Treatment Strategy for Breast Benign Intraductal Papilloma: A Meta-Analysis.

Currently, the optimal treatment approach for breast benign intraductal papilloma (IDP) diagnosed via biopsy remains uncertain. There is ongoing debate regarding the feasibility of clinical follow-up and the criteria for selective surgical excision. This study aims to conduct a meta-analysis to determine the rate of upgrade from breast benign IDP and identify predictive factors associated with the conversion of benign IDP to high-risk lesions or carcinoma, which could guide healthcare practitioners in selecting the appropriate clinical treatment strategy. We conducted a comprehensive search across multiple databases (PubMed, Web Of Science, Cochrane Library, and Embase) for studies published between 2012 and 2023 that evaluated upgrade rates and predictive factors of breast benign IDP diagnosed via biopsy. In addition, we included studies that reported on the clinical follow-up of patients with breast benign IDP. In total, 32 studies comprising 7371 cases of biopsy-diagnosed breast benign IDP were included. Among these cases, 720 demonstrated an upgrade to high-risk lesions or carcinoma, resulting in an upgrade rate of 6.94% [95% confidence interval (CI): 3.0-8.0%]. A subgroup of 1713 patients was clinically followed up, demonstrating an average follow-up duration of 30.95 months. Among them, 26 cases experienced an upgrade to high-risk lesions or carcinoma, yielding an upgrade rate of 1.51% (95% CI 0.00-2.00). Furthermore, we identified nine predictive factors associated with the upgrading of breast benign IDP, which included age at diagnosis, personal history of breast cancer, family history of breast cancer, multiple IDPs, lesion size ≥ 10 mm, palpable mass, calcification, and the presence of mass and asymmetry in mammographic findings. Although the conversion rate of breast benign IDP to high-risk lesions or carcinoma is relatively low, timely identification of predictive factors associated with benign IDP upgrades may help selecting the optimal clinical treatment strategy, such as surgery for patients with benign IDP presenting one or more predictive factors, while clinical follow-up for those without specific risk factors.

Challenging diagnosis of male intraductal papilloma masquerading as eccrine hidradenoma in the breast: Case report.

RATIONALE: This article presents a challenging case involving an elderly male patient with a misdiagnosed intraductal mammary papilloma initially identified as a sweat adenoma through ultrasound imaging. The study aims to explore the histopathology, clinical presentations, and sonographic features of both conditions, emphasizing the contributing factors to the diagnostic misstep. PATIENT CONCERNS: A 61-year-old male reported a persistent left breast mass, along with pain and swelling, spanning a 6-month duration. DIAGNOSES: Ultrasound examination indicated a deep, square, mixed-echo mass in the left nipple, initially suggestive of a sweat adenoma. However, subsequent pathological analysis following resection under general anesthesia confirmed an intraductal papilloma. INTERVENTION: The patient underwent surgical resection of the left breast mass under general anesthesia. OUTCOME: Post-surgery, the patient exhibited satisfactory recovery; however, regrettably, he was lost to follow-up. LESSONS: This study underscores the challenge in differentiating between clear cell sweat adenoma and male intraductal mammary papilloma solely based on ultrasonic characteristics. It emphasizes the susceptibility of ultrasound-based diagnoses to misinterpretation, highlighting the critical need for a comprehensive pathological examination to establish a definitive diagnosis.

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.

Bloody nipple discharge due to intraductal papilloma in an adolescent girl.

An early adolescent girl was referred to our breast surgery clinic with multiple right-sided breast masses and several months of unilateral bloody nipple discharge. MRI demonstrated multiple enhancing masses in the right breast with intrinsic hypertensive T1 signal of the ducts extending to the nipple. A biopsy showed partially sclerosed intraductal papillomas without atypia or malignancy. Following extensive counselling with the patient and her family, two palpable breast masses and a single central breast duct responsible for bloody nipple discharge were fully excised. Histopathological analysis showed unique overlapping features of resembling intraductal papilloma, nipple adenoma and fibroadenomas. The patient has had resolution of her bloody nipple discharge and excellent cosmetic outcomes post-surgery. Intraductal papilloma is rare in the adolescent population and the risk of concurrent and future malignancy is not well established. Thus, a tailored approach to the work-up and management of paediatric breast masses is essential.

