Rare Tumor Research Articles

Hepatoblastoma: Experience of the paediatric haematology and oncology department, Hassan II university hospital of Fez.

Introduction: Hepatoblastoma is the most common malignant hepatic tumour in children. However, it is a rare disease, representing approximately 2% of childhood tumours. The treatment combines chemotherapy with surgical excision. The objective of this study was to describe the epidemiological, clinical, therapeutic and progressive aspects of hepatoblastoma treated in the paediatric haematology and oncology department at the University Hospital Hassan II of Fès. Patients and Methods: This was a descriptive and retrospective study conducted over a 11-year period. All patients aged 0 to 15 years who were admitted and treated for hepatoblastoma were included. Results: 24 patients met the study criteria, including 9 boys and 15 girls. The average age at diagnosis was 11.52 months ± 4.9. The most common reason for consultation was abdominal distension. Hepatomegaly was observed in 50% of cases. The average tumour size was 116 mm. At the time of diagnosis, one-third of patients had pulmonary metastases, and all patients were classified as high risk. Therapeutically, 19 patients (79.17%) received chemotherapy and 16 (66.67%) underwent surgery. On the evolutionary level, we observed a recovery without events in 10 (41.67%) patients. Conclusion: hepatoblastoma is a rare tumour, but remains the most common hepatic tumour in children. Despite progress in diagnostic and therapeutic means, the mortality rate is significant.

Extended Endoscopic Endonasal Approach for Giant Pediatric Craniopharyngiomas: Technical Note and Case Series.

Giant pediatric craniopharyngiomas are rare tumors whose clinical and surgical management is extremely challenging. A variety of open transcranial approaches has been used to resect these lesions. Although there has been an increasing acceptance of the endoscopic endonasal approach (EEA) for the resection of pediatric craniopharyngiomas in recent years, many surgeons continue to recommend against the use of the EEA for giant pediatric craniopharyngiomas. This study aimed to evaluate the feasibility of extended EEA for giant craniopharyngiomas in the pediatric population. All consecutive pediatric patients with giant craniopharyngiomas (diameter >4 cm) who underwent endoscopic endonasal surgery at our institution were retrospectively reviewed. Data on demographic information, preoperative assessment, imaging features, surgical results, complications, and recurrences were recorded and analyzed. A total of 16 pediatric patients with an average age of 12 years were identified. The mean maximum diameter and volume of the tumors were 4.35 cm and 24.1 cm3, respectively. Gross total resection was achieved in 13 patients (81.3%) and subtotal resection in 3 patients (18.7%). Postoperatively, partial or complete anterior pituitary insufficiency occurred in 100% of patients, and 62.5% developed new-onset diabetes insipidus. Visual function improved in 9 patients (56.3%) and remained stable in 7 patients (43.7%). Postoperative cerebrospinal fluid leakage occurred in 2 patients and was successfully repaired through the EEA. During a mean follow-up of 44.3 months, 18.8% of patients had a >9% increase in body mass index, and 93.8% of patients successfully returned to school or work. Two patients (12.5%) suffered a recurrence. Disease control was achieved in 16 patients (100%) at final follow-up. The extended EEA allows adequate access to this challenging tumor and enables complete resection and visual improvement with a reasonable approach-related complication rate.

Analysis of causes and prognostic impact of tube occlusion during hyperthermic intraperitoneal chemotherapy for appendiceal pseudomyxoma peritonei

