Kottangal, Madhavan, Kuruvilla, Parameswaran, and Kollathodi: Spindle cell oncocytoma, a misdiagnosed rare entity of the pituitary – A case report with review of literature and special emphasis on the morphological differentials


Introduction

Spindle cell oncocytoma (SCO), a benign nonendocrinal neoplasm of the anterior pituitary gland, was previously thought to arise from the adenohypophysis's folliculostellate cells.1, 2 But the recent studies and reports suggest pituicytes as the cell of origin3 of the tumor. It is a WHO grade 1 tumor, first reported and named "Spindle cell oncocytoma" by Roncaroli et al. in 2002.2  However, from 2002 to 2021 March, < 50 cases have been reported in the English literature.3 Due to their location and nonfunctional nature, these tumors are often misdiagnosed as nonfunctional pituitary adenomas. The careful histomorphological and immunohistochemical examination helps to have the correct diagnosis. SCO is a spindle cell neoplasm with dense eosinophilic cytoplasm having immunoreactivity for vimentin, thyroid transcription factor(TTF1), epithelial membrane antigen (EMA), galectin-3, and S100.2 The highly vascular and adherent nature often makes the tumor challenging to resect.1, 2, 3, 4, 5, 6

Case Report

A 61-year-old female with a past history of diabetes mellitus, hyperthyroidism, and hypertension had two episodes of dizziness and one episode of loss of consciousness and was referred to our institution for further workup. She was diagnosed with hyponatremia and had a temporal field cut. Her MRI brain showed a well-defined enhancing altered signal intensity lesion involving the sellar region with expansion of sella and suprasellar extension measuring approximately 1.6 x 2.4 x 2cm (Figure 1). Radiologically and clinically, the lesion was pituitary macroadenoma, for which an endoscopic trans-nasal trans-sphenoidal decompression was done.

Figure 1

Magnetic Resonance Imaging (MRI) sagittal post-contrast and MRI axial post-contrast showed a well-defined enhancing altered signal intensity lesion involving the sellar region with expansion of sella and suprasellar extension measuring approximately 1.6 x 2.4 x 2cm

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Grossly the tumor was grey-white, friable, and soft. Microscopically a spindle cell neoplasm with cells arranged in fascicle and bundles were seen (Figure 2). Cells had elongated bland nuclei with fine chromatin and a moderate amount of dense eosinophilic cytoplasm (Figure 3). Interspersed prominent vascular channels were also noted. Mitosis was scanty, 0-1/10hpf, and no necrosis was seen.

Figure 2

Hematoxylin and eosin-stained (H& E) sections in 200x objective showed spindle cells arranged in fascicle and bundles

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Figure 3

Hematoxylin and eosin-stained (H & E) sections in 400x objective showed spindle cells with elongated bland nuclei, fine chromatin, and a moderate amount of dense eosinophilic cytoplasm

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Immunohistochemistry showed strong diffuse nuclear positivity for TTF1 (Figure 4), moderate positivity for EMA (Figure 5), and S100 (Figure 6). The cells were negative for GFAP and synaptophysin. Ki67 proliferation index was 1-2% (Figure 7). With the histomorphological and immunohistochemical findings, the diagnosis of spindle cell oncocytoma, sellar mass was made. The post-operative period was uneventful, and the patient was discharged and is being followed up.

Figure 4

Immunohistochemistry stain for Thyroid Transcription Factor 1 (TTF1) showed strong diffuse positivity

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Figure 5

Immunohistochemistry stain for Epithelial Membrane Antigen (EMA) showed moderate positivity

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Figure 6

Immunohistochemistry stain for S100 showed strong positivity

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Figure 7

Immunohistochemistry stain for Ki 67 showed a proliferation of 1-2%

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Table 1

The histomorphological and immunohistochemical features of SCO and its morphological differentials

Spindle cell oncocytoma

Spindle cells in fascicles. Cells have dense granular and eosinophilic cytoplasm.

Positive- TTF1, EMA, S100, vimentin, and galactin 3:

Negative - GFAP, Synaptophysin, :chromogranin.

Pituicytoma

Short fascicles of spindly/ epithelioid cells.

Positive -TTF1, S100, vimentin, variable GFAP

Negative- EMA, CK, synaptophysin, chromogranin, pituitary hormones

Meningioma

Syncytial /epithelioid / spindle cells in classic whorls. Cells with indistinct cell borders.

Positive- EMA, PR, SSTR2A, vimentin, S100

Negative- TTF1, GFAP, synaptophysin, pituitary hormones

Sellar schwannoma

Biphasic with Antony A and Antony B areas. Spindle cells with wavy nuclei.

