Richter’s Transformation as leptomeningeal infiltration in a Chronic Lymphocytic Leukemia patient receiving Venetoclax. Could blood-brain barrier be a disease “sanctuary” during Venetoclax treatment?

We present a unique Richter’s transformation case in CNS with identical to CLL clonal origin in a patient treated with Venetoclax. With our case we make implications on whether Venetoclax penetrates the blood-brain barrier and we address the debating issue of the appropriate Venetoclax dose in case of drug-drug interactions.

LINC-05. PRIMARY CENTRAL NERVOUS SYSTEM EWING SARCOMA IN PEDIATRIC AND AYA PATIENTS: 2 INSTITUTIONS EXPERIENCE IN BUENOS AIRES ARGENTINA

INTRODUCTION Ewing Sarcoma (ES) is defined by molecular markers, being t(11;22)(q24;q12) the most frequent. Intracranial ES usually shows as metastases from extracranial sites. Primary central nervous system (CNS) lesions are extremely rare. MATERIAL AND METHODS Retrospective review of clinical records from patients with primary CNS ES, assessed at 2 institutions in Argentina between 2007–2019. Translocation was evidenced in all cases through molecular testing. Clinical characteristics, imaging, histopathology, and treatment response were evaluated. Extracranial and osseous lesions were excluded. RESULTS 15 patients. Median age at beginning of symptoms: 8 yo (2–20). Most patients had intracranial hypertension syndrome (14/15). In brain MRI, 5/15 supratentorial lesions, 4/15 posterior fosa, 1/15 medullary, 2/15 supra and infratentorial, and 3/15 lesions diffuse leptomeningeal infiltration. Histopathologic findings showed diffuse pattern with small round blue cells in most cases, other patterns were also described. CD99 marked positive in all cases. Misdiagnosis with glial tumors (4/15), medulloblastoma (6/15) and infectious diseases (3/15); led to median delay to accurate diagnosis of 3 months (range 0–67). After correct diagnosis patients were treated with standard ES treatment (6 VIDE cycles plus radiotherapy) in 14/15 patients. Vincristine, irinotecan and temozolamide was used as second line treatment in all relapse cases whenever possible. EFS was 22 months (2- 65). OS at 5 years of follow-up was 46,67% (mean OS 31 mo). CONCLUSION Even though molecular assessment led to accurate diagnosis in all cases, treatment response and outcome showed two different groups of patients with long and very short survival. Adaptative therapy should be considered.

Granulocytic Sarcoma with Meningeal Leukemia. A Case Report

The case of a 63-year-old woman is presented who developed 18 years after undergoing allogenic bone marrow transplantation for chronic myeloid leukaemia a granulocytic sarcoma localised in the presacral region. Complete radiologic remission was obtained with the administration of imatinib. She developed a metachron granulocytic sarcoma in the right frontal region associated to leptomeningeal infiltration. Complete clinical and near complete radiological remission was obtained with the administration of nilotinib. The patient was finally lost of progression of the frontal and meningeal localisations 45 months after the presentation of the first presacral lesion. Throughout the follow-up no sign of systemic leukaemia was detected.

Multiple myeloma with multiple neurological presentations

Multiple myeloma is a haematological malignancy with clonal plasma cell proliferation and production of monoclonal immunoglobulins. Its neurological complications are relatively common, caused by both the disease and the treatment. Neurologists should therefore be familiar with its neurological manifestations and complications. We describe a 40-year-old woman who presented with lower cranial neuropathies mimicking variant Guillain-Barré syndrome, with normal brain and spinal cord imaging and cerebrospinal fluid (CSF) albuminocytological dissociation, and subsequently diagnosed with IgD myeloma. She relapsed repeatedly with differing neurological presentations: numb chin syndrome and twice with impaired vision, first from cerebral venous sinus thrombosis and later from leptomeningeal infiltration of the optic chiasm. We discuss the neurological complications of myeloma, emphasising the need to consider it in a wide variety of neurological presentations and repeatedly to reassess its associated neurological diagnoses. We also highlight the complexity of myeloma treatment.

Giant Congenital Melanocytic Nevi and Neurocutaneous Melanosis

Introduction. The major medical concern with giant congenital melanocytic nevi CMN is high risk of developing cutaneous melanoma, leptomeningeal melanoma, and neurocutaneous melanocytosis.Case Report. A 30-year-old woman with a giant congenital melanocytic nevus covering nearly the entire right thoracodorsal region and multiple disseminated melanocytic nevi presented with neurological symptoms. Cerebral magnetic resonance imaging revealed a large expansive lesion in the left frontal region. Postsurgically pathological diagnosis revealed characteristics of melanoma. Immunohistochemical examination showed S100(+), HMB45(+), MelanA(+), and MiTF(+). She received radiotherapy with temozolomide followed by two more chemotherapy cycles with temozolomide. She followed a rapidly progressive course, reflecting widespread leptomeningeal infiltration, and she died of multiorgan failure seven months after diagnosis of cerebral melanoma.Discussion. This patient was diagnosed as having a neurocutaneous melanosis with malignant widespread leptomeningeal infiltration. Diffuse spinal involvement is unusual and is described in only another patient.

Eosinophil Infiltrates in Pilocytic Astrocytomas of Children and Young Adults

ObjectiveEosinophils may affect each stage of tumour development. Many studies have suggested that tumour-associated tissue eosinophilia (TATE) is associated with favourable prognosis in some malignant tumours. However, only a few studies exist on TATE in central nervous system (CNS) tumours. Our recent study exhibited eosinophils in atypical teratoid/rhabdoid tumours (AT/RTs), pediatric malignant CNS tumours with divergent differentiation. This study examines eosinophils in pilocytic astrocytomas (PAs).MethodsThe study included 44 consecutive cases of patients with PAs and no concurrent CNS inflammatory disease.ResultsWe found eosinophils in 19 (43%) of 44 PAs (patient age range, 0.5-72 years). Eosinophils were intratumoural and clearly distinguishable. The density of eosinophils was rare to focally scattered. PAs containing eosinophils were located throughout the CNS. Furthermore, eosinophilic infiltration was identified in 18 (62%) of 29 pediatric (age range, 0.5-18 years) PAs but only 1 (7%) of 15 (p<0.001, significantly less) adult (age range, 20-72 years) PAs. Eosinophilic infiltration showed no significant differences between PAs with and without MRI cystic formation, surgical procedures, or PAs with and without leptomeningeal infiltration. In comparison, eosinophils were absent in 10 pediatric (age range, 0.5-15 years) ependymomas (or anaplastic ependymomas).ConclusionsThese results suggest that eosinophils are common in pediatric PAs but rare in adult PAs. This difference is probably related to the developing immune system and different tumour-specific antigens in children. TATE may play a functional role in the development of pediatric PAs, as well as some other pediatric CNS tumours such as AT/RTs.