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.

The Diagnostic Value of microRNA Expression Analysis in Detecting Intraductal Papillomas in Patients with Pathological Nipple Discharge.

Patients with pathological nipple discharge (PND) often undergo local surgical procedures because standard radiologic imaging fails to identify the underlying cause. MicroRNA (MiRNA) expression analysis of nipple fluid holds potential for distinguishing between breast diseases. This study aimed to compare miRNA expression levels between nipple fluids from patients with PND to identify possible relevant miRNAs that could differentiate between intraductal papillomas and no abnormalities in the breast tissue. Nipple fluid samples from patients with PND without radiological and pathological suspicion for malignancy who underwent a ductoscopy procedure were analyzed. We used univariate and multivariate regression analyses to identify nipple fluid miRNAs differing between pathologically confirmed papillomas and breast tissue without abnormalities. A total of 27 nipple fluid samples from patients with PND were included for miRNA expression analysis. Out of the 22 miRNAs examined, only miR-145-5p was significantly differentially expressed (upregulated) in nipple fluid from patients with an intraductal papilloma compared to patients showing no breast abnormalities (OR 4.76, p = 0.046), with a diagnostic accuracy of 92%. miR-145-5p expression in nipple fluid differs for intraductal papillomas and breast tissue without abnormalities and, therefore, has potential as a diagnostic marker to signal presence of papillomas in PND patients. However, further refinement and validation in clinical trials are necessary to establish its clinical applicability.

Diagnostic and Therapeutic Roles of Microdochectomy and Subareolar Ducts Excision for Pathological Nipple Discharge in Lagos.

BACKGROUND: Pathological nipple discharge (PND) comprises less than 10% of presentation in breast clinics. Data on the management of nipple discharge (ND) in our environment are scarce. AIM: To review management outcome in cohorts of patients with PND in our institution between December 2010 and October 2020. METHODOLOGY: This is a retrospective review of consecutive patients managed for PND between 2010 and 2020. Demographical characteristics, clinical features, investigation results and management outcome were retrieved from the clinical records for analysis. A cross-sectional survey via telephone conversation/clinic consultation was carried out to monitor patients for post-operative complications and recurrence. RESULTS: There were 25 patients (18 microdochectomies and 7 subareolar duct excisions) in the study with a median age of 44 (37.5-49.5) years. The median duration of symptoms before presentation was 3 (2.5-5.5) months. The major characteristics of ND in the study cohort were: single duct orifice in 18 patients (72%) spontaneous ND in 14 patients (56%); right ND in 15 patients (60%); and bloody ND in 21 patients (84 %). Only one patient had a family history of breast cancer. Intraductal papilloma diagnosed in 9 patients (36%) was the most common cause of PND. Breast cancer was an underlying aetiology in 28% of patients in the series. Six out of 7 patients with breast cancer diagnosis were <50years. CONCLUSION: Most women with PND in our practice were young with predominance of spontaneous bloody discharge. Intraductal papilloma was the most common cause of PND in this study. Breast cancer accounted for about a third of cases.

