Diagnostic pathology of equine intracranial neoplasms

Neoplasia is rare in horses and central nervous system (CNS) neoplasia is so rare that, pituitary adenomas excluded, no specific intracranial neoplasms are mentioned in Cotchin's preliminary work describing the epidemiology of equine neoplasia (Cotchin, 1977). Moreover, an early survey identified 28 nervous tissue tumours in horses but none were reported in the central nervous system (Hayes Jr. et al., 1975). However, as de Sousa et al. (2025) highlight in the accompanying case report, equine intracranial neoplasia can cause significant clinical disease and histopathology is essential to making a complete diagnosis, albeit inevitably through post-mortem examination. Herein follows a brief discussion of a variety of intracranial tumours reported in horses and their histopathological diagnostic features with a summary of their immunohistochemical (IHC) characteristics in Table 1. Non-neoplastic causes of intracranial space-occupying lesions, for example, cholesterol granulomas, must always remain on the list of differential diagnoses but lie outside the remit of this commentary. Any readers seeking further details and descriptions of the characteristics of these lesions are encouraged to pursue some of the references at the end of this commentary, or indeed the associated case report. Only reported once in a horse, a 10-year-old Thoroughbred mare (Reppas & Harper, 1996) but it is the most common intra-axial neoplasm in dogs. Grossly, the mass may be well-circumscribed, glistening and gelatinous, often with multiple haemorrhagic and necrotic foci. These tumours of the myelin-producing cell of the CNS classically have a dense honeycomb appearance with clear cytoplasm segregated by visible cell surface membranes supported by an abundance of small blood vessels. Typically, the mitotic count is low (Knottenbelt et al., 2015). Rare but reported in horses aged 4–15 years old affecting the cerebral cortex and optic disc (Cavasin et al., 2020; Gelatt et al., 1971; Gericota et al., 2010). Due to their solid white to grey appearance, they may be difficult to distinguish from the normal brain tissue, noticeable only from the way they distort the neighbouring structures. Some astrocytomas extend within the meninges and flatten the brain (Knottenbelt et al., 2015). Astrocytes are identifiable by their peripheral processes, giving the cytoplasm a star appearance, especially in low-grade tumours. However, medium to high-grade astrocytomas can be difficult to recognise as these distinctive processes are lost, and even low-grade astrocytomas are poorly demarcated and infiltrative; therefore, IHC can greatly assist the diagnosis. Ependymal cells line the ventricles of the brain but are distinct from cerebrospinal fluid (CSF) producing choroid plexuses. Ependymomas most often arise in the third or fourth ventricles in aged animals (Knottenbelt et al., 2015), with the recent case report being a rare exception. Primary tumours cause damage through expansion and compression of neighbouring tissue; for example, one horse presented with hypernatraemia and adipsia secondary to an ependymoma compressing and interfering with the osmoregulatory function of the neurohypophysis (Heath et al., 1995). Generally large, poorly defined and bulging, due to their involvement in regulating the flow of CSF, ependymomas can cause dilation of the ventricle and, in humans, are recognised to metastasise to the ventricular system and meninges through the CSF. The histological morphology can be densely cellular acinar, papillary and duct-like structures of simple to stratified epithelium. Rosettes, with central neuropil and pseudorosettes, with a central blood vessel, may be seen. The cells can have a variable mitotic rate and nuclear appearance (Knottenbelt et al., 2015). These tumours of the CSF-producing epithelium are reported in horses aged 4–11 years old and the majority were benign papillomas. They appear grossly as a grey-white to red friable, well-circumscribed granular mass in the lateral, third, or fourth ventricle. Histologically, neoplastic cells form simple or stratified papillary projections and are cuboidal to columnar (Knottenbelt et al., 2015). Recently, a choroid plexus carcinoma was reported in a 4-year-old horse, defined by histological invasion of the neuropil (Almeida et al., 2024). By far the most common intracranial neoplasm reported in horses is pituitary adenoma, classically affecting the melanotrophs of the pars intermedia where increasing age is the greater risk factor for adenomatous rather than hyperplastic change (Perez-Ecija et al., 2018). Often endocrinologically active, they can cause signs of pituitary pars intermedia dysfunction (hypertrichosis, skeletal muscle atrophy and abnormal fat distribution). Grossly, an enlargement of the pituitary gland, found at the base of the skull in the hypophyseal fossa, is evident during necropsy (Figure 1). A five-tier histological grading system for the pars intermedia is used to categorise pituitaries as normal, through hyperplastic and microadenomatous to macroadenomatous based on whether the trabeculae, cords, nests and pseudoacini of cells form discrete nodules or not, and the estimated diameter of any nodules. Often, when adenomas are present, there is also hyperplasia of the surrounding tissue. Macroadenomas frequently contain follicles with central colloid (Knottenbelt et al., 2015). IHC staining for trophic hormones produced in the pituitary gland, including ACTH, POMC and MSH, can highlight neoplastic cells. The authors are aware of one case report of a pituitary adenocarcinoma in a horse (Martens & Rosenbruch, 1984) but they are not generally recognised in the current literature. Very rarely reported in horses, these tumours of large