Giant cell glioblastoma with lipogenic differentiation in a patient with neurofibromatosis type 1: A case report.

A 45-year-old woman with neurofibromatosis type 1 (NF1) developed a tumor in the left frontal lobe that showed features of giant cell glioblastoma (GC-GB). In addition to the typical GC-GB features, the tumor showed lipogenic differentiation, with many atypical lipoblasts and mature adipocytes. Tumor cells, including the lipogenic cells, were immunoreactive for GFAP, S-100 protein, ATRX, and p53. They were negative for IDH1-R132H, BRAF V600E, synaptophysin, NeuN, p16, mismatch repair proteins, and CD34. The patient is free from recurrence at approximately two years postoperatively. This is the fifth reported case of NF1-associated GC-GB (the second adult case). NF1 gene mutation might have played a role in the pathogenesis of lipogenic differentiation of GC-GB. The differential diagnosis of lipidized GC-GB from gliosarcoma or anaplastic pleomorphic xanthoastrocytoma is briefly discussed.

The effect of shunt removal on the quality of life in patients with congenital hydrocephalus.

BACKGROUND: Although there have been reports investigating the quality of life of patients who underwent ventriculoperitoneal shunting or endoscopic third ventriculostomy (ETV) for congenital hydrocephalus, there have been no studies of the quality of life of patients after ventriculoperitoneal shunt (VPS) removal. In the present study, a survey of pediatric and congenital hydrocephalus patients was conducted to compare the quality of life of patients with a remaining VPS with that of patients who had the shunt removed. METHODS: Between February 2020 and November 2021, an outpatient survey was administered to patients 8 years of age and older who had undergone VPS due to a diagnosis of congenital hydrocephalus. The Hydrocephalus Outcome Questionnaire (HOQ) was used to assess the quality of life for this study. The HOQ scores (overall health score, physical health score, cognitive health score, and social-emotional health score) were compared among three groups: a VPS-remaining group, VPS-removed with endoscopic third ventriculostomy (ETV) group, and VPS-removed without ETV group. RESULTS: The total number of patients who underwent VPS for hydrocephalus was 71, with 47 in the VPS-remaining group, 14 in the shunt-removed with ETV group, and 10 in the shunt-removed without ETV group. The HOQ overall health score was 0.68 for the VPS-remaining group, 0.74 for the shunt-removed with ETV group, and 0.74 for the shunt-removed without ETV. There were no significant differences between the VPS-remaining group and the VPS-removed with or without ETV groups (p = 0.3255, 0.4178, respectively). CONCLUSION: There was no significant difference in the quality of life between patients with a remaining VPS and those who had their VPS removed with or without ETV.

5-Aminolevulinic acid fluorescence-guided endoscopic surgery for deep-seated intraparenchymal tumors.

AIM: The usefulness of 5-aminolevulinic acid (5-ALA) fluorescence-assisted surgery for maximum resection of malignant gliomas has been established. However, its usefulness when combined with endoscopic surgery for deep-seated tumors has not been well established. In this study, whether 5-ALA photodynamic diagnosis (PDD) is feasible and useful for endoscopic surgery was investigated. METHODS: A specially designed endoscope for PDD that delivers white light or blue light (375-440 nm) as excitation light was used. The fluorescence emitted by the tumor was evaluated in the cavity during resection or at the tip of the sheath during biopsy. The intensity of fluorescence was classified into three categories: strong, vague, and negative. RESULTS: A total of 30 intraparenchymal tumors were observed with a neuroendoscope and 5-ALA PDD; 16 patients underwent resection, and 14 underwent biopsy. Overall, 67% (20/30) of tumors showed positive fluorescence of protoporphyrin IX. High-grade gliomas (HGGs) including glioblastoma (GBM) and anaplastic astrocytoma (AA) showed strong fluorescence in 47% (7/15), vague fluorescence in 33% (5/15), and negative fluorescence in 20% (3/15) of cases. Low-grade gliomas (LGGs) showed vague fluorescence in 33% (1/3) and negative fluorescence in 67% (2/3). Diffuse large B-cell lymphoma (DLBCL) showed vague fluorescence in 38% (3/8) and negative fluorescence in 63% (5/8). Metastatic tumors showed strong fluorescence in 25% (1/4) and vague fluorescence in 75% (3/4). In the comparison of fluorescence evaluation, a significant difference was observed only in the comparison between HGGs and DLBCL (p = 0.049). CONCLUSION: These results suggest that 5-ALA PDD-assisted endoscopic surgery is feasible and useful for deep-seated intraparenchymal tumors.

