Scientific Letter
Li Fraumeni Syndrome
Síndrome de Li-Fraumeni
Francisco Ruiz Gómez
, Ricardo de Miguel Ibañez, Almudena Moreno Serrano, Tomás Pérez Dominguez, Juan Carlos Palomo Sánchez
Corresponding author
Servicio de Cirugía General y Digestiva, Hospital Virgen de la Luz, Cuenca, Spain
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At the age of 11, she had been diagnosed with osteosarcoma of the right proximal humerus, with no metastasis. She had been treated with the SEOP 2001 chemotherapy protocol (ifosfamide days 1–5 and adriamycin 25<span class="elsevierStyleHsp" style=""></span>mg/m<span class="elsevierStyleSup">2</span> days 1–3) before and after surgery with right interscapulothoracic disarticulation. The patient had residual neuroma, which was followed-up annually until July 2017. Family history included a maternal grandfather who had died from lung cancer (age 69) and paternal grandfather from prostate cancer (age 78). Physical examination revealed a distended, painful abdomen in the left hypochondrium and a mass, but no abdominal guarding. Lab work showed leukocytosis, neutrophilia and CRP 340. CT scan detected a heterogeneous mass measuring 10×5<span class="elsevierStyleHsp" style=""></span>cm in the left hypochondrium, which was extensively necrotic and abscessed, displacing neighboring structures and presenting air-fluid level. Other observations included: splenomegaly with areas suggestive of infarctions, liver with no focal lesions, kidneys without findings, no pathological lymphadenopathies, and moderate intraperitoneal free fluid.</p><p id="par0020" class="elsevierStylePara elsevierViewall">The surgery identified a purulent peritonitis of 2.5<span class="elsevierStyleHsp" style=""></span>L with a dependent mass of the distal transverse colon embedded anterior to the splenic hilum. At a posterior level, it was in contact with the tail of the pancreas and the greater curvature of the stomach up to the fundus. No space-occupying lesions were palpated in the liver. After left hemicolectomy and splenectomy with primary reconstruction of the intestinal tract, the patient recovered the transit on the fifth postoperative day and was discharged after extension studies with brain and breast MRI, as well as a genetic study at the National Oncology Research Center (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">The pathological anatomy study identified a gastrointestinal stromal tumor (GIST) that was multifocal, low-grade and fusiform, measuring 5×3<span class="elsevierStyleHsp" style=""></span>cm, with free surgical margins and no lymphovascular or perineural invasion. There were less than 50 mitoses per high-power field (G1), and no evidence of necrosis was observed. Peritoneal cytology was negative for malignancy. Immunohistochemical panel showed: CD117 positive (++); Dog1 focal positivity; CKAE1/AE3 negative; S100 negative (−); CD34 positive (+); Ki-67 proliferative in approximately 10%–15% cellularity; and actin negative (−) (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>).</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">A history of pediatric cancer should lead us to the hypothesis of a hereditary cancer predisposition syndrome, especially with a family history or concurrent congenital abnormalities. Conditions associated with increased risk of childhood cancer include: genodermatosis (neurofibromatosis type 1 and tuberous sclerosis), overgrowth syndromes (Beckwith-Wiedemann syndrome and Proteus syndrome) and adult cancer syndromes with an increased risk of childhood and adolescent cancer (LFS and Li-Fraumeni-like syndrome (LFLS).<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">LFS is a cancer predisposition syndrome with autosomal dominant inheritance. Patients with LFS are at increased risk of developing multiple primary tumors, with an 83% risk of having a second primary if the first neoplasm was diagnosed between 0 and 19 years.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">There are 2 forms of presentation: LFS and SFLL.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a> The classic definition of LFS requires a diagnosis of sarcoma before age 45, together with a first-degree relative with any cancer before age 45, as well as a first or second-degree relative with any cancer before age 45 or a sarcoma diagnosed at any age.