neoplasm that seems to be of some value in predicting the subsequent clinical course of the disease. This conclusion is based on the results of a pilot study of 8 cases of ileal carcinoids with liver and lymph node metastases. It was found that 4 cases with a rapidly progressive fatal disease had a higher proportion on non-diploid tumour cell nuclei than 4 cases still alive and at full work 5 years after the diagnosis of liver metastases. However, the number of aneuploid tumour cell nuclei was negligible in both groups.