Multiple Intraductal Papilloma Research Articles

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.

Juvenile papillomatosis of the breast (Swiss cheese disease) has frequent associations with PIK3CA and/or AKT1 mutations

Juvenile papillomatosis (JP), the so-called Swiss cheese disease, is a rare benign breast disease of young adults. An association (up to 28%) with breast cancer within the family of affected patients has been reported. A multinodular cystic breast mass lesion and calcifications characterizes JP in imaging studies. The histological picture is diverse and comprises multiple intraductal papillomas, usual ductal hyperplasia, ductectasias, perifocal sclerosing adenosis, and calcification. Patients with complete excision of JP lesions have an excellent follow-up; breast cancer develops only on a very low subset of patients. Molecular background of JP has not been investigated until now. In this study, we addressed mutational analysis of JP cases and correlated these results with follow-up and family history in context with a comprehensive review of the JP literature. We identified 13 cases fulfilling the criteria of JP. All patients were women with a median age of 38 years (26-50 years). Follow-up information was available for 11 of 13 patients. Sufficient paraffin-embedded tissue and good DNA quality for next-generation sequencing (NGS) was available for 10 patients. Paraffin blocks were microdissected in the area of intraductal proliferative disease; the tissue cores underwent NGS analysis using the Oncomine Comprehensive Panel. In 5 of 10 patients, we found PIK3CA mutations; in 2 of 10 patients, we found AKT1 mutations in known hot spot regions. Further mutations in MET, FGFR3, PTEN, ATM, NF1, and GNAS genes were detected in individual patients. Some of these mutations were present at high allele frequencies suggesting germ line mutations. Two of 3 patients with positive family history had PIK3CA mutation; one patient with positive family history had an AKT1 mutation. One patient who subsequently developed invasive ductal carcinoma in the contralateral breast possibly had a germ line ATM mutation. Our results confirm hot spot mutations in PIK3CA and AKT1 genes in JP associated with positive family history for breast cancer, although these mutations are not specific for JP. The genetic link between JP, positive family history, and subsequent risk of breast cancerneeds to be analyzed in further studies.

Multiple intraductal papillomas of breast clinically masquerading as malignancy

Intraductal papilloma is characterized by proliferation of epithelial and myoepithelial cells overlying fibro-vascular stalks creating an arborescent structure within the lumen of duct. Some times multiple papillomas with florid proliferation of epithelium may be confused with malignancy. A case of multiple intraductal papillomas of breast with ulceration of overlying skin and large lump leading to clinical diagnosis of malignancy is documented here. A 45-year-old female presented with ulcerated mass of six months duration in the left breast. On examination, a firm, immobile lump of 8x 10 cm in size involving nipple with excoriation of surrounding skin and serosanguinous discharge from nipple was present. There was no axillary lymphadenopathy. No family history of carcinoma breast was present. Fine needle aspiration smears showed benign cellular changes with apocrine metaplasia. Biopsy from an area adjacent to nipple showed intraductal papilloma. Simple mastectomy showed lobulated dirty white mass with well circumscribed nodules below the nipple and areola. On histology with immunohistochemistry a diagnosis of multiple intraductal papillomas was made. Patient is on regular follow-up and doing well. The case highlights the problem in differentiating marked papillomatosis from a malignant lesion of breast and importance of biopsy with immunohistochemistry in such cases for proper management.

Fiberoptic Ductoscopy-Guided Intraductal Biopsy Improve the Diagnosis of Nipple Discharge

Fiberoptic ductoscopy (FDS)-guided intraductal biopsy is a minimally invasive technique developed to obtain pathologic diagnoses for patients with spontaneous nipple discharge. We performed biopsies of 53 intraductal lesions from March 2006 to April 2007 followed by surgical microdochectomy. FDS-guided intraductal biopsy was shown to be a minimally invasive, safe, and convenient technique with a high ability (90.6%) to get adequate samples. Twenty-seven solitary papillomas, 12 multiple intraductal papilloma, five ductal hyperplasia, three ductal carcinoma in situ, and one invasive ductal carcinoma were diagnosed. Compared with conventional microdochectomy, FDS-guided intraductal biopsy can significantly increase the detection rate of solitary papilloma (40.7% versus 92.6%, p < 0.05). It should be a routine procedure after intraductal lesion found by screening FDS. Since it would underestimate all multiple intraductal papilloma and some (50%) cancer, microdochectomy is inevitable if biopsies show atypical ductal hyperplasia.

