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Biomedical subjects

D L Page

Publications and source records attributed to D L Page.

At least 127 records · Page 7Linked to original sources
PubMed1993

Proliferative and nonproliferative breast disease in atomic bomb survivors. Results of a histopathologic review of autopsy breast tissue.

BACKGROUND: The risk of female breast cancer in association with radiation dose is well established, on the basis of follow-up studies of the atomic bomb survivors and other exposed populations. This association is especially strong for women exposed before 20 years of age and appears to be much weaker among women exposed after 40 years of age. METHODS: Breast tissue samples from 88 high-dose and 225 low-dose autopsy cases from the Radiation Effects Research Foundation Life Span Study sample were examined in detail to determine whether nonproliferative and proliferative breast lesions are associated with radiation dose. RESULTS: Prevalence of proliferative disease in general and atypical hyperplasia in particular were positively associated with radiation dose. The associations were strongest for subjects who were between 40 and 49 years of age at the time of the bombing. CONCLUSIONS: It is hypothesized that the strongest association in women 40 to 49 years of age may be related to the age dependence of radiation-induced breast cancer, in that potential cancers induced in this age group by radiation exposure may receive too little hormonal promotion to progress to frank cancers.

Adolescent↗
PubMed1993

Mesenchymal hamartoma of liver. A regional ischemic lesion of a sequestered lobe.

OBJECTIVE: To evaluate histologic and gross features of mesenchymal hamartoma of liver and similar lesions in relation to determining likely pathogenesis. DESIGN: Case series of patients presenting to a tertiary care hospital over 16 years. PATIENTS: Three children with mesenchymal hamartoma ranging from newborn to 11 months of age and one 12-year-old girl with torsion of an accessory lobe of liver. MAIN OUTCOME MEASURES: Similarity of gross vascular and segmented anomalies as well as apparent consequent histologic features of mesenchymal hamartoma to those of torsion of an accessory lobe of liver indicate that they are pathogenetically related. RESULTS: Dissecting microscopic examination revealed a single vascular supply in one case and remote thrombi in two cases of mesenchymal hamartoma evaluated. The histologic features of mesenchymal hamartoma (hypocellular central zone and hypercellular periphery) were duplicated in the lobe of liver with torsion. CONCLUSIONS: Mesenchymal hamartoma represents a lesion with an anomalous solitary vascular supply that may evolve into its specific pattern with stromal cysts as a result of early ischemic changes.

Adolescent↗
PubMed1993

Diagnostic criteria and cancer risk of proliferative breast lesions.

Breast cancer risk assessment in women following a benign breast biopsy is a promising area with regard to intermediate endpoint determination, and has been particularly fostered by the consensus agreement concerning the risk attributed to specific diagnoses [1]. Several recent studies have largely verified this approach [2-4], and a recent report demonstrates general agreement among most expert pathologists regarding diagnostic criteria for these lesions [5]. However, in a limited number of cases, determining exact levels of risk for individual patients has been problematic as a result of a failure by pathologists to achieve consensus on diagnostic criteria for these same lesions. This situation has arisen primarily because it is much more tenable to disagree over subjective diagnostic criteria, than it is to argue with robustly supported epidemiological data. Without agreement on reproducible diagnostic criteria, widely promulgated consensus risk estimates for these specific histologic entities are no longer applicable. In addition, those individuals who choose different diagnostic criteria for proliferative breast lesions fail to realize that the terminology, epidemiological risk estimates, and diagnostic criteria used by Dupont and Page are inexorably linked. Since the publication of the consensus statement [1], those using the terms of "atypical ductal hyperplasia" and "atypical lobular hyperplasia" have by default accepted the diagnostic criteria of Dupont and Page. Therefore, surgical pathologists who desire to make use of the consensus risk estimates must familiarize themselves with diagnostic criteria for the various histologic entities that comprise proliferative disease of the breast as defined by Dupont and Page [6].(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy↗
PubMed1993

Anatomic indicators (histologic and cytologic) of increased breast cancer risk.

