Mammary Myofibroblastoma: Case Report and Immunohistochemical Comparison with Stromal Hyperplasias Showing Bimodal CD34+ and Factor XIIIa+ Fibrohistiocytic Immunophenotype

Abstract

Normal inter- and intralobular mammary stroma has a “fibrohistiocytic” immunophenotype rich in primitive CD34+ dendritic fibroblasts accompanied by scattered Fac- tor XIIIa+ (FXIIIa+) histiocytes. Actin or desmin+ stromal myofibroblasts are not found in nondisease states. Mam-marry myofibroblastoma (M) is a stromal tumor, seen more commonly in males than in females, whose precise histo-genesis is uncertain. We compared a 2.8 cm brown lobulated benign M from the breast of a 72 year old man with 3 examples of male mammary hyperplasia (gynecomastia-G) and 6 examples of psudoangiomatous stromal hyperplasia (PASH) of the female breast to assess, with double labeling, myofibroblastic stromal differentiation, cell proliferation, hormone receptor status in indigenous stromal cell subsets. We used CD34, FXIIIa, desmin, alpha-smooth muscle actin estrogen (ER), progesterone (PR), and androgen (AR) receptors, and Ki-67 (MIB-1). The M had variably strong but widespread CD34 reactivity in 50–70% of the spindled cells and CD34 was weaker in plump atypical cells that were focally present. The CD34+ fibroblastic cells were diffusely admixed with 40–50% FXIIIa+ dendritic histiocytes. A subset of the CD34+ cells that included the more atypical cells were myofibroblasts that expressed actin (5%) and desmin (30%). The FXIIIa+ histiocytes were distinct from the CD34/actin/desmin+ cells by double staining. Most tumor cells (CD34 or FXIIIa+) expressed AR>PR>ER, and the MIB-1 index was 2%, included both CD34 and FXIIIa+ cells in the cycling fraction. Fibroblasts-G were CD34+ and only focally and weakly actin+, with small FXIIIa+ dendritic histiocytes. Fibroblasts in PASH were variably CD34+ and actin+, often with inverse reactivity. FXIIIa+ cells were 20–40% of PASH cells and were plump, vacuolated, and dendritic. M-like cellular areas in 1 PASH strongly expressed CD34, actin, and desmin PASH had generally weaker, more focal hormone receptor reactivity than M and M-like areas in PASH. We detected Ki-67+ cycling FXIIIa+ histiocytes along with the cycling fibroblasts in 2 PASH. We conclude that mammary stromal hyperplasias and M are composed of proliferating CD34+ fibroblasts and FXIIIa+ histiocytes. M>PASH>G in showing transition from the “resting” CD34+ fibroblast phenotype to actin or desmin+ myofibroblastic phenotype, often with inverse CD34 and actin expression. Accumulating evidence suggests that the numerous FXIIIa+ dendritic histiocytes probably modulate fibroblast spreading and adhesion, cytoskeletal organization, and matrix production. An as yet unknown role for hormonal control of myofibroblastic proliferations is also likely in view of increasing receptor expression and myoid differentiation. (The J Hitotechnol 21:335–342, 1998)