eISSN: 1509-572x
ISSN: 1641-4640
Folia Neuropathologica
Current issue Archive Manuscripts accepted About the journal Editorial board Journal's reviewers Abstracting and indexing Subscription Contact Instructions for authors Ethical standards and procedures
SCImago Journal & Country Rank
vol. 48

Original article
Spindle cell oncocytoma of the adenohypophysis – a clinicopathological and ultrastructural study of two cases

Ewa Matyja
Maria Maksymowicz
Wiesława Grajkowska
Włodzimierz Olszewski
Grzegorz Zieliński
Wiesław Bonicki

Folia Neuropathol 2010; 48 (3): 175-184
Online publish date: 2010/10/04
Article file
- Spindle cell.pdf  [0.39 MB]
Get citation
JabRef, Mendeley
Papers, Reference Manager, RefWorks, Zotero


Spindle cell oncocytoma (SCO) is a rare, benign, non-endocrine neoplasm of the anterior pituitary gland that occurs in adults and follows a benign cli­nical course corresponding to WHO grade I. This tumour was initially described by Roncaroli et al. in 2002 [21] and included as a distinct histopathological subtype of pituitary tumours in the 2007 WHO classification of tumours of the central nervous system [11,18,23].
The clinical and radiological features of SCO are similar to non-functioning pituitary macroadenomas [7,10]. The histological pattern is characterized by non-epithelial spindle cells with abundant eosinophilic, variably oncocytic cytoplasm exhibiting conspicuous accumulation of mitochondria. The neoplastic cells are immunoreactive for EMA, vimentin and galectin-3 but are negative for pituitary hormones [11]. To date, only 14 cases of SCO have been reported in the literature [3,5,6,8,10,17,21,26]. The prognosis of SCO remains uncertain, as long-term follow-up study in most reported cases is not yet available.
We present two additional cases of this unusual entity to evaluate its immunomorphological and ultrastructural profile. These cases of SCO occurred in females aged 63 years (Case 1) and 65 years (Case 2), who presented with pan-hypopituitarism, head­ache and visual field defect. Clinically and radiologically both tumours suggested non-functioning pituitary macroadenomas. One patient was admitted with tumour recurrence appearing 3 years after first surgery. The primary tumour, initially misdiagnosed as schwannoma, was removed by transsphenoidal surgery and the second one by frontal craniotomy. For purpose of this report, retrospective analysis of the biopsy mate­rial from sellar-region lesions originally diagnosed as nonfunctional and oncocytic tumours during a period of 12 years (from 1998 to 2010) was performed.

Material and methods

The biopsy tumour specimens were fixed in 10% formalin, embedded in paraffin and routinely stained with hematoxylin and eosin (H&E). Immunohistochemical staining was performed on paraffin-embedded specimens according to the labelled EnVision Flex Visualization System (Dako, K8000) with DAB as chromogen using antibodies against: S-100 protein (dilution 1 : 3000), vimentin (dilution 1 : 100), epithelial membrane antigen (EMA, dilution 1 : 100), glial fibrillary acidic protein (GFAP, dilution 1 : 100), smooth muscle actin (SMA, dilution 1 : 100), desmin (dilution 1 : 100), CD34 (dilution 1 : 100), CD68 (dilution 1 : 100), chromogranin A (dilution 1 : 100), synaptophysin (dilution 1 : 100), cytokeratin AE1/AE3 (CK, dilution 1 : 100), Ki-67 (MIB1, dilution 1 : 100) – all antibodies from Dako; galectin-3 (dilution 1 : 100, Novocastra), ante­rior pituitary hormones or subunits: prolactin (PRL, dilution 1 : 200), growth hormone (GH, dilution 1 : 500), ACTH (dilution 1 : 500), b-TSH (dilution 1 : 200), b-FSH (dilution 1 : 500), b-LH (dilution 1 : 500) – all antibo­dies from LAB VISION and the glycoprotein a-subunit (dilution 1 : 100, Novocastra). MIB-1 labeling index was established.
For electron microscopy, the small pieces of tissue were fixed in 2.5% cold glutaraldehyde for 1 hour, washed in cacodylate buffer, postfixed in 1% osmium tetroxide, dehydrated in graded alcohols and embedded in Epon 812. Ultrathin sections were counterstained with uranyl acetate and lead citrate and examined in a Philips CM 120 BioTWIN electron microscope.


