Pituicytoma

Pituicytoma Robert J. Kowalski, MD, Richard A. Prayson, MD, and Marc R. Mayberg, MD Pituicytoma is a rare, low-grade neoplasm that originates in the neurohypophysis of the pituitary gland. We report the clinicopathologic features of a pituicytoma arising in a 52-year-old man who presented with a mass and panhypopituitarism, clinically suggestive of a pituitary adenoma. The tumor was marked by a proliferation of elongated cells arranged in bundles and interlacing fascicles. The tumor demonstrated positive staining with S-100 protein and glial fibrillary acid protein antibodies. The tumor did not stain with antibodies to cytokeratin, synaptophysin, chromogranin, anterior pituitary hormones, or p53. An MIB-1 labeling index of 1.1% was observed. The tumor was subtotally resected and recurred 11 months after the initial surgery. The literature on this rare tumor will be reviewed and differential diagnosis discussed. Ann Diagn Pathol 8: 290-294, 2004. © 2004 Elsevier Inc. All rights reserved. Index Words: Pituicytoma, pituitary gland, neurohypophysis, tumor

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RIMARY TUMORS arising in the neurohypophysis of the pituitary gland are rare, with granular cell tumors representing the most common type. Less commonly, pituicytomas (infundibulomas) arising presumably from pituicytes have been described. Pituicytes are glial cells that normally reside in the neurohypophysis and pituitary stalk. Relatively few reports of pituicytoma exist in the literature.1-7 We report a case of pituicytoma arising in a 52-year-old man which was clinically thought to represent a pituitary adenoma. The histologic appearance and immunohistochemical profile is described and differential diagnosis discussed. Methods and Materials All available histologic materials were reviewed. A representative section of tumor was selected for immunostaining. Immunostains were performed using an avidin-biotinylated immunoperoxidase methodology with microwave processing as previously described.8,9 The antibody dilutions used and source of antibodies are summarized in Table 1. An

From the Departments of Neurosurgery and Anatomic Pathology, Cleveland Clinic Foundation, Cleveland, OH. Address reprint requests to Richard A. Prayson, MD, Department of Anatomic Pathology (L25), Cleveland Clinic Foundation, 9500 Euclid Ave, Cleveland, OH 44195. © 2004 Elsevier Inc. All rights reserved. 1092-9134/04/0805-0006$30.00/0 doi:10.1016/j.anndiagpath.2004.07.006

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MIB-1 labeling index was determined as the percentage of positive staining tumor cell nuclei; 1,000 tumor cells were evaluated from the region of the tumor with the most staining. The medical record was reviewed for pertinent clinical information regarding presentation and treatment. Case Report A 52-year-old, right-handed man was referred for a presumed nonsecretory pituitary macroadenoma presenting with hypopituitarism. He described a 15-year history of gynecomastia and progressively decreased libido, which had been especially prominent over the previous 3 to 6 months. In the course of his evaluation, a low testosterone level was noted and a subsequent endocrine work-up showed a mild to moderate panhypopituitarism. He had a history of an excised goiter and was taking thyroid hormone replacement. The hypopituitarism prompted a magnetic resonance imaging (MRI) study, which showed a 3.0 ⫻ 2.8 cm heterogenous enhancing sellar mass with suprasellar extension and distortion of the optic chiasm. The tumor was solid and appeared well circumscribed (Fig 1). The patient denied any visual changes, and visual field tests were normal. There was no history of headaches, change in mental status, or other neurologic symptoms. After being started on testosterone and cortisone, he noted a marked improvement in his energy level and libido. A transphenoidal resection was performed, but

Annals of Diagnostic Pathology, Vol 8, No 5 (October), 2004: pp 290-294

Pituicytoma Table 1. Summary of Immunohistochemical Staining of Pituicytoma Immunostaining Antibody

S-100 protein

Dilution

1:200

Source

Dako, Carpinteria, CA GFAP 1:600 Dako Synaptophysin 1:20 Dako Chromogranin 1:100 Dako Cytokeratin 1:200 Boehringer AE1/3 Mannheim Indianapolis, IN ACTH 1:1000 Dako PL 1:800 Dako GH 1:2500 Dako FSH 1:600 Dako LH 1:640 Dako TSH 1:8000 Dako P53 1:20 Dako MIB-1 LI 1:10 Novocastra Laboratories New Castle Upon Tyne, UK

