Distinctive Eosinophilic Cytoplasmic Inclusion Bodies in Melanocytic Nevi: An Immunohistochemical and Ultrastructural Study.
Wonwoo Shon, David A Wada, Lawrence E Gibson, Thomas J Flotte, Bernd W Scheithauer. Mayo Clinic, Rochester, MN
Background: In 2004, Gottlieb noted cytoplasmic eosinophilic inclusion bodies in occasional melanocytes of both congenital and acquired nevi, stating that they may represent degenerative changes in an organelle, presumably melanosomes. Despite their distinctive features, no further pathologic findings have been formally reported. To our knowledge these inclusion bodies have not previously been described in Spitz nevi.
Design: Skin biopsies from 4 patients with known diagnoses of compound melanocytic nevus with congenital features (case No. 1, 2, and 3) or atypical Spitz nevus (case No. 4), all containing cytoplasmic eosinophilic inclusion bodies, were selected for histochemical, immunohistochemical and ultrastructural study. An additional 20 cases of malignant melanoma were examined for the presence of these distinctive cytoplasmic inclusions.
Results: In H&E-stained sections, the degree of density and eosinophilia of the cytoplasmic inclusion bodies varied with their size, smaller inclusions being more pale and homogenous, whereas larger inclusions showed a discernable dense core. Inclusions tended to be within multinucleate melanocytes featuring abundant vacuolated cytoplasm. They were ubiquitin-immunopositive and negative for tyrosinase, keratin, and vimentin. A panel of histochemical stains (PAS, Fontana, and Congo Red) showed no reactivity. Ultrastructurally, the inclusion bodies were nonmembrane-bound, ranged in size 4 to 7 µm and consisted of radiating filamentous structures with or without an electron dense core. Electron probe x-ray microanalysis showed no significant peaks when compared with tissue background. None of the malignant melanomas studied demonstrated inclusion bodies resembling those encountered in the present cases.
Conclusions: The inclusion bodies observed in our study do not resemble other cytoplasmic inclusion bodies histologically or ultrastructurally observed in melanocytic lesions. Being nonmembrane-bound, filamentous structure with or without an electron dense core, they were unrelated normal of degenerate melanosomes. We postulate they may be related to dysfunction of ubiquitin-mediated protein degradation occurring in melanocytes. Further studies focusing upon the composition and evolution of the inclusions may shed light upon their clinical significance and perhaps establish their utility in the differential diagnosis of melanocytic nevi and malignant melanoma.
Tuesday, March 1, 2011 9:30 AM
Poster Session III # 124, Tuesday Morning