Saphenous nerve schwannoma as a cause of vascular claudication - case report and review of the literature.

Schwannomas are peripheral nerve tumours that are uncommon. They typical present with a palpable mass, pain or neurological changes. We describe a saphenous nerve schwannoma compressing the superficial femoral artery and causing vascular claudication. We also review the literature.

Facing the challenges of very rare tumors of pediatric age: The European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) background, goals, and achievements.

It has become increasingly clear in recent years that we need to develop ad hoc strategies to combat very rare tumors (VRT) of pediatric age. In 2008, several schemes being run in different countries were pooled together to create the European Cooperative Study Group for Pediatric Rare Tumors (EXPeRT) project: a cooperative study group that aimed to promote research in the relatively uncharted territory of rare tumors of pediatric age. EXPeRT members were able to activate different levels of cooperation to achieve their goals, and to obtain dedicated funding by participating in EU-financed projects. Their experiences emphasize the merits of networking, seeking new partnerships, joining forces, and pooling resources to extend the reach of research efforts, and ultimately improve the quality of patient care. Between 2018 and 2021, the EXPeRT has been active in establishing the Pediatric Rare Tumors Network - European Registry (PARTNER). This project had the main purposes of building a European common registry of pediatric VRT, but also the major task of developing diagnostic and treatment guidelines for VRT (or at least part of them). These clinical recommendations are the subject of a series of papers on Pediatric Blood and Cancer.

Paediatric very rare tumours registration and management in European countries with low health expenditure average rates.

PURPOSE: Within the Paediatric Rare Tumours Network-European Registry (PARTNER) project, we aimed to evaluate the situation on the registration and management of paediatric patients affected by very rare tumours (VRT) in the European low health expenditure average rates (LHEAR) countries. METHODS: A survey regarding infrastructure, organisation, and clinical decision-making information on VRT was designed. This survey was distributed to the representatives of LHEAR countries involved in the activities of the PARTNER Work Package 7. RESULTS: Eighteen answers from 17 countries were collected regarding the national organisation, methods of registration of VRT cases, the availability of medical experts in VRT, the access to updated diagnostic and therapeutic procedures (such as proton therapy, immunotherapy and, targeted therapies), and research on paediatric VRT. A high variability in the registration and management of patients with VRT has been observed with additional wide inequalities in pathology review, uniformity of clinical decisions, availability of selected procedures, and diagnostic and research tools. CONCLUSION: In the majority of LHEAR countries, no clinical or research structures have been implemented for children and adolescents with VRT. Therefore, VRT still have an orphan status in these countries. These significant differences on the technology access and use between European regions need to be addressed.

Large mirror brain metastases from primary undifferentiated sarcoma of the breast: case report and review of the literature.

Primary breast sarcomas are rare high-grade tumors with a reported incidence of <1% of breast malignancies. Its dissemination to the CNS is exceptional and only one is found in the literature. The authors described the case of a 22-year-old female with history of a breast undifferentiated sarcoma that present with two large bilateral retrolenticular brain metastases. Both lesions were excised in the same procedure and she underwent adjuvant therapy. She died 24 months after surgery. Despite being aggressive lesions, aggressive treatment of primary breast sarcomas including brain metastases excision, should be considered in order to improve overall survival.

Organizing Pneumonia: A Clinical Challenge in a Child With Previous Rhabdomyosarcoma.

Organizing pneumonia is a pulmonary disease of undefined etiology, with few reported cases in children. It may be secondary to chemotherapy, radiation therapy, infectious agents, or hematopoietic cell transplantation. We present a case of an 18-year-old boy who presented to a follow-up consult with respiratory symptoms at the age of 11 years, 8 years after finishing treatment for a prostatic relapse of a pelvic rhabdomyosarcoma. Chest radiography revealed nodular opacities in the left lung, the one in the left lower lobe with silhouette sign with the left hemidiaphragm. Chest computerized tomography showed 2 nodular lesions in the left upper lobe, one of them cavitated, and another nodular lesion in the left lower lobe; 2 of these nodules had surrounding ground-glass opacities. Microbiological work-up, including tuberculosis screening, was negative. Biopsy revealed findings suggestive of organizing pneumonia. He presented spontaneous resolution. This case presented a diagnostic challenge due to rarity of this condition and its indetermined association with the patient's history of rhabdomyosarcoma. With this case, the authors alert that organizing pneumonia must be considered in patients presenting with pulmonary lesions with a history of previous hematopoietic stem cell transplants, lung irradiation, or immunosuppression. Pulmonary metastases and secondary tumors must be considered as a differential diagnosis in patients with a heavily treated relapsed rhabdomyosarcoma.

