Introduction: Paediatric brain tumours in the sellar-suprasellar region are often associated with arginine vasopressin peptide deficiency (AVPD), either at diagnosis caused by the tumour itself or during follow-up as a consequence of treatments. The purpose of this research was to retrospectively describe the neuroradiological characteristics and the timing of AVPD development in a cohort of paediatric patients with craniopharyngioma (CP) or germ cell tumours (GCTs). Methods: We evaluated brain MRI at tumour diagnosis and at the onset of AVPD, as well as recorded clinical, endocrinological, and histopathological data, treatments, and outcome. Results: Seventy-two patients with AVPD were included: 46 CPs (M:F = 25:21) and 26 GCTs (M:F = 18:8). CPs were suprasellar (63%), sellar (4%), or both (33%). GCTs were suprasellar (65%), pineal (24%), or bifocal (11%). No statistically significant differences were noted in tumour size between CP and GCT. Posterior pituitary bright spot absence was reported at diagnosis or at follow-up (as surgery consequence) in all patients with AVPD, indicating that the absence of hyper-intensity is a cardinal feature of AVPD. When measurable, pituitary stalk was thickened in most GCT patients (61.5%). At AVPD diagnosis in GCT, the mean age was 11.9 years; 18 (69%) patients had AVPD at the time of tumour diagnosis, 5 (19.3%) before the diagnosis with a latency of 24.4 months (range 4–48), and 3 (11.5%) during follow-up (mean 24 months, range 4–60) due to tumour recurrence. GCT patients presented with severe endocrinological manifestations (18/26), headache and vomiting (10/26), visual impairment (5/26), and behavioural changes with fatigue (1/26). In CP, the mean age at AVPD diagnosis was 10.3 years; 7 (15.2%) patients had AVPD at time of tumour diagnosis, 37 (80.5%) developed it shortly after neurosurgery, and 2 patients (4.3%) after 2 and 4 months from surgery, respectively. Clinically, headache and visual abnormalities were the most frequent clinical symptoms at diagnosis of CP (39/46, 84.8%), with hydrocephalus (16/46, 35%) and displacement of optic chiasm (29/46, 63%) at the initial MRI. While the vast majority of CP patients (93%) received only surgery, all GCT patients received radiation therapy in addition to or instead of surgery. Conclusion: An early differential diagnosis in children with AVPD and brain tumours is supported by a good understanding of the clinical features and imaging findings. Expert follow-up is necessary.

Arginine vasopressin peptide deficiency (AVPD) is a rare condition characterized by inadequate production or release of arginine vasopressin peptide from the pituitary gland. Histologically, AVPD results from death or degeneration of the neurons that arise in the supraoptic and paraventricular nuclei of the hypothalamus. Arginine vasopressin peptide helps regulate water balance in the body, so its deficiency leads to the production of large volumes of dilute urine (polyuria) with excessive thirst (polydipsia). Clinically, polyuria is characterized by a urine volume more than 2 L/m2/24 h or approximately 150 mL/kg/24 h at birth, 100–110 mL/kg/24 h until the age of 2 years, and 40–50 mL/kg/24 h in the older child and adult [1‒3].

AVPD can be caused by various factors, including head trauma, local surgery, tumours, infections, inflammation as Langerhans cell histiocytosis, autoimmune diseases, or genetic defects affecting the pituitary gland. Diagnosis involves water deprivation tests and 1-deamino-8-d-arginine vasopressin trial. The measurement of plasma copeptin in response to an appropriate osmotic stimulus is a potentially innovative method for diagnosing AVPD [4‒6]. More recently, Winzeler et al. [7] discovered that arginine infusion is a non-osmotic stimulus of the posterior pituitary, as demonstrated by increased copeptin concentrations in healthy adults and children, and that arginine-stimulated copeptin concentrations can accurately distinguish between patients with primary polydipsia and AVPD. Treatment typically involves replacement therapy with synthetic ADH analogue, helping individuals with AVPD maintain water balance and alleviate symptoms.

