Gastrointestinal juvenile-like (inflammatory/hyperplastic) mucosal polyps in neurofibromatosis type 1 with no concurrent genetic or clinical evidence of other syndromes
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Gastrointestinal “juvenile-like (inflammatory/hyperplastic) mucosal polyps” (JLIHMPs) have been proposed as a neurofibromatosis type 1 (NF1)-specific gastrointestinal manifestation. Juvenile polyposis syndrome (JPS) has also been reported in a NF1 patient, harboring concurrent NF1 and SMAD4 germline mutations. Additionally, NF1-like cafe-au-lait spots have been described in biallelic mismatch repair deficiency, another condition featuring gastrointestinal polyps. The SMAD4 and BMPR1A genes that are involved in 50–60% of JPS cases have not been investigated in the ~ 20 published cases of NF1-associated JLIHMPs with the exception of the abovementioned patient with concomitant JPS and NF1. NF1 defects have been found in the only two cases exhaustively tested. Therefore, JLIHMP has been questioned as an independent, NF1-specific entity. Incidental associations between NF1 and gastrointestinal polyposes at risk for gastrointestinal carcinoma should not be overlooked, given their implications in terms of clinical surveillance. We describe two patients featuring JLIHMPs in clinically/genetically proven NF1, in the absence of SMAD4 and BMPR1A mutations. In one case, the intervening mucosa was markedly inflamed, unlike JPS. We suggest that JLIHMP probably represents a gastrointestinal lesion specific to NF1.
KeywordsHyperplastic polyp Inflammatory polyp Juvenile polyp Molecular diagnosis Neurofibromatosis von Recklinghausen disease
We are grateful for our patients’ generosity in participating in this research.
RR conceived and designed the study and wrote the manuscript; GR and GS performed DNA Sanger sequencing; MGP and MG performed MLPA analysis; GQ, SeA, and GZ collected clinical data; GQ and SeA performed surgery; GR, MCG, FC, MGP, SaA, MG, GZ, and RR analyzed data. All authors critically reviewed the manuscript and gave final approval for publication.
This work was supported by the Università Cattolica del Sacro Cuore (Linea D1 grant number R4124500212 to RR). Gloria Ravegnini is supported by a MSD Italia fellowship granted by and on behalf of Merck Sharp & Dohme Corporation.
Compliance with ethical standards
Informed consent was obtained from all individual participants included in the study. All procedures performed were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Conflict of interest
The authors declare that they have no conflict of interest.
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