Kaposiform Lymphangiomatosis in a Male Adolescent: A Clinical Challenge and the Role of Genetics.

Kaposiform lymphangiomatosis (KLA) is a rare and aggressive generalized lymphatic anomaly (GLA), with distinctive clinical, radiology, morphologic, and genetic features. It does not have a current standard treatment and presents poor overall prognosis. Somatic mutations in the RAS pathway were reported as the likely driver for the majority of patients. We report a case of a 17-year-old male adolescent who was referred to the emergency department due to a severe anemia. Laboratory workup confirmed the anemia and revealed coagulation factor consumption and fibrinolysis. Chest-abdomen-pelvis computed tomography revealed an extensive cervical, mediastinal, abdominal and retroperitoneal "hematoma." During admission, progressive pancytopenia, and disseminated intravascular coagulation were observed, and the hypothesis of a tumor/neoplastic etiology was considered. A thoracoscopy revealed a moderate hemorrhagic pleural effusion and a mediastinal mass resembling a "hemolymphangiomatosis" malformation, which was biopsied. Histology displayed a lymphatic-venous malformation. The patient was presented at the multidisciplinary Vascular Anomalies Center and, due to the complex vascular anomaly diagnosis, oral sirolimus monotherapy was initiated. Four years later, the patient remains clinically stable, with stability of the lesion's dimensions and characteristics. A p.Q61R variant in the NRAS gene [NM_002524.4: c.182A>G, p.(Gln61Arg)], with 5% allelic fraction and 1993x coverage was detected. In conjunction with clinical and pathological findings, it allowed KLA final diagnosis. This case reinforces the importance of a high index of clinical suspicion and highlights the need of referring these cases to referral to Vascular Anomalies Centers.

Congenital Infantile Myofibroma: The Importance of Molecular Diagnosis.

Infantile myofibromatosis is an uncommon soft tissue neoplasm that may present at birth or in early infancy. Although rare, this neoplasm is one of the most common benign fibrous tumors of infancy. Even though these tumors do not spread, they can compress or damage nearby organs. There is not an established management protocol, but it is advisable to maintain periodic clinical and imagological control until stability. Watchful waiting is an option to consider in the absence of problematic symptoms and visceral involvement. We report a case of solitary infantile myofibromatosis, without visceral involvement. It showed an initial rapid growth, raising concern among medical doctors and motivating soft tissue biopsy, always recommended as the clinical picture deviates from the classic presentation. Histology interpretation is often challenging, making genetics and clinical evaluation essential to exclude and prevent the misdiagnosing of more aggressive lesions.

Multifocal Infantile Hepatic Hemangiomas Complicated by Consumptive Hypothyroidism: The Benefits of Early Diagnosis and Treatment.

Infantile hepatic hemangiomas (IHH) account for 12% of all childhood hepatic tumors. Most IHH are diagnosed within the first 6 months of life and involute spontaneously; however, some require medical treatment. The present report describes a case of multifocal IHH associated with subcutaneous and lingual hemangiomas, complicated by consumptive hypothyroidism and successfully managed with oral propranolol and thyroid replacement therapy, without documented adverse effects. Consumptive hypothyroidism is a rare complication of IHH, but suggestive of multifocal/diffuse subtypes. The authors intend to reinforce the importance of early referral to a Vascular Anomalies Center and treatment with propranolol in selected patients.

Adrenal carcinoma as the first manifestation of a Li­Fraumeni syndrome in three paediatric patients.

Not required for clinical vignette.

Endobronchial mucoepidermoid carcinoma in a child with postinfectious bronchiolitis obliterans.

Endobronchial mucoepidermoid tumors are rare neoplasms. Due to nonspecific symptoms, diagnosis can be challenging, but early diagnosis and treatment are crucial for prognosis. We present the case of a boy, with chronic respiratory insufficiency due to bronchiolitis obliterans, that presented worsening exertional dyspnea at 12 years. Spirometry showed unexpected deterioration of respiratory function and a computed tomography scan revealed an obstructive polypoid mass in the intermediate bronchus. Given the severe basal ventilatory compromise and risk associated with surgical treatment, rigid bronchoscopy, and laser photocoagulation were performed, with clinical and functional improvement. The histological examination revealed a low-grade mucoepidermoid carcinoma. The option for a minimally invasive procedure requires careful follow-up due to the risk of tumor recurrence.

