Spindle Cell Oncocytoma Research Articles

Thyroid Transcription Factor 1 Expression in Sellar Tumors: A Histogenetic Marker?

Pituicytomas are rare low-grade gliomas of the neurohypophysis. Their morphology and variable immunophenotype have led to speculation that they arise from pituicytes. Given the role of thyroid transcription factor 1 (TTF-1) in the developing rodent infundibulum and its expression in the adult rat neurohypophysis, we speculated that TTF-1 would be a marker of human pituicytes. Using immunohistochemistry, we found that TTF-1 is strongly expressed in fetal and adult human pituicytes. A survey of sellar masses demonstrated specific TTF-1 expression in pituicytomas (n = 3), atypical pituicytomas (n = 2), and granular cell tumors (n = 4), indicating a common pituicyte lineage. TTF-1 expression in spindle cell oncocytomas (n = 8) is less easily explained but invites speculation. Our observations may have implications for the classification of these rare sellar neoplasms, all the while acknowledging the morphological diversity of pituicyte-related neoplasms.

Recurrent spindle cell oncocytoma of the pituitary, a case report and review of literature

Spindle cell oncocytoma (SCO) is a rare non-functioning tumour of the pituitary which has just been formally recognized as a distinct entity by the 2007 WHO classification of brain tumours. We report a case of SCO who presented with symptoms of visual blurring, weight loss, intermittent vomiting and excessive tiredness of several months duration. Investigations revealed a bitemporal visual field defect, a panhypopituitary hormonal profile and a large pituitary tumour with suprasellar extension. He underwent a successful trans-sphenoidal resection of the pituitary tumour but it subsequently recurred twice at 9 months interval which required further two debulking procedures. A diagnosis of SCO was made based on its unique histologic and staining properties. To date there are only ten reported cases of SCO in total with only two of these cases being recurrent. Our case displayed the most aggressive clinical course despite having a low Ki-67 index contrary to the previously reported cases of recurrent SCO.

Spindle cell oncocytoma of the adenohypophysis: report of a case with marked cellular atypia and recurrence despite adjuvant treatment

Spindle cell oncocytoma (SCO) of the adenohypophysis is a recently defined pituitary tumor mimicking a non-functioning macroadenoma and composed of mitochondrion rich tumor cells, positive for S-100, vimentin, epithelial membrane antigen and galectin-3 but lacking cytokeratins, pituitary hormones, and neuroendocrine markers. Derivation from pituitary folliculostellate cells (FSCs) has been suggested based upon immunohistochemical and ultrastructural characteristics shared by SCO and FSCs. 10 cases of SCO have been reported to date; of these, 8 underwent a benign clinical course and 2 recurred. We report a case of SCO with typical histologic and immunohistochemical features in addition to marked cellular pleomorphism and nuclear atypia. It showed slow regrowth over a 30-month period of follow-up despite combined surgical and radiotherapy. Despite the benign course of most reported cases, additional experience with longer follow-up are needed to assess clinical, histopathologic, and proliferative indices and their relevance to optimal therapy for this rare pituitary tumor.

Galectin-3 Expression is Ubiquitous in Tumors of the Sellar Region, Nervous System, and Mimics

Galectin-3 expression has been reported in spindle cell oncocytoma, certain pituitary adenoma subtypes, astrocytomas, oligodendrogliomas, and meningiomas. We evaluated galectin-3 protein expression by immunohistochemistry in 201 cases of a variety of nervous system and sellar tumors, as well as mRNA expression by reverse transcription-polymerase chain reaction in formalin-fixed paraffin-embedded tissue in a subset (20 cases). Immunohistochemical results were evaluated in a semiquantitative fashion on a 4-tiered scale (0 to 3). Strong (3+) immunoreactivity was seen in most of the cases (61%), followed by 2+(22%), and 1+(13%) staining. Only 4% of the lesions studied were immunonegative. Galectin-3 mRNA was present in 15 of the 18 cases (83%) in which reverse transcription-polymerase chain reaction was successful. Significant differences in protein expression were noted in the following 2 settings: specific meningioma subtypes (P=0.004, Fisher exact test) wherein clear cell meningioma demonstrated weak protein expression when compared with other meningioma variants. No significant difference was noted with respect to World Health Organization grade. Galectin-3 was also strongly expressed in benign nerve sheath tumors but only moderately expressed in malignant peripheral nerve sheath tumors (P=0.0009, Fisher exact test). Although galectin-3 positivity is a key feature of the immunophenotype of spindle cell oncocytoma, its consistent expression in other morphologically similar tumors (meningioma, pituicytoma, nerve sheath tumors, granular cell tumor, metastases) makes it of little use in the differential diagnosis of sellar region tumors, a setting in which it should be discouraged. Diagnostic uses of this marker may be limited to specific settings, including some meningioma subtypes and nerve sheath tumors.