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">The inclusion criteria have been modified in the last 30 years by Birch, Eeles 1 and 2, and Chompret in 2001. In 2009, the Chompret criteria were redefined: patient with LFS spectrum cancer (sarcoma, breast, central nervous system tumor, leukemia, bronchoalveolar carcinoma) before the age of 46 and a first or second-degree relative with an LFS spectrum tumor (except previous breast cancer) before the age of 56 or multiple tumors. It is also defined as a patient with multiple tumors, at least 2 LFS spectrum, the first occurring before age 46, or an adrenocortical carcinoma or choroid plexus carcinoma at any age or breast cancer before age 36 without BRCA1 or BRCA2 mutation.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">In 1990, inactive forms of the TP53 gene were observed in sporadic forms of many tumors associated with LFS, thereby discovering a definitive association between TP53 and LFS.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">6</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">In germ cells, there are more than 250 mutations in the TP53 gene.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a> A TP53 gene mutation can be identified in patients with no family history because of insufficient family history, germline mosaicism or a <span class="elsevierStyleItalic">de novo</span> mutation of the TP53 gene.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">Clinical criteria for LFS/LFSL can estimate the probability of germ cell mutation in the TP53 gene: 70% of families with the classic criteria of LFS, 32% Chompret criteria, 25% modified Chompret, 25% Birch criteria, 14% Eeles 1 and 8% Eeles 2 criteria.<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">9,10</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">The development of new clinical markers under study in carriers of TP53 germline mutations (decrease in telomere length), as well as the increasingly common use of multiple genetic tests, will continue to expand the new phenotypes beyond the classic description of LFS in the future.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a></p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Ruiz Gómez F, de Miguel Ibañez R, Moreno Serrano A, Pérez Dominguez T, Palomo Sánchez JC. Síndrome de Li-Fraumeni. Cir Esp. 2019;97:600–602.</p>" ] ] "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 564 "Ancho" => 1500 "Tamanyo" => 192032 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">GIST surgical specimen.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 421 "Ancho" => 1500 "Tamanyo" => 86857 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">CT images of the mass.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0055" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Li-Fraumeni syndrome: cancer risk assessment and clinical management" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "K.A. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 October | 23 | 7 | 30 |
| 2024 September | 45 | 15 | 60 |
| 2024 August | 37 | 14 | 51 |
| 2024 July | 37 | 11 | 48 |
| 2024 June | 23 | 10 | 33 |
| 2024 May | 29 | 7 | 36 |
| 2024 April | 26 | 3 | 29 |
| 2024 March | 39 | 7 | 46 |
| 2024 February | 61 | 8 | 69 |
| 2024 January | 43 | 4 | 47 |
| 2023 December | 46 | 7 | 53 |
| 2023 November | 63 | 10 | 73 |
| 2023 October | 55 | 5 | 60 |
| 2023 September | 59 | 4 | 63 |
| 2023 August | 34 | 4 | 38 |
| 2023 July | 64 | 5 | 69 |
| 2023 June | 57 | 5 | 62 |
| 2023 May | 73 | 5 | 78 |
| 2023 April | 73 | 3 | 76 |
| 2023 March | 73 | 6 | 79 |
| 2023 February | 56 | 12 | 68 |
| 2023 January | 60 | 3 | 63 |
| 2022 December | 46 | 5 | 51 |
| 2022 November | 72 | 6 | 78 |
| 2022 October | 29 | 6 | 35 |
| 2022 September | 30 | 8 | 38 |
| 2022 August | 20 | 8 | 28 |
| 2022 July | 30 | 11 | 41 |
| 2022 June | 10 | 8 | 18 |
| 2022 May | 18 | 15 | 33 |
| 2022 April | 25 | 5 | 30 |
| 2022 March | 36 | 8 | 44 |
| 2022 February | 42 | 10 | 52 |
| 2022 January | 24 | 8 | 32 |
| 2021 December | 20 | 9 | 29 |
| 2021 November | 34 | 11 | 45 |
| 2021 October | 28 | 7 | 35 |
| 2021 September | 22 | 8 | 30 |
| 2021 August | 35 | 5 | 40 |
| 2021 July | 44 | 9 | 53 |
| 2021 June | 29 | 10 | 39 |
| 2021 May | 28 | 9 | 37 |
| 2021 April | 42 | 5 | 47 |
| 2021 March | 30 | 8 | 38 |
| 2021 February | 24 | 7 | 31 |
| 2021 January | 11 | 8 | 19 |
| 2020 December | 16 | 10 | 26 |
| 2020 October | 4 | 3 | 7 |
| 2020 September | 16 | 9 | 25 |
| 2020 August | 8 | 6 | 14 |
| 2020 July | 6 | 4 | 10 |
| 2020 June | 6 | 10 | 16 |
| 2020 May | 4 | 3 | 7 |
| 2020 April | 7 | 7 | 14 |
| 2020 March | 4 | 2 | 6 |
| 2020 January | 1 | 2 | 3 |
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