A ventricular catheter that migrated into the fourth ventricle successfully removed using a neuroendoscope.

BACKGROUND: In order to remove a foreign body in the ventricle, such as a ventricular drainage catheter, craniotomy and corticotomy are required to access the ventricle. A case in which a catheter in the 4th ventricle was safely removed with a flexible neuroendoscope is reported. CASE DESCRIPTION: A 47-year-old man underwent coil embolization and ventricular drainage for subarachnoid hemorrhage. 10 days after the operation, he tore off the ventricular drainage catheter and the catheter remained intracranially. The tip of the catheter was in the 4th ventricle and the operation to remove remaining catheter with a neuroendoscope was performed. Using a neuroendoscope, we could remove the catheter safely and did not detect the complications. CONCLUSION: To date, there have been no reports of cases in which a drainage catheter in the ventricle was removed using a flexible endoscope. This case suggests that a flexible endoscope is useful for removing a foreign body from the ventricle less invasively.

5-ALA fluorescence-guided endoscopic surgery for mixed germ cell tumors.

5-Aminolevulinic acid (5-ALA) fluorescence-guided surgery is widely used for detection and planning of resection of malignant gliomas and other brain tumors. However, no reports have described 5-ALA fluorescence-guided surgery or direct visualization of germ cell tumors. Here, we report two cases of germ cell tumors in which a positive 5-ALA fluorescent signal was visualized with a neuroendoscope. Both cases had a tumor in the pineal region that was associated with hydrocephalus. The patients underwent surgery after administration of 5-ALA. After ventricular puncture of the anterior horn, we could observe the ventricular wall and tumor using the Karl Storz Photodynamic diagnosis system endoscope. Then, biopsy of the pineal tumor and endoscopic third ventriculostomy were performed in both cases. In case 1, a 22-year-old man, part of the ventricular wall and tumor tissue showed red fluorescence. In case 2, a 16-year-old man, part of the fornix and infundibular recess showed red fluorescence, and the tumor showed relatively weak red fluorescence. The histopathological diagnosis of both cases was pure germinoma. This is the first report of direct visualization of mixed germinomas with 5-ALA fluorescence-guided endoscopic surgery. This method not only allows visualization of the tumor mass, but may also be useful for detailed observation in the ventricular wall.

Refractory Delayed Pneumocephalus after Transsphenoidal Cyst Drainage for Rathke's Cleft Cyst in a Patient with a Cerebrospinal Fluid Shunt.

A 75-year-old man presented with bilateral lower limb weakness to our hospital from another clinic. Radiological examinations implied the possibilities of idiopathic normal pressure hydrocephalus (iNPH) and a suprasellar cyst, but both were observed conservatively at that time. Due to the progressive gait disturbance, a lumboperitoneal shunt was implanted 1 year later. The clinical symptoms improved, but the cyst had grown after another year, causing visual impairment. Transsphenoidal drainage of the cyst was performed, but delayed pneumocephalus occurred. Repair surgery was performed with temporary suspension of shunt function, but pneumocephalus relapsed two and a half months after the resumption of shunt flow. In the second repair surgery, the shunt was removed because it was assumed that it would prevent closure of the fistula by lowering intracranial pressure. Two and a half months later, after confirming involution of the cyst and no pneumocephalus, a ventriculoperitoneal shunt was implanted, and cerebrospinal fluid (CSF) leakage has not relapsed since then. The coexistence of idiopathic normal pressure hydrocephalus (iNPH) and Rathke's cleft cyst (RCC) is rare, but it can occur. RCC can be cured by simple drainage, but delayed pneumocephalus can occur in cases whose intracranial pressure decreases due to CSF shunting. When simple drainage without sellar reconstruction for RCC is attempted after CSF shunting for coexistent iNPH, attention should be paid to changes in intracranial pressure, and it is desirable to stop the flow of the shunt for a certain period.

A case of acute hydrocephalus due to a giant prolactinoma rescued by transventricular neuroendoscopic tumorectomy.

