Recent molecular studies have indicated that ductal carcinoma in situ (DCIS)-associated myoepithelial cells (MECs) show differences from MECs in normal breast tissue. Such alterations may influence the progression of DCIS to invasive cancer. The purpose of this study was to investigate further phenotypic alterations in DCIS-associated MECs. Paraffin sections of 101 cases of DCIS (56 without and 45 with associated invasive carcinoma) were immunostained for 7 MEC markers: smooth muscle actin, smooth muscle myosin heavy chain (SMMHC), calponin, p63, cytokeratin (CK) 5/6, CD10, and p75. In each case, the distribution and intensity of staining for each marker in DCIS-associated MECs was compared with that in MECs surrounding normal ductal-lobular structures on the same slide. In 85 cases (84.2%), DCIS-associated MECs showed decreased expression of one or more MEC markers when compared with normal MECs. The proportion of cases that showed reduced expression was 76.5% for SMMHC, 34.0% for CD10, 30.2% for CK5/6, 17.4% for calponin, 12.6% for p63, 4.2% for p75, and 1% for smooth muscle actin. Reduced MEC expression of SMMHC was significantly more frequent in high grade than in non-high-grade DCIS (84.8% vs. 61.5% of cases, P=0.01). We conclude that DCIS-associated MECs show immunophenotypic differences from MECs surrounding normal mammary ductal-lobular structures. The biologic significance of this remains to be determined. However, these results indicate that the sensitivity of some MEC markers is lower in DCIS-associated MECs than in normal MECs. This observation should be taken into consideration when selecting MEC markers to help distinguish in situ from invasive breast carcinomas.

Wolfram syndrome or DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy and deafness) is a neurodegenerative disorder characterized by diabetes mellitus and optic atrophy as well as diabetes insipidus and deafness in many cases. We report the post-mortem neuropathologic findings of a patient with Wolfram syndrome and correlate them with his clinical presentation. In the hypothalamus, neurons in the paraventricular and supraoptic nuclei were markedly decreased and minimal neurohypophyseal tissue remained in the pituitary. The pontine base and inferior olivary nucleus showed gross shrinkage and neuron loss, while the cerebellum was relatively unaffected. The visual system had moderate to marked loss of retinal ganglion neurons, commensurate loss of myelinated axons in the optic nerve, chiasm and tract, and neuron loss in the lateral geniculate nucleus but preservation of the primary visual cortex. The patient’s inner ear showed loss of the organ of Corti in the basal turn of the cochleae and mild focal atrophy of the stria vascularis. These findings correlated well with the patient’s high-frequency hearing loss. The pathologic findings correlated closely with the patient’s clinical symptoms and further support the concept of Wolfram syndrome as a neurodegenerative disorder. Our findings extend prior neuropathologic reports of Wolfram syndrome by providing contributions to our understanding of eye, inner ear and olivopontine pathology in this disease.

Myoepithelial cells surrounding spaces involved by ductal carcinoma in situ show phenotypic differences from normal myoepithelial cells. Myoepithelial cells are also present around entrapped glandular spaces in benign sclerosing lesions of the breast, but the immunophenotype of these myoepithelial cells has not been characterized. We evaluated myoepithelial cell immunophenotype in 48 benign sclerosing lesions using antibodies to 7 myoepithelial cell markers (smooth muscle actin, calponin, smooth muscle myosin heavy chain, p63, CD10, cytokeratin 5/6, and p75). Staining intensity of the myoepithelial cells surrounding entrapped glands was compared with that of myoepithelial cells surrounding normal ducts and lobules on the same section. When compared with normal breast ducts and lobules on the same slide, myoepithelial cells associated with benign sclerosing lesions showed reduced expression of cytokeratin 5/6 in 31.8% of cases, smooth muscle myosin heavy chain in 20.9%, CD10 in 15.2%, p63 in 9.3%, and calponin in 6.4%. In 15.9% of cases, myoepithelial cells surrounding entrapped glands showed complete absence of staining for cytokeratin 5/6. None of the cases showed reduced myoepithelial cell expression of smooth muscle actin or p75. The proportion of radial scars/complex sclerosing lesions and sclerosing adenosis with reduced expression was significantly different for CD10 (26.9% and 0% respectively; P=0.01) and p63 (17.4% and 0% respectively; P=0.05). We conclude that myoepithelial cells associated with benign sclerosing lesions of the breast may show immunophenotypic differences from normal myoepithelial cells. This needs to be taken into consideration when selecting myoepithelial markers to help distinguish benign sclerosing lesions from invasive breast cancer.