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.

Intraductal Papillomas.

The most common manifestation of papillary breast disease is intraductal papilloma (IDP). As breast disease management becomes more refined, increasing attention has been directed at determining which IDPs require excision, and which can be monitored. This article will discuss the most common factors currently impacting personalized decision-making.

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.

Upgrade rates of intraductal papilloma with and without atypia diagnosed on core needle biopsy and clinicopathologic predictors.

Surgical excision of breast intraductal papilloma (IDP) without atypia diagnosed on core needle biopsy (CNB) is controversial as the risk of upgrade to malignant lesions is not well established. This study investigates upgrade rates of benign and atypical IDP to ductal carcinoma in situ (DCIS) and invasive carcinoma (IC) and clinicopathologic predictors. We identified 556 cases of IDP diagnosed on CNB at a single institution from 2010 to 2020 after excluding patients with a history of breast carcinoma, ipsilateral high-risk lesion, radiologic/pathologic discordance, or less than 2 years of follow-up if no excision within 1 year. Of these, 97 biopsies were consistent with atypical IDP and 459 were benign IDP. Surgical excision was performed for 318 (57.2%), and the remaining 238 (42.8%) underwent active monitoring. The upgrade rate for IDP without atypia was 2/225 (0.9%; 1 DCIS and 1 IC). Of 93 surgically excised atypical IDPs, 19 (20.4%) upgraded (14 DCIS and 5 IC). Of 238 nonexcised IDPs followed clinically (range, 24-140 months, mean 60 months), there was no subsequent breast cancer diagnosed at the IDP site on follow-up. Mean age of patients was 56 yr ± 12.6 SD without upgrade, 63 yr ± 10.6 SD (P = .027) with DCIS, and 61 yr ± 10.8 SD (P = .35) with IC. Atypical IDP was more likely to upgrade if biopsied by stereotactic guidance (8/19, 42.1% P = .035). At our institution, we had an exceedingly low upgrade rate for benign IDP. Overall, patients with upgrade to DCIS were older. For atypical IDP, upgrade was seen in higher proportions of stereotactic biopsies.

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 on Breast Biopsy: Upstaging Rate and Implications for Practice Guidelines.

BACKGROUND: The recommendation for management of intraductal papilloma has not been clearly established and its surgical excision criteria remain controversial. This study determines the institutional malignancy upstage rate of benign intraductal papillomas and identifies risk factors for upstage. METHODS: Retrospective review was conducted on female patients who were diagnosed with intraductal papillomas without atypia on core needle biopsy at Atrium Health Wake Forest Baptist Hospital between 1/2012 and 6/2021. Patients were excluded if there was a concomitant malignancy or atypia or deemed to be discordant with imaging. Features associated with upstage on imaging and histopathology were obtained from the electronic medical record. RESULTS: This study included 245 intraductal papillomas without atypia in 231 women (mean age, 59.1 ± 12.3 [SD] years). Approximately 31% (76/245) of the papillomas were excised, whereas 69% (169/245) of the papillomas underwent surveillance. Of the patients who underwent excisional biopsy, upstage rate for DCIS was 1.3% (1/76) and 5.3% (4/76) for atypia. All of the papillomas upstaged to DCIS or atypia had lesion size ≥10 mm on imaging. Out of the 139 intraductal papillomas that underwent radiologic surveillance, two (1.4%) developed malignancy and three (2.2%) developed atypia. DISCUSSION: The risk of upstaging of intraductal papilloma without atypia to malignancy remains extremely low. Therefore, routine surgical excision may not be necessary. While the papillomas upstaged to either malignancy or atypia have size abnormality ≥10 mm, other potential selective excision criteria should be explored to further decrease the risk of an upstage.

Comparison of vacuum-assisted excision (VAE) and breast lesion excision system (BLES) in the treatment of intraductal papillomas.

