—  SPECIALTY CONFERENCE  —

Breast Pathology

Case 2 - Breast Myxoma

Juan P. Palazzo, Jefferson University, Philadelphia, PA





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Clinical History
A seventy five year old female was diagnosed in a screening mammography with a focal asymmetry in the upper outer left breast. By ultrasound, there was an ovoid, hypoechoic mass with indistinct margins and no calcifications. Twenty years ago the patient had an invasive ductal carcinoma of the left breast and six years ago she had an invasive ductal carcinoma of the right breast. A wide local excision was performed.


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Introduction:
A 75 year-old female presented with a 1.4 cm non-calcified focal asymmetry in her upper outer left breast detected on screening mammogram. Ultrasonography showed an ovoid, hypoechoic mass with indistinct margins. The mass was not attached to the overlying skin which was unremarkable. Twenty years ago the patient had an invasive ductal carcinoma of the left breast and seven years ago she had an invasive ductal carcinoma of the right breast. She had a wide local excision of the breast.

Pathological/Microscopic Findings and any Immunohistochemical or Other Studies:
The cut section of the breast specimen revealed a 1.8 cm, well circumscribed mass, whitish in colour and gelatinous in appearance. Histologically, a hypocellular lesion with an abundant myxoid matrix, entirely surrounded by a thin fibrous pseudocapsule, was seen. The cellular component was represented by bland-looking, mono- or bi-nucleated round- to spindle/stellate-shaped cells with pale and eosinophilic cytoplasm. Some of these cells exhibited dendritic-like cytoplasmic processes . The nuclei were round to oval in shape, with one or two nucleoli. Only focally a mild degree of nuclear atypia was present. There was no evidence of mitotic activity or necrosis. The tumor stroma was composed of an abundant loose matrix positive with alcian blue at pH2.5, negative with periodic acid-Schiff, in which haphazardly arranged thick eosinophilic collagen bands could be focally identified. Vacuolar stromal changes were seen throughout the tumor, sometimes simulating univacuolar lipoblasts, especially when they were close to neoplastic cells. In addition, fluid-filled cystic spaces, frequently containing interspersed red blood cells, were also seen; small-sized blood vessels were scattered throughout the tumor stroma. A plexiform capillary-like or a curvilinear vascular pattern was not observed. A few mast cells and lymphocytes were seen within myxoid stroma. Mammary lobules or ducts were not entrapped within tumor. No evidence of epithelial atypical lesions or cancer was observed in the breast parenchyma surrounding the myxoid lesion. Immunohistochemically, neoplastic cells were strongly and diffusely positive for vimentin and only focally for calponin . No immunoreactivity was obtained with any of the other antibodies (actin, desmin, myogenin, S-100 protein, CD34, CD99, CD10 CD117, pancytokeratin, EMA, p63 and HMB45).

Differential Diagnoses:
The lesions reported in the breast with myxoid stromal changes are: superficial angiomyxoma [9], nodular mucinosis (first reported as nerve sheath myxoma) [16, 17], nodular fasciitis (myxoid variant) [18], neurofibroma (myxoid variant) [19, 20], myofibrolastoma (myxoid variant) [21, 22], myxofibrosarcoma [23], myxoid liposarcoma [24], and mucocele-like tumors [15]. In addition, many other benign and malignat tumors can be composed of myxoid changes. Some of these lesions are nodular fasciitis, solitary fibrous tumor, benign peripheral nerve sheath tumor, sarcomatoid/metaplastic carcinoma and mucocele-like lesions. See below for discussion of the differential diagnosis.

Final Diagnosis:
Breast Myxoma

Case Discussion:
Myxomas can arise in soft tissues, bone, sinonasal cavities, maxillary antrum, and in other organs [1, 2, 3]. Although a computerized literature search has revealed five cases of myxoma of the breast [4, 5, 8, 9, 10], only three well documented cases are available [4, 5, 8]. In fact, one case reported with the term "myxoma of the breast" could well represent a superficial angiomyxoma, due to the close relationship with subcutis and its multinodular appearance both at the gross and microscopic examination [9]. Another case of breast myxoma involved the subcutaneous tissue of a 37-year-old woman who experienced multiple local recurrences referred as "myxosarcoma" and "myxoid liposarcoma" [10]. It is likely that this case was a primary subcutaneous "myxoid sarcoma" not otherwise specified in the first diagnosis and not a true "myxoma".

Radiologic images of myxoma of the breast parenchyma are available only in one previously reported case [5]. The tumor presented as a palpable lesion which at mammography appeared as a noncalcified mass with circumscribed borders [5]. On the contrary, the present case shows that myxoma of the breast parenchyma may present as a solitary and asymptomatic lesion, which can be identified as a focal asymmetry and ovoid mass with indistinct margins at mammography and ultrasonography, respectively. Unfortunately, radiologic images are nonspecific [5] and the diagnosis of breast myxoma is based on histological examination. The main diagnostic criteria for myxoma are: hypocellularity, abundant myxoid matrix, round- to stellate- to spindle-shaped cells, low vascularization and lack of significant cytological atypia, mitotic activity, plexiform and curvilinear vasculature [1, 2, 3]. Although the histological diagnosis of myxoma is usually straightforward in appropriate sites (soft tissue, heart), it is the unusual location, including breast parenchyma, that can cause some diagnostic problems.