Among neoplastic aetiologies, intracranial germ cell tumour (IC-GCT) and craniopharyngioma (CP) are the most common. AVPD may be caused by the tumour mass itself via cellular disruption or may follow pituitary surgery. In such situations, it may be transient or permanent. In this paper, we characterize clinical and radiological features of paediatric patients with permanent AVPD and brain tumours, at diagnosis and after long-term follow-up. Understanding of these features will increase knowledge for the early differential diagnosis and accurate therapeutic strategies.

Patients

We retrospectively analysed data of 72 paediatric patients (age <18 years) diagnosed with AVPD and CP or GCT between January 1996 and December 2022 and followed up at King’s College Hospital, London, UK, and The Royal Marsden Hospital, Sutton, UK. Patients who did not present or develop AVPD were not included.

At the time of AVPD onset, we performed laboratory tests and brain MRI and recorded auxological data (height and weight) and clinical symptoms. We followed UK guidelines regarding CP management and follow-up [8]. Among laboratory data, we included electrolyte monitoring, hormonal assessment for growth hormone, insulin-like growth factor-1, adrenocorticotropic hormone, plasma cortisol (F), thyroid-stimulating hormone (TSH), free thyroxine, prolactin, follicle-stimulating hormone, luteinizing hormone, progesterone (P), testosterone (T), and estradiol; serum and cerebral spinal fluid (CSF) tumour markers (alpha-fetoprotein [AFP] and beta-human chorionic gonadotropin [BHCG]) were assessed in case of suspected GCT. Since laboratory tests were performed in different institutions, we stratified serum and CSF tumour markers into 4 categories: normal (BHCG <5 U/L, AFP <10 ng/mL), mild (BHCG 5–25 U/L, AFP 10–50 ng/mL), moderate (BHCG 25–500 U/L, AFP 50–1,000 ng/mL), and severe (BHCG >500 U/L, AFP >1,000 ng/mL) elevation. The different endocrinopathies were diagnosed as follows:

  • AVPD, diagnosed based on clinical assessment, abnormal serum and urine electrolytes, and osmolality results, in some cases, water deprivation test

  • GHD, diagnosis based on poor growth velocity and/or pituitary radiation dose and reduced/absent response to insulin or glucagon stimulation test

  • Hypothyroidism, either central (defined as a low T4 level with low or inappropriately normal TSH) or compensated (defined as a high TSH level with a normal T4 level)

  • Adrenal insufficiency, diagnosed as low serum cortisol level in the morning and poor response to provocative test (low-dose Synacthen® test or insulin-induced hypoglycaemia test)

  • Hypogonadotropic hypogonadism, manifested with delayed/arrested puberty in adolescents, menstrual abnormalities in adult women, and lack of libido in men.

The histological diagnosis was confirmed in accordance with the WHO classification of CNS tumours in effect at the time of the biopsy/resection. The MRI scans were performed on 1.5 Tesla scanner. All patients had sagittal, coronal, and axial MRI evaluations, which included T1-weighted imaging (T1WI) and T2-weighted imaging (T2WI). T1WI sequences were also performed after intravenous injection of gadolinium contrast medium (Gd-DTPA). The tumour volume was calculated according to the following formula: volume (cm3) = sagittal × coronal × axial diameters × 0.5. If available, we recorded posterior pituitary bright spot and the position and shape of the pituitary stalk. The pituitary stalk was considered thickened if the maximum measurement on sagittal and coronal images was ≥3 mm, and thickened stalks were graded as minimally thickened (3.0–4.5 mm), moderately thickened (4.5–6.5 mm), or severely thickened (>6.5 mm).

Statistical Analysis

Measures of central tendency (mean or median when appropriate) were used to describe population continuous characteristics, while categorical variables were presented as numbers and percentages. χ2 test and ANOVA were used to compare brain MRI findings between CP and GCT at the time of tumour or AVPD diagnosis. A p value <0.05 was considered statistically significant. All statistical analyses were performed in STATA (StataCorp).

