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.

The Incidence of Adjacent Synchronous Invasive Carcinoma and/or Ductal Carcinoma In Situ in Patients with Intraductal Papilloma without Atypia on Core Biopsy: Results from a Prospective Multi-Institutional Registry (TBCRC 034).

BACKGROUND: Available retrospective data suggest the upgrade rate for intraductal papilloma (IP) without atypia on core biopsy (CB) ranges from 0 to 12%, leading to variation in recommendations. We conducted a prospective multi-institutional trial (TBCRC 034) to determine the upgrade rate to invasive cancer (IC) or ductal carcinoma in situ (DCIS) at excision for asymptomatic IP without atypia on CB. METHODS: Prospectively identified patients with a CB diagnosis of IP who had consented to excision were included. Discordant cases, including BI-RADS > 4, and those with additional lesions requiring excision were excluded. The primary endpoint was upgrade to IC or DCIS by local pathology review with a predefined rule that an upgrade rate of ≤ 3% would not warrant routine excision. Sample size and confidence intervals were based on exact binomial calculations. Secondary endpoints included diagnostic concordance for IP between local and central pathology review and upgrade rates by central pathology review. RESULTS: The trial included116 patients (median age 56 years, range 24-82) and the most common imaging abnormality was a mass (n = 91, 78%). Per local review, 2 (1.7%) cases were upgraded to DCIS. In both of these cases central pathology review did not confirm DCIS on excision. Additionally, central pathology review confirmed IP without atypia in core biopsies of 85/116 cases (73%), and both locally upgraded cases were among them. CONCLUSION: In this prospective study of 116 IPs without atypia on CB, the upgrade rate was 1.7% by local review, suggesting that routine excision is not indicated for IP without atypia on CB with concordant imaging findings.

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.

Intraductal oncocytic papillary neoplasm of the pancreas: A systematic review.

BACKGROUND: Intraductal oncocytic papillary neoplasm of the pancreas (IOPN-P) is a rare subtype of intraductal papillary mucinous neoplasm (IPMN). This study was performed to summarize the clinicopathological features and management of IOPN-P. METHODS: English-language articles were searched from MEDLINE and EMBASE from the first report of IOPN-P in 1996 until 1 May 2019 following the methodology in the PRISMA guidelines. RESULTS: In total, 66 patients from 24 full articles were included in the final data analysis. The patients' average age was 61 years, and the male/female ratio was 1. Most lesions were large (average size, 5.50 cm), located in the pancreatic head, and found either incidentally or by uncharacteristic abdominal symptoms. IOPN-P was usually a cystic and solid lesion with or without mural nodules on radiological examination. A definitive diagnosis was often acquired from fine needle aspiration biopsy or postoperative pathology. All tumors were diagnosed as carcinoma in situ or minimally invasive carcinoma, necessitating surgical resection. The prognosis of IOPN-P was better than that of other IPMN subtypes, even when metastasis occurred. Recurrence after surgical resection of IOPN-P was rare. CONCLUSIONS: IOPN-P is rare among IPMN subtypes with unique pathological characteristics. Because of the nontypical symptoms and radiological findings, a definitive preoperative diagnosis usually depends on multimodal examinations. Management and surveillance of IOPN-P after surgical resection should be differentiated from those of other pancreatic benign cystic lesions because of its relative malignancy, but IOPN-P should also be differentiated from other IPMN subtypes and malignant cystic tumors because of its favorable prognosis.

Underestimation of breast cancer in intraductal papillomas treated with vacuum-assisted core needle biopsy.