CONTEXTE: L'écoulement mamelonnaire pathologique (EMP) représente moins de 10 % des cas présentés dans les cliniques du sein. Les données sur la prise en charge de l'écoulement mamelonnaire (EM) dans notre environnement sont rares. OBJECTIF: Examiner les résultats de la prise en charge dans des cohortes de patientes présentant un écoulement mamelonnaire pathologique dans notre établissement entre décembre 2010 et octobre 2020. MÉTHODOLOGIE: Il s'agit d'une revue rétrospective des patientes consécutives prises en charge pour un DP entre 2010 et 2020. Les caractéristiques démographiques, les caractéristiques cliniques, les résultats des examens et les résultats de la prise en charge ont été extraits des dossiers cliniques pour analyse. Une enquête transversale par conversation téléphonique/consultation en clinique a été réalisée pour surveiller les complications post-opératoires et les récidives chez les patients. RÉSULTATS: L'étude a porté sur 25 patients (18 microdochectomies et 7 excisions du canal sous-aréolaire) dont l'âge médian était de 44 ans (37,5-49,5). La durée médiane des symptômes avant la consultation était de 3 (2,5-5,5) mois. Les principales caractéristiques de la MN dans la cohorte de l'étude étaient les suivantes : orifice unique dans 18 patients (72 %), MN spontanée chez 14 patients (56%), MN droite chez 15 patients (60 %) et MN sanglante chez 21 patients (84 %). Une seule patiente avait des antécédents familiaux de cancer du sein. Le papillome intraductal diagnostiqué chez 9 patientes (36 %) était la cause la plus fréquente de la MN. Le cancer du sein était une cause sous-jacente chez 28 % des patientes de la série. Six des sept patientes chez qui un cancer du sein a été diagnostiqué avaient moins de 50 ans. CONCLUSION: Dans notre pratique, la plupart des femmes souffrant de DPN étaient jeunes, avec une prédominance d'écoulements sanglants spontanés. Le papillome intraductal était la cause la plus fréquente de DPN dans cette étude. Le cancer du sein représentait environ un tiers des cas. Mots-clés: Cancer du sein, Écoulement, Mamelon, Pathologique.

The effect of delay of excisional biopsy on upstage rate for atypical ductal hyperplasia, flat epithelial atypia, intraductal papilloma, and radial scar.

PURPOSE: When Core Needle Biopsy (CNB) demonstrates Atypical Ductal Hyperplasia (ADH), Flat Epithelial Atypia (FEA), Intraductal Papilloma (IDP), or Radial Scar/Complex Sclerosing Lesion (RS), excisional biopsy (EB) is often performed to rule out underlying malignancy with upstage rates (UR) ranging between 1 and 20%. The COVID-19 pandemic led to delayed EB for many patients. We sought to evaluate whether this delay was associated with higher UR. METHODS: We performed a retrospective analysis of women who underwent CNB and then EB for ADH, FEA, IDP, or RS between 2017 and 2021 using an IRB-approved repository. UR was evaluated by days between CNB and EB. RESULTS: 473 patients met inclusion. 55 were upstaged to cancer (11.6%). 178 patients had pure ADH on CNB and 37 were upstaged (20.8%). 50 patients had pure FEA and 3 were upstaged (6%). 132 had pure IDP and 7 were upstaged (5.3%). 98 had pure RS and 1 was upstaged (1%). 7/15 (46.7%) had a combination of diagnoses or diagnosis with palpable mass and were upstaged. Days between CNB and EB were < 60 for 275 patients (58.1%), 60-90 for 108 (22.8%), 91-120 for 43 (9.1%), and > 120 for 47 (9.9%). There was no significant difference in UR (10.9% for < 60, 14.8% for 60-90, 7% for 90-120, and 12.8% for > 120, p = 0.54). UR for ADH was clinically increased after 60 days (27.8 vs. 17.5%), but this did not reach statistical significance (p = 0.1). CONCLUSION: Surgical delay was not associated with an increased UR.

Papillary lesions of the breast - review and practical issues.

Papillary lesions of the breast represent a heterogeneous group of neoplasm featuring fibrovascular cores covered by epithelial cells with or without intervening myoepithelial cells. According to the World Health Organization classification of breast tumors, papillary lesions of the breast are further classified into intraductal papilloma (including intraductal papilloma with atypical ductal hyperplasia /ductal carcinoma in situ), papillary ductal carcinoma in situ, encapsulated papillary carcinoma, solid papillary carcinoma (in situ and invasive) and invasive papillary carcinoma. The overlapping morphological features and immunohistochemical profiles make accurate diagnosis of breast papillary lesion a challenge for pathologists. In this review, the morphological and relevant immunohistochemical features of papillary lesions are discussed, with further emphasis on some commonly encountered practical diagnostic issues. A simple diagnostic algorithm will be established. The relevant molecular characteristics will be discussed as well.

