Immunohistochemical Subtypes of Growth Hormone-Secreted Pituitary Adenoma and Association with the Clinical Course and Secondary Malignancy

ABSTRACT Objective: Most of the acromegaly cases are caused by growth hormonesecreting pituitary adenoma. Pituitary adenomas are classified histologically into sparsely granulated adenoma (SGA) and densely granulated adenoma (DGA). SGAs have been reported to elicit a more aggressive clinical course and therapy resistance. The aim of this study was to investigate the immunohistochemical subtype of patients with pituitary adenoma and their relationship with the clinical course of the disease. Material and Methods: In the period between 2000 and 2016, about 40 (F21, M19) patients with acromegaly who were diagnosed and operated for pituitary adenoma at our university hospital were included in this study. The medical history of patients, duration of the disease, and comorbidities were assessed. Based on current guidelines for acromegaly management, we determined the serum growth hormone [with 75 g “oral glucose tolerance test” (OGTT)], insulin-like growth factor 1 (IGF-1) levels, as well as computed tomography (CT) or magnetic resonance imaging of the pituitary gland. Immunohistochemical staining of postoperative tissue materials and subtypes of pituitary adenomas were evaluated by an experienced cytopathologist. Results: Of the 40 acromegaly patients included in the study, 25 patients were evaluated as sparsely granulated and the remaining 15 patients were evaluated as densely granulated. The mean age of SG adenomas (40.6±9.7 vs. 48.6±5.7, p=0.04) was significantly lower. At the first visit, 64% of SG adenomas were macroadenoma while only 35% of DG adenomas were macroadenoma and the difference was not statistically significant (p=0.43). SG adenomas’ pre-treatment GH, IGF1 values (29.2 ng/mL, 800 ng/mL versus 8.4 ng/mL, 445 ng/mL, p=0.02) and post-treatment GH, IGF1 values (4.1 ng/mL, 440 ng/mL versus 0.4 ng/mL, 152 ng/mL, p=0.03) were significantly higher. While endocrine remission is more common in DG adenomas; organomegaly, abnormal echocardiographic findings (left ventricular hypertrophy) and multinodular goiter were more common in SG adenomas. Malignancy (renal cell Ca, thyroid Ca, larynx Ca) was detected in four patients and histopathological diagnosis of these patients was detected as SG adenoma. Conclusion: The immunohistochemical subtype of the pituitary adenoma may have the potential to affect the clinical course and therapy of acromegaly. SGA is more prone to cavernous sinus invasion, comorbidity and resistance to therapy. Carcinogenesis associated with malignancy was more common in patients with SGA. However, further studies are needed to confirm our findings.