Sue A. Bartow

Prevalence of benign, atypical, and malignant breast lesions in populations at different risk for breast cancer. A forensic autopsy study

A forensic autopsy series of 519 women more than 14 years old was studied for prevalence of benign, atypical, and occult malignant breast lesions. The women included Anglos (non‐Hispanic whites), Hispanics, and American Indians from New Mexico and Eastern Arizona. These three ethnic/racial groups are at markedly different risk for the development of breast cancer (Anglo 89 of 100,000) women per year, Hispanic 45.5, and American Indian 24.9. There were striking ethnic/racial and age‐related differences in both the prevalence and magnitude of all forms of nonproliferative and proliferative fibrocystic disease. The various subsets of fibrocystic disease were highly associated with each other. Such lesions as apocrine metaplasia, sclerosing adenosis, and lobular microcalcification showed as much difference according to ethnic/racial background and age as the more common cystic change and duct epithelial hyperplasia. Atypical lobular and ductal hyperplasia, carcinoma fit situ, and occult invasive carcinoma were uncommon and also occurred in ethnic/racial groups in a pattern that parallels the cancer risk in those groups.

Comparative efects of ischemia, bacteria, and substrate on the pathogenesis of intestinal necrosis

This study was undertaken to evaluate the relative contribution of ischemia, bacteria, and luminal substrate, the pathogenetic components of necrotizing enterocolitis (NEC), to the development of intestinal necrosis. Sprague-Dawley rats, either germ-free (No. = 25) or conventionally colonized (No. = 20) underwent laparotomy. Isolated ileal segments were created, two per rat. Ischemia was produced in one segment by application of a microaneurysm clip; the other segment served as a control. Segments were injected with 1 mL of either normal saline, dilute Similac formula, or standard formula. Groups were as follows: Group I (germ-free), received saline; Group II (germ-free), dilute formula; Group III (germ-free), standard formula; Group IV (conventional), saline; Group V (conventional), dilute formula; Group VI (conventional), standard formula. At 48 hours, the rats were evaluated for survival, gross bowel integrity, histologic severity of necrosis (graded 0 to 4+), and bacteriology. Gross analysis of bowel integrity showed no lesions in the ischemic segments of the germ-free rats (Groups I, II, and III) and necrosis in 75% of conventionally colonized animals (Groups IV, V, and VI; P less than 0.001). Microscopic necrosis was more common (P less than 0.001) in ischemic segments of conventional rats than in ischemic segments of germ-free rats. There was no difference in necrosis attributable to ischemic time or to the presence of either standard or dilute formula. Of the three pathogenetic factors evaluated, the presence of bacteria was most crucial to the development of bowel necrosis in this model. Improved treatment and prevention of NEC may depend upon suppression and/or modification of the gut flora.

Dense breast stromal tissue shows greatly increased concentration of breast epithelium but no increase in its proliferative activity

IntroductionIncreased mammographic density is a strong risk factor for breast cancer. The reasons for this are not clear; two obvious possibilities are increased epithelial cell proliferation in mammographically dense areas and increased breast epithelium in women with mammographically dense breasts. We addressed this question by studying the number of epithelial cells in terminal duct lobular units (TDLUs) and in ducts, and their proliferation rates, as they related to local breast densities defined histologically within individual women.MethodWe studied deep breast tissue away from subcutaneous fat obtained from 12 healthy women undergoing reduction mammoplasty. A slide from each specimen was stained with the cell-proliferation marker MIB1. Each slide was divided into (sets of) areas of low, medium and high density of connective tissue (CT; highly correlated with mammographic densities). Within each of the areas, the numbers of epithelial cells in TDLUs and ducts, and the numbers MIB1 positive, were counted.ResultsThe relative concentration (RC) of epithelial cells in high compared with low CT density areas was 12.3 (95% confidence interval (CI) 10.9 to 13.8) in TDLUs and 34.1 (95% CI 26.9 to 43.2) in ducts. There was a much smaller difference between medium and low CT density areas: RC = 1.4 (95% CI 1.2 to 1.6) in TDLUs and 1.9 (95% CI 1.5 to 2.3) in ducts. The relative mitotic rate (RMR; MIB1 positive) of epithelial cells in high compared with low CT density areas was 0.59 (95% CI 0.53 to 0.66) in TDLUs and 0.65 (95% CI 0.53 to 0.79) in ducts; the figures for the comparison of medium with low CT density areas were 0.58 (95% CI 0.48 to 0.70) in TDLUs and 0.66 (95% CI 0.44 to 0.97) in ducts.ConclusionBreast epithelial cells are overwhelmingly concentrated in high CT density areas. Their proliferation rate in areas of high and medium CT density is lower than that in low CT density areas. The increased breast cancer risk associated with increased mammographic densities may simply be a reflection of increased epithelial cell numbers. Why epithelium is concentrated in high CT density areas remains to be explained.

Age and race related changes in mammographic parenchymal patterns

The relationship between breast parenchymal patterns and age was examined in a nonselected, nonreferred group. The three major racial‐ethnic subgroups represented have markedly different incidences of breast cancer, with Anglos (nonHispanic caucasians), Hispanics, and American Indians having higher to lower incidence rates of breast cancer, respectively. Mammograms were performed in 519 victims of nonhospital, nonnatural or unexplained deaths in New Mexico. The percentage of dense breast patterns (DY + P2) decreased with age for all groups. American Indian women showed a much earlier shift to a lower density parenchymal pattern than Anglo or Hispanic women. At older ages Indian women continued to have a slightly lower percentage of dense breast patterns than the other groups. The changes in breast parenchymal pattern with age and ethnic groups may reflect factors related to risk of breast cancer.