Case 1

A 63-year-old woman was admitted to Neurosurgical Department with a diagnosis of clinically endocrine inactive anterior pituitary adenoma. She presented with a 3-year history of worsening headache and vertigo with symptoms of fatigue and sleepiness of several months duration. During the last 3 month she suffered from nausea and transitional morning vomiting. She lost her weigh about 10 kg and developed the edema of her face and legs. Examination of her visual fields revealed a bitemporal hemianopsia. Preoperative laboratory endocrine tests showed discrete prolactin (PRL) evaluation, marked decrease of follicle-stimulating hormone (FSH) and luteinizing hormone (LH), very low range of estradiol and progesterone with signs of hipogonadotropic hypogonadism and very low range of cortisol. The thyroid-stimulating hormone (TSH) was within normal range with low fT3 and fT4 secretion.
The magnetic resonance imaging (MRI) demonstrated a solid, well-defined, homogeneously enhancing mass in the pituitary region, measuring 21 × 18 × 19 mm (Fig. 1). The tumour mass expanded the sella turcica and caused deformity and effacement of the optic chiasm. The cavernous sinuses were not involved. The tumour was gross totally removed by transsphenoidal surgery. The patient was recommenced on replacement therapy with hydrocortisone and Eltroxin. After 7 weeks the dose of Hydrocortison was reduced. No recurrences were noted at the 28-month follow-up examinantion.

Pathological findings

Histopathologically, the tumour was composed predominantely of compact, interwoven fascicles of plump spindled cells with abundant eosinophilic, often oncocytic or finely granular cytoplasm (Fig. 2A). Cell nuclei exhibited mild atypia and hyperchromasia and only focally nuclear polymorphism could be observed (Fig. 2B). Mitoses were seen sporadically and necrosis was absent. The rich numerous lymphocytic infiltration within neoplastic tissue was ob­served.
Immunohistochemically, the majority of tumour cells were immunoreactive for vimentin (Fig. 3A), S-100 protein (Fig. 3B) and epithelial membrane antigen (Fig. 3C). The neoplastic cells exhibited intense cytoplasmic immunostaining for anti-mitochondrial antibody – galectin-3 (Fig. 3D) but they were immunonegative for GFAP (Fig. 4A), anterior pituitary hormones (Fig. 4B) (prolactin, growth hormone, TSH, ACTH, FSH, LH, glycoprotein a-subunit), chromogranin, synaptophysin, CK (Fig. 4C), smooth muscle actin, desmin, CD34 and CD68. The MIB1 labeling index was about 5% with focal increase of proliferation activity (Fig. 4D).
Ultrastructurally, the neoplastic cells displayed spindle and polygonal morphology. Their cytoplasm revealed accumulation of mitochondria with lamellar cristae (Fig. 5). The intermediate intercellular junctions and well-formed desmosomes could be seen. The lysosomes were present, sometimes surrounded by bundles of intermediate filaments. No secretory granules were identified.

Case 2

A 65-year-old woman was admitted to Neurosurgery Department with symptoms of pituitary tumour recurrence. She was initially operated due to a well defined, sellar-region mass measuring 25 × 13 × 16 mm. At first admission, she presented with pituitary hormone insufficiency and bitemporal hemianopsia. The clinical and preoperative imaging features lead to preoperative diagnosis of a non-functioning macroadenoma. The primary tumour was removed by transsphenoidal surgery, followed by histopathological diagnosis of schwannoma. Three years later, neuroimaging demonstrated recurrence of sellar-region tumour. Preoperative endocrine studies showed pituitary hormone insufficiency, including a low range of cortisol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), growth hormone (GH) and thyroid-stimulating hormone (TSH). On MRI studies the tumour measured 18 × 19 × 21 mm and exhibited a significant suprasellar extension. The tu­mour was gross totally excised by frontal right cranio­tomy. Pathological examination of the material from both surgery established the diagnosis of spindle cell oncocytoma in both, primary and recurrent tumour. A pituitary hormonal profile was consistent with pan-hypopituitarism. Twenty months after surgery there was no evidence of tumour recurrence.

