Large cell neuroblastoma: a distinct phenotype of neuroblastoma with aggressive clinical behavior

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.

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).

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).

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.