Spindle Cell Oncocytoma Research Articles

6672 Pituicytomas and Spindle Cell Oncocytomas: Rare Posterior Pituitary Tumors

Abstract Disclosure: Y. Park: None. A. Shen: None. M. Christie: None. J. Wentworth: None. C.J. Yates: None. J. King: None. Background: Pituicytomas and spindle cell oncocytomas (SCO) are rare non-functioning benign posterior pituitary tumors that can present as suprasellar or sellar-suprasellar masses.[1] Pituicytomas originate from the pituicytes in the neurohypophysis and infundibulum of the pituitary gland.2 SCO were previously thought to derive from the adenohypophysis,3 however, are now classified as a tumor of the neurohypophysis characterized by immunohistochemical reactivity to thyroid transcription factor 1 (TTF1).4 According to the World Health Organization 2021 classifications, pituicytomas, granular cell tumors and SCO may represent morphologic variations of the same tumor expressing TTF1.5 Due to their rarity, their clinical characteristics are not yet well-defined and can be mistaken as non-functioning pituitary adenomas. Methods: We retrospectively reviewed the clinical data of two patients with pituicytomas and two patients with SCO confirmed on histopathology at our institution, evaluating their clinical characteristics and management outcomes. Results: Two male patients, aged 59 and 79, were diagnosed with pituicytoma, and two male patients, aged 33 and 55 were diagnosed with SCO. Three presented with visual impairment from mass effects and three patients had hypogonadotropic hypogonadism. None had pre-operative arginine vasopressin (AVP) deficiency. All lesions were isointense on T1-weighted, and most were hyperintense on T2-weighted magnetic resonance imaging. Three cases had non-gross total resection due to hypervascularity. Postoperatively, two patients developed AVP deficiency and three developed persistent anterior pituitary insufficiency (Table 1). Pituicytomas had a Ki67 of 1-3%, and SCO had a Topoisomerase labelling index of <1%. In one case of pituicytoma, due to tumor recurrence 2 years after initial surgery, adjuvant radiotherapy was considered. However, the patient developed a severe peri-tumoral subarachnoid hemorrhage and died prior to receiving radiotherapy. In contrast, the progression of the residual SCO occurred at a slower rate. Discussions: Posterior pituitary tumor differentials are broad, including pituicytoma, SCO, granular cell tumor, craniopharyngioma, meningioma and germinoma;6 hence, histopathological diagnosis is crucial. Although benign, pituicytomas and SCO can result in increased morbidity and postoperative complications, such as AVP deficiency and hypopituitarism. Recurrence and progression are common.7, 8 Gross total resection is optimal, but this is difficult due to hypervascularity.9 Our case of peri-tumoral subarachnoid hemorrhage resulting in death emphasizes the hypervascular nature of pituicytomas. Patients with pituicytomas and SCO should be monitored for tumor progression or recurrence and hemorrhagic complications. Adjuvant radiotherapy may be considered for the management of tumor recurrence. Presentation: 6/3/2024

Intraventricular pituicytoma: illustrative case.

Pituicytoma is a rare glial neoplasm from pituicytes of the neurohypophysis or infundibulum. It occurs in the sella and suprasellar area, and it is extremely uncommon to observe intraventricular pituicytoma without affecting the infundibulum or infundibular recess. A 69-year-old man had suffered progressive dementia for 6 months. Magnetic resonance imaging revealed a solid, homogeneously enhancing mass with flow voids within the anterior third ventricle. The sella, suprasellar area, infundibulum, and infundibular recess were unaffected. The patient underwent a transcallosal transchoroidal approach, which ended in partial removal of the tumor due to significant tumoral bleeding. A second surgery resulted in its subtotal removal. The tumor had bipolar cells, and their nuclei were immunoreactive for thyroid transcription factor-1. A DNA methylation analysis corresponded to the methylation class of pituicytoma, granular cell tumor, and spindle cell oncocytoma. Pituicytoma was the diagnosis based on these results. A systematic review identified 5 intraventricular pituicytoma cases. Intraventricular pituicytoma can grow without involvement of the infundibulum or infundibular recess. The current case suggests that pituicytes of the hypothalamic tuber cinereum can also give rise to pituicytoma. Because of the hypervascular nature of intraventricular pituicytomas, it is imperative to control intraoperative bleeding with attention to the adjacent hypothalamus. https://thejns.org/doi/10.3171/CASE24247.

