Papillary lesions of the breast

Papillary lesions of the breast represent a heterogeneous group of lesions including benign papillomas, papillomas with focal epithelial atypia, fully fledged ductal carcinoma in situ (DCIS) or lobular neoplasia, papillary DCIS, encapsulated papillary carcinomas without or with invasion, solid papillary carcinomas, and invasive papillary carcinomas. A micropapillary pattern characterized by lack of fibrous stalks within the papillae is observed in micropapillary DCIS and invasive micropapillary carcinoma. In addition, a variety of other rare breast lesions reveals a papillary architecture such as tall cell carcinoma with reversed polarity (TCCRP) and mucinous cystadenocarcinoma, adenomyoepithelioma, and secretory carcinoma. In addition, benign lesions such as usual ductal hyperplasia, apocrine metaplasia, gynecomastia, and juvenile papillomatosis may show a papillary or micropapillary architecture. Fragments of a benign papilloma in a breast biopsy are considered a lesion of uncertain malignant potential (B3 in the European classification) and excision is mostly recommended. Although the knowledge about molecular pathology of papillary breast lesions has increased, there is not sufficient evidence for diagnostically useful molecular features, yet. The aim of this review is to provide an update on papillary and micropapillary lesions with emphasis on problematic areas for daily diagnostic work including biopsies.

Expression of Malic Enzyme 3 in Breast Cancer and Precancerous Lesions: a Promising Novel Biomarker for Carcinogenesis and Prognosis

Purpose: While malic enzymes 1 (ME1) was correlated with breast cancer progression and prognosis, the association of ME3 (a homologue of ME1) with breast cancer is not known. The aim of this study is to explore the potential of ME3 as a biomarker in breast cancer carcinogenesis and prognosis.Methods: A total of 107 patients confirmed with breast cancer were enrolled. The ME3 expression was evaluated by IHC and correlated with clinicopathological indicators.Results: The ME3 positive immunostaining rate was higher in normal breast tissues and decreased stepwise from normal (97.60%) to usual ductal hyperplasia (91.1%), atypical ductal hyperplasia (64.2%), carcinoma in situ (62.5%) and invasive carcinoma (45.5%). Similarly, the decreasing tendency was observed for ME3 positive immunostaining rate from Tis (75.0%) through T1 (62.5%) and T2 (37.5%) to T3 (33.3%) and from stag 0 (75.0%) through I (72.0%), II (44.4%) to III (24.1%). ME3 expression was related with negative lymph node metastasis. Patients with positive expression of ME3 had better outcome. By incorporating ME3 into tumor TNM staging, the area under receiver operating characteristic curve for the 5-year survival was increased from 84.0% to 87.5%. Conclusions: ME3 may be a promising biomarker for better prognosis for breast cancer patients.

Unilateral Usual Ductal Hyperplasia in A 22 Years Old Male Patient: A Case Report

Background: Benign breast disease have been broadly classified into non-proliferative lesions, proliferative lesions without atypia and hyperplasia with atypia. Proliferative disease, such as usual ductal hyperplasia, is associated with a 1.5 to 2 fold increased risk of developing invasive carcinoma. We reported a case of usual ductal hyperplasia in a young male. Case: A 22-year-old male complained of discomfort and enlargement of unilateral breast. Physical examination at that time revealed a palpable mass in the lateral upper quadrant of the patient’s left breast, three centimeters from nipple areola complex. The examination of axilla didn’t reveal any lymph node enlargement on both sides. His vital signs were normal without any abnormalities found on examination. Ultrasonography examination demonstrated fibroglandular tissue in the left breast with the volume of 11.13 cm3, consist of 4.8 cm length, 2.9 cm width and 0.8 cm depth. Excisional tumor biopsy was done on his left breast. Usual duct cell hyperplasia was present in microscopic examination with chronic inflammatory cells spreading around the fibrotic stromal cell. Physical examination, radiologic examination, and biopsy were all performed in this patient. Although the accuracy of the triple test is high, benign concordant results do not obviate further surveillance of a palpable mass. We advised our patient to routinely follow-up his condition every 6 months for 1 to 2 years, especially if there any changes found on his breasts. Conclusion: Any guidelines and further studies regarding patient’s follow-up examination after biopsy for male breasts tumor are needed in order of better understanding about this disease.

A human organoid system that self-organizes to recapitulate growth and differentiation of a benign mammary tumor

As 3D culture has become central to investigation of tissue biology, mammary epithelial organoids have emerged as powerful tools for investigation of epithelial cell polarization and carcinogenesis. However, most current protocols start from single cells suspended in Matrigel, which can also restrict cell differentiation and behavior. Here, we show that the noncancerous mammary cell line HMT-3522 S1, when allowed to spontaneously form cell aggregates (“spheroids”) in medium without Matrigel, switches to a collective growth mode that recapitulates many attributes of “usual ductal hyperplasia” (UDH), a common benign mammary lesion. Interestingly, these spheroids undergo a complex maturation process reminiscent of embryonic development: solid-cell cords form their own basement membrane, grow on the surface of initially homogeneous cell aggregates, and form asymmetric lumina lined by two distinct cell types that express basal and luminal cytokeratins. This sequence of events provides a cellular mechanism that explains how the characteristic crescent-shaped, asymmetrical lumina form in UDH. Our results suggest that HMT-3522 S1 spheroids are useful as an in vitro model system to study UDH biology, glandular lumen formation, and stem cell biology of the mammary gland.

Use of immunohistochemical analysis of CK5/6, CK14, and CK34betaE12 in the differential diagnosis of solid papillary carcinoma in situ from intraductal papilloma with usual ductal hyperplasia of the breast

Objectives: The aim of this study was to use immunohistochemistry to differentiate solid papillary carcinoma in situ from intraductal papilloma with usual ductal hyperplasia (IPUDH). Three types of high-molecular-weight cytokeratins (CKs) – CK5/6, CK14, and CK34betaE12 – were targeted. Methods: We studied 17 patients with solid papillary carcinoma in situ and 18 patients with IPUDH diagnosed by at least two pathologists. Immunohistochemical analyses used antibodies to CK5/6, CK14, and CK34betaE12 to make the differential diagnosis of solid papillary carcinoma in situ versus IPUDH. Immunohistochemical staining was scored as 0–5 using Allred score. Results: Immunohistochemistry with CK5/6 and CK14 antibodies produced scores of 0–3 in all patients with solid papillary carcinoma in situ and 2–5 in all patients with IPUDH. Immunohistochemical staining with CK34betaE12 antibody produced scores of 1–3 in all patients with solid papillary carcinoma and 3–5 in all patients with IPUDH. In tissues from patients with IPUDH, significantly more cells were stained with CK34betaE12 than CK5/6 ( p < 0.05) or CK14 ( p < 0.05). Conclusion: The immunoreactivity of CK5/6, CK14, and CK34betaE12 antibodies was useful to differentiate solid papillary carcinoma in situ from IPUDH. CK34betaE12 is especially useful for distinguishing solid papillary carcinoma from IPUDH.