Pathological findings

Histopathologically, the neoplastic tissue from the primary and recurrent tumour revealed the identical pattern. Both tumours were composed of spindled or epithelioid cells arranged in interlacing fascicles. Majority of cells exhibited abundant eosinophilic cytoplasm, often with oncocytic or granular features (Fig. 6A). Mitoses were seen only occasionally and necrosis was absent.
Immunohistochemically, the tumour cells were po­sitive for vimentin (Fig. 6B), S100 protein (Fig. 6C) and focally positive for EMA (Fig. 6D). Tumour exhibited strong immunostaining of galactin-3 (Fig. 6E). Tumour cells were immunonegative for pituitary hormones (GH, PRL, FSH, LH, TSH, ACTH), GFAP, CK (AE1/AE3), GFAP, SMA, CD34, CD68 and neuroendocrine markers chromogranin and synaptophysin. The MIB-1 labelling index was about 1% in the original tumour and in the recurrent neoplasm (Fig. 6F).
Ultrastructurally, the majority of cells exhibited elongated cells with irregular surfaces and numerous long, interlacing processes. The cytoplasm of neoplastic cells were packed with abundant mitochondria with lamellar structures (Fig. 7A). Some cells exhibited enlarged, sometimes giant mitochondria with disrupted cristae (Fig. 7B). The intermediate junctions were seen occasionally. A few lysosomes were seen but there were no neurosecretory granules.