Treatment modalities and outcomes of granular cell tumors and spindle cell oncocytomas of the pituitary gland: an analysis of two national cancer databases.

Spindle cell oncocytomas (SCO) and granular cell tumors (GCT) are rare primary pituitary neoplasms; the optimal treatment paradigms for these lesions are unknown and largely unexplored. Thus, using national registries, we analyze the epidemiology, management patterns, and surgical outcomes of SCOs and GCTs. The National Cancer Database (NCDB; years 2003-2017) and the Surveillance, Epidemiology, and End Results Program (SEER; years 2004-2018) were queried for patients with pituitary SCOs orGCTs. Incidence, extent of surgical resection, and rate of postoperative radiation use for subtotally resected lesions comprised the primary outcomes of interest. All-cause mortality was also analyzed via time-to-event Kaplan-Meier curves. SCOs and GCTs have an annual incidence of 0.017 and 0.023 per 1,000,000, respectively. They comprise 0.1% of the benign pituitary tumors registered in NCDB. A total of 112,241 benign pituitary tumors were identified in NCDB during the study period, of which 83 (0.07%) were SCOs and 59 (0.05%) were GCTs. Median age at diagnosis was 55years, 44% were females, and median maximal tumor diameter at presentation was 2.1cm. Gross total resection was achieved in 54% patients. Ten patients (7%) had postoperative radiation. Comparing patients with GCTs versus SCOs, the former were more likely to be younger at diagnosis (48.0 vs. 59.0, respectively; p < 0.01) and female (59% vs. 34%, p = 0.01). GCTs and SCOs did not differ in terms of size at diagnoses (median maximal diameter: 1.9cm vs. 2.2cm, respectively; p = 0.59) or gross total resection rates (62% vs. 49%, p = 0.32). After matching SCOs and GCTs with pituitary adenomas on age, sex, and tumor size, the former were less likely to undergo gross total resection (53% vs. 72%; p = 0.03). Patients with SCOs and GCTs had a shorter overall survival when compared to patients with pituitary adenomas (p < 0.01) and a higher rate of thirty-day mortality (3.1% vs 0.0%; p = 0.013). SCOs and GCTs are rare pituitary tumors, and their management entails particular challenges. Gross total resection is often not possible, and adjuvant radiation might be employed following subtotal resection.

Suprasellar granular cell tumor: A rare case report

Granular cell tumor (GCT) originating from the sellar and suprasellar regions, specifically from the neurohypophysis, is a rare neoplasm. Symptomatic GCT of the neurohypophysis is exceedingly rare, being &lt;70 cases described so far. GCTs predominantly exhibit benign behavior, while the malignancy rate remains at 2%. Imaging is quite unspecific and diagnosis is difficult to establish preoperatively. Histopathology and immunohistochemistry serve as the definitive diagnostic approach for GCTs and help in distinguishing GCT from other pituitary tumors, including pituitary adenoma, pituicytoma, and spindle cell oncocytoma. These tumors are resistant to radiotherapy and chemotherapy, necessitating surgical resection as the primary treatment modality. Due to the potential absence of distinct tumor masses and local tissue infiltration by tumor cells, complete excision is crucial, with resection extent extending beyond areas of infiltration. Here, we present a rare case of GCT originating from the posterior pituitary in the suprasellar region. On immunohistochemistry, tumor cells expressed diffusely thyroid transcription factor-1, S-100 protein, and vimentin confirming the diagnosis of supra-sellar GCT. The reported case is noteworthy for the rarity of the clinicopathological entity.

