The 2017 World Health Organization classification of tumors of the pituitary gland

In 2017 the World Health Organization recognized clinically aggressive adenomas as “high-risk pituitary adenomas”. These include the sparsely granulated somatotroph adenoma, the Crooke’s cell adenoma, the silent corticotroph adenoma and the plurihormonal Pit-1-positive adenoma (subtype 3) 1).

The 2017 World Health Organization classification of tumors of the pituitary gland, in addition to hormone immunohistochemistry, recognizes the role of other immunohistochemical markers including but not limited to pituitary transcription factors. Recognizing this novel approach, the fourth edition of the WHO classification has abandoned the concept of “a hormone-producing pituitary adenoma” and adopted a pituitary adenohypophyseal cell lineage designation of the adenomas with subsequent categorization of histological variants according to hormone content and specific histological and immunohistochemical features. This new classification does not require a routine ultrastructural examination of these tumors. The new definition of the Null cell adenoma requires the demonstration of immunonegativity for pituitary transcription factors and adenohypophyseal hormones Moreover, the term of atypical pituitary adenoma is no longer recommended. In addition to the accurate tumor subtyping, assessment of the tumor proliferative potential by mitotic count and Ki-67 index, and other clinical parameters such as tumor invasion, is strongly recommended in individual cases for consideration of clinically aggressive adenomas. This classification also recognizes some subtypes of pituitary neuroendocrine tumors as “high-risk pituitary adenomas” due to the clinical aggressive behavior; these include the sparsely granulated somatotroph adenoma, the lactotroph adenoma in men, the Crooke's cell adenoma, the silent corticotroph adenoma, and the newly introduced plurihormonal Pit-1-positive adenoma (previously known as silent subtype III pituitary adenoma). An additional novel aspect of the new WHO classification was also the definition of the spectrum of thyroid transcription factor-1 expressing pituitary tumors of the posterior lobe as representing a morphological spectrum of a single nosological entity. These tumors include the pituicytoma, the spindle cell oncocytoma, the granular cell tumor of the neurohypophysis, and the sellar ependymoma 2).

see Pituitary adenoma classification.

Pituitary carcinoma.

Pituitary blastoma.

Tumors of the posterior pituitary.

Neuronal and paraneuronal tumors


Mesenchymal and stromal tumors

Germ cell tumors

Secondary tumors

In this edition, major changes are recommended in several areas of the classification of tumors of the adenohypophysis.

These changes include the following:

1.- a novel approach for classifying pituitary neuroendocrine tumors according to pituitary adenohypophyseal cell lineages

2.- changes to the histological grading of pituitary neuroendocrine tumors with the elimination of the term “atypical adenoma;”

3.- introduction of new entities like the pituitary blastoma and re-definition of old entities like the null cell adenoma.

The 2017 World Health Organization classification of tumors of the pituitary gland is very practical and mostly based on immunohistochemistry for pituitary hormones, pituitary-specific transcription factors, and other immunohistochemical markers commonly used in pathology practice, not requiring routine ultrastructural analysis of the tumors. Evaluation of tumor proliferation potential, by mitotic count and Ki-67 labeling index, and tumor invasion is strongly recommended on individual case basis to identify clinically aggressive adenomas. In addition, the classification offers the treating clinical team information on tumor prognosis by identifying specific variants of adenomas associated with an elevated risk for recurrence.

Changes in the classification of non-neuroendocrine tumors are also proposed, in particular those tumors arising in the posterior pituitary including pituicytoma, granular cell tumor of the posterior pituitary, and spindle cell oncocytoma. These changes endorse those previously published in the 2016 WHO classification of CNS tumors. Other tumors arising in the sellar region are also reviewed in detail including craniopharyngiomas, mesenchymal and stromal tumors, germ cell tumors, and hematopoietic tumors. It is hoped that the 2017 WHO classification of pituitary tumors will establish more biologically and clinically uniform groups of tumors, make it possible for practicing pathologists to better diagnose these tumors, and contribute to our understanding of clinical outcomes for patients harboring pituitary tumors 3).

Non-neuroendocrine tumors are a distinct group of low-grade neoplasms of the sellar region that express thyroid transcription factor 1 4).

García-Sáenz M, Uribe-Cortés D, González-Virla B, Mendoza-Zubieta V, Vargas-Ortega G. Silent pituitary plurihormonal adenoma: clinical relevance of immunohistochemical analysis. Rev Med Inst Mex Seguro Soc. 2019 Apr 1;57(1):48-55. English, Spanish. PubMed PMID: 31071255.
Mete O, Lopes MB. Overview of the 2017 WHO Classification of Pituitary Tumors. Endocr Pathol. 2017 Sep;28(3):228-243. doi: 10.1007/s12022-017-9498-z. Review. PubMed PMID: 28766057.
Lopes MBS. The 2017 World Health Organization classification of tumors of the pituitary gland: a summary. Acta Neuropathol. 2017 Oct;134(4):521-535. doi: 10.1007/s00401-017-1769-8. Epub 2017 Aug 18. Review. PubMed PMID: 28821944.
Shibuya M. Welcoming the new WHO classification of pituitary tumors 2017: revolution in TTF-1-positive posterior pituitary tumors. Brain Tumor Pathol. 2018 Apr;35(2):62-70. doi: 10.1007/s10014-018-0311-6. Epub 2018 Mar 2. Review. PubMed PMID: 29500747.
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