MANAGEMENT OF ENDOCRINE DISEASE: Clinicopathological classification and molecular markers of pituitary tumours for personalized therapeutic strategies

Abstract

Pituitary tumours, the most frequent intracranial tumour, are historically considered benign. However, various pieces of clinical evidence and recent advances in pathological and molecular analyses suggest the need to consider these tumours as more than an endocrinological disease, despite the low incidence of metastasis. Recently, we proposed a new prognostic clinicopathological classification of these pituitary tumours, according to the tumour size (micro, macro and giant), type (prolactin, GH, FSH/LH, ACTH and TSH) and grade (grade 1a, non-invasive; 1b, non-invasive and proliferative; 2a, invasive; 2b, invasive and proliferative and 3, metastatic). In addition to this classification, numerous molecular prognostic markers have been identified, allowing a better characterisation of tumour behaviour and prognosis. Moreover, clinical and preclinical studies have demonstrated that pituitary tumours could be treated by some chemotherapeutic drugs or new targeted therapies. Our improved classification of these tumours should now allow the identification of prognosis markers and help the clinician to propose personalised therapies to selected patients presenting tumours with a high risk of recurrence.

Differential Effects of PI3K and Dual PI3K/mTOR Inhibition in Rat Prolactin-Secreting Pituitary Tumors

“…Aggressive pituitary tumors and carcinomas have to date shown persistent resistance to hormonal therapy with dopamine agonists or somatostatin analogs and as such represent a therapeutic challenge (1). Although conventional chemotherapies are largely ineffective (2,3), recent case reports using temozolomide, an oral alkylating agent used in the management of glioblastoma, have given some hope, especially at early stages (4)(5)(6).…”

Pituitary adenoma: a literature review

“…Diag no zë nu sta to ma ávai raus am þiaus as menims (16-79 m.), vi du ti nið kai 37 m. pa cien tams [4]. Pa gal dy dá HA yra skirs to mos á mik ro ade no mas (ma þiau nei 1 cm dia met ro), mak ro a de no mas (1 cm ir di des nio dia metro) ir la bai di de les ade no mas (dau giau nei 4 cm dy dþio) [5]. Daþ niau sios yra mik ro ade no mos, su da ran èios 50-60 % at ve jø [6].…”

“…Daþ niau sios yra mik ro ade no mos, su da ran èios 50-60 % at ve jø [6]. Nors HA yra lai ko mos ge ry bi niais aug liais, vis dau giau moks li nin kø ma no, kad to kia sam prata tu ri kis ti: 30-45 % jø yra lin ku sios plis ti á aky tuo sius ar pleið ta kau lio an èius, yra at spa rios gy dy mui ir lin ku sios atsi nau jin ti [5]. Be vie ti nio spau di mo su kel tø reið ki niø, HA ga li su kel ti ir en dok ri no lo gi nius su tri ki mus, tai gi kli ni ka tam pa la bai ávai ri ir sun ki na sa va lai kae diag nos ti kà, ku ri yra ypaè svar bi ag re sy viø HA at ve ju.…”

“…Pa sak dau gu mos moks li nin kø, ne uþ ten ka HA dy dþio, hor mo ni nio ak ty vu mo ir his to lo gi niø po ky èiø, kad bû tø ga li ma spraes ti apie kli ni ki nae ei gà, gy dy mo efek ty vu mà ir nu sta ty ti prog no zae, tai gi yra dis ku tuo ja ma, kaip ga li ma pato bu lin ti esa mas kla si fi ka ci jas [3,5,8]. Ra ve rot ir au to riai siû lo kli ni ko pa to lo gi nae kla si fi ka ci jà, ku ri ap ima ne tik HA dy dá ir ti pà pa gal pro du kuo ja mà hor mo nà, bet ir aug lio stadi jà (1 a sta di ja -ne in va zi në, 1 b sta di ja -ne in va zi në, bet pro li fe ruo jan ti ade no ma, 2 a sta di ja -in va zi në, 2 b -in vazi në ir pro li fe ruo jan ti ade no ma, 3 sta di ja -ce reb ros pi na linës ar sis te mi nës me ta sta zës), ku ri bû tø nu sta to ma ra dio logið kai ar ope ra ci jos me tu.…”

“…Ra ve rot ir au to riai siû lo kli ni ko pa to lo gi nae kla si fi ka ci jà, ku ri ap ima ne tik HA dy dá ir ti pà pa gal pro du kuo ja mà hor mo nà, bet ir aug lio stadi jà (1 a sta di ja -ne in va zi në, 1 b sta di ja -ne in va zi në, bet pro li fe ruo jan ti ade no ma, 2 a sta di ja -in va zi në, 2 b -in vazi në ir pro li fe ruo jan ti ade no ma, 3 sta di ja -ce reb ros pi na linës ar sis te mi nës me ta sta zës), ku ri bû tø nu sta to ma ra dio logið kai ar ope ra ci jos me tu. Taip pat jø kri te ri juo se yra at siþvel gia ma á mi to ti ná ak ty vu mà (dau giau nei 2/10 di de lio pa di di ni mo lau ke, Ki-67 (3 % ir dau giau) ir p53 (tei giamas -dau giau nei 5 tei gia mi bran duo liai/10 di de lio pa di dini mo lau ke) [5]. Pa na ðià sis te mà siû lo Va sil je vic ir au toriai, nau do jan tys pas ta ruo sius tris kri te ri jus pro li fe ra ci jai nu sta ty ti: jei bent 2 ið jø yra tei gia mi, prie sta di jos ra ðo ma "b" rai dë, jei ma þiau -"a" [3].…”