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Anticancer Research Jul 2019Spindle cell oncocytoma (SCO) is a rare non-neuroendocrine neoplasm of the pituitary gland. In general, surgical excision and radiation therapy is performed. However,...
BACKGROUND
Spindle cell oncocytoma (SCO) is a rare non-neuroendocrine neoplasm of the pituitary gland. In general, surgical excision and radiation therapy is performed. However, local recurrences are frequently seen, requiring repeated surgical and radio-oncological interventions. Thus, mutational analysis of the tumor and targeted therapy may represent a valuable therapy option in these patients.
CASE REPORT
A 38-year-old female patient with past medical history of 6 surgeries (two transsphenoidal and four transcranial), radiation therapy, and chemoradiation therapy due to several recurrences of a SCO, presented for follow-up imaging. MRI of the brain showed growth of a tumor in the right parasellar region consistent with a new local recurrence, which due to its size and location was considered to be not resectable. Molecular analysis of a previously surgically removed tumor showed a BRAF V600E mutation and thus, combined targeted inhibition of the MAPK/ERK signaling pathway using a BRAF inhibitor and a MEK inhibitor was started. Due to drug-induced panniculitis, MEK inhibitor had to be stopped and BRAF inhibitor only was continued, which was well tolerated by the patient. Subsequent imaging revealed tumor regression already four weeks after therapy initiation and no disease progression has been observed to date.
CONCLUSION
A SCO patient with BRAF V600E mutation was successfully treated using targeted inhibition of the MAPK/ERK signaling pathway. Under therapy, tumor regression was observed and the patient has been free of progressive disease for more than two years now. Thus, mutational analysis and targeted inhibition may offer an effective treatment option for SCO patients, while potential side-effects to this therapy, like observed in our case, can occur and needs to be adequately treated.
Topics: Adenoma, Oxyphilic; Adult; Female; Humans; MAP Kinase Signaling System; Mutation; Panniculitis; Pituitary Neoplasms; Protein Kinase Inhibitors; Proto-Oncogene Proteins B-raf
PubMed: 31262927
DOI: 10.21873/anticanres.13549 -
Endocrine Pathology Sep 2019The 2017 World Health Organization classification of central nervous system and endocrine tumors have introduced significant changes in the diagnostic criteria for... (Review)
Review
The 2017 World Health Organization classification of central nervous system and endocrine tumors have introduced significant changes in the diagnostic criteria for pituitary lesions. The aim of our paper is to describe the epidemiological, clinico-pathological, and radiological features of a single consecutive institutional surgical series of rare pituitary lesions, using these new criteria. Of the 316 endoscopic endonasal trans-sphenoidal approaches performed for pituitary lesions between 2010 and 2018, 15 rare lesions were encountered. These included metastases, pituitary carcinomas, pituicytomas, granular cell tumor, primary pituitary lymphomas, germinoma, mixed gangliocytoma-adenoma, hypophysitis, and pituitary hyperplasia. Their clinical, radiological, and pathological features are herewith presented along with a literature review that enabled us to propose an algorithm to facilitate a diagnosis for rare pituitary lesions.
Topics: Diagnostic Techniques, Endocrine; Humans; Pituitary Diseases; Rare Diseases; Retrospective Studies; Tertiary Care Centers; Thyroid Function Tests
PubMed: 31209729
DOI: 10.1007/s12022-019-09581-6 -
World Neurosurgery Sep 2019Granular cell tumors (GCTs), pituicytomas, and spindle cell oncocytomas are rare, nonfunctioning pituitary tumors sharing positive staining of thyroid transcription...
OBJECTIVE
Granular cell tumors (GCTs), pituicytomas, and spindle cell oncocytomas are rare, nonfunctioning pituitary tumors sharing positive staining of thyroid transcription factor 1. We present our series, the first single-institutional report with long-term surgical follow-up of all 3 tumor types.
METHODS
Our institutional pathology database was queried for these 3 pathologic diagnoses. Clinical records were assessed for clinical presentation, preoperative and postoperative endocrine status, tumor location on imaging, surgical characteristics, pathology results, and tumor recurrence.
RESULTS
Data were analyzed for 4 patients with GCTs, 4 with pituicytomas, and 3 with spindle cell oncocytomas. The most common symptoms at presentation were vision changes (64%), headache (55%), endocrine abnormalities (55%), and fatigue (46%). GCTs were the only subtype to present exclusively in the infundibulum and the only subtype in our series to be treated with a transcranial transsylvian approach to resection (n = 2). In our study, in contrast to other reports, estimated blood loss was less than 300 mL in all patients. Imaging confirmed gross total resection in all 11 cases with no known recurrences at a mean (standard deviation) follow-up of 4.7 (3.7) years.