ganglion (neuronal) cells may have a predilection for the cerebellum. Their soft, grey appearance resembles grey matter, demonstrating how recognising deviation from the normal distribution of grey and white matter in the brain is essential for identifying lesions. Neoplastic cells are large and may be multinucleated. Silver stains can aid visualisation of their cytoplasmic processes (Knottenbelt et al., 2015). Olfactory neuroblastomas are malignant and invasive, with reports of metastasis through the cribriform plate and to the eye. Grossly, there are irregular grey, red, or yellow areas, due to being well-vascularised and prone to multifocal haemorrhage and necrosis. Their histologic appearance can resemble a round cell tumour, as the cells have round nuclei and scant cytoplasm, but sometimes pseudorosettes and rosettes are present and tumour giant cells are reported. The IHC profile is highly variable, ergo electron microscopy is required for a definitive diagnosis, particularly when differentiating these tumours from neuroendocrine carcinoma (Knottenbelt et al., 2015; Martí-García et al., 2023). A rare mixed tumour of neuronal and glial cells; only one case has been reported in horses (Easton-Jones et al., 2019). This grey mass comprised two populations of neoplastic cells which stained positive for either synaptophysin or glial fibrillary acidic protein (GFAP) indicating neuronal and astrocytic lineages respectively. The single reported case is of a pink to grey mass bridging the cerebellum to the pons of a 6-month-old gelding that had the typical presentation of a medulloblastoma; a mass of sheets of cells with rosettes in a juvenile animal (Palmisano et al., 2023). MRI may identify meningiomas as extra-axial, in contrast to the previously described intra-axial masses, although infiltration of neuroparenchyma is reported in some of the rare equine cases of meningioma. They are yellow, red, grey to white, globular, ovoid or plaque-like and can be solid to firm with lobulation and, usually, a visible attachment to the meninges (Knottenbelt et al., 2015). Their histological appearance varies greatly, but the WHO human meningioma system can be applied to describe transitional, meningothelial, psammomatous, fibrous, angiomatous, microcystic, chordoid, atypical, malignant and papillary subtypes (Vandevelde, 2012). The pineal gland aids in the regulation of biological diurnal rhythms and can be the site of tumours of the primitive neuroectodermal cells, a pineoblastoma. Histologically indistinguishable from a medulloblastoma, a single reported case in a horse was diagnosed based on its location and the lack of involvement of the cerebellum (Holshuh & Howard, 1982). Lymphoma is one of the more common equine neoplasms and T cell rich, large B cell lymphoma (TCRLBCL) is the predominant subtype. Three cases of TCRLBCL involving the nervous system are reported in horses (Rissi et al., 2023). Typically, lymphoma is grossly white to cream and the histological appearance is of monomorphic lymphocytes often exhibiting features of malignancy: multinucleation, high mitotic counts and prominent nucleoli. IHC for immune cell markers aids characterisation of the precise type of lymphoma. Melanoma is especially common in grey horses and is prone to metastasis, although reports of intracranial melanoma are very rare. Multiple organs were affected in one case without neurological signs (Metcalfe et al., 2013) but in another, a solitary intracranial mass compressed the brainstem and was deemed responsible for antemortem dysphagia (Covington et al., 2004). In both cases, the masses were heavily pigmented (black). Histologically, melanomas can be highly pleomorphic with polygonal and/or fusiform cells, but pigmentation is common. However, IHC often is required to confirm the diagnosis. Malignant vascular tumours are notorious in the veterinary field and, although less commonly reported in horses than in small animals, cerebral metastasis of haemangiosarcoma to the brain is reported in a Welsh pony. There were concurrent metastases in the spinal column, lungs, myocardium, adrenal glands, kidneys, diaphragm, intestinal serosa, mesentery and abdominal adipose tissue (Farber et al., 2024). The gross masses were red and gelatinous with frequent haemorrhages. Haemangiosarcomas can be identified by their histological resemblance to invasive blood-filled endothelial channels with confirmatory IHC. One report details a metastatic nasal anaplastic adenocarcinoma that invaded through the cribriform plate into the cranial vault as well as metastasised to the parotid salivary gland, cervical lymph nodes and the lungs (Davis et al., 2002). Adenocarcinomas are formed of epithelial cells arranged in lobules, acini, or ducts often with evidence of secretory material. This case is reported as anaplastic, indicating marked variation in cell morphology. There are a variety of reported intracranial neoplasms despite them remaining a rare diagnosis that relies on post-mortem examination. While the majority of types of tumours only exert clinical effects through a local mass effect, acting as benign space-occupying lesions, some neoplasms are malignant and the most common presentation of intracranial neoplasia remains PPID. The authors hope readers can better appreciate the heterogeneity of intracranial neoplasia and take home a greater understanding of how histological patterns allow pathologists to distinguish between grossly very similar masses. H. G. Miller: Conceptualization; writing – original draft; writing – review and editing. A. Suarez-Bonnet: Conceptualization; writing – original draft; writing – review and editing. There are no funders to report for this submission. No conflicts of interest have been declared. Not required for this clinical commentary.