Demographics

Seventy-two patients were included: 26 GCT patients (M:F = 18:8) and 46 CP patients (M:F = 25:21). Among CP, 63% were suprasellar, 4% sellar, and 33% both. Among GCT, 65% were suprasellar, 24% pineal, and 11% multifocal. In CP, the median age at AVPD diagnosis was 10.3 years (min 2.8, max 16), 7.2% of patients (7/46) had AVPD at the time of tumour diagnosis, 80.5% (36/46) of patients showed AVPD immediately following neurosurgery, and 2.3% (1/36) and 4.3% (2/36) developed AVPD 2 and 4 months after surgery, respectively. The mean age at AVPD diagnosis in CGT was 11.9 years (min 6.9, max 17.7). AVPD was present in 18 (69%) patients at the time of tumour diagnosis, 5 (19.3%) patients prior to tumour diagnosis with a latency of 24.4 months (range 4–48), and 3 (11.5%) patients after a median follow-up period of 24 months (range 4–60) due to tumour recurrence (Table 1).

Table 1.

General demographics data of study population divided into two groups according to the type of tumour (CGT and CP)

Cause of AVPDPatients, NSex (M/F)Age
GCT 26 18/8 11.9 
CP 46 25/21 10.3 
Cause of AVPDPatients, NSex (M/F)Age
GCT 26 18/8 11.9 
CP 46 25/21 10.3 

Clinical Manifestations at Diagnosis and Pathology

Our patients showed various levels of anterior pituitary dysfunction as summarized in Table 2. We reported the main clinical manifestations in both GCT and CP groups:

  • 1.

    GCT: In 10/26 cases (38.5%), hormonal deficiencies manifested as presenting symptoms of brain tumour. In addition, 10/26 patients (38.5%) experienced headache and vomiting, 5/26 (19.3%) visual impairment, and 1/26 (3.7%) behavioural changes and fatigue. Among the endocrinological manifestations at diagnosis, we noted 18/26 (69%) AVPD, 16/26 (61.5%) central adrenal insufficiency, 17/26 (65%) thyroid dysfunctions, 6/26 (23%) poor growth, and 2/26 (0.8%) pseudo-precocious puberty. Suprasellar and pineal GCTs showed different clinical presentations. In our series, the first symptom was headache and vomiting (indirect sign of hydrocephalus) in 60% of pineal GCTs, while 80% of suprasellar GCTs showed hormonal deficiencies as the first symptom. Serum AFP levels were increased in 6/26 (23%) patients of which 4 (67%) and 2 (33%) had a severe and moderate increase, respectively. Serum BHCG levels were increased in 8/26 (31%) patients of which 4 (50%) were mildly, 2 (25%) moderately, and 2 (25%) severely. CSF samples showed an increase in AFP values in 5/26 (19%) patients of which 1 (20%) was mild, 3 (60%) were moderate, and 1 (20%) was severe. CSF BHCG values were increased in 7/26 (27%) patients of which 2 (28%) were mild and 5 (72%) moderate. According to the WHO histological classification of IC-GCT, 18/26 (69.2%) patients had germinomas, 8/26 (30.8%) non-germinomatous GCT, 3/8 (37.5%) mixed germinoma and teratoma, 4/8 (50%) teratoma, and 1/8 (12.5%) yolk sac tumour. The gross appearance was usually grey-white, fish-meat-like. The immunohistochemistry showed positivity for CD117, PLAP, or OCT3/4.

  • 2.

    CP: The most frequent clinical symptoms of children with CP at tumour diagnosis were headache and visual abnormalities (39/46, 84.8% collectively), of which 3/39 (7.7%) also had AVPD. Ten patients (21.7%) showed endocrinological disorders, of which 7 (70%) presented with AVPD and 3 (30%) with short stature at diagnosis. According to the WHO classification, adamantinomatous CP was the most frequent variant (95.6%). Although it was often grossly oil-like and of solid tissue mixed with cystic component, when described in the other cases CP had a grey-white and soft tissue appearance. Cholesterol crystals and inflammatory cells were the predominant histopathological findings.

