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BACKGROUND: Papillomas of the breast pose challenges for treatment decisions as their risk for transformation to breast cancer is low but not negligible. To spare low-risk patients the burden of substantial treatment side effects, prognostic indicators are needed for cancerous progression. The secreted metastasis mediator Osteopontin (OPN) is a marker for breast cancer aggressiveness, and its variants are prognosticators for transformation in diverse premalignant breast lesions. Here, we test whether the presence of OPN-c or OPN-exon-4 in papillomatous lesions may reflect progression risk. METHODS: By immunohistochemistry, we analyze OPN-c and OPN-exon-4 in papillomas from 114 women as well as correlations between staining and progression. In departure from prior spliced OPN biomarker publications, we utilize novel monoclonal antibodies. RESULTS: Fewer than 5% of OPN-c pathology score 0-1 (intensity) versus almost 18% of score 2-3 experienced cancer in follow-up. Nine of 12 women, who progressed, had pathology scores of 2-3 for OPN-c intensity at the time of initial diagnosis, and none had a score of 0. When developing a combined risk score from intensity plus percent positivity for OPN-c, the progression risk for patients with low score was 3.2%, for intermediate score was 5.7%, and for high score was 18.8%. Papillomas in patients, who were later diagnosed with cancer in the contralateral breast, displayed stronger staining positivity than non-progressors. CONCLUSION: OPN splice variant immunohistochemistry on biopsies of breast papillomas will allow counseling of the patients on their risk to develop breast cancer at a later time.

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BACKGROUND: Breast intraductal papilloma is a heterogeneous group. The aim of the study is to investigate the intraductal breast papilloma and its coexisting lesions retrospectively in real-world practice. METHODS: We retrospectively identified 4450 intraductal breast papilloma and its coexisting lesions. RESULTS: About 18.36% of intraductal papilloma coexisted with malignant lesions of the breast, 37.33% coexisted with atypia hyperplasia (AH), 25.24% coexisted with benign lesions, and only 19.10% coexisted without concomitant lesions. In addition, 36.80% of intraductal breast papilloma had nipple discharge, 51.46% had a palpable breast mass, and 16.45% had both nipple discharge and a palpable breast mass. About 28.18% experienced discomfort or were asymptomatic. Furthermore, 98.99% had ultrasound abnormalities, and 53.06% had intraductal hypoechogenicity upon ultrasound. 31.89% had mammographic distortion, and 14.45% had microcalcification upon mammography. Intraductal breast papilloma with malignancy had significant correlations with clinical manifestations. CONCLUSION: Coexisting malignancy was also related to ultrasound abnormality (BIRADS 4C and 5), mammographic distortion, and microcalcification upon mammography but was not related to the intraductal hypoechoic upon ultrasound. Coexisting atypical hyperplasia correlated with nipple discharge but not palpable mass, mammographic distortion, or intraductal hypoechoic upon ultrasound. The coexisting AH was also related to abnormality upon ultrasound or microcalcification compared with the benign lesions. The intraductal papilloma coexists with malignancy or AH accounted for more than 50%, and the clinical information on papilloma and its coexisting lesions is nonspecific. We recommended surgical treatment for benign intraductal papillary lesions.

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BACKGROUND: Papillary breast lesions may be benign, atypical, and malignant lesions. Pathological and clinical differentiation of breast papillomas can be a challenge. Unlike malignant lesions, benign breast papillomas are not classically associated with lymph node and distant metastasis. We report a unique case of a recurrent, benign breast papilloma presenting as an aggressive malignant tumor. CASE PRESENTATION: Our patient was a 56-year-old postmenopausal African American woman who was followed in the breast clinic with a long history of multiple breast papillomas. She underwent multiple resections over the course of 7-9 years. After being lost to follow-up for 2 years, she once again presented with a slowly enlarging left breast mass. Subsequent imaging revealed a predominantly cystic mass in the left breast, as well as a suspicious hypermetabolic internal mammary node and a hypermetabolic nodule in the pretracheal space. Biopsy of the internal mammary node demonstrated papillary neoplasm with benign morphology and immunostains positive for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2/Neu. Due to the clinical picture concerning for malignancy, the patient was then started on endocrine therapy with palbociclib and letrozole before surgery. She then underwent simple mastectomy and sentinel lymph node dissection with negative nodes and pathology once again revealing benign papillary neoplasm. She underwent adjuvant chest wall radiation for 6 weeks and received letrozole following completion of her radiation therapy. She was without evidence of disease 30 months after surgery. CONCLUSIONS: We present an unusual case of multiple recurrent peripheral papillomas with entirely benign histologic features exhibiting malignant behavior over a protracted period of many years, with an invasion of pectoralis musculature and possibly internal mammary and mediastinal nodes. Her treatment course included multiple surgeries (ultimately mastectomy), radiation therapy, and endocrine therapy.