Pituitary adenomas represent about 90% of all mass lesions of sella turcica and 10-20% of all intracranial tumours. According to 2004 WHO classification of neuroendocrine tumours [1] and forth edition of 2007 WHO classification of nervous system tumours [11], the mass lesions of pituitary region include pituitary adenomas, pituitary carcinoma, hyperplasia of pituitary gland and other primary neoplasms of sella turcica i.e. craniopharyngioma, Ratke cleft cysts, meningioma, chordoma, gangliocytoma, astrocytoma, granular cell tumour, lymphoma, germinoma, hemangiopericytoma and spindle cell oncocytoma.
Spindle cell oncocytoma (SCO) is a rare, recently identified non-endocrine sellar-region lesion that manifests in adults with clinical presentation indistinguishable from other functionally inactive, non-hormone-producing macroadenomas [6,17]. SCO of the adenohypophysis may arise as an intrasellar, suprasellar, or intrasellar/suprasellar mass, sometimes invading the cavernous sinus. On MR images this tumour is of solid appearance with contrast enhancement, similar to pituitary macroadenomas. To date, pituitary spindle cell oncocytomas have been reported sporadically and only 14 cases of SCO was documented in the literature [3,5,6,8,10,17,21,26]. The reported cases were in adults ranging from 26 to 71 years (mean: 56 years). The majority of them presented with pan-hypopituitarism and visual defects, nausea, vomiting or headache. The incidence of SCOs is difficult to determine, but Kloub et al. [17] accounted for approximately 0.4% of all operated sellar tumours. The majority of documented SCOs represent lesions of a benign clinical course, corresponding to WHO grade I and characterized by favorable prognosis. Numerous cases exhibited the long lasting follow-up without recurrences after subtotal resection and proton beam therapy [6]. However, some reports demonstrated recurrences of SCO after the initial tumour resection and documented high Ki-67 labeling, mitotic activity and necrosis, indicating the more aggressive clinical behavior of these lesions [17]. One report evidenced late recurrence with subclinical intratumoral bleeding [2]. Also one of our patients undergone initial surgery with tumour resection followed by tumour recurrence after 3 years.
We performed the retrospective analysis of sellar-region lesions originally diagnosed as nonfunctional and oncocytic tumours. During a period of 12 years (from 1998 to 2010), the re-review of surgical specimens of two thousand unselected tumours of adenohypophysis from Poland established the diagnosis of SCO only in two presented herein cases of pituitary tumours. This data supports the rarity of this entity.
The differential diagnosis of SCO ought to consi­der different oncocytic and/or granular cell lesions of pituitary region [12,24]. Various sellar mass lesion might be confused with spindle cell oncocytoma of pituitary, including schwannoma, pituitary adenoma with oncocytic change, oncocytic null cell adenoma, granular cell tumour, pituicytoma, paraganglioma, meningioma with oncocytic features and solitary fibrous tumour. These neoplasms of different histoge­nesis might be more or less spindled in appearance and often associated with oncocytic changes. The detailed immunohistochemical studies are helpful in differential diagnosis. The differentiation of SCO and oncocytic pituitary adenoma is important as the second one is of higher aggressiveness. Most cases of pituitary adenomas reveal immunoreactivity for chromogranin, synaptophysin and/or selected pituitary hormones. A subtype of null cell adenoma with oncocytic changes have a higher risk of recurrence after radiotherapy, thus their correct diagnosis is of clinical importance. Granular cell tumours of neurohypophysis usually lack the typical spindle cell morphology cha­racteristic for SCO. These tumours are composed of plump or