OBJECTIVES: The aims of the study were as follows: 1) to determine the applicability of vacuum-assisted core needle biopsy in the diagnosis and management of intraductal papillomas of the breast; 2) to define factors which increase the risk for underestimation of breast cancer. MATERIAL AND METHODS: Between 2002-2017, a total of 222 cases of intraductal papillomas were diagnosed in one center (201 using vacuum-assisted core-needle ultrasound-guided biopsy and 21 using stereotactic biopsy). All patients under- went scheduled follow-up imaging. RESULTS: Pure papillomas were diagnosed in 158 women, whereas papillomas with atypia, in this case atypical ductal hyperplasia (ADH), were found in 29 subjects. In the latter group, 3 cases of invasive carcinoma and 5 cases of ductal carci- noma in situ (DCIS) were detected using open surgical biopsy. Breast cancer underestimation in that group of patients was 20%. Overall, ADH, whose presence increases the risk for BC by thirteen-fold as compared to other accompanying lesions, proved to be the most important predictive factor. Also, age, non-radical biopsy excision, and high BI-RADS ultrasound and mammogram scores increased the probability of malignancy. During the control follow-up, no cases of IP recurrence in the primary localization were observed in the group without open surgical biopsy. CONCLUSIONS: Vacuum-assisted core needle biopsy is an efficient tool in the diagnosis and management of intraductal papillomas of the breast. Surgical excision is not indicated in cases when a pure intraductal papilloma, and data correlation between the diagnosis and the clinical presentation were confirmed. Regardless, caution is advised if residual lesions were left and in older populations. Open surgical biopsy should remain the standard of care in cases with atypia and discordance between clinical and pathology data.

Intraductal papilloma of the breast - management.

In light of the growing availability of ultrasound testing and invasive diagnostic methods of the breast in everyday gyneco- logic practice, lesions of uncertain malignant potential, classified histologically as B3, have become a significant health issue. Intraductal papillomas (IPs) are the most common pathology in that group of lesions. Despite their benign histologic appearance, IPs may accompany malignant growths and the diagnosis made on the basis of biopsy material carries the risk of breast cancer (BC) underestimation. The article presents a review of the available literature on the management of patients diagnosed with intraductal papilloma at a standard core needle biopsy or vacuum-assisted core needle biopsy. The management is not uniform and depends not only on the verification technique or the accompanying pathological growths, but also on the result of clinical-pathological correlations. As it turns out, open surgical biopsy should not necessarily be recommended to every affected woman, and a growing number of sources have recently suggested that a control program would be sufficient in many cases. Thus, it is vital for gynecologists to be able to differentiate between those women who may be included in the annual ultrasound control program and those who require further surgical management.

Is human papillomavirus associated with breast cancer or papilloma presenting with pathologic nipple discharge?

PURPOSE: There are little data on the presence or interaction of human papillomavirus (HPV) in intraductal papilloma or Breast cancer (BC) presenting with pathologic nipple discharge (PND). The study aimed to determine whether the HPV-genotypes are identifiable in papilloma or carcinoma of the breast by real-time PCR with broad-spectrum genotyping. METHODS: Formalin-fixed-paraffin-blocks obtained from the patients who were suffering from PND and underwent ductoscopic papilloma extraction (n = 27) or segmental/total mastectomy for cancer diagnosis (n = 18). HPV-DNAs were identified by PCR with broad-spectrum genotyping. Mc Nemar test was used to compare cancer-involved cases to normal-adjacent tissue concerning HPV positivity. Chi-Square test was used to analyze the association for receptor status in HPV positive cancer-involved cases. RESULTS: The mean age (±SD) was 49 ± 16 in papilloma and 52 ± 14 in BC patients, respectively. We found high prevalence of HPV in papilloma and carcinoma: 29.6% (n = 8) and 44.4% (n = 8), respectively. The most common type identified in breast lesions was HPV-11, and the others were HPV- 6, -11, -39, and -82. Cancer-involved samples were more contaminated by HPV in comparison to normal-adjacent tissues (p = 0.016). In HPV positive cancer-involved cases, hormone receptors were found to be more positive than HER2-Neu (p = 0.035). CONCLUSIONS: Our data suggest that HPV might be a causative agent for the development of papilloma and carcinoma of the breast in some cases presenting with PND. HPV positive breast cancers are more likely to be hormone positive. Further studies needed for validation regarding the integration of HPV-DNAs into the human genome that causes BC.

Collagen Type XI Alpha 1 Expression in Intraductal Papillomas Predicts Malignant Recurrence.