Background: A giant prolactinoma extending to the suprasellar area and causing hydrocephalus may be life-threatening and should be treated promptly. A case of a giant prolactinoma with acute hydrocephalus that underwent transventricular neuroendoscopic tumor resection followed by cabergoline administration is presented. Case Description: A 21-year-old man had a headache lasting for about a month. He gradually developed nausea and disturbance of consciousness. Magnetic resonance imaging showed a contrast-enhanced lesion that extended from the intrasellar space to the suprasellar space and into the third ventricle. The tumor obstructed the foramen of Monro and caused hydrocephalus. A blood test showed marked elevation of prolactin (16,790 ng/mL). The tumor was diagnosed as a prolactinoma. The tumor in the third ventricle had formed a cyst, and the cyst wall blocked the right foramen of Monro. The cystic component of the tumor was resected using an Olympus VEF-V flexible neuroendoscope. The histological diagnosis was pituitary adenoma. The hydrocephalus improved rapidly and his consciousness became clear. After the operation, he was started on cabergoline. The tumor size subsequently decreased. Conclusion: Prompt partial resection of the giant prolactinoma by transventricular neuroendoscopy resulted in early improvement of hydrocephalus with less invasiveness, allowing subsequent treatment with cabergoline.

Primary central nervous system lymphoma of the tectal plate in adult.

Background: Primary central nervous system lymphoma (PCNSL) originating in the brainstem is uncommon. In particular, PCNSL confined to the tectal plate in adults has never been reported in the past. The case of a 53-year-old man who was diagnosed with PCNSL in the tectal plate is reported. Case Description: The patient was referred to our hospital with a 1-month history of disorientation and magnetic resonance imaging showed hydrocephalus with an enhancing lesion in the tectum. Preoperative blood tests showed a high serum soluble interleukin-2 receptor level of 624 U/ml. Through a single burr hole, endoscopic third ventriculostomy and biopsy of the lesion were simultaneously performed with a flexible endoscope. The histological examination confirmed diffuse large B-cell lymphoma. The patient underwent chemotherapy and radiotherapy. Conclusion: Malignant lymphoma of the tectum may occur in adults. By measuring the soluble interleukin-2 level preoperatively, it was possible to include malignant lymphoma in the differential diagnosis. In addition, the use of a neuroendoscope permits biopsy and hydrocephalus treatment to be performed simultaneously.

5-Aminolevulinic acid fluorescence-guided endoscopic surgery for intraventricular tumors.

Background: In recent years, the efficacy of 5-aminolevulinic acid photodynamic diagnosis (5-ALA PDD) has been reported for various types of brain tumors, including malignant glioma. In addition, many reports have been published on the usefulness of neuroendoscopic surgery for intraventricular lesions. However, no systematic report is available on the combined use of 5-ALA PDD and neuroendoscopy for various intraventricular tumors. Methods: We report 17 consecutive patients with intraventricular tumors. All patients received oral 5-ALA preoperatively and underwent endoscopic surgical treatment (resection or biopsy). We use a rigid endoscope with a built-in PDD system for intraoperative observation. Results: Seven resections and 10 biopsies were performed. Histopathological diagnosis was confirmed in all 17 cases. Gross total resection was achieved in six of seven cases. The fluorescence positivity rates for each tumor were glioblastoma 100% (2/2), low-grade glioma 67% (2/3), subependymoma 0% (0/1), medulloblastoma 100% (1/1), pineoblastoma 0% (0/1), germ cell tumor 75% (3/4), diffuse large B-cell lymphoma 33% (1/3), and metastatic tumor 100% (2/2). Conclusion: Our method has the potential to improve detection of residual tumors in blind spots and deep areas, as well as the accuracy and safety of biopsy procedures for intraventricular lesions that are difficult to view and treat under a microscope.

Stent-Assisted Coil Embolization of Ruptured Blood Blister-Like Aneurysm of the Basilar Artery: A Case Report and Literature Review.

Objective: Blood blister-like aneurysms (BBA) often develop on the anterior wall of the internal carotid artery, and few cases have been reported at other sites. We report a case of stent-assisted coil embolization in the acute phase for a ruptured BBA of the basilar artery. Case Presentation: A 53-year-old woman underwent emergency stent-assisted coil embolization for subarachnoid hemorrhage due to a ruptured BBA in the main trunk of the basilar artery. Seven months after the operation, cerebral angiography confirmed no recurrence and a good clinical course. Conclusion: Stent-assisted coil embolization for BBA may be one treatment option.

