Congenital metastatic neuroblastoma with placental involvement as a rare cause of non-immune fetal hydrops.

Non-immune hydrops fetalis represents the end-stage status of a variety of diseases, including metastatic tumors. We report a case of non-immune hydrops fetalis associated with multiple disseminated echogenic nodular lesions detected by ultrasound and confirmed by magnetic resonance. Cordocentesis demonstrated anemia and thrombopenia. Differential diagnosis included histiocytosis X, acute leukemia or metastatic disease. A stillbirth was diagnosed at week 25 + 6. The autopsy revealed hydrops fetalis, a right adrenal gland mass, multiple disseminated nodules histologically composed of small round blue cells positive for synaptophysin, and placental involvement, concordant findings with congenital undifferentiated neuroblastoma Stage M. No chromosomal abnormalities were associated, nor amplification abnormalities in MYCN and ALK genes. Metastatic neuroblastoma should be considered in the differential diagnosis of non-immune hydrops fetalis associated with multiple nodular lesions.

Spontaneous twin anemia-polycythemia sequence from two donors to one recipient in a monochorionic triamniotic pregnancy: Case report and review of the literature.

Monochorionic triamniotic (MCTA) pregnancies present a high number of complications, mainly due to the presence of unbalanced vascular anastomoses, such as twin anemia-polycythemia sequence (TAPS). Previous reported cases related to TAPS are in twin pregnancies or only affect the monochorionic component of dichorionic triamniotic (DCTA) pregnancies. We report an exceptional case, the only one reported as far as we know, of a MCTA pregnancy that developed a TAPS in which the three triplets are implicated, from two donors to one recipient. The pregnancy had been previously sonographically diagnosed as DCTA pregnancy and this could not explain the clinical results. The pathological study of the placenta showed the presence of three monochorionic dividing membranes, a congested area in the recipient parenchyma and two non-congested areas in the donor's parenchyma that confirmed the clinical findings. Pathological study of multiple placentas should always be done because it provides understanding of pregnancy complications.

Maternal and perinatal outcomes and placental pathologic examination of 29 SARS-CoV-2 infected patients in the third trimester of gestation.

AIM: On December 31, 2019, an unknown outbreak of pulmonary disease was reported in China. The novel coronavirus SARS-CoV-2 was the etiologic agent of this disease, and responsible of the current pandemic of COVID-19. Accumulated evidence on placental features is based most on case-reports and small case-series, with differing results. METHODS: We gathered a cohort of 29 infected pregnant mothers who delivered 32 newborns, and had placentas available for pathologic examination. Placentas were compared with a control group. RESULTS: Of the 29 mothers, clinical and radiological features were similar to what was already described in COVID-19. Pregnancy modified some analytical parameters. One of the mothers succumbed to the disease. Of the 32 newborns, 1 developed an early infection, with positive reverse-transcriptase polymerase chain reaction (RT-PCR) at 48 h of life, with an initial RT-PCR negative. SARS-CoV-2 presence was assessed on placental tissue with immunohistochemistry and RT-PCR, both were negative. All newborns had good clinical outcomes. No differences in morphological placental findings were found among both groups. CONCLUSION: Lack of statistically significant differences among case and control groups suggest that placentas from SARS-CoV-2 infected mothers represent a cohort of normal placentas only submitted because of maternal SARS-CoV-2 status. To the best of our knowledge, no irrefutable cases of vertical transmission have been yet described. Other authors have failed to demonstrate presence of viral RNA in placental tissue. Accumulated knowledge suggests that if vertical transmission is possible, it is a rare event.

Treatment of infantile fibrosarcoma associated to an abdominal aortic aneurysm with larotrectinib: a case report.

Infantile fibrosarcoma (IFS) is a rare pediatric tumor which often presents the ETV6-NTRK3 gene fusion. NTRK3 encodes the neurotrophin-3 growth factor receptor tyrosine kinase, a druggable therapeutic target. Selective tropomyosin receptor kinase (TRK) inhibitors, such as larotrectinib, have shown efficacy and safety in the treatment of IFS. We report a case of an abdominal IFS diagnosed in a newborn associated with an aortic aneurysm that was successfully treated with larotrectinib without relevant adverse effects.

Hsa-miR-139-5p is a prognostic thyroid cancer marker involved in HNRNPF-mediated alternative splicing.