Surgical Follow-Up and Clinical Presentation of 142 Breast Papillary Lesions Diagnosed by Ultrasound-Guided Core-Needle Biopsy

The clinical management of breast intraductal papilloma (IDP) remains controversial. The objective of this study was to survey a large cohort of benign IDP diagnosed on core needle biopsy (CNB) and to evaluate their clinical presentation and potential risk of associated atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), ductal carcinoma in situ (DCIS) or invasive carcinoma as identified by follow-up surgical excision. We analyzed 345 IDP on CNB; 142 (41.2%) received a subsequent surgical excision while 203 (58.8%) cases did not. Specimens were categorized as IDP, IPD+ADH, IDP+ALH, and DCIS. In patients with surgical follow-up the upgrade to a lesion of greater clinical significance was analyzed according to race, clinical presentation and multiplicity of papillomas. Of the 142 cases, 125 (93.9%) patients had a single IDP, while 17 cases were among 8 patients with multiple IDPs. Patients were predominantly asymptomatic with CNB obtained as follow-up to an abnormal mammogram. Among solitary benign IDP, nearly 25% were upgraded (p < 0.001): 14.0% to ADH and 10.5% to DCIS. For patients with IDP+ADH on initial CNB, 22.2% were upgraded to DCIS. Of the asymptomatic cases 11.4% were upgraded to DCIS, while none of the symptomatic patients showed such upgrade (p < 0.001). In patients with no surgical excision 17 (8.3%) continue to have an abnormal mammogram. We recommend routine mammogram and surgical excision of all IDPs identified on CNB because almost one-fourth (24.5%) of solitary IDP at CNB were upgraded to either ADH or DCIS and the majority of cases were asymptomatic.

Papilomas intraductales de mama en paciente afectada de síndrome de Costello

Costello syndrome is a multisystemic congenital disorder with a very low prevalence. The pathogenesis remains unclear and predisposes to the development of tumors of ectodermal origin. Diagnosis is clinical, based on findings of mental and growth retardation and a characteristic phenotype. We report the case of a patient with Costello syndrome who was referred to our unit with a suspected diagnosis of intraductal papilloma based on the presence of various episodes of nipple discharge. Postoperative histopathological study confirmed the diagnosis of multiple intraductal papilloma. We review the literature on the topic and discuss the advisability of aggressive surgical therapy, given the predisposition of these patients to develop both benign and malignant tumors.

Trends in benign breast tumors in Japanese women, 1973-1995: experience of Hiroshima Tumor Tissue Registry.

Although some benign breast lesions such as multiple intraductal papilloma have been pointed out as a risk factor for breast cancer, there is little documentation about trends in the incidence of benign tumors of the breast in Japanese women. The author conducted an epidemiological study using data abstracted from the Hiroshima Tumor Tissue Registry file, which includes cases of malignant and benign neoplasms in Hiroshima prefecture between 1973 and 1995. A total of 17 064 cases of female breast tumor were registered in the file between 1973 and 1995. The registration rate for fibroadenoma of the female breast was 19.5 among females and peaked during the 5‐year period 1983–1987, while the fibroadenoma registration rate in Hiroshima gradually decreased between 1988 and 1995. The registration rate for intraductal papilloma has risen substantially in Hiroshima, with about a 5‐fold increase among females between 1973 and 1995. The mean proportion of fibroadenoma cases accompanied by malignant tumors of the breast was 1.85%, and there was no significant change in the mean proportion between 1973 and 1995 (P=0.17). On the other hand, the mean proportion of intraductal papilloma cases accompanied by malignant tumors of the breast gradually rose with about a 14‐fold increase among females between 1973 and 1995. The significance of intraductal papilloma as a risk factor for breast cancer may have increased.

Clonal analysis of benign and malignant human breast tumors by means of polymerase chain reaction.

