Case 1 -

Pituicytoma, WHO Grade I M. Beatriz Lopes University of Virginia Health Sciences Center Charlottesville, VA

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Clinical History The patient is a 51-year-old who was incidentally found to have pituitary macroadenoma on workup for nasal bleeding and sinusitis. A sellar lesion was noticed on the CT scan which prompted an MRI. The MRI demonstrated a 1.8 x 1.6 x 1.7 cm tumor (Figure 1), most consistent with a macroadenoma. This lesion was displacing the optic chiasm superiorly. In retrospect, the patient has been having blurry vision on the left side associated with headaches for a few months. The patient denies any symptoms consistent with pituitary excess or deficiency syndromes. Her menstrual cycles have been abnormal for the last 3 years. She denies any breast discharge, changes to her hands or feet size or facial appearance, and she denies a significant weight gain. She denies any significant mood disturbances. Her physical examination was unremarkable. The scalp has no focal alopecia. The bony structures of the face are within normal limits. There is no prognathism of the lower jaw. There is no dental malocclusion in the mandibular teeth. Pupils are equal, round, and reactive to light. Extraocular muscles are intact. The neck exam does not reveal any thyromegaly or thyroid nodules. Her laboratorial exams showed a cortisol of 14 at 7:45 in the a.m., growth hormone 0.1, prolactin 9.1, free T4 0.8, TSH 3.1, and ACTH 25; all values within the normal range. FSH and LH were 12.6 and 4.2 respectively, adequate for a peri-menopausal age. The patient underwent a sublabial trans-sphenoidal surgical resection of the lesion. Case 1 - Slide 1 Click to view with ImageScope Click to view with a Web-Based Viewer Case 1 - Figure 1 T1-weighted sagittal MRI and T1-weighted MRI with gadolinium (left) showing a sellar-suprasellar lesion with compression of the optic chiasma. Case 1 - Figure 2 Elongated, fibrillary cells arranged in fascicular pattern. Case 1 - Figure 3 High magnification highlights the fibrillary nature of the tumor cells. Case 1 - Figure 4 Sharp demarcation with normal anterior pituitary is seen on H&E and reticulin (Figure 5). Case 1 - Figure 5 The tumor cells lack pericellular deposition of reticulin. Reticulin impregnation highlights the sharp demarcation with the anterior pituitary. Case 1 - Figure 6 Tumor cells are strongly immunoreactive for GFAP. Case 1 - Figure 7 A subset of cells shows immunoreactivity for vimentin. Case 1 - Figure 8 The majority of tumor cells are immunoreactive for S-100. Case 1 - Figure 9 Ultrastructural analysis reveals spindle cells with abundant intermediate filaments. There is no pericellular deposition of basal lamina-like materials. Case 1 - Figure 10 The cells lack neurosecretory granules and abundant mitochondria. Introduction: This case discusses the differential diagnosis of spindle- cell neoplasms that may involve the pituitary gland. Pathological/Microscopic Findings and any Immunohistochemical or Other Studies: The tumor is composed of elongate, spindle-shape cells arranged in fascicles. There is no particular arrangement of the tumor cells including Verocay bodies or meningothelial whorls. The tumor shows sharp demarcation from the anterior pituitary. There is no identification of the posterior pituitary in the specimen. Immunohistochemistry shows diffuse and strong reactivity for GFAP and S-100. Vimentin is also immunoreactive in many of tumor cells. There is no demonstration of EMA (not shown), chromogranin (not show) or pituitary hormones (not show). Ultrastructural studies show spindle-cells with the cytoplasm filled with intermediate filaments. Neurosecretory granules are not seen. Mitochondrial population is within normal limits. There is no evidence of basal lamina-like depostion around the tumor cells. Differential Diagnoses: 1. Pituicytoma 2. Spindle cell oncocytoma of the adenohypophysis 