Result

Diffuse positive Focal positive Negative Negative Negative

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4); scattered glial fibrillary acid protein (GFAP) immunoreactivity was also observed. The tumor did not stain with antibodies to synaptophysin, chromogranin, cytokeratin AE1/3, p53, or anterior pituitary hormones (adrenocorticotrophic hormone, prolactin, growth hormone, follicle-stimulating hormone, luteinizing hormone, and thyroid stimulating hormone). An MIB-1 labeling index of 1.1% was determined. Discussion

Negative Negative Negative Negative Negative Negative Negative 1.1%

Abbreviations: GFAP, glial fibrillary acidic protein; ACTH, adrenocorticotrophic hormone; PL, prolactin; GH, growth hormone; FSH, follicle-stimulating hormone; LH, luteinizing hormone; TSH, thyroid-stimulating hormone; LI, labeling index.

was limited by the vascularity of the lesion. A postoperative MRI at 6 weeks showed that the residual tumor rim did not involute into the central cavity, and was still contiguous with the optic chiasm, which was not distorted. With hormone replacement, the patient has felt extremely well and has not had any visual symptoms, headaches, or other problems. Eleven months postoperatively, there was evidence of tumor progression on MRI and the patient received a course of radiation therapy. Histologically, the tumor consisted of a sheets of spindled cells arranged in interlacing fascicles and bundles (Fig 2). The cells were marked by prominent eosinophilic cytoplasm and distinct cell borders (Fig 3). Nuclei were oval to elongated with small nucleoli. There was no evidence of Rosenthal fibers, granular bodies, or Herring bodies. Only rare mitotic figures were identified (highest count, 1 mitotic figure/10 high power fields). Vascular proliferative changes, calcification, and necrosis were not present. The immunohistochemical staining results are summarized in Table 1. The tumor showed diffuse positive staining with S-100 protein antibody (Fig

Pituicytomas presumably arise from pituicytes, which are specific glial cells that are the predominant nucleated cells of the pituitary neurohypophysis and infundibulum. The proximity of pituicytes to vessels and their configuration, with cell cytoplasm enveloping axonal termination, suggest that the normal pituicyte may play a role in the regulation of hormone release. It has also been suggested that the pituicytoma may arise from folliculo-stellate cells of the normal adenohypophysis.1,10 These cells presumably regulate the secretion of endocrine cells and can function as stem cells with the potential to differentiate into endocrine type cells. Cases of true pituicytomas are rare in the literature.1-7 The largest series to date consisted of nine tumors pooled from several large institutions and reported by Brat et al in 2000.6 Their series con-

Figure 1. T1-weighted MRI study with gadolinum enhancement of a relatively circumscribed appearing pituicytoma.

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Figure 2. Low-magnification appearance of pituicytoma demonstrating a vaguely lobulated pattern.

sisted of six men and three women, who ranged in age from 30 to 83 years. The most common presentations included visual symptoms in five patients, headaches in four patients, and similar to the current case, hypopituitarism in two patients. On imaging, most tumors were solid, enhancing masses, located either in the sellar (N ⫽ 4) or suprasellar area (N ⫽ 5). The histopathologic features in the current case are similar to those reported by Brat et al.6 The

Figure 3. A mixture of rounded and spindled cells with mild nuclear pleomorphism marks pituicytoma.

tumor is typically marked by a proliferation of somewhat elongated cells arranged loosely into bundles or fascicles with a storiform pattern. Cell proliferation is low, as evidenced by the paucity of mitotic figures and low cell proliferation indices (MIB-1 labeling index of 1.1% in the current case and MIB-1 labeling indices ranging from 0.5 to 2% as reported by Brat et al6). The immunohistochemical profile, as typified by the current case, is marked by diffuse S-100 protein immunoreactivity

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Figure 4. Diffuse positive immunostaining with S-100 protein antibody is characteristic of pituicytoma.