Anatomic indicators of increased breast cancer risk have regularly been identified as hyperplastic lesions, analogous to other body sites. Most of these have been shown to indicate a later increased risk anywhere in either breast and should thus be regarded as indicators or markers of increased risk. Unfortunately, these are largely identified incidentally to current methods of detection. Specific combined histologic and cytologic criteria for the definition of these lesions have been evaluated for both their reproducibility of diagnosis and outcome variables. Several studies agree that usual patterns of hyperplasia of at least moderate degree indicate an increased risk of later breast carcinoma between 1.5 and 2 times that of the general population. The specifically defined examples of atypical hyperplasia, lesions of relative rarity, are found in 4-5% of biopsies (depending upon method of detection) and recognize a risk in the range of 4-5 times that of the general population controlled for age and duration of follow-up. Thus, several cohort studies using comparable criteria for definition of the anatomic lesions have found similar clinical outcomes. Other approaches to histologic definition have produced a lesser degree of separation between the non "atypical" and other forms of hyperplasia. Although it is not clear whether we are dealing with continuous variables or discrete histologic/cytologic variables, it is clear that when combined criteria are used, a greater degree of predictability is obtained. Other related risk features include most predominantly family history, which when present with atypical hyperplasia indicates an increased risk beyond that of either alone. Other means of detection of these various lesions, such as fine needle aspiration cytology, have not been verified. True non-obligate precursors of breast cancer are probably confined to low grade and non-comedo ductal carcinomas of the breast.

Breast↗
PubMed1993

Antitumor effects of GBS toxin: a polysaccharide exotoxin from group B beta-hemolytic streptococcus.

A group B streptococcus (GBS) isolated from human neonates diagnosed with sepsis and respiratory distress ("early-onset disease") produces a polysaccharide exotoxin (GBS toxin) that, when infused in sheep, causes lung pathophysiology similar to that seen in humans. Histological studies have demonstrated that GBS toxin induces a strong inflammatory response in the lung, with pulmonary sequestration of granulocytes and extensive capillary endothelial damage. The susceptibility of humans to GBS toxin is age-dependent and limited to about 4 days after birth. It is rarely evident thereafter. This suggests that the binding of GBS toxin to the target endothelium occurs via specific components in the developing lung endothelial cells of the newborn that are later lost. We report here that GBS toxin can also bind to developing endothelium associated with neoplasia and induce an inflammatory response. GBS toxin was shown by immunohistochemistry to bind to capillary endothelium of human large-cell carcinomas. In nude mice bearing human tumor xenografts, intravenously administered GBS toxin caused tumor necrosis and hemorrhagic lesions, and substantially inhibited the rate of growth of the tumors. In BALB/c mice bearing Madison lung tumors, GBS toxin induced an inflammatory response resulting in marked changes in tumor morphology, including vasodilation, endothelial and tumor cell necrosis, invasion of lymphocytes and macrophages, and capillary thrombosis. In these tumor models, no evidence of toxicity to the vasculature of other tissues was observed. The reported pathophysiology of GBS in human neonates, the lack of disease in non-neonates colonized with GBS, and these results suggest that GBS toxin may have potential as a well tolerated agent in cancer therapy of some human tumors.

Adenocarcinoma↗
PubMed1993

Pathology of preinvasive and excellent-prognosis breast cancer.

Recent advances in breast cancer treatment have made recognition of different prognostic groups mandatory. In addition, further experience with screening-detected lesions has resulted in the definition of new associations. Therapeutic approaches to these frequently microscopic lesions continue to be the source of much debate. The subtyping of ductal carcinoma in situ is also an area of continuing controversy. This article reviews recent studies of excellent-prognosis carcinomas as well as premalignant and other histologically defined lesions that indicate an increased risk for the development or recurrence of carcinoma. Advances in fine needle aspiration biopsy and in hormone receptor assays are also reviewed.

