Melanocytic “ball-in-mitts” and “microalveolar structures” and their role in the development of cellular blue nevi

Abstract 

To test the hypothesis of whether cellular blue nevi (CBN) may originate from “ordinary” compound and dermal nevi, a total of 275 melanocytic nevi including 59 CBN, 34 ordinary blue nevi, 87 combined nevi (including 43 so-called clonal nevi), 35 deep penetrating nevi, and 60 ordinary compound and dermal nevi (30 of each) were studied for the presence of so-called ball-in-mitts and microalveolar structures. A ball-in-mitts structure was defined as a single centrally placed melanocyte with a round to oval nucleus (the “ball” cell) and a clear, dusty, or pigmented cytoplasm encircled by a single dendritic cell (the “mitt” cell) with an oval to spindle-shaped nucleus and slender bipolar processes containing melanin and surrounding at least one fourth of the ball's diameter. A microalveolar structure was defined as a group of 2 to 10 centrally placed melanocytes with round to oval nuclei and clear, dusty, or pigmented cytoplasm (balls) surrounded by one or more cells (mitts) with spindle-shaped nuclei and slender bipolar processes containing melanin. Microscopically, ball-in-mitt and microalveolar structures were detected in all types of nevi studied, with the highest incidence in combined nevi (82%), CBN (76%), and ordinary “nonblue” nevi (73%). In CBN, ball-in-mitts and microalveolar structures tended to be located in the deeper portion of the lesions, whereas in ordinary nonblue nevi, they were most often found superficially, just below the epidermis; in clonal nevi, these structures were often confined to the “clonal” parts. Immunohistochemically, ball-in-mitts and microalveolar structures were positive for HMB45. Ultrastructurally, the balls tended to have round to oval nuclei, whereas the mitts possessed oval, elongated to spindled nuclei. Melanosomes were found in various stages in the cells of both structures. The cytoplasm of the mitts typically formed elongated polar processes, sometimes with club-like widenings at the ends, completely or partially encircling the balls. In the microalveolar structures, the adjacent cells forming the mitts surrounded the ball cells like a chain. Our study suggests that some or even most cases of CBN may evolve from ordinary nonblue nevi. This process may involve several steps and is probably reflected by the appearances of combined nevi, deep penetrating nevi, and CBN. These nevi often show a morphological overlap, and ball-in-mitts and microalveolar structures found in various stages of their development seem to greatly account for this overlap.

Keywords: Cellular blue nevus, Blue nevus, Combined nevus, Clonal nevus, Deep penetrating nevus, Melanoma