polygonal cells with eosinophylic, granulated and PAS-positive cytoplasm. Moreover, the granular cells are not strongly positive for S-100 protein. The differential diagnosis of pituicytoma was also essential. These tumours are derived from the glial stroma of neurohypophysis and exhibit spindle and epithelioid cell morphology. Pituicytomas are vimentin and S-100 protein positive but usually lack EMA reactivity and show glial fibrillary acidic protein expression [4]. Also oncocytic meningioma, an unusual variant of meningioma with aggressive behavior and recurrences, ought to be taken into consideration in differential diagnosis of sellar-region tumours and immunohistochemical features are important for criti­cal diagnosis [22].
Our two presented cases demonstrated the chara­cteristic clinicopathological features of spindle cell oncocytoma of the adenohypophysis. Our second case was initially considered as intrasellar benign nerve sheath tumour due to its S-100 protein positi­vity typical for schwannomas and immunonegativity for pituitary hormones. However, the primary tumour lacked the histological pattern of Antoni A or B morphology and the final diagnosis of SCO was established based upon combined morpholo­gic, immunohistochemical and ultrastructural features.
The main ultrastructural characteristics of SCOs include cytoplasmic accumulation of mitochondria, whereas the secretory granules and desmosomes are rarely encountered [6,17,21]. The neoplastic cells of SCOs exhibited only a few lysosomes in contrast to granular cells observed in granular astrocytomas, which cytoplasm was filled with electron-dense gra­nular material limited by a single membrane and autophagic vacuoles, whereas numerous condensed electron-dense, bizarrely-shaped mitochondria were observed only occasionally [25]. Moreover, in Case 2 some tumour cells showed a few giant mitochondria with severely destructed internal matrix, the feature not previously described in SCOs.
The nature and histogenesis of SCO remains uncertain, nevertheless both immunohistochemical and ultrastructural features of these unique lesion suggest its derivation from folliculostellate cells (FSCs) of the adenohypophysis [9,13,21]. FSCs are hete­rogeneous, non-hormone secreting stellate cells of the anterior pituitary, that represent about 5-6% of all cells in the adenohypophysis and provide a structural sustentacular elements for the endocrine cells [14,15]. FSCs are considered as a type of stem cells in the adult pituitary gland [14,15]. These cells are im­mu­nopositive for S-100 protein, vimentin, EMA and occasionally GFAP [11,14,23,27]. Recent studies have demonstrated expression of galactin-3 in the human pituitary restricted to FSCs and ACTH and PRL producing adenomas [11,16,19-21]. The ultrastructural features of FSCs suggest that FSCs may represent an adult stem cell progenitor population.
Concluding, the diagnosis of SCOs in reported herein two cases of pituitary tumours, one of which was recurrent, was confirmed by immunohistoche­mical and ultrastructural profiles. Clinically and radiologically these tumours suggested nonfunctioning pituitary macroadenomas. The tumours were less than 25 mm in diameter and they did not reveal invasive growth. The immunorectivity for vimentin, S100, and galectin-3 was consistent with diagnosis of spindle cell oncocytoma and the tumours displayed chara­cteristic ultrastructural features, especially presence of numerous swollen mitochondria with lamellar cristae and short intercellular junctions, without neurosecretory granules.
Both, immunohistochemical and electron microscopic examination is essential for distinguishing SCO from other entities with overlapping oncocytic features. In the current WHO classification, the SCO corresponds to grade I, but its prognosis and biologic spectrum remains uncertain and long-term follow-up is required.


