Elsevier

Human Pathology

Volume 58, December 2016, Pages 54-61
Human Pathology

Original contribution
Characterization of the leiomyomatous variant of myofibroblastoma: a rare subset distinct from other smooth muscle tumors of the breast,☆☆

https://doi.org/10.1016/j.humpath.2016.07.018Get rights and content

Summary

Mammary myofibroblastoma is a benign spindle cell tumor that can show variable morphologic patterns and lines of differentiation. Myofibroblastoma belongs to a family of CD34-positive tumors with similar morphology that show a deletion of 13q14, which includes RB1 and FOXO1A genes. A subset of these tumors demonstrates distinct smooth muscle differentiation. We aimed to characterize 4 cases of the leiomyomatous variant of myofibroblastoma arising in the breast by clinicopathological, immunohistochemical, and molecular means. All 4 examples arose in women aged 41 to 62 years (median, 46.5 years). Tumors ranged in size from 1.7 to 2.5 cm (median, 2.2 cm). Morphologically, all tumors were characterized by bundles of smooth muscle cells with elongated cigar-shaped nuclei and eosinophilic cytoplasm. All 4 tumors showed diffuse positive staining with desmin, caldesmon, smooth muscle actin, estrogen receptor, and Bcl-2. CD34 staining was diffusely positive in 2 cases, was weak and patchy in 1 case, and was negative in 1 case. Two (50%) of 4 tumors showed deletion of RB1 by fluorescence in situ hybridization. Loss of Rb staining was seen in 1 tumor with RB1 deletion by fluorescence in situ hybridization, whereas intact Rb staining was observed in 1 nondeleted case studied. In conclusion, this rare variant of myofibroblastoma is a distinct subgroup of tumors among an already uncommon category of (smooth muscle) breast tumors. Some reported examples of “parenchymal leiomyoma” may represent the leiomyomatous variant of myofibroblastoma.

Introduction

Tumors of smooth muscle derivation are exceedingly rare in the breast, largely in part due to the absence of indigenous smooth muscle in this anatomic site, with the exception of the nipple. Still, reports of benign smooth muscle dominant tumors such as leiomyomas and myoid (or “muscular”) hamartomas have been described in the literature [1], [2], [3], [4], [5], [6], [7], [8], [9], [10], [11]. In addition, other benign mammary entities are known to occasionally demonstrate smooth muscle differentiation to varying degrees such as fibroadenomas, phyllodes tumors, and myofibroblastomas. Because of the rarity of these tumors, a critical review of benign mammary smooth muscle tumors has not been performed. This invariably perpetuates the ambiguity of not only classifying them in practice but also understanding them as part of distinct subgroup possessing specific clinical, morphologic, immunohistochemical, and/or molecular features.

Mammary myofibroblastoma is a benign stromal tumor characterized by bland spindle cells growing in fascicles with intervening bands of collagen and variable amounts of fat. Various morphologic variants have been described, including cellular, infiltrating, epithelioid, and myxoid, among others, and some show heterologous differentiation in the form of mature chondroid, osseous, or leiomyomatous components [12], [13]. In recent years, myofibroblastoma and morphologically similar nonmammary CD34-positive tumors including (extra) mammary-type myofibroblastoma, spindle cell lipoma, and cellular angiofibroma of vulva have been found to share a deletion of 13q14, which includes RB1 and FOX01A genes [14], [15], [16], [17], [18]. In reported cases of mammary myofibroblastomas specifically, deletion of 13q14 has been found in 78.5% (11/14) of examples studied [14], [16], [18], [19], [20], [21]. Identifying this common deletion in CD34-positive tumors motivated us to better characterize a rare variant of myofibroblastoma that can be nonimmunoreactive for CD34—considered a hallmark of mammary myofibroblastomas, which in its absence may pose a diagnostic pitfall. Moreover, we aimed to better understand how the leiomyomatous variant of myofibroblastomas fits in the overall context of benign smooth muscle tumors in the breast.

Section snippets

Case selection

This study was conducted under an institutional review board—approved protocol. Four cases of mammary myofibroblastoma with leiomyomatous differentiation were identified from our surgical pathology and breast consultation files. Slides were reviewed by 2 breast pathologists (T. D., S. S.). Clinical data were obtained from electronic patient records and from submitting pathologists and clinicians.

Immunohistochemistry

Immunohistochemical staining was accomplished using the Bond III Autostainer (Leica Microsystems,

Results

A summary of the clinicopathological, immunohistochemical, and cytogenetic features of studied cases is outlined in Table 2.

Discussion

After its initial characterization nearly 3 decades ago by Wargotz et al [13], several morphologic variants of mammary myofibroblastoma have been described [12], [13]. A relatively less common variant of mammary myofibroblastoma is one that demonstrates smooth muscle differentiation. The differential diagnosis of leiomyomatous myofibroblastoma includes other benign tumors such as leiomyoma, myoid hamartoma, and fibroepithelial tumors with prominent stromal myoid metaplasia. The list of

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    Disclosures: None.

    ☆☆

    Conflicts of interest: None.

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