Arnold, Marlene

Vajtai, Istvan

Vassella, Erik

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LETTER TO THE EDITORIstvan Vajtai Æ Marlene Arnold Æ Erik VassellaOligodendroglioma with neurocytic differentiation and characteristicloss of heterozygosity on chromosomes 1p and 19qReceived: 29 August 2005 / Revised: 6 September 2005 / Accepted: 6 September 2005 / Published online: 13 October 2005 Springer-Verlag 2005Neuronal diﬀerentiation in neoplasms of the centralnervous system (CNS) has been known to occur either asa polyphenotypic trait of primitive neuroectodermaltumors (PNET) or in the form of composite lesionsincorporating well-deﬁned neuronal and glial elements(e.g., ganglioglioma).Interest in the pathology of neoplasms with mixedneuronal-glial properties has been revived in particularby studies on the diﬀerentiation potential of centralneurocytomas [4]. On the one hand, so-called ‘‘oligo-dendroglioma mimics’’—among them extraventricularneurocytomas—came to be appreciated; on the other,the issue of neuronal diﬀerentiation in bona ﬁde oligo-dendrogliomas has been further elaborated [2]. The lat-ter aspect recently resulted in a report by Perry et al. [6]on four supratentorial inﬁltrative gliomas of adults witholigodendroglial histology, evidence of neuronal immu-nophenotype, and demonstration of co-deletions onchromosomes 1p and 19q by ﬂuorescent in situ hybrid-ization (FISH) analysis. A similar case was subsequentlypublished by Mrak et al. [5].We recently had the opportunity to observe anadditional example of the above constellation bystudying the brain tumor from a 66-year-old femalepresenting with seizures. This contrast-enhancing andpartially calciﬁed left temporal mass of 5·5·4 cm(Fig. 1a) was removed by surgery. Histology revealedcharacteristic features of a oligodendroglioma completewith ‘‘secondary structures’’ of Scherer (i.e., perineuro-nal satellitosis, subpial accumulation of tumor cells).Focally brisk mitotic activity with a mean MIB-1labeling index of near 25%, as well as microvascularproliferation, qualiﬁed this tumor as anaplastic (WHOgrade III). Rhythmic palisades or ‘‘marching ﬁles’’ werea prominent feature; these occasionally coalesced toform vague neurocytic type (Homer Wright-like) ro-settes (Fig. 1b–d). Throughout the tumor strongimmunoreactivity for synaptophysin was noted (Fig. 1e,f). Staining for chromogranin-A and neuroﬁlamentprotein, as evidence of more advanced neuronal(gangliocytic) maturation, was absent in tumor cells.Polyacrylamide gel electrophoresis of PCR-ampli-ﬁed microsatellite markers revealed loss of heterozy-gosity (LOH) on both chromosome 1p36 (D1S468,D1S228, D1S214) and 19q13 (D19S412) in DNAextracted from tumor tissue as compared with non-tumorous somatic DNA obtained from a prior ton-sillectomy specimen (Fig. 1g, h).The genotype documented here is considered acharacteristic ‘‘molecular signature’’ of oligodendro-gliomas, and adds further support to the existence ofneuronal diﬀerentiation within tumors that otherwisefulﬁll accepted clinicopathological criteria of oligo-dendroglioma. These include, among others: occur-rence in adults, supratentorial location, overtlyinﬁltrative growth and a propensity to recur for bothlow- and high-grade lesions, in contradistinction fromextraventricular neurocytomas, which are essentially, ifnot exclusively, low-grade [2, 6]. Notably, the latterFig. 