LAUSR

Pituitary carcinoma (PC) is a very rare tumor entity of the sella turcica, representing 0.1–0.5% of all PitNETs tumors [1–5]. Based on the WHO Classification, it is defined as pituitary tumor with confirmed craniospinal and/or systemic metastases [6]. Most of them present CNS only (45,2%) or extra CNS (38,7%) metastases. Synchronous extraand CNS metastases are less common (16,1%) [7]. It is not known whether the tumors develop predominantly from PitNETs after a longer clinical course or de novo [8]. PCs can be hormonally inactive or active (ACTH-, PRL-, GH-, TSHFSH-, LH-secreting), but far most of them are ACTHor PRL-secreting tumors [8, 9]. There is little known about the genetic background of this tumor entity, because most of the information comes from case reports and singular larger case series. ATRX [10, 11], CDKN2A [11], CDKN2B [11], SDHB [12], TP53 [11, 13] mutations have been identified in primary [13] and ATRX [10, 11], CDKN2A [11], CDKN2B [11], H-Ras [14] mutations in metastatic tumors. MSH2 germline mutation was described in one case report [15]. PTEN mutations were reported without localization [16]. The tumors have a poor prognosis with a 66% mortality rate after 1 year and up to 80% after 8 years [1, 17]. Treatment options include surgery, chemotherapy, hormonal therapy, and/or radiotherapy. There are many different chemotherapeutic protocols. To the most commonly used chemotherapeutics include temozolomide, CCNU+ 5-fluoruracil. Especially in ACTH-secreting PCs other agents, which lower ACTH and cortisol secretion, are additionally used. As most ACTH-secreting tumors express somatostatin receptor type 5, pasireotide as potent somatostatin analog with high affinity to somatostatine receptor type 5 showed significant suppression of ACTH and cortisol secretion [18]. Mitotane and ketoconazole as steroidogenesis inhibitors can support the treatment by reducing the cortisol levels and present an alternative to bilateral adrenalectomy [10, 19, 20]. In this paper, we present the case of an ACTH-secreting PC with liver and thoracic vertebrae metastases. For further characterization, DNA from the primary tumor and liver metastases were isolated. DNA sequencing revealed TP53, NF1 mutations in the primary tumor, and TP53, NF1, PTEN, and ATRX mutations in liver metastases. Based on our results and the literature, we discuss the genetic origin of PC and the molecular principles of their metastases (Fig. 1).