Breast Neoplasms↗
PubMed1993

Histopathology: old principles and new methods.

Histopathology remains the benchmark and the only reliable means for diagnosing breast cancer in either invasive or preinvasive stages and for classifying morphologically distinct special types of breast cancer that exhibit different prognoses. Careful epidemiological research performed in tandem with histopathology had demonstrated that certain preinvasive lesions progress to invasive cancer at high frequency, and the detection of these lesions seems certain to increase with increased mammographic screening. Comedo and non-comedo DCIS represent examples of distinct preinvasive lesions in which differing histopathology reflects altered biological behaviour. Certain morphological varieties of invasive cancer are also associated with different biological outcomes, notably the special histological types such as tubular, lobular and medullary. Distinguishing these heterogeneous forms of breast cancer is crucial for diagnosis, prognostic prediction and the acquisition of research material for clinically relevant molecular epidemiological studies.

Breast Neoplasms↗
PubMed1993

Clinical correlates of false-negative fine needle aspirations of the breast in a consecutive series of 1,005 patients.

Fine needle aspiration (FNA) of the breast is a useful diagnostic tool in the management of lesions of the breast. However, false-negatives invariably occur and can detract from the usefulness of the technique. The current study of 16 patients with false-negative FNA of the breast from a consecutive series of 1,005 patients was undertaken in an attempt to better understand the clinical correlates most often associated with false-negative diagnoses. Pre-FNA physical examination and mammographic findings were correlated with the gross and microscopic features of these 16 patients. All 16 patients had palpable findings. Mammographic abnormalities were divided into three categories--highly suspicious for malignant tumor (n = 7), indeterminate (n = 3) and negative (n = 4). Mammograms were not available for two patients. The carcinomas ranged in size from 0.8 to 6.5 centimeters (mean of 1.9 centimeter). Thirteen of 16 carcinomas were 2 centimeters or less. Of the small tumors, histologic factors revealed no special type (NST) in six patients and special type carcinoma in seven patients. The notably large tumor (6.5 centimeters) was of high grade and demonstrated an unusual diffusely infiltrative pattern histologically extending between normal mammary lobules. Overall, special type carcinomas comprised seven of 16 patients. All of these carcinomas, as well as six of nine NST were paucicellular, that is, more than 20 percent area containing tumor cells. The current study supports the findings of others that small tumor size, paucicellularity and special type histologic factors contribute to false-negative diagnoses of FNA of the breast.

Adult↗
PubMed1993

Loss of expression of fodrin (a structural protein) in cystic changes of human breast.

BACKGROUND: Formation of cysts in the human female breast remains a common clinical problem with few pathogenic theories suggested, and none proven. EXPERIMENTAL DESIGN: We studied the immunohistochemical distribution of a structural protein, fodrin (a nonerythroid spectrin) within benign conditions of the breast. RESULTS: Whereas normal breast epithelium expressed fodrin, all breast cysts were consistently negative for fodrin expression. Both larger, tension cysts as well as the smaller microcysts seen in a special pattern of lobular atrophy were uniformly negative. CONCLUSIONS: Lack of fodrin may be a secondary event in cystic alterations of the breast. However, loss of this structural protein may be responsible for altered structural integrity of breast acini, resulting in or fostering the formation of cysts.

Adult↗
PubMed1992

Indicators of increased breast cancer risk in humans.