Brachytherapy for Pediatric Patients at Gustave Roussy Cancer Campus: A Model of International Cooperation for Highly Specialized Treatments.

PURPOSE: Childhood cancer is rare, and treatment is frequently associated with long-term morbidity. Disparities in survival and long-term side effects encourage the establishment of networks to increase access to complex organ-conservative strategies, such as brachytherapy. We report our experience of an international cooperation model in childhood cancers. METHODS AND MATERIALS: We examined the outcome of all children referred to our center from national or international networks to be treated according to a multimodal organ-conservative approach, including brachytherapy. RESULTS: We identified 305 patients whose median age at diagnosis was 2.2 years (range, 1.4 months to 17.2 years). Among these patients, 99 (32.4%) were treated between 2015 and 2020; 172 (56.4%) were referred from national centers; and 133 (43.6%) were international patients from 31 countries (mainly Europe). Also, 263 patients were referred for primary treatment and 42 patients were referred for salvage treatment. Genitourinary tumors were the most frequent sites, with 56.4% bladder/prostate rhabdomyosarcoma and 28.5% gynecologic tumors. In addition to brachytherapy, local treatment consisted of partial tumor resection in 207 patients (67.9%), and 39 patients (13%) had additional external radiation therapy. Median follow-up was 58 months (range, 1 month to 48 years), 93 months for national patients, and 37 months for international patients (P < .0001). Five-year local control, disease-free survival, and overall survival rates were 90.8% (95% confidence interval [CI], 87.3%-94.4%), 84.4% (95% CI, 80.1%-89.0%), and 93.3% (95% CI, 90.1%-96.5%), respectively. Patients referred for salvage treatment had poorer disease-free survival (P < .01). Implementation of image guided pulse-dose-rate brachytherapy was associated with better local control among patients with rhabdomyosarcoma referred for primary treatment (hazard ratio, 9.72; 95% CI, 1.24-71.0). At last follow-up, 16.7% patients had long-term severe treatment-related complications, and 2 patients (0.7%) had developed second malignancy. CONCLUSIONS: This retrospective series shows the feasibility of a multinational referral network for brachytherapy allowing high patient numbers in rare pediatric cancers. High local control probability and acceptable late severe complication probability could be achieved despite very challenging situations. This cooperation model could serve as a basis for generating international reference networks for high-tech radiation such as brachytherapy to increase treatment care opportunities and cure probability.

Arteriovenous fistula of the filum terminale masqueraded as a failed back surgery syndrome - A case report and review of literature.

BACKGROUND: The filum terminale arteriovenous fistulas (FTAVFs) are a very rare type of spinal vascular malformation. Clinically, these lesions could present with a progressive ascending myelopathy also called FoixAlajouanine syndrome. Due to the rarity of these vascular malformation, some can be misdiagnosed, submitted to unnecessary spinal surgery, and even masqueraded as a failed back surgery syndrome. Based on the present case and related literature, we review all the cases with similar history and describe factors that should raise awareness for diagnosis of this spinal vascular malformation. CASE DESCRIPTION: We present a case of a patient with a FTAVF at the level of L5-S1 that presented with a FoixAlajouanine syndrome. He had been previously submitted to a lumbar decompressive laminectomy without sustained improvement. After the identification and surgical treatment of the vascular malformation, he had progressive neurological improvement. CONCLUSION: FTAVF is a very rare spinal intradural spinal vascular malformation that can be masqueraded as a failed back surgery syndrome. In these cases, signs of ascending myelopathy should prompt awareness and vascular voids must be carefully evaluated in MRI.

