Contributed by Fabio Rogerio, MD, PhD1; Jo„o Vitor Gerdulli Tamanini1; Gunter Gerson, MD2; Thiago Costa Haiter1; Luciano de Souza Queiroz, MD, PhD1; Mateus Dal Fabbro, MD3
Departments of 1Pathology and 3Neurology, State University of Campinas (UNICAMP), Campinas, Brazil.
Department of 2Pathology and Forensic Medicine, Federal University of CearŠ (UFC), Fortaleza, Brazil.
A 79-year-old woman was admitted with sporadic headache for over 5 years and slow growth of feet. On physical examination, coarse facial features, prognathism and enlargement of hands were also noted. There were no visual complaints. Blood tests indicated increased levels of growth hormone (GH; 9.36 ng/mL; normal values: 0.06 - 5.00 ng/mL) and somatomedin C (insulin-like growth factor 1 (IGF-1); 420.00 ng/mL; normal values (> 65 years): 55.00 - 200.00 ng/mL). Peripheral concentrations of other pituitary hormones were normal. CT and MRI scans showed an expansive lesion occupying the sella and measuring 12.2 x 5.7 x 7.65 mm with neither suprasellar extension nor invasion of the sphenoidal sinus (Figs. 1a and 1b). On MRI, the lesion was iso- or slightly hyperintense on T1-weighted images and no contrast enhancement was detected. The presumably remaining pituitary gland was noticed as an enhancing tissue displaced to the left. Comparisons of exams over 5 years indicated stable lesion volume. A transsphenoidal resection was performed. The specimen was submitted in totum to histological analysis.
Histological analysis showed a lesion mainly composed of cells arranged in clusters in a delicately fibrillated background reminiscent of neuropil, which contained abundant thick hyalinized collagen, reticulin fibers (demonstrable only with special stains) and lymphocyte-rich inflammatory foci (Fig. 1c). The preponderant cell type corresponded almost exclusively to abnormal neurons, mostly rounded, with abundant cytoplasm often with peripherally located Nissl bodies. Bi- or multinucleation were also detected (Fig. 1d). Vacuoles were seen in variable number and size in several of those neurons, some of which also contained cytoplasmic hyaline inclusion bodies. No obvious glial-like cells were apparent. Mitotic figures, vascular proliferation and/or necrosis were not found. On immunohistochemistry, neurons were positive for MAP2 (Fig. 1e) and non-phosphorylated neurofilament (SMI-32) (Fig. 1f), which disclosed abnormally oriented processes. Cytoplasmic corpuscles were strongly positive for AE1AE3 (Fig. 1g) and weakly for GFAP (Fig. 1h). Axons in the background stained with neurofilament protein. GFAP showed no cells with astrocytic morphology. Cellular proliferation marker (Ki-67) was only positive in inflammatory cells and always negative in neuron like cells (Fig. 1i). GH-positive cells were detected in the periphery of some of the fragments and likely represented normal adenohypophyseal tissue (Fig. 1j). What is your diagnosis?