Robert W. McDivitt

Histologic types of benign breast disease and the risk for breast cancer

Specific histologic types of benign breast disease (BBD) may increase breast cancer risk. The authors analyzed data from a population‐based, case‐control study of women aged 20 to 54 with newly diagnosed breast cancer and control subjects randomly selected from the general population. A panel of pathologists classified the histologic findings of biopsy slides for 433 women with breast cancer and 261 control subjects, all of whom had a history of biopsy for BBD, as to the presence of epithelial hyperplasia, atypia, and other histologic features. When compared with women who had never had a breast biopsy, women with BBD without hyperplasia had an odds ratio of 1.5 (95% confidence limits [CL] 1.3 to 1.9), women with hyperplasia without atypia had an odds ratio of 1.8 (CL = 1.3, 2.4), and women with hyperplasia and atypia had an odds ratio of 2.6 (CL = 1.6, 4.1). Fibroadenoma was an independent risk factor for breast cancer (odds ratio = 1.7; CL = 1.1, 2.5). These findings suggest that women with BBD with epithelial hyperplasia either with or without atypia and women with fibroadenoma should be monitored carefully because of their elevated risk for breast cancer. Cancer 1992; 69:1408‐1414.

A proposed classification of breast cancer based on kinetic information derived from a comparison of risk factors in 168 primary operable breast cancers

Flow cytometric DNA analysis was performed on 168 consecutive primary operable breast cancers and the results correlated with thymidine labeling, estrogen receptor (ER) and progesterone receptor values, and various histologic parameters. Seventy‐five cancers (45.0%) were diploid and 93 (55.0%) aneuploid. In 83.9% of aneuploid cancers, the DNA index fell between 1.1 and 2.0. Thirteen cancers were hypertetraploid and three hypodiploid. The percent of S‐phase cancers (SpF) varied from 1.1% to 24.4%, with a mean of 8.0% and a median of 7.1%. The mean SpF of diploid cancers was 5.2%; of aneuploid cancers, 10.3%. There was no significant correlation between SpF or ploidy and tumor size or axillary lymph node status. The thymidine labeling index (TLI) varied from 0.2 to 23.1, with a mean of 7.5 and a median of 6.1. There was good correlation between TLI and SpF (r = 0.892, P = 0.0001). ER‐negative tumors had a significantly higher mean SpF (10.3%) than did ER‐positive tumors (6.7%), but there was no significant correlation between ploidy and receptor positivity or negativity. There was a good correlation between invasive tumor necrosis, poor cytologic differentiation, aneuploidy, and above‐median SpF. Only a fair correlation was observed between mitotic rate and SpF. A classification of invasive breast cancers based on ploidy and SpF is proposed.

Tubular carcinoma of the breast. Clinical and pathological observations concerning 135 cases.

Clinical and pathological features of 135 tubular carcinomas are discussed. Tumor silc varied from 0.2 to 2.5 cm with a mean diameter of 0.9 cm. In situ carcinoma was found associated with tubular cancer in 86 cases (63.6%). In 82 of 86 (95.3%) it was of micropapillary/cribriform intraductal type. Twelve of 109 patients in whom axillary; diseais was performed were found to have axillary metastases. Six patients (4) developed recurrent or disseminated metastatic carcinoma during a mean follow-up period of 7.2 years. Two of these patients are dead of disease. Tubular carcinoma shneld be distinguished from microglandular adenosis, an uncommon form of selerosing adenosis.