Papillary neoplasms of the breast including upgrade rates and management of intraductal papilloma without atypia diagnosed at core needle biopsy.

Papillary neoplasms of the breast are a heterogeneous group of epithelial tumors nearly entirely composed of papillae. Their classification rests on the characteristics of the epithelium and the presence and distribution of the myoepithelial cells along the papillae and around the tumor. Papillary neoplasms of the breast can be diagnostically challenging, especially if only core needle biopsy (CNB) material is available. This review summarizes salient morphological and immunohistochemical features, clinical presentation, and differential diagnoses of papillary neoplasms of the breast. We include a contemporary appraisal of the upgrade rate to carcinoma (invasive carcinoma and ductal carcinoma in situ [DCIS]) and atypical hyperplasias in surgical excision specimens obtained following CNB diagnosis of papilloma without atypia, and a review of the available follow-up data in cases without immediate surgical excision.

Benign Breast Intraductal Papillomas Without Atypia at Core Needle Biopsies: Is Surgical Excision Necessary?

PURPOSE: The aim of this study was to determine the upgrade rate of image-guided core needle biopsy (CNB)-proven benign breast intraductal papillomas (IDPs) without atypia to high-risk benign lesions or malignancy after surgical excision. METHODS: A retrospective database search at a single institution identified 102 adult female patients with benign breast IDPs without atypia diagnosed on imaging-guided CNBs who subsequently had surgical excisions between 2011 and 2016. Patient characteristics, imaging features, biopsy techniques, and the pathology reports from imaging-guided CNBs and subsequent surgical excisions were reviewed. The upgrade rate to malignancies or high-risk benign lesions was determined at the patient level. RESULTS: The upgrade rate to malignancy was 2.9% (3/102), including two cases of ductal carcinoma in situ (DCIS) and one case of microinvasive (< 1 mm) ductal carcinoma arising from DCIS. The upgrade rate to high-risk benign lesions was 7.8% (8/102), with seven cases of atypical ductal hyperplasia and one case of atypical lobular hyperplasia. A personal history of breast cancer and a larger mean lesion size were significantly associated with an upgrade to malignancy (p < 0.05). CONCLUSIONS: The management of benign breast IDPs without atypia detected on imaging-guided CNBs is controversial. Our results suggest risk stratification is important in approaching these patients. Although surgical excision should be considered for all benign breast IDPs without atypia, observation with serial imaging may be appropriate in selected low-risk patients. This approach will save many women from surgeries and decrease the cost of medical care.

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.

Bloody nipple discharge in Carney complex: A case report.

Carney complex (CNC) is an extremely rare, autosomal dominant genetic syndrome consisting of pigmented skin and mucosal changes with multiple endocrine and nonendocrine tumors, including the breast. Breast tumors are typically multiple and benign and are most commonly reported as myxoid fibroadenomas and/or intraductal papillomas. We present a young female patient with known CNC who presented with copious bloody nipple discharge with multiple breast lumps and discuss the breast imaging features regarding this complex and often underrecognized genetic condition.

Histopathological evaluation of minor salivary gland papillary-cystic tumours: focus on genetic alterations in sialadenoma papilliferum and intraductal papillary mucinous neoplasm.

