Tumors and adenomas: “to NET or not to NET.”

 From the desk of Jorge D. Faccinetti Pituitary World News co-founder – There seems to be a debate going on in the scientific and clinical pituitary world about what to call pituitary adenomas. The simple interpretation of the discussion centers on one group arguing to continue to classify them as pituitary adenomas, the other, changing the classification to Pituitary Neuro Endocrine Tumors or Pit-NET’s.

Since this is something that could potentially affect us all, we thought it was worth taking a look, and sharing some thoughts on the subject. And, since there is so much discussion about voice-of-the-patient initiatives, this is a perfect opportunity to offer our voice.

My first reaction: do we really care what they call them, unless, changing or redefining their nomenclature affects how a patient is treated, or how research and knowledge of pituitary disease are advanced. However, after reading some of the literature on the subject, it is much more evident to me that changing the name and designation of these tumors may confuse more than clarify. The arguments made by the proponents of change don’t offer any real advantages to patients and, as mentioned in the documents attached, may, in fact, confuse and increase patient anxiety.

During the process of digging a bit deeper to understand both points of view, we felt it was essential to get input from patients, and subsequently use those opinions to write an article that offers our views. Here are some of the particulars:

__________

The paper, A tale of pituitary adenomas: to NET or not to NET: Pituitary Society position statement. Authored by Ken K. Y. Ho · Maria Fleseriu · John Wass · Aart van der Lely · Ariel Barkan · Andrea Giustina · Felipe F. Casanueva · Anthony P. Heaney · Nienke Biermasz · Christian Strasburger · Shlomo Melmed, offers an excellent explanation of the debate.  This is an excerpt from a section of the paper cited above: (you can review an abstract of the article here)

 “Tumor and adenoma definitions 

As defined by standard textbooks, a tumor is a non-specific word connoting a neoplasm, an abnormal growth of cells, which can either be benign or malignant. An adenoma is a benign tumor arising from glands in epithelial tissue. According to the Club proposal, the rationale for using ‘tumor’ is the recognition of similarities to NETs in ‘unpredictable malignant behavior.’ However, tumor is a non- specific term for a neoplasm. The connotation that tumors harbor unpredictable malignant behaviors brings an unwarranted change to a time-honored definition. 

Replacing ‘adenoma’ with ‘tumor’ creates additional ambiguity because it implies that pituitary adenomas do not necessarily originate from the glandular structures of epithelial tissues, evoking confusion and inaccuracies about their lineage origin. If replacing adenoma with tumor is adopted, the proposal not only embeds a sinister tone to neutral nomenclature but could also wrongly denote that pituitary neoplasms may not arise from glandular epithelial tissue.” 

__________

In the paper Aggressive pituitary tumours and carcinomas: two sides of the same coin? Jacqueline Trouillas, Pia Burman, Ann McCormack, Stephan Petersenn, Vera Popovic, Olaf Dekkers Gerald Raverot,proponents of the name change argue that some aggressive pituitary adenomas are exactly the same as pituitary carcinoma, and that is very relevant for a smaller percentage cases.

These excerpts provide additional background:

 Abstract The European Society of Endocrinology (ESE) survey reported on the largest cohort of 125 aggressive pituitary tumours (APT) and 40 pituitary carcinomas (PC). Whilst the survey focused on treatment effectiveness, all pathological data were not explored in detail. Here, we comment on some interesting pathological findings, notably the difference between APT and PC.

 Comment The ESE collaborative study demonstrated a high degree of similarity between the 125 APTs, defined as ‘an invasive tumour with rapid growth, multiple recurrences and resistance to standard therapies’ and the 40 PCs with metastatic disease.

 The paper explores the differences between aggressive pituitary adenomas and pituitary carcinomas. Here are some additional excerpts:  

“Nevertheless, as has been demonstrated, APT and PC are clinically and histologically similar, so we suggest that APTs are ‘tumours with malignant potential without metastasis’. It is one of the reasons why it has been proposed to change the term pituitary adenomas to Pituitary NeuroEndocrine Tumours (PitNET) (5). However, it must be underlined that the majority of pituitary tumours (50– 60%) are benign (adenomas) and that the great majority of malignant tumours remain well differentiated. We propose the following diagram (Fig. 2) of pituitary tumour behaviour, knowing that hyperplasia was never observed before or associated with tumour formation and assuming that the great majority of patients are cured or controlled by surgery, with or without radiotherapy or standard medical therapies.”

ConclusionIn conclusion, the diagnosis of a malignant pituitary tumour remains difficult. Given that both APT and PC result in premature death as a result of tumour progression, we propose that an aggressive pituitary tumour is considered a tumour with malignant potential. The management of these patients must be multidisciplinary, with a dialogue between the endocrinologist, the neurosurgeon and the pathologist.” 

__________

To add a bit more background, I asked Dr. Blevins to weigh in on the arguments and give us his thoughts on the matter. Here are his views.

Dr. Blevins writes:

 This excellent article, by Dr. Ho and others, precisely echoes my thoughts and feelings, and the views of those who do pituitary pathology at UCSF, regarding the proposed changes in the naming and designation of pituitary adenomas.  

The pituitary is a distinct gland. Many of these so-called NETs, or neuroendocrine tumors, derive from neuroendocrine cells that do not form or come from a gland, but instead are scattered throughout the gastrointestinal and respiratory systems and other tissues. They are important in the function of these other organs systems and release hormones that, mostly, act locally, and not so much in distant tissues. Pituitary tumors, or adenomas, or whatever you want to call them, even though the cells are neuroendocrine, come from a distinct anatomic location and deserve a classification of their own. Pituitary hormones may have what we refer to as autocrine and paracrine actions. Still, they mostly have endocrine actions in that the hormones are secreted into the bloodstream and act on distant tissues. This is very distinct and different when compared to most neuroendocrine cells that go awry and form neuroendocrine tumors. Furthermore, in other distinct neuroendocrine tissues, such as the islet cells of the pancreas, the adrenal medullae , the parathyroid glands, etc., tumors are characterized according to their site and/or cell type and they’re not classified, for now at least, as pancreatic neuroendocrine tumors, parathyroid neuroendocrine tumors, or adrenal medulla neuroendocrine tumors. In some ways, I understand the “pituitary pathology club” want and desire to recognize that these tumors are more than adenomas, and many of them are of intermediate aggressiveness between a simple benign tumor and a carcinoma. I wanted to do this for years! I’ve long been a proponent of defining some of these invasive tumors as low-grade carcinomas. I will say, however, that a change in nomenclature is not going to do anything at all to clarify this issue and raise awareness of the points to be made but, instead, will confuse the issue for physicians and patients alike.  

My advice to the club and the proponents of the changes will be to drop their proposed recommendation and get back to the figurative drawing board!”  Dr. Lewis Blevins is the Medical Director of the California Center for Pituitary Disorders at the University of California, San Francisco, and co-founder of Pituitary World News.

_________

If you are interested in learning more and obtaining access to the papers mentioned in the article, please email us a request.  We look forward to your participation.

Thank you all for taking the time to read these materials, consider the implications, and sharing your thoughts and opinions. We look forward to hearing from you.  Thank you,

PWN

 

Image by Gerd Altmann from Pixabay

© 2019, Pituitary World News. All rights reserved.

LEAVE A REPLY

Please enter your comment!
Please enter your name here