A 65-year-old woman presents with a palpable, mobile mass in the 2 o’clock position of the right breast. Ultrasound shows a circumscribed, homogenous, hypoechoic 2.3 cm mass. Needle core biopsy shows short fascicles of proliferating spindle cells with bland oval nuclei, background of stromal collagen, foci of adipocytes, and patchy perivascular lymphocytic infiltrate. Immunohistochemical studies reveal the proliferating cells are strongly desmin, ER, PR, and vimentin positive with negative staining for p63, CK5, CD34, CD68, SMA, S100, and HMB-45.
The correct answer is ...
The correct answer is: myofibroblastoma.
A myofibroblastoma is a benign mammary stromal tumor, which can present as a slow-growing, painless mass (1). A myofibroblastoma is composed of fibroblasts and myofibroblasts. The epithelial and myoepithelial cells are not involved (2).
While myofibroblastomas can grow as large as 15 cm in diameter, most are noted to be less than 3 cm (1). Grossly, myofibroblastomas are well-circumscribed, unencapsulated masses with rubbery cut surfaces (2). Microscopic examination reveals bland, spindled cells in short, intersecting fascicles with thick collagen bundles woven throughout (1). The mitotic activity of a myofibroblastoma is minimal (3). Mature adipose tissue may be present.
Immunohistochemical studies are positive for desmin, CD34, ER, PR, and AR. A majority (70%-80%) of cases will show a loss of RB1 expression due to a 13q14 deletion identified by fluorescent in situ hybridization (FISH) studies (1).
Myofibroblastomas have a good prognosis. After surgical resection, myofibroblastomas do not tend to recur. It is thought that the etiology of myofibromas is hormone-based, with most cases presenting in elderly males and post-menopausal females (2).
The clinical presentation of this case combined with the histomorphology and staining pattern is compatible with this diagnosis.
Invasive lobular carcinoma
Invasive lobular carcinoma generally presents with a palpable breast mass and radiologic findings of a spiculated mass. Grossly, invasive lobular carcinoma appears as an ill-defined lesion. The classic morphology shows proliferative, discohesive cells that invade through the breast stroma in a single-file linear pattern (4). The lesional cells show round-to-ovoid nuclei, a thin rim of cytoplasm, and occasional cytoplasmic inclusions (4, 5). Invasive lobular carcinoma is noted for the loss of E-cadherin expression, most commonly due to the CDH1 gene mutations, causing the lesional cells to become discohesive and display the characteristic invasive pattern (6).
Immunohistochemistry for invasive lobular carcinoma will be positive for ER, PR (about 70%), and negative for E-cadherin (1).
Metaplastic spindle cell carcinoma
Metaplastic carcinoma is actually a group of invasive breast carcinomas with neoplastic epithelial differentiation toward squamous or other mesenchymal components (1). This includes a spindle cell carcinoma displaying atypical, elongated spindle cells with moderate to high cytologic atypia and associated inflammation (7). Metaplastic spindle cell carcinoma tends to present in advanced stages in association with DCIS, and carries a poor prognosis (1, 7).
Immunohistochemistry studies show positivity for p63, high molecular weight keratins, and AE1/AE3. The proliferating cells will be negative for ER, PR, HER2 (triple negative), desmin, and CD34 (7).
Nodular fasciitis is a benign proliferation of fibroblast/myofibroblast cells. Nodular fasciitis tends to be a rapidly growing tumor, over the span of several weeks, ultimately becoming self-limiting over the course of a few months (8). Grossly, nodular fasciitis appears as a well-circumscribed encapsulated mass. The morphology of nodular fasciitis shows bland-appearing myoblasts or fibroblasts with a mixture of myxoid or collagen stroma, varied cellularity, brisk mitotic activity, and increased vasculature with extravasated red blood cells (9).
Immunophenotype of nodular fasciitis will be SMA positive with focal desmin expression while being negative for cytokeratin, CD34, S100, and beta-catenin.(1)
Rachel Horton, D.O.
Resident, Anatomic and Clinical Pathology
Charles Sturgis, M.D.
Senior Associate Consultant, Anatomic Pathology
Professor of Laboratory Medicine and Pathology
Mayo Clinic College of Medicine and Science