Pediatric Head and Neck Tumors Associated with Li-Fraumeni Syndrome

Abstract

Introduction: Cancer predisposition syndromes are germline pathogenic variants in genes that greatly raise the risk of developing neoplastic diseases. One of the most well-known is Li-Fraumeni syndrome (LFS), which is due to pathogenic variants in the TP53 gene. Children with LFS have higher risks for multiple malignancies before adulthood, often with rare and aggressive subtypes. Objective: To examine head and neck manifestations of LFS in children treated at a tertiary children’s hospital over a 20-year period. Methods: A retrospective review of LFS children with neoplastic disease presenting in traditional Otolaryngologic head and neck subsites from 2000 to 2019, with patient charts reviewed for relevant clinical, imaging, and operative data. Results: Of the 40 LFS patients initially identified, 27 neoplastic tumors were identified in 20 children within this cohort (20 primary, 7 second primary). Head and neck subsites aside from the brain or orbit were involved in 22% (6/27) of these tumors, representing 20% (4/20) of primary tumors and 29% (2/7) of second primary tumors. Both second primaries within the head and neck were within the radiation fields of the first primary tumor. The mean ages at primary and second primary diagnosis were 4.6 years (SD 3.5) and 12 years (SD 1.4), respectively. The male/female ratio was 1:6 among all patients with head and neck tumors. All 6 head and neck tumors were sarcomas. Rhabdomyosarcoma ( N = 3, 50%) was the most common pathology, and the other 3 demonstrated rare tumor pathological subtypes (synovial cell sarcoma, pleomorphic myxoid liposarcoma, mandibular osteosarcoma). The neck was the most common subsite (75%) within this group for primary tumor presentation. Conclusion: This study identifies a high potential for head and neck involvement in children with LFS, which has not been previously described in the literature. Otolaryngological care should be included in a multidisciplinary care team surveilling these patients.

Pleomorphic Liposarcoma Unraveled: Investigating Histopathological and Immunohistochemical Markers for Tailored Diagnosis and Therapeutic Innovations

“…Furthermore, Sinclair et al reported the case of a 15-year-old female with Li–Fraumeni syndrome who developed a perineal mass, which was diagnosed as myxoid pleomorphic liposarcoma [ 63 ]. A retrospective review of malignancies encountered in children with Li–Fraumeni children has been carried out by Rodriguez et al and included 20 children within a cohort of patients diagnosed with this condition [ 64 ]. Researchers reveal that 6 out of 27 malignancies reported in the analyzed group were sarcomas of the head and neck and were all demonstrated as rare entities—rhabdomyosarcoma, synovial sarcoma, and myxoid pleomorphic sarcoma [ 64 ].…”

“…A retrospective review of malignancies encountered in children with Li–Fraumeni children has been carried out by Rodriguez et al and included 20 children within a cohort of patients diagnosed with this condition [ 64 ]. Researchers reveal that 6 out of 27 malignancies reported in the analyzed group were sarcomas of the head and neck and were all demonstrated as rare entities—rhabdomyosarcoma, synovial sarcoma, and myxoid pleomorphic sarcoma [ 64 ]. The study identifies a propensity for head and neck involvement of tumors associated with Li–Fraumeni syndrome and recommends a multidisciplinary care team surveilling the affected patients [ 64 ].…”

“…Researchers reveal that 6 out of 27 malignancies reported in the analyzed group were sarcomas of the head and neck and were all demonstrated as rare entities—rhabdomyosarcoma, synovial sarcoma, and myxoid pleomorphic sarcoma [ 64 ]. The study identifies a propensity for head and neck involvement of tumors associated with Li–Fraumeni syndrome and recommends a multidisciplinary care team surveilling the affected patients [ 64 ].…”

“…This study highlights the aggressive clinical behavior of liposarcoma developing within the abdominal cavity, as lesions can be diagnosed in a locally advanced stage, and surgical resection can be difficult. Studies also acknowledge that pleomorphic liposarcoma of the retroperitoneum can be associated with acute severe systemic complications, apart from its locally infiltrative and distant metastatic potential [ 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 ]. As an example, Chen et al reported a case of retroperitoneal pleomorphic liposarcoma associated with massive tumor embolism of the inferior vena cava and pulmonary arteries, discovered in a 54-year-old woman [ 65 ].…”

Diagnosis of pleomorphic myxoid liposarcoma: Does it provoke germline testing for Li–Fraumeni syndrome?

“…7 Typical sarcomas in LFS occur specific to various age groups such as rhabdomyosarcoma in childhood, osteosarcoma in the second decade, and leiomyosarcomas and liposarcomas in adulthood. 8 So far, there are reports of four cases of pleomorphic myxoid liposarcoma occurring in patients with LFS [9][10][11][12] (Table S3). Definitive treatment of pleomorphic myxoid liposarcoma is wide local excision followed by adjuvant radiation.…”