Myofibroblastoma of breast

Myofibroblastoma is a rare benign mesenchymal tumor of the breast that may present in various soft tissues and extramammary sites ¹, ². These various extramammary sites include the armpit, head, neck, tonsil, parotid gland, tongue, lung, paratesticular area, groin (inguinal area), vulva, vagina, popliteal fossa, soft tissues of retroperitoneum, abdominal wall, rectum, meninges, prostate, suprasellar area ³, ⁴, ⁵, ⁶, ⁷, ⁸, ⁹, ¹⁰, ¹¹. Although most of the reported myofibroblastoma cases were located in breast ¹², myofibroblastoma of breast is extremely rare, representing less than 1% of breast tumors ¹³.

The first case of breast myofibroblastoma was described in 1987 by Wargotz, Weiss, and Norris ¹⁴, myofibroblastoma typically presents as a slow growing, well circumscribed, solitary mass ranging from 1 cm to 4 cm in size. However, larger masses measuring up to 13 cm have also been reported ¹⁵. Although breast myofibroblastoma has been reported in adults of either gender, it is most frequently seen in older males and in postmenopausal women ¹⁴, however extramammary myofibroblastoma affect a wide age range including children ⁸.

Characteristically, myofibroblastomas present as a solitary, painless, firm, and freely mobile mass which grows slowly for several months or years ¹², ¹⁶.

Myofibroblastoma of breast mainly occurs in men between 25 and 87 years of age with 64 being the median ¹⁷; however, myofibroblastoma of breast also occurs in women in the age range of 25 to 80 years (mainly postmenopausal) ¹⁸, ¹⁹. Myofibroblastoma of breast commonly presents unilaterally near the nipple with no predilection for a particular breast quadrant. One case of bilateral myofibroblastomas has been reported in a 25-year-old female ²⁰.

Myofibroblastoma of breast follows an indolent course over months to years and often remains hidden until a firm, painless mass is noted clinically ³. The usual clinical presentation is a unilateral painless lump that is not adherent to overlying or underlying structures ³.

Asymptomatic myofibroblastoma of breast cases are often detected on routine screening mammograms in females, and incidentally detected on computed tomography scan in males.

The appearances of myofibroblastoma on imaging are nonspecific ¹⁵. Myofibroblastoma of breast appears on radiographic imaging as homogenous, lobulated, and lacking microcalcifications ³. On ultrasound, myofibroblastoma of breast often cannot be differentiated from a fibroadenoma ²¹. Due to their nonspecific imaging findings, tissue sampling is necessary and helps makes the pathologic diagnosis.

Given the nonspecific radiological appearances, the final diagnosis of myofibroblastoma requires a needle core biopsy.

Myofibroblastoma is a benign soft tissue tumor of the breast composed of myofibroblasts ²¹. These myofibroblasts are spindle-shaped mesenchymal cells and are present in various quantities throughout all tissues ²². They are the predominant cell type in fibrocontractive diseases, contracting wounds, and granulation tissue. The putative function of these cells is to generate force and tissue tension via contractile elements with the utilization of myosin light chain phosphorylation ²³.

Microscopically, myofibroblastoma of breast tumors lack epithelial breast elements and are composed of thick collagenous bands separating fascicles of spindle cells. Histologic analysis can further characterize this tumor into multiple variants: infiltrative, epithelioid, cellular, collagenized, myxoid, deciduoid, lipomatous, palisading, and atypical ²⁴.

Microscopically, myofibroblastomas histological variants include epithelioid, deciduous, collagenous, fibrous, lipomatous, cellular, myxoid, or infiltrative types ²⁵, ³. Mammary ducts and lobules involvement are absent in the typical histological subtypes and the adjacent breast parenchyma may form a pseudocapsule ²⁶.

Immunohistochemically, the majority of myofibroblastomas are positive for vimentin and CD34 and variably positive for desmin and smooth muscle actin (SMA) ¹⁵. It is also positive for CD10, CD99, estrogen, progesterone receptors, and BCL-2 protein and only focally positive for h-caldesmon. S100 protein, HMB-45, epithelial markers (EMA and pancytokeratins), and C-kit (CD117) are consistently negative ¹⁵. There is variable positivity for estrogen receptor (ER) and progesterone receptor (PgR) ²⁷. Immunohistochemical results are consistent with the fibroblastic/myofibroblastic nature of the neoplastic cells ²⁸. Unlike mammary-type myofibroblastoma (myofibroblastoma of breast), myofibroblastoma that primarily arises in the lymph nodes exhibits nuclear palisading. Some reported cases represent an unreported variant of mammary-type myofibroblastoma closely mimicking schwannoma ²⁹.