Practical breast carcinoma cell kinetics: Review and update

SummaryThe S-phase fraction (SPF) measured by flow cytometry of DNA and the thymidine labeling index (TLI) measured autoradiographically indicate the proportion of carcinoma cells currently synthesizing DNA and reflect the rate of proliferation. The TLI and SPF are lognormally distributed. The median TLI performed to maximize precursor uptake is near 5% (5 labeled carcinoma cells per 100), the mean near 7%, and the range from less than 1% to near 40%. Corresponding values for the SPF measured by DNA flow cytometry are slightly higher when appropriate measures are taken to reduce background debris counts and other artefacts. Residual elevation of SPF above TLI may result from S-phase arrested cells. Flow cytometric histograms show that clearly aneuploid cell lines exist in 50–80% of primary breast carcinomas. Aneuploid breast carcinomas have higher mean TLI than diploid breast carcinomas, and therefore proliferate more rapidly. They also more frequently lack estrogen receptor (ER). Carcinomas with minimal nuclear anaplasia, particularly those of tubular, mucinous, infiltrating lobular and adenocystic types have low TLI and SPF, whereas carcinomas with highly anaplastic nuclei, including medullary carcinomas, have high TLI and SPF. TLI and SPF correlate inversely with ER and PgR content, have no relationship to axillary lymph nodal status, and have a weak positive correlation with tumor size and a weak negative correlation with age. High TLI predicts a high risk of early relapse after primary therapy for both node-negative and node-positive carcinomas. Carcinomas that produce brain metastases have particularly high TLI. Current evidence suggests that high SPF and aneuploidy may prove to have prognostic significance like TLI.

DNA flow cytometry of breast carcinoma after acetic-acid fixation

ABSTRACT Aqueous acetic acid was used to fix and store specimens of tissue prior to dissociation into nuclear suspensions for flow cytometric quantitation of DNA. the optimum concentration was 20 volumes of glacial acetic acid in 80 volumes of distilled water. Both neoplastic and benign nuclei were easily released from the fixed tissue blocks by slicing and shaking. Residual undissociated tissue was suitable for microscopic examination to confirm its identity. the nuclei fluoresced brightly after staining with propidium iodide, and yielded histograms similar to those from unfixed samples. Acetic‐acid fixation resulted in slightly broader G1 and G0 peaks in the DNA histograms in comparison to unfixed cells, but fluorescent debris was less and correlation between the flow cytometric S‐phase fraction (SPF) and in vitro thymidine labelling index (TLI) was better than with unfixed cells. Twenty‐one of thirty‐nine acetic‐acid‐fixed breast carcinomas had DNA indices in excess of 1.0 (increased nuclear DNA content in comparison to benign cells), and eighteen had DNA indices of 1.0 (normal or near‐normal). the SPF was usually in excess of the TLI, but the two were significantly correlated (r= 0.72, P>0.0001). However, a significant correlation of SPF with TLI held only for the group with DNA index < 1.0. DNA indices < 1.0 were associated with high SPF and TLI, and high SPF and TLI each associated with low content of estrogen receptor.

Primary renal angiosarcoma: A case report

A 67 year old white male presented with a two week history of mild hematuria and flank pain. Various radiologic studies demonstrated a vascular mass in the right kidney. At nephrectomy a large renal angiosarcoma with fixation to the liver and multiple pulmonary metastases was found.

Flow cytometric analysis of breast needle aspirates

This study investigated two hypotheses: (1) sufficient cells may be obtained by needle aspiration of breast nodules to produce good flow cytometric DNA profiles; and (2) benign breast lesions do not produce aneuploid GOG1 peaks, and therefore a distinct aneuploid peak is sufficient for a diagnosis of malignancy. Breast specimens received in Surgical Pathology between December 1985 and February 1987 were aspirated, and the cells stained with propidium iodide for flow cytometric DNA analysis. A total of 344 specimens were aspirated, of which 204 (59%) were malignant and 140 (41%) benign. One hundred fifty‐three malignant and 111 benign specimens contained sufficient cells for analysis. Cytologic smears were available for 177 malignant and 123 benign specimens. DNA histograms were considered diagnostic of malignancy if an aneuploid peak was present which contained at least 20% of the cells in the distribution, and had a DNA index ≥1.2. Using these criteria, 73 of 153 (48%) carcinomas could be identified. None of the benign lesions satisfied these criteria. One fibroadenoma with atypical hyperplasia produced a distinct peak which contained < 5% of the cells in the histogram, and had a DNA index of 1.25. Flow cytometric analysis provides objective data that complement the subjective cytologic interpretation of fine needle aspirates.