Myoepithelial cells in solid variant of intraductal papillary carcinoma of the breast: a potential diagnostic pitfall and a proposal of an immunohistochemical panel in the differential diagnosis with intraductal papilloma with usual ductal hyperplasia
We examined myoepithelial status in intraductal papillary carcinoma (IPC) along with the expression of high-molecular weight cytokeratin (HMWK) and neuroendocrine markers, with special reference to the differential diagnosis of solid intraductal papillary carcinoma(SIPC) and intraductal papilloma with usual ductal hyperplasia (IP-UDH). Twenty-six (93%) of the twenty-eight intraductal papillomas (IP) had myoepithelial cells in >70% of the epithelial-stromal interface of the intraluminal proliferating component. Six (29%) of twenty-one SIPC had almost complete myoepithelial layer like IP-UDH at the epithelial-stromal interface. HMWK (34 beta E-12) was diffusely positive in 14 (93%) of 15 IP-UDH, but 16 (76%) of 21 SIPC were completely negative for HMWK. Neuroendocrine markers were positive in 14 (67%) of SIPC, but all 28 IPs were completely negative. If only the presence of myoepithelial cells is emphasized as a benign hallmark, about 30% of SIPCs may be underdiagnosed as IP-UDH. However, by using a combination of myoepithelial markers, HMWK, and neuroendocrine markers, all of the 36 solid intraductal papillary lesions were properly classified as benign and malignant. Solid intraductal papillary lesions meeting at least two of the following criteria are highly likely to be malignant: (1) absence of myoepithelial cells(<10% of epithelial-stromal interface of intraluminal proliferating component), (2) negative HMWK(<10%), (3) positive neuroendocrine markers (>10%).
[Show abstract][Hide abstract] ABSTRACT: Solid papillary carcinoma (SPC) is an uncommon breast tumor that occurs mainly in elderly women. It is composed of well-circumscribed large cellular nodules consisting of low-grade cells with neuroendocrine differentiation (rosette-like formation and expression of synaptophysin and chromogranin), and are separated by hyalinized fibrovascular cores. Mucin production is another characteristic feature of this lesion. SPC has been considered a noninvasive breast lesion ie, a variant of ductal carcinoma in situ involving larger ducts, and can be associated with invasive carcinoma in more than half of the cases. The invasive carcinoma arising in the background of SPC is typically of low grade, either colloid or "neuroendo-crine-like" type, positive for estrogen receptor and progesterone receptor and negative for Her-2. Overall, SPC tends to exhibit an indolent behavior. Lymph node and distant metastases can occur rarely but are generally limited to cases of SPC with invasive carcinoma or SPC with areas suspicious for invasion. A 76-year-old woman was diagnosed with a new density on routine screening mammography. The density measured 1.0 cm and showed no evidence of suspicious architectural distortion or calcifications. On ultrasound, a 9.0 7.0 5.0 mm slightly hypoechoic mass with microlobulated margins corresponding to the area of mammographic density was identified. An ultrasound-guided core biopsy was preformed and the lesion was diagnosed as "low grade ductal carcinoma in situ (DCIS) with papillary features." Microscopic examination of the subsequent excisional biopsy re-vealed a fairly well circumscribed nodule of solid cellular prolifer-ation surrounded by a fibrous wall (Fig. 1). The neoplastic cells within the nodule were monotonous with plasmacytoid features, granular eosinophilic cytoplasm, round nuclei, and conspicuous nucleoli (Fig. 2). Rare mitotic figures were identified. The epithelial cells were supported by fibrovascular cores, some with hyalinized stroma. Clusters of neoplastic cells were focally separated by extra-cellular mucin confined to the nodule (Fig. 3). The breast tissue adjacent to the nodule showed stromal fibrosis and lobular atrophy. By immunohistochemistry (IHC), the neoplastic cells expressed synaptophysin throughout the lesion and were negative for chromo-granin (Fig. 4). Immunostain for p63 showed discontinuous nuclear labeling at the periphery of the nodule and scattered positivity within the nodule along the fibrovascular cores (Fig. 5A). Smooth muscle myosin heavy chain antibody discontinuously highlighted the pe-riphery of the nodule and stained the vascular walls within the fibrovascular cores (Fig. 5B). The morphology and immunoprofile of the lesion were diagnostic of solid papillary carcinoma (SPC) of the breast.
Pathology Case Reviews 01/2009; 14(11):157-161. DOI:10.1097/PCR.0b013e3181b6ad5d
[Show abstract][Hide abstract] ABSTRACT: Immunohistochemistry may be helpful in the diagnosis of various breast lesions. It can be used to assist in distinguishing benign and malignant conditions, or to clarify the histological subtype of invasive carcinomas. There are several markers relatively frequently utilised. Myoepithelial markers (p63, alpha-SMA, smooth muscle myosin heavy chain, and others) are useful to highlight myoepithelial cells. They are employed to verify myoepithelial cell lining in intraductal papillary lesions, or to recognise peripheral myoepithelial cells for non-invasive carcinoma, although their staining results are not always excellent. High molecular weight cytokeratins (CK5/6, CK14, 34betaE12) typically show a mosaic-like pattern of expression in benign papillary/hyperplastic lesions, and are mostly negative in ductal in situ carcinoma, but some exceptions exist. Neuroendocrine differentiation (confirmed by anti-chromogranin A or synaptophysin) suggests malignancy in solid and papillary intraductal epithelial proliferations. The significance of immunohistochemical evaluation of apocrine lesions is still controversial. Negative E-cadherin staining is used for making confirmative diagnosis of lobular carcinoma, with a specificity and sensitivity of approximately 90%. Cytokeratins, especially the antibody 34betaE12, are of value to differentiate spindle cell carcinoma from phyllodes tumour. There are some other useful markers for characterising certain histological subtypes. Nevertheless, for accurate diagnosis, it is essential to correlate the immmunohistochemical staining results with the histological findings.
[Show abstract][Hide abstract] ABSTRACT: Papillary lesions of the breast represent a heterogeneous group with differing biological behaviour. Correct diagnosis is crucial but may be difficult, as many benign and malignant papillary lesions have similar appearances. Immunohistochemistry plays a useful role in their differentiation. Myoepithelial markers can help in differentiating papilloma from papillary carcinoma, as the former usually shows a continuous layer of myoepithelial cells. In intracystic papillary carcinoma, there is controversy as to the presence of a complete myoepithelial cell layer around these lesions. p63 is the marker of choice as the staining is nuclear, cross-reactivity is minimal, and sensitivity is high. Papilloma may frequently be complicated by superimposed different types of epithelial hyperplasia, which range from usual to atypical or even ductal carcinoma in situ, and they many be morphologically similar. Basal cytokeratins (CKs) are useful to differentiate these entities; as usual hyperplasia is positive for basal CKs with a mosaic staining pattern. CK5/6 is probably the best marker. Neuroendocrine markers (chromogranin A and synaptophysin) may be positive in papillary carcinoma, particularly in the solid type, and there may be some overlap with the ductal carcinoma in situ with spindle cells or endocrine ductal carcinoma in situ. A panel of CK5/6, p63 and neuroendocrine markers can be useful in the diagnostic investigation of problematic papillary lesions of the breast. As the experience with these markers remains rather limited, it is too early to recommend basing treatment choices on these marker studies alone. Complete removal of lesion is probably still the treatment of choice.
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