Epidemiology, Genetics and Pathophysiology of Pituitary Tumors

Pituitary tumors or tumors of the sella turcica include pituitary neuroendocrine tumors, Rathke's cleft cysts, craniopharyngiomas, tuberculum sellae, planum sphenoidale meningiomas, germ cell tumors, and hypophysitis. In addition, some rare tumors, such as pituicytomas, granular cell tumors, spindle cell oncocytomas, and chordomas or chondrosarcomas, arise from the parasellar regions. The treatment strategy is completely different for each lesion; therefore, accurate diagnosis is essential.

Pituitary spindle cell oncocytoma presented as pituitary apoplexy, case study

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Epigenetic Alteration of H3K27me3 as a Possible Oncogenic Mechanism of Central Neurocytoma

Central neurocytoma (CN) is a low-grade neuronal tumor that mainly arises from the lateral ventricle (LV). This tumor remains poorly understood in the sense that no driver gene aberrations have been identified thus far. We investigated immunomarkers in fetal and adult brains and 45 supratentorial periventricular tumors to characterize the biomarkers, cell of origin, and tumorigenesis of CN. All CNs occurred in the LV. A minority involved the third ventricle, but none involved the fourth ventricle. As expected, next-generation sequencing performed using a brain-tumor-targeted gene panel in 7 CNs and whole exome sequencing in 5 CNs showed no driver mutations. Immunohistochemically, CNs were robustly positive for FGFR3 (100%), SSTR2 (92%), TTF-1 (Nkx2.1) (88%), GLUT-1 (84%), and L1CAM (76%), in addition to the well-known markers of CN, synaptophysin (100%) and NeuN (96%). TTF-1 was also positive in subependymal giant cell astrocytomas (100%, 5/5) and the pituicyte tumor family, including pituicytoma and spindle cell oncocytoma (100%, 5/5). Interestingly, 1 case of LV subependymoma (20%, 1/5) was positive for TTF-1, but all LV ependymomas were negative (0/5 positive). Because TTF-1-positive cells were detected in the medial ganglionic eminence around the foramen of Monro of the fetal brain and in the subventricular zone of the LV of the adult brain, CN may arise from subventricular TTF-1-positive cells undergoing neuronal differentiation. H3K27me3 loss was observed in all CNs and one case (20%) of LV subependymoma, suggesting that chromatin remodeling complexes or epigenetic alterations may be involved in the tumorigenesis of all CNs and some ST-subependymomas. Further studies are required to determine the exact tumorigenic mechanism of CN.

Primary papillary epithelial tumor of the sella and posterior pituitary tumor show similar (epi)genetic features and constitute a single neuro-oncological entity.

"Primary papillary epithelial tumor of the sella (PPETS)" is a recently described rare tumor entity of the central nervous system (CNS) with stereotypic location in the sella. Comprehensive molecular investigations and epigenetic profiles of PPETS have not been performed to date. We report a comprehensive clinical, histopathologic, and molecular assessment of 5 PPETS cases in comparison with a cohort composed of 7 choroid plexus papilloma (CPP), 7 central neurocytoma (CN), 15 posterior pituitary tumor (PPT) including 4 pituicytoma, 6 granular cell tumors of the sellar region (GCT), and 5 spindle cell oncocytoma. All PPETS had good outcomes. Immunohistochemically, PPETS tumors showed positive staining with TTF1, EMA, AE1/AE3, MAP2, and Vimentin, but were negatively stained with Syn, GFAP, CgA, and S100, and sporadically stained with Ki-67. In unsupervised hierarchical clustering and t-distributed stochastic neighbor embedding analyses of DNA-methylation data, PPETS and PPT tumors formed a distinct cluster irrespective of their histologic types. However, PPETS tumors did not cluster together with CPP and CN samples. Similar findings were obtained when our samples were projected into the reference cohort of the brain tumor classifier. Substantial fractions of the PPETS and PPT tumors shared broadly similar chromosomal copy number alterations. No mutations were detected using targeted next-generation sequencing. Though more cases are needed to further elucidate the molecular pathogenesis of these tumors, our findings indicate that PPETS and PPT tumors may constitute a single neurooncological entity.

