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Neurology India
Medknow Publications on behalf of the Neurological Society of India
ISSN: 0028-3886 EISSN: 1998-4022
Vol. 58, Num. 2, 2010, pp. 316-318

Neurology India, Vol. 58, No. 2, March-April, 2010, pp. 316-318

Case Report

Primary pituitary fibrosarcoma presenting with multiple metastases: A case report and literature review

1 Department of Neurosurgery, The Affiliated Hospital of Medical College, Qingdao University, Qingdao - 266003; and Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing - 100730, China
2 Department of Neurosurgery, The Affiliated Hospital of Medical College, Qingdao University, Qingdao - 266003, China
3 Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing - 100730, China

Correspondence Address: Ren-Zhi Wang, Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 100730, Beijing, China,

Date of Acceptance: 01-Feb-2010

Code Number: ni10080

PMID: 20508360

DOI: 10.4103/0028-3886.63792


Even though many cases of pituitary fibrosarcoma (PF) have been reported, the etiologic classification of these tumors, however, remains undefined. Moreover, owing to the paucity of available case studies, the clinical characteristics of primary pituitary fibrosarcoma (PPF) have not been fully described. We report a 26-year-old female with pathologically confirmed PPF, who presented with features of elevated intracranial pressure, oculomotor nerve palsy, field defects and panhypopituitarism. Despite the combination therapy, which included tumor removal, radiotherapy, and chemotherapy, magnetic resonance imaging demonstrated multiple intracranial and extracranial metastases at a seven-month follow-up, and the survival duration from diagnosis was only 11 months. Based on a review of the literature, we propose preliminary etiologic classification criteria for PF as well as a new therapeutic approach to reduce PPF recurrence and metastasis, including extended surgical resection and postoperative whole-brain radiotherapy.

Keywords: Metastases, pituitary fibrosarcoma, pituitary adenoma, radiotherapy


Since the first description of a patient of pituitary fibrosarcoma (PF) with co-occuring chromophobe adenoma in 1959 by Terry et al.[1] , several additional cases have been reported. [2],[3],[4],[5],[6],[7],[8],[9],[10],[11] Almost all these cases have been considered to be radiotherapy-induced complication in patients with pituitary adenoma or craniopharyngioma [2],[3],[4],[5],[6] or a spontaneous malignant transformation of prolactinoma. [7],[8],[9] Till date only two cases of primary PF (PPF), unrelated to irradiation or adenoma, have been published. [10],[11] Here we report a third pathologically confirmed case of PPF.

Case Report

A 26-year-old female was admitted to our institution with complaints of severe headache, vomiting, diplopia, and diabetes insipidus of four weeks duration. A physical examination revealed slightly limited abduction of the left eye and bitemporal hemianopia. Laboratory blood testing showed panhypopituitarism: cortisol 0.88 ug/dl (4.0-22.3), prolactin 49.14 ng/ml (< 25), FSH 1.1 mIU/mL (1.27-113.59), LH2 0.3 mIU/mL (1.2-58.64), T3 0.36 ng/ml (0.66-1.92), T4 3.75 ug/dl (4.3-12.5), FT3 1.44 pg/ml (1.80-4.10), FT4 0.52 ng/dL (0.81-1.89). Magnetic resonance imaging (MRI) showed a heterogeneous gadolinium-enhanced sellar lesion that approached the optic chiasm and laterally bulged into the left cavernous sinus; a normal pituitary gland could not be separately identified [[Figure - 1]a and b]. The patient underwent neuronavigation-guided subtotal tumor resection via a trans-sphenoidal approach. The sellar floor and dura were eroded. We were able to suction the solid tumor, which was relatively firm and appeared grayish and vascular. After surgery, hormone replacement therapy for panhypopituitarism, adjuvant chemotherapy, and fractionated sellar irradiation were initiated. At seven months following the resection, the patient was readmitted with complaints of somnolence, unilateral blindness, tinnitus, and decreased hearing. A neurological examination revealed palsy of the left III, IV, VI, VIII, and XI cranial nerves. Ophthalmic examination revealed evident proptosis and complete vision loss in the left eye. Superficial cervical painless lymphadenectasis was palpable on the left side. Repeated MRI revealed multiple intracranial and cervical metastases and moderate obstructive hydrocephalus [[Figure - 1]c and d]. There was no evidence of distant metastasis from abdominal ultrasound and chest computed tomography. An infratentorial craniotomy was performed to remove a cerebellar metastasis completely. The patient died from cerebral herniation secondary to occipital metastasis hemorrhage four months after the operation [Figure - 1]e.

