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Neues aus der Tumorpathologie der Hypophyse

New aspects of tumor pathology of the pituitary

  • Schwerpunkt: Neuroendokrine Tumoren
  • Published:
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Zusammenfassung

Hypophysenadenome müssen zur erforderlichen klinisch-pathologischen Korrelation und Prognoseeinschätzung detailliert strukturell und immunhistologisch (somatotropes Hormon [STH], Prolaktin, adrenokortikotropes Hormon [ACTH], Thyreoidea-stimulierendes Hormon [TSH], follikelstimulierendes Hormon [FSH], luteinisierendes Hormon [LH], Ki-67, p53) untersucht und nach Strukturmerkmalen insbesondere der Granulierungsdichte und nach dem Hormongehalt klassifiziert werden. Bei fehlender Übereinstimmung mit der Klinik müssen dafür Erklärungen gefunden werden. Alle aktiven Adenomtypen können auch als inaktive („silent“) Adenome auftreten. Erhöhte Ki-67-Werte (> 3 %), signifikante p53-Expressionen und Mitosenachweis identifizieren die atypischen Adenome, deren biologische Relevanz noch unklar ist und die auch nicht generell als Präneoplasie des Hypophysenkarzinoms gelten. Hypophysenkarzinome sind durch den zwingenden Nachweis von Metastasen charakterisiert. Ausgedehnte lokale Invasionen oder sehr stark erhöhte Proliferationsmarker reichen für diese Diagnose nicht aus. Kraniopharyngeome sind in (intra- oder supraselläre) adamantinöse und (nur supraselläre) papilläre Typen zu klassifizieren. Regressive Veränderungen finden sich nur bei adamantinösen Typen. Stärkere Regressionen erschweren die Differenzialdiagnose zu sekundär veränderten plattenepithelial-metaplastischen Rathke-Zysten. Ein Nachweis nukleärer β-Catenin-Expression sichert die Diagnose eines adamantinösen Kraniopharyngeoms. Papilläre Kraniopharyngeome sind durch BRAF-Mutationen charakterisiert, die hilfreich bei der Differenzialdiagnose sein können. Neurohypophysäre Pituizytome, adenohypophysäre Spindelzellonkozytome und neurohypophysäre Granularzelltumoren sind ausnahmslos TTF-1-positiv und gelten heute als Varianten eines einheitlichen hypophysären Spindelzelltumors.

Abstract

Pituitary adenomas have to be studied in detail for structural characteristics, especially regarding the degree of granulation and immunohistochemical hormone expression, such as growth hormone (GH), prolactin, adrenocorticotropic hormone (ACTH), thyroid stimulating hormone (TSH), follicle stimulating hormone (FSH), luteinizing hormone (LH) and proliferation markers (e.g. Ki-67 and p53) for correlation to clinical data and assessment of the prognosis. If histological and immunostaining data do not correlate to the patient data, explanations for the discrepancies must be found. All active adenoma types can also be present as inactive, so-called silent adenomas showing the same features. An increased Ki-67 index (> 3 %), significant nuclear expression of protein p53 and mitoses are characteristic of atypical adenomas. Up to now the biological relevance of these atypical adenomas, especially their role as preneoplasms for pituitary carcinomas has not been fully elucidated. The only proof of a pituitary carcinoma is the existence of metastases. Extensive local invasion and a greatly increased Ki-67 index are not sufficient for this diagnosis. Craniopharyngiomas have to be classified into adamantinomatous types (intrasellar and suprasellar) and papillary types (only suprasellar). Regressive changes are found in adamantinomatous types only. Strong regression may lead to difficulties in the differential diagnosis of Rathke’s cleft cysts with squamous metaplasia. Demonstration of nuclear expression of beta-catenin in these cases enables the diagnosis of craniopharyngioma. Papillary craniopharyngiomas are characterized by BRAF mutations that may be helpful in the differential diagnosis. All pituicytomas of the neurohypophysis, all spindle cell oncocytomas of the anterior pituitary and all granular cell tumors of the posterior pituitary express thyroid transcription factor 1 (TTF-1) and are thought to be variants of a common uniform spindle cell tumor of the pituitary.

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Danksagung

Meinen einsendenden Neurochirurgen verdanke ich das vielfältige Tumormaterial und viele anregende Gespräche sowie gemeinsame Projekte. Mein besonderer Dank gilt den Sponsoren des Hypophysentumorregisters, der Novartis Pharma GmbH (Nürnberg), der Novo Nordisk Pharma GmbH (Mainz), der Pfizer Pharma GmbH (Karlsruhe) und der Ipsen Pharma GmbH (Ettlingen), ohne die die Untersuchungen nicht finanzierbar gewesen wären.

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  1. Institut für Neuropathologie der Universität Hamburg, Universitätsklinikum Hamburg-Eppendorf (UKE), Martinistraße 52, 20246, Hamburg, Deutschland

    W. Saeger

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W. Saeger, Hamburg

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Saeger, W. Neues aus der Tumorpathologie der Hypophyse. Pathologe 36, 293–300 (2015). https://doi.org/10.1007/s00292-015-0025-z

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