LBMON173 Non-functioning Seller Masses: Tumor Types, Surgical Management And Course Over Time

Abstract Introduction Pituitary adenomas (PA) are common. However, not all sellar tumors are PA. The specific diagnosis of a sellar mass can be difficult. Although there is abundant literature on PA, other types of sellar masses are not well described. In particular, their course over time and response to therapy are not well known. In this study, our objectives were to review non-functioning sellar masses treated with trans sphenoidal surgery (TSS) over the last 15 years to understand their types, success of surgery, and course over time. Patients and Methods We retrospectively reviewed all cases of non-functioning sellar masses managed at our hospital over the last 15 years (January 2007-December 2021). Out of 181 sellar masses that were resected by TSS during this period, 91 were functional PA and 90 were non-functional sellar masses. These sellar masses included non-functioning pituitary adenomas and other non-pituitary seller masses operated at our center during the above period and are the subject of this study. Results The patients included 29 (32%) females and 61 (68%) males with a median age of 41 years (range 13-75 years). The sellar masses were non-functional PA in 50 (55.6%)cases, atypical PA in 30 (33.3%) cases and non-PA in 10 (11%) cases. The 10 non-PA tumors included craniopharyngioma 3 cases, meningioma 3 cases, chordoma 1 case, giant cell tumor of the bone 1 case, spindle cell oncocytoma 1 case and Rathke cyst 1 case. The median largest tumor diameter was 3.15 cm (Interquartile range 2.2-4. 0). Only 5 cases (5.6%) were intrasellar, the other 85 cases (94.4%) had suprasellar (75 cases, 83%) and/or parasellar (32 cases, 35.6%) extension. Necrosis/cystic changes on MRI were present in 24 cases (26.7%). TSS was performed in 86 cases (95.6%) and transcranial surgery in 4 (4.4%) cases. The surgeries were complicated by transient central DI in 21 cases (23.3%), permanent CDI in 6 cases (6.7%), CSF leak in 8 cases (9%), bleeding in 2 (2.2%), stroke in 3 (3.3%) and partial or panhypopituitarism in 58 cases (64.4%). Twenty-two (24.4%) patients underwent a second TSS, 6 (6.7%) transcranial surgery, 32 (35.6%) external radiotherapy. At a median follow-up of 8.5 years (IQ range 4.63-12.18), only 19 (21%) patients had no evidence of residual tumor on follow-up MRI. The other 71 (79%) cases continued to have evidence of residual tumor, either completely intrasellar in 30 (33.3%) cases or with the suprasellar or parasellar residual component in 41 (45.6%) cases. Conclusions Non-functioning PA and other non-pituitary sellar tumors constitute 50% of sellar masses. Most are non-functioning PA, but atypical PA and other non-PA tumors can masquerade as PA. Most of these Non-functioning sellar masses are large with supra and parasellar extension. Surgery effectively reduces tumor size but is rarely curative and frequently complicated by hypopituitarism of variable severity and local complications. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Spindle Cells Oncocytoma and Rathke’s Cyst; A Collision Sellar Tumor– Brief Communication &amp; Case Report

Collision tumors comprising of pituitary adenomas with other sellar neoplasms are rare. Histological examination is necessary since preoperative studies cannot guarantee an accurate diagnosis. A 66-year-old man with headache and progressive visual alterations, MRI showed a sellar tumor that was diagnosed as pituitary adenoma and graduated as HV IIIc. He underwent surgery and two lesions were resected, one on the cavernous sinus and the other one in sellar region. The lesion of the venous sinus corresponds to a cyst covered by a ciliated pseudostratified epithelium that was diagnosed as Rathke's cyst, and the second one was formed by a neoplastic lesion of elongated cells with focal cellular atypia in a sarcomatous pattern, forming fascicles alternating with a pattern formed by medium eosinophilic cells predominantly in elongated cells in a stroma with abundant sinusoids. For immunohistochemistry, the epithelium of the cyst was PTTG-1, cytokeratin 6/8, and chromogranin positive, while the other lesion was positive chromogranin, FSH, LH PTTG-1, TTF-1, while the spindle cells area was positive immunoreaction for PTTG-1, GFAP, S-100, and VIM and weak expression for TTF-1. These histologic and immunohistochemical findings are suggestive of spindle cells oncocytoma and Rathke cyst, is a rare sellar collision tumor. The expression of TTF-1 in the spindle cell oncocytoma with the idea of common histogenesis for pituicytoma and SCOs and raise the possibility of more aggressive growth in SCOs as compared to pituicytoma.