Table 2.

Summary of principal endocrinological deficiencies in our cohort

Endocrinological deficitGCTCP
Panhypopituitarism 13 32 
GH + TSH + ACTH 10 
GH + ACTH + GnRH  
GH + TSH  
TSH + ACTH + GnRH  
GH + GnRH  
TSH + ACTH 
TSH+ GnRH  
ACTH  
Endocrinological deficitGCTCP
Panhypopituitarism 13 32 
GH + TSH + ACTH 10 
GH + ACTH + GnRH  
GH + TSH  
TSH + ACTH + GnRH  
GH + GnRH  
TSH + ACTH 
TSH+ GnRH  
ACTH  

GH, growth hormone; ACTH, adrenocorticotropic hormone.

MRI Features

The main MRI characteristics of the tumours are listed in Table 3.

1. GCT

Most GCTs (96.2%) were hypo-/iso-intense in T1WI (hypo:iso = 20:5) and 80.1% iso-/hyper-intense in T2WI (iso:hyper = 15:6). All cases showed avid contrast enhancement MRI performed in 3:26 8.6% patients before surgery but after radiotherapy and/or chemotherapy showed mild enhancement. About 20% of cases presented heterogeneous enhancement. The majority of GCT (65.4%) had a maximum diameter >3 cm. Fourteen GCT patients showed pituitary stalk thickening at diagnosis: between 3 and 4.5 mm (19.2%), between 4.5 and 6 mm (19.2%), and >6 mm (23.1%).

Table 3.

Main MRI characteristics of the tumours

MRI featuresGCT, %CP, %
T1WI signal 
 Hypo-intense 77.0 95.6 
 Iso-intense 19.2 4.4 
 Hyper-intense 3.8 
T2WI signal 
 Hypo-intense 23.1 
 Iso-intense 57.8 
 Hyper-intense 23.1 98 
Mean lesion volume, cm3 11.6 13.3 
Max diameter, cm 
 <1 7.77 
 1–2 15.4 19.6 
 2–3 11.5 21.7 
 >3 65.4 58.7 
Bright spot 
 Present 11.5 32.6 
 Absent 88.5 67.4 
Epicentre 
 Sellar-suprasellar 65 100 
 Pineal 24 
 Multifocal 11 
Optic chiasma 
 Normal 46 47 
 Uplift 54 63 
Hydrocephalus 
 Present 42.3 32.6 
 Absent 57.7 67.4 
Pituitary stalk 
 Normal 38.5 37 
 3.0–4.5 mm 19.2 
 4.5–6.5 mm 19.2 10 
 >6.5 mm 23.1 
 Not evaluable 39 
MRI featuresGCT, %CP, %
T1WI signal 
 Hypo-intense 77.0 95.6 
 Iso-intense 19.2 4.4 
 Hyper-intense 3.8 
T2WI signal 
 Hypo-intense 23.1 
 Iso-intense 57.8 
 Hyper-intense 23.1 98 
Mean lesion volume, cm3 11.6 13.3 
Max diameter, cm 
 <1 7.77 
 1–2 15.4 19.6 
 2–3 11.5 21.7 
 >3 65.4 58.7 
Bright spot 
 Present 11.5 32.6 
 Absent 88.5 67.4 
Epicentre 
 Sellar-suprasellar 65 100 
 Pineal 24 
 Multifocal 11 
Optic chiasma 
 Normal 46 47 
 Uplift 54 63 
Hydrocephalus 
 Present 42.3 32.6 
 Absent 57.7 67.4 
Pituitary stalk 
 Normal 38.5 37 
 3.0–4.5 mm 19.2 
 4.5–6.5 mm 19.2 10 
 >6.5 mm 23.1 
 Not evaluable 39 

The mean tumour volume was 11.6 cm3 with uplift of the optic chiasm in 54% of cases. In addition, 24% of cases were bifocal (simultaneous localization in the pineal gland) and 11% were multifocal.

