Cell clusters overlying focally disrupted mammary myoepithelial cell layers and adjacent cells within the same duct display different immunohistochemical and genetic features: implications for tumor progression and invasion

INTRODUCTION: Our previous studies detected focal disruptions in myoepithelial cell layers of several ducts with carcinoma in situ. The cell cluster overlying each of the myoepithelial disruptions showed a marked reduction in or a total loss of immunoreactivity for the estrogen receptor (ER). This is in contrast to the adjacent cells within the same duct, which were strongly immunoreactive for the ER. The current study attempts to confirm and expand previous observations on a larger scale. METHODS: Paraffin sections from 220 patients with ER-positive intraductal breast tumors were double immunostained with the same protocol previously used. Cross-sections of ducts lined by ≥ 40 epithelial cells were examined for myoepithelial cell layer disruptions and for ER expression. In five selected cases, ER-negative cells overlying the disrupted myoepithelial cell layer and adjacent ER-positive cells within the same duct were separately microdissected and assessed for loss of heterozygosity and microsatellite instability. RESULTS: Of the 220 cases with 5698 duct cross-sections examined, 94 showed disrupted myoepithelial cell layers with 405 focal disruptions. Of the 94 cases, 79 (84%) contained only ER-negative cell clusters, nine (9.6%) contained both ER-negative and ER-positive cell clusters, and six (6.4%) contained only ER-positive cell clusters overlying disrupted myoepithelial cell layers. Of the 405 disruptions, 350 (86.4%) were overlain by ER-negative cell clusters and 55 (13.6%) were overlain by ER-positive cell clusters (P < 0.01). Microdissected ER-negative and ER-positive cells within the same duct from all five selected cases displayed a different frequency or pattern of loss of heterozygosity and/or microsatellite instability at 10 of the 15 DNA markers. CONCLUSIONS: Cells overlying focally disrupted myoepithelial layers and their adjacent counterparts within the same duct displayed different immunohistochemical and molecular features. These features potentially represent an early sign of the formation of a biologically more aggressive cell clone and the myoepithelial cell layer breakdown possibly associated with tumor progression or invasion

Osseous involvement in calcific tendinitis: a retrospective review of 50 cases

The purpose of this study was to describe the spectrum of radiologic and pathologic manifestations of calcific tendinitis involving bone. We retrospectively reviewed 50 cases of calcific tendinitis involving underlying bone. Clinical data reviewed included patient age and sex and lesion location. Images reviewed included radiographs (n = 44), CT scans (n = 13), MRIs (n = 16), and bone scintigrams (n = 13). Radiologic examinations were evaluated for the presence of cortical erosion, periosteal reaction, and marrow extension. Pathology confirmation was available in 37 cases. The average age of patients was 50 years (range, 16-82 years), with 29 female patients (58%). Calcific tendinitis with associated bone involvement was seen most commonly in the femur (40%) and the humerus (40%). Concretions were most commonly solid-appearing (50%). Cortical erosion was the most common manifestation of osseous involvement (78% of cases). Marrow involvement was shown in 18 (36%) of 50 cases. Marrow extension was most commonly seen in the lesser and greater tuberosities of the humerus, which accounted for 61% (11/18) of cases. Focal increased radionuclide uptake was seen in 13 (100%) of 13 cases. Calcific tendinitis presenting with osseous destruction, marrow changes, and soft-tissue calcifications may be confused with neoplasm both radiologically and pathologically. Recognition of the atypical presentation of this common disease may prevent unnecessary biopsy