Rapid deterioration of an asymptomatic lumbosacral lipoma due to formation of an extracanalicular syrinx: case report.

The authors present the case of a 1-month-old girl with a lumbosacral lipoma who then developed an extracanalicular syrinx and experienced rapid deterioration. The patient's initial MRI study, obtained before she became symptomatic, revealed a spinal lipoma with a syrinx in contact with the lipoma-cord interface. She was initially asymptomatic but developed loss of motor function in the left leg 14 days after MRI. Emergency surgery was performed. Intraoperative findings revealed a swollen spinal cord. Lipomatous tissue on the caudal side of the conus was removed subtotally, and the central canal was opened. Expansion of the syrinx was observed intraoperatively. Postoperatively, the patient's left leg paresis remained. Postoperative MRI revealed rostral and extracanalicular expansion of the syrinx. This is the first report on the rapid deterioration of a conus lipoma due to extracanalicular expansion of a syrinx. Careful follow-up and repeat MRI should be considered for patients with spinal lipomas with syringomyelia, especially when the syrinx is attached to the lipoma-cord interface.

ICOSLG-mediated regulatory T-cell expansion and IL-10 production promote progression of glioblastoma.

BACKGROUND: Targeting immune checkpoint proteins has recently gained substantial attention due to the dramatic success of this strategy in clinical trials for some cancers. Inducible T-cell co-stimulator ligand (ICOSLG) is a member of the B7 family of immune regulatory ligands, expression of which in cancer is implicated in disease progression due to regulation of antitumor adaptive immunity. Although aberrant ICOSLG expression has been reported in glioma cells, the underlying mechanisms that promote glioblastoma (GBM) progression remain elusive. METHODS: Here, we investigated a causal role for ICOSLG in GBM progression by analyzing ICOSLG expression in both human glioma tissues and patient-derived GBM sphere cells (GSCs). We further examined its immune modulatory effects and the underlying molecular mechanisms. RESULTS: Bioinformatics analysis and GBM tissue microarray showed that upregulation of ICOSLG expression was associated with poor prognosis in patients with GBM. ICOSLG expression was upregulated preferentially in mesenchymal GSCs but not in proneural GSCs in a tumor necrosis factor-α/nuclear factor-kappaB-dependent manner. Furthermore, ICOSLG expression by mesenchymal GSCs promoted expansion of T cells that produced interleukin-10. Knockdown of the gene encoding ICOSLG markedly reduced GBM tumor growth in immune competent mice, with a concomitant downregulation of interleukin-10 levels in the tumor microenvironment. CONCLUSIONS: Inhibition of the ICOSLG-inducible co-stimulator axis in GBM may provide a promising immunotherapeutic approach for suppressing a subset of GBM with an elevated mesenchymal signature.

Serial volumetric assessment of the natural history and growth pattern of incidentally discovered meningiomas.

OBJECT: Due to advances in neuroimaging and the increasing use of imaging to screen for brain disease ("brain checkups"), meningiomas are now often detected as an incidental finding. The natural history of these asymptomatic meningiomas remains unclear, however. In this study, the authors investigated the natural history and growth pattern of incidentally detected meningiomas using serial volumetric assessment and regression analysis. METHODS: In 70 patients with incidentally discovered meningiomas who underwent follow-up for longer than 1 year, tumor volumes were calculated volumetrically at each follow-up visit, and tumor growth was determined. In patients with tumor growth, regression analysis was performed to determine the pattern of growth. RESULTS: Forty-four tumors exhibited growth and 26 did not. In a regression analysis, 16 of the tumors that grew followed an exponential growth pattern and 15 exhibited linear growth patterns. The presence of calcification was the only imaging characteristic that significantly distinguished the group with tumor growth from that without, although no radiological characteristics significantly distinguished the exponential growth group from the linear growth group. Two patients with obvious tumor growth underwent surgical removal and the pathological specimens extracted showed a high proliferative potential. CONCLUSIONS: The authors found that incidentally discovered meningiomas did not always follow an exponential growth pattern but often exhibited more complex patterns of growth. Serial monitoring of tumor volumes and regression analysis may reveal the growth pattern of incidental meningiomas and provide information useful for determining treatment strategy.

Phase II clinical trial of Wilms tumor 1 peptide vaccination for patients with recurrent glioblastoma multiforme.