CONCLUSIONS
We present a single-institution series of rare thyroid transcription factor 1-staining posterior pituitary tumors of the sellar region. Key novel findings include gross total resection with no tumor recurrence at nearly 5 years of mean follow-up and no cases of excess or uncontrolled blood loss. Our findings reinforce the observation that GCTs present in the suprasellar space.
Topics: Adenoma, Oxyphilic; Adult; Aged; Biomarkers, Tumor; Female; Granular Cell Tumor; Humans; Male; Middle Aged; Pituitary Gland; Pituitary Neoplasms; Retrospective Studies; Thyroid Nuclear Factor 1
PubMed: 31132506
DOI: 10.1016/j.wneu.2019.05.132 -
Acta Neuropathologica Communications May 2019Pituicytoma is a rare, poorly characterized tumor of the sellar region that is thought to be derived from neurohypophyseal pituicytes. Resection of pituicytomas is often...
Pituicytoma is a rare, poorly characterized tumor of the sellar region that is thought to be derived from neurohypophyseal pituicytes. Resection of pituicytomas is often associated with significant morbidity including diabetes insipidus and panhypopituitarism. Most of the literature on this tumor exists as small case series or case reports. Here we describe a cohort of fourteen pituicytoma resections from eleven patients. The average follow-up on these cases is 3.7 years with some patients having over 10 years of follow-up data available in the electronic medical record. Pituicytomas were frequently misdiagnosed on pre-operative imaging, and surgical resection was associated with persistent endocrine abnormalities. Histologically, the tumors showed a range of morphologies from epithelioid to spindled. All tumors were positive for TTF-1 with variable immunostaining for other markers including GFAP, EMA, S100, SSTR2A, and synaptophysin. Within this cohort are two patients with atypical pituicytomas which showed increased cellularity, pleomorphism, mitoses and elevated Ki-67 proliferation indexes when compared to non-atypical pituicytomas. Next generation sequencing performed on three tumors revealed alterations in genes involved in the MAPK pathway. Additionally, immunohistochemical staining for phosphorylated-ERK was positive in the majority of tumors. Increased awareness of the neoplastic entity and identification of targetable mutations have the potential to decrease the morbidity associated with resection of pituicytomas.
Topics: Adult; Aged; Biomarkers, Tumor; Female; Humans; Immunohistochemistry; MAP Kinase Signaling System; Male; Middle Aged; Pituitary Neoplasms; Proto-Oncogene Proteins B-raf
PubMed: 31046843
DOI: 10.1186/s40478-019-0722-6 -
Reviews in Endocrine & Metabolic... Jun 2019In 2017, the World Health Organization established that pituicytoma, granular cell tumor (GCT), spindle cell oncocytoma (SCO) and sellar ependymomas (SE) are posterior... (Review)
Review
In 2017, the World Health Organization established that pituicytoma, granular cell tumor (GCT), spindle cell oncocytoma (SCO) and sellar ependymomas (SE) are posterior pituitary tumors (PPT). They probably arise from the pituicytes and may constitute a unique histopathological entity. We carried out a systematic review using PubMed's database. A total of 266 patients with pathological diagnosis of PPT (135 pituicytomas, 69 GCT, 47 SCO, 8 SE and 7 mixed histology tumors) were analyzed. Gender distribution was identical and median age at diagnosis was 48 ± 21.8 years. Main presentation symptoms were visual disorders (n = 142; 58.1%), headache (n = 99; 40.5%), hypopituitarism (n = 84; 34.4%), hypercortisolism (n = 10; 4.1%), polyuriapolydipsia (n = 6; 2.4%) and acromegaly features (n = 5; 2.0%). On MRI, 122 (47.6%) patients showed sellar with suprasellar extension masses, 67 (23.1%) were suprasellar and 63 (24.6%) exclusively sellar. Median tumor size was 22.0 ± 14.2 mm. Two hundred sixty four patients underwent surgery, transphenoidal access was selected in 132 (64.4%) and craniotomy in 58 (28.3%). Complications were hypopituitarism (n = 70; 42.1%), diabetes insipidus (n = 55; 33.1%) and hemorrhage (n = 50; 30.1%). Tumor persisted in 93 patients (45.6%) and recurred in 13 (6.4%). Regarding comparison between main types of PPT, SCO patients were diagnosed later (60.0 vs 47.0 vs 47.0 years, p = 0.023), the tumor was larger 25.0 mm [10.8] vs 20.0 mm [14.2] vs 2.0 mm [15.0] and they were frequently sellar with suprasellar extension tumors (71.7% vs 46.2% vs 32.8%, p = 0.003) compared to pituicytoma and GCT. In conclusion, PPT are rare tumors and have been misdiagnosed mainly as non-functioning pituitary adenomas. Different types of PPT share similar epidemiology, clinical manifestations and surgical outcomes. Surgery is the only curative option but complications and subtotal resection are common.
