Case of the Month: Breast Pathology
May 2012 Case of the Month authored by UF PathLabs' Breast Pathology Unit Director Samer Z. Al-Quran, M.D.
A 50-year-old female presented with a 3 cm right breast mass. A lumpectomy was performed at an outside hospital, and a diagnosis of poorly differentiated invasive ductal carcinoma of breast was rendered; however, immunohistochemical studies showed that the tumor cells were pancytokeratin (-), p63 (-) and e-cadherin (-). The case was referred to our laboratory for a second opinion.
Examination of histologic sections shows a well-circumscribed soft-tissue tumor without a surrounding capsule (Figure 1).
Figure 1: A low-power photomicrograph shows a tumor with well-circumscribed margins.
It is composed of oval-to-polygonal epithelioid cells with abundant foamy eosinophilic-to-clear cytoplasm. The epithelioid cells are variably admixed with round, polygonal, and spindle-shaped cells and are arranged in multiple lobules (Figure 2a). The lesional cells include binucleated and multinucleated forms that are mainly arranged in nests surrounded by thick hyalinized collagen bundles (Figures 2b and 2c).
Figure 2: This composite photomicrograph details the histologic features of epithelioid cell-myofibroblastoma.
There is a mild-to-moderate degree of nuclear pleomorphism. Mitotic figures are not readily identifiable. Elsewhere, the tumor is composed of spindle cells (Figure 2d) with myxoid stroma and thick eosinophilic collagen bands.
Fibrocystic changes were present in the breast tissue surrounding the mass, including fibrosis of mammary stroma, cystic change, apocrine metaplasia and sclerosing adenosis associated with microcalcifications
Immunohistochemical studies performed in our laboratory show that the cells are desmin (+), SMA (+), focally calponin (+), CD34 (+), CD31 (-), Cytokeratin AE1/AE3 (-), cytokeratin CAM 5.2 (-) and S-100 protein (-) (Figure 3).
Figure 3: Immunohistochemistry for desmin
The principal differential diagnosis challenge in this case was to rule-out invasive carcinoma, namely invasive lobular carcinoma of breast. No in-situ carcinoma was identified in this case, and the lack of immunoreactivity with several cytokeratins (pancytokeratin, AE1/AE3 and CAM 5.2) essentially rule out this diagnosis. Another possibility is metaplastic carcinoma, which in some cases can assume an epithelioid appearance and; be associated with DCIS; or exhibit overt epithelial differentiation. In cases where none of these features are present, immunohistochemical studies for cytokeratins and p63 can be helpful in making this diagnosis. In the current stains, both p63 and cytokeratins were negative and no in-situ component was identified.
Clinical Features: Myofibroblastoma (MFB) is a rare benign tumor that affects both women and men with a peak age onset of 50 - 75 years. Patients usually present with a painless, mobile and slowly growing breast mass. In most cases, the mass is less than 4 cm, but occasionally, it can be very large. It can also occur outside the breast, including in lymph nodes. MFB is a slightly hypoechoic compressible mass on ultrasonography
- Gross Features: MFB is usually a rubbery-firm, well-circumscribed and lobulated mass with homogenous cut surfaces of gray-to-pink whorled or lobulated tissue.
- Histologic Features (Classic Type): MFB is circumscribed with no true capsule. It is composed of uniform spindle (myofibroblastic) cells with round-to-oval nuclei arranged in a nested pattern or short fascicles with intervening thick bands of hyalinized collagen. It may show mild nuclear pleomorphism, and the mitotic activity is either rare or absent. Variable amounts of fat can be present. There are usually no entrapped mammary ducts or lobules. Mast cells or perivascular lymphoplasmacytic c infiltrates mat be present. Some cases with myxoid change, and others with chondroid and smooth muscle metaplasia have been described
- Immunophenotype: MFB can be immunoreactive with antibodies against vimentin, CD34, actin, desmin, CD99 and CD10. Most MFB are positive for estrogen, progesterone and androgen receptors. The immunoreactivity can be focal and variable. Cytokeratins, EMA, S-100 protein, HMB-45 and c-Kit (CD117) are consistently negative.
- Morphologic Variants: Several morphologic variants of mammary MFB have been described in addition to the classic type including: collagenized/fibrous, epithelioid, cellular, myxoid, deciduoid-like, atypical and infiltrative variant.
- Epithelioid-Cell MFB: This is a rare morphologic variant of MFB that is predominantly (> 50%) or exclusively composed of cells with epithelioid morphology. It is may be challenging to recognize this variant, and it can be a potential diagnostic pitfall. It has some histologic features that are similar to the classic type with well-circumscribed margins and a variable amount of intratumoral mature fatty component. The characteristic epithelioid cells are variably admixed with a minority of round, polygonal and spindle-shaped cells. They have low mitotic activity (up to two mitoses/10 high-power fields) with a mild-to-moderate degree of nuclear pleomorphism. Different growth patterns have been reported, including alveolar, single-cell, single-file, solid, and fascicular growth patterns. In some cases, close admixture of atypical epithelioid cells with intratumoral adipocytes may impart a pseudo-infiltrative appearance. In other cases, the growth pattern may resemble invasive lobular carcinoma. The cells in this variant are positive for desmin with variable immunoreactivity for actin and CD34 and most importantly no immunoreactivity for cytokeratins.
It is important to be aware of the multiple cytomorphologic patterns of MFB and the overlap in their clinical presentation, radiologic findings and morphology with other benign and malignant breast lesions. Epithelioid-cell MFB may be a particular diagnostic challenge, especially when evaluating needle-core biopsies. Recognizing the characteristic morphologic features and the use of immunohistochemical studies are greatly helpful to avoid a misdiagnosis of malignancy.