Since myofibroblastoma is a benign lesion, surgery need not be compulsory ²⁵. However, surgery with complete resection is the recommended treatment for myofibroblastoma of breast since these lesions may recur if not entirely excised ¹⁷. Due to its circumscription with good cleavage planes; these tumors are usually easily excised ³⁰. Furthermore, patients should be followed-up for a minimum of 24 months. There are no reports in the literature regarding the malignant transformation of these lesions ²⁵.

Figure 1. Myofibroblastoma of breast

Figure 2. Myofibroblastoma of breast mammography and ultrasound

Footnote: Typical images of myofibroblastoma from mammography and ultrasound. (A) Mammography of the left breast from one of the patients with myofibroblastoma demonstrates an oval mass with circumscribed margins measuring 34 mm. (B) Ultrasound shows an isoechoic oval mass with circumscribed margins and posterior acoustic enhancement. The radiology categorized this lesion as BI-RADS Category 4 B – suspicious for malignancy, biopsy recommended. [Source ¹⁷ ]

Figure 3. Myofibroblastoma pathology outlines

Footnotes: (A) Myofibroblastoma of breast tumor consists of fascicular arrangement of spindle cells with scanty collagen fibers in hematoxylin–eosin and (B) a rich reticulinic network stained black with Gömöri impregnation. (C) The tumor cells are diffusely marked by CD34 and present focal positivity for desmin (D) and smooth muscle antigen (E). The p53 (F) and Ki67 index (G) is less than 5%. More than 90% of the cells express estrogen receptor (H).

Myofibroblastoma symptoms

Gynecomastia (breast enlargement in males) is an inconsistent finding ³¹. Myofibroblastoma of breast is usually identified as an asymptomatic, slow-growing mass, well-defined, nontender and mobile on clinical examination ⁸, ⁹. Myofibroblastoma can also arise in extra-mammary sites, along the embryonic milk-line, which extends from the armpit to the inguinal region and have been reported in the literature different sites including the armpit, head, neck, tonsil, parotid gland, tongue, lung, paratesticular area, groin (inguinal area), vulva, vagina, popliteal fossa, soft tissues of retroperitoneum, abdominal wall, rectum, meninges, prostate, suprasellar area ³, ⁴, ⁵, ⁶, ⁷, ⁸, ⁹, ¹⁰, ¹¹.

Myofibroblastoma complications

No long-term complications were identified in the literature, except those associated and expected from the type of surgical intervention, either breast-conserving surgery or mastectomy ²⁵.

Myofibroblastoma cause

Myofibroblastoma of the breast is a benign tumor of mesenchymal origin associated from a loss in Rb expression due to a deletion or rearrangement in the long arm of chromosome 13, at position 14 (13q14) ³², similar to spindle cell lipoma and cellular angiofibroma ³³. This Rb gene is normally a widely expressed nuclear phosphoprotein that plays a key role in regulation of the cell cycle. Interestingly, however, myofibroblastomas have also been reported in surgical incision sites following the excision of a different breast cancer ³⁴. This may be partly due to the secondary migration of fibroblast cells to assist in granulation tissue formation.

To better elucidate the pathophysiology of myofibroblastoma, it is crucial to understand the molecular mechanisms controlling the growth and proliferation of myofibroblasts.

Myofibroblasts respond to tissue injury. The injured cells or cells with malignant potential produce cytokines, including transforming growth factor β1 ²⁵. This helps the fibroblasts to migrate into the injured tissue. This process is followed by the development of smooth muscle actin fibers, which eventually transform into myofibroblasts with contractility. The contraction in the injured tissue increases the speed of healing and repair ²⁷.

Myofibroblastoma diagnosis

The diagnostic algorithm for myofibroblastoma typically includes a triple assessment approach consisting of: 1) clinical evaluation, 2) appropriate imaging studies, and 3) core needle biopsy ²⁵.

Clinical evaluation should include detailed history taking, including assessment for cyclical pain, recent trauma, nipple or skin changes, or nipple discharge. Further emphasis must be laid on past medical and surgical history, previous cancers, family history of malignancies, social history, and medications.

It is always important to assess gynecologic and obstetric history in women, including age at menarche, menopause, and any prior oral contraceptive use or hormone replacement therapies. In men, it is important to assess the use of androgen deprivation therapies if treated for prostate cancer in the past.

Given the nonspecific radiological appearances of myofibroblastoma ³⁵, the final diagnosis of myofibroblastoma requires a needle core biopsy.

Most cases of breast myofibroblastoma were diagnosed either on mammograms in the female patients or chest CT of the male patients ³¹. On mammography, myofibroblastoma appears as a round or oval, well-circumscribed dense mass with rare coarse calcifications ³⁴, ³⁶.

When the diagnosis of myofibroblastoma is suspected with microscopic examination, an immunohistochemical investigation needs to be conducted with antibody panels to aid differentiation from other lesions ³⁷. Reported cases show a variant of mammary-type myofibroblastoma closely mimicking schwannoma ²⁹.