PURPOSE: This study aims to compare the feasibility of VAE and BLES in the treatment of intraductal papillomas. MATERIAL AND METHODS: Patients with a suspected intraductal papilloma who underwent a BLES or a VAE procedure were included in this retrospective study. The BLES procedures were performed between November 2011 and June 2016 and the VAE procedures between May 2018 and September 2020 at the Department of Radiology of Helsinki University Hospital (HUH). The procedures were performed with an intent of complete removal of the lesions. RESULTS: In total, 72 patients underwent 78 BLES procedures and 95 patients underwent 99 VAE procedures. Altogether 52 (60%) papillomas with or without atypia were completely removed with VAE, whereas 24 (46%) were completely removed with BLES, p = 0.115. The median radiological size of the high-risk lesions completely removed with BLES was 6 mm (4-12 mm), whereas with VAE it was 8 mm (3-22 mm), p = 0.016. Surgery was omitted in 90 (94.7%) non-malignant breast lesions treated with VAE and in 66 (90.4%) treated with BLES, p = 0.368. CONCLUSION: Both VAE and BLES were feasible in the treatment of intraductal papillomas. In most non-malignant lesions surgery was avoided, but VAE was feasible in larger lesions than BLES. However, follow-up ultrasound was needed more often after VAE. The histopathologic assessment is more reliable after BLES, as the lesion is removed as a single sample.

Does previous history of cancer or atypia predict histologic upgrade for pure intraductal papillomas diagnosed via core biopsy? A study of 490 cases at a single institution.

BACKGROUND: Management of pure intraductal papillomas (IDP) without atypia diagnosed on core needle biopsy (CNB) remains controversial given highly variable rates of upgrade in the literature. AIM: We sought to identify clinical and histologic factors that predict upgrade to atypia or malignancy in a large population. METHODS AND RESULTS: A retrospective review was performed of all cases of pure IDP diagnosed on CNB and then surgically excised at a single institution from 2008 to 2018. Clinical, radiologic, and pathologic factors were compared in the no upgrade, upgrade to atypia, or upgrade to cancer groups. Univariate analysis was performed comparing no upgrade and upgrade to cancer or atypia. Four hundred and thirty nine patients were identified with a total of 490 IDP and a median age of 50 years (range 16-85). Of these patients, 54 (12.3%) were upgraded to atypia after surgical excision and five (1.1%) were upgraded to cancer. The presence of multiple papillomas in a single patient was a significant predictor of upgrade to cancer or atypia (p < .01), as well as age over ≥55 years (p < .01) and a prior history of cancer (p < .01). No other clinical, radiologic and histologic factors were found to be significant predictors of upgrade. 40/439 (9.1%) patients in the total cohort had prior history of cancer, and of these, 2/40 (5%) were found to have a new cancer after excision. CONCLUSIONS: In patients with pure IDP on CNB, the upgrade rate to malignancy was 1.1%, while 12.3% were upgraded to atypia. The clinical significance of identifying atypia in a papilloma is unknown, especially in a patient with a prior history of atypia or cancer. However, the majority of patients who were upgraded to either atypia or cancer had no prior history of high-risk or malignant breast disease and are therefore considered true clinical upgrades. As such excision for IDP should be considered.

Intraductal Papilloma Arising From the Minor Salivary Glands of the Larynx: A Case Report.

It is rare for intraductal papilloma, a benign papillary tumor, to occur in the salivary glands. To our knowledge, intraductal papilloma occurring in the minor salivary glands of the larynx has not been reported. In this report, we describe a case of intraductal papilloma that occurred in the minor salivary glands of the larynx. A woman in her 30s presented with hoarseness and dyspnea since a year. Fiber-optic laryngoscopy revealed a submucosal tumor involving the left aryepiglottic fold and the left false vocal fold. Computed tomography and magnetic resonance imaging revealed a 17 × 15 × 10 mm3 mass with homogenous isodensity, with regular, well-defined margins located on the left aryepiglottic fold and the left false vocal fold. Surgical resection was performed, and subsequently a diagnosis of intraductal papilloma was made by pathologic evaluation. During the follow-up period of over 3 years, the lesion has not recurred. In conclusion, intraductal papilloma of the minor salivary glands should be considered in the differential diagnosis of laryngeal submucosal tumors.

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.

Upgrade Rate and Predictive Factors for Breast Benign Intraductal Papilloma Diagnosed at Biopsy: A Meta-Analysis.

