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We determined temporal bone anatomy in patients with unilateral attic cholesteatoma. We compared the affected and normal ears of ten patients with unilateral attic cholesteatoma using three-dimensionally reconstructed high-resolution computed tomography images of the temporal bone. We determined the eustachian tube angle, eustachian tube length, sizes of the tympanic orifice of the eustachian tube, the pars flaccida, and the mastoid cavity, and distances of the pars flaccida and the tympanic orifice of the eustachian tube from the epitympanic roof. No significant differences were found between the normal and affected ears with regard to the size of the eustachian tube orifice, eustachian tube length or distances of the pars flaccida and the tympanic orifice of the eustachian tube from the epitympanic roof. By contrast, the mastoid cavity and the eustachian tube angle were significantly larger in the normal ears than in the affected ears [mean, 6.99 cm(3) (S.D.,4.9 cm(3)) vs. 1.28 cm(3) (0.81 cm(3)) and 16.7° (4.12°) vs. 13.89° (5.30°), respectively]. The pars flaccida was significantly smaller in the normal ears [1.07 cm (0.31 cm)] than in the affected ears [2.19 cm (0.77 cm)]. The inherent anatomy of the eustachian tube may be particularly important in the formation of attic cholesteatomas.

Expression of the PMLRARα fusion dominant-negative oncogene in the epidermis of transgenic mice resulted in spontaneous skin tumors attributed to changes in both the PML and RAR pathways [1]. To determine the contribution of PML to skin tumor susceptibility, transgenic mice were generated on an FVB/N background, that overexpressed the human PML protein in epidermis and hair follicles under the control of the bovine keratin 5 promoter. PML was highly expressed in the epidermis and hair follicles of these mice and was also increased in cultured keratinocytes where it was confined to nuclear bodies. While an overt skin phenotype was not detected in young transgenic mice, expression of keratin 10 (K10) was increased in epidermis and hair follicles and cultured keratinocytes. As mice aged, they exhibited extensive alopecia that was accentuated on the C57BL/6J background. Following skin tumor induction with 7, 12-dimethylbenz[a]anthracene (DMBA) as initiator and 12-O-tetradecanoylphorbol-13-acetate (TPA) as promoter, papilloma multiplicity and size were decreased in the transgenic mice by 35%, and the conversion of papillomas to carcinomas was delayed. Cultured transgenic keratinocytes underwent premature senescence and upregulated transcripts for p16 and Rb but not p19 and p53. Together, these changes suggest that PML participates in regulating the growth and differentiation of keratinocytes that likely influence its activity as a suppressor for tumor development.