BackgroundAppendiceal pseudomyxoma peritonei (PMP), a rare tumor from mucinous appendiceal origins, is treated with Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC). However, tubing blockages during HIPEC treatment pose a common challenge, impeding the smooth progression of therapy. Few studies to date have explored the incidence and risk factors of tube occlusion during HIPEC in patients with appendiceal PMP, as well as its adverse impact on postoperative complications.MethodsFrom October 2017 to June 2023, a total of 80 patients with appendiceal PMP undergoing combined CRS and HIPEC were included in this study. Tubing blockage events were strictly defined, with patients experiencing blockages during HIPEC treatment allocated to the study group, while those with unobstructed perfusion were assigned to the control group. A comparative analysis was conducted between the two groups regarding post-HIPEC health assessments and occurrence of complications. Risk factors for luminal occlusion during closed HIPEC procedures were identified through univariate and multivariate analysis of data from 303 HIPEC treatments.ResultsTubing blockages occurred in 41 patients (51.3%). The study group experienced prolonged gastrointestinal decompression time (4.1 ± 3.0 vs. 2.5 ± 1.7 days, P = 0.003) and prolonged time to bowel movement (6.1 ± 2.3 vs. 5.1 ± 1.8 days, P = 0.022) compared to the control group. There was no significant difference in the incidence of complications between the two groups. The 1-year survival rate postoperatively was 97%, and the 3-year survival rate was 81%, with no association found between tubing blockage and poorer survival. Additionally, In 303 instances of HIPEC treatment among these 80 patients, tube occlusion occurred in 89 cases (89/303, 29.4%). Multivariable logistic regression analysis revealed age, diabetes, hypertension, and pathology as independent risk factors for tube occlusion.ConclusionTubing blockages are a common occurrence during HIPEC treatment, leading to prolonged postoperative gastrointestinal functional recovery time. When patients are elderly and have concomitant hypertension and diabetes, along with a histological type of low-grade mucinous tumor, the risk of tube occlusion increases. However, this study did not find a significant correlation between tubing blockage and the incidence of postoperative complications or overall patient survival.

Inflammatory fibroid polyp– a rare aetiology for adult ileocolic intussusception

AbstractWe report a case of an adult ileocolic intussusception secondary to an inflammatory fibroid polyp (IFP), a rare and unexpected association between a surgical condition, and an underlying histopathological process. Intussusception is an uncommon surgical diagnosis in adults, and an IFP is rare mesenchymal tumour. Surgical intervention of the intussusception in an adult patient, given the uncertain aetiology of the lead point, is recommended as gold standard.

Colorectal Sarcomatoid Carcinoma: 30-Year Experience.

Background: Primary colorectal sarcomatoid carcinoma is a rare and aggressive malignant neoplasm that displays mixed epithelial and mesenchymal differentiation, with uncertain histogenesis. First described in 1986, there is a paucity of literature related to this condition and there are no evidence-based treatment guidelines. The aim of our study is to present our 30-year experience with primary colorectal sarcomatoid carcinoma. Methods: Retrospective single-center analysis of all patients treated for primary colorectal sarcomatoid carcinoma from 1992 to 2022. The primary outcome was response to treatment strategy and overall survival. Results: A total of six cases met eligibility criteria. Three were male (50%) with a mean age at diagnosis of 59years (range, 49-72). Four neoplasms were located in the rectum (66%) and two in the colon. Mean tumor size at diagnosis was 4.8cm (range, 2.8-7.0). Three patients were treated endoscopically and three underwent oncologic surgical resection. Five experienced recurrence and one expired from other comorbidities. The mean survival among those with colonic and rectal sarcomatoid carcinoma was 7months (range, 3-11) and 39months (range, 9-60), respectively. Discussion: Primary colorectal sarcomatoid carcinoma is a rare malignant tumor with poor prognosis. Treatment modalities have not been standardized and despite multimodal therapy, disease recurrence and/or metastasis is likely to occur. Further studies are necessary to determine optimal treatment to improve outcomes.

Tertiary lymphoid structures as a potential prognostic biomarker for combined hepatocellular-cholangiocarcinoma.

Combined hepatocellular-cholangiocarcinoma (cHCC-CCA), as a rare primary hepatic tumor, is challenging to accurately assess in terms of the clinical outcomes and prognostic risk factors in patients. This study aimed to clarify the function of tertiary lymphoid structure (TLS) status in predicting the outcome of cHCC-CCA and to preliminarily explore the possible mechanism of TLS formation. The TLSs, with different spatial distributions and densities, of 137 cHCC-CCA were quantified, and their association with prognosis was assessed by Cox regression and Kaplan-Meier analyses. We further validated TLS possible efficacy in predicting immunotherapy responsiveness in two cHCC-CCA case reports. TLS composition and its relationship to CXCL12 expression were analysed by fluorescent multiplex immunohistochemistry. A high intratumoural TLS score was correlated with prolonged survival, whereas a high TLS density in adjacent tissue indicated a worse prognosis in cHCC-CCA. Mature TLSs were related to favorable outcomes and showed more CD8 + T cells infiltrating tumor tissues. We further divided the cHCC-CCA patients into four immune grades by combining the peri-TLS and intra-TLS, and these grades were an independent prognostic factor. In addition, our reported cases suggested a potential value of TLS in predicting immunotherapy response in cHCC-CCA patients. Our findings suggested that CXCL12 expression in cHCC-CCA tissue was significantly correlated with TLS presence. The spatial distribution and density of TLSs revealing the characteristics of the cHCC-CCA immune microenvironment, significantly correlated with prognosis and provided a potential immunotherapy response biomarker for cHCC-CCA.

Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) complicated with intestinal obstruction and perforation.

We report the case of a patient who comes to the emergency department with abdominal pain, oral intolerance and bloody stools, being diagnosed with intestinal obstruction secondary to a jejunal tumor with contained perforation. A laparotomy was performed with resection of the jejunal tumor and taking biopsies from lesions with similar characteristics in the rest of the small bowel compatible with monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL). The monomorphic epitheliotropic intestinal T-cell lymphoma is a rare intestinal tumor with a poor prognosis that is characterized by the proliferation of intraepithelial lymphocytes. The abdominal symptoms are nonspecific and the known major complications are intestinal perforation and obstruction. There is no standard therapeutic approach, being a combination of surgical resection, chemotherapy and autologous stem cell transplant.

Decoding BCOR-ITD Sarcomas: Case Report of a Rare Pediatric Tumor With Challenges in Diagnosis.

Sarcomas characterized by BCOR gene alterations, are a distinct clinico-pathological group of high-grade tumors, that represent 5% of small round cell tumors without EWSR or FUS fusion. Diverse genetic alterations characterize this group, including BCOR-CCNB3 gene fusion being the most common alteration and less frequently internal tandem duplications (ITDs). We present a compelling case of a 3-year-old girl diagnosed with a high-grade nasoethmoidal sarcoma exhibiting BCOR-ITD. The diagnostic process illustrates the histological and immunophenotypic spectrum, requiring an extensive immunohistochemical panel and diverse molecular tests for accurate classification. Additionally, this case highlights the challenges in detecting BCOR-ITDs using different NGS panels, advocating for alternative molecular approaches. Our patient after 10 months since diagnosis is alive with progressive disease. This emphasizes the urgency for ongoing research to refine diagnostic methods and develop effective therapeutic strategies for these rare and aggressive tumors.

Extra-skeletal intracranial mesenchymal chondrosarcoma: systematic-literature review.

Intracranial mesenchymal chondrosarcoma (IMC) is a rare malignant tumor in pediatric population. IMC can present as extra- or intra-axial lesion in pediatric patients, though the former is commoner causing raised intracranial pressure (ICP). Radiological diagnosis is a challenge in these cases, as is it difficult to differentiate these from other extra-axial neoplasms due to the wide differential diagnosis in pediatric population. We aim to systematically review the literature and present a rare case of extraskeletal intracranial mesenchymal chondrosarcoma treated with safe maximal resection. A systematic review of literature was conducted in accordance with PRISMA guidelines. PubMed and Scopus databases were queried using the search terms, "primary intracranial chondrosarcoma", "extraskeletal mesenchymal chondrosarcoma", "mesenchymal chondrosarcoma" and "pediatric". Presentation, surgical management and outcome of a 15-year-old male with an extraskeletal IMC are also described. The search yielded 25 articles which met the inclusion criteria. These published records consisted of 33 IMC cases with mean age at presentation of 9.81 ± 5.2years (range 2months to 18years). Frontal region was the commonest locations (11, 33.3%). Most common presentation was headache (14, 42.4%). All patients underwent surgical intervention: gross total resection (20, 60.6%), subtotal resection (9, 27.3%) and no extent mentioned (4, 12.1%). No adjuvant therapy was received in 15 patients (45.5%). On latest follow-up, 11 patients (33.3%) are on remission, 5 patients (15.2%) are symptom free, 3 patients (9.1%) had recurrence, 2 patients (6.1%) had metastasis and 9 patients (27.3%) expired. IMC is a rare entity in pediatric population with imaging findings which are non-characteristic leading to its diagnostic challenge. It can masquerade as other extra-axial intracranial neoplasm (meningioma or hemangiopericytoma). Combination of clinico-radiological and pathological examination can help in accurate diagnosis. SafeMaximal resection followed by radiotherapy is the preferred treatment strategy.