Teaching Neuro Image : Spindle cell oncocytoma of the pituitary gland

A 76-year-old man had worsening generalized weakness and headache for several months. MRI showed a solid enhancing sellar mass suggestive of a pituitary macroadenoma (figure 1). Differential diagnoses included pituicytoma, paraganglioma, meningioma, and solitary fibrous tumor. Due …

The 2007 WHO Classification of Tumours of the Central Nervous System

The fourth edition of the World Health Organization (WHO) classification of tumours of the central nervous system, published in 2007, lists several new entities, including angiocentric glioma, papillary glioneuronal tumour, rosette-forming glioneuronal tumour of the fourth ventricle, papillary tumour of the pineal region, pituicytoma and spindle cell oncocytoma of the adenohypophysis. Histological variants were added if there was evidence of a different age distribution, location, genetic profile or clinical behaviour; these included pilomyxoid astrocytoma, anaplastic medulloblastoma and medulloblastoma with extensive nodularity. The WHO grading scheme and the sections on genetic profiles were updated and the rhabdoid tumour predisposition syndrome was added to the list of familial tumour syndromes typically involving the nervous system. As in the previous, 2000 edition of the WHO ‘Blue Book’, the classification is accompanied by a concise commentary on clinico-pathological characteristics of each tumour type. The 2007 WHO classification is based on the consensus of an international Working Group of 25 pathologists and geneticists, as well as contributions from more than 70 international experts overall, and is presented as the standard for the definition of brain tumours to the clinical oncology and cancer research communities world-wide.

Papillary Tumor of the Pineal Region and Spindle Cell Oncocytoma of the Pituitary: New Tumor Entities in the 2007 WHO Classification

We have reviewed the features of two recently described intracranial tumors, which have been formally recognized as distinct entities by the 2007 WHO Classification of Brain Tumours: Papillary tumor of the pineal region and spindle cell oncocytoma of the pituitary gland. Their salient clinicopathological features, differential diagnosis, histogenetic hypothesis and outcome are discussed.

Spindle cell oncocytoma of the adenohypophysis: Report of a case with a 16-year follow-up

Spindle cell oncocytoma (SCO) is a recently described, rare neoplasm of the anterior pituitary. Clinically and radiologically simulating a non-functioning macroadenoma, its eponymous fusiform cells display a non-epithelial phenotype with conspicuous cytoplasmic accumulation of mitochondria. We report a case of SCO retrospectively identified in a biopsy specimen 16 years after transsphenoidal operation of a 48-year-old woman. Presenting symptoms were adynamia and transient decrease of visual acuity. Neuroimaging showed an isointense, enhancing, sellar-centered mass 1.8 cm in diameter without evidence of invasive growth. No postoperative adjuvant therapy was administered. The patient was left with panhypopituitarism, yet no recurrence was seen during follow-up. Initially diagnosed as a null cell adenoma of oncocytic type, repeat immunohistochemistry showed the characteristic coexpression of S100 protein, vimentin, and epithelial membrane antigen. Oncocytic granula stained intensely with antimitochondrial antibody 113-1, and were negative with the lysosomal marker CD68. Anterior pituitary hormones tested negative, and there was no evidence of neuroendocrine differentiation using antibodies to synaptophysin and chromogranin. Few cells stained for glial fibrillary acidic protein (GFAP). SCO has been proposed to represent a neoplasm of folliculo-stellate cells (FSCs). While the dynamic properties of the latter are incompletely characterized, and indeed no specific marker allows for their identification, overlapping features of SCO with look alikes, in particular pituicytoma, point to FSCs being a potential adult stem cell. The favorable outcome of the present case further argues for SCO to be considered a low-grade neoplasm. Moderate tumor size, lack of invasiveness, and low proliferation rate are likely predictors of benign behavior.