3. Schwannoma 4. Meningioma Final Diagnosis: Pituicytoma, WHO grade I Case Discussion: Pituicytomas are a special subtype of low-grade astrocytoma that originates in the posterior pituitary or infundibulum. These astrocytic tumors have been in the past denominated as posterior pituitary astrocytomas or infundibulomas; however, the WHO recommends the denomination of pituicytomas for the tumors [11]. Pituicytomas are believed to originate from pituicytes, the intrinsic glial cells of the posterior pituitary gland, from where the name "pituicytoma" is derived. They are rare tumors; the most comprehensive review reported nine of such cases [1]. The majority of the tumors involve adults (5th and 6th decades), with a slight male predominance [11]. Clinical Presentation: The clinical presentation of pituicytomas depends primarily on their size and mass effect in adjacent structures of the sella. The majority of patients presents with visual symptoms and signs of hypopituitarysm. Rarely, the patients may have signs and symptoms of diabetes insipidus. Therefore, the clinical presentation is very similar to large, non-functioning pituitary adenomas. Imaging Findings: MR imaging findings are not specific, but usually show a well-circumscribed and solid intrasellar mass, most of the time with suprasellar extension. The tumor usually presents low signal intensity on T1WIs, low to intermediate intensity on T2WIs, and fairly homogenous enhancement on postcontrast T1WIs [9]. Pathological findings: Histologically, the tumors are composed of elongate, piloid astrocytes arranged in fascicles, in a pattern that resembles pilocytic astrocytoma. However, the tumors lack typical biphasic pattern of pilocytic astrocytomas, formation of Rosenthal fibers, and eosinophilic granular bodies. The tumor cells are typically immunoreactive for vimentin and S-100 protein. The majority of the pituicytomas express GFAP, but the immunoreactivity is variable and may be absent [1, 2, 3]. Although pituicytomas are generally negative for EMA, focal EMA immunoreactive has been documented in some cases [1, 2]. Pituicytomas do not show any immunoreactivity for neuroendocrine markers including chromogranin or for pituitary hormones. The MIB-1 labeling index is generally low. Differential diagnoses: Differential diagnoses include spindle cell oncocytoma of the adenohypophysis, schwannoma, and meningioma. All three of these tumors may have similar histological appearance of a low-grade spindle-cell tumor with cells arranged in fascicles, however each tumor has diagnostic particularities. Immunohistochemical and ultrastructural examinations are essential for performing the correct diagnosis. Schwannomas and meningiomas are in practical terms easier to differentiate from pituicytomas than spindle cell oncocytomas. Although schwannomas are strongly and diffusely immunoreactive for S-100 protein, they only rarely show GFAP immunoreactivity; pericellular reticulin deposition, as seen by light microscopy, and basal membrane- like material demonstrated by electron microscopy are features rarely seen in pituicytomas [7]. As for meningiomas, the strong EMA immunoreactivity in the majority of tumors, lack of GFAP immunoreactivity, and the presence of interdigitating cell processes and desmosomes at ultrastructural analysis are diagnostic. The most difficult differential diagnosis is the spindle cell oncocytoma. Spindle cell oncocytomas are immunoreactive for EMA, vimentin, S-100, and galectin-3; they do not express GFAP [5, 8]. As mentioned previously, GFAP immunoreactivity in pituicytomas is variable and may even be absent. Although pituicytomas are generally negative for EMA, focal EMA immunoreactive has been documented in some cases [1, 2]. Ultrastructural analysis may be helpful for the distinction of these two entities, but not without reservations. Pituicytoma cells containing abundant cytoplasmic filaments and scattered "intermediate" intercellular