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Case Reports
. 2023 Aug 17:14:1213283.
doi: 10.3389/fgene.2023.1213283. eCollection 2023.

Case report: PIK3CA somatic mutation leading to Klippel Trenaunay Syndrome and multiple tumors

Viola Bianca Serio  1   2 , Maria Palmieri  2   3 , Simona Innamorato  1   2 , Lorenzo Loberti  1   2   4 , Chiara Fallerini  1   2 , Francesca Ariani  1   2 , Enrica Antolini  1   2 , Jasmine Covarelli  1   2 , Massimo Vaghi  5   6 , Elisa Frullanti  2   3 , Alessandra Renieri  1   2   4 , Anna Maria Pinto  4
Affiliations
Case Reports

Case report: PIK3CA somatic mutation leading to Klippel Trenaunay Syndrome and multiple tumors

Viola Bianca Serio et al. Front Genet. .

Abstract

We report a case of Klippel Trenaunay Syndrome that was monitored both clinically and molecularly over a period of 9 years. A somatic mosaic mutation of PIK3CA (p(E545G)) was identified using both cfDNA NGS liquid biopsy and tissue biopsy. At the age of 56, due to intervening clonal mutations in PIK3CA background, she developed a squamous cell carcinoma in the right affected leg which was treated surgically. Nine years later, lung bilateral adenocarcinoma arose on PIK3CA mutated tissues supported by different clonal mutations. One year later, the patient died from metastases led by a new FGFR3 clone unresponsive to standard-of-care, immunotherapy-based. Our results highlight the presence of a molecular hallmark underlying neoplastic transformation that occurs upon an angiodysplastic process and support the view that PIK3CA mutated tissues must be treated as precancerous lesions. Importantly, they remark the effectiveness of combining cfDNA NGS liquid and tissue biopsies to monitor disease evolution as well as to identify aggressive clones targetable by tailored therapy, which is more efficient than conventional protocols.

Keywords: Klippel-Trenaunay Syndrome; NGS-liquid biopsy; case report; squamous cell carcinoma adenocarcinoma; tailored therapy.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Patient’s family tree.
FIGURE 2
FIGURE 2
Lymphoscintigraphy: Lack of superficial and deep lymphatics in the right lower limb Lymphatic malformations are often associated to Klippel Trenaunay malformation.
FIGURE 3
FIGURE 3
T(1) weighted picture of the leg.
FIGURE 4
FIGURE 4
Preoperative picture of the right leg.
FIGURE 5
FIGURE 5
Operatory specimen.
FIGURE 6
FIGURE 6
Healing of the surgical wound with skin graft.
FIGURE 7
FIGURE 7
T(2) weighted picture of the lower limbs. Hypertrophy of the soft tissues is present together with dilated ectatic superficial and deep veins. Presence of a neoplastic tissue involving skin and subcutaneous tissue on the peroneal side of the right lower limb.
FIGURE 8
FIGURE 8
Local recurrence direct phlebography with blue patent. Evidence of dermal backflow.
FIGURE 9
FIGURE 9
Ct scan demonstrating a mass in the left lung.
FIGURE 10
FIGURE 10
Ct scan demonstrating a mass in the right lung.
See this image and copyright information in PMC

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