A neoplasm arising in adenohypophysial tissue that is composed of epithelial neuroendocrine cells of PIT1-lineage that express PIT1 and growth hormone (Asa and Perry 2020).
These tumors represent approximately 12% of surgically resected pituitary neuroendocrine tumors (Mete et al. 2018). They are almost evenly divided between densely granulated and sparsely granulated variants.
Somatotroph tumors can occur at almost any age; the mean age at diagnosis is 50 years for densely granulated tumors and 40 years for sparsely granulated tumors (Mete et al. 2018). However, these ages reflect what is known to be an average of a 10-year delay from onset of signs and symptoms to diagnosis.
There is no gender predilection for these tumors.
Somatotroph tumors usually arise in the sella turcica. They are usually macrotumors (>1 cm) at the time of diagnosis. They may arise in the sphenoid sinus where ectopic adenohypophysial tissue may be found.
Clinical and Biochemical Features
The vast majority of somatotroph tumors present with acromegaly and/or gigantism, as well as signs and symptoms of a sellar masses with headache and visual field loss. The main biochemical finding is elevated IGF-1 that reflects an integrated measure of GH; actual GH measurements may vary because of pulsatile secretion. Patients with densely granulated tumors usually have florid clinical features and very high levels of IGF1 and GH associated with smaller tumors that are hypointense on T2 weighted MRI. Patients with sparsely granulated tumors usually have more subtle clinical features and less dramatic elevations of IGF1 and GH, despite having much larger tumors that are hyperintense on T2 weighted MRI (Asa et al. 2017). Hypopituitarism is uncommon.
Surgery is the treatment of choice. Patients with residual unresectable tumor can be treated with somatostatin analogues and growth hormone receptor blockade with pegvisomant. Pretreatment prior to surgery may improve surgical outcomes. Patients with densely granulated somatotroph tumors are more likely to respond to somatostatin analogues and those with sparsely granulated tumors are more likely to require GH antagonist therapy (Asa et al. 2017; Ezzat et al. 2019).
If diagnosed early and the tumor is small and surgically resectable, the outcome is excellent. However, most patients have parasellar extension that precludes complete resection. Long-term medical therapy usually can control clinical and biochemical disease. The sequelae of GH excess are not reversible and failure of control can lead to long-term complications including cardiac disease, osteoarthritis, colonic polyps, and increased risk of malignancies.
These tumors have no specific gross morphologic features. They are usually soft and friable.
Densely granulated somatotroph tumors (Fig. 1) are the classical acidophilic tumors associated with acromegaly; they are composed of solid nests and sheets of large cells with abundant acidophilic cytoplasm and relatively monotonous nuclei. By electron microscopy, the large tumor cells have well-formed rough endoplasmic reticulum and Golgi complexes, and the cytoplasm is filled with large, relatively uniform electron dense secretory granules.
These tumors express nuclear PIT1 and cytoplasmic GH that is intensely positive in densely granulated tumors but may be weak and focal in sparsely granulated tumors. The densely granulated tumors also usually express alpha subunit of glycoprotein hormones. Somatotroph tumors are negative for TPIT, ER, GATA3, SF1, ACTH, PRL, TSH, FSH, and LH. Staining for keratins is characteristically perinuclear in densely granulated tumors. The hallmark of the sparsely granulated variant is the fibrous body that is decorated by the CAM 5.2 antibody or antibodies to cytokeratin 18.
The most common genetic alteration in pituitary neuroendocrine tumors is the presence of activating GNAS mutations in about half of somatotroph tumors; these are usually the densely granulated tumors (Spada et al. 1990). In contrast, sparsely granulated somatotroph tumors are found in patients with germline AIP mutations that are seen in the familial isolated pituitary adenoma (FIPA) syndrome (Vierimaa et al. 2006). While sporadic sparsely granulated tumors do not have AIP mutations, they may have epigenetic downregulation of that gene (Denes et al. 2015).
Mammosomatotroph tumor, plurihormonal tumor of PIT1-lineage, metastatic neuroendocrine tumor.
References and Further Reading
- Asa, S. L., & Perry, A. (2020). Tumors of the pituitary gland (AFIP atlas of tumor pathology, series 5). Silver Spring: ARP Press.Google Scholar
- Spada, A., Arosio, M., Bochicchio, D., Bazzoni, N., Vallar, L., Bassetti, M., et al. (1990). Clinical, biochemical and morphological correlates in patients bearing growth hormone-secreting pituitary tumors with or without constitutively active adenylyl cyclase. The Journal of Clinical Endocrinology and Metabolism, 71, 1421–1426.CrossRefGoogle Scholar