1 Native axial CT scan to show focally calciﬁed tumor in lefttemporal lobe (a). Histologically, beside classic ‘‘honeycomb’’pattern (b) and rhythmic palisades (c), some scattered groups ofneurocytic type rosettes (d) were occasionally seen. Most tumorcells show intense positivity for synaptophysin (e). On a consec-utive section (f), the corresponding area reveals only scant residualneuroﬁlament-positive axons in inﬁltrated brain parenchyma.SYBR gold-stained electrophoresis gels (Spreadex) to show lossof microsatellite markers on chromosome 1p36 (g) and 19q13 (h) intumor-derived DNA versus normal somatic control (T tumor, Nnormal control, s length standard). b–d Hematoxylin and eosin; e, fimmunohistochemistry. Bars 50 lmcI. Vajtai (&) Æ M. ArnoldDepartment of Clinical Pathology, Institute of Pathology,University of Berne, Murtenstrasse 31, Postfach 62,3010 Berne, SwitzerlandE-mail: istvanvajtai@yahoo.comTel.: +41-31-6323210Fax: +41-31-6329938E. VassellaLaboratory of Molecular Pathology, Institute of Pathology,University of Berne, Berne, SwitzerlandActa Neuropathol (2005) 110: 520–522DOI 10.1007/s00401-005-1091-8only seldom harbor LOH 1p/19q [7]. Although obvi-ously rare, the ‘‘oligodendroglioma with neurocyticdiﬀerentiation’’ may evolve to a paradigm with his-tological and genetic features that will eventuallyprove reproducible enough to warrant consideration asan emerging entity [3].521From a practical standpoint, it is important for thepathologist to become aware of the existence of ‘‘oligo-dendrogliomas with neurocytic diﬀerentiation’’ so as notto intuitively bias interpretation of synaptophysin-immunoreactive ‘‘honeycombing’’ CNS tumors towardseither low-grade oligodendrogliomamimics, or the highlymalignant PNET.In a more general context of CNS tumor biology, the‘‘oligodendroglioma with neurocytic diﬀerentiation’’further substantiates the variously perceived occurrenceof neuronal characteristics in diﬀusely inﬁltrating glio-mas [8]. With ostensibly ‘‘composite’’ lesions (e.g., gan-glioglioma, dysembryoplastic neuroepithelial tumor,etc.) on one end of the spectrum, and an inﬁltratingglioma of hybrid glial-neuronal phenotype on the other,speculation about a purported pluripotential cell oforigin (e.g., the N-O cell) thus comes full circle [9]. Al-though the very existence of the latter is only supportedby circumstantial evidence, neoplastic transformation ofadult neuroectodermal precursors with stem cell prop-erties is currently being entertained as a possible sourceof at least a subset of gliomas [1].References1. Berger F, Gay E, Pelletier L, Tropel P, Wion D (2004) Devel-opment of gliomas: potential role of asymmetrical cell division ofneural stem cells. Lancet Oncol 5:511–5142. Brat DJ, Scheithauer BW, Eberhart CG, Burger PC (2001) Ex-traventricular neurocytomas. Pathologic features and clinicaloutcome. Am J Surg Pathol 25:1252–12603. Cenacchi G, Giangaspero F (2004) Emerging tumor entitiesand variants of CNS neoplasms. J Neuropathol Exp Neurol63:185–1924. Deimling A von, Kleihues P, Saremaslani P, Yasargil MG,Spoerri O, Sudhof TC, Wiestler OD (1991) Histogenesis anddiﬀerentiation potential of central neurocytomas. Lab Invest64:585–5915. Mrak RE, Yasargil MG, Mohapatra G, Earel J, Louis DN(2004) Atypical extraventricular neurocytoma with oligoden-droglioma-like spread and an unusual pattern of chromosome1P and 19Q loss. Hum Pathol 35:1156–11596. Perry A, Scheithauer BW, Macaulay RJB, Raﬀel C, Roth KA,Kros JM (2002) Oligodendrogliomas with neurocytic diﬀerenti-ation. A report of 4 cases with diagnostic and histogeneticimplications. J Neuropathol Exp Neurol 61:947–9557. Perry A, Fuller CE, Banerjee R, Brat DJ, Scheithauer BW (2003)Ancillary FISH analysis for 1p and 19q status: Preliminaryobservations in 250 gliomas and oligodendroglioma mimics.Front Biosci 8:1-98. Varlet P, Soni D, Miquel C, Roux FX, Meder JF, Chneiweiss H,Daumas-Duport C (2004) New variants of malignant glioneu-ronal tumors: a clinicopathological study of 40 cases. Neuro-surgery 55:1377–13929. Williams BP, Read J, Price J (1991) The generation of neu-rons and oligodendrocytes from a common precursor. Neuron7:685–693522

Oligodendroglioma with neurocytic differentiation and characteristic loss of heterozygosity on chromosomes 1p and 19q

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Oligodendroglioma with neurocytic differentiation and characteristic loss of heterozygosity on chromosomes 1p and 19q

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