Specific atypical histological patterns of epithelial hyperplasia (AH) indicate a medically relevant risk of breast cancer development in 5-10% of women with otherwise benign biopsies. This risk is about four times that of similar women, i.e., of the same age and at risk for the same length of time. These relative risks are not stable with time and fall 10-15 years after detection. Absolute risk for invasive breast cancer after AH is about 10% in 10-15 years after biopsy and is most certain for perimenopausal women. Proliferative disease without atypia predicts only a slight elevation of risk with a relative risk (RR) of 1.5 to 2 times that of the general population. There is such a strong interaction between family history and AH that it is relevant to consider women with atypical hyperplasia who have a positive family history (FH) of breast cancer separately from those who do not. The absolute risk of breast cancer development in women with AH without a FH was 8% in 10 years (RR about 4), whereas those with a positive family history experienced a risk of about 20% at 15 years (RR of about 10). This interaction of AH and FH has also been observed in other recent studies. Low replacement doses of conjugated estrogen after menopause do not further elevate risk beyond that identified by histology.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy↗
PubMed1992

Stratified diagnostic approach to fine needle aspiration of the breast.

The clinical value of fine needle aspiration (FNA) of the breast is enhanced by incorporating into the cytologic diagnosis explicit comments on the level of diagnostic certainty. This stratification of diagnostic certainty is based predominantly on the cytologic features but occasionally also takes into consideration the clinical situation. Strong clinical and mammographic suspicion of mammary carcinoma associated with FNA, diagnostic of typical, intermediate to high-grade mammary carcinoma, warrants proceeding to definitive therapy without further diagnostic studies. False-positive results are virtually eliminated by placing cases with any uncertainty into a "probable" category, which does not support definitive therapy. In addition, oversimplified "benign versus malignant" approaches to FNA diagnoses ignore the heterogeneity of breast masses, with in situ and low-grade carcinomas warranting special clinical management and usually being placed in the "probable" category. Thus, malignant diagnoses are stratified into "definite" and "probable," with only the former supporting definitive therapy. Within our recent series of 1,005 FNAs of the breast, we were able to confirm the diagnosis in all 62 patients with a "definite" carcinoma diagnosis, and only 3 of 25 "probable" cancer diagnoses were benign at tissue biopsy. Thus, false-positive results were successfully avoided in the "definite" category. Furthermore, a much greater incidence of unusual and good prognosis tumor types were identified by the "probable" category. If the clinical setting is relatively suspicious only, a definitive diagnosis of cancer by FNA is rare and not necessary because the clinical question to be addressed is only whether to biopsy. This approach to FNA diagnosis, unlike the oversimplified "benign versus malignant" scheme, provides an approach that is more likely to result in optimal therapy for breast neoplasms, with low-grade or in situ carcinomas requiring special clinical management since these types of cancers are found predominantly in the "probably malignant" category. It also provides additional security against false-positive diagnoses by incorporating clinical level of certainty statements into FNA diagnostic categories, which more closely reflect the diversity and inherent complexity in the appropriate diagnosis and therapy of mammary carcinomas.

Biopsy, Needle↗
PubMed1992

Expression of mitoses per thousand cells and cell density in breast carcinomas: a proposal.

A method of standardizing mitotic counts is described. This provisional approach, which expresses mitoses as a percentage of breast cancer cells present, holds the promise of facilitating interlaboratory agreement as well as providing a measure of tumor cellularity, probably an independent prognostic indicator in its own right. We suggest that this approach or one similar to it will maximize the evaluation and quantitation of proliferative activity from routinely available histologic material. Furthermore, the method is accomplished with little added effort beyond the customary histologic evaluation.

Breast Neoplasms↗
PubMed1992

Primitive neuroepithelial tumors with vermiform processes (filiform neuroepithelial tumors). Immunocytochemical and ultrastructural study of 2 cases.

Two unique, poorly-differentiated neuroepithelial tumors are described, one in a 35-year-old woman with an anterior mediastinal tumor and one in a 71-year-old woman with a left femoral mass. Immunocytochemical stains demonstrated Neuron specific enolase in both tumors and Chromogranin in one. Electron microscopy showed the cells of both neoplasms to contain abundant, thick, vermiform, organelle-free processes, previously described solely in large cell lymphomas. Rare dense-core granules were present, and very few processes were suggestive of neurites. These observations enlarge the spectrum of poorly differentiated neuroepithelial tumors.

Adult↗