HIPTCN: Prospective Observational Study of Hypocoagulated Head Trauma Patients with Normal Admission Computed Tomography Scan.

INTRODUCTION: Our national protocol for traumatic brain injury dictates that hypocoagulated patients with mild trauma and initial tomography scan with no intracranial traumatic changes must be hospitalized for 24 hours and do a post-surveillance tomography scan. The main goal of this study was to evaluate the clinical relevance of these measures. MATERIAL AND METHODS: A prospective observational study was undertaken in four hospitals. Adult hypocoagulated traumatic brain injury patients with a normal tomography scan were included. The main outcomes evaluated were rate of delayed intracranial hemorrhage, rate of admission in a neurosurgical department, rate of complications related with surveillance and rate of prolonged hospitalization due to complications. An analysis combining data from a previously published report was also done. RESULTS: A total of 178 patients were included. Four patients (2.3%) had a delayed hemorrhage and three (1.7%) were hospitalized in a neurosurgery ward. No cases of symptomatic hemorrhage were identified. No surgery was needed, and all patients had their anticoagulation stopped. Complications during surveillance were reported in seven patients (3.9%), of which two required prolonged hospitalization. DISCUSSION: The rate of complications related with surveillance was higher than the rate of delayed hemorrhages. The initial period of in-hospital surveillance did not convey any advantage since the management of patients was never dictated by neurological changes. Post-surveillance tomography played a role in deciding about anticoagulation suspension and prolongation of hospitalization. CONCLUSION: Delayed hemorrhage is a rare event and the need for surgery even rarer. The need for in-hospital surveillance should be reassessed.

Introdução: O nosso protocolo nacional para traumatismos cranioencefálicos recomenda que doentes hipocoagulados com trauma craniano ligeiro e tomografia inicial sem alterações traumáticas intracranianas sejam hospitalizados 24 horas e façam uma tomografia computorizada pós-vigilância. O principal objetivo deste estudo foi avaliar a relevância clínica dessas medidas. Material e Métodos: Foi realizado em quatro hospitais um estudo prospetivo e observacional. Foram incluídos adultos hipocoagulados com trauma craniano e tomografia normal. Os principais outcomes avaliados foram: taxa de hemorragia intracraniana tardia, taxa de internamento numa enfermaria de neurocirurgia, taxa de complicações relacionadas com a vigilância e taxa de hospitalização prolongada por complicações. Resultados: Foram incluídos um total de 178 doentes. Quatro doentes (2,3%) apresentaram hemorragia tardia e três (1,7%) foram mantidos hospitalizados numa enfermaria de Neurocirurgia. Não foram documentados casos de hemorragia tardia sintomática. Nenhuma cirurgia foi necessária e em todos estes doentes a anticoagulação foi interrompida. Durante a vigilância, foram relatadas complicações em sete doentes (3,9%), dos quais dois exigiram hospitalização prolongada. Discussão: A taxa de complicações relacionadas com a vigilância foi maior do que a taxa de hemorragia tardia. O período inicial de vigilância intra-hospitalar não trouxe qualquer vantagem, já que o manejo dos doentes nunca foi ditado por alterações neurológicas. A tomografia pós-vigilância desempenhou um papel importante na decisão sobre a suspensão da anticoagulação e o prolongamento da hospitalização. Conclusão: A hemorragia tardia é um evento raro e a necessidade de cirurgia ainda mais. Deve ser reavaliada a necessidade de vigilância intra-hospitalar.

Giant Malignant Peripheral Nerve Sheath Tumor of the Scalp: Case Report and Review of the Literature.