Papillary thyroid carcinoma in a 7-year-old boy presenting with a goitre without microcalcifications and enlarged cervical lymph nodes.

The most frequent type of thyroid malignancy in children is papillary thyroid carcinoma (PTC), which usually presents as a thyroid nodule, but may also present as a diffuse infiltration with microcalcifications. Herein, we report the case of an uncommon presentation of a PTC in a 7-year-old boy. The child was referred for a goiter with cervical lymphadenopathies. Ultrasonography showed a hypervascularised goiter without microcalcifications but with numerous bilateral cervical nodular formations. A lymph node biopsy revealed metastatic thyroid cancer, hence a total thyroidectomy and complete neck dissection were performed. Histopathology confirmed a PTC. Ablative 131I, 30 mCi was performed 4 months postsurgery. At the end of this treatment, a metastatic lung nodule was identified. Since then, another three ablative 131I treatments have been administered. Thyroid cancers presenting as a diffuse infiltration without microcalcifications are rare. In the presence of lymphadenopathies, thyroid cancer needs to be suspected, even without microcalcifications.

Platinum-drugs Ototoxicity in Pediatric Patients With Brain Tumors: A 10-Year Review.

PURPOSE: Platinum-derived chemotherapy is one of the cornerstones in the treatment of central nervous system tumors in children. We aimed to assess the incidence of hearing loss in children after the exposure to platinum drugs. MATERIAL AND METHODS: Retrospective study of prospectively collected data on children consecutively diagnosed with brain tumors and treated with platinum derivatives at a tertiary referral hospital between January 2006 and December 2015. We analyzed multiples variables, such as: age at diagnosis, tumor location, hydrocephalus, platinum drug type, radiotherapy, and follow-up time. The final sample size was 51 patients. RESULTS: The median age at diagnosis was 6 years. The median overall follow-up time was 75 months. The incidence of ototoxicity was 23.5%. Rates of hearing loss with carboplatinum were lower than with cisplatinum. A statistically significant association occurred between the presence of hydrocephalus, radiotherapy exposure, infratentorial tumor location, and ototoxicity after treatment with platinum derivatives. CONCLUSIONS: Childhood central nervous system tumors nowadays exhibit improved cure and survival rates. However, the ototoxicity resulting from the chemotherapy treatment may accompany patients for the rest of their lives. This study reveals that this occurrence is not negligible, and the association of radiotherapy and the presence of hydrocephalus can be potentiating factors.

Multinodular Goiter Progression Toward Malignancy in a Case of DICER1 Syndrome: Histologic and Molecular Alterations.

OBJECTIVES: Multinodular goiter (MNG) and well-differentiated thyroid carcinoma (WDTC) are emerging phenotypes of DICER1 syndrome. METHODS: Histologic and molecular findings of botryoid-type embryonal rhabdomyosarcoma (bERMS) and thyroid nodules from a 12-year-old DICER1 mutation carrier (p.Arg1060Ilefs*7) were investigated, providing interesting clues for understanding thyroid carcinogenesis. RESULTS: The patient had bERMS at age 7 years. The thyroid was enlarged and multinodular (61 g). Histologically, some nodules were classified as adenomatous and others as tumors with "intermediate" nuclei. One displayed vascular invasion and was classified as WDTC not otherwise specified (NOS). Somatic DICER1 mutations were identified in bERMS, two tumors with "intermediate" nuclei and WDTC. No somatic DICER1 mutations were found in adenomatous nodules. No molecular alterations were detected in BRAF600, NRAS61, HRAS12/61, KRAS12/61, TERT promoter, RET/PTC1, RET/PTC3, and PAX8/PPARγ. CONCLUSIONS: The findings obtained from this single case support the assumption that DICER1 syndrome-related WDTC NOS may develop on a background of MNG, via a stepwise process, involving DICER1 somatic mutations and additional molecular events, distinct from the classic pathways of papillary/follicular carcinoma.

