Clinicopathological Features of Growth Hormone-Producing Pituitary Adenomas in 242 Acromegaly Patients: Classification according to Hormone Production and Cytokeratin Distribution

Abstract

The aim of this study was to clarify the relationship between the histological features of GH-producing adenomas surgically resected at the Toranomon Hospital and the clinical features of the patients. Histological examinations, including immunohistochemistry for anterior pituitary hormones and cytokeratin (CK), were performed on 242 consecutively excised GH-producing pituitary adenomas. Immunohistochemistry showed 45% of the adenomas to be monohormonal and 55% to be plurihormonal, producing GH-PRL (77%), GH-TSH (13%), and GH-PRL-TSH (10%). One-fourth of the monohormonal GH adenomas had a dot-like pattern of CK immunoreactivity in the majority of the tumor cells (>80%); they were significantly more common in female or younger patients and usually tended to be larger and more invasive than monohormonal GH adenomas with perinuclear CK. Interestingly, CK-immunonegative adenomas were found in only 5% of the patients; they also showed a tendency to be larger, suggesting that they are a distinct type of GH adenoma with clinically aggressive features. Serum hormone levels correlated well with tumor size only in GH-producing adenomas with a perinuclear pattern of CK immunoreactivity. Each histological subtype of adenoma, classified according to the pattern of CK immunoreactivity, was associated with distinct clinical characteristics. This information is useful for understanding the pathophysiology of acromegaly-causing GH-producing adenomas.

Differential somatostatin receptor (SSTR) 1–5 expression and downstream effectors in histologic subtypes of growth hormone pituitary tumors

“…Compared to previously published literature, in our cohort there was no difference in age, gender or tumor volume between two different GH tumors subtype patients likely due to our smaller sample size (Bakhtiar et al, 2010,Mazal et al, 2001,Kiseljak-Vassiliades et al, 2014,Bando et al, 1992,Obari et al, 2008,Mori, Inoshita, Takahashi-Fujigasaki et al, 2013). The response to surgery was dramatically different in patients with DG compared to SG growth hormone tumors similar to prior reports (Bakhtiar et al, 2010,Mazal et al, 2001,Kiseljak-Vassiliades et al, 2014).…”

Growth hormone tumor histological subtypes predict response to surgical and medical therapy

“…The distribution of GH tumors in our series (54.9% SG, 30.4% DG and 14.7% intermediate) was within the range of prior literature, which actually has been quite variable, with DG representing 39-79%, SG 13-35% and intermediate 5-57% of GH subtypes (see Table 2) [18,30,27,31,28,20,29,36,37]. These wide ranges may be attributed to variable subtyping classification systems used, as well as the grouping of DG and intermediate subtypes together, as preferred by some authors [29].…”

“…In our analysis, we combined DG and intermediate groups and confirmed that SG tumors more often occur in younger patients compared to DG [27,20,28,30,37]. Several studies reported that SG tumors are more frequently found in female patients [18,29,37,32]; however, in our population, and in agreement with four previous reports, there was no correlation between the gender and GH tumor subtype [28,30,20,31,29]. …”

“…Although cavernous sinus invasion characteristics and optic chiasm compression did not statistically differ, we noted a trend towards higher rate of invasive characteristics in SG tumors. Other groups have used the Wilson modification of Hardy's criteria and/or Knosp criteria and suggested that SG tumors are both larger and have more suprasellar extension or diffuse sellar invasion [27,18,20,28,38,37]. In contrast, a recent study from Fougner et al, reported no difference in tumor volume or tumor invasiveness between GH tumor subtypes, but small numbers of SG tumors likely limited the statistical power in that study [31].…”

Low 06-Methylguanine-DNA Methytransferase (MGMT) and Pan-Cytokeratin (PAN-CK) Expression via Immunohistochemistry in Pituitary Adenomas

“…Mori et al examined the pathological features of acromegaly. This study indicates that subclassification based on CK distribution will help to identify clinically aggressive monohormonal GH adenomas but not plurihormonal adenomas (35). In somatotroph adenomas, cases with oncocytic change showed higher percentages of Ki-67 (P = 0.05), but no correlation with extrasellar extension or cytokeratin staining (dot pattern versus perinuclear) was found (36).…”