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

Guillet, Carole; Rechsteiner, Markus; Bellini, Elisa; Choschzick, Matthias; Moskovszky, Linda; Dedes, Konstantin J.; Papassotiropoulos, Bärbel; Varga, Zsuzsanna

doi:10.1016/j.humpath.2020.02.002

Cited by 8 publications

(6 citation statements)

References 36 publications

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“…Our study confirms the findings of Guillet et al [3], who recently reported PIK3CA and AKT1 mutations in 5 of 10 and 2 of 10 cases of JP, respectively. In our study and that of Guillet et al [3], it was the epithelial hyperplastic component of JP that was sequenced. It is unclear whether these mutations would be evident in other components of JP.…”

Section: Discussionsupporting

confidence: 93%

“…Histologically, JP is characterized by a constellation of proliferative and nonproliferative changes, the most distinct being abundant large cysts, giving the gross appearance of Swiss cheese [1]. Since the description of JP as a distinct entity by Rosen [1], multiple studies have reported a significant family history of breast carcinoma cancer in patients developing JP [2–4], suggesting a relationship between JP and breast carcinoma. Furthermore, patients with JP have coexisting breast carcinoma or subsequently develop carcinoma in approximately 10% of cases [4,5].…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, patients with JP have coexisting breast carcinoma or subsequently develop carcinoma in approximately 10% of cases [4,5]. Recently, Guillet et al reported recurrent PIK3CA or AKT1 hotspot mutations in benign JP lesions in the first published study of the molecular features of JP, expanding the spectrum of benign breast lesions with these mutations [3]. Nonetheless, the genetic relationship between JP and coexisting breast carcinoma has not yet been documented.…”

Section: Introductionmentioning

confidence: 99%

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Whole‐exome sequencing analysis of juvenile papillomatosis and coexisting breast carcinoma

D’Alfonso

Pareja

Paula

et al. 2020

The Journal of Pathology CR

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Juvenile papillomatosis (JP) of the breast is a rare benign mass‐forming lesion occurring in young women, which is histologically characterized by a constellation of proliferative changes and large cysts, giving it the gross appearance of Swiss cheese. A subset of patients with JP report a family history of breast carcinoma and/or coexisting or subsequent breast carcinoma. We performed whole‐exome sequencing of the hyperplastic epithelial component of three JPs, including one with coexisting ductal carcinoma in situ (DCIS) and invasive ductal carcinoma of no special type (IDC‐NST). JPs harbored clonal somatic PIK3CA hotspot mutations in two cases. In the JP with coexisting DCIS and IDC‐NST, these lesions were clonally related to the associated JP, sharing a clonal PIK3CA E542K somatic hotspot mutation. JP showed a paucity of copy number alterations, whereas the associated DCIS and IDC‐NST showed concurrent 1q gains/16q losses, hallmarks of estrogen receptor (ER)‐positive breast cancers. We observed JP to harbor a dominant aging‐related mutational signature, whereas coexisting DCIS and IDC‐NST showed greater exposure to an APOBEC signature. Taken together, our findings suggest that, at least in a subset of cases, JP might constitute the substrate from which DCIS and invasive breast carcinomas develop.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Whole‐exome sequencing analysis of juvenile papillomatosis and coexisting breast carcinoma

D’Alfonso

Pareja

Paula

et al. 2020

The Journal of Pathology CR

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“…Driver mutations activating the PI3K/AKT pathway are commonly found in breast carcinomas and benign papillomas (Guillet et al, 2020). The additional variants in PIK3R1 , which encodes an inhibitory protein upstream of AKT1, may further promote AKT1 activation and related signaling pathways such as the MAPK pathway (Cheung et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

Late‐onset Proteus syndrome with cerebriform connective tissue nevus and subsequent development of intraductal papilloma

Modlin

Slavotinek

Darling

et al. 2022

American J of Med Genetics Pt A

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Proteus syndrome (PS) is a rare segmental overgrowth disorder caused by a mosaic activating variant in AKT1. The features of PS are often not present at birth but develop during the first few years of life. We describe a 55‐year‐old female, whose first symptom of overgrowth, a cerebriform connective tissue nevus, occurred at 19 years of age. We report the identification of the AKT1 c.49G > A p.(Glu17Lys) variant in this progressive lesion, the bony overgrowth, and recurrence after surgical intervention. In the sixth decade of life, this individual developed intraductal papillomas within her right breast which were confirmed to contain the same activating AKT1 variant as the connective tissue nevus. While similar neoplasms have been described in an individual with Proteus syndrome, none has been evaluated for the presence of the AKT1 variant. The tumor also contained two likely pathogenic variants in PIK3R1, c.1392_1403dupTAGATTATATGA p.(Asp464_Tyr467dup) and c.1728_1730delGAG p.(Arg577del). The finding of additional genetic variation putatively affecting the PI3K/AKT pathway in the neoplastic tissue may provide preliminary evidence of a molecular mechanism for tumorigenesis in PS. The late onset of symptoms and molecular characterization of the breast tumor expand the clinical spectrum of this rare disorder.

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“…Recently, juvenile papillomatosis of the breast has been found to have frequent associations with PIK3CA and/or AKT1 mutations. 2 Another recent study identified clonal somatic PIK3CA hotspot mutations in 2 of 3 cases of juvenile papillomatosis, including 1 with an associated ductal carcinoma in situ and invasive ductal carcinoma. 3 Interestingly, the in situ and invasive carcinomas and the juvenile papillomatosis had a somatic clonal PIK3CA E542K hotspot mutation.…”

mentioning

confidence: 99%

Juvenile Papillomatosis of Breast

Chen

Erickson

2021

Mayo Clinic Proceedings

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

Cited by 8 publications

References 36 publications

Whole‐exome sequencing analysis of juvenile papillomatosis and coexisting breast carcinoma

Whole‐exome sequencing analysis of juvenile papillomatosis and coexisting breast carcinoma

Late‐onset Proteus syndrome with cerebriform connective tissue nevus and subsequent development of intraductal papilloma

Juvenile Papillomatosis of Breast

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