AIMS: Minor salivary gland tumours showing a predominant papillary-cystic structure are rare, and constitute a mixture of various types of neoplasm; thus, the histopathological assessment of these tumours poses a significant diagnostic challenge. We aimed to delineate the histological characteristics of these tumours and further mutational aspects with a particular focus on sialadenoma papilliferum (SP) and intraductal papillary mucinous neoplasm (IPMN). METHODS AND RESULTS: We retrieved 28 papillary-cystic tumours of the minor salivary glands, and performed histological re-evaluation and mutation analyses of several key oncogenes. The histological classifications were as follows: SP (n = 10), SP-like intraductal papillary tumour (SP-IPT) (n = 2), IPMN (n = 9), intraductal papilloma, cystadenoma, and cystadenocarcinoma (two, three and two respectively). Whereas SP typically consisted of a combination of exophytic squamous epithelium and endophytic intraductal papillary infoldings, SP-IPT lacked the exophytic component. SP and SP-IPT frequently harboured BRAF V600E mutations (75.0%), which were identified in both squamous and ductal components. IPMN was characterised by a well-demarcated cystic lesion filled exclusively with a papillary proliferation of mucinous cells and a high rate of AKT1 E17K mutations (88.9%). Intraductal papillomas were unilocular cystic lesions with intraluminal papillary growth of bland columnar cells. In contrast, both cystadenomas and cystadenocarcinomas showed a multicystic appearance with a papillary configuration. Cystadenocarcinomas invaded the surrounding tissue and were composed of markedly atypical tumour cells. CONCLUSION: The appropriate interpretation of histological findings and specific genetic alterations (e.g. BRAF V600E and AKT1 E17K in SP and IPMN) would be useful for the correct diagnosis of minor salivary gland papillary-cystic tumours.

Immunohistochemical staining as supportive diagnostic tool for pseudomyxoma peritonei arising from intraductal papillary mucinous neoplasm: A report of two cases and literature review.

BACKGROUND/OBJECTIVES: Pseudomyxoma peritonei (PMP) arising from an intraductal papillary mucinous neoplasm of the pancreas (IPMN) is a rare condition. The diagnosis of IPMN as the origin of PMP is mainly inferred from the clinical course and the exclusion of PMP from other organs. The pathological diagnosis has not yet been established. To evaluate the usefulness of immunohistochemical staining for the diagnosis of the primary lesion of PMP as IPMN. METHODS: There are 2 cases of PMP arising from IPMN between March 2010 and December 2019 at National Center for Global Health and Medicine. A PubMed search that reported PMP arising from IPMN identified 16 additional cases. Diagnostic methods and clinicopathological features of 18 cases were compared. RESULTS: Four cases including our two cases used immunohistochemical staining for the diagnosis of PMP arising from IPMN. The correspondence of the immunohistochemical staining between PMP and IPMN was shown in the three cases including previously reported two cases and one of our two cases to identify the primary lesion of PMP as IPMN. In addition, we revealed that the comparison of the immunostaining pattern of PMP with the representative immunostaining pattern of the candidate primary lesions is helpful for the diagnosis of the primary lesion of PMP. CONCLUSIONS: Immunohistochemical staining is helpful to identify the primary lesion of PMP as IPMN.

Pathology of breast papillary neoplasms: Community hospital experience.

In this study, 550 breast papillary neoplasms collected in a community hospital over more than ten years were reviewed and analyzed. This included 457 intraductal papillomas, 53 papillary carcinomas, 35 papillary DCIS and five invasive papillary carcinomas. The diagnostic rate of papillary neoplasms increased over time, likely due to better recognition by pathologists. Intraductal papillomas occurred most frequently in the upper outer quadrants and contained ADH/DCIS in 19% of cases. A total of 28% of non-incidental papillomas were associated with ADH/DCIS, and 29% of patients with papillomas had ADH/DCIS in adjacent tissue; nearly half of papillomas that were > 1 cm in size contained ADH/DCIS in the papilloma or adjacent to it. No single feature could predict an upgrade on excision for non-atypical intraductal papillomas diagnosed on core biopsy. There was no significant difference in the association of ADH/DCIS with central or peripheral papillomas. The overall upgrade rate of non-atypical intraductal papillomas to DCIS on excision was 2%, which justifies the conservative management of non-atypical sub-centimeter lesions. Papillary carcinomas occurred in older than intraductal papilloma patients and were most frequent in the upper quadrants. Although classically devoid of a myoepithelial cell layer, papillary carcinomas may contain some residual or even an ample myoepithelial cell layer in the papillae. An association between papillary carcinoma and conventional invasive carcinoma was found in 40% of EPCs and 89% of SPCs. Papillary DCIS was usually low- or intermediate-grade. The presence of a myoepithelial cell layer in the papillae was not inconsistent with this diagnosis. Invasive papillary carcinoma may have two histologic patterns: papillary and cribriform.

