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22 February 2024 - Case of the Month #536

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Thanks to Drs. Victoria Jones and Kristen Muller, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, USA for contributing this case and discussion and to Dr. Julie Jorns, Medical College of Wisconsin, Milwaukee, Wisconsin, USA for reviewing the discussion.

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Case of the Month #536

Clinical history:
A 55 year old woman underwent a breast needle core biopsy after routine mammography that showed a slight interval size increase of a subcentimeter nodule.

Microscopic images:

What is your diagnosis?

Click here for diagnosis, test question and discussion:

Diagnosis: Myofibroblastoma

Test question (answer at the end):
Which genetic alteration occurs in myofibroblastoma?

  1. 13q14 deletion
  2. MYC amplification
  3. MYH9-USP6 fusion
  4. PIK3CA mutation





Mammary type myofibroblastoma is a benign spindle cell tumor of the breast and soft tissue characterized by 13q14 alterations leading to loss of Rb1 protein expression. These tumors belong to a family of CD34 positive neoplasms with similar morphology and deletion of 13q14 including spindle cell lipomas, cellular angiofibromas and superficial acral fibromyxomas. In the breast, myofibroblastomas typically occur in men and postmenopausal women and present as a painless, slow growing, mobile mass. Radiographically, myofibroblastomas appear as well circumscribed, lobulated, homogenous, solid masses devoid of microcalcifications. They frequently measure 1 - 4 cm and have a smooth, lobulated external surface and rubbery, gray to white, whorled, cut surface. Microscopically, myofibroblastomas are well circumscribed lesions composed of uniformly bland, short to elongated spindled cells arranged as short haphazard intersecting fascicles admixed with bands of hyalinized collagen with or without variable amounts of adipose tissue. Since first reported in 1987, several morphologic variants have been described, including collagenized or fibrous, cellular, infiltrative, myxoid, deciduoid, lipomatous, epithelioid and atypical variants. Immunohistochemical expression of desmin, CD34, ER, PR, AR, BCL2 and CD10 is typical for most myofibroblastomas. Rb is negative in the vast majority of myofibroblastomas owing to the underlying molecular abnormality of recurrent monoallelic loss of 13q14, which encompasses RB1 and FOXO1 loci. Importantly, myofibroblastomas lack expression of keratins, which is helpful in the workup of an epithelial neoplasm (i.e. invasive lobular carcinoma).

This case is an example of an epithelioid myofibroblastoma. In contrast to a conventional myofibroblastoma, the cells in an epithelioid myofibroblastoma are oval to polygonal and arranged in clusters, cords, groups or linear strands. They may show bi- or multinucleation, eccentrically placed nuclei, nucleoli and well defined cell borders. On core needle biopsy, areas of single file arrangement are seen which may mimic invasive lobular carcinoma. Helpful clues to avoid this consequential diagnostic pitfall include the presence of a well circumscribed border, the absence of mitotic figures and the notable intersecting collagen bundles. Immunohistochemical studies may be misleading, as myofibroblastomas and the vast majority of invasive lobular carcinomas are positive for ER and PR. Additional immunohistochemical workup, including CD34 and desmin (which should be negative in invasive lobular carcinomas) and keratins (which should be negative in myofibroblastomas) will aid in the correct diagnosis in difficult cases. One should also keep in mind the existence of CD34 deficient myofibroblastoma for which characteristic staining with other immunohistochemical markers will aid in diagnosis. Local excision is curative, as myofibroblastoma is a benign entity with no increased risk of recurrence or malignancy.

Arch Pathol Lab Med 2008;132:1813, Virchows Arch 2002;440:249, Am J Surg Pathol 1987;11:493, Am J Surg Pathol 2016;40:361, Histol Histopathol 2016;31:1, Breast J 2018;24:55

Test question answer:
A. 13q14 deletion. Myofibroblastoma harbors a recurrent monoallelic loss of the 13q14 region, which includes RB1. There is subsequent loss of RB1 on immunohistochemistry.

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