Increased red cell distribution width in Fanconi anemia: a novel marker of stress erythropoiesis.

BACKGROUND: Red cell distribution width (RDW), a classical parameter used in the differential diagnosis of anemia, has recently been recognized as a marker of chronic inflammation and high levels of oxidative stress (OS). Fanconi anemia (FA) is a genetic disorder associated to redox imbalance and dysfunctional response to OS. Clinically, it is characterized by progressive bone marrow failure, which remains the primary cause of morbidity and mortality. Macrocytosis and increased fetal hemoglobin, two indicators of bone marrow stress erythropoiesis, are generally the first hematological manifestations to appear in FA. However, the significance of RDW and its possible relation to stress erythropoiesis have never been explored in FA. In the present study we analyzed routine complete blood counts from 34 FA patients and evaluated RDW, correlating with the hematological parameters most consistently associated with the FA phenotype. RESULTS: We showed, for the first time, that RDW is significantly increased in FA. We also showed that increased RDW is correlated with thrombocytopenia, neutropenia and, most importantly, highly correlated with anemia. Analyzing sequential hemograms from 3 FA patients with different clinical outcomes, during 10 years follow-up, we confirmed a consistent association between increased RDW and decreased hemoglobin, which supports the postulated importance of RDW in the evaluation of hematological disease progression. CONCLUSIONS: This study shows, for the first time, that RDW is significantly increased in FA, and this increment is correlated with neutropenia, thrombocytopenia, and highly correlated with anemia. According to the present results, it is suggested that increased RDW can be a novel marker of stress erythropoiesis in FA.

Identification of previously unrecognized FAP in children with Gardner fibroma.

Fibromatous soft tissue lesions, namely desmoid-type fibromatosis and Gardner fibroma, may occur sporadically or as a result of inherited predisposition (as part of familial adenomatous polyposis, FAP). Whereas desmoid-type fibromatosis often present ß-catenin overexpression (by activating CTNNB1 somatic variants or APC biallelic inactivation), the pathogenetic mechanisms in Gardner fibroma are unknown. We characterized in detail Gardner fibromas diagnosed in two infants to evaluate their role as sentinel lesions of previously unrecognized FAP. In the first infant we found a 5q deletion including APC in the tumor and the novel APC variant c.4687dup in constitutional DNA. In the second infant we found the c.5826_5829del and c.1678A>T APC variants in constitutional and tumor DNA, respectively. None of the constitutional APC variants occurred de novo and both tumors showed nuclear staining for ß-catenin and no CTNNB1 variants. We present the first comprehensive characterization of the pathogenetic mechanisms of Gardner fibroma, which may be a sentinel lesion of previously unrecognized FAP families.

[Neurofibromatosis type 1 - a malignant evolution in pediatric age]. / Neurofibromatose tipo 1 - uma evolução maligna em idade pediátrica.

Neurofibromatosis type 1 is an autosomal dominant disease affecting one in 3000 to one in 4000 people, with a great variability of clinical expression. Individuals affected with neurofibromatosis type 1 have an increased risk of developing both benign and malignant tumors, supporting the classification of tumor predisposition syndrome. The most common tumor is the neurofibroma, a heterogeneous benign nerve sheath tumor, which represents the primary clinical characteristic of neurofibromatosis. The case reported refers to a adolescent boy with neurofibromatosis type 1 diagnosed at 20 months, who presented progressive growth of dorsal and lumbar intraspinal tumors since six years of age and diagnosis of malignant nerve sheath tumors at 17 years of age. In addition to describing a rare presentation of neurofibromatosis, because of location and early onset of complications, the authors discuss the difficulties of the therapeutic approach of this case.