Despite the progress achieved in the treatment of breast cancer, there are still many unsolved clinical issues, being the diagnosis, prognosis, and treatment of papillary diseases, one of the highest challenges. Because of its unpredictable clinical behavior, treatment of intraductal papilloma has generated a great controversy. Even though considered as a benign lesion, it presents high rate of malignant recurrence. This is the reason why there are clinicians supporting a complete excision of the lesion, while others support an only expectant follow-up. Previous results of our group suggested that procollagen 11 alpha 1 (pro-COL11A1) expression correlates with infiltrating phenotype in breast lesions. We analyzed the correlation between expression of pro-COL11A1 in intraductal papilloma and their risk of malignant recurrence. Immunohistochemistry of pro-COL11A1 was performed in 62 samples of intraductal papilloma. Ten out 11 cases relapsed as carcinoma presents positive staining for COL11A1, while just 17 out of 51 cases with benign behaviour present immunostaining. There were significant differences (P < 0.0001) when comparing patients with malignant recurrence versus nonmalignant relapse patients. These data suggest that pro-COL11A1 expression is a highly sensitive biomarker to predict malignant relapse of intraductal papilloma and it can be used as indicative factor for prevention programs.

Predictors of malignancy in pure branch duct type intraductal papillary mucinous neoplasm of the pancreas: A nationwide multicenter study.

BACKGROUND/OBJECTIVES: Prediction of malignancy in patients with BD-IPMNs is critical for the management. The aim of this study was to elucidate predictors of malignancy in patients with 'pure' BD-IPMNs who had a main pancreatic duct (MPD) diameter of ≤5 mm according to the most recent international consensus criteria and in whom MPD involvement was excluded on postoperative histology. METHODS: We identified 177 patients with 'pure' BD-IPMNs based on preoperative imaging and postoperative histology from 15 tertiary referral centers in Korea. BD-IPMNs with low-grade (n = 72) and moderate-grade (n = 66) dysplasia were grouped as benign and BD-IPMNs with high-grade dysplasia (n = 10) and invasive carcinoma (n = 29) were grouped as malignancy. RESULTS: On univariate analysis, particular symptoms (jaundice and clinical pancreatitis), CT findings (cyst size > 3 cm, the presence of enhancing mural nodules) and EUS features (the presence of mural nodules, the mural nodule size > 5 mm) were significant risk factors predicting malignant BD-IPMNs. Multivariate analysis revealed that the cyst size > 3 cm (odds ratio = 9.9), the presence of enhancing mural nodules on CT (odds ratio = 19.3) and the mural nodule size > 5 mm on EUS (odds ratio = 14.9) were the independent risk factors for the presence of malignancy in BD-IPMNs (p < 0.001). CONCLUSIONS: The cyst size > 3 cm, the presence of enhancing mural nodules on CT, the mural nodule size > 5 mm on EUS are three independent predictors of malignancy in patients with 'pure' BD-IPMNs.

Profile of benign breast diseases in western Saudi Arabia. An 8-year histopathological review of 603 cases.

OBJECTIVES: To describe the histopathological patterns of benign breast diseases (BBD) among Saudi patients. METHODS: This is a retrospective review of BBD reports of Saudi patients of both genders and all age  groups seen between January 2006 and December 2013 at King Fahad Hospital, Madinah, Kingdom of Saudi Arabia. RESULTS: Out of the total 1005 breast biopsies, 603 cases (60%) were BBD. The female to male ratio was 30.7:1. The overall mean age for BBD was 27.5 years, with an age range of 14-80 years. The most common lesion was fibroadenoma (FA) accounting for 44.3% of cases (mean age: 23.5 years), followed by 23.4% fibrocystic change (FCC) (mean age: 37.1 years). Both lesions had a peak occurrence in the third decade. Inflammatory lesions constituted 13.9% of cases. Most common were granulomatous mastitis (3.5%), chronic mastitis (3.3%), and acute mastitis with abscess (3.1%). Other major lesions encountered were fibroadenomatoid hyperplasia (3.1%), intraductal papilloma (2.8%), and benign phylloides tumor (2.6%). All benign diagnoses in male patients were gynecomastia and most patients (68.4%) were under 40 years. CONCLUSION: In this study, BBD constituted 60% of breast lumps, and were mostly FA and FCC. The BBD peaked at the 20-29 year age range. 

Breast-feeding and benign breast disease.