The importance lies in differentiating the myofibroblastoma from other benign or malignant soft tissue tumors of the breast. It is most often confused with spindle cell lipoma. These two benign entities are composed of spindle cells positive for CD34 staining on immunohistochemistry and are admixed with mature adipocytes. Both spindle cell lipoma and myofibroblastoma are associated with the loss of chromosome 13q14 ³⁸.

However, one of the differentiating features between these two entities is the finding of a less prominent adipose tissue component in spindle cell lipoma. In myofibroblastoma, the stroma is very prominent and is also hyalinized. Additionally, spindle cell lipomas do not stain positive for desmin, whereas myofibroblastoma is always positive ³⁹.

Imaging

The appearance of myofibroblastoma on imaging is non-specific ³⁵.

On mammography, myofibroblastoma appears as a round or oval, well-circumscribed dense mass with rare coarse calcifications ³⁴, ³⁶.

In men, the benign appearance of myofibroblastoma needs to be contrasted with the appearance of breast cancer, which parallels that of breast cancer in women ⁴⁰.

On ultrasonography, myofibroblastoma presents as a homogeneous hypoechoic well-circumscribed solid mass that resembles fibroadenoma ³⁵. However, some show a mass with a variable oval or irregular configuration and heterogeneous echo pattern, with more distal acoustic attenuation due to the incorporation of fat tissue and other types of tissue in the tumor. Applying the doppler modality may demonstrate peripheral hypervascularization of the tumor ³¹, ¹⁷.

Although not often done, MRI findings of myofibroblastoma show a homogeneously contrast-enhanced, circumscribed mass with internal septations and hyperintense signal in T2-weighted images with diffusion restriction surrounded by a hypointense capsule and plateau kinetics ⁴¹, ⁴².

Furthermore, some studies identified that the apparent diffusion coefficient (ADC) could be a useful MRI finding in distinguishing myofibroblastoma from other malignant lesions. Since low values of ADC are detected in malignant lesions, higher ADC values are likely representative of myofibroblastoma ⁴³.

Tissue diagnosis

Fine-needle aspiration (FNA) or an ultrasound-guided core needle biopsy may be performed for diagnosis. However, due to a lack of cellularity, fine needle aspiration shows non-specific whorls of spindle cells with benign ovoid nuclei or non-diagnostic results ⁹, ⁴². Most cases of breast myofibroblastomas have been diagnosed with the tissue specimen retrieved by core-needle biopsy ³¹.

Myofibroblastoma pathology outlines

A myofibroblastoma is composed of oppositional spindle-shaped cells that are present in short traversing fascicles with a background of keloidal-like eosinophilic collagen bands ²⁵. It is well-demarcated from normal breast parenchyma by a pseudo-capsule ²⁶.

Macroscopically, myofibroblastoma demonstrates a well-demarcated pale pink or tan round mass-like appearance ¹⁵, ¹⁶.

Microscopically, myofibroblastomas histological variants include epithelioid, deciduous, collagenous, fibrous, lipomatous, cellular, myxoid, or infiltrative types ²⁵. Duct or lobule involvement is characteristically absent and the adjacent breast parenchyma may form a pseudocapsule ²⁶.

On immunohistochemistry, myofibroblastoma is positive for CD34, vimentin, CD10, CD99, estrogen receptors, progesterone receptors, BCL-2 protein, and variably positive for SMA, desmin, androgen receptors, and h-Caldesmon. It is negative for CD117 (C-kit), EMA, pan-cytokeratin, HMB-45, and S100. There is variable positivity for estrogen receptor (ER) and progesterone receptor (PgR) ²⁷. These results are aligned with the fibroblastic or myofibroblastic nature of the neoplastic cells ¹⁵, ⁴⁴, ³³.

Immunohistochemically, myofibroblastoma is negative for nuclear staining of Rb in over 90% of the cases ⁸. This is in contrast to solitary fibrous tumors, fibromatosis, and nodular fasciitis, which are intact for Rb staining.

Myofibroblastoma treatment

Since myofibroblastoma is a benign lesion, surgery need not be compulsory ²⁵. However, since all the previously reported cases underwent surgical excision, the long-term stability and implications of an unresected myofibroblastoma are not clearly understood. Moreover, myofibroblastoma can be treated with local excision for symptomatic relief ¹⁵, ³⁷, ¹⁶.

Surgical excision is considered curative and local recurrence is not a recognized feature of myofibroblastoma. Moreover, patients should be followed-up for a minimum of 24 months. There are no reports in the literature regarding the malignant transformation of these lesions ²⁵.

Myofibroblastoma prognosis

The prognosis for myofibroblastoma is excellent after surgical excision ²⁵. Local recurrence or malignant transformation is not a recognized feature of myofibroblastoma ¹⁵, ³⁷, ¹⁶. Patients should be followed-up for a minimum of 24 months. There are no reports in the literature regarding the malignant transformation of these lesions ²⁵.

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