Journal of Endocrinological Investigation
Advances and controversies in the classication and grading
of pituitary tumors
E. R. Laws Jr.
· D. L. Penn
· C. S. Repetti
Received: 18 April 2018 / Accepted: 11 May 2018
© Italian Society of Endocrinology (SIE) 2018
Background Pituitary tumors are common lesions, and they represent the second most frequent primary brain tumor. Their
classiﬁcation has undergone several changes over time. The World Health Organization conducts periodic expert review/
consensus meetings and publishes the results as recommendations for changes in classiﬁcation, based on advances in
molecular and genetic advances. This paper summarizes the results of the 2017 WHO Classiﬁcation, which recommends
several important changes.
Purpose This paper provides a review of the major changes and issues leading to an understanding of the basis for a new
pituitary tumor classiﬁcation. They include the rejection and modiﬁcation of prior conceptual and pathological characteristics
of these neoplasms. There is also considerable concern related to invasive and recurrent pituitary tumors which follow a less
benign course than the typical pituitary adenoma.
Methods A review of the outcome data for the previously designated “atypical” pituitary tumor category revealed that the
former criteria were not adequate to support their ability to predict with accuracy the clinical course of a given tumor. A
similar review was accomplished regarding the role of the p53 tumor suppressor mutation. Again, there was no reliable
contribution of p53 status to tumor aggressiveness. Other changes have occurred regarding the cytogenetic lineage of the
various subtypes of pituitary adenoma. The transcription factors Pit-1, SF-1, and TPit play a major role in determining tumor
subtypes and have become part of the classiﬁcation criteria.
Results These advances now help provide the background for more reliable and consistent classiﬁcation of pituitary adeno-
mas. Further deﬁnition of aggressive characteristics such as cavernous sinus and dural invasion remain to be considered in
the quest to make more accurate prognostic projections based on histopathological analysis.
Conclusions The 2017 WHO Classiﬁcation of Pituitary Tumors provides a more solid basis for accurate and reliable prog-
nostic assessment of these lesions. Further progress undoubtedly will be made as the recommendations of this update are
incorporated in to routine use.
Keywords Pituitary adenomas · Pituitary tumors · Classiﬁcation · PitNet · Pituitary transcription factors
It is fascinating to reﬂect upon the evolution of the clas-
siﬁcation of pituitary adenomas, the second most common
primary brain tumor in humans [1, 2]. From the early days
of tinctorial evaluation as chromophobe, acidophil, and
basophil lesions, great advances have steadily been made
in our ability to eﬀectively characterize pituitary adeno-
mas and their pathobiology [3–5]. With improvements in
histopathological analysis techniques, it became apparent
that some pituitary adenomas expressed abnormal levels of
speciﬁc hormones on the cellular level, often resulting in
increased systemic levels, and that some demonstrated no
pituitary speciﬁc or systemic elevation in hormone activity.
The advance of immunohistochemical staining for various
pituitary hormones formed a major part of subsequent clas-
siﬁcation systems [6–8]. These were temporarily sophisti-
cated by ultrastructural features from electron microscopy,
and later, by the discovery of tumor-speciﬁc transcription
factors and promoters that currently form the presumed
* E. R. Laws Jr.
Department of Neurological Surgery, Brigham and Women’s
Hospital, Harvard Medical School, 60 Fenwood Road, BTM,
4th Floor, Boston, MA 02115, USA