Spindle cell oncocytoma of the adenohypophysis: report of two cases

Spindle cell oncocytoma of the adenohypophysis is a recently described, spindle and granular cell, S-100 protein-positive, GFAP-negative, neuroendocrine marker-negative, mitochondria-rich neoplasm of uncertain histogenesis that can clinically and radiologically mimic pituitary adenoma. We present two cases of this entity to extend understanding of this unusual tumor. The first case was a 26-year-old man who presented with a 6-month history of progressive headache, blurred vision in the right eye, nausea, vomiting and impotence. Magnetic resonance imaging (MRI) revealed a rounded, 1.5to 2-cm homogeneously enhancing mass in the pituitary region, which involved the right cavernous sinus, impinged on the temporal lobe and expanded the sella. At transsphenoidal exploration, the mass was firm and difficult to dissect. Following this procedure, visual acuity in the right eye worsened and he underwent a right pterional craniotomy with subtotal resection of the tumor, with residual tumor remaining around the carotid artery. The patient received proton beam radiotherapy to a total dose of 54 Gy over a period of 2 months, during which his vision improved significantly. He has been followed with serial MRI, visual and endocrine examinations for 7 years and remains stable, without tumor regrowth. The second case was a 55-year-old woman who presented with headache and progressive visual deterioration over 6 months, worse in the left than right eye, as well as a 10-day history of vomiting. MRI showed a 6.5·3.3·4 cm sellar and parasellar mass. A transsphenoidal gross total excision was performed. The tumor was highly vascular with destruction of the sellar floor. Six months following surgery, her visual acuity is improved and she has no evidence of recurrence. The two tumors were histologically similar. Case 1 was predominantly composed of spindle cells in a fascicular arrangement (Fig. 1A) with foci of oncocytic appearance (Fig. 1B). Case 2, although also largely spindled in appearance, had more polygonal cells that formed ill-defined lobules (Fig. 1C, D). The cells in both cases had abundant, granular eosinophilic cytoplasm and nuclei that were only mildly pleomorphic. Neither mitotic activity nor necrosis was noted. On immunohistochemical evaluation, the tumor cells were positive for both S-100 protein (Fig. 1E) and epithelial membrane antigen, but did not stain for GFAP, pituitary hormones (prolactin, growth hormone, TSH, ACTH, FSH, LH), chromogranin or synaptophysin . The MIB1 index was approximately 1% in case 1 and 8% in case 2. Electron microscopy was performed on case 2, and showed the tumor cells to be rich in mitochondria with scattered rare secretory granules, but without complex membrane interdigitations or desmosomes (Fig. 1F). Only seven spindle cell oncocytomas of the adenohypophysis have been reported to date [5, 10]. These seven patients were older adults (ranging from 53 to 76 years), five presenting with pan-hypopituitarism and four complaining of visual defects. All five of the lesions initially reported [10] were considered benign since they lacked invasion and showed low proliferative activity. The mean follow-up period for this first series was 3 years, with the longest follow-up 68 months; none of the five tumors had recurred or metastasized. Kloub et al. [5], however, reported two cases of spindle cell oncocytoma of the adenohypophysis that recurred, raising a question about the predicted behavior of these lesions. Although the morphological features of the two primary tumors were not predictive of aggressive behavior, the recurrent tumors had high Ki-67 labeling indices (18–20%) in addition to one recurrent case with mitotic activity and necrosis. These higher proliferation S. Dahiya AE E. T. Hedley-Whyte AE D. N. Louis (&) Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA E-mail: dlouis@partners.org

Spindle Cell Oncocytoma of the Adenohypophysis

The recently described "spindle cell oncocytoma of the adenohypophysis" is a very rare and often misdiagnosed entity. A benign biologic behavior has been suggested based on the absence of recurrences with a median follow-up of 3 years. Herein, we present 2 cases of recurrent spindle cell oncocytomas. One patient is a 71-year-old woman (case no. 1) and the other a 76-year-old man (case no. 2). Recently, both underwent transsphenoidal reexploration for recurrent "pituitary adenoma." Patient no. 1 had initial surgery 11 years ago with a recurrence after 3 years that was initially stable. Ultimately, a partial resection was performed after compression of optic pathways by the tumor, and approximately 1 year later, re-resection was carried out. Patient no. 2 had initial surgery 10 years ago with recurrence and resection after 3 years. He recently presented with a large mass that involved the pituitary fossa and base of the skull, with extension into the nasopharynx and nasal cavity. The primary and recurrent lesions of both cases showed similar architecture with interlacing fascicles of spindle cells that alternated with areas of epithelioid-like cells that exhibited eosinophilic, granular cytoplasm. Neoplastic cells were positive for vimentin, S-100 protein, and epithelial membrane antigen, and negative for glial fibrillary acidic protein, chromogranin, and pituitary hormones. Increased mitotic activity was noted in 1 lesion (case no. 2), although both cases had high Ki-67 indices (18% and 20%, respectively). The ultrastructural features of both cases were characteristic with intracytoplasmic accumulations of large mitochondria. The histopathologic features of these lesions are consistent with spindle cell oncocytoma of the adenohypophysis. In summary, we are reporting 2 cases of recurrent spindle cell oncocytoma of adenohypophysis with longer follow-up than previously published cases, suggesting the possibility of a more aggressive behavior than has been initially considered.