Cytomorphologic Features Found in Cerebrospinal Fluid Specimens of Hemophagocytic Lymphohistiocytosis Patients.

OBJECTIVES: Central nervous system involvement is present in 70% of patients with hemophagocytic lymphohistiocytosis (CNS-HLH). CNS-HLH is defined by neurologic deficits, neuroimaging abnormalities, or positive cerebrospinal fluid (CSF) findings. The CSF cytomorphologic spectrum of CNS-HLH, however, has not been well investigated. METHODS: A retrospective review was performed on 64 CSF specimens from pediatric and adult patients with HLH. Ten patients had clinicoradiologic evidence of CNS involvement. RESULTS: We identified five CSF cytomorphologic patterns: (1) hemophagocytosis, (2) vacuolated macrophages without evidence of hemophagocytosis, (3) monocytes and/or nonvacuolated macrophages, (4) acellular specimens, and (5) bloody specimens. Patterns 1 and 2 were common in CNS-HLH and rare in patients without CNS involvement. The CSF cytomorphologic patterns did not correlate well with WBC counts or protein concentration. CONCLUSIONS: Our study offers a comprehensive view of the cytomorphologic features seen in CSF specimens from patients with HLH.

Significance of minimal residual disease in pediatric mixed phenotype acute leukemia: a multicenter cohort study.

The rarity of mixed phenotype acute leukemia (MPAL) has precluded adequate data to incorporate minimal residual disease (MRD) monitoring into therapy. Fluidity in MPAL classification systems further complicates understanding its biology and outcomes; this includes uncertainty surrounding the impact of shifting diagnostic requirements even between iterations of the World Health Organization (WHO) classification. Our primary objective was to address these knowledge gaps. To do so, we analyzed clinicopathologic features, therapy, MRD, and survival in a centrally-reviewed, multicenter cohort of MPAL uniformly diagnosed by the WHO classification and treated with acute lymphoblastic leukemia (ALL) regimens. ALL induction therapy achieved an EOI MRD negative (<0.01%) remission in most patients (70%). EOI MRD positivity was predictive of 5-year EFS (HR = 6.00, p < 0.001) and OS (HR = 9.57, p = 0.003). Patients who cleared MRD by EOC had worse survival compared with those EOI MRD negative. In contrast to adults with MPAL, ALL therapy without transplantation was adequate to treat most pediatric patients. Earlier MRD clearance was associated with better treatment success and survival. Prospective trials are now necessary to validate and refine MRD thresholds within the pediatric MPAL population and to identify salvage strategies for those with poor predicted survival.

A Pediatric Case of Transformed Mycosis Fungoides in a BRCA2 Positive Patient.

Cutaneous T-cell lymphomas are very rare in children. Although mycosis fungoides is the most common of these rare cutaneous T-cell lymphomas in children, transformation to an aggressive malignancy remains extremely uncommon, and there are no clear guidelines for clinical management in the pediatric population. In addition, the increased usage of next-generation sequencing for pediatric patients with unusual malignancies may result in the discovery of pathogenic germline mutations, though the association between these mutations and the patient's cancer is not always clear. We present here a unique pediatric case of transformed mycosis fungoides in a patient with BRCA2 mutation.

Splenic myoid angioendothelioma mimicking metastatic disease in an 8-year-old with Stage IV Wilms' tumour.

Myoid angioendothelioma are rare and benign vascular tumours of the spleen. Radiographic evaluation and diagnosis is often challenging and subjecting tissue samples to immuhistochemical analysis is often required to make a definitive diagnosis. Myoidangioendotheliomas can be managed with open or laparoscopic splenectomy with minimal risk of recurrent disease. Herein, we present a case of a myoid angioendothelioma in a patient with stage IV Wilms' tumour.

Extramedullary Hematopoiesis Presenting as Bilateral Glomus Tympanicum-First Case Report in a Pediatric Patient and With Bilateral Presentation.