At diagnosis, a posterior pituitary bright spot was absent in 88.5% of cases and pathological thickening of the pituitary stalk was reported in 53.8%. Posterior pituitary bright spot absence was significantly associated (p value: 0.00001) with AVPD. Hydrocephalus was present in 42.5% of cases.

2. CP

The majority of CP had T1WI central hypo-intensity (95%) and rim hyper-intensity. The prevalent solid component was hypo-intense in nearly all cases (hypo:iso = 44:2), and 98% had T2WI hyper-intensity.

Most CP showed a heterogeneous enhancement due to calcific and cystic components. After radiotherapy and/or chemotherapy, they showed mild enhancement with some macrostructural changes as reduction of solid components and rise of cystic ones. A total of 58.7% had a maximum diameter >3 cm, and none was <1 cm. In total, the mean volume was 13.3 cm3 with uplift of the optic chiasm in 63% of cases. CPs were suprasellar (63%), sellar (4%), or both (33%).

Posterior pituitary bright spot was absent in 67.4% of cases at diagnosis and not evaluable in all cases after surgery. After surgery to remove a CP, there can be residual tissue changes, such as inflammation, oedema (swelling), or changes in blood flow, which may appear as areas of increased brightness on imaging. Pituitary stalk thickness was not evaluated in 39% of cases, as the stalk was incorporated into tumour mass, making it hard to assess and distinguish from the lesion on MRI. At diagnosis, hydrocephalus was present in 67.4% of cases and absent in 32.6%. No statistical differences were found in tumour size and mean volumes between CP and GCT (p value = 0.87). Absence of a pituitary bright spot at diagnosis was more frequent in GCT than in CP (p value = 0.47). Posterior pituitary bright spot absence was significantly associated (p value: <0.0005) with AVPD.

Treatment and Outcome

  • 1.

    GCT: Overall, 22/26 cases underwent surgery (7 complete resection, 15 partial resection) followed by radiotherapy. In addition, 20/26 underwent chemotherapy. Overall, 16/26 received surgery, radiotherapy, and chemotherapy. Three patients died during follow-up.

  • 2.

    CP: Overall, 43/46 cases underwent surgery (19 complete resection, 24 partial resection). Radiation treatment was given to 28 individuals. Of them, 7/28 received stereotactic treatment and 21/28 proton therapy. Four patients died during follow-up.

In this observational, retrospective cohort study, we analysed brain MRI of paediatric patients with AVPD and CP or GCT at diagnosis and at the onset of AVPD, recording clinical, endocrinological, and histopathological data, treatments, and outcome. We tried to improve differential diagnosis between these types of brain tumours.