Tumor pathology showed spindle cells arranged in interlacing bundle pattern containing pleomorphic nuclei and frequent mitotic figures with a Ki67 labeling index of 80% [[Figure - 2]a and b]. Immunohistologic analysis demonstrated that the tumor cells were strongly stained for P53 [Figure - 2]c; moderately stained for vimentin; and negative for SMA, CD99, S-100, desmin, EMA, CD34, CD117, AE1/AE3, GFAP, and CgA.


Primary pituitary spindle cell tumor is an uncommon neoplasm. A differential diagnosis generally includes fibrosarcoma, pituicytoma, spindle cell oncocytoma (SCO), and solitary fibrous tumor (SFT). In this patient immunohistologic studies demonstrated that the tumor was moderately positive for vimentin and negative for epithelial, glial, neural crest, and hematologic markers; the best available classification was thus thought to be fibrosarcoma. [10] The lack of S-100 and GFAP expression allowed us to discriminate the tumor from pituicytoma and SCO, whereas the lack of CD34 staining ruled out SFT. PFs originating from the pituitary gland are exceedingly rare with only two previously published case reports. [10],[11] The clinical features of this tumor are summarized in [Table - 1]. All three cases initially presented with headache, diplopia, and moderately decreased plasma levels of cortisone, thyroxin, and gonadotropin. Early PPF seems to be associated with a characteristic triad of symptoms: headache, oculomotor nerve palsy, and panhypopituitarism, which may result from direct invasion and compression of the anterior pituitary gland and adjacent structures, such as the sella dura and the cranial nerves running through the cavernous sinus.

Similar to primary intracerebral fibrosarcoma, previous published descriptions of PPF had documented a tendency for postoperative recurrence and metastases. [10],[11],[12] Lopes et al. [10] reported local PPF recurrence seven months after gross total resection, although metastasis was not detected, likely due to the relatively short follow-up period. Similarly, Massier et al. [11] described a patient with PPF in whom local tumor recurrence was detected three months postoperatively and a number of metastases were observed 22 months after gross resection. In accordance with these cases, the most prominent clinical feature in our case was rapidly developing metastases, which were found in such intracranial regions as the medial temporal lobe, left cerebellum, cerebellar tentorium, and occipital lobe, as well as in extracranial areas, including the ethmoid sinus, orbital fossa, and cervical lymphonodes [[Figure - 1]c-e, [Figure - 2]d]. This broad metastatic pattern may indicate that PPF can metastasize via multiple mechanisms, including local contiguous spread, cerebral spinal fluid seeding, lymph transfer, and intravascular pathways, which had been confirmed in the metastasis of pituitary carcinoma. [13]

Our clinical observations indicates that PPF is highly malignant and progresses rapidly, This is further corroborated by the high levels of P53 expression and the Ki67 labeling index of 80% seen in our patient. In contrast to these observations in PPF, Nagasaka et al. [8] found a Ki67 labeling index of 7.2% and slightly increased P53 expression in a patient with secondary PF, in whom prolactinoma underwent a sarcomatous transformation following five years of bromocriptine therapy. Sarcomatous changes in sellar lesions do not necessarily indicate malignant or metastatic potential; few patients with PF secondary to sellar radiotherapy or pituitary adenoma showed relapse or metastasis after total resection. [1],[2],[3],[4],[5],[6],[7],[8],[9] These differences in clinical presentation and histopathology demonstrate that, compared with secondary PF, PPF has a higher of grade malignancy, including rapid recurrence after resection and early metastasis.

Three different etiologic forms of PF have been documented in the literature: (1) radiotherapy-induced fibrosarcomatous transformation of pituitary lesions, such as adenoma or craniopharyngioma, which comprises the overwhelming majority of all PF case reports; [2],[3],[4],[5],[6] (2) spontaneous fibrosarcomatous transformation of primary prolactinoma without a recognizable cause; [1],[7],[8],[9] and (3) spontaneous fibrosarcomatous changes in the pituitary gland, which may metastasize to other areas of the head and pathologically appears to be the most malignant of the three types. [10],[11] The patient in this report had the third form of PF, and was limited to a lifespan of only 11 months from diagnosis despite a multimodal treatment regimen combining surgery, chemotherapy, and radiotherapy. Similarly, the patient described by Massier et al. [11] survived for only 26 months following gross total tumor resection, gamma knife radiosurgery, and intensity-modulated radiotherapy. The authors attributed the poor prognosis associated with PPF to rapid tumor relapse and multiple metastases. [11] Further, despite pituitary gland preservation during PPF resection, all reported PPF patients required hormone replacement therapy for severe panhypopituitarism. We believe that pituitary gland preservation may increase the chance of PPF recurrence and metastasis. Thus, immediate whole-brain radiotherapy following aggressive surgical resection of the tumor and pituitary gland may reduce recurrence and metastasis while extending survival in patients with PPF.