BACKGROUND: Current standard management for intraductal papilloma (IDP) diagnosed at biopsy indicates complete surgical resection, but there are increasing controversies over whether and when routine excision is indeed necessary. OBJECTIVE: The aim of this study was to determine the carcinoma upgrade rate and identify the associated predictive factors for IDP diagnosed at biopsy by meta-analysis. METHODS: We searched the PubMed and EMBASE databases for studies published from 2009 to 2020 that investigated the upgrade rate and predictive factors of IDP diagnosed at biopsy. RESULTS: A total of 7016 IDP cases diagnosed at biopsy and histologically examined after surgical excision were pooled from 44 original studies. The pooled prevalence of IDP in breast biopsy findings was 4.6% [95% confidence interval (CI) 4.4-4.7%] and the majority of IDP tumors were benign. The pooled upgrade rates to carcinoma for benign IDP and atypical IDP were 5.0% (95% CI 4.4-5.5%) and 36.0% (95% CI 32.7-39.2%), respectively. In addition, we identified 10 predictive upgrade factors for benign IDP, including Breast Imaging Reporting and Data System (BI-RADS) 5, BI-RADS 4C, mass and calcification in the mammographic finding, bloody nipple discharge, imaging-histological discordance, peripheral IDP, palpable mass, BI-RADS 4B, microcalcification, and lesion size ≥ 1 cm. The upgrade rates associated with these predictive factors ranged from 7.3 to 31.1%. CONCLUSION: Surgical excision appears a reasonable recommendation for atypical IDP. Patients with benign IDP exhibiting one or more predictive factors might benefit from surgical excision, while patients with asymptomatic benign IDP without these predictive factors can be managed by imaging surveillance.

Intraductal Papilloma of the Breast: Prevalence of Malignancy and Natural History Under Active Surveillance.

BACKGROUND: The optimal management of intraductal papillomas (IPs) without atypia diagnosed on needle core biopsy (NCB) is unclear. This study analyzed the malignancy risk of immediately excised IPs and characterized the behavior of IPs under active surveillance (AS). METHODS: We retrospectively reviewed the pathology and imaging records of patients diagnosed with IPs without atypia on NCB during a 10-year period (1999-2019). The malignancy upgrade rate was assessed in patients who had an immediate surgical excision, and the rates of both radiographic progression and development of malignancy were assessed in a cohort of patients undergoing AS. RESULTS: The inclusion criteria were met in 152 patients with 175 IPs with a mean age of 51 ± 13 years. The average size of the IPs on initial imaging was 8 ± 4 mm. Most of the lesions (57%, n = 99) were immediately excised, whereas 76 (43%) underwent AS with interval imaging with a median follow-up period of 15 months (range, 5-111 months). Among the immediately excised IPs, surgical pathology revealed benign findings in 97% (n = 96) and ductal carcinoma in situ in 3% (n = 3). In the AS cohort, 72% (n = 55) of the IPs remained stable, and 25% (n = 19) resolved or decreased in size. At 2 years, 4% had increased in size on imaging and were subsequently excised, with ductal carcinoma in situ (DCIS, n = 1) and benign pathology (n = 1) noted on final pathology. CONCLUSIONS: In a large series of breast IPs without atypia, no invasive carcinoma was observed after immediate excision, and 96% of the lesions had not progressed on AS. This suggests that patients with IP shown on NCB can safely undergo AS, with surgery reserved for radiographic lesion progression.

Classical Lobular Carcinoma In Situ Arising From an Intraductal Papilloma of the Breast: A Case Report.

Intraductal papilloma of the breast is a benign, mass-forming, proliferative lesion with a papillary architecture confined within a duct. Lobular neoplasia can rarely arise from an intraductal papilloma of the breast. In this article, we report the morphologic features of a rare case of classical LCIS (lobular carcinoma in situ) arising from an intraductal papilloma in a 76-year-old woman. The monomorphic dyscohesive cells were present between the myoepithelial and luminal epithelial layer in the periphery of the papilloma. These cells partially obliterated the spaces between the papillae forming solid sheets. The monomorphic dyscohesive cells showed lack of E-cadherin expression and uniform staining for estrogen receptor. We review the histologic differential diagnosis and stress the importance of correct classification to ensure optimal care for patients. We also propose a new criterion for the distinction of lobular neoplasia within a papilloma.