Positive – S100, SOX10

Negative – GFAP, TTF1, synaptophysin, and chromogranin.

Solitary Fibrous Tumour

Spindle to ovoid cells in fascicles, bundles, and clusters. Variably collagen stroma and prominent staghorn vascular channels.

Positive- CD34, STAT6,CD99, variable positivity for EMA, Bcl2

Negative- TTF1, S100, SOX10,GFAP, Synaptophysin.

Paraganglioma

Polygonal/ elongated cells in trabecular and zellballen pattern. Cells have round nuclei, salt and pepper chromatin, and a moderate amount of cytoplasm.

Positive-Synaptophysin, chromogranin, NSE, CD 56, S100 in sustentacular cells

Negative-TTF1, EMA, GFAP

Null cell adenoma

Cells are acidophilic, basophilic, or chromophobic.  Cells have moderately abundant cytoplasm, uniform nuclear morphology, stippled chromatin, and inconspicuous nucleoli

Positive- Synaptophysin, pituitary hormones, and variable chromogranin

Negative- TTF1, EMA, S100, GFAP

Discussion

SCO is a very rare nonfunctioning and misdiagnosed tumor of the anterior pituitary, accounting for 0.1% to 0.4% of all the tumors in the sellar region. Previously the tumor was thought to arise from the folliculostellate cells of the adenohypophysis of the anterior pituitary.1, 2 But recent studies and reports suggest that this tumor has similar immunohistochemical characters to the tumors arising from the pituicytes. The nonneoplastic pituicytes, pituicytomas, SCOs, and granular cell tumors stain positive for TTF-1. However, folliculostellate cells are negative for TTF-1, which points out that SCO has a common lineage arising from the pituicytes and is now considered a variant of pituicytoma.4

Clinically and radiologically, the tumor is often misinterpreted as a nonfunctioning pituitary adenoma. This tumor is commonly seen in the older adult group with no sex predilection. The presenting symptoms are usually nonspecific, including visual disturbances, headaches, and panhypopituitarism, mainly due to the mass effect on the optic chiasm and pituitary gland.3, 5, 7

The radiologic features of SCO are also considered to be nonspecific and are indistinguishable from a pituitary adenoma. However, new findings in radiology were described by Hasiloglu et al. in their report of three cases, the early intense contrast enhancement in DCE-T1W1, which denotes the hypervascular nature of the tumor and the T2-weighted imaging showing millimetric hypointense foci and linear signal void areas.7 In addition, in SCO, Kim DJ et al. described the segmental enhancement inversion, the periphery showing a spoke-wheel pattern of early arterial enhancement, and late central stellate enhancement, a feature commonly noted in renal oncocytoma with a critical size.3 They proposed that the central fibrous stellate scar causing enhancement inversions is a specific finding for SCO of the sellar turcica.

Till now, the accurate diagnosis of SCO is purely based on histomorphological and immunohistochemical features. Microscopically, the tumor shows spindle cells with bland elongated nuclei and a moderate eosinophilic/ granular cytoplasm, arranged in interlacing fascicles and whorls with intervening vascular channels. The tumor has scanty mitosis and usually no necrosis. However, case reports with anaplastic features with rapid progression and recurrence are also reported.3

The morphological differentials considered are pituicytoma, meningioma, schwannoma, solitary fibrous tumor(SFT), paraganglioma, and null cell adenoma with oncocytic change. Immunohistochemistry plays a vital role in the diagnosis. The tumor is positive for TTF1, S100, EMA, galactin-3 and negative for GFAP, synaptophysin, chromogranin, CD34. The positivity of TTF1 helps to differentiate from tumors like meningioma and SFT.1, 2, 3, 4, 5, 6

The histomorphological and immunohistochemical features of SCO and its morphological differentials are summarized in Table 1.8, 9, 10, 11, 12, 13

Surgery is the primary mode of treatment. Trans sphenoidal and transcranial approaches had been reported. Due to the tumor's highly vascular and adherent nature, the transcranial method has been preferred by some surgeons.14 Cases with adjuvant radiation treatment with proton beam therapy and Gamma Knife Radiosurgery are also reported.5

Though indolent and slow-growing tumor, the patient needs to be closely followed up with serial MRI as there are many reports of recurrence. Current studies have reported co-occurring MEN1 frameshift mutation (p.L117fs) and somatic HRAS (p.Q61R) activating point mutation. The MAPK activation pathway-associated mutations in SND1 and FAT1 were also noted in SCO. So the MAPK signaling pathway is now considered a targeted therapy for spindle cell oncocytoma, which can be used as a powerful adjunct for aggressive and recurring tumors refractory to surgical resection.15

Conclusion

Spindle cell oncocytomas are often misdiagnosed clinically and radiologically as other tumors of the pituitary. The various pathological studies like light microscopy and immunohistochemistry help the pathologist to arrive at a correct diagnosis. The spindle cell morphology with cells having granular/ eosinophilic cytoplasm and positive stain for TTF1 clench the diagnosis. Though benign, slow-growing tumors, these tumors can recur and have aggressive behavior. So a close follow-up of the patient is mandatory. Since there is a paucity of reported cases with long-term follow-up, large series of case studies need to be performed to know the exact behavior and prognosis of the tumor.