It is critical to identify biomarkers and functional networks associated with aggressive thyroid cancer to anticipate disease progression and facilitate personalized patient management. We performed miRNome sequencing of 46 thyroid tumors enriched with advanced disease patients with a median follow-up of 96 months. MiRNome profiles correlated with tumor-specific histopathological and molecular features, such as stromal cell infiltration and tumor driver mutation. Differential expression analysis revealed a consistent hsa-miR-139-5p downexpression in primary carcinomas from patients with recurrent/metastatic disease compared to disease-free patients, sustained in paired local metastases and validated in publicly available thyroid cancer series. Exogenous expression of hsa-miR-139-5p significantly reduced migration and proliferation of anaplastic thyroid cancer cells. Proteomic analysis indicated RICTOR, SMAD2/3 and HNRNPF as putative hsa-miR-139-5p targets in our cell system. Abundance of HNRNPF mRNA, encoding an alternative splicing factor involved in cryptic exon inclusion/exclusion, inversely correlated with hsa-miR-139-5p expression in human tumors. RNA sequencing analysis revealed 174 splicing events differentially regulated upon HNRNPF repression in our cell system, affecting genes involved in RTK/RAS/MAPK and PI3K/AKT/MTOR signaling cascades among others. These results point at the hsa-miR-139-5p/HNRNPF axis as a novel regulatory mechanism associated with the modulation of major thyroid cancer signaling pathways and tumor virulence.

Fulminant Sepsis Caused by Leclercia adecarboxylata in a Premature Neonate: Case Report and Review of the Literature.

Hospital-acquired infections are especially evident in premature infants because of prolonged stays and the need for invasive procedures. Leclercia adecarboxylata is an uncommon emerging Gram-negative bacterium that has been described in catheter and noncatheter-related infections, immunocompromised patients and less frequently affecting healthy subjects. We report a case with a postmortem diagnosis of a 24-week-old premature neonate who died as a complication of nosocomial sepsis related to an infection by L. adecarboxylata. Although the cases of L. adecarboxylata infection in children have been rarely reported, this case appears to be the first in which an infection by L. adecarboxylata is accompanied by focal spontaneous ileal perforation.

Classification of follicular-patterned thyroid lesions using a minimal set of epigenetic biomarkers.

Objective: The minimally invasive fine-needle aspiration cytology (FNAC) is the current gold standard for the diagnosis of thyroid nodule malignancy. However, the correct discrimination of follicular neoplasia often requires more invasive diagnostic techniques. The lack of suitable immunohistochemical markers to distinguish between follicular thyroid carcinoma and other types of follicular-derived lesions complicates diagnosis, and despite most of these tumours being surgically resected, only a small number will test positive for malignancy. As such, the development of new orthogonal diagnostic approaches may improve the accuracy of diagnosing thyroid nodules. Design: This study includes a retrospective, multi-centre training cohort including 54 fresh-frozen follicular-patterned thyroid samples and two independent, multi-centre validation cohorts of 103 snap-frozen biopsies and 33 FNAC samples, respectively. Methods: We performed a genome-wide genetic and epigenetic profiling of 54 fresh-frozen follicular-patterned thyroid samples using exome sequencing and the Illumina Human DNA Methylation EPIC platform. An extensive validation was performed using the bisulfite pyrosequencing technique. Results: Using a random forest approach, we developed a three-CpG marker-based diagnostic model that was subsequently validated using bisulfite pyrosequencing experiments. According to the validation cohort, this cost-effective method discriminates between benign and malignant nodules with a sensitivity and specificity of 97 and 88%, respectively (positive predictive value (PPV): 0.85, negative predictive value (NPV): 0.98). Conclusions: Our classification system based on a minimal set of epigenetic biomarkers can complement the potential of the diagnostic techniques currently available and would prioritize a considerable number of surgical interventions that are often performed due to uncertain cytology. Significance statement: In recent years, there has been a significant increase in the number of people diagnosed with thyroid nodules. The current challenge is their etiological diagnosis to discount malignancy without resorting to thyroidectomy. The method proposed here, based on DNA pyrosequencing assays, has high sensitivity (0.97) and specificity (0.88) for the identification of malignant thyroid nodules. This simple and cost-effective approach can complement expert pathologist evaluation to prioritize the classification of difficult-to-diagnose follicular-patterned thyroid lesions and track tumor evolution, including real-time monitoring of treatment efficacy, thereby stimulating adherence to health promotion programs.

Malignant teratoma of the thyroid in a pregnant woman.

Most teratomas involving the thyroid gland are benign and occur in children. However, the adult cases reported are mostly malignant. Many of the cases previously described in the medical literature have fatal outcome because of spread of the tumor refractory to treatment. We report a case of primary malignant teratoma of the thyroid in a 38-year-old pregnant black woman. She was treated with a combination of surgery, and postoperative chemotherapy with good initial response.

[Annular elastolytic giant cell granuloma: a case report located in non-sun exposed areas]. / Granuloma elastolítico anular de células gigantes: a propósito de un caso localizado en áreas no fotoexpuestas.

Annular elastolytic giant cell granuloma (AEGCG) is an uncommon entity clinically characterized by erythematous annular plaques with atrophic and hypopigmented center, that predominates in sun-exposed zones. The histology shows a granulomatous infiltrate without palisading image, made up of lymphocytes, histiocytes and giant cells, with phagocytosis of elastic fibers, without necrobiosis or mucin deposit. We present the case of a male patient with atypical clinical manifestation on the non-sun exposed skin and AEGCG characteristic histology.