Gonadal tumor development in 46,XX disorders of gonadal development.

Background: Differences/disorders of sex development (DSD) are congenital conditions in which the development of chromosomal, gonadal, or anatomical sex is atypical. Objective: The aim of this study is to report the histological characteristics and immunoexpression patterns of gonadal parenchyma in patients with 46,XX testicular and ovotesticular DSD, with a focus on the detection of germ cell malignancies. Design: Inclusion criteria were SRY-negative 46,XX testicular and ovotesticular DSD with available samples from gonadal biopsy or gonadectomy for the review of histological findings. Gonadal histology was assessed on hematoxylin and eosin-stained sections and immunohistochemical analysis. Histopathological criteria from the last World Health Organization classification of urogenital tumors were used to identify undifferentiated gonadal tissue, gonadoblastoma, and dysgerminoma. Results: Median age at first histological evaluation of gonadal samples was 1.46 years (range: 0.16-16 years). Totally 15 patients were classified as ovotesticular and only 1 as testicular DSD. Most individuals had bilateral ovotestes (12/15). No histological alterations were found in the ovarian parenchyma, while signs of dysgenesis were seen in all cases of testicular parenchyma. In 4/15 ovotesticular DSD, a prepubertal biopsy failed to identify ovarian parenchyma. We detected early prepubertal preinvasive and invasive malignancies in this cohort (five patients had undifferentiated gonadal tissue, five gonadoblastoma, and one dysgerminoma). Conclusion: 46,XX disorders of gonadal development are historically considered at a low risk for germ cell cancer, and the need for assessment of gonadal histology has been questioned. The finding of early germ cell malignancies in our cohort brings awareness and needs further research.

Progressive nodular histiocytosis in a 9-year-old boy treated with cobimetinib.

Progressive nodular histiocytosis is a rare variant of non-Langerhans cell histiocytosis that affects the skin and mucous membranes and displays a progressive clinical course and poor response to treatment. We describe a case of severe progressive nodular histiocytosis harboring a KRAS p.G12S mutation in a 9-year-old boy, refractory to chemotherapy, who was successfully treated with the MEK inhibitor cobimetinib. This is the first report of the use of MEK inhibition for this histiocytosis subtype in a pediatric patient.

Pediatric adrenocortical tumors cohort characteristics and long-term follow-up at a single Argentinian tertiary center.

Pediatric adrenocortical tumors are rare and heterogeneous endocrine malignancies. OBJECTIVES: To report clinical, biochemical, and histological features, staging, and therapeutic interventions in a cohort of 28 patients treated at a single tertiary center. METHODS: A retrospective review of medical records of children with PACT (diagnosed before <18 years of age) followed between 1987-2018 at Hospital de Pediatría Garrahan, Buenos Aires, Argentina. RESULTS: Mean age at diagnosis was 4.6 years (range, 0.3-17.3 years) and median follow-up was 4.17 years (range, 0-12 years). Female to male ratio was 2.5:1. Signs and symptoms that prompted medical intervention were hormonal overproduction (57%), abdominal complaints (36%), and hypertensive encephalopathy (7%). In patients with clinically virilizing tumors (n=16) mean height standard deviation score (SDS) and bone age advance were significantly higher while body mass index (BMI) SDS was significantly lower than in those with clinical Cushing's (n=10) (p<0.05). Serum dehydroepiandrosterone sulfate (DHEAS) levels were significantly higher in stage IV than in stage I (p=0.03). Total adrenalectomy was performed in 26 patients. Eight patients (stage III-IV) received adjuvant chemotherapy. Five-year overall and disease-free survival were 100% for ST I-II, and 51% (95% CI 21-82) and 33% (95% CI 1.2-65) for ST III-IV, respectively (p=0.002). No statistical difference was found when comparing 2-year parameters with and without adjuvant chemotherapy. CONCLUSIONS: Height SDS and BMI SDS seem to mirror hormonal secretion in pediatric adrenocortical tumors. Higher DHEAS levels were found in patients with more advanced disease. Further large-scale studies are needed to validate a possible role for DHEAS as a biochemical marker of tumor stage and to draw robust conclusions on the use of adjuvant chemotherapy.

Nefroma mesoblastico congénito: reporte de un caso / Congenital mesoblastic nephroma: case report

El nefroma mesoblastico congénito es un tumor renal infrecuente, pero común en el periodo neonatal. De comportamiento benigno y pronóstico excelente en su variedad clásica pero en el subtipo celular puede presentar recurrencia local, invasión retroperitoneal y metástasis pulmonares y cerebrales. El tratamiento es la nefrectomía radical. Los factores pronósticos son la edad menor a tres meses y la resección quirúrgica completa. Paciente de 17 días nacida a las 35 semanas por polihidramnios, con diagnóstico prenatal de masa abdominal. Al examen físico masa en flanco derecho e hipertensión arterial (121/79 mm Hg, TAM 77mm Hg). Ecografía abdominal con riñón derecho aumentado de tamaño y voluminosa formación sólida, de 4,4 x 4,3 x 4,8 cm, heterogénea y vascularizada al Doppler en polo inferior. Tomografía de abdomen con formación nodular heterogénea de 5,0 x 4,1 x 5,1 cm en polo inferior del riñón derecho. Se realizó nefrectomía radical derecha sin complicaciones. Evolución en los últimos 20 meses satisfactoria y libre de enfermedad.

Congenital mesoblastic nephroma is an uncommon renal tumor, but frequent in neonates. Classical variety usually benign with excellent prognosis. Cellular cases may be recurrent with retroperitoneal invasion, brain and lung metastasis. Radical nephrectomy is the treatment of choice. Relevant prognostic factors are diagnosis before three months of age and complete resection. A 17 day old patient, borned at 35 weeks due to polyhydramnios, with prenatal diagnosis of abdominal mass. On examination, right flank abdominal mass and arterial hypertension (121/79 mm Hg, MAP 77 mm Hg). Abdominal ultrasound showed an enlarged right kidney with a voluminous solid heterogeneous mass, 4.4 x 4.3 x 4.8 cm in the lower pole, vascularized on Doppler scan. Computed tomography showed a big 5.0 x 4.1 x 5.1 cm, nodular, heterogeneous mass in the lower pole of the right kidney. Right radical nephrectomy was performed with an uneventful recovery. Follow up for the last 20 months satisfactory and free of disease.