Topics: Animals; Granular Cell Tumor; Humans; Pituitary Neoplasms
PubMed: 30864049
DOI: 10.1007/s11154-019-09484-1 -
Endocrine Apr 2019
Topics: Craniopharyngioma; Humans; Pituitary Gland, Posterior; Pituitary Neoplasms; Research Design
PubMed: 30838515
DOI: 10.1007/s12020-019-01864-6 -
Acta Neurochirurgica Apr 2019For the precise removal of pituitary tumors, preserving the surrounding normal structures, we need real-time intraoperative information on tumor location, margins, and...
BACKGROUND
For the precise removal of pituitary tumors, preserving the surrounding normal structures, we need real-time intraoperative information on tumor location, margins, and surrounding structures. The aim of this study was to evaluate the benefits of a new intraoperative real-time imaging modality using indocyanine green (ICG) fluorescence through an endoscopic system during transsphenoidal surgery (TSS) for pituitary tumors.
METHODS
Between August 2013 and October 2014, 20 patients with pituitary and parasellar region tumors underwent TSS using the ICG fluorescence endoscopic system. We used a peripheral vein bolus dose of 6.25 mg/injection of ICG, started with a time counter, and examined how each tissue type increased and decreased in fluorescence through time.
RESULTS
A total of 33 investigations were performed for 20 patients: 9 had growth hormone secreting adenomas, 6 non-functioning pituitary adenomas, 3 Rathke's cleft cysts, 1 meningioma, and 1 pituicytoma. After the injection of ICG, the intensity of fluorescence of tumor and normal tissues under near-infrared light showed clear differences. We could differentiate tumor margins from adjacent normal tissues and define clearly the surrounding normal structures using the different fluorescent intensities time changes and tissue-specific fluorescence patterns.
CONCLUSIONS
The ICG endoscopic system is simple, user-friendly, quick, cost-effective, and reliable. The method offered real-time information during TSS to delimit pituitary and parasellar region tumor tissue from surrounding normal structures. This method can contribute to the improvement of total removal rates of tumors, reduction of complications after TSS, saving surgical time, and preserving endocrinological functions.
Topics: Adenoma; Endoscopy; Female; Fluorescence; Humans; Indocyanine Green; Male; Middle Aged; Neurosurgical Procedures; Pituitary Neoplasms; Postoperative Complications; Surgery, Computer-Assisted
PubMed: 30762125
DOI: 10.1007/s00701-018-03778-0 -
Pituitary Feb 2019Spindle cell oncocytomas (SCOs) are very rare tumors of the posterior pituitary with potential for locally aggressive behaviour. Their treatment includes surgery and...
PURPOSE
Spindle cell oncocytomas (SCOs) are very rare tumors of the posterior pituitary with potential for locally aggressive behaviour. Their treatment includes surgery and possibly radiotherapy, however other options are lacking. Somatostatin receptors (SSTs) are a possible therapeutic target for somatostatin analogues and their expression has been demonstrated recently in closely related pituicytomas, but there are no data about their presence in SCOs.
METHODS
We collected five cases of SCO from four patients including one recurrent case. Immunohistochemical detection of TTF1, GFAP, CD68, SST, SST, SST, SST and D2 dopamine receptor (D2DR) was performed. Intensity, percentage of positive cells and pattern of expression was evaluated in semiquantitative fashion. Protein expression of SST and D2DR was further evaluated by western blot.
RESULTS
Mean patient age was 61.8 years (range 47-71 years) with male to female ratio 1:1. In one patient, samples from the original tumor and its recurrence 16 years later were assessed. TTF1 was positive in all five cases, no expression of GFAP and CD68 was seen. Immunohistochemical expression of SST was noted in 1/5 cases, SST in 2/5 cases, including recurrent case but not the original case. SST was expressed in 3/5 tumors and D2 dopamine receptor in 4/5 cases. Western blot was successfully performed in four samples. SST, SST and D2DR expression was identified in all the samples, including two cases originally negative for SST and one case negative for SST by immunohistochemistry. The number of positive cells and level of expression varied among different areas of the same tumors. No expression of SST was observed. In the patient with the recurrent tumor, intensity of SST, SST and D2DR expression varied between original tumor and its recurrence.
CONCLUSIONS
We demonstrated presence of different SST subtypes and D2DR in spindle cell oncocytomas. The most commonly expressed subtype was SST and SST, while no expression of SST was observed. Expression showed spatial heterogeneity and temporal changes as seen in the recurrent case. The biological meaning of SSTs expression in SCOs is unclear as well as whether it may be exploited in treatment of selected cases.
