Relationship between focal cortical dysplasia and epilepsy-associated low-grade tumors: an immunohistochemical study GIANLUCA MARUCCI, 1 MATTEO MARTINONI 2 and MARCO GIULIONI 2 1 Section of Pathology “M. Malpighi”, Bellaria Hospital, University of Bologna, Bologna; and 2 Division of Neurosurgery, Bellaria Hospital, Bologna, Italy Marucci G, Martinoni M, Giulioni M. Relationship between focal cortical dysplasia and epilepsy- associated low-grade tumors: an immunohistochemical study. APMIS 2013; 121: 22–9. We retrospectively analyzed 29 seizure-associated temporal lobe low-grade tumors to evaluate the utility of CD34 and bcl-2 expression in clarifying the relationship of these tumors with different classes of focal cortical dysplasia (FCD). CD34 immunostained 75% of gangliogliomas (GG) and 60% of pleomorphic xanthoastrocytomas. FCD type IIIb [i.e. abnormal cortical layering associated with a glioneuronal tumor, according to the new International League Against Epilepsy (ILAE) classification] presented CD34-immunopositive cells in 2/9 (22.2%) cases, whereas FCD type II in 6/ 7 (85.7%) cases, a difference statistically significant (p = 0.0117). Bcl-2 immunostained 9/12 (75%) gangliogliomas and 2/3 (66.6%) gangliocytomas. The cases of FCD type IIIb resulted negative for Bcl-2, whereas 4/7 cases (57.1%) of FCD type II showed immunopositive cells. These differences in Bcl-2 expression between FCD type IIIb and FCD type II resulted statistically significant (p = 0.0088). Abnormal cortical layering, overall, represents the kind of FCD more commonly asso- ciated with seizure-related low-grade tumors, whereas FCD type II is more frequently associated with GG. The profile of CD34 and Bcl-2 expression exhibited by GG is more similar to that observed in FCD type II. Such immunoprofile suggests the existence of a common pathogenesis linking glioneuronal tumors and FCD type II. Key words: Cortical dysplasia; ganglioglioma; dysembryoplastic neuroepithelial tumor; epilepsy; glioneuronal tumors. Gianluca Marucci, Sezione di Anatomia Patologica “M. Malpighi”, Ospedale Bellaria, Via Altura 3, Bologna 40139, Italy. e-mail: gianluca.marucci@ausl.bologna.it Low-grade glial-glioneuronal tumors (GNTs) represent an increasingly recognized pathologic substrate (1–4) in the setting of medically intractable chronic epilepsy. These tumors most commonly arise in the temporal lobe, particu- larly in the temporo-anterior-basal-mesial site (5). A significant part of these neoplasms, particu- larly ganglioglioma (GG) and dysembryoplastic neuroepithelial tumor (DNT), is associated with malformations of cortical development, in par- ticular focal cortical dysplasia (FCD) (30–80% of cases) (1, 4–8). The new ILAE classification system for FCD (9) distinguishes three FCD categories. FCD type I indicates cases with abnormalities in cortical architecture as defined by radial microcolumns (FCD type Ia), tangen- tial layer alterations (FCD type Ib), or by a combination of both (FCD type Ic). FCD type II is characterized by large and dysmorphic neurons, without (FCD type IIa) or with the presence of balloon cells (FCD type IIb). Fur- thermore, in comparison with the previously adopted classification (10), FCD type III has Received 3 March 2012. Accepted 24 May 2012 22 APMIS 121: 22–29 © 2012 The Authors APMIS © 2012 APMIS DOI 10.1111/j.1600-0463.2012.02938.x