A Novel Variant in the TP53 Gene Causing Li-Fraumeni Syndrome.

Li-Fraumeni syndrome (LFS) is an autosomal dominant hereditary cancer syndrome associated with germline pathogenic variants in the tumor protein p53 (TP53) gene and elevated risk of a broad range of early-onset malignancies. Patients with LFS are at risk of a second and third primary tumor. A 15-month-old girl consulted for clitoromegaly and pubic hair. Adrenal ultrasound detected a large left adrenal tumor. Left total adrenalectomy confirmed adrenocortical carcinoma. Family history revealed multiple highly malignant neoplasms at an early age across five generations, and a genetic dominant trait seemed probable. Whole-genome sequencing was performed. Multiple members of the family were found positive for a novel likely pathogenic variant (c. 892delGinsTTT, p. Glu298PhefsX48, NM_000546.6) in the TP53 gene, causing the loss of normal protein function through non-sense-mediated mRNA decay. According to the PSV1 supporting criteria and the Auto PVS1 online tool this frameshift variant: hg19/17-7577045-TC-TAAA:NM_000546.6 has a very strong, definitive clinical validity for LFS with autosomal dominant inheritance. Proper guidance resulted in timely diagnosis of a second tumor (primary osteosarcoma) in the index case and in the early detection of breast and cervical cancer in her young mother. Patients with cancer predisposition syndromes like LFS require close multidisciplinary cancer surveillance and appropriate referral to expert centers.

A case of cystic dysplasia of the rete testis in a 17-months-old boy.

Cystic dysplasia of the testis (CDT) is a benign, congenital malformation of the testis and a rare cause of painless scrotal swelling in children, mimicking testicular cancer. It is commonly unilateral, often associated with ipsilateral wolffian duct and ureteral abnormalities. Cystic dysplasia of the rete testis (CDT) represents a diagnostic challenge made easier if age, precise localisation, typical ultrasonographic features, the presence or absence of associated genitourinary malformations, as well as tumor markers are considered. The definite treatment of such a benign lesion is testis-sparing surgery, however in most cases watch and wait strategy can be recommended. We present a case of cystic dysplasia of the testis in a 17-month-old boy with right multicystic dysplastic kidney, epididymal cyst, history of vesicoureteral reflux (VUR), as well as of solitary umbilical artery. We performed epididymidal cyst enucleation and right testicular biopsy.

Retrospective study of the surgical management and outcome of nonrhabdomyosarcoma soft tissue sarcomas of the groin and axilla in children.

PURPOSE: The incidence of pediatric nonrhabdomyosarcoma soft tissue sarcomas (NRSTSs) of the groin and axilla is unknown, and the optimal surgical approach to these patients is unclear. METHODS: We conducted a retrospective study of patients treated at St Jude Children's Research Hospital from January 1962 to March 2007 for NRSTSs of the groin and axilla. Demographic variables, tumor pathology, clinical management, and outcome were reviewed. RESULTS: Of the 300 patients treated for NRSTSs, only 10 had tumors of the axilla or groin (6 of whom had synovial sarcoma). Surgical interventions included wide resection of the tumor (n = 7), marginal resection (n = 1), subtotal resection (n = 1), and biopsy only (n = 1). Six patients underwent lymph node sampling; all were negative for tumor. Short- and long-term surgical complications were rare. Four patients received adjuvant chemotherapy (n = 3) and/or radiotherapy (n = 2). At a median follow-up of 8.5 years, 7 of the 10 were surviving free of disease. Two of these patients died of tumor progression (1 with metastases at diagnosis and 1 with an unresectable tumor at diagnosis), and one patient who was free of NRSTS died of secondary breast carcinoma. CONCLUSIONS: Pediatric NRSTSs of the axilla and groin are rare, but outcomes are similar to those of other patients with NRSTS. Wide local excision of the tumor with preservation of good limb function should be the surgical goal and may be sufficient therapy in some cases.

Should contralateral exploratory thoracotomy be advocated for children with osteosarcoma and early unilateral pulmonary metastases?

PURPOSE: Children presenting with osteosarcoma and pulmonary metastases have poor survival rates. The standard approach to treating unilateral metastases is ipsilateral thoracotomy with complete resection of the metastases whenever possible. We analyzed whether contralateral exploratory thoracotomy is beneficial in these patients. METHODS: We reviewed the records of all osteosarcoma patients presenting with or developing early pulmonary metastases (within 24 months of diagnosis) at the St Jude Children's Research Hospital (Memphis, Tenn) between June 1980 and September 2005. Demographics, imaging results, treatment protocols, surgical procedures, and recurrence, survival, and timeline data were assessed. RESULTS: Of the 109 patients, initial pulmonary involvement was radiographically identified as unilateral in 81 (74%) and bilateral in 28 (26%) patients. Of the patients presenting with unilateral pulmonary metastases, 2 years later, 13 (16%) had recurrence in the ipsilateral and 19 (23%) in the contralateral lung. In 2 (2.4%) patients, metastases recurred bilaterally. There was no evidence of statistically significant difference between the incidence of recurrence in the ipsilateral and contralateral lung (P = .18). CONCLUSIONS: Children with osteosarcoma and unilateral pulmonary metastases had similar incidence of recurrence in the ipsilateral and contralateral lung. Their survival rates were also not significantly different. Therefore, contralateral exploratory thoracotomy in patients presenting with unilateral pulmonary metastases will probably not improve survival.