Benign breast disease (BBD) is very common among women in their fertile age, but its correlation with breast reproductive function remains unclear. Our study aimed to investigate the relation between BBD and breast-feeding. We collected data on 105 women with BBD and 98 controls, focusing on their reproductive history and breast-feeding. We analysed data by R (version 2.12.1) considering p < 0.05 as significant. The results showed that fibroadenoma represented the most frequent BBD (55%), followed by fibrocystic changes (19%), intraductal papilloma (6%) and inflammatory breast disorders (5%). The mean age was 31.5 years (± 6.1), BMI 21.2 kg/m² (± 3.4) and age at menarche 13.0 years (± 1.5). Duration of breast-feeding was not significantly different between controls and BBD types (p = NS). Selecting women with fibroadenoma breast-feeding duration directly correlated with the number of benign lesions (p < 0.05), which remains significant also by multivariate analysis. It was concluded that there seemed to be no difference in breast-feeding among BBDs types, but lactation may influence the number of fibroadenomas. Moreover, prospective studies would better define the correlation between lactation and BBDs.

Carcinoma within solitary ductal papilloma of the breast.

BACKGROUND: Solitary ductal papilloma of the breast, traditionally considered a benign disorder, was recently found to have malignant potential, especially when associated with atypical ductal hyperplasia. METHODS: All patients diagnosed with solitary ductal papilloma at a tertiary medical center from 1994 to 2004 were identified by a database search. Background, clinical and pathological data were collected for those with a carcinoma within the papilloma, and their pathological specimens were revised. RESULTS: Of the 3849 breast biopsies performed in our medical center during the study period, 77 (2%) yielded a solitary ductal papilloma. In 12 cases (15.6% of all solitary ductal papillomas; 0.3% of all breast biopsies), a carcinoma was found within the papilloma. Ten were diagnosed as carcinoma in situ and 2 as microinvasive carcinoma. CONCLUSION: In the present series, the incidence of carcinoma within solitary ductal papilloma was 15.6%, indicating that solitary ductal papillomas have malignant potential. SUMMARY: Carcinoma within solitary ductal papilloma of the breast was found in 15.6% of all papillomas. This seems to indicate a malignant potential of papillomas and the need for surgical excision.

The management of lobular neoplasia identified on percutaneous core breast biopsy.

The management of lobular neoplasia (LN) found on percutaneous core biopsy remains a clinical dilemma. The purpose of this study was to establish guidelines for the management of LN when obtained on percutaneous core needle biopsy. A retrospective review of the Breast Imaging Tissue Sampling Database at New York Presbyterian Hospital-Columbia Comprehensive Breast Center was performed from 1998 to 2000. A total of 1460 percutaneous core breast biopsies were performed using 11- or 14-gauge needles with LN identified in 43 biopsies from 34 patients. Eleven biopsies were ultrasound guided for nonpalpable masses and 32 were stereotactically guided for mammographically detected densities (10) and microcalcifications (22). The 43 LN biopsies were divided into three groups based on additional findings associated with LN on core biopsy: group I (n = 19), LN with invasive cancer or ductal carcinoma in situ (DCIS); group II (n = 11), LN plus a second indication for open surgical biopsy, such as atypical ductal hyperplasia (ADH), radial scar, phyllodes tumor, or intraductal papilloma; and group III (n = 13), LN plus benign fibrocystic changes. In group I, 19 of 19 biopsies (100%) yielded invasive cancer or DCIS on surgical biopsy versus 3 of 11 (27%) for group II, and 1 of 13 (8%) for group III. Outcomes in group III are described as follows: three patients were lost to follow-up, three patients did not undergo surgical biopsy but demonstrated more than 1 year of mammographic stability following core biopsy. Of the remaining seven patients, two had LN and ADH on surgical biopsy (one had a contralateral cancer), one had atypical lobular hyperplasia (with a contralateral cancer), two had LN and benign fibrocystic changes, one had LN and intraductal papilloma, and one had LN and invasive ductal carcinoma (IDC) with DCIS (with a contralateral cancer). These results suggest that surgical biopsy is indicated for patients with LN when found on core biopsy and when the biopsy demonstrates invasive cancer, DCIS, or other indications for surgical biopsy such as ADH, or in the examination of a patient with a synchronous contralateral breast cancer. The diagnosis of LN alone without these indications on percutaneous biopsy may not warrant routine surgical biopsy.

Surgery of cystic neoplasms.