Recommendation to improve the WHO classification of posterior pituitary tumors as a unique entity: evidence from a large case series.

Introduction Most studies reporting posterior pituitary tumors (PPTs) are small case series or single cases.Methods Patients with a histological diagnosis of PPT from January 2010 to December 2021 in a tertiary center were identified. We reported clinical symptoms, endocrine assessments, radiological and pathological features, and surgical outcomes of PPTs.Results A total of 51 patients (23 males, 51.3 ± 10.3 years old) with PPT were included in this study. Major symptoms were visual defects, headache, and hypopituitarism, while diabetes insipidus was uncommon (9.8%). The typical radiological feature was homogeneous enhancement (84.3%) of a regular-shaped mass on T1 contrast imaging without cystic change, calcification, or cavernous sinus invasion. We achieved gross total resection in 38/51 patients (74.5%). Pathologically, all tumors showed thyroid transcription factor 1 immunoreactivity. Among 29 patients with suprasellar PPTs, postoperative hemorrhage due to tumor residue was encountered in 2/15 cases in the transcranial group and 0/14 in the endoscopy group. Patients with spindle cell oncocytoma (SCO) were more likely to be surgically treated (25% vs 0%, P = 0.018), harbor a higher Ki-67 index (16.7% vs 0% > 5% P = 0.050), and present a lower 2-year recurrence-free survival rate (67.5% vs 90.9%) compared with patients with pituicytoma or granular cell tumor.Conclusion PPTs should be considered in the differential diagnosis of patients with sellar and suprasellar masses with a regular lesion with homogeneous enhancement. SCOs had high proliferation activity and risk of recurrence.

Abstract #1165466: Rare Pituitary Spindle Cell Oncocytoma Presenting as Headache

Pituitary tumors have a prevalence of approximately 16.7% in the general population. The tumors regularly present with innocuous symptoms and are often incidentally identified on imaging. Pituitary adenomas are the most common types of sellar tumors of the anterior pituitary. Here we discuss an uncommon, benign tumor of the posterior pituitary initially assumed to be a macroadenoma.

Overview of the 2022 WHO Classification of Pituitary Tumors.

This review summarizes the changes in the 5th Edition of the WHO Classification of Endocrine and Neuroendocrine Tumors that relate to the pituitary gland. The new classification clearly distinguishes anterior lobe (adenohypophyseal) from posterior lobe (neurohypophyseal) and hypothalamic tumors. Other tumors arising in the sellar region are also discussed. Anterior lobe tumors include (i) well-differentiated adenohypophyseal tumors that are now classified as pituitary neuroendocrine tumors (PitNETs; formerly known as pituitary adenomas), (ii) pituitary blastoma, and (iii) the two types of craniopharyngioma. The new WHO classification provides detailed histological subtyping of a PitNET based on the tumor cell lineage, cell type, and related characteristics. The routine use of immunohistochemistry for pituitary transcription factors (PIT1, TPIT, SF1, GATA3, and ERα) is endorsed in this classification. The major PIT1, TPIT, and SF1 lineage-defined PitNET types and subtypes feature distinct morphologic, molecular, and clinical differences. The "null cell" tumor, which is a diagnosis of exclusion, is reserved for PitNETs with no evidence of adenohypophyseal lineage differentiation. Unlike the 2017 WHO classification, mammosomatotroph and acidophil stem cell tumors represent distinct PIT1-lineage PitNETs. The diagnostic category of PIT1-positive plurihormonal tumor that was introduced in the 2017 WHO classification is replaced by two clinicopathologically distinct PitNETs: the immature PIT1-lineage tumor (formerly known assilent subtype 3 tumor) and the mature plurihormonal PIT1-lineage tumor. Rare unusual plurihormonal tumors feature multi-lineage differentiation. The importance of recognizing multiple synchronous PitNETs is emphasized to avoid misclassification. The term "metastatic PitNET" is advocated to replace the previous terminology "pituitary carcinoma" in order to avoid confusion with neuroendocrine carcinoma (a poorly differentiated epithelial neuroendocrine neoplasm). Subtypes of PitNETs that are associated with a high risk of adverse biology are emphasized within their cell lineage and cell type as well as based on clinical variables. Posterior lobe tumors, the family of pituicyte tumors, include the traditional pituicytoma, the oncocytic form (spindle cell oncocytoma), the granular cell form (granular cell tumor), and the ependymal type (sellar ependymoma). Although these historical terms are entrenched in the literature, they are nonspecific and confusing, such that oncocytic pituicytoma, granular cell pituicytoma, and ependymal pituicytoma are now proposed as more accurate. Tumors with hypothalamic neuronal differentiation are classified as gangliocytomas or neurocytomas based on large and small cell size, respectively. This classification sets the standard for a high degree of sophistication to allow individualized patient management approaches.