As already known [3, 9‒12] and confirmed in our cohort, AVPD can be associated with certain types of brain tumours including GCT and CP. Of interest, in our cohort a larger proportion of patients with CP had AVPD. Partenope et al. [13] found that 85.7% of GCT showed AVPD at diagnosis. In addition, Liu et al. [12] reported that in Taiwanese infants with AVPD, GCT was the most typical aetiology (52.6%) of acquired infiltrative illness or tumour. On the contrary, the proportion of GCT among patients who developed an infiltrative disease or tumour was substantially lower in previous studies (21.1–26.7%) [3, 9, 11]. The timing of AVPD in these tumours can vary and may be already present at the onset of symptoms and diagnosis, depending on tumour location and size, as well as its impact on the pituitary gland and surrounding structures. However, in other cases, AVPD may develop or manifest later as the tumour progresses or increases in size or due to surgery only. Most of our CP patients developed AVPD soon after neurosurgery. Our findings are similar to those published by Bajpai et al. [14]. CP patients frequently develop deficiencies in pituitary function after surgery, and previous studies [15‒17] showed that pituitary insufficiency could be present in almost 100% of long-term survivors. On the contrary, AVPD was often an early clinical manifestation in our GCT population, as described in other studies [17, 18]. AVPD affects regulation of water balance in the body. Prompt identification and management of AVPD are important, as it can lead to excessive thirst, increased urine output, and electrolyte imbalances [2, 3]. Presenting symptoms of brain tumours can include visual disturbances, hormonal imbalances, headaches, or other neurological deficits. These clinical manifestations can provide valuable clues about the nature and location of the tumour itself. Suprasellar GCTs were usually present with anterior pituitary dysfunction as the initial symptom. On the contrary, pineal GCTs typically showed visual disturbances or headache. This occurs because of the obstruction of the flow of CSF, leading to an increase in fluid pressure and subsequent symptoms of hydrocephalus [19]. Similarly in our cohort, the majority of pineal GCTs were presented with headache and vomiting, whereas most of suprasellar GCTs displayed endocrine disorders as the first symptom. Moreover, in our cohort, headache and visual abnormalities were the most frequent symptoms at diagnosis of CP and were related to hydrocephalus and displacement of optic chiasm visible at first MRI. Also, GCT located near the optic nerves or optic chiasma may cause persistent or worsening headache that is unresponsive to over-the-counter pain medications and vision disturbances, such as blurred vision, double vision, or loss of peripheral vision. Increased intracranial pressure can lead to nausea and vomiting, particularly in the morning or with changes in position. Less frequently some individuals with GCT may experience changes in behaviour, irritability, mood swings, or personality changes, as reported by 1 patient in our cohort. Anterior pituitary dysfunctions (pubertal disorders, poor growth, hypothyroidism, central adrenal insufficiency) are associated with CP as well as with suprasellar GCT. Endocrinological disorders were present at diagnosis in 38.5% of GCT patients and in 21.7% of CP patients, congruently with previous data for GCT [20] but in contrast to known prevalence of endocrinopathies as primary manifestations in CP (52–87%) [21]. This may reflect the difficulties faced by physicians and primary care services in diagnosis of endocrine disorders which often remain unnoticed or underestimated, causing delayed diagnosis of brain tumours [22, 23]. IC-GCTs can disrupt normal pubertal development and cause various pubertal dysfunctions, especially suprasellar germinomas. Some of the pubertal dysfunctions that can occur as a result of IC-GCTs include gonadotropin independent or central precocious puberty, delayed puberty, and hypogonadotropic hypogonadism. The posterior pituitary bright spot, also known as the posterior pituitary T1W hyper-intensity, is a normal finding on MRI scans and represents the accumulation of ADH in the posterior pituitary. In AVPD, the lack of ADH production or release from the hypothalamus and posterior pituitary gland leads to decreased levels of ADH in the body [24]. As a result, there is no or minimal accumulation of ADH in the posterior pituitary, which can be visualized as the absence of the bright spot on MRI scan. Bright spot absence was reported at diagnosis or at follow-up (as surgery consequence) in all our patients with AVPD, indicating that the absence of hyper-intensity is a cardinal feature of AVPD [25]. However, it is important to note that the absence of the bright spot can also be seen in other non-tumoral conditions affecting the posterior pituitary, such as primary pituitary disorders or pituitary stalk abnormalities. Thickening of the entire pituitary stalk can be associated with AVPD in some cases. This condition is known as “thickened pituitary stalk syndrome” or “hypothalamic-pituitary stalk abnormality with DI.” Thickening of either the entire pituitary stalk or just the proximal portion was the second most common abnormality on MRI scans in our cohort. In 38.5% of the patients with GCT, the pituitary stalk was normal (<3 mm). The exact mechanism linking pituitary stalk thickening and AVPD is not fully understood. It is believed that the inflammation or immune-mediated processes involved in certain conditions can lead to damage and swelling of the pituitary stalk, disrupting the normal production, storage, or release of ADH [26].

