Craniopharyngiomas with a mixed histological pattern: the missing link to the intriguing pathogenesis of adamantinomatous and squamous‐papillary varieties?

We read with great interest the manuscript by Okada et al. reporting the coexistence of adamantinomatous and squamous-papillary elements on a large intraventricular craniopharyngioma (CP). First and foremost, we would like to point out the importance of this case because it provides compelling evidence against the classic sharp histological classification into adamantinomatous and papillary CP variants.With the present letter, we want to discuss some additional topographical, histological and molecular evidence, which supports the differentiation of a mixed CP variety and may contribute to a better understanding of CP pathogenesis. CP is one of the most intriguing histopathological entities. Several important questions regarding CP’s origin and histological classification have remained unsolved since the first definition of this tumor by the German pathologist Jacob Erdheim in 1904. A major source of confusion is due to the high variability regarding the patient’s age at presentation, topographical extension, morphological configuration and biological behavior among CPs. Some thorough pathologic investigations on CPs, published long ago, remarked on the considerable degree of variation in the growth patterns of these epithelial tumors. However, the World Health Organization has kept in force the traditional classification into two major pathological variants, adamantinomatous CP (aCP) and squamous-papillary CP (pCP), within the latest classification of brain tumors. The epithelium of aCP resembles to that of the enamel organ or the calcifying odontogenic cysts of the jaw. In contrast, the epithelium of pCP which is compact and presents papillary projections within the surrounding tissues, resembles the structure of the oral mucosa. Several authors have presented evidence against such a rigid classification into aCPs and pCPs. Carol K. Petito was one of the first pathologists who questioned the validity of this distinction, after observing in her series of 245 CPs a high rate of lesions (approximately 33%) presenting a mixture of both variants. In the following decades, the existence of mixed or transitional forms between the papillary and adamantinomatous types was confirmed in both large series and well-described individual cases. In the series of 131 CPs reviewed by Szeifert et al. 38% of the cases belonged to the adamantinomatous group, 26% corresponded to the squamous epithelial type and 15% of the cases corresponded to a mixed variant combining features from both types. In the series of 56 patients studied by Miller et al. three cases showed a mixed histological pattern, one in a child and two in adults. Crotty et al. also reported four cases of mixed CPs in his seminal review of the squamous-papillary type, three of these cases exhibited alternating areas with definite adamantinomatous and papillary-squamous differentiation while in the fourth lesion the epithelium displayed an intermingled appearance. To the best of our knowledge, at least another three well-described cases of mixed CPs have been published to date; interestingly, all of them were developed within the third ventricle and were diagnosed in adult patients. On the basis of the previous body of evidence, the mixed CP type should not be considered as a rarity, but rather as a definite variant showing overlapping histological features from the aCP and pCP varieties. A proper recognition of mixed CPs is important not only for academic reasons, but also may give additional insights into the uncertain pathogenesis of CPs. The definition of two distinct histological CP variants and the preferential association of each one to a specific age group has favored the proposal of two main hypotheses concerning the origins of these lesions. The “embryogenetic theory” states that adamantinomatous CPs, mostly found in children, originate from epithelial remnants of the Ratkhe’s pouch/craniopharyngeal duct left over during embryogenesis of the pituitary gland which would have had a neoplastic transformation. On the other hand, the “metaplastic theory” was formulated for squamouspapillary lesions, usually found in adults, which suggests that they originate from metaplasia of adenohypophyseal cells within the pituitary gland. Nevertheless, the available evidence cannot give any separate explanation about Correspondence: Ruth Prieto, MD, PhD, Department of Neurosurgery, Virgen de La Salud Hospital, Av. Barber 30, CP 45004 Toledo, Spain. Email: rprieto29@hotmail.com Published online 27 March 2013. bs_bs_banner