Unfortunately, there are no immunohistochemical markers helpful in confirming the morphological diagnosis of myxoma. In this regard, neoplastic cells show a variable, often focal, expression of a-smooth muscle actin, desmin, CD34 and factor XIIIa [1, 2, 3]. In the present case, apart from vimentin, cells expressed calponin. Similar immunohistochemical findings were observed in a myxoma of the renal capsule, suggesting a myofibroblastic nature of the constitutive cells [11]. Awareness of the possibility that myxoma may occasionally occur in the breast parenchyma is crucial to avoid confusion with a wide variety of benign and malignant lesions which could be predominantly myxoid in nature. These lesions include nodular fasciitis, reactive spindle cell nodules, solitary fibrous tumor/hemangiopericytoma, spindle cell lipoma, leiomyoma, benign fibrous histiocytoma, benign peripheral nerve sheath tumor, inflammatory myofibroblastic tumor, follicular dendritic cell tumor, dermatofibrosarcoma, leiomyosarcoma, fibrosarcoma/malignant fibrous histiocytoma, low/high grade myofibroblastic sarcoma, malignant peripheral nerve sheath tumor, rhabdomysarcoma, fibromatosis/nodular fasciitis-like low-grade sarcomatoid/metaplastic carcinoma and mucocele-like tumors [12, 13, 14, 15]. However, the lesions most commonly reported in the breast with diffuse myxoid stromal changes are: superficial angiomyxoma [9], nodular mucinosis (first reported as nerve sheath myxoma) [16, 17], nodular fasciitis (myxoid variant) [18], neurofibroma (myxoid variant) [19, 20], myofibrolastoma (myxoid variant) [21, 22], myxofibrosarcoma [23], myxoid liposarcoma [24], and mucocele-like lesions [15]. Briefly, malignant soft tissue tumors are easily ruled out on the basis of the absence of significant nuclear pleomorphism, mitotic activity, curvilinear vasculature (myxofibrosarcoma), lipoblasts and plexiform vasculature (myxoid liposarcoma). Low-grade sarcomatoid/metaplastic carcinoma exhibiting a fibromatosis/nodular fasciitis-like pattern can be excluded with the use of immunohistochemistry for low molecular weight keratins which identify epithelial foci with spindle cell morphology [14]. Lastly, the extracellular matrix of mucocele-like tumors stain positively with PAS and contain epithelial elements which can be highlighted by pancytokeratin and EMA [15].

Among benign myxoid lesions, superficial angiomyxoma is a dermal/subcutaneal lesion [1] which can extend into the underlying breast parenchyma [9]. Unlike myxoma, it has a typical multilobular appearance both at gross and microscopic examination due to the presence of fibrous septa [1]. Nodular mucinosis typically occurs under the nipple, with poorly circumscribed margins due to the arrangement of myxoid stroma into small nodules [16, 17]. Nodular fasciitis (myxoid variant) is a fibro-myofibroblastic pseudosarcomatous lesion with, at least focally, infiltrative margins, composed of spindle-shaped cells which are typically positive for a-smooth muscle actin [18, 25]. A variable number of inflammatory cells, including extravasated red blood cells, is a typical feature of this reactive lesion [25]. Myxoid myofibroblastoma is a myofibroblastic tumor which typically expresses desmin and variable a-smooth muscle actin, CD34, bcl-2, CD99, CD10 and estrogen/progesterone/androgen receptors [21, 22]. Lastly, myxoid neurofibroma is a tumor that expresses S100 protein and CD34 [19].

The histogenesis of breast myxoma is still to be determined. Most of the benign mesenchymal tumors of the breast belong to the category of "benign spindle cell tumors of the mammary stroma", likely arising from a common precursor fibroblast-like cell resident in the hormonally active intralobular stroma [13, 26, 27]. This is suggested by a basic common morphological and immunohistochemical profile, including the expression of desmin, a-smooth muscle actin, CD34, bcl-2 protein, CD99, CD10, estrogen, progesterone and androgen receptors [26, 27]. Accordingly, we evaluated the expression of these markers in our case, to assess if breast myxoma falls within the spectrum of the "benign tumors of the mammary stroma". Neoplastic cells were negative for all markers and did not express any sex steroid hormone receptors, suggesting that breast myxoma is a separate entity which likely arises from a mesenchymal precursor cell resident in the interlobular stroma.

Conclusion(s):
Myxomas are uncommon lesions of the breast. Tumors can be incidentally detected at mammographic screening. Histologically, an encapsulated, hypocellular, myxoid tumor with low vascularization is characteristic. Morphology remains preeminent in the diagnosis of a breast myxoma, while immunohistochemistry may help to exclude other entities. The histogenesis of breast myxomas is unknown. The lack of expression of desmin, a-smooth muscle actin, CD34, CD99, CD10, bcl-2 protein, estrogen/progesterone/androgen receptors, all markers characteristically expressed by "the benign spindle cell tumors of the mammary stroma", would suggest that breast myxoma does not fall into this tumor category and that its putative precursor mesenchymal cell resides in the interlobular.

Take Home Messages:
  • Myxoid changes can be seen in a wide variety of breast lesions, both benign and malignant

  • It is important to correlate imaging and pathological findings including immunohistochemistry to differentiate these lesions and to exclude malignant tumors with myxoid changes

  • The differential diagnoses can be more difficult when myxoid lesions are present in core biopsies, but the same diagnostic criteria should be applied

  • Soft tissue tumors with myxoid changes can present in the breast and their appearances are the same as those seen in extrammary locations

References:
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