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In many centers internationally, current standard of care is to excise all papillomas of the breast, despite recently reported low rates of upgrade to malignancy on final excision. The objective of this study was to determine the upgrade rate to malignancy in patients with papilloma without atypia. A retrospective review of a prospectively maintained database of all cases of benign intraductal papilloma in a tertiary referral symptomatic breast unit between July 2008 and July 2018 was performed. Patients with evidence of malignancy or atypia on core biopsy and those with a history of breast cancer or genetic mutations predisposing to breast cancer were excluded. One hundred and seventy-three cases of benign papilloma diagnosed on core biopsy were identified. Following exclusions, the final cohort comprised of 138 patients. Mean age at presentation was 51. Mean follow-up time was 9.6 months. The most common symptom was a lump (40%). Of the 124 patients who underwent excision, three had ductal carcinoma in situ and there were no cases of invasive disease, giving an upgrade rate to malignancy of 2.4%. Upgrade to other high-risk lesions (atypical lobular and ductal hyperplasia and lobular carcinoma in situ) was demonstrated in 15 cases (12.1%). Benign papilloma was confirmed in 100 cases (81.5%), and 6 (4.8%) had no residual papilloma found on final excision. Twelve patients (8.7%) were managed conservatively. Of those, one later went on to develop malignancy. Patients with a diagnosis of benign papilloma without atypia on core biopsy have a low risk of upgrade to malignancy on final pathology, suggesting that observation may be a safe alternative to surgical excision. Further research is warranted to determine which patients can be safely managed conservatively.

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Papillary breast lesions are a heterogeneous group of neoplasms of diverse imagenological, clinical and morphological presentation that display different behaviour, prognosis and, therefore, controversial diagnosis and management. The aim of this study is to propose an algorithm for the management of mammary lesions. MATERIALS AND METHODS: We show a retrospective review of breast imaging reporting, percutaneous needle biopsy information, histological-pathological reports and subsequent management. RESULTS: A total of 7,920 biopsies were reviewed. Only 136 biopsies from 130 patients with papillary lesions met the inclusion criteria. There was a correlation between the pathologic findings from percutaneous biopsy and the final surgical histologic result in patients with surgery recommendation in all but 2 (2.12%) cases in which the surgery results were upgraded to a malignant disease. CONCLUSIONS: The algorithm proposed in this paper for the management of mammary lesions significantly reduces the possibilities of upgrading and favours decision making between follow-ups or surgery in patients with papillary lesions of the breast.

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Papillomas of the female breast is a relatively frequent lesion, and the majority are benign when excised. However, some may host malignant or premalignant areas. Consequently, it is a worldwide accepted principle to excise the lesion whenever diagnosed. However, this leads to a large number of patients having an unnecessary operation. The present study was designed to investigate whether we could find clinical, radiological and pathological factors in the preoperative, diagnostic setting that could identify patients hosting a benign papilloma in order to avoid operation. The patient material consisted of 260 patients, all with a preoperative diagnosis of a papillomatous process in core biopsy. The lesion was excised, and 71% had a benign lesion. The rest had lesions ranging from premalignant to malignant. In the clinical, radiological and histopathological investigations conducted, we were not able to identify factors that statistically significant could predict whether the lesion was benign or malignant. However, our data showed a higher prevalence of malignant and premalignant lesions for older patient, larger lesions, and lesions found at a longer distance from the papilla. We conclude that, since almost 30% of the patients in our study ended up with a premalignant or malignant diagnosis, where no statistically significant preoperative factors could indicate a benign outcome, operation is warranted in all patients with a preoperative diagnosis of a papillomatous lesion.

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Papillary lesions of the breast range from benign to atypical to malignant. Although papillomas without frank cancer are benign, their management remains controversial. When a core needle biopsy of a lesion yields a diagnosis of intraductal papilloma with atypia, excision is generally recommended to rule out a concurrent malignant neoplasm. For intraductal papillomas without atypia, however, recommendations for excision versus observation are variable. The aims of this study are to evaluate the rate of concurrent malignancies for intraductal papilloma diagnosed on core needle biopsy and to assess the long-term risk of developing cancer after the diagnosis of a papillary lesion. This single institution retrospective study analyzed 259 patients that were diagnosed with intraductal papilloma (IDP) by core needle biopsy from 1995 to 2010. Patients were grouped by initial diagnosis into three groups (papilloma without atypia, papilloma with atypia, and papilloma with atypical duct hyperplasia or atypical lobular hyperplasia (ADH/ALH) and followed up for long-term outcomes. After a core needle biopsy showing IDP with atypia or IDP + ADH/ALH, surgical excision yielded a diagnosis of concomitant invasive or ductal in situ cancer in greater that 30% of cases. For intraductal papilloma without atypia, the likelihood of cancer was much lower. Moreover, even with excision, the finding of intraductal papilloma with atypia carries a significant risk of developing cancer long-term, and such patients should be followed carefully and perhaps should be considered for chemoprevention.

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Objective To analyze MRI features of breast intraductal papilloma,to improve the acquaintance of this disease.Methods The preoperative MRI images (T2 WI-SPAIR,DWI,ADC,TIC and MIP)of eight patients with breast intraductal papilloma confirmed by surgery were reviewed retrospectively,which were compared with the postoperative pathology.The morphology,distribution, enhanced methods and signal characteristics of the lesion were summarized.Results Of 8 cases,the lession was dormant,and MRI revealed three patterns:the first type was occult papilloma,which presented distention of ducts and no solid nodule in 3 cases (37.5%);the second type showed tiny nodules in bar-like dilatation of ducts in 3 cases (37.5%);and the third type presented small round nodules scattering distribued in terminal ductules in 2 cases (25%).The maximum diameter of nodular lesions was 0.4-1.0 cm(average 0.7 cm).The lesions on T2 WI-SPAIR showed equal signal intensity or mixed signals with isointensity/hypointensity,and dilatation catheter.enhancement. The ADC and TIC value were various,therefore,diagnosis of the tumor should be combined with morphology and associated symptoms. Conclusion At early stage,the occult focus of breast intraductal papilloma can be sensitively detected and localized on MRI.It reveals that MRI has advantage in showing morphology of lesion and functional imaging,which is of important value in clinical diagnosis and early treatment.

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The incidence of asymptomatic papilloma has increased with the rising popularity of core needle biopsy for breast lesions. In this study, the risk of benign papilloma without atypia for subsequent breast carcinoma during follow-up was evaluated. From January 2000 to December 2010, among 39,461 women with breast ultrasonography, 37,847 women with benign papilloma on biopsy or excision, with benign diseases on biopsy, and with only ultrasonography performed were recruited. Women with concurrent or prior high-risk lesions (atypia, phyllodes tumor, or lobular neoplasm) or malignancies, or with a follow-up period of less than 12 months were excluded. The eligible 12,302 women were classified into three groups; papilloma (n = 265, patients with benign papilloma without atypia at excision), benign (n = 3,066, patients with benign results other than high risk results on core needle biopsy), and ultrasonography (n = 8,971, patients who underwent ultrasonography only without biopsy or surgery). The relative risks (RRs) of the papilloma and benign groups were calculated with intervals of 2 years using the Poisson regression analysis with age, family history, follow-up period, and breast parenchymal density being adjusted, and the ultrasonography group was used as a reference. The RR of the papilloma group was 4.8 (95% confidence interval [CI], 2.5-9.0), significantly higher than 1.5 (95% CI, 1.0-2.1) of the benign group. In the first 2 years, the RR of the papilloma group was 5.2 (95% CI, 2.2-12.6) but it dropped to 2.2 (95% CI, 0.5-9.2) during the next 2 years. Afterward, the RR increased over time although statistical significance was not achieved. Benign papilloma without atypia increased breast cancer risk fivefold when the ultrasonography group was used as a reference, higher than other benign lesions.

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