LETTER TO THE EDITOR Cerebellar Melanoneurons: An Overlooked and Potentially Important Cell Population To the Editor: In several brain autopsies, we en- countered pigmented neurons in the cere- bellum. These cells were described in a masterful study of “cerebellar mel- anoneurons” in humans and in other pri- mates by Cowen (1). The author encouraged fellow neuropathologists and neuroanatomists not to overlook a distinc- tive population of pigmented neurons lo- cated in the roof and lateral edges of the fourth ventricle. We did not find a more recent publication that mentions them, and discussion with colleagues suggested that knowledge of these cells is limited. Here, we present a brief review of the lit- erature and photomicrographs to high- light this distinctive neuronal population and bring these neglected and likely im- portant cells back to the attention of neu- ropathologists and researchers. The first account we found of these cells was by Meynert in 1872 (2). He described these neurons as “black cells” constituting a discrete nucleus that he designated “substantia ferrugi- nea superior,” distinct from the locus ceruleus (“substantia ferruginea”). He described their location as being in the roof of the rhomboid fossa, medial to the brachium. A few decades later Ger- man neurologist and neuroanatomist Louis Jacobsohn mentioned these pig- mented cells, which he also felt merited their own nucleus, the “nucleus pig- mentosus tegmento-cerebellaris” (3). He described the cells as extending from the lateral angle of the fourth ven- tricle to the fastigial nucleus of the cer- ebellum, caudally to the abducens nucleus, and rostrally to the trigeminal nucleus. He noted that the neurons can be isolated, but occasionally form clus- ters located ventral to the fastigial nu- cleus. After Jacobsohn’s report we find just a few more accounts of these neu- rons. Some authors regard them as be- ing part of the locus ceruleus (Table). These medium to large neurons are present near the ependyma in the ventricular roof as shown beautifully in sagittal section by Bogerts (5), who found that their locations extend to the caudal poles of substantia nigra and ventral tegmental area (Fig. 1A). The cells display variable amounts of cyto- plasmic pigment (Fig. 1B). Despite some knowledge from these references of the cells’ morphology, distribution, and pigmentation at various ages and in several species, there is scarce infor- mation about their afferent and effer- ent pathways, neurotransmitter production, normal neurophysiologic role, or potential role in disease. We found only a few accounts, none more recent than 1986, of a potentially im- portant cluster of neurons located in the fourth ventricular roof, many of which contain neuromelanin granules. Their function and potential dysfunction are areas to be explored in future studies. Javier Redding, MD, Meaghan Morris, MD, PhD Department of Pathology, Johns Hopkins University, Baltimore, Maryland Matthias Holdhoff, MD, PhD Department of Oncology, Johns Hopkins University, Baltimore, Maryland David W. Nauen, MD, PhD Department of Pathology, Johns Hopkins University, Baltimore, Maryland REFERENCES 1. Cowen D. The melanoneurons of the human cerebellum(nucleus pigmentosus cerebellaris) and homologues in the monkey. J Neuropathol Exp Neurol 1986;45:205–21 2. Meynert T. Vom Gehirneder S€ augetiere. In: Stricker S, ed. Handbuch der Lehre von den Geweben. Leipzig; Engelmann; Zweit Bd 1872:775 3. Jacobsohn L. € Uber die Kerne des menschlichen Hirnstamms (Medulla oblongata, Pons und Pedunculus cerebri). Anhang zu den Abhand- lungen der Ko ¨nigl Preuss Akademie der Wis- senschaften vom Jahre 1909. Berlin 1–70 4. Braak H. On the pars cerebellaris loci coerulei within the cerebellum in man. Cell Tissue Res 1975;160:279–82 5. Bogerts B. A brainstem atlas of catecholamin- ergic neurons in man, using melanin as a natu- ral marker. J Comp Neurol 1981;197:63–80 TABLE. Proposed Names for (Often) Pigmented Cerebellar Neurons Proposed Name Author Year Reference Substantia ferruginea superior Meynert 1872 (2) Nucleus pigmentosus tegmento-cerebellaris Jacobsohn 1909 (3) Pars cerebellaris loci coeruleus Braak 1975 (4) Group A4 Bogerts 1981 (5) Nucleus pigmentosus cerebellaris Cowen 1986 (1) 242 V C 2019 American Association of Neuropathologists, Inc. All rights reserved. J Neuropathol Exp Neurol Vol. 79, No. 2, February 2020, pp. 242–243 doi: 10.1093/jnen/nlz127 Downloaded from https://academic.oup.com/jnen/article-abstract/79/2/242/5680515 by guest on 22 July 2020