BACKGROUND: Malignant peripheral nerve sheath tumors (MPNSTs) are rare nervous system tumors that rarely appear on the scalp. About half of the scalp MPNSTs described in the literature have reached giant dimensions at the time of diagnosis. The surgical treatment is the gold standard for this type of tumor. Some authors suggest adjuvant radiotherapy for local tumor control, although there is uncertainty about its advantages and its use is not without risks. CASE DESCRIPTION: We present the case of a 31-year-old man who presented with a large necrotic scalp tumor of the left frontoparietal convexity. magnetic resonance imaging showed a large extra-axial tumor, measuring 17 x 17 x 8 cm, centered on the soft tissues, with skull erosion and signs of dural invasion, although with no intradural component. The tumor was surgically removed and the osteocutaneous defect was reconstructed with a latissimus dorsi muscle free flap. The anatomopathologic diagnosis was MPNST. The patient then underwent adjuvant radiotherapy. After 7 months he developed a progressive right hemiparesis and magnetic resonance imaging showed results compatible with cerebral radiation necrosis. This motor deficit improved with corticotherapy. After 9 months the patient went back to his home country and was subsequently lost to follow-up. CONCLUSIONS: Giant MPNSTs of the scalp are highly aggressive lesions that should primarily be treated in a surgical fashion. Although adjuvant radiotherapy has been used routinely for local tumor control, there is uncertainty about its advantages.

Burkitt leukemia with numb chin syndrome and cavernous sinus involvement.

Cavernous sinus syndrome is a rare event. Non-Hodgkin lymphomas, are one possible cause. Neurological presentation of these lymphomas is also exceptional. We report the case of an 11-year-old boy that developed a right third cranial nerve palsy and numbness in the distribution of the right mental nerve, with normal CSF, and enlargement of cavernous sinus on the same side, who was diagnosed Burkitt leukemia.

Enhancement of antineoplastic action of 5-aza-2'-deoxycytidine by phenylbutyrate on L1210 leukemic cells.

Epigenetic changes, such as aberrant DNA methylation that silences tumor suppressor genes (TSGs), can play an important role in the development of leukemia. The DNA methylation inhibitor, 5-aza-2'-deoxycytidine (5-AZA-CdR), can reactivate these silent TSGs and is an interesting agent to investigate for therapy of leukemia. It has been reported that the effectiveness of 5-AZA-CdR to reactivate TSG can be enhanced by inhibitors of histone deacetylase (HDIs). HDIs can convert a compact chromatin structure to an open configuration that facilitates gene expression. An interesting HDI is phenylbutyrate (PB), which has shown some clinical activity for the therapy of leukemia. In this report we have investigated the antineoplastic activity of 5-AZA-CdR and PB alone and in combination on murine L1210 lymphoid leukemic cells. The in vitro treatment of 5-AZA-CdR and PB in combination produced a greater inhibition of growth, DNA synthesis, and also a greater reduction on colony formation on both L1210 and human HL-60 leukemic cells as compared to either drug alone. The combination also produced a synergistic activation of the TSG, p15CDN2B, in the L1210 cells. In mice with L1210 leukemia the combination showed enhanced antineoplastic activity. We also observed an enhancement of the antineoplastic activity of this combination in mice with L1210 leukemia. These data provide a rationale to investigate 5-AZA-CdR and PB in patients with advanced leukemia.

Activation of expression of p15, p73 and E-cadherin in leukemic cells by different concentrations of 5-aza-2'-deoxycytidine (Decitabine).

BACKGROUND: Inactivation of genes that suppress neoplasia by aberrant DNA methylation is a key event that occurs during the development of leukemia. The inhibitor of DNA methylation, 5-aza-2'-deoxycytidine (5AZA), which can re-activate these genes, is under clinical investigation for therapy of leukemia. The objective of this study was to determine the concentrations of 5AZA that will re-activate target silent genes in human leukemic cell lines. MATERIALS AND METHODS: RT-PCR was used to evaluate the effect of concentrations of 1 to 100 ng/ml of 5AZA on the re-activation of p15 and p73 in KG1a myeloid leukemic cells and E-cadherin in HL-60 myeloid leukemic cells. The effect of 5AZA on inhibition of growth, DNA synthesis and colony formation in these cell lines was also investigated. RESULTS: The extent of activation of the target genes was dependent on the concentration of 5AZA. For p15, pronounced activation was observed at 10 ng/ml or greater. For p73 and E-cadherin significant activation was observed at 100 ng/ml of 5AZA. Maximal inhibition of growth, DNA synthesis and colony formation occurred at 100 ng/ml. CONCLUSION: The in vitro antineoplastic and gene re-activation activity of 5AZA is dependent on the concentration of this analog. These data may be helpful in the design of the optimal dose-schedule of 5AZA for the clinical therapy of leukemia.