and more variable GFAP staining. Neuroendocrine, keratin, and anterior pituitary hormone markers are negative. We also did not observe p53 staining, which has not to our knowledge been previously examined in these tumors. Ultrastructural features of these tumors include intermediate molecular weight cytoplasmic filaments, abundant mitochondria, and intermediate junctions.1,5,6 Previously, reports have indicated a generally benign clinical course for these tumors. In the Brat et al series,6 six tumors underwent gross total resection and three tumors were subtotally resected. Five tumors did not recur with follow-up intervals ranging from 13 to 99 months. Two subtotally resected tumors locally recurred at 20 and 26 months, and the remaining subtotally resected tumor was stable 8 months postoperatively. In the three tumors reported by Figarella-Branger et al,5 no recurrence were noted 2 years, 4 years, and 11 years after surgery. In the current report, the subtotally resected tumor recurred 11 months later. Although data are limited, most tumors behave in a benign fashion with a risk of recurrence being associated with subtotal resection. Currently, there does not appear to be any clear-cut role for adjuvant chemotherapy or radiation therapy in the management of these tumors, although experience is limited. The differential diagnosis focuses on other tumors that arise in the vicinity of the sella. Granular

cell tumors are the most common primary tumors of the neurohypophysis. Although granular cell tumors may have focal spindled areas, they tend to be marked by cells with more abundant, eosinophilic granular cytoplasm. The immunohistochemical profile between the two tumors may be similar, although GFAP immunoreactivity is somewhat uncommon in granular cell tumors. It is thought that granular cell tumors may arise from a different subgroup of pituicytes. Historically, pilocytic astrocytomas involving the pituitary stalk have been erroneously referred to as pituicytomas.11 Although both tumors are glial in derivation, pilocytic astrocytomas are unique tumors with distinctive morphology including a biphasic pattern (compact and loose), Rosenthal fibers, granular bodies, and areas of intense GFAP immunoreactivity. On imaging studies, pituitary adenoma may enter the differential diagnosis. In contrast to the pituicytoma, adenomas are generally more epithelial in appearance, although rare spindled adenomas exist. Adenomas are generally S-100 protein and GFAP negative and frequently stain with synaptophysin. Spindled meningiomas or rare sellar schwannomas may also mimic pituicytoma. The pituicytoma lacks whorling, psammoma bodies, nuclear pseudoinclusions (cytoplasmic invaginations), and collagen deposition; features that mark meningioma. A

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minority of meningiomas stain with S-100 protein, usually focally, in contrast to the strong diffuse immunoreactivity observed in pituicytoma. Also, meningiomas do not stain with GFAP. Schwannomas clinically are characterized by Antoni A and B patterns, Verocay bodies, and thickened vessels, none of which are features of pituicytoma. Although both tumors share similar S-100 protein immunoreactivity, GFAP staining is not a feature of schwannoma. Acknowledgment The authors thank Denise Egleton for her assistance in the preparation of this manuscript.

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resonance imaging and pathological analysis of a pituicytoma: Case report. Neurosurgery 1994;35:314-317 3. Jenevein EP: A neurohypophyseal tumor originating from pituicytes. Am J Clin Pathol 1964;41:522-526 4. Schultz AB, Brat DJ, Oyesiku NM, et al: Intrasellar pituicytoma in a patient with other endocrine neoplasms. Arch Pathol Lab Med 2001;125:527-530 5. 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;104:313-319 6. Brat DJ, Scheithauer BW, Staugaitis SM, et al. A distinctive low-grade glioma of the neurohypophysis. Am J Surg Pathol 2000;24:362-368 7. Scothorne CM: A glioma of the posterior lobe of the pituitary gland. J Pathol Bacteriol 1955;69:109-112 8. Tubbs RR, Sheibani K: Immunohistology of lymphoproliferative disorders. Semin Diagn Pathol 1984;1:272-284 9. Goldblum JR, Shannon R, Kaldjian EP, et al: Immunohistochemical assessment of proliferative activity in adrenocortical neoplasms. Mod Pathol 1993;6:663-668 10. Inoue K, Couch EF, Takano K, et al: The structure and function of folliculo-stellate cells in the anterior pituitary gland. Arch Histol Cytol 1999;62:205-218 11. Rossi M, Bevan JS, Esiri MM, et al: Pituicytoma (pilocytic astrocytoma). J Neurosurg 1987;67:768-772