 1. Al-Shraim M, Asa SL. The 2004 World Health Organization classification of pituitary tumors: what is new? Acta Neuropathol (Berl) 2006; 111: 1-7.  
2. Borges MT, Lillehei KO, Kleinschmidt-Demasters BK. Spindle cell oncocytoma with late recurrence and unique neuroimaging characteristics due to recurrent subclinical intratumoral bleeding. J Neurooncol 2010 [Epub ahead of print].  
3. Borota OC, Scheithauer BW, Fougner SL, Hald JK, Ramm-Pettersen J, Bollerslev J. Spindle cell oncocytoma of the adenohypophysis: report of a case with marked cellular atypia and recurrence despite adjuvant treatment. Clinical Neuropathol 2009; 28: 91-95.  
4. Brat DJ, Scheithauer BW, Staugaitis SM, Holtzman RN, Morgello S, Burger PC. Pituicytoma: a distinctive low-grade glioma of the neurohypophysis. Am J Surg Pathol 2000; 24: 362-368.  
5. Coiré CI, Horvath E, Smyth HS, Kovacs K. Rapidly recurring folliculostellate cell tumor of the adenohypophysis with the morphology of a spindle cell oncocytoma:case report with electron microscopic studies. Clinical Neuropathol 2009; 28: 303-308.  
6. Dahiya S, Sarkar C, Hedley-Whyte ET, Sharma MC, Zervas NT, Sridhar E, Louis DN. Spindle cell oncocytoma of the adenohypophysis: report of two cases. Acta Neuropathol 2005; 110: 97-99.  
7. Dekkers OM, Hammer S, de Keizer RJ, Roelfsema F, Schutte PJ, Smit JW, Romijn JA, Pereira AM. The natural course of non-functioning pituitary macroadenomas. Eur J Endocrinol 2007; 156: 217-224.  
8. Demssie YN, Joseph J, Dawson T, Roberts G, de Carpentier J, Howell S. Recurrent spindle cell oncocytoma of the pituitary, a case report and review of literature. Pituitary 2009 [Epub ahead of print].  
9. Devnath S, Inoue K. An insight to pituitary folliculo-stellate cells. J Neuroendocrinol 2008; 20: 687-691.
10. Farooq MU, Bhatt A, Chang HT. Teaching neuroimage: spindle cell oncocytoma of the pituitary gland. Neurology 2008; 71: e3; http://www.neurology.org/cgi/content/full/71/2/e3.
11. Fuller G, Scheithauer BW, Roncaroli F, Wesseling P. Spindle cell oncocytoma of the adenohypophysis. In: Louis DN, Ohgaki H, Wiestler OD, Cavanee WK (eds.). WHO Classification of Tumours of the Central Nervous System World Health Organization Classification of Tumours. 4th ed. IARC, Lyon 2007; pp. 245-246.
12. Giangaspero F, Cenacchi G. Oncocytic and granular cell neoplasms of the central nervous system and pituitary gland. Semin Diagn Pathol 1999; 16: 91-97.
13. Hori S, Hayashi N, Fukuoka J, Kurimoto M, Hamada H, Miyajima K, Nagai S, Endo S. Folliculostellate cell tumor in pituitary gland. Neuropathology 2009; 29: 78-80.
14. Horvath E, Kovacs K. Folliculo-stellate cells of the human pituitary: a type of adult stem cell? Ultrastruct Pathol 2002; 26: 219-228.
15. Inoue K, Mogi C, Ogawa S, Tomida M, Miyai S. Are folliculo-stellate cells in the anterior pituitary gland supportive cells or organ-specific stem cells? Arch Physiol Biochem 2002; 110: 50-53.
16. Jin L, Riss D, Ruebel K, Kajita S, Scheithauer BW, Horvath E, Kovacs K, Lloyd RV. Galectin-3 Expression in Functioning and Silent ACTH-Producing Adenomas. Endocrinol Pathol 2005; 16: 107-114.
17. Kloub O, Perry A, Tu PH, Lipper M, Lopes MB. Spindle cell oncocytoma of the adenohypophysis: report of two recurrent cases. Am J Surg Pathol 2005; 29: 247-253.
18. Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, Scheithauer BW, Kleihues P. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 2007; 114: 97-109. Erratum in: Acta Neuropathol 2007; 114: 547.
19. Riss D, Jin L, Qian X, Bayliss J, Scheithauer BW, Young WF, Vidal S, Kovacs K, Raz A, Lloyd RV. Differential expression of galectin-3 in pituitary tumors. Cancer Res 2003; 63: 2251-2255.
20. Rodriguez FJ, Scheithauer BW, Roncaroli F, Silva AI, Kovacs K, Brat DJ, Jin L. Galectin-3 expression is ubiquitous in tumors of the sellar region, nervous system, and mimics: an immunohistochemical and RT-PCR study. Am J Surg Pathol 2008; 32: 1344-1352.
21. Roncaroli F, Scheithauer BW, Cenacchi G, Horvath E, Kovacs K, Lloyd RV, Abell-Aleff P, Santi M, Yates AJ. 'Spindle cell oncocytoma' of the adenohypophysis: a tumor of folliculostellate cells? Am J Surg Pathol 2002; 26: 1048-1055.
22. Roncaroli F, Riccioni L, Cerati M, Capella C, Calbucci F, Trevisan C, Eusebi V. Oncocytic meningioma. Am J Surg Pathol 1997; 21: 375-382.
23. Roncaroli F, Scheithauer BW. Papillary tumor of the pineal region and spindle cell oncocytoma of the pituitary: new tumor entities in the 2007 WHO Classification. Brain Pathol 2007; 17: 314-318.
24. Tallini G. Oncocytic tumors. Virchows Arch 1998; 433: 5-12.
25. Wierzba-Bobrowicz T, Lewandowska E, Matyja E, Dziduszko J, Koszewski W, Stepień T, Błazejewska-Hyzorek B. Granular cell astrocytoma. A case report with immunohistochemical and ultrastructural characterization. Folia Neuropathol 2008; 46: 286-293.
26. Vajtai I, Sahli R, Kappeler A. Spindle cell oncocytoma of the adenohypophysis: report of a case with a 16-year follow-up. Pathol Res Pract 2006; 202: 745-750.
27. Yamashita M, Qian ZR, Sano T, Horvath E, Kovacs K. Immunohistochemical study on so-called follicular cells and folliculostellate cells in the human adenohypophysis. Pathol Int 2005; 55: 244-247.
Copyright: © 2010 Mossakowski Medical Research Centre Polish Academy of Sciences and the Polish Association of Neuropathologists. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0) License (http://creativecommons.org/licenses/by-nc-sa/4.0/), allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material, provided the original work is properly cited and states its license.
Quick links
© 2021 Termedia Sp. z o.o. All rights reserved.
Developed by Bentus.