junctions [1, 3, 11]. A key element for the diagnosis of spindle cell oncocytoma, as revealed by its name, is the presence of abundant accumulation of mitochondria [5, 8]. However, abundant mitochondria have been described in 3/3 pituicytomas analyzed by Brat et al. [1] and in the case studied by Figarella-Branger et al. [3]. The similarities between pituicytoma and spindle cell oncocytoma appear to not be restricted to their morphological and immunohistochemical aspects. The recent observation of TTF-1 expression in normal pituicytes and tumors of the pituitary region, including pituicytomas, granular cell tumors of the neurohypophysis, and spindle cell oncocytoma, raises the possibility that these tumors may represent different variants of a common pathogenetic origin [6]. Histogenesis: Pituicytomas have long been considered arising from pituicytes, a modified glial cell of the neurohypophysis believed to regulate neurohypophysial hormone secretion [4]. As discusssed above, the recent description of TTF-1 expression in normal pituicytes and pituicytomas has emphasized the leading hypothesis that pituicytomas are histogenetically related to pituicytes [6]. However, an alternative origin from the folliculo-stellate cells (FSC) has also been proposed based upon ultrastructural similarities between FSCs and pituicytomas [2]. Likewise, Ulm et al. [10] have suggested a derivation from FSC based upon the presence of bcl-2 immunoreactivity in both FSCs and pituicytomas, and lack of bcl-2 immunoreactivity in the neurohypophysis. Prognosis: Due to their rarity, the precise clinical behavior of these astrocytomas is not fully identified. However, the majority of the cases reported thus far behaved as low-grade tumors, with some tendency for recurrence after subtotal excision [9]. Conclusion(s): Pituicytomas are rare astrocytic tumors from the posterior pituitary that can manifest with clinical and radiological features similar to non-functioning pituitary adenomas. The differential diagnosis between pituicytomas and other spindle-cell tumors involving the pituitary gland region may be problematic. Careful histological, immunohistochemical and ultrastructural examination of these tumors is recommended for appropriate diagnosis. References: Brat DJ, Scheithauer BW, Staugaitis SM et al. Pituicytoma. A distinctive low-grade glioma of the neurohypophysis. Am J Surg Pathol. 2000; 24: 362-8. Cenacchi G, Giovenali P, Castrioto C, et al. Pituicytoma: ultrastructural evidence of a possible origin from folliculo-stellate cells of the adenohypophysis. Ultrastruct Pathol. 2001; 25:309-12. Figarella-Branger D, Dufour H, Fernandez C, et al. Pituicytomas, a mis-diagnosed benign tumor of the neurohypophysis: report of three cases. Acta Neuropathol. 2002; 104: 313-9. Hatton GI. Pituicytes, glia, and control of terminal secretion. J Exp Biol. 1988; 139: 67-79. Kloub O, Perry A, Tu PH, et al. Spindle cell oncocytoma of the adenohypophysis: report of two recurrent cases. Am J Surg Pathol. 2005; 29:247-53. Lee EB, Tihan T, Scheithauer BW, et al. Thyroid transcription factor 1 expression in sellar tumors: a histogenetic marker? J Neuropathol Exp Neurol. 2009; 68:482- 8. Maartens NF, Ellegala DB, Vance ML, et al. Intrasellar schwannomas: report of two cases. Neurosurgery. 2003; 52:1200-6. Roncaroli F, Scheithauer BW, Cenacchi G, et al. 'Spindle cell oncocytoma" of the adenohypophysis: a tumor of follicostellate cells?. Am J Surg Pathol. 2002; 26: 1048-55. Shah B, Lipper MH, Laws ER, et al. Posterior pituitary astrocytoma: a rare tumor of the neurohypophysis: a case report. AJNR Am J Neuroradiol. 2005; 26:1858-61. Ulm AJ, Yachnis AT, Brat DJ, et al. Pituicytoma: report of two cases and clues regarding histogenesis. Neurosurgery. 2004; 54: 753-8. Wesseling P, Brat DJ, Fuller GN. Pituicytoma. In: Louis DN, Ohgaki H, Wiestler OD, Cavenee WK (eds): WHO Classification of Tumours of the Central Nervous System. IARC, Lyon. 2007.