Multiplex PCR analysis of apocrine lesions shows frequent PI3K-AKT pathway mutations in both benign and malignant apocrine breast tumors.

Pathological diagnosis of intraductal apocrine lesions can be challenging, because even benign apocrine lesions often show atypical cytology, and immunohistochemistry is of little assistance. A new diagnostic method for apocrine lesions is desirable. The mutations present in apocrine lesions have not been well studied. We performed a MassARRAY multiplex polymerase chain reaction (PCR) study of benign and malignant apocrine lesions, which included 152 mutations of 18 genes. We found that four of 11 benign lesions showed AKT1 or PIK3CA mutations, one of four noninvasive apocrine carcinomas showed a FBX4 mutation, two of 15 invasive apocrine carcinomas showed a PIK3CA mutation, and one invasive apocrine carcinoma showed both PIK3CA and TP53 mutations. The mutation frequency did not differ significantly between benign and malignant lesions (p = 0.683). We demonstrated that both benign and malignant apocrine lesions may contain mutations of genes in the PI3K-AKT pathway, this pathway could be a good therapeutic target of these diseases.

Mutational Analysis of AKT1 and PIK3CA in Intraductal Papillomas of the Breast with Special Reference to Cellular Components.

The pathologic feature of intraductal papillomas is defined as a papillary structure composed of a fibrovascular stromal core lined by luminal epithelial cells and myoepithelial cells. We used droplet digital PCR for the mutational analysis of AKT1 (E17K) and PIK3CA (H1047R, E542K, and E545K) in 60 papillomas. AKT1 and PIK3CA mutations were detected in 12 (20%) and 17 (28%) of the papillomas, respectively. In five tumors harboring mutations, mutational analysis of AKT1 or PIK3CA was performed separately using luminal epithelial cells and myoepithelial cells sorted using anti-cytokeratin 19 antibody and anti-α smooth muscle actin antibody. The two types of cells from a given papilloma had the identical mutation. Three patients with the PIK3CA mutation-positive papilloma developed breast cancers at the resection site of the papilloma, but none of these subsequent breast cancers had the PIK3CA mutation. These results indicate that a papilloma stems from a bipotent progenitor cell that contains the AKT1 or PIK3CA mutation and proliferates and differentiates to form the papilloma. Papilloma can be a risk factor for developing breast cancer but is unlikely to be its obligate precursor.

Treatment and Outcome of 341 Papillary Breast Lesions.

BACKGROUND: Papillary breast lesions constitute a pathological heterogeneous group and display diverse clinical and imaging features. This study was conducted to analyze the upgrade rate of intraductal papilloma diagnosed on core needle biopsy and to assess the possible risk factors associated with upgrade to higher-risk lesions. We also examined the long-term outcomes in patients who received resection of the papillary lesions. MATERIALS AND METHODS: The clinical and pathology records of 324 female patients who were diagnosed with papillary lesions based on core needle biopsy (CNB) from February 2010 to October 2016 at our institution were retrospectively analyzed. Patients were grouped by initial diagnosis into two groups (papilloma with or without atypia) and followed-up for long-term outcomes. For the upgrade to higher-risk lesions after excision, upgraded lesions were compared with benign papillomas for the collected variables. RESULTS: A total of 341 lesions were included for final analysis, and all were available for follow-up. Papillomas with or without atypia diagnosed by CNB were found in 9 and 332 lesions, respectively. Papillomas without atypia on CNB were treated by open excision (n = 265) or vacuum-assisted biopsy (VAB) (n = 67), which yielded similar event-free rate (p = 0.19). The upgrade rate of this group to higher-risk lesions was 9.9%. Peripheral (p = 0.011) lesions in postmenopausal (p = 0.001) or older (p = 0.001) patients with papillomas without atypia based on CNB showed significantly higher upgrade rates. Papillomas with atypia on CNB were all managed by open excision, and concurrent malignancy was found in two lesions. CONCLUSION: In conclusion, our results support benign papillary lesions based on CNB require further treatment. Peripheral lesions occurring in older or postmenopausal women are at higher risk for upgrade.