Granular Cell Tumor and Spindle Cell Oncocytoma of the Pituitary Gland: Imaging and Intraoperative Cytology Diagnostic Dilemmas and Management Challenges.

Tumors arising from the posterior pituitary gland are rare and closely resemble pituitary adenoma in presentation and imaging. Most of them come as a histopathologic surprise. We have analyzed the posterior pituitary tumors managed in our institute and have discussed the dilemmas in imaging, challenges in intraoperative squash cytology, and surgical management. We retrospectively reviewed our operative database of pituitary tumors over the past 10 years, which included five posterior pituitary tumors (three granular cell tumors [GCTs] and two spindle cell oncocytomas [SCOs]). Clinical, imaging, and endocrine characteristics; intraoperative details; histopathologic features; and postoperative outcomes were collected and analyzed. The mean age of the patients was 47 years. All patients presented with varying degrees of vision loss. Radiology revealed a sellar / suprasellar lesion with the pituitary gland seen separately in two of three GCTs, whereas a separate pituitary gland could not be identified in both the SCOs. Pituitary adenoma was a radiologic diagnosis in only two of five cases. Three patients underwent a transsphenoidal surgery, whereas two underwent surgery by the transcranial approach. Intraoperative cytology was challenging, though a possibility of posterior pituitary tumor was considered in three of four cases, whereas one was considered meningioma. All the tumors were very vascular and influenced the extent of resection. GCTs and SCOs are relatively uncommon tumors that are difficult to diagnose on preoperative imaging. Intraoperative squash cytology too can pose challenges. A preoperative suspicion can prepare the surgeon for surgery of these hypervascular tumors. The transcranial approach may be necessary in cases of uncertainty in imaging.

Skull Base Tumors: Neuropathology and Clinical Implications.

Tumors that arise in and around the skull base comprise a wide range of common and rare entities. Recent studies have advanced our understanding of their pathogenesis, which in some cases, have significantly influenced clinical practice. The genotype of meningiomas is strongly associated with their phenotype, including histologic subtype and tumor location, and clinical outcome. A single molecular alteration, NAB2-STAT6 fusion, has redefined the category of solitary fibrous tumors to include the previous entity hemangiopericytomas. Schwannomas, both sporadic and familial, are characterized by near ubiquitous alterations in NF2 , with additional mutations in SMARCB1 or LZTR1 in schwannomatosis. In pituitary adenohypophyseal tumors, cell lineage transcription factors such as SF-1, T-PIT, and PIT-1 are now essential for classification, providing a more rigorous taxonomy for tumors that were previously considered null cell adenomas. The pituicyte lineage transcription factor TTF-1 defines neurohypophyseal tumors, which may represent a single nosological entity with a spectrum of morphologic manifestations (ie, granular cell tumor, pituicytoma, and spindle cell oncocytoma). Likewise, the notochord cell lineage transcription factor brachyury defines chordoma, discriminating them from chondrosarcomas. The identification of nonoverlapping genetic drivers of adamantinomatous craniopharyngiomas and papillary craniopharyngiomas indicates that these are distinct tumor entities and has led to successful targeted treatment of papillary craniopharyngiomas using BRAF and/or mitogen-activated protein kinase inhibitors. Similarly, dramatic therapeutic responses have been achieved in patients with Langerhans cell histiocytosis, both with BRAF -mutant and BRAF -wildtype tumors. Familiarity with the pathology of skull base tumors, their natural history, and molecular features is essential for optimizing patient care.