In conclusion, we believe that diagnosis of sellar-suprasellar region (SSR) masses must comprehensively consider clinical manifestations, tumour markers, and MRI features. This is fundamental for an accurate diagnosis and for subsequent decisions regarding treatment to be chosen. We propose that the following circumstances warrant GCT consideration for children with SSR masses and AVPD at onset: polyuria and polydipsia, early and delayed puberty, short stature, and headaches [27]; a rise in BHCG levels in the blood or CSF (>5 IU/L), as well as a rise in AFP levels that could point to the presence of a non-germinomatous GCT component; brain MRI demonstrating hypo-/iso-intensity T1, iso-/hyper-intensity T2, and often homogeneous or heterogeneous enhancement with cysts or bleeding [28, 29]. Additionally, the diagnosis would be aided by enhancement in the pineal body, which is another typical location for GCT in children [30]. Although CP is the most frequent in SSR masses in children, AVPD seldom occurs at diagnosis [31]. Therefore, CP should be considered in the following circumstances: fewer nonspecific symptoms, with short stature being the most prevalent; symptoms unrelated to the endocrine system, such as headache and vision problems [3, 27, 28]. In 40–50% of children with CP, obesity and eating disorders are present, which reduces their ability to expend energy and increases their risk for metabolic syndrome, cardiovascular disease, including sudden death events, multisystem morbidity, and mortality [17]. MRI often displayed heterogeneous enhancement and hyper-intensity in T1WI and T2WI, while the solid component in T2WI might be varied, normal levels of AFP and BHCG. In our cases of CP and GCT with DI where the pituitary has been identified on MRI, the bright spot was absent at diagnosis or after treatment.

GCTs are typically treated with a combination of surgical resection, chemotherapy, and radiotherapy. The specific treatment plan depends on factors such as tumour location, size, and histological subtype. Chemotherapy regimens often include platinum-based agents like cisplatin and etoposide. On the contrary, complete or partial surgery is the standard treatment for CPs. The goal of surgery is to achieve maximal tumour removal while minimizing damage to surrounding structures, particularly the hypothalamus and pituitary gland. Radiotherapy can be added when complete surgical resection is not possible or if the tumour recurs. In our series, the majority of CP patients (93%) received just surgery, whereas all GCT patients received radiation therapy.

Differential diagnosis is an important issue to consider when evaluating patients with AVPD. Besides GCT and CP, also traumatic brain injury, infections, Langerhans cell histiocytosis, and autoimmune disorders should be considered [6]. Neuroimaging, tumour markers, clinical aspects, and, in selected cases, histological analysis are necessary to complete the diagnostic workup. Our study outlined some neuroradiological characteristics that may be helpful to differentiate CP and GCT early.

In conclusion, CP and GCT are the “two sides” of the same coin: they share some clinical aspects (especially AVPD); however, they are distinct conditions (with completely different treatments and outcomes) that need to be recognized as soon as possible for the best possible management. A clear understanding of clinical and imaging features in AVPD associated with different brain tumours will increase knowledge for the early differential diagnosis and accurate therapeutic strategies. Specialist management and follow-up are required.

This study protocol was reviewed and approved by Biomedical Research Centre at The Royal Marsden and the ICR, approval number SE969. This study was performed in accordance with the ethical standards of the local institutional Ethics Committees and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Written informed consent was obtained from the parent/legal guardian of participants prior to the study.

The authors have no conflicts of interest to declare.

The authors declare no funding was received.

Conception and design of work: S.C. and A.A. Data acquisition, analysis, and interpretation: S.C. and M.T. Drafting of work: S.C. and C.P. Critical revision and final approval of version: A.A. and V.B.A. All authors have responsibility for all aspects of the work, ensuring that issues relating to the accuracy or integrity of any part of the work are investigated and resolved appropriately.

All data generated or analysed during this study are included in this article. Further enquiries can be directed to the corresponding author.

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