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.

Excision recommended in high-risk patients: Revisiting the diagnosis of papilloma on core biopsy in the context of patient risk.

We investigate the clinical history, past medical history, and risk status in women with benign intraductal papillomas(IDP). We observed an upgrade rate of 3.9% to ductal carcinoma in situ (DCIS) and upgrade rate of 10.7% to a high-risk lesion. Prior or concurrent atypia or cancer and high-risk status had a significant increase risk of upgrade. Surgical excision of papillomas is recommended especially in high-risk patients and women with concurrent or history of atypia or malignancy.

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.

INTEND II randomized clinical trial of intraoperative duct endoscopy in pathological nipple discharge.

BACKGROUND: The majority of lesions resulting in pathological nipple discharge are benign. Conventional surgery is undirected and targeting the causative lesion by duct endoscopy may enable more accurate surgery with fewer complications. METHODS: Patients requiring microdochectomy and/or major duct excision were randomized to duct endoscopy or no duct endoscopy before surgery. Primary endpoints were successful visualization of the pathological lesion in patients randomized to duct endoscopy, and a comparison of the causative pathology between the two groups. The secondary endpoint was to compare the specimen size between groups. RESULTS: A total of 68 breasts were studied in 66 patients; there were 31 breasts in the duct endoscopy group and 37 in the no-endoscopy group. Median age was 49 (range 19-81) years. Follow-up was 5·4 (i.q.r. 3·3-8·9) years in the duct endoscopy group and 5·7 (3·1-9·0) years in no-endoscopy group. Duct endoscopy had a sensitivity of 80 (95 per cent c.i. 52 to 96) per cent, specificity of 71 (44 to 90) per cent, positive predictive value of 71 (44 to 90) per cent and negative predictive value of 80 (52 to 96) per cent in identifying any lesion. There was no difference in causative pathology between the groups. Median volume of the surgical resection specimen did not differ between groups. CONCLUSION: Diagnostic duct endoscopy is useful for identifying causative lesions of nipple discharge. Duct endoscopy did not influence the pathological yield of benign or malignant diagnoses nor surgical resection volumes. Registered as INTEND II in CancerHelp UK clinical trials database (https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-study-looking-at-changes-inside-the-breast-ducts-of-women-who-have-nipple-discharge).

Are we overtreating intraductal papillomas?

BACKGROUND: The management of intraductal papillomas (IDPs) diagnosed on core needle biopsy (CNB) remains controversial regarding whether excision is required. We evaluated whether excision of IDPs might be overtreatment based on a consecutive patient population where all IDPs were routinely excised. MATERIALS AND METHODS: We retrospectively reviewed the records of consecutive patients treated with excision of IDPs at our institution from 2009 to 2016. We evaluated the rate of upgrade of IDPs on CNB and factors predicting for malignant upgrade. RESULTS: Of 153 CNB specimens, 136 (88.9%) were IDPs without atypia and 14 (9.2%) showed atypia. The overall upgrade rate on final pathology was 7.3% with 1.3% for invasive cancer, 2.7% for ductal carcinoma in situ, and 3.3% for atypical ductal hyperplasia. Of the 14 patients with atypia on CNB, two of these patients (14.2%) were found to have ductal carcinoma in situ. In the absence of atypia on CNB, upgrade rates were 1.5% for invasive and 1.5% for in situ carcinoma. Personal history of breast cancer and magnetic resonance imaging-guided biopsy predicted for malignant upgrade. CONCLUSIONS: IDPs on CNB have a low chance of harboring an occult malignancy. Given the low probability of upgrade to invasive breast cancer, it is reasonable to consider watchful surveillance in the absence of a prior personal history of breast cancer or atypia on CNB.