Large cell neuroblastoma

Abstract

BACKGROUND Among cases of undifferentiated and poorly differentiated tumors in the neuroblastoma (Schwannian stroma–poor) category, the authors histologically identified a group of rare tumors, known as large cell neuroblastomas (LCNs), that are composed of large cells with sharply outlined nuclear membranes and 1–4 prominent nucleoli. METHODS Histologic and immunohistochemical features of LCN were characterized. Morphologic characteristics, clinical features, and MYCN status were compared between LCNs and conventional neuroblastomas documented in the files of two European centers (the Sir James Spence Institute of Child Health, Royal Victoria Infirmary, University of Newcastle, Newcastle upon Tyne, United Kingdom, and the Medical and Health Sciences Center, University of Pécs, Pécs, Hungary). RESULTS Of 92 peripheral neuroblastic tumors (pNTs; including neuroblastoma [n = 81]; ganglioneuroblastoma, intermixed [n = 6]; and ganglioneuroblastoma, nodular [n = 5]), 7 (7.6%) qualified as LCN. All 7 LCNs were classified as having unfavorable histology (UH) according to the International Neuroblastoma Pathology Classification. The LCNs were composed of monomorphous undifferentiated neuroblasts and shared certain histologic features, such as a high incidence of high mitosis‐karyorrhexis index and a low incidence of calcification, with other neuroblastomas in the conventional UH (c‐UH) group. These features were significantly different from those of neuroblastomas in the conventional favorable histology (c‐FH) group. On immunohistochemical analysis, LCN tumor cells were positive for neuron‐specific enolase (5 of 5 cases), protein gene product 9.5 (5 of 5 cases), synaptophysin (5 of 5 cases), tyrosine hydroxylase (focally in 3 of 3 cases), and NB84 (3 of 5 cases) and negative for CD99. Patients with LCN and patients with c‐UH disease had similar clinical features (diagnosis at age > 1 year, often with distant metastasis). The clinical features of these patients also were significantly different from those of patients with c‐FH disease. Further analysis demonstrated that the LCN group was significantly different from both the c‐UH and c‐FH groups with respect to MYCN status (MYCN amplification, 4 of 5 vs. 3 of 17 vs. 8 of 17, respectively; P = 0.023) and survival rate (4‐year expected survival, 0% vs. 71% vs. 17%, respectively; P < 0.01). CONCLUSIONS Because of its unique clinicopathologic features, the authors propose that LCN be recognized as a distinct entity within the undifferentiated and poorly differentiated subtypes of the neuroblastoma category. Cancer 2004;100:390–7. © 2003 American Cancer Society.

Preclinical Models for Neuroblastoma: Establishing a Baseline for Treatment

“…Overall, these data are consistent with previous characterization of the TH-MYCN neuroblastomas and they suggest that the mouse neuroblastomas most closely resembled a class of aggressive human neuroblastoma tumors classified as large cell neuroblastoma [27]–[29]. This subgroup of tumors is composed of cells that are markedly larger than other NB subgroups and have unique, sharply outlined nuclear membranes and 1–4 prominent nucleoli.…”

Peripheral neuroblastic tumors with genotype–phenotype discordance: A report from the Children's Oncology Group and the International Neuroblastoma Pathology Committee

“…MYCN amplified pNTs, typically having UH and associated with a poor clinical prognosis, are often characterized as NB-UD/PD having prominent nucleoli [13,14,21]. In the MYCN amplified pNTs, an excess amount of N-myc protein expression and subsequent MYC-MAX heterodimer formation is critical for initiating the molecular mechanism of aggressive behavior by changing the expression of multiple target genes [30–33].…”

“…Accordingly, MYCN -amplified tumors typically demonstrate the characteristic histology of neuroblastoma, undifferentiated/poorly differentiated subtype (NB-UD/PD) with a high mitosis-karyorrhexis index (MKI), and are classified into the Unfavorable Histology (UH) group. It is also reported that the presence of prominent nucleoli in neuroblastoma cells is a sign of MYCN amplification [13,14], with a high specificity and a low sensitivity, in pNTs [15]. …”

Pathology in pediatric oncological surgical diseases

“…Hastalığın ender bir klinik durumu da opsomyoklonus ataksi sendromudur. Başlıca metastaz bölgeleri kemik, lenf düğümü, deri ve karaciğerdir (55)(56)(57) .…”

“…Ayrıca görüntüleme yöntemleri olarak ultrasonografi, manyetik rezonans görüntüleme ve bazı seçilmiş hastalarda bilgisayarlı tomografiden hasta yönetiminde yararlanılır. Görüntüleme teknikleri ile kitlenin lokalizasyonu yanı sıra kalsifikasyon ve nekrozun değerlendirilmesi amaçlanmaktadır (53)(54)(55)(56)(57)(58) .…”