Pulmonary involvement in children with Langerhans cell histiocytosis.

BACKGROUND: Pulmonary Langerhans cell histiocytosis (pLCH) is a rare disease, mostly a component of multisystemic LCH. We aimed to investigate the clinical features and treatment results in children with pLCH. METHODS: We retrospectively reviewed the clinical, radiological, and treatment data of 37 patients with pLCH, diagnosed from 1974 to 2022. RESULTS: 10% (n=37) of 367 patients with LCH had lung involvement. The median age was 1.8 years (range: 0.4 & 17.7) with a male-to-female ratio of 2.3. At admission 29.7% (n=11) presented with respiratory symptoms. Imaging showed a spectrum from nodular opacities to multiple cysts. All but one patient had multisystem disease. Twenty-nine received vinblastine-containing therapy. Ten-year event-free (EFS) and overall survival (OS) rates were 47.8% and 63.3%, respectively. In children younger and older than two years of age, the 10-year EFS was 53.3% vs. 40.2% and the 10-year OS was 58.7% vs. 68.8%, respectively. In children with and without risk organ involvement, 10-year EFS was 51.9% vs. 46.3% and 10-year OS was 51.9% vs. 73.7%. CONCLUSIONS: Lung and multisystem involvement are significant concerns in LCH, highlighting the need for careful management to reduce morbidity and mortality.

Further expanding the phenotype of anti-Ku antibody associated disease in children and adolescents.

Anti-Ku autoantibodies are associated with several autoimmune inflammatory diseases. We aimed to review our anti-Ku positive pediatric patients in this study. Four pediatric patients (all female) who had anti-Ku positivity were included (Patients 1-2-3 with idiopathic inflammatory myopathy (IIM); Patient 4 with chronic urticaria). Patient 1 (onset:10.5 years) had proximal muscle weakness, Raynaud phenomenon, sclerodactyly, hyperpigmentation, joint contracture, and tenosynovitis. The disease course was progressive despite treatment with corticosteroids, intravenous immunoglobulin (IVIG), plasma exchange, and 11 different immunosuppressive drugs. Patient 2 (onset:15 years) presented with proximal muscle weakness, fatigue, weight loss. She recovered normal muscle strength after treatment with corticosteroids, IVIG, methotrexate, cyclosporine A, mycophenolate mofetil. Patient 3 (onset:10 years) had juvenile dermatomyositis with proximal muscle weakness, Gottron's papules, and calcinosis. She also had anti-NXP2 positivity. Remission was achieved with corticosteroids, methotrexate, azathioprine, and infliximab. Muscle biopsy findings revealed a variable spectrum of necrosis, regeneration, perifascicular pattern, and inflammation. Patient 4 had only chronic urticaria (onset: 6.5 years). The striking features of this series were heterogeneity in clinical presentations including solely chronic urticaria and IIM; variable response to immunosuppressive treatments; and histopathology revealing a spectrum of necrosis, regeneration and inflammatory infiltration. Expanding the spectrum of anti-Ku positivity will allow better understanding of anti-Ku-associated phenotype clusters.

AP-1-dependent fibrosis: Exploring its potential role in the pathogenesis of placental transmogrification of the lung (PTL) via tissue-level transcriptome analysis.