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

Spindle cell oncocytoma (SCO) of the pituitary is a rare tumor of the adenohypophysis occurring in the sellar/suprasellar region. This tumor has been recognized as a distinct entity by the WHO Classification of CNS tumor in 2007. Spindle cell oncocytoma of the pituitary gland accounts for 0.1–0.4% of all sellar region tumors and is predominantly seen in the older adult population. This rare entity simulates clinical and radiological features of pituitary adenoma and is often misdiagnosed. Though WHO grade 1, the tumor can recur and have invasive properties. Herein, we report a 61-year-old woman with panhypopituitarism and temporal field cut, clinically and radiologically diagnosed as pituitary macroadenoma, while the histomorphological and immunohistochemistry features helped in arriving at a diagnosis of Spindle Cell Oncocytoma. The clinicopathological, histomorphological, immunohistochemical, and molecular properties of the tumor are further discussed.

SURG-15. PITUITARY SPINDLE CELL ONCOCYTOMA: A CASE REPORT AND LITERATURE REVIEW

Abstract BACKGROUND Spindle cell oncocytoma (SCO) of the pituitary gland is an extremely rare non-functional WHO grade 1 tumor. SCO are often misdiagnosed as nonfunctional pituitary adenomas on pre-operative imaging. They are often hypervascular and locally adherent, which increases hemorrhage risk and limits surgical resection, leading to increased risk of recurrence. We report a case of SCO treated at our institution and provide a review of the current literature. METHODS A 75-year-old male with a history of hypertension, left thalamic stroke, Parkinson’s disease, and normal pressure hypertension presented to neurosurgery clinic with bitemporal hemianopsia, hyponatremia, and abnormal gait and mobility. Imaging showed an enhancing intra- and suprasellar, hyperdense tumor mass measuring 3.0 cm in diameter. We performed a systemic literature search in the PubMed database to identify previous reports of spindle cell oncocytoma. After exclusion of studies that did not meet criteria, 32 publications were selected for critical reading. RESULTS The patient underwent an endoscopic transsphenoidal resection of the tumor via a multi-disciplinary team. The tumor was fibrous and adherent to the intrasellar dura, with gross invasion of the diaphragm sella, necessitating partial resection of the diaphragm. The defect was repaired, and the patient made an uncomplicated recovery. Post-operatively, the patient experienced improved vision. Upon literature review, SCO present in older adults with an average age of 56.2 ± 14.7 with visual deficits (67.9%), headache (33.3%), hypopituitarism (24.7%), and nausea (11.1%). Full resection was achieved in 38.6% of cases leading to recurrence rate of 23.5% with an average time until recurrence of 32.5 months (range 1-120 months). CONCLUSION Careful surgical technique is needed due to SCO hypervascularity and strong adherence to minimize risk of injury to surrounding neurovascular structures. Long-term follow up is recommended due risk of recurrence.