Source of Funding

None.

Conflict of Interest

The authors declare no conflict of interest.

Acknowledgments

Department of Neurosurgery & Department of Radiology, Aster MIMS Hospital, Kozhikode, Kerala, India.

References

1 

GN Fuller BW Scheithauer The The 2007 Revised World Health Organization (WHO) Classification of Tumours of the Central Nervous System: newly codified entitiesBrain Pathol2007173304710.1111/j.1750-3639.2007.00084.x

2 

F Roncaroli BW Scheithauer G Cenacchi E Horvath K Kovacs RV Lloyd Spindle cell oncocytoma' of the adenohypophysis: a tumor of folliculostellate cells?Am J Surg Pathol200226810485510.1097/00000478-200208000-00010

3 

DJ Kim S Lee MS Kim JH Hwang MH Hahm Spindle cell oncocytoma of the sella turcica with anaplastic features and rapid progression in short-term follow-up: a case report with proposal of distinctive radiologic featuresJ Pathol Transl Med2009553225910.4132/jptm.2021.01.27

4 

O Mete MB Lopes SL Asa Spindle cell oncocytomas and granular cell tumors of the pituitary are variants of pituicytomaAm J Surg Pathol201337111694910.4132/jptm.2021.01.27

5 

AMG Larsen DJ Cote HA Zaidi WL Bi PJ Schmitt JB Iorgulescu Spindle cell oncocytoma of the pituitary glandJ Neurosurg201813125172510.3171/2018.4.JNS18211

6 

CM Yip HP Lee PP Hsieh Pituitary spindle cell oncocytoma presented as pituitary apoplexyJ Surg Case Rep201920196rjz17910.1093/jscr/rjz179

7 

ZI Hasiloglu E Ure N Comunoglu N Tanriover B Oz N Gazioglu New radiological clues in the diagnosis of spindle cell oncocytoma of the adenohypophysisClin Radiol201671993710.1016/j.crad.2016.04.022

8 

M Feng JD Carmichael V Bonert S Bannykh AN Mamelak Surgical management of pituicytomas: case series and comprehensive literature reviewPituitary201417539941310.1007/s11102-013-0515-z

9 

G Zada MBS Lopes S Mukundan E Laws G Zada M Lopes S Mukundan E Laws Meningioma of the Sellar and Parasellar RegionAtlas of Sellar and Parasellar LesionsSpringerCham201610.1007/978-3-319-22855-6_28

10 

T Oishi S Takehara Y Yamamura M Tomida S Ito K Kuriki "Pure" Suprasellar Schwannoma Presented with Communicating Hydrocephalus: A Case ReportNMC Case Rep J201743837

11 

X Yang Q Jiang B Yu Solitary fibrous tumor located in the sella turcica: A report of two cases and review of the literatureOncol Lett20151013548

12 

SB Lyne SP Polster S Fidai P Pytel B Yamini Primary Sellar Paraganglioma: Case Report with Literature Review and Immunohistochemistry ResourceWorld Neurosurg201912532610.1016/j.wneu.2019.01.094

13 

JP Almeida CC Stephens JM Eschbacher MM Felicella KCJ Yuen WL White Clinical, pathologic, and imaging characteristics of pituitary null cell adenomas as defined according to the 2017 World Health Organization criteria: a case series from two pituitary centersPituitary20192255149

14 

S Dahiya C Sarkar ET Hedley-Whyte MC Sharma NT Zervas E Sridhar Spindle cell oncocytoma of the adenohypophysis: report of two casesActa Neuropathol2005110197910.1007/s00401-005-1009-5

15 

MB Miller WL Bi LA Ramkissoon YJ Kang M Abedalthagafi DS Knoff MAPK activation and HRAS mutation identified in pituitary spindle cell oncocytomaOncotarget2016724370546310.18632/oncotarget.9244



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Article History

Received : 13-08-2021

Accepted : 23-09-2021

Available online : 23-11-2021


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https://doi.org/10.18231/j.ijpo.2021.112


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