To the best of our knowledge, this is the first case report of middle ear extramedullary hematopoiesis (EMH) in a pediatric patient as well as the first bilateral presentation reported in both children and adults. We report a 13-year-old African-American female with sickle cell disease who developed bilateral hearing loss, with magnetic resonance imaging findings consistent with bilateral glomus tympanicum (GT). Upon excisional biopsy, however, EMH was diagnosed histologically. Besides its novelty, this case highlights the importance of considering EMH in the differential diagnosis of GT including cases with bilateral presentation that may be otherwise highly suggestive of the familial form of GT.

Technological update of the video-endoscopic approach of the diagnosis and staging of tumors in children.

The pediatric patient is often difficult to diagnose, especially since the surgical pathology is tumoral. Establishing the histopathological diagnosis of a tumor, staging of a disease and certifying the existence of rare pediatric affections are three of the motives for which the specialists frequently appeal to an exploratory laparoscopy, accompanied by biopsy procedures. The paper presents the laparoscopic biopsy experience of the team from the Department of Pediatric Surgery, "Maria Sklodowska Curie" Emergency Clinical Hospital for Children, Bucharest, Romania. From 2000 to 2013, 95 such procedures were performed (7.76% of a total of 1224 laparoscopic interventions). In many cases, the laparoscopy had an exclusive diagnostic purpose, of whose success has been primarily responsible the targeted biopsy. Current issues are discussed, centered on the most advanced technologies used in minimally invasive approach of pediatric malignancies, referring to the effect of minimizing the possible complications that can arise from this type of intervention. The authors concluded that laparoscopic technique is the method of choice in comparison to other ways of biopsy (classical surgery, ultrasound guidance, tomography, etc.), and it is characterized by a high diagnostic value.

Prominent microvascular proliferation in clinically aggressive neuroblastoma.

PURPOSE: Tumor vasculature is disorganized and glomeruloid microvascular proliferation (MVP) has been identified as a poor prognosticator in some adult cancers. To determine the clinical significance of MVP, including glomeruloid MVP in neuroblastoma, we initially examined vessel architecture in tumor sections from 51 children diagnosed at Children's Memorial Hospital (CMH) and subsequently evaluated 154 neuroblastoma tumors on a tissue microarray constructed at Children's Hospital of Philadelphia (CHOP). EXPERIMENTAL DESIGN: H&E sections were examined for the presence of structurally abnormal vessels and further characterized by immunostaining for CD31 and von Willebrand factor to highlight endothelial cells and alpha-smooth muscle actin for pericytes. Tumors with thickened walls containing a complete layer of hypertrophic endothelial cells plus additional layers of vascular mural cells were classified as MVP positive. Associations between MVP and established clinicopathologic features and outcome were assessed. RESULTS: In both series, MVP was significantly associated with Schwannian stroma-poor histology (CMH, P = 0.008; CHOP, P < 0.001) and decreased survival probability (CMH, P = 0.017; CHOP, P = 0.014). In the CHOP series, MVP was associated with high-risk group classification (P < 0.001), although this association was not seen in the smaller CMH cohort. CONCLUSIONS: The association between MVP and poor outcome provides further support for the concept that angiogenesis plays an important role in determining the biological behavior of neuroblastoma tumors. Our results also indicate that angiogenesis is regulated differently in Schwannian stroma-rich versus stroma-poor neuroblastoma tumors. Further studies investigating the activity of angiogenic inhibitors in children with clinically aggressive stroma-poor neuroblastoma are warranted.

Simultaneous presentation of multiple myeloma and acute monocytic leukemia.

Acute leukemia frequently has been described as a late complication of chemotherapy with alkylating agents in patients treated for multiple myeloma. However, the simultaneous occurrence of multiple myeloma and acute leukemia in the same patient, without previous exposure to chemotherapy, is a rare association. We describe a case of concomitant involvement by multiple myeloma and acute monocytic leukemia. To our knowledge, only 9 such cases have been reported in the literature to date. We discuss the criteria used in diagnosing the 2 separate diseases and the possible mechanisms responsible for this occurrence.