1.Terry RD, Hyams VJ, Davidoff LM. Combined nonmetastasizing fibrosarcoma and chromophobe tumor of the pituitary. Cancer 1959;12:791-8.  Back to cited text no. 1  [PUBMED]  
2.Pieterse S, Dinning TA, Blumbergs PC. Postirradiation sarcomatous transformation of a pituitary adenoma: a combined pituitary tumor. Case report. J Neurosurg 1986;56:283-6.  Back to cited text no. 2    
3.Prabhu SS, Aldape KD, Gagel RF, Benjamin RS, Trent JC, McCutcheon IE. Sarcomatous change after sellar irradiation in a growth hormone-secreting pituitary adenoma. Can J Neurol Sci 2003;30:378-83.  Back to cited text no. 3  [PUBMED]  [FULLTEXT]
4.Sato K, Hayashi M, Komai T, Kubota T, Kawano H, Handa Y. Clinical and histological study of pituitary fibrosarcoma following radiotherapy for pituitary adenoma. Case report. Neurol Med Chir (Tokyo) 1990;30:888-92.  Back to cited text no. 4  [PUBMED]  
5.Gnanalingham KK, Chakraborty A, Galloway M, Revesz T, Powell M. Osteosarcoma and fibrosarcoma caused by postoperative radiotherapy for a pituitary adenoma. Case report. J Neurosurg 2002;96:960-3.   Back to cited text no. 5  [PUBMED]  [FULLTEXT]
6.Ahmad K, Fayos JV. Pituitary fibrosarcoma secondary to radiation therapy. Cancer 1978;42:107-10.  Back to cited text no. 6  [PUBMED]  
7.Moro M, Giannini C, Scheithauer BW, Lloyd RV, Restall P, Eagleton C, et al. Combined sellar fibrosarcoma and prolactinoma with neuronal metaplasia: report of a case unassociated with radiotherapy. Endocr Pathol 2004;15:149-58.  Back to cited text no. 7  [PUBMED]  
8.Nagasaka T, Nakashima N, Furui A, Wakabayashi T, Yoshida J. Sarcomatous transformation of pituitary adenoma after bromocriptine therapy. Hum Pathol 1998;29:190-3.  Back to cited text no. 8  [PUBMED]  [FULLTEXT]
9.Tachibana E, Saito K, Wakabayashi T, Nagasaka T, Furui T, Yoshida J. Sarcomatous transformation of a prolactinoma associated with development of a fatal internal carotid artery pseudoaneurysm--case report. Neurol Med Chir (Tokyo) 2000;40:427-31.  Back to cited text no. 9  [PUBMED]  [FULLTEXT]
10.Lopes MB, Lanzino G, Cloft HJ, Winston DC, Vance ML, Laws ER Jr. Primary fibrosarcoma of the sella unrelated to previous radiation therapy. Mod Pathol 1998;11:579-84.  Back to cited text no. 10  [PUBMED]  
11.Massier A, Scheithauer BW, Taylor HC, Clark C, Llerena L. Sclerosing epithelioid fibrosarcoma of the pituitary. Endocr Pathol 2007;18:233-8.  Back to cited text no. 11  [PUBMED]  [FULLTEXT]
12.Gaspar LE, Mackenzie IR, Gilbert JJ, Kaufmann JC, Fisher BF, Macdonald DR, et al. Primary cerebral fibrosarcomas. Clinicopathologic study and review of the literature. Cancer 1993;72:3277-81.  Back to cited text no. 12  [PUBMED]  
13.Koyama J, Ikeda K, Shose Y, Kimura M, Obora Y, Kohmura E. Long-term survival with non-functioning pituitary carcinoma - case report. Neurol Med Chir (Tokyo) 2007;47:475-8.  Back to cited text no. 13  [PUBMED]  [FULLTEXT]

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