Placental transmogrification of the lung (PTL) is a rare pulmonary condition characterized by the presence of immature placental villous structures. The etiology and molecular mechanisms underlying this disease remain largely unknown. This functional study aimed to identify the molecular signatures in the pathogenesis of PTL via comprehensive transcriptome analysis. Comparative transcriptomic assessment of PTL tissue and stromal cells showed differential expression of 257 genes in PTL tissue and 189 genes in stromal cells. Notably, several transcription factors and regulators, including FOSB, FOS, JUN, and ATF3, were upregulated in PTL tissue. Additionally, genes associated with the extracellular matrix and connective tissue, such as COL1A1, MMP2, and SPARC, were significantly altered, indicating possible fibrotic changes. Gene set enrichment analysis highlighted the role of vascular development and extracellular matrix organization, and the Activator Protein-1 (AP-1) transcription factor was significantly activated in PTL tissue. Furthermore, the analysis highlighted an overlap of 25 genes between PTL tissue and stromal cells, underscoring the importance of shared molecular pathways in the pathogenesis of PTL. Among the shared genes, JUND, COL4A2, COL6A2, IGFBP5, and IGFBP7 were consistently upregulated, highlighting the possible involvement of AP-1-mediated signaling and fibrotic changes in the pathogenesis of PTL. The present findings pave the way for further research into the molecular mechanisms underlying PTL and offer novel insights for therapeutic interventions. Given the rarity of PTL, these molecular findings represent a significant step forward in our understanding this enigmatic disease.

A Single-center Experience of Radiotherapy in Pediatric Ewing Sarcoma/Primitive Neuroectodermal Tumor of the Chest Wall.

AIM: To evaluate the treatment results, prognostic parameters, and treatment-related toxicity in patients with Ewing sarcoma (ES)/primitive neuroectodermal tumor (PNET) of the chest wall who underwent surgery, chemotherapy, and radiotherapy (RT) in a tertiary referral center. METHODS: The data of 24 patients under 18 years of age with a histologic diagnosis of ES/PNET in the chest wall that received RT in our department between February 2003 and July 2020 were retrospectively evaluated. RT was applied to the primary site±whole involved chest wall and to the whole lung in patients with lung metastasis. RESULTS: The median age was 8.5 years (range: 1.5 to 17 y), 15 (63%) patients were female and 9 were male (37%). The tumor localization was extrathoracic in 18 (75%) and intrathoracic in 6 (25%) patients. Mediastinal lymph node and distant metastasis (DM) was present in 5 (21%) and 4 (16%) cases at diagnosis, respectively. The median follow-up after RT was 47 months (range: 11 to 162 mo). The 2-year and 5-year overall survival, event-free survival, local recurrence-free survival, and pleural recurrence-free survival were 83% and 48%, 48% and 42%, 74% and 48%, and 61% and 52%, respectively. The overall local control rate was 83% and the pleural control rate was 67%. RT was well tolerated, with 1 case of grade 3 acute dermatitis and 1 case of grade 3 subacute radiation pneumonitis. Late toxicity was observed in 3 (13%) cases. CONCLUSION: Long-term survival can be achieved with extended-field RT even in patients with ES/PNET of the chest wall with DM. The low toxicity rates allow us to draw the conclusion that RT with modern techniques is an effective and safe treatment modality for these patients.

Ganglioneuromas in Childhood: Hacettepe Experience With 70 Cases.

BACKGROUND: Ganglioneuromas (GNs) are rare benign peripheral neuroblastic tumors (PNTs). We shared our institutional experience with childhood GNs. METHODS: Records of the children with PNTs between January 1995 and December 2021 were reviewed, and cases with histopathological diagnoses of GN were identified. Clinical, laboratory, radiological, and histopathological findings, image-defined risk factors (IDRFs), procedures, and overall outcomes were recorded. RESULTS: Of 668 cases with PNTs, 70 (10.4%) had GNs. The median age was 7.4 years (range, 2.6-15.7 years) (girls/boys, 41/29). Common presenting complaints were abdominal pain and cough; 33/70 cases (47.1%) were diagnosed incidentally. Primary tumors were in the abdomen in 41/70, the thorax in 25/70, the neck in 3 cases, and the pelvis in one. The median tumor size was 6.5 cm (range, 1.4-17). Fifty cases (71.4%) were staged as INRG-L1; 20 cases with IDRFs (15 single, five >1) were staged as INRG-L2. Complete and partial tumor resections were performed in 58/70 and 6/70 cases, while 6 had no resection. The overall complication rate was 17.1% (11/64). At a median follow-up of 9 years, five were lost to follow-up; 65 were alive. One patient with gross residue underwent total resection due to progression 13 years after the surgery, and one in the unresected group was lost to follow-up. Ten other cases without a complete resection experienced no tumor progression. CONCLUSIONS: Ganglioneuromas are benign PNTs, and most are free of IDRFs. Even without complete resection, long-term outcomes are excellent. Guidelines should be devised considering the high surgical complication rates and benign course of GNs. LEVEL OF EVIDENCE: Case series, IV.

Childhood interstitial lung disease in Turkey: first data from the national registry.

The childhood interstitial lung diseases (chILD) Turkey registry (chILD-TR) was established in November 2021 to increase awareness of disease, and in collaboration with the centers to improve the diagnostic and treatment standards. Here, the first results of the chILD registry system were presented. In this prospective cohort study, data were collected using a data-entry software system. The demographic characteristics, clinical, laboratory, radiologic findings, diagnoses, and treatment characteristics of the patients were evaluated. Clinical characteristics were compared between two main chILD groups ((A) diffuse parenchymal lung diseases (DPLD) disorders manifesting primarily in infancy [group1] and (B) DPLD disorders occurring at all ages [group 2]). There were 416 patients registered from 19 centers. Forty-six patients were excluded due to missing information. The median age of diagnosis of the patients was 6.05 (1.3-11.6) years. Across the study population (n = 370), 81 (21.8%) were in group 1, and 289 (78.1%) were in group 2. The median weight z-score was significantly lower in group 1 (- 2.0 [- 3.36 to - 0.81]) than in group 2 (- 0.80 [- 1.7 to 0.20]) (p < 0.001). When we compared the groups according to chest CT findings, ground-glass opacities were significantly more common in group 1, and nodular opacities, bronchiectasis, mosaic perfusion, and mediastinal lymphadenopathy were significantly more common in group 2. Out of the overall study population, 67.8% were undergoing some form of treatment. The use of oral steroids was significantly higher in group 2 than in group 1 (40.6% vs. 23.3%, respectively; p = 0.040).   Conclusion: This study showed that national registry allowed to obtain information about the frequency, types, and treatment methods of chILD in Turkey and helped to see the difficulties in the diagnosis and management of these patients. What is Known: • Childhood interstitial lung diseases comprise many diverse entities which are challenging to diagnose and manage. What is New: • This study showed that national registry allowed to obtain information about the frequency, types and treatment methods of chILD in Turkey and helped to see the difficulties in the diagnosis and management of these patients. Also, our findings reveal that nutrition should be considered in all patients with chILD, especially in A-DPLD disorders manifesting primarily in infancy.

Esophageal Carcinoma in Children: Report of 2 Cases and a Review of the Literature.

Esophageal carcinoma in children and adolescents is extremely rare. Here, we report 2 cases of pediatric esophageal carcinoma presenting with progressive dysphagia. There was not any underlying specific risk factor in our cases. The histopathological subtypes were adenocarcinoma in one and squamous cell carcinoma in another case. Response to combined modality treatment was good in the case of adenocarcinoma, while the patient with squamous cell carcinoma was unresponsive to treatment and died of the progressive disease. We reviewed the pediatric cases of esophageal carcinoma reported in the literature. Progressive dysphagia was observed in 89% of these cases. One third of pediatric cases had underlying risk factors. Squamous cell carcinoma is a more common type of childhood esophageal carcinoma. In contrast to adults, pediatric esophageal squamous cell carcinoma may distribute throughout the esophagus. Esophageal adenocarcinoma was seen in the distal esophagus in pediatric cases. Metastatic disease was found in 48% of pediatric patients at presentation, and the prognosis is poor. Collaborative efforts are needed for success in the treatment of esophageal carcinoma.

Imaging Features of Pediatric Sarcoidosis.

Sarcoidosis is a granulomatous inflammatory disease of uncertain cause. It occurs most commonly in young and middle-aged adults and less frequently in children; therefore, few data on pediatric sarcoidosis exist in the literature. The diagnosis and management of sarcoidosis remain challenging because of diverse and often nonspecific clinical and imaging findings. In addition, the clinical picture varies widely by age. Prepubertal and adolescent patients often present with adult-like pulmonary disease; however, early-onset sarcoidosis is typically characterized by the triad of arthritis, uveitis, and skin rash. Sarcoidosis is mostly a diagnosis of exclusion made by demonstrating noncaseating granulomas at histopathologic examination in patients with compatible clinical and radiologic findings. Although sarcoidosis often affects the lungs and thoracic lymph nodes, it can involve almost any organ in the body. The most common radiologic manifestation is pulmonary involvement, characterized by mediastinal and bilateral symmetric hilar lymphadenopathies with perilymphatic micronodules. Abdominal involvement is also common in children and often manifests as hepatomegaly, splenomegaly, and abdominal lymph node enlargement. Although neurosarcoidosis and cardiac sarcoidosis are rare, imaging is essential to the diagnosis of central nervous system and cardiac involvement because of the risky biopsy procedure and its low diagnostic yield due to focal involvement. Being familiar with the spectrum of imaging findings of sarcoidosis may aid in appropriate diagnosis and management. ©RSNA, 2023 Test Your Knowledge questions are available in the supplemental material.

Low-Grade Injury following Testicular Torsion: A Multicenter Study Confirming a Disturbing Possibility.

INTRODUCTION: There is an ongoing debate whether to perform orchiectomy or orchidopexy following testicular torsion (TT) in cases where the testis seems non-viable. The main problem is lack of objective criteria defining testicular viability. The aim of this study was to investigate the grade of injury in orchiectomy specimens obtained from cases of TT and its association with clinical findings. METHODS: This multicenter retrospective study involved double-blinded reassessment of the patient files and the pathological specimens using Mikuz classification to analyze the relation between clinical and pathological findings. RESULTS: A total of 289 patient charts from 14 centers were reviewed and 228 were included in this study. Twenty (8.8%) patients had grade 1 injury which refers to reversible injury. The clinical findings of these 20 patients were compared to 208 patients with higher grades of injury. As expected, there was statistically significant difference regarding duration of symptoms (p < 0.001); however, range was wide in both groups (as long as 96 h for grade 1 and as short as 7 h for higher grades). There was no statistically significant difference in any other variable including age (median 14 for both, p = 0.531), symptoms (pain: 19/20 vs. 189/202, p = 0.801; swelling: 13/19 vs. 168/197, p = 0.094), absence of blood flow in Doppler US (15/19 vs. 164/197, p = 0.635), or degree of torsion (median 720° for both, p = 0.172). CONCLUSION: Our study revealed necessity for better criteria to define viability of testis following TT. Histopathological injury appeared to be reversible even in some patients with more severe perioperative findings, late admission, or high degree of twisting. Our findings support the tendency for testicular fixation instead of orchiectomy as none of the clinical or perioperative findings could be attributed to high-grade injury.

Hemoglobin cast nephropathy: a rare but serious complication of hemolysis in a pediatric patient.

BACKGROUND: Intravascular hemolysis is a serious and rare condition in children and causes the release of hemoglobin and heme into circulation, which have proinflammatory properties. These substances lead to inflammation, oxidative stress, apoptosis, and organelle dysfunction that lead to acute kidney injury (AKI). We report a pediatric case diagnosed with hemolysis-associated hemoglobin cast nephropathy due to autoimmune hemolytic anemia. CASE: A 4-year-old boy, who was admitted to another hospital with complaints of fever and dark urine for one day, developed anemia and kidney failure in the follow-up, was referred to our hospital. In physical examination, pallor and icterus on the sclera were noted. The patient had low hemoglobin and haptoglobin levels concomitant with high levels of serum lactate dehydrogenase, urea and creatinine. A peripheral blood smear showed marked spherocytes without schistocytes. A kidney biopsy was performed due to ongoing overt hemolysis and dialysis requirement, which showed findings consistent with hemoglobin cast nephropathy. Although the initial polyspecific direct antiglobulin test (DAT) was negative, due to persistent intravascular hemolysis DAT was studied monospecifically and showed IgM antibody positivity. Therefore, a diagnosis of autoimmune hemolytic anemia was made, and corticosteroid treatment was started. Hemolysis immediately ceased and the need for erythrocyte transfusion and dialysis disappeared. CONCLUSIONS: Acute kidney injury associated with hemoglobin cast nephropathy is an extremely rare condition in childhood. Although the initial course is severe and potentially life-threatening, the prognosis is favorable with the treatment of the underlying cause and management of AKI. Therefore, pediatricians should be aware of this rare clinical entity during clinical practice.

Fatal thrombotic microangiopathy in an infant with COVID-19: a case report.

BACKGROUND: While macrovascular thrombosis is common in adult COVID-19 patients, thrombotic microangiopathy as a part of endothelitis might play an important role in severe organ dysfunction. Thrombocytopenia-associated multiple organ failure (TAMOF) is a thrombotic microangiopathy syndrome that is associated with endothelial damage. Herein, we aim to report a pediatric TAMOF case related to SARS-CoV-2 infection which has been scarcely reported to date. CASE: A 7-month-old boy who became severely ill after being infected with SARS-CoV-2 required advanced critical care treatments such as continuous renal replacement therapy, therapeutic plasma exchange, and extracorporeal membrane oxygenation. A heart and lung biopsy obtained during sternotomy showed thrombotic microangiopathy. Despite early plasma exchange, mortality was inevitable because of severe liver failure. CONCLUSIONS: This case report implies that SARS-CoV-2 infection could cause TAMOF in children. To the best of our knowledge, this is the second SARS-CoV-2-induced pediatric TAMOF case. More studies are needed to determine alternative treatments for patients with TAMOF who are resistant to conventional therapies.

Primary ovarian tumors in children: a single center experience of 124 patients.

BACKGROUND: Primary ovarian tumors are rare in the pediatric age group. We reviewed our 40-year experience with ovarian tumors to evalute the clinical features and treatment results in a single institution. METHODS: Between January 1975 and October 2015, 124 girls with primary ovarian tumor were diagnosed and treated in our center. Tumors were identified with biopsy or total resection and/or serum markers. Seventy four children were included in the treatment analysis. RESULTS: Median age for 124 children was 11.0 years (0.73-17.63). The main complaint was abdominal pain in 85 patients (68.5%). One hundred and five patients (84.6%) had total one-sided salpingo-oophorectomy and five patients had bilateral salpingo-oophorectomy. Amongst 124 cases, 29 patients had mature teratoma, which was the most common tumor in this study. Dysgerminoma (n=21) was the most common malignant histopathologic type. Stage I disease was diagnosed in 57.2% and stage IV in 6.6% of the patients. Five year overall survival (OS) and event-free survival (EFS) for 124 children were 82.5% and 76.3% respectively. For 74 children who received treatment, 5-year OS and EFS were 75.2% and 67.1%, respectively. Age (p < 0.017), histopathological subgroup (p < 0.001), stage (p =0.003) and chemotherapy protocols (p =0.049) were significant prognostic factors for OS. CONCLUSIONS: The survival rates in children with ovarian tumors were comparable with studies in the literature. Although patients treated with platin based regimens had better survival rates, prognosis was still poor for the patients in advanced stages. This should be the focus for further studies and improvements.

Endoscopic treatment of periampullary duodenal duplication cyts in an 18-month-old girl.

BACKGROUND: Duodenal duplication cysts (DDC) are rare congenital anomalies of the gastrointestinal tract and periampullary localization with anatomical variants including biliary and pancreatic duct anomalies remains a surgical challenge. Endoscopic treatment of the periampullary DDC (PDDC) communicating with the pancreaticobiliary duct in an 18-month-old girl is presented to discuss the endoscopic treatment options in children. CASE: An 18-month-old girl with a normal prenatal ultrasound (US) was asymptomatic until complaining of abdominal pain and vomiting at 10-months of age. Abdominal US revealed a 1.8 × 2 cm cystic mass adjacent to the second part of the duodenum. The amylase and lipase levels were slightly increased while she was symptomatic. Magnetic resonance cholangiopancreaticography (MRCP) showed a thick cyst wall measuring 1.5 × 2 cm at the second part of the duodenum, consistent with DDC that was suspected to be communicating with the common bile duct. Upper gastrointestinal endoscopy confirmed a bulging cyst in the duodenum lumen. The puncture and injection of the cyst with contrast material confirmed the communication of the duplication cyst with the common bile duct. The unroofing of the cyst was performed with endoscopic cautery. The biopsy obtained from the cystic mucosa revealed normal intestinal histology. Oral feeding was initiated six hours after the endoscopy. The patient has been followed for the last 8 months uneventfully. CONCLUSIONS: Endoscopic treatment of PDDC with various anatomical variants can be considered an alternative to surgical excision in children.

Precursor B-cell Lymphoblastic Lymphoma in Children: Hacettepe Experience.

The purpose of the study was to review the clinical and pathologic characteristics and treatment results of children with precursor B-cell lymphoblastic lymphoma. Of 530 children diagnosed with non-Hodgkin lymphomas between 2000 and 2021, 39 (7.4%) were identified as having precursor B-cell lymphoblastic lymphoma. Clinical characteristics, pathologic, radiologic, laboratory data, treatments, responses, and overall outcomes were recorded from hospital files and analyzed. The median age of 39 patients (males/females, 23/16) was 8.3 years (range 1.3 to 16.1). The most common sites of involvement were the lymph nodes. At a median follow-up of 55.8 months, 14 patients (35%) had a recurrence of disease (11 stage IV, 3 stage III); 4 were in complete remission with salvage therapies, 9 died of progressive disease and one died due to febrile neutropenia. Five-year event-free survival and overall survival rates were 65.4% and 78.3% for all cases, respectively. Survival rates were higher in patients with a complete remission at the end of induction therapies. The survival rates were lower in our study compared with other studies, which could be explained by the high relapse rate and higher incidence of advanced-stage disease due to bone marrow involvement. We demonstrated a prognostic impact of treatment response at the end of the induction phase. Cases with a disease relapse have poor prognosis.

Magnetic resonance elastography in evaluation of liver fibrosis in children with chronic liver disease.

BACKGROUND: Magnetic resonance elastography (MRE) has been used to stage liver fibrosis in adults. We aimed to assess the agreement between the Ishak scoring system and magnetic resonance elastography-measured liver stiffness (MRE-LS) in children. This study included all the children who underwent abdominal MRE and liver biopsies between February 2018 and January 2021. The correlation between MRE-LS and Ishak fibrosis stage, MRE parameters, and clinical and biochemical markers affecting this relationship was investigated. RESULTS: A total of 52 patients (31 male; a median age of 11.8 years) were included in the study. The MRE-LS values were significantly different between Ishak fibrosis stages (p = 0.036). With a cut-off value of 2.97 kilopascals, MRE-LS had sensitivity, specificity, PPV, NPV and accuracy values of 90.9%, 82.9%, 58.8%, 97.1%, and 84.6%, respectively, for differentiating mild/moderate fibrosis (F0, 1, 2, 3) from severe fibrosis (F ≥ 4). Although MRE-LS was moderately correlated with Ishak fibrosis score and histological activity index and weakly correlated with aspartate aminotransferase, hepatic steatosis, and R2*, only Ishak fibrosis score was a significant predictor of MRE-LS. MRE-measured spleen stiffness was weakly correlated with the Ishak fibrosis score. CONCLUSIONS: MRE has high sensitivity and specificity for evaluating liver fibrosis in children. MRE may be used to evaluate liver fibrosis in pediatric patients.