Clinical Characteristics, Patterns of Care, and Treatment Outcomes of Radiation-Associated Sarcomas

Radiation-associated sarcomas (RASs) are rare tumors with limited contemporary data to inform prognostication and management. We sought to identify the clinical presentation, patterns of care, and prognostic factors of RASs. RAS patients treated at a single institution from 2015 to 2021 were retrospectively reviewed for clinicopathologic variables, treatment strategies, and outcomes. Thirty-eight patients were identified with a median follow-up of 30.5 months. The median age at RAS diagnosis was 68.4 years (27.9–85.4), with a median latency from index radiotherapy (RT) of 9.1 years (3.7–46.3). RAS histologies included angiosarcoma (26%), undifferentiated pleomorphic sarcoma (21%), and osteosarcoma (18%). Most were high-grade (76%). Genomic profiling revealed low tumor mutational burden, frequent inactivating TP53 mutations (44%), CDKN2A deletions (26%), and MYC amplifications (22%), particularly in breast angiosarcomas. Of 38 patients, 33 presented with localized disease, 26 of whom were treated with curative intent. Overall, the median progression-free survival (PFS) was 9.5 months (1.4–34.7), and the overall survival (OS) was 11.1 months (0.6–31.6). Patients with localized vs. metastatic RASs had a longer PFS (HR 3.0 [1.1–8.5]; p = 0.03) and OS (HR, 3.0 [1.04–8.68]; p = 0.03). Among localized RAS patients, high grade was associated with shorter OS (HR, 4.6 [1.04–20.30]; p = 0.03) and resection with longer OS (mean 58.8 vs. 6.1 months, HR, 0.1 [0.03–0.28]; p < 0.001). Among patients undergoing resection, negative margins were associated with improved OS (mean 71.0 vs. 15.5 months, HR, 5.1 [1.4–18.2]; p = 0.006). Patients with localized disease, particularly those undergoing R0 resection, demonstrated significantly better outcomes. Novel strategies are urgently needed to improve treatment outcomes in this challenging group of diseases.

H3K27-Altered Diffuse Glioma of the Spinal Cord in Adult Patients: A Qualitative Systematic Review and Peculiarity of Radiological Findings

Background: Primary spinal cord diffuse gliomas (SpDG) are rare tumors that may harbor, like diffuse intrinsic pontine gliomas (DIPG), H3K27M mutations. According to the WHO (2021), SpDGs are included in diffuse midline H3K27-altered gliomas, which occur more frequently in adults and show unusual clinical presentation, neuroradiological features, and clinical behavior, which differ from H3 G34-mutant diffuse hemispheric glioma. Currently, homogeneous adult-only case series of SpDG, with complete data and adequate follow-up, are still lacking. Methods: We conducted a qualitative systematic review, focusing exclusively on adult and young adult patients, encompassing all studies reporting cases of primitive, non-metastatic SpDG with H3K27 mutation. We analyzed the type of treatment administered, survival, follow-up duration, and outcomes. Results: We identified 30 eligible articles published between 1990 and 2023, which collectively reported on 62 adult and young adult patients with primitive SpDG. Postoperative outcomes were assessed based on the duration of follow-up, with outcomes categorized as either survival or mortality. Patients who underwent surgery were followed up for a mean duration of 17.37 months, while those who underwent biopsy had a mean follow-up period of 14.65 months. Among patients who were still alive, the mean follow-up duration was 18.77 months. The radiological presentation of SpDG varies widely, indicating its lack of uniformity. Conclusion: Therefore, we presented a descriptive scenario where SpDG was initially suspected to be a meningioma, but was later revealed to be a malignant SpDG with H3K27M mutation.

Complex decision making in a patient with lung cancer with incidentally found fast-growing atrial mass

Atrial myxomas are typically found in the left atrium and are the most common among overall rare cardiac tumors. Herein, we describe the clinical course of a 72-year-old female with non-small cell lung adenocarcinoma found to have an atrial mass during an imaging for evaluation for lung cancer progression. Differentiating between distinct types of masses can pose a challenge to the treatment team especially in the setting of exiting malignancy. This case demonstrates the complex decision making involved in the diagnosis, and timing of intervention to remove atrial mass in patients with frailty and a fast-growing cardiac mass.