Intestinal obstruction due to colonic stricture following neonatal necrotizing enterocolitis.

After resolution of acute necrotizing enterocolitis (NEC), six of 31 surviving infants (19%) developed late ischemic stricture of the colon. Stricture occurred after both medical and surgical treatment for NEC, and in both functional and defunctionalized bowel. In medically-treated infants, the symptoms of intestinal obstruction usually began six to eight weeks after NEC. Surgically-treated infants developed asymptomatic strictures distal to an enterostomy. Barium enema was the appropriate diagnostic study for both groups. Operative management consisted of segmental colonic resection with frequent use of enterostomy. On histopathologic examination, resected strictures showed a spectrum of the reparative process after intestinal ischemia, ranging from obliterative scar to near-normal colon. Because delayed diagnosis led to the death of one of our infants, we recommend a barium enema for early diagnosis of stricture about six weeks after NEC, whether initial treatment was medical or surgical. In a recent infant, two colonic strictures were thus diagnosed and resected prior to development of symptoms of intestinal obstruction.

Radiographic microcalcification and parenchymal pattern as indicators of histologic “high‐risk” benign breast disease

Breast tissue from a forensic autopsy series of 486 women (15 to 98 years of age) was studied radiographically and by histologic sampling. Prevalence of Wolfe P2/Dy parenchymal patterns decreased with age. Radiographic nonvascular microcalcification and histologic presence of marked ductal epithelial hyperplasia and lobular microcalcification increased with age. Both of these histologic parameters of increased risk for breast cancer correlated with the presence of radiographic microcalcification and Wolfe P2/Dy parenchymal pattern. The predictive value of the radiographic parameters for presence of “high‐risk” proliferative fibrocystic change increased with age.

Expression of the estrogen receptor gene in developing and adult human breast

SummaryAlthough studies of the estrogen receptor gene abound in rodent models and breast cancer cell lines, little is known about expression of this gene in normal human breast. Information regarding the physiology of this genes expression is important if we are to elucidate abnormalities of the gene that may be involved in breast carcinogenesis. We evaluated levels of mRNA expression of the estrogen receptor (ER) gene and its protein product in a set of 89 breasts from clinically normal female infants, children, adolescents, and adult premenopausal and post-menopausal women. mRNA expression of the gene varied with the hormonal status. Relatively higher levels of gene transcripts were found in breasts of peri-menarchal girls, women in the luteal phase of the menstrual cycle, and in those with fibrocystic change. Higher levels were also occasionally found in breasts of infants and in most pre-adolescent children. Lower levels were seen in breasts of women in the follicular phase of the menstrual cycle, during pregnancy, and after menopause. Nuclear protein staining was common in breasts of normal children and peri-menarchal adolescents, and in post-menopausal atrophic breasts. Nuclear ER protein was infrequently detected in reproductive aged womens breasts, but was more often seen in follicular than in luteal menstrual phase or pregnant breast. ER protein was more frequently seen in post-menopausal than in pre-menopausal breasts with fibrocystic change. The results fit a model in which circulating levels of estrogen are inversely related to levels of mRNA transcribed from the estrogen receptor gene in normal physiologic states. Abnormally high levels of gene transcription may occur in some cases of fibrocystic change.

Intralobar pulmonary sequestration: A clinical and pathological spectrum

Pulmonary sequestration is a mass of abnormal pulmonary tissue that does not communicate with the tracheobronchial tree and is supplied by an anomalous systemic artery. Whereas extralobar sequestration is clearly congenital, intralobar sequestration, which frequently presents in older children with pathological findings showing acute and chronic inflammation, may have an acquired origin secondary to frequent infections. Several large autopsy series support an acquired etiology of intralobar sequestration. Four cases of intralobar sequestration are presented that demonstrate a spectrum of inflammatory change that support its congenital, rather than acquired origin. Case 1 was a newborn who presented with tachypnea and a right lower lobe density. Resection at 3 weeks of age showed no inflammation in the sequestration specimen. Case 2 presented as a newborn infant with congestive heart failure. Pulmonary sequestration was confirmed by arteriogram. Resection at 3 months of age showed chronic inflammation. Case 3 presented at 7 months of age with chronic pneumonia. The resected specimen demonstrated moderately severe acute and chronic inflammation. Case 4 presented as a 6 year old. The operative specimen showed extensive bronchiectatic changes with marked acute and chronic inflammation. These cases support the congenital origin of intralobar sequestration and suggest a temporal progression from no inflammation to severe acute and chronic inflammation.

Debridement of Periumbilical Necrotizing Fasciitis: Importance of Excision of the Umbilical Vessels and Urachal Remnant

The operation of a neonate with periumbilical necrotizing fasciitis consisted of (1) excision of infected skin, fat, and fascia (including the umbilicus); (2) a limited laparotomy, with ligation and excision of the umbilical vessels and urachal remnant; and (3) placement of a temporary silastic patch over the central abdominal defect. Pathological sections confirmed the spread of infection along the vessels and urachal remnant. Excision of the vessels and urachal remnant may be crucial to survival from periumbilical necrotizing fasciitis.

Balloon catheter dilatation of focal intestinal strictures following necrotizing enterocolitis

Dilatation with a balloon catheter was successfully employed for 9 focal intestinal strictures which occurred in 5 infants following necrotizing enterocolitis. Eight of the 9 strictures were located in defunctionalized colon distal to an enterostomy; no infant had clinical intestinal obstruction. Because the dilatation achieved distal patency, subsequent closure of the enterostomy was accomplished without a formal laparotomy. The balloon dilatation technique may be valuable in the management of focal strictures that are not causing clinical intestinal obstruction.