OBJECT: The object of this study was to investigate the safety and clinical responses of immunotherapy targeting the WT1 (Wilms tumor 1) gene product in patients with recurrent glioblastoma multiforme (GBM). METHODS: Twenty-one patients with WT1/HLA-A*2402-positive recurrent GBM were included in a Phase II clinical study of WT1 vaccine therapy. In all patients, the tumors were resistant to standard therapy. Patients received intra-dermal injections of an HLA-A*2402-restricted, modified 9-mer WT1 peptide every week for 12 weeks. Tumor size, which was obtained by measuring the contrast-enhanced area on magnetic resonance images, was determined every 4 weeks. The responses were analyzed according to Response Evaluation Criteria in Solid Tumors (RECIST) 12 weeks after the initial vaccination. Patients who achieved an effective response continued to be vaccinated until tumor progression occurred. Progression-free survival and overall survival after initial WT1 treatment were estimated. RESULTS: The protocol was well tolerated; only local erythema occurred at the WT1 vaccine injection site. The clinical responses were as follows: partial response in 2 patients, stable disease in 10 patients, and progressive disease in 9 patients. No patient had a complete response. The overall response rate (cases with complete or partial response) was 9.5%, and the disease control rate (cases with complete or partial response as well as those in which disease was stable) was 57.1%. The median progression-free survival (PFS) period was 20.0 weeks, and the 6-month (26-week) PFS rate was 33.3%. CONCLUSIONS: Although a small uncontrolled nonrandomized trial, this study showed that WT1 vaccine therapy for patients with WT1/HLA-A*2402-positive recurrent GBM was safe and produced a clinical response. Based on these results, further clinical studies of WT1 vaccine therapy in patients with malignant glioma are warranted.

Immunohistochemical analysis of adhesion molecules and matrix metalloproteinases in malignant CNS lymphomas: a study comparing primary CNS malignant and CNS intravascular lymphomas.

Two distinct forms of malignant lymphomas can invade the central nervous system (CNS). Although primary CNS malignant lymphomas (PCNSMLs) invade the brain parenchyma, intravascular lymphomas (IVLs) form tumor cell aggregates in the vasculature and produce stroke-like symptoms and cognitive impairment. Although the tumor cells are mostly of B-cell origin in both types of lymphoma, their biological behavior is different, and the detailed mechanism(s) underlying this difference are not well understood. We studied the expression level of the adhesion molecules intercellular adhesion molecule-1 (ICAM-1) and integrin-beta1 in tumor tissue samples from patients with primary CNS lymphoma (n = 8) and intravascular lymphoma (n = 2) using immunohistochemical analysis. We also assessed the expression of the matrix metalloproteinases (MMP)-2 and MMP-9. ICAM-1 was positive in six and integrin-beta1 was positive in seven patients among eight PCNSML patients. MMP-2 and MMP-9 were expressed in all PCNSML. In contrast, none of them was positive in both IVL cases. Our findings suggest that adhesion molecules and MMPs are essential for malignant lymphoma cell invasion from the vasculature into the brain parenchyma and that they may be the key determinants for malignant lymphoma cells to behave as PCNSML or IVL cells.

Expression of WT1 protein and correlation with cellular proliferation in glial tumors.

The expression of Wilms' tumor gene WT1 protein was investigated immunohistochemically in 73 glial tumors, including 60 astrocytic tumors, eight oligodendroglial tumors, and five ependymal tumors. WT1 protein was detected in 70 of the 73 glial tumors (95.9%) examined. Almost all glioblastomas, anaplastic astrocytomas, anaplastic ependymomas, and anaplastic oligodendrogliomas expressed high levels of WT1 protein. A significant (p < 0.001) correlation was found between WT1 protein expression and MIB-1 staining index. Histological examination found that WT1 protein was strongly expressed in the anaplastic portions and areas with perivascular proliferation and high cellularity, implying that WT1 gene might be important in glial tumor cell proliferation. WT1 gene is overexpressed in various types of solid tumors and WT1 protein is a target antigen for cancer immunotherapy. This study indicates that many malignant glial tumors are good candidates for cancer immunotherapy targeting WT1 protein and that WT1 protein expression could be used as a proliferation marker in glial tumors.

Enlarging pediatric ectopic Rathke's cleft cyst in the prepontