Malignant upgrade rate and associated clinicopathologic predictors for concordant intraductal papilloma without atypia: A systematic review and meta-analysis.

Previously reported upgrade rates for benign breast intraductal papilloma (IDP) are widely variable. However, many previous studies have failed to consider radiologic-pathologic discordance of lesions. This review aims to synthesize malignant upgrade data for benign, concordant IDP at surgical excision. Thirteen studies were included in our meta-analysis. The pooled estimate for percentage underestimation of carcinoma was 1.4% (95% CI: 0.8%-2.0%). We conclude that these lesions can be safely managed by active surveillance.

Intraductal papilloma with atypical ductal hyperplasia and neuroendocrine differentiation as a possible precursor lesion of solid papillary carcinoma.

Breast papillary neoplasms include a wide range of tumor types, and their pathological diagnosis is sometimes difficult. Furthermore, the etiology of these lesions is still not fully understood. We report the case of a 72-years-old woman referred to our hospital with bloody discharge from the right nipple. An imaging study detected a cystic lesion, including a solid component contiguous with the mammary duct, in the subareolar region. The lesion was then removed by segmental mastectomy. Pathological examination of the resected specimen revealed an intraductal papilloma with atypical ductal hyperplasia. Moreover, the atypical ductal epithelial cells expressed neuroendocrine markers. The presence of an intraductal papillary lesion with neuroendocrine differentiation suggests solid papillary carcinoma. Thus, this case suggests that intraductal papilloma could be a precursor of solid papillary carcinoma.

Ultrasound-Guided Vacuum-Assisted Excision to Treat Intraductal Papilloma.

BACKGROUND: To evaluate the value of ultrasound-guided vacuum-assisted excision (US-guided VAE) in the treatment of intraductal papillomas, including intraductal papillomas with atypical ductal hyperplasia (ADH), and to evaluate the lesion characteristic features affecting the local recurrence rate. MATERIALS AND METHODS: Between August 2011 and December 2020, 91 lesions of 91 patients underwent US-guided VAE and were diagnosed with intraductal papilloma with or without ADH. The recurrence rate of intraductal papilloma was evaluated on follow-up US. The lesion characteristic features were analyzed to identify the factors affecting the local recurrence rate. RESULTS: The local recurrence rate of intraductal papillomas removed by US-guided VAE was 7.7% (7/91), with the follow-up duration 12-92 months (37.4 ± 23.9 months). Of the 91 patients, five cases diagnosed as intraductal papilloma with ADH did not recur, with the follow-up time 12-47 months (26.4 ± 14.4 months). There were no malignant transformation in all 91 cases during the follow-up period. All 7 patients recurred 7-58 months (22.8 ± 19.2 months) after US-guided VAE. There were no significant differences between the non-recurrence and recurrence groups in terms of age, side, distance from nipple, lesion size, BI-RADS category, with ADH, or history of excision (p > 0.05). CONCLUSIONS: US-guided VAE is an effective method for the treatment of intraductal papilloma, including intraductal papilloma with ADH. It avoids invasive surgical excision, but regular follow-up is recommended to prevent recurrence or new onset due to multifocality. Any suspicious lesions during the follow-up should be actively treated.

Radiologic and Pathologic Findings of Axillary Intraductal Papilloma Arising in Accessory Breast Tissue: A Case Report and Literature Review.

INTRODUCTION: This is a rare case report of axillary intraductal papilloma arising in accessory breast tissue. CASE PRESENTATION: A 49-year-old woman presented to our clinic with a palpable right axillary mass that had first appeared 6 months earlier. Mammography and ultrasonography of the right axilla revealed an ovoid mass surrounding accessory breast tissue. Ultrasound-guided 14-G core-needle biopsy was performed and pathologically revealed intraductal papilloma without atypia. CONCLUSION: Since ectopic breast tissue is affected by the same pathologic processes as normal breast tissue, a core-needle biopsy can be used to identify the suspicious lesions in axillary breast tissue.

Intraductal Papilloma With Carcinoma of the Breast Described by Dedicated Breast 18F-FDG PET.

ABSTRACT: Intraductal papilloma (IDP) is a benign tumor of the breast. However, IDP has been reported to show high uptake of 18F-FDG using whole-body PET. We experienced IDP with low-grade ductal carcinoma in situ using dedicated breast PET, which is more sensitive than whole-body PET. The 18F-FDG uptake of the whole tumor was high, and differentiation between the carcinoma and the residual benign lesion was difficult. This is the first report of IDP detected with dedicated breast PET. Diagnosis of IDP is sometimes controversial; papilloma may show glucose uptake similar to that of low-grade carcinoma.

Multidisciplinary Review of Intraductal Papilloma of the Breast can Identify Patients who may Omit Surgical Excision.

BACKGROUND: The purpose of this study was to define contemporary management recommendations regarding who would benefit from surgical excision of intraductal papilloma (IDP). METHODS: A prospective database from a single institution identified patients with IDP on percutaneous biopsy from February 2015 to September 2020. Categorical patient demographic, biopsy, and pathologic variables were analyzed using Fisher's exact test and continuous demographic and imaging variables using the Mann-Whitney U test. RESULTS: IDP was present in 416 biopsies, at a median age of 56 years. The median size was 0.9 cm, and the majority had greater than 50% of the target excised by biopsy. Surgical excision was performed for 124 of 416 biopsies (29.8%). Upgrade to malignancy was identified in 14 (11.3%): 8 to ductal carcinoma in situ (DCIS) and 6 to invasive cancer. Upgrade was significantly associated with concurrent ipsilateral breast cancer (p = 0.027), larger imaging size (p = 0.045), <50% excised with biopsy (p = 0.02), and atypia involving IDP (p = 0.045). Age, clinical presentation, and concurrent contralateral cancer were not significantly associated with upgrade. Lowest upgrade risk (0%) was in pure IDP ≤1 cm with >50% removed by biopsy. Of 401 biopsies that either did not upgrade or undergo excision, 7 (1.7%) developed subsequent breast cancer over a median follow-up of 23.5 months (interquartile range [IQR] 11,41), none at IDP site. CONCLUSIONS: After multidisciplinary review, the management of IDP can be stratified into low- and high-risk for upgrade groups using key criteria. Low-risk group may omit surgical excision, because those patients have 0% risk of upgrade over the limited short-term follow-up.

High-Risk Lesions Detected by MRI-Guided Core Biopsy: Upgrade Rates at Surgical Excision and Implications for Management.

OBJECTIVE. The purpose of our study was to evaluate the upgrade rates of high-risk lesions (HRLs) diagnosed by MRI-guided core biopsy and to assess which clinical and imaging characteristics are predictive of upgrade to malignancy. MATERIALS AND METHODS. A retrospective review was performed of all women who presented to an academic breast radiology center for MRI-guided biopsy between January 1, 2015, and November 30, 2018. Histopathologic results from each biopsy were extracted. HRLs-that is, atypical ductal hyperplasia (ADH), lobular carcinoma in situ (LCIS), atypical lobular hyperplasia (ALH), radial scar, papilloma, flat epithelial atypia (FEA), benign vascular lesion (BVL), and mucocelelike lesion-were included for analysis. Clinical history, imaging characteristics, surgical outcome, and follow-up data were recorded. Radiologic-pathologic correlation was performed. RESULTS. Of 810 MRI-guided biopsies, 189 cases (23.3%) met the inclusion criteria for HRLs. Of the 189 HRLs, 30 cases were excluded for the following reasons: 15 cases were lost to follow-up, six cases were in patients who received neoadjuvant chemotherapy after biopsy, two lesions that were not excised had less than 2 years of imaging follow-up, and seven lesions had radiologic-pathologic discordance at retrospective review. Of the 159 HRLs in our study cohort, 13 (8.2%) were upgraded to carcinoma. Surgical upgrade rates were high for ADH (22.5%, 9/40) and FEA (33.3%, 1/3); moderate for LCIS (6.3%, 3/48); and low for ALH (0.0%, 0/11), radial scar (0.0%, 0/28), papilloma (0.0%, 0/26), and BVL (0.0%, 0/3). Of the upgraded lesions, 69.2% (9/13) were upgraded to ductal carcinoma in situ (DCIS) or well-differentiated carcinoma. ADH lesions were significantly more likely to be upgraded than non-ADH lesions (p = .005). CONCLUSION. ADH diagnosed by MRI-guided core biopsy warrants surgical excision. The other HRLs, however, may be candidates for imaging follow-up rather than excision, especially after meticulous radiologic-pathologic correlation.

Evaluating the usefulness of breast strain elastography for intraductal lesions.

PURPOSE: Strain elastography for imaging lesion stiffness is being used as a diagnostic aid in the malignant/benign discrimination of breast diseases. While acquiring elastography in addition to B-mode images has been reported to help avoid performing unnecessary biopsies, intraductal lesions are difficult to discriminate whether they are malignant or benign using elastography. An objective evaluation of strain in lesions was performed in this study by measuring the elasticity index (E-index) and elasticity ratio (E-ratio) of lesions as semi-quantitative numerical indicators of the color distribution of strain. We examined whether ductal carcinoma in situ (DCIS) and intraductal papilloma could be distinguished using these semi-quantitative numerical indicators. METHODS: In this study, 170 ultrasonographically detected mass lesions in 162 cases (106 malignant lesions and 64 benign lesions)-in which tissue biopsy by core needle biopsy and vacuum-assisted biopsy, or surgically performed histopathological diagnosis, was performed-were selected as subjects from among 1978 consecutive cases (from January 2014 to December 2016) in which strain elastography images were acquired, in addition to standard B-mode breast ultrasonography, by measuring the E-index and E-ratio. RESULTS: The cut-off values for E-index and E-ratio in the malignant/benign discrimination of breast lesions were determined to be optimal values at 3.5 and 4.2, respectively, based on receiver operating characteristic (ROC) curve analysis. E-index sensitivity, specificity, accuracy, and AUC value (area under the curve) were 85%, 86%, 85%, and 0.860, respectively, while those for E-ratio were 78%, 74%, 74%, and 0.780, respectively. E-index yielded superior results in all aspects of sensitivity, specificity, accuracy, and AUC values, compared to those of E-ratio. The mean E-index values for malignant tumors and benign tumors were 4.46 and 2.63, respectively, indicating a significant difference (P < 0.001). E-index values of 24 DCIS lesions and 25 intraductal papillomas were 3.88 and 3.35, respectively, which showed a considerably close value, while the false-negative rate for DCIS was 29.2%, and the false-positive rate for intraductal papilloma was as high as 32.0%. CONCLUSION: E-index in strain elastography yielded better results than E-ratio in the malignant/benign discrimination of breast diseases. On the other hand, E-index has a high false-negative rate and false-positive rate for intraductal lesions, a factor which should be taken into account when making ultrasound diagnoses.

Breast Imaging Reporting and Data System Classification for Central-Type Intra-Ductal Papillary Masses: Current Problems and Evaluation of Modified Parameters.

The Breast Imaging Reporting and Data System (BI-RADS) standards have limitations regarding classifying and managing central intra-ductal papillary masses. Changes to the standards are necessary to provide early and effective treatment. To summarize the ultrasonographic imaging features of central mammary ductal papillary masses, this retrospective study included 56 participants. In identifying benign versus malignant lesions, the most significant indicators were angular edges and the long diameter of the tumor parallel to the duct. In the comparison of diagnostic efficacy for central mammary ductal tumors, the post-operative pathologic malignant upgrade rate of BI-RADS was 33.3%, and that of the new standard criteria was 14.2%. The angle of the wall of the tumor relative to the duct was most helpful. When BI-RADS is used to evaluate a papillary mass in a central duct, it is more accurate when the tumor is parallel to the duct than parallel to the skin.

The Role of Combined Diffusion-Weighted Imaging and Dynamic Contrast-Enhanced MRI for Differentiating Malignant From Benign Breast Lesions Presenting Washout Curve.

PURPOSE: The aim of this study is to evaluate the diagnostic performance of combined breast magnetic resonance imaging (MRI) protocol including dynamic contrast-enhanced MRI (DCE-MRI) and diffusion-weighted imaging (DWI) in patients with enhancing lesions that demonstrated washout curve and to determine whether applying apparent diffusion coefficient (ADC) cutoff value could improve the diagnostic value of breast MRI. METHODS: The retrospective study included 116 patients with 116 suspicious breast lesions, which showed washout curve on DCE-MRI, who underwent subsequent biopsy. Morphologic characteristics on DCE-MRI and ADC values on DWI were evaluated. Apparent diffusion coefficient values and morphologic features of benign and malignant lesions were compared. Diagnostic values of DCE-MRI and combined MRI, including DCE-MRI and DWI (applying an ADC cutoff value) for distinguishing malignancy from benign lesions, were calculated. RESULTS: Of the 116 breast lesions, 79 were malignant and 37 were benign. The ADC value of malignant tumors (median ADC, 0.72 × 10-3 mm2/s) was significantly lower than that of benign lesions (median ADC, 1.03 × 10-3 mm2/s; P < .000). The sensitivity and specificity of an ADC cutoff value of 0.89 × 10-3 mm2/s were 92% and 95%, respectively. Dynamic contrast-enhanced MRI alone presented 100% sensitivity and 59.4% specificity. Adding an ADC cutoff value of 0.89 × 10-3 mm2/s provided 100% sensitivity and 81% specificity, which would have prevented biopsy for 21.6% of benign lesions without missing any malignancies. CONCLUSION: Applying an ADC cutoff value to DCE-MRI provides an improvement in the diagnostic value of breast MRI for differentiating among lesions presenting washout curve.

A retrospective observational study of intraductal breast papilloma and its coexisting lesions: A real-world experience.

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.

Unusual recurrent metastasizing benign breast papilloma: a case report.

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.

Upgrade rate of intraductal papilloma without atypia on breast core needle biopsy: A clinical, radiological and pathological correlation study.

BACKGROUND: The aim of the study was to determine the upgrade rate on excision of intraductal papilloma (IDP) without atypia diagnosed on breast core needle biopsy (CNB). METHODS: We searched our pathology department database for breast CNB with a diagnosis of IDP from 2013 to 2018. The exclusion criteria included radiologic-pathologic discordance, atypia on the same CNB, absence of histologic slides to review or absence of excision information. Upgrade was defined as ductal carcinoma in situ (DCIS) or invasive cancer identified on excision. RESULTS: 126 IDP without atypia cases from 94 patients were identified. The upgrade rate was 1.58% (2/126). Both upgrade cases showed DCIS with low and intermediate nuclear grade. Histologic size of IDP ≥1 cm was the only statistically significant predictor factor for an upgrade on excision. CONCLUSION: The results suggest that non-surgical management of patients with radiologic-pathologic concordant IDP without atypia diagnosed on CNB may be appropriate in routine practice.

Papilomatosis juvenil: revisión a propósito de 2 casos / Juvenile papillomatosis: Review of 2 cases

La papilomatosis juvenil (PJ) es una lesión mamaria benigna, poco frecuente y de carácter proliferativo. Se caracteriza por ser una proliferación exofítica multifocal de varios papilomas dentro de un segmento mamario. Generalmente afecta a mujeres jóvenes de menos de 30 años de edad. Suele presentarse como una tumoración mamaria indolora, simulando un fibroadenoma. La biopsia percutánea guiada por ecografía permitirá detectar la naturaleza de la lesión y descartar patología maligna asociada. Se describe una serie de 2 casos con similar presentación clínica pero difiriendo en el manejo una vez analizados los antecedentes familiares y las circunstancias individuales de cada uno de ellos

Juvenile papillomatosis (JP) is a rare breast lesion of a proliferative and benign nature. It is noted for being a multifocal exophytic proliferation of several papillomas within a breast segment. It usually affects young women under 30 years of age, and usually presents as a painless breast mass, simulating a fibrous adenoma. The ultrasound guided percutaneous biopsy will enable the diagnosis to be confirmed, as well as to rule out any associated malignant disease. A description is presented on series of 2 cases with similar clinical presentation, but differing in management after analysing the family history and the individual circumstances of each of them

Retrospective statistical analysis on the diagnostic value of ductography based on lesion pathology in patients presenting with nipple discharge.

PURPOSE: To compare sensitivities and specificities of ductography to noninvasive imaging studies in determining the cause of nipple discharge and assess the value of ductography on the basis of pathologic results. METHODS: In this retrospective review of women with nipple discharge who underwent ductography between January 1, 2005 and October 30, 2015, at our institution, we compared ductography with noninvasive imaging results (mammography, ultrasound, MRI) to determine its relative diagnostic sensitivity, specificity, and relative accuracy. Diagnosis was defined from pathology results, clinical notes, and minimum of 1-year follow-up monitoring. The primary endpoints include accuracy, sensitivity, specificity, positive predictive value, and negative predictive value. The analyses were carried out in different configurations to compare results by the following pathologic categories: cancer, high-risk lesion, intraductal papilloma (IP) without atypia, and benign pathology and/or normal imaging results. RESULTS: In patients with breast cancer, ductography and noninvasive breast imaging had similar sensitivities. In patients with a high-risk lesion, ductography was significantly more sensitive than noninvasive imaging modalities. In patients with intraductal papilloma without atypia, ductography was more sensitive than noninvasive imaging, but the difference was of only borderline significance. For women with benign pathology and/or normal imaging, noninvasive imaging showed a significantly higher specificity than ductography. CONCLUSION: In the absence of standard diagnostic algorithm for patients presenting with nipple discharge, the clinician has numerous options to choose a diagnostic approach that will yield the most accurate information with the least disruption to the patient. Our results indicate the value of ductography compared to value of noninvasive imaging modalities when cancer is suspected and when high risk lesion is suspected. While we show the sensitivity of ductography is similar to noninvasive imaging modalities in the setting of cancer, the sensitivity of ductography is statistically valuable for diagnosing high-risk lesions. Our hope is that this study will emphasize more research and more understanding in clinical utility and management of high-risk lesions, leading to patient-focused algorithm for diagnosing the etiology of abnormal nipple discharge.

Ultrasound-guided 7-gauge vacuum-assisted core biopsy: Could it be sufficient for the diagnosis and treatment of intraductal papilloma?

The aim of this study was to evaluate whether ultrasound-guided 7-gauge vacuum-assisted core biopsy is sufficient for the diagnosis and treatment of intraductal papilloma and to evaluate the lesion characteristics and histologic features affecting the excision rate of papilloma with vacuum-assisted core biopsy. Between March 2008 and October 2016, 2816 patients underwent US-guided, 7-gauge vacuum-assisted core biopsy (VACB). In them, 101 (3.6%) were demonstrated to have intraductal papilloma by pathology. The accurate diagnostic rate and excision rate of intraductal papilloma after vacuum-assisted core biopsy were evaluated by open surgical biopsy or follow-up US. The lesion characteristics and histologic features were analyzed to identify factors affecting the excision rate of papilloma after VACB. Of the 101 intraductal papillomas, 83 (82.2%) cases were benign papilloma. Two cases were intraductal papilloma accompanied by invasive carcinoma. Sixteen (15.8%) cases were with signs of atypical hyperplasia. In them, one intraductal papilloma accompanied by severe atypical hyperplasia underwent further surgery, and it was demonstrated to have intraductal papilloma accompanied by invasive carcinoma. The accurate diagnostic rate of intraductal papillomas by 7-gauge VACB was 99.0% (100/101). There was no recurrence or malignant transformation in 85.1% (86/101) intraductal papillomas after 7-gauge vacuum-assisted core biopsy. Intraductal papilloma with largest diameter <1 cm, with clear margin, without branch involvement or calcification had a significantly higher excision rate. Seven-gauge VACB is an effective method for the diagnosis of intraductal papilloma of the breast. If histopathological examination confirms a benign character of the lesion, surgery may be avoided but regular follow-up is recommended. If histopathological examination confirms a papilloma with moderate to severe atypical hyperplasia, it was strongly recommended for surgical excision. Lesion characteristics and histologic features could affect the excision rate of intraductal papillomas with VACB.