Fibroadenoma of the breast: analysis of associated pathological entities--a different risk marker in different age groups for concurrent breast cancer.

BACKGROUND: Fibroadenoma, one of the most common benign breast lesions, has a characteristic age-specific incidence and is associated with other pathological entities in 50% of cases. The clinical or imaging diagnosis of fibroadenoma may be erroneous, and in some cases is found to be invasive cancer. The clustering of such entities, their correlation with age, and the risk of synchronous breast malignancy are uncertain. OBJECTIVE: To explore the possibility of any significant clustering of fibroadenoma-associated benign breast diseases and to assess the possible risk of concomitant breast cancer. METHODS: We analyzed the pathological results of 147 women undergoing excisional biopsies for fibroadenoma diagnosed pre-operatively either by clinical examination and imaging (n = 17) or by radiology alone (n = 30). The inter-relationships among all entities associated with fibroadenoma were studied by hierarchical cluster analysis. The correlation of the various pathologies with the risk of invasive breast cancer in relation to the patient's age was also evaluated. RESULTS: Fibroadenoma-associated pathologies were found in 48% of the cases: sclerosing adenosis (23%), duct ectasia (17.7%), apocrine metaplasia (15.6%), florid fibrocystic disease (12.9%), duct papillomatosis (11.6%), infiltrating duct carcinoma (5.4%), duct carcinoma in situ (3.4%), and 1 case of lobular carcinoma in situ (0.6%). An orderly internal hierarchy and three significant clusters emerged: a) epithelial apocrine metaplasia, duct ectasia and sclerosing adenosis (similarity coefficients 16.0, 11.0 and 8.0 respectively); b) papillomatosis, florid fibrocystic disease and calcifications (similarity coefficients of 6.0, 4.0 and 2.0 respectively); and c) infiltrating duct carcinoma and duct carcinoma in situ (similarity coefficients of 1.8 and 1.6 respectively). Seven of the eight patients with breast cancer were older than 40 years. CONCLUSIONS: In about half of the cases fibroadenoma was associated with other pathological entities clustered in an orderly hierarchy. The rarity of synchronous breast cancer in the younger age group and its more common association with fibroadenoma in the older age groups dictate a different approach to each. The finding of fibroadenoma in women older than 40 indicates the need for surgical excision.

In vivo molecular imaging of met tyrosine kinase growth factor receptor activity in normal organs and breast tumors.

Molecular imaging techniques allow visualization of specific gene products and their physiological processes in living tissues. In this study, we present a new approach for molecular imaging of endogenous tyrosine kinase receptor activity. Met and its ligand hepatocyte growth factor scatter factor (HGF/SF), which mediate mitogenicity, tumorigenicity, and angiogenesis, were used as a model. HGF/SF and Met play a significant role in the pathogenesis and biology of a wide variety of human epithelial cancers and, therefore, may serve as potential targets for cancer prognosis and therapy. We have shown previously that in vitro activation of Met by HGF/SF increases oxygen consumption. In this study, we demonstrate that Met activation in vivo by HGF/SF alters the hemodynamics of normal and malignant Met-expressing tissues. Tumor-bearing BALB/C mice were i.v. injected with HGF/SF and imaged using magnetic resonance imaging (MRI) and Doppler ultrasound. Organs and tumors expressing high levels of Met showed the most substantial alteration in blood oxygenation levels as measured by blood oxygenation level depended (BOLD)-MRI. No significant alteration was observed in tumors or organs that does not express Met. In the liver, which expresses high levels of Met, MRI signal alteration of about 60% was observed. In the kidneys, signal alteration was approximately 30%, and no change was observed in muscles. The extent of MRI signal alteration was also in correlation with HGF/SF doses. Injection of 7 and 170 ng/g body weight resulted in signal alteration of 5% and 30%, respectively, in tumors. Doppler ultrasound measurements demonstrated that these MRI changes are at least partially attributable to altered blood flow. These hemodynamic alterations, measured by MRI and Doppler ultrasound, were used in this study for the molecular imaging of Met activity in vivo. This novel molecular imaging technique may be used for in vivo diagnosis, prognosis, and therapy of Met-expressing tumors.

The use of magnetic resonance imaging in the differential diagnosis between starch and fecal peritonitis.

Granulomatous peritonitis, caused by the starch from the surgeons' gloves, is a hypersensitivity reaction that can complicate abdominal surgery and mimic other causes of peritonitis. The diagnosis of this entity is difficult to make, and relies on a high index of suspicion. We suggest the use of magnetic resonance imaging to facilitate the diagnosis of this condition, based on an experimental animal model. 84 rats were subjected to laparotomy, and the abdominal cavity was exposed to either saline solution, talc solution, starch solution or fecal material by creating a cecal perforation. TI-weighted magnetic resonance images, with and without gadolinum enhancement, were taken after 3, 5 and 10 days. The animals were then sacrificed and the abdominal contents were evaluated both macroscopically and microscopically. Both talc and starch caused gross adhesions involving the entire abdominal viscera, and microscopy revealed signs of inflammation and fibrosis. Starch induced reactive granulomas. The adhesions in the cases of fecal peritonitis were confined to the area of the perforation. MR images of the starch peritonitis group was remarkable for a diffuse pathological process with enhancement of the omentum and the peritoneum after gadolinum injection. The MR readings of the fecal peritonitis group showed a localized process with no diffuse enhancement of the peritoneum. The striking differences between the magnetic resonance images of starch and fecal peritonitis in rats suggest that this modality is both sensitive and specific in diagnosing starch peritonitis in a rat model. Early non-invasive diagnosis of these separate entities would ease the establishment of the appropriate treatment. We are currently investigating the use of MRI imaging in suspected starch peritonitis in humans.