Neoplastic cysts of the pancreas have been recognized since the nineteenth century, and although differences between neoplastic and proliferative cysts were acknowledged, they were treated similarly, first by marsupialization and later by internal drainage. Increased awareness of the malignant potential of neoplastic cysts, as well as advances in surgical techniques, made excision the preferred treatment for these lesions as early as the 1940s, but errors in diagnosis were frequent, and even to this date, continue to account for cases of pancreatic cystic tumors treated by drainage.

Histology of cystic tumors of the pancreas.

The cystic tumors of the pancreas constitute a considerable diagnostic challenge because of their overlapping clinical, radiologic, and pathologic features. They may be difficult to differentiate from one another and from benign lesions such as pseudocysts. Because many of the tumors in this group are potentially curable, correct diagnosis is essential for proper patient management. Even when correctly diagnosed, thorough microscopic evaluation is required for the mucin-producing tumors to correctly determine their degree of malignant progression in any given case. Most recently, molecular analysis of these tumors has demonstrated definitively that the serous and mucinous types of cystic neoplasms of the pancreas are unrelated pathogenetically. Conversely, molecular data indicate similarities between the mucinous types of cystic tumors and ductal adenocarcinoma of the pancreas, but the essential molecular differences that underlie the differences in biological behavior are as yet undetermined.

Diagnosis and fine needle aspiration of intraductal papillary mucinous tumor by endoscopic ultrasound.

A recently established clinical entity, intraductal papillary mucinous tumor (IPMT) of the pancreas embraces a spectrum of pathology ranging from benign to malignant disease. IPMT must be differentiated from other cystic neoplasms of the pancreas, as well as inflammatory cystic lesions. As the pancreas lies in close proximity to the gastric and duodenal walls, endoscopic ultrasonography (EUS) is ideally suited for imaging the pancreas. Additionally, EUS facilitates fine needle aspiration of pancreatic cysts and/or a dilated pancreatic duct for cytologic and tumor marker analysis. This article presents a brief history of IPMT, differential diagnosis, current imaging modalities, findings of cytologic and tumor marker analysis, prognosis, and treatment strategy. Special emphasis is dedicated to the role of EUS, as well as EUS with fine needle aspiration.

Benign and malignant mammary tumors induced by DMBA in female Wistar rats.

This study pretends to characterize 7, 12-dimetylbenz[a]anthracene-induced benign and malignant tumors. One hundred and twenty female Wistar rats were randomly allocated to two groups: Control Group and Induction Group; IG animals were given a single dose of DMBA and killed 24 weeks after. Other tumors besides breast tumors were diagnosed, mainly tumors of the salivary glands and ovarian benign epithelial tumors. Incidence of breast disorders was about 60%. Macroscopic mammary tumors varied in dimension from 2 mm to 55 mm. Malignant breast tumors (n = 56) were essentially invasive ductal carcinomas (91.1%), G1 (92.2%), presenting histologic characteristics of good prognosis. Predominant benign breast disorders consisted of glandular (68.6%) and atypical (20%) hyperplasias reproducing histologic types of human breast diseases. Different individual susceptibility to DMBA apparently occurs; while some rats never developed neoplasias, others exhibited several tumors.

Ductal abnormalities detected with galactography: frequency of adequate excisional biopsy.

OBJECTIVE: Galactography (ductography) is a contrast examination of the mammary ducts performed to identify and localize intraductal growths that may be the cause of spontaneous discharge from the nipple. The objective of this study was to correlate the radiologic-pathologic findings in patients with abnormal findings on galactograms in order to determine how often the biopsy specimens included the lesions seen at galactography. MATERIALS AND METHODS: We retrospectively studied all galactograms with abnormal findings obtained in women who subsequently had biopsy at our institution between 1981 and 1991. Galactograms and tissue specimens from 29 women who had 30 biopsies were included. The standard technique was used to perform galactography. Biopsies were performed by using standard surgical technique for duct excision. The histopathologic findings were retrospectively reviewed by a pathologist to determine whether the biopsy specimens included the lesions seen at galactography. RESULTS: In six (20%) of the 30 biopsies, the lesion shown by galactography was not seen on histopathologic review. In the other 80%, the lesion was successfully identified on histopathologic examination. CONCLUSION: Our finding that the abnormality shown by galactography was not completely excised in one in five cases indicates that greater cooperation between the surgeon, radiologist, and pathologist is essential to ensure that all lesions are properly removed.