The tumors of the sellar region are variable. Among these tumors, pituitary adenoma is the most frequent, occurs with a mean incidence of approximately 5.1 cases per 100,000 per year[1], accounting for about 15% of all intracranial tumors[2], whereas cranipharyngioma is relatively infrequent, account for approximately 3%[3]. Collision tumors represent two or more morphologically and pathologically different tumors that are attached to each other, comprise single or diverse pathological components of pituitary adenoma, craniopharyngioma, Rathke cleft cyst, chordoma, gangliocytoma, primary lymphoma. The prevalence rates of collision tumors in the sellar region are not available. The most common combinations are pituitary adenoma with Rathke cleft cyst, while the collision of pituitary adenoma and craniopharyngioma is extremely rare. Up to now, there are minority cases previously documented. Compared with pituitary adenoma, craniopharyngioma poses more particular therapeutic difficulties for resection based on the intimate association with critical neurovascular anatomies. Clinical presentations of collision tumors are wide-ranging, depend on the size, the location and the type of tumor. Typically the result of tumor bulk and mass effect on adjacent structures, including headaches, retro-orbital pain, nausea and vomiting, diabetes insipidus, as well as symptoms acquired from pituitary hormonal deficiency or excess, these features are similar to those of pituitary adenoma or craniopharyngioma alone.
The patient reported a several-months history of daily fatigue with visual field loss. The symptoms were resulting from electrolyte disturbance with hypovolemia and optic nerve compression. Serum sodium returned to normal after the sodium chloride supplement. The pathophysiological mechanisms underlying hyponatremia(HN) and hypovolemia remain unclear, cerebral salt-wasting syndrome (CSWS) may get a clue. It is caused by natriuresis, which is followed by volume depletion and negative sodium balance. The concept of CSWS was first proposed by Peters et al. in 1950 as an important cause of HN in patients with acute or chronic damage of the central nervous system (CNS)[4], without a clear-cut mechanism, Bitew et al. demonstrating that impaired sympathetic neural input to the juxtaglomerular apparatus may reduce proximal tubule sodium, urate, and water reabsorption and also decrease renin and aldosterone release[5]. While Berendes et al. indicated that the natriuretic factors, such as atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), may play important roles in this condition[6]. In contrast, HN secondary to SIADH is a result of excess of renal water reabsorption through inappropriate antidiuretic hormone (ADH) secretion. Determinating volume status in hyponatremic patients is the key point in differential between CSWS and SIADH. This patient showed typical clinical features of CSWS. Cui et al. found there were different clinical characteristic of SIADH and CSWS in different types of neurological disorders. Patients with old age (> 60 years or ≤ 7 years), female sex, tumor size, rate of decline of blood sodium, low sodium concentration on postoperative days 1–2, and long operation time, otherwise, patients with Cushing’s disease, craniopharyngioma or Rathke’s cleft cyst were the risk factors of NH in those with cerebral tumor. SIADH was common in adult patients; however, CSWS was the main cause of hyponatremia among pediatric patients, which was inconsistent with this case[7]. In this case, volume depletion and negative sodium balance resulted in hyponatremia, and replacement of water and sodium was therapeutically effective treatment. While simple fluid restriction is effective in the treatment of hyponatremia in uncomplicated SIADH.
The rate of visual disturbance was high in collision tumor. Our patient accords with this clinical characteristic. Orga et al. reported visual loss was the most common presentation (39%) followed by endocrine abnormality and headache in pituitary adenoma[8]. Another research investigated the clinical characteristics of ophthalmic findings in Korean patients diagnosed with pituitary adenoma, 12.4% (66 in 534 patients) had visual disturbance[9]. While Hasegawa et al. reported twenty-two cases, of which seventeen suffered from impaired vision when diagnosed with different types of collision tumor, the ratio was higher than single tumor, one likely explanation is that tumor burden increased[10].
The patient presented typical laboratory results of hypopituitarism, the preoperative endocrine tests showed decreased pituitary hormones, including low levels of adrenocorticotropic hormone (ACTH), plasma cortisol, growth hormone (GH), luteinizing hormone(LH), follicle-stimulating hormone (FSH), as well as decreased free T4 and T3 without elevated thyroid-stimulating hormone (TSH). The available endocrine data confirmed that 10 of 20 collision tumor patients had hypopituitarism, with hypogonadism occurring most frequently[10]. The hypothalamic–pituitary–adrenal(HPA) axis, hypothalamic–pituitary–thyroid(HPT) axis, and hypothalamic–pituitary–gonadal(HPG) axis were involvement in this patient, which was exceptionally rare and also mentioned by Moshkin et al. in a different patient[11].