Clonal analysis was conduced on a variety of benign and malignant human breast tumors using the method based on restriction fragment length polymorphism (RFLP) of the X 120 chromosome-linked phosphoglycerokinase gene and on random inactivation of the gene by methylation. Breast carcinoma was shown to be monoclonal in origin, consistent with a somatic mutational theory. Precancerous lesions such as atypical ductal hyperplasia and multiple intraductal papilloma were also found to be monoclonal, indicating that certain genetic changes had been accumulated in these lesions. Solitary intraductal papilloma was found to be monoclonal. Since this tumor is composed of two types of cells, luminal epithelial cells and myoepithelial cells, it was suggested that the origin of solitary intraductal papilloma is a precursor cell which is capable of differentiating into both luminal and myoepithelial cells. The fact that fibroadenoma is polyclonal indicates that this tumor is not neoplasia but hyperplasia of a lobule. Epithelial component of phyllodes tumor was found to be polyclonal but stromal component was found to be monoclonal. Thus, phyllodes tumor is considered to be a neoplasm of stromal cells but not of epithelial cells.

Are Patients with Solitary or Multiple Intraductal Papillomas at a Higher Risk of Developing Breast Cancer?

Solitary and multiple intraductal papillomas are proliferative lesions. As such, these lesions could be presumed to put the patient at increased risk for the development of breast cancer. This review summarizes several selected series of patients with papillomas, and discusses some of the difficulties in determining the exact risk for these patients. Conflicting data exist with regard to solitary papilloma, but the most recent series do find an elevated risk associated with this lesion. Multiple papillomas are associated with both coexisting cancer and with the subsequent development of breast cancer.

The operative management of intraductal papilloma of the breast

Intraductal papillary tumors of the breast exhibit bloody nipple discharge with often no evidence of a palpable tumor, making discrimination between benign and malignant lesions sometimes difficult for pathologists and surgeons. However, appropriate surgical management requires correct differentiation between these lesions. According to previously reported 3-dimensional analyses of intraductal papillary lesions, solitary papilloma originates in the large ducts while multiple papilloma originates in the peripheral ducts and often coexists with intraductal carcinoma. We performed selected ductolobular segmentectomy on both solitary and multiple intraductal papilloma, and even on small foci of intraductal carcinoma which were found inadvertently. The favorable results of this surgery include a fine cosmetic appearance, functional breast feeding and no recurrence of papilloma during the 2 to 7 year follow-up period. In this article, the operative method of selected ductolobular segmentectomy is described.

Invasive papillary breast carcinoma: mammographic and sonographic appearance.

A retrospective study of the records of xeromammographic examinations of 940 patients with invasive carcinoma of the breast diagnosed during an 11-year period in an out-patient facility yielded four cases of invasive papillary carcinoma. In each of these four patients, xeromammography demonstrated multiple, round or oval, circumscribed areas of density in one quadrant of a breast. Sonographic examination of three patients showed the lesions to be solid. Two patients had previously had multiple benign intraductal papillomas, and one patient had had a solitary papilloma in the same breast. The possible association of invasive papillary carcinoma with previous multiple intraductal papillomas suggests that close clinical and radiographic monitoring of these patients may be necessary.

Association of breast carcinoma and multiple intraductal papillomas: an histological and immunohistochemical investigation.

To identify histological preneoplastic lesions and early neoplastic foci, a histological and immunohistochemical study has been conducted on a series of 18 cases with the rare association of multiple intraductal papillomas and in situ breast carcinoma. The pathological and clinical data of these cases have been collated. A close anatomical and spatial association between the benign papillomas and areas of in situ carcinoma (mostly of the cribriform type) was a frequent finding. In agreement with the results of our previous investigations, cytoplasmic CEA has been found to be a marker of intraductal carcinomas, while staining for actin has been found useful to identify the myoepithelial cells present in benign papillomas as opposed to carcinomas. The immunohistochemical procedures for these two markers have been conducted on parallel sections; alternatively, an immunoperoxidase/immuno-galactosidase sequence has been applied on the same section. The results indicate that, in cases with multiple papillomas, CEA-positive, myoepithelial cell-free carcinomatous areas can be anatomically associated with and even present inside the benign-looking papillary lesions. These findings can be interpreted as evidence of a malignant transformation of intraductal papillomas, or, less likely, of their 'cancerization' by ductal carcinoma.