Diffuse Intraductal Breast Papillomatosis in a 34-Year-Old Female With Maffucci Syndrome: A Case Report.

Abstract

Purpose: This report aims to raise clinical awareness of a rare case of Maffucci syndrome in a 34-year-old female presenting with diffuse intraductal breast papillomatosis. It further explores a possible hypothesis-generating pathogenic association between Maffucci syndrome and a specific subtype of papillary breast neoplasia in the context of shared molecular pathways involved in disease pathogenesis.

Introduction: Maffucci syndrome is a rare, congenital, nonhereditary disorder characterized by enchondromas, hemangiomas, and skeletal deformities, typically presenting in early childhood. Since its initial description in 1881, fewer than 300 cases have been reported, with an estimated prevalence of < 1 in 27 million. Somatic mutations in IDH1 and IDH2 are key drivers of Maffucci syndrome and are also implicated in malignancies such as gliomas, chondrosarcomas, intrahepatic cholangiocarcinoma, and acute myeloid leukemia. Most relevant to this case, tall cell carcinoma with reversed polarity (TCCRP)-a rare subtype of papillary breast carcinoma-is characteristically associated with hotspot IDH2 R172 mutations, a molecular feature otherwise uncommon in both breast carcinomas and Maffucci syndrome. Only one documented case of an IDH1-mutated solid papillary carcinoma with reversed polarity (SPCRP) exists in the current literature.

Case description: The patient is a 34-year-old female with Maffucci syndrome, diagnosed in childhood via clinical and radiographic evaluation, with a history of skeletal and vascular complications, including primary chondrosarcomas of the left scapula, right distal patella, and right proximal tibia. She initially presented in 2016 with left-sided hemorrhagic nipple discharge, prompting serial imaging and biopsies that identified recurrent intraductal papillary lesions, consistently benign on core needle biopsy and surgical excision. A right-sided lesion was excised in 2022, followed by two left-sided lesions resected in 2023 and 2024. Mammography in November 2024 revealed three nodular lesions in the left lateral breast, characterized as complex cystic masses, with core needle biopsy confirming benign intraductal papillomas without atypia. Although subsequent imaging demonstrated stability of these lesions on follow-up ultrasound in June 2025, the longitudinal course illustrates a recurrent pattern of intraductal papillary lesion development over time.

Conclusions and importance: This case raises the possibility of an association between Maffucci syndrome and recurrent papillary breast lesions. In the absence of molecular confirmation, this relationship remains speculative and should be regarded as hypothesis generating, underscoring the need for further investigation with genetic and immunohistochemical correlation rather than changes to established breast cancer screening guidelines.