Abdominal inflammatory myofibroblastic tumor a clinicopathologic study with reappraisal of biologic behavior.

BACKGROUND AND PURPOSE: Inflammatory myofibroblastic tumor (IMT) is a proliferative lesion of controversial nosology and uncertain prognosis. In an attempt to acquire further understanding of pathogenesis and biologic behavior, we surveyed abdominal IMTs managed over the last 12 years at a single institution. METHODS: Intra-abdominal IMTs treated between 1995 and 2007 were reviewed concerning demographic, clinical, and pathologic features as well as therapeutic management and outcome. All specimens were reevaluated by histologic examination and immunohistochemistry. RESULTS: There were 7 patients (4 males; age range, 28 days to 14 years). Five lesions were located in alimentary tract: 1 gastric presenting with bleeding, 1 hepatic presenting with a thoracic wall mass, 1 pancreatic and 2 colonic presenting with obstructive symptoms. One splenic IMT was found incidentally. The remaining case arose from the adrenal gland and presented with a palpable mass. The gastric and adrenal IMTs had evidence of a previous or concomitant infectious setting. Five lesions were excised. The pancreatic IMT underwent a drainage procedure followed by steroid administration, and the hepatic lesion received antibiotics. Histopathology revealed characteristic findings of IMT. Expression of anaplastic lymphoma kinase was negative in all cases. At a median follow-up of 6 years (range, 3-15), all children were asymptomatic with no recurrences. The hepatic and pancreatic IMT displayed complete and near total regression, respectively. CONCLUSION: A benign behavior of abdominal IMTs was observed even in patients not undergoing surgical excision. Although IMT remains a surgical disease, a conservative approach may be reasonable in select cases.

Allogeneic hematopoietic stem-cell transplantation for leukocyte adhesion deficiency.

OBJECTIVES: Leukocyte adhesion deficiency is a rare primary immune disorder caused by defects of the CD18 beta-integrin molecule on immune cells. The condition usually presents in early infancy and is characterized by deep tissue infections, leukocytosis with impaired formation of pus, and delayed wound healing. Allogeneic hematopoietic stem-cell transplantation offers the possibility of curative therapy, and with patient numbers at any individual center being limited, we surveyed the transplant experience at 14 centers worldwide. METHODS: The course of 36 children with a confirmed diagnosis of leukocyte adhesion deficiency who underwent hematopoietic stem-cell transplantation between 1993 and 2007 was retrospectively analyzed. Data were collected by the registries of the European Society for Immunodeficiencies/European Group for Blood and Marrow Transplantation, and the Center for International Blood and Marrow Transplant Research. RESULTS: At a median follow-up of 62 months (extending to 14 years), the overall survival rate was 75%. Myeloablative conditioning regimens were used in 28 patients, and reduced-intensity conditioning in 8 patients, with no deaths in this subgroup. Survival rates after matched family donor and unrelated donor transplants were similar, with 11 of 14 matched family donor and 12 of 14 unrelated donor recipients alive; mortality was greatest after haploidentical transplants, after which 4 of 8 children did not survive. Twenty-seven transplant recipients were alive, with full donor engraftment in 17 cases, mixed multilineage chimerism in 7 patients, and mononuclear cell-restricted chimerism in an additional 3 cases. CONCLUSIONS: Hematopoietic stem-cell transplantation offers long-term benefit in leukocyte adhesion deficiency and should be considered as an early therapeutic option if a suitable HLA-matched stem-cell donation is available. Reduced-intensity conditioning was particularly safe, and mixed-donor chimerism seems sufficient to prevent significant symptoms, although careful long-term monitoring will be required for these patients.