Navigating diagnostic challenges—distinguishing malignant melanoma and clear cell sarcoma of soft tissues: a case report and review of the literature

BackgroundWithin the spectrum of melanocytic-differentiated tumors, the challenge faced by pathologists is discerning accurate diagnoses, with clear cell sarcoma of soft tissues standing out as a rare and aggressive neoplasm originating from the neural crest. Accounting for 1% of all soft tissue sarcomas, clear cell sarcoma of soft tissues poses diagnostic complexities, often misidentified owing to its phenotypic resemblance to malignant melanoma. This chapter delves into the intricacies of clear cell sarcoma of soft tissues, its epidemiology, characteristic manifestations, and the imperative need for a comprehensive diagnostic approach involving immunohistochemical and molecular analyses.Case presentationA compelling case unfolds as a 25-year-old male from Morocco, initially misdiagnosed with malignant melanoma, experiences tumor recurrence on the second toe. With no history of trauma or familial neoplasia, the patient’s clinical journey is explored, emphasizing the importance of detailed clinical examinations and radiological assessments. The chapter elucidates the histopathological findings, immunohistochemical spectrum, and the correlation between clinical parameters and diagnostic inference, ultimately leading to metatarsal amputation. This clinical vignette highlights the multidimensional diagnostic process in soft tissue neoplasms, emphasizing the synergistic role of clinical, radiological, and histopathological insights.ConclusionThe diagnostic challenges inherent in melanocytic-differentiated tumors, exemplified by the rarity of soft tissue clear cell sarcoma, underscore the essential role of an integrated diagnostic approach. This concluding chapter emphasizes the perpetual collaboration required across pathology, clinical medicine, and radiology for nuanced diagnostic precision and tailored therapeutic strategies. The rarity of these soft tissue malignancies necessitates ongoing interdisciplinary engagement, ensuring the optimization of prognosis and treatment modalities through a comprehensive understanding of the diagnostic intricacies presented by clear cell sarcoma of soft tissues.

Presence of herpesviruses, parvoviruses, and polyomaviruses in sinonasal lymphoma.

Sinonasal lymphoma (SL) is a rare lymphatic neoplasm of the nasal cavities, paranasal sinuses and nasopharynx. Whereas some risk factors for SL subtypes have been identified, their aetiology is unknown. Along with other predisposing factors, the viral association of lymphomas, such as Epstein-Barr virus (EBV) and Burkitt and Hodgkin lymphomas, is well-established. Modern molecular biology techniques have enabled the discovery of novel human viruses, exemplified by the protoparvovirus cutavirus (CuV), associated with cutaneous T-cell lymphoma. These findings, and the anatomical location of the sinonasal tract with its rich microbiome and infectious agents, justify in-depth studies among SL. We analysed the presence of 20 viruses of Orthoherpesviridae, Parvoviridae, and Polyomaviridae by qPCR in 24 SL tumours. We performed RNAscope in situ hybridisation (RISH) to localize the viruses. Parvovirus-specific IgG was analysed by enzyme immunoassay and targeted next-generation sequencing (NGS) was applied to detect CuV in plasma. We detected viral DNA in 15/24 (63%) tumours; nine of EBV, six of human herpesvirus (HHV) -7, four each of HHV-6B and parvovirus B19, two of cytomegalovirus, and one each of CuV and Merkel-cell polyomavirus. We found tumours with up to four viruses per tumour, and localized CuV and EBV DNAs by RISH. Two of the ten plasma samples exhibited CuV IgG, and one plasma sample demonstrated CuV viremia by NGS. Viruses were frequent findings in SL. The EBV detection rate was high in diffuse large B-cell lymphoma, and co-detections with other viruses were prevalent.

Pediatric central nervous system (CNS) neuroblastoma: A case report

Background: Neuroblastomas are rare tumors activated by the FoxR2 gene commonly found in pediatric patients. Due to the novelty of these tumors, there is no standard diagnostic profile. However, they have been found to express Olig2, MAP2, SOX10, ANKRD55, and synaptophysin, and they can be identified with magnetic resonance imaging (MRI). Treatment with chemotherapy combined with stem cell rescue and craniospinal irradiation can improve non-infant patient outcomes. Case Description: We report a case of a 2-year-old patient who was diagnosed with a neuroblastoma through MRI imaging and pathology that confirmed FoxR2 gene activation. The tumor was successfully removed. However, the tumor was not high-grade like most FoxR2 neuroblastomas. Conclusion: The unusual presentation of a low-grade FoxR2 neuroblastoma demonstrates the necessity to conduct further research into the characteristics of these tumors.