On the other hand, hyperprolactinemia was a common feature and observed in 11 of 20 patients in the repoted literature[10], Cusimano et al. hypothesized that the pathogenesis of lactotroph hyperplasia and prolactinoma was closely linked to the loss of inhibitory hypothalamic dopaminergic input caused by pituitary stalk compression by craniopharyngioma[12], but this would not explain the occurrence of nonfunctioning collision adenomas[13].
In this case, preoperative MRI showed different signal intensities attached to each other, and the patient underwent a transsphenoidal surgery approach for subtotal tumor resection. Unfortunately, MRIs are obtained after one year of the surgery which identified the recurrence of the lesion, while at this time, the patient present slightly impaired vision but without other correlated manifestations, so further follow-up was continued. The subsequent reexamination was postponed for personal reasons until present time, two years after the primary surgery, the MRIs showed the lesion progressively increased in size and the patient complained that the visual acuity of her both eyes had deteriorated. With this regard, the patient requires secondary surgery. Given the similarities of the clinical and imaging features, another 47-year-old patient underwent a first transsphenoidal surgery with subtotal tumor resection and a second operation using an interhemispheric transcallosal approach for total microsurgical resection[13]. A definitive diagnosis of a collision sellar lesion is highly difficult, physical characteristics of collision lesions were not specific intraoperatively, it was only when the histopathologic review confirmed that the collision tumor was identified. Sahli et al.concluded that a clinical diagnosis could have been made with greater awareness and suspicion of these entities, as well as acknowledgement of its unusual imaging characteristics[14]. Certain imaging characteristics may be beneficial in raising suspicion, including calcifications, nonenhancing cystic lesions, or locally destructive components in conjunction with a suspected pituitary adenoma[15]. Several characteristics including a sellar-suprasellar lesion with different signal intensities, calcifications, and cystic changes were observed in previous cases, which were subsequently confirmed collision tumor by postoperative histological examination[13, 16]. Still, the tumor manifestations are highly variable, it remains a significant challenge for the clinician to make an accurate diagnosis.
The pathogenesis of mixed pituitary adenoma with craniopharyngiomas remains unclear and it is not known whether they are collision tumors derived from independent stem cells or whether they originate from a single stem cell undergoing divergent differentiation. Some reported cases represent collision tumors which pituitary adenomas and craniopharyngiomas are present in different parts of the gland or are closely paratactic but not compounded[10, 12, 13, 16–21]. The more rare pathological form is mixed sellar tumors formed of admixed craniopharyngioma and pituitary adenoma components[11, 22–25]. One particularly striking question here is whether different tumor formation can be interpreted by different tumor developing mechanism. The development of the components of collision tumors can be entirely independent, growth factors capable of stimulating may contribute to parallel growth of pituitary adenoma and craniopharyngioma.
Pituitary adenomagenesis's underlying mechanisms are less understood, however it is believed to include a multistep process with a variety of initiating and promoting elements. The majority of pituitary adenomas are monoclonal, indicating that there has been a genetic mutation at the molecular level that has caused cell transformation as the initial event and tumor progression as a result of growth factor or hormonal stimulation. The over- or underexpressed oncogenes like gsp, the pituitary tumor-transforming gene(PTTG), the multiple endocrine neoplasia type I gene, the p16 and Gadd45y, missense mutations derived by GNAS, USP8, IDH1, signal amplification mediated by GPR101, P13KCA, HMGA2, novel variants recently confirmed through whole exome sequencing (WES) such as MEN1, KIF5A, BRAF, USP48, NR3C1, PABPC1, GRB10 and growth factors like TGF-α and β, EGF, and FGF, as well as IL-6 have all been shown to play a role in the development of adenomas[26, 27]. In contrast, the adamantinomatous type of craniopharyngiomas has been found to have β-catenin gene mutations as well as nuclear redistribution of β-catenin expression, which have not been identified in pituitary adenomas[28], this suggests that the Wnt signaling pathway has been reactivated [29], while expression of α-, β-, and γ-catenin proteins is decreased in adenomas as compared to normal pituitary tissue[30].
On the other hand, it is not surprising that craniopharyngioma and pituitary adenoma can coexist as they share a same embryonic ancestor, Rathke's pouch, though the pathogenesis is still unclear. Mixed tumors may derive from a single stem cell undergoing divergent differentiation. Finzi et al. reported the existence of hybrid cells exhibiting traits of both pituitary adenoma and craniopharyngioma[25]. Gokden et al. discribed a craniopharyngioma component that was mixed in with a pituitary adenoma without separating into two separate mass lesions or histologic demarcation, their case showed focal changes of transition from ordinary pituitary adenoma to squamoid to adamantinomatous areas[23], it may support the metaplastic hypothesis for the development of these composite neoplasms. The presence of a stem cell/progenitor cell population in the mouse pituitary gland lends credence to the possibility of a metaplastic change in the pituitary adenoma[31, 32].