February 2021 — Neuropathology
A 74-year-old man presented with symptoms of ongoing fatigue. His serologic studies demonstrated a minimally elevated prolactin, a borderline low cortisol, low gonadotropins, and a borderline low free T4. An MRI demonstrated a 2.2 x 2.4 x 1.9 cm heterogeneously enhancing mass filling and expanding the sella. He subsequently underwent a brain biopsy.
What is your diagnosis?
- Pituitary adenoma
- Spindle cell oncocytoma
- Granular cell tumor of the sellar region
The correct answer is ...
The diagnosis in this case is: spindle cell oncocytoma.
Spindle cell oncocytoma (SCO) is a rare, non-neuroendocrine neoplasm of the posterior pituitary gland. This entity was originally described in 2002 by Roncaroli et al., and, based on ultrastructural characteristics, was hypothesized to originate from folliculostellate cells of the anterior pituitary gland.1 By microscopy, SCO are typically composed of fascicles and lobules of spindle to epithelioid [TLL1] cells with a variable amount of eosinophilic cytoplasm [Figures 2-4].2 By immunohistochemistry, SCO typically express TTF-1 and S100 with variable expression of GFAP and EMA [Figure 5]. SCO are negative for chromogranin [Figure 5].2
The cell of origin of SCO is still unresolved. However, more recent studies suggest that the shared TTF-1 immunoreactivity of non-neoplastic pituicytes, pituicytomas, granular cell tumors, and SCO may suggest a similar origin of these tumors from the pituicytes of posterior pituitary gland.3-4 The three morphologically distinct tumors from pituicytes may be linked to the existence of multiple subtypes of pituicytes in the normal neurohypophysis and their shared ultrastructural characteristics. 4-5
Ultrastructurally, the neoplastic cells of SCO often are filled with mitochondria [Figures 6-7[TLL2] ]. This is in contrast to granular cell tumor of the sellar region, which is typically negative for GFAP and by electron microscopy has lysosome-rich cytoplasm.2
Pituitary adenoma is an incorrect answer in this case. SCO can present with identical clinical symptoms and imaging findings to a nonfunctioning pituitary macroadenoma [Figure 1]. However, by immunohistochemistry pituitary adenoma is positive for chromogranin and negative for TTF-1.2 Schwannoma is an incorrect answer in this case. Schwannomas have rarely been reported as occurring in the sellar region and may have similar clinical symptoms to a nonfunctioning pituitary macroadenoma.6 A helpful distinguishing feature from SCO is that schwannomas are negative for TTF-1 by immunohistochemistry.2
- Roncaroli F, Scheithauer BW, Cenacchi G, et al. ‘Spindle cell oncocytoma’ of the adenohypophysis: a tumor of folliculostellate cells? The American Journal of Surgical Pathology. 2002;26(8):1048-1055.
- Ed. Louis DN. WHO Classification of Tumours of the Central Nervous System. 4th edition. World Health Organization; 2016.
- Lee EB, Tihan T, Scheithauer BW, Zhang PJ, Gonatas NK. Thyroid transcription factor 1 expression in sellar tumors: a histogenetic marker? J Neuropathol Exp Neurol. 2009;68(5):482-488.
- Mete O, Lopes MB, Asa SL. Spindle cell oncocytomas and granular cell tumors of the pituitary are variants of pituicytoma: The American Journal of Surgical Pathology. 2013;37(11):1694-1699.
- Takei Y, Seyama S, Pearl GS, Tindall GT. Ultrastructural study of the human neurohypophysis. II. Cellular elements of neural parenchyma, the pituicytes. Cell Tissue Res. 1980;205(2):273-287.
- Perez MT, Farkas J, Padron S, Changus JE, Webster EL. Intrasellar and parasellar cellular schwannoma. Annals of Diagnostic Pathology. 2004;8(3):142-150.
Kathryn Eschbacher, M.D.
Resident, Anatomic Pathology and Neuropathology
Aditya Raghunathan, M.D., M.P.H.
Consultant, Anatomic Pathology
Associate Professor of Laboratory Medicine and Pathology
Mayo Clinic College of Medicine and Science