Topics: Acromegaly; Adenoma, Oxyphilic; Adult; Female; Humans; Male; Middle Aged; Receptors, Dopamine D2; Receptors, Somatostatin; Thyroid Cancer, Papillary; Thyroid Diseases
PubMed: 30607746
DOI: 10.1007/s11102-018-00935-7 -
World Neurosurgery Jan 2019The endoscopic endonasal approach is widely used for treating giant pituitary adenomas. However, a small subset of tumors is still challenging to treat, and the risk of...
BACKGROUND
The endoscopic endonasal approach is widely used for treating giant pituitary adenomas. However, a small subset of tumors is still challenging to treat, and the risk of complications increases when an endoscopic endonasal approach alone is used. The simultaneous combined endoscopic endonasal and transcranial approach is a surgical option for such difficult adenomas; however, very few studies have described the technical nuances and benefits of this approach.
METHODS
We treated 3 patients with giant pituitary adenoma and 1 patient with pituicytoma. Radiologic findings and clinical outcomes were retrospectively reviewed.
RESULTS
All patients had preoperative visual disturbances. A pterional approach was combined with an endoscopic endonasal approach to treat all the patients. Near-total and subtotal tumor removal was accomplished in 3 patients; however, only partial tumor removal was possible in 1 patient. Postoperative visual function improved in 3 patients, but there were no changes in 1 patient. There were no major complications; however, each patient developed either adrenocorticotropic hormone (ACTH) and thyroid-stimulating hormone deficiency or ACTH deficiency and persistent diabetes. Importantly, no cerebrospinal fluid leakage was observed in the patients.
CONCLUSIONS
Our simultaneous combined endoscopic and transcranial approach offers safe tumor resection and a low rate of complications. In this procedure, it is important that tumor debulking be performed by the main surgeon via a single surgical route and not by 2 surgeons using the simultaneous endonasal and transcranial approach, to avoid interference in the surgical field. This approach may be considered as a surgical option for carefully selected tumors in the sellar region.
Topics: Adenoma; Aged; Female; Humans; Male; Middle Aged; Natural Orifice Endoscopic Surgery; Neurosurgical Procedures; Nose; Pituitary Neoplasms
PubMed: 30336293
DOI: 10.1016/j.wneu.2018.10.047 -
Endocrine Jan 2019In 2017, the WHO established that pituicytoma, granular cell tumour (GCT) and spindle cell oncocytoma (SCO) are posterior pituitary tumours (PPT). Recent data suggests...
PURPOSE
In 2017, the WHO established that pituicytoma, granular cell tumour (GCT) and spindle cell oncocytoma (SCO) are posterior pituitary tumours (PPT). Recent data suggests that these tumours probably arise from the pituicytes and may constitute a spectrum of a unique histopathological entity. Our aim is to report the clinical findings and surgical outcomes of 16 patients with PPT. We also evaluated the tissue specimens available in light of current knowledge.
METHOD
Cross-sectional study with retrospective data.
RESULTS
PPT were 7 pituicytomas, 3 GCT and 6 SCO. Patients mean age was 55 years old and 75% were female. Basal hormonal study showed hyperprolactinemia (43.7%) and hypopituitarism (37.5%). There was no case of diabetes insipidus (DI). MRI showed sellar/suprasellar masses with mean size of 19.7mm. PPT was not suspected in any patient. Fifteen patients underwent surgery and complications were common: 20% had perioperative bleeding (one patient died because of a massive haemorrhage), 57.1% hypopituitarism, 35.7% permanent DI and 21.4% underwent a second surgery. Pathological findings shown positivity for thyroid transcription factor 1, vimentin and negativity for cytokeratin and chromogranin A in all specimens evaluated. S100 protein was positive in 88.8% of tumours. Ki67 was ≥ 3% in 66.6% and ranged from 4-7% in SCO.
CONCLUSION
PPT have similar histology, clinical features and are frequently misdiagnosed as nonfunctioning pituitary tumours. However, post-surgical complications including haemorrhage are common. A high clinical suspicion is needed to presume the diagnosis prior surgery and diminish the high morbidity of these tumours.
Topics: Adenoma, Oxyphilic; Adult; Aged; Cross-Sectional Studies; Female; Granular Cell Tumor; Humans; Hyperprolactinemia; Hypopituitarism; Magnetic Resonance Imaging; Male; Middle Aged; Neurosurgical Procedures; Pituitary Gland, Posterior; Pituitary Neoplasms; Postoperative Complications; Postoperative Hemorrhage; Retrospective Studies; Sella Turcica; Treatment Outcome
PubMed: 30276594
DOI: 10.1007/s12020-018-1774-2