Genetic and epigenetic characterization of posterior pituitary tumors

Pituicytoma (PITUI), granular cell tumor (GCT), and spindle cell oncocytoma (SCO) are rare tumors of the posterior pituitary. Histologically, they may be challenging to distinguish and have been proposed to represent a histological spectrum of a single entity. We performed targeted next-generation sequencing, DNA methylation profiling, and copy number analysis on 47 tumors (14 PITUI; 12 GCT; 21 SCO) to investigate molecular features and explore possibilities of clinically meaningful tumor subclassification. We detected two main epigenomic subgroups by unsupervised clustering of DNA methylation data, though the overall methylation differences were subtle. The largest group (n = 23) contained most PITUIs and a subset of SCOs and was enriched for pathogenic mutations within genes in the MAPK/PI3K pathways (12/17 [71%] of sequenced tumors: FGFR1 (3), HRAS (3), BRAF (2), NF1 (2), CBL (1), MAP2K2 (1), PTEN (1)) and two with accompanying TERT promoter mutation. The second group (n = 16) contained most GCTs and a subset of SCOs, all of which mostly lacked identifiable genetic drivers. Outcome analysis demonstrated that the presence of chromosomal imbalances was significantly associated with reduced progression-free survival especially within the combined PITUI and SCO group (p = 0.031). In summary, we observed only subtle DNA methylation differences between posterior pituitary tumors, indicating that these tumors may be best classified as subtypes of a single entity. Nevertheless, our data indicate differences in mutation patterns and clinical outcome. For a clinically meaningful subclassification, we propose a combined histo-molecular approach into three subtypes: one subtype is defined by granular cell histology, scarcity of identifiable oncogenic mutations, and favorable outcome. The other two subtypes have either SCO or PITUI histology but are segregated by chromosomal copy number profile into a favorable group (no copy number changes) and a less favorable group (copy number imbalances present). Both of the latter groups have recurrent MAPK/PI3K genetic alterations that represent potential therapeutic targets.

Pituitary spindle cell oncocytoma: illustrative case.

BACKGROUNDSpindle cell oncocytoma (SCO) of the pituitary gland is an extremely rare nonfunctional World Health Organization grade I tumor. SCOs are often misdiagnosed as nonfunctional pituitary adenomas on the basis of preoperative imaging. They are often hypervascular and locally adherent, which increases hemorrhage risk and limits resection, leading to increased risk of recurrence. The authors report a case of SCO treated at their institution and provide a review of the current literature.OBSERVATIONSSCO of the pituitary gland can be a rare cause of progressively growing pituitary tumors that presents similarly to nonfunctional pituitary adenoma. Endoscopic transsphenoidal resection of the tumor by a multidisciplinary team allowed total resection despite local adherence of the tumor. Postoperatively, the patient’s visual symptoms improved with persistence of secondary adrenal insufficiency and secondary hypothyroidism.LESSONSCareful resection is needed due to SCO’s characteristic hypervascularity and strong adherence to minimize local structure damage. Long-term follow-up is recommended due to the tendency for recurrence.

Co-occurrence of Pituitary Neuroendocrine Tumors (PitNETs) and Tumors of the Neurohypophysis.

Between 1996 and 2020, 12,565 cases were enrolled in the German Registry of Pituitary Tumors including 10,084 PitNETs (10,067 adenomas and 19 carcinomas obtained surgically and 193 adenomas diagnosed at autopsy) as well as 69 spindle cell tumors of the neurohypophysis (64 surgical specimens and 5 autopsies). In six patients (1 post mortem and 5 surgical specimens), PitNETs as well as posterior lobe tumors were found in the specimens. Two of the PitNETs were sparsely granulated prolactin-producing tumors, combined in one case with a granular cell tumor and in one case with a pituicytoma. One of the PitNETs revealed that autopsy was a sparsely granulated GH tumor combined with a neurohypophyseal granular cell tumor. Two PitNETs were null cell adenomas combined with a pituicytoma and a spindle cell oncocytoma, respectively. Further, one Crooke cell tumor was combined with a spindle cell oncocytoma. In five cases, the PitNETs were larger than the posterior lobe tumors and accounted for the clinical symptoms. Previously, four cases of co-existing pituitary anterior and posterior lobe tumors were described in the literature, comprising two ACTH PitNETs, one gonadotrophic PitNET and one null cell PitNET, each in combination with a pituicytoma. PitNETs and concomitant granular cell tumor or spindle cell oncocytoma, as observed in our cohort, have not been reported before.