Sinonasal cancer incidence in Lombardy, Italy, 2008-20.

Epithelial sinonasal cancers (SNC) are rare tumours with recognized associations with known/suspected occupational carcinogens (wood/leather dust, nickel/chromium compounds and formaldehyde). In Italy, a national SNC registry organized as a network of regional registries was established by law in 2008. To describe SNC time trends, occupational exposures and geographical distribution in Lombardy, North-West Italy, based on population registry data (2008-20). The Lombardy SNC Registry records epithelial SNCs using various sources. Interviews to collect occupational history are performed using a standardized questionnaire. Using several standard populations, we calculated yearly crude and age-standardized rates (ASRs per 100,000 person-years). Standardized incidence ratios (SIR) at municipality level were calculated, and Bayesian models were fitted to produce smoothed SIR maps. We recorded 827 cases (553 men, 274 women). Crude (world standardized) ASRs were 0.9 (0.4) in men and 0.4 (0.2) in women, with no time trends. Interviews were obtained for 485 (88%) men and 223 (81%) women. Among men, 217 (45%) had been exposed to occupational carcinogens (wood/leather dust: 150/65 cases, 31%/13%), while only 36 women (16%) were exposed. Among 201 men with adenocarcinoma, exposure to wood/leather dust occurred in 103/50 cases (75%/50%). Areas with elevated SIRs associated with leather dust were found in the Western areas. Exposure to wood dust was more widespread. This study found a high frequency of occupational exposures (wood and leather dust), particularly in men with SNC. Employment in shoe industries clustered in the Western part, while work in furniture industries was less spatially structured.

Impact of CDK Inhibitors on TBXT Expression in Chordoma Cell Lines Including the First Stable Cell Line of a High-Grade Chordoma

Chordomas are very rare malignant neoplasms of the bone occurring almost exclusively along the spine. As the tumours are thought to arise from notochordal remnants, the vast majority of chordomas express the TBXT gene, resulting in detectable nuclear amounts of its gene product brachyury. This T-Box transcription factor is commonly recognised as being essential in chordoma cells, and limiting TBXT expression is thought to be the key factor in controlling this tumour. Although the tumour is rare, distinct molecular differences and vulnerabilities have been described with regard to its location and the progression status of the disease, rendering it mandatory for novel cell lines to reflect all relevant chordoma subtypes. Here, we describe a novel chordoma cell line arising from the pleural effusion of a disseminated, poorly differentiated chordoma. This cell line, U-CH22, represents a highly aggressive terminal chordoma and, therefore, fills a relevant gap within the panel of available cell culture models for this orphan disease. CDK7 and CDK9 inhibition was lately identified as being effective in reducing viability in four chordoma cell lines, most likely due to a reduction in brachyury levels. In this study, we determined the capability of the CDK7 inhibitor THZ1 and the CDK1/2/5/9 inhibitor dinaciclib to reduce TBXT expression at mRNA and protein levels in a broad range of nine cell lines that are models of primary, recurrent, and metastasised chordoma of the clivus and the sacrum.

Genetic Landscape and Its Prognostic Impact in Children With Langerhans Cell Histiocytosis.

Langerhans cell histiocytosis (LCH) is a rare myeloid neoplasm that predominantly affects young children. To investigate genetic alterations and their correlation with clinical characteristics and prognosis in pediatric LCH. We performed targeted sequencing to detect mutations in LCH lesions from pediatric patients. A total of 30 genomic alterations in 5 genes of the MAPK pathway were identified in 187 of 223 patients (83.9%). BRAF V600E (B-Raf proto-oncogene, serine/threonine kinase) was the most common mutation (51.6%), followed by MAP2K1 (mitogen-activated protein kinase kinase 1) alterations (17.0%) and other BRAF mutations (13.0%). ARAF (A-Raf proto-oncogene, serine/threonine kinase) and KRAS (KRAS proto-oncogene, GTPase) mutations were relatively rare (2.2% and 0.9%, respectively). Additionally, FNBP1 (formin-binding protein 1)::BRAF fusion and MAP3K10 (mitogen-activated protein kinase kinase 10) mutations A17T and R823C were identified in 1 case each, with possible constitutive activation of ERK1/2 phosphorylation. BRAF V600E was more frequent in patients with risk organ involvement, while MAP2K1 mutation was more prevalent in patients with single-system LCH (P = .001). BRAF V600E was associated with craniofacial bone, skin, liver, spleen, and ear involvement (all P < .05). Patients with other BRAF mutations had a higher proportion of spinal column involvement (P = .006). Univariate analysis showed a significant difference in progression-free survival among the 4 molecular subgroups for patients treated with first-line therapy (P = .02). According to multivariate analysis, risk organ involvement was the strongest independent adverse prognostic factor (hazard ratio, 8.854; P < .001); BRAF or MAP2K1 mutation was not an independent prognostic factor. Most pediatric patients with LCH carry somatic mutations involving the MAPK pathway, correlating with clinical characteristics and outcomes for first-line chemotherapy.

A Bosniak III Cyst Unmasking Tubulocystic Renal Cell Carcinoma in an Adolescent: Management with Selective Arterial Clamping and Robotic Enucleation

The Bosniak classification of renal cysts aims to provide a probabilistic risk assessment indicating the likelihood of malignancy from imaging findings. Originally designed to classify adult renal cysts based on computed tomography findings, the Bosniak classification has been extended to pediatric patients, with some adjustments made with the aim of accommodating magnetic resonance imaging (MRI) and ultrasonography (US). Bosniak IV lesions are rare in adolescents, indicating localized renal cell carcinoma and requiring surgical intervention. In contrast, Bosniak III lesions can be treated conservatively, although there is a lack of specific guidelines on their management. We present a case of a 14-year-old boy with a Bosniak III lesion, which was incidentally detected during the US evaluation of a left varicocele. After a 12-month follow-up, MRI revealed progression to a Bosniak IV cyst. Robot-assisted tumor enucleation was performed with selective artery clamping when the patient was 15. Histopathology showed tubulocystic renal cell carcinoma without adverse features. Immunocytochemistry supported a favorable prognosis of this rare tumor (&lt;1% of renal tumor), thus obviating the need for adjuvant treatment. At the 18-month follow-up, no recurrence or distant metastasis were observed. This case highlights the importance of an aggressive treatment in persistent Bosniak III and Bosniak IV renal cysts in children and adolescents and the necessity to offer a nephron-sparing surgery.

Clinical management of typical and atypical carcinoids/neuroendocrine tumors in ENETS centres of excellence (CoE): Survey from the ENETS lung NET task force.

Lung carcinoid tumours are neuroendocrine neoplasms originating from the bronchopulmonary tract's neuroendocrine cells, accounting for only 1%-3% of all lung cancers but 30% of all neuroendocrine tumours. The incidence of lung carcinoids, both typical and atypical, has been increasing over the years due to improved diagnostic methods and increased awareness among clinicians and pathologists. The most recent WHO classification includes a subgroup of lung carcinoids with atypical morphology and higher mitotic count and/or Ki67 labelling index. Despite appropriate surgery, the 5-year survival rate for atypical carcinoids barely exceeds 50%-70%. The role of adjuvant therapy in lung carcinoids is not well-defined, and clinical decisions are generally based on the presence of high-risk features. Long-term follow-up is essential to monitor for recurrence, although the optimal follow-up protocol remains unclear. To address the lack of consensus in clinical management decisions, the European Neuroendocrine Tumor Society (ENETS) initiated a survey among 20 expert centres. The survey identified varied opinions on approaches to imaging, surgery, use of adjuvant therapy, and follow-up protocols. Notably, the absence of dedicated multidisciplinary lung neuroendocrine tumour boards in some centres was evident. Experts agreed on the need for a prospective adjuvant trial in high-risk patients, emphasizing the feasibility of such a study. In conclusion, the study highlights the need for a more uniform adoption of existing guidelines in the management of lung carcinoid tumours and emphasizes the importance of international collaboration to advance research and patient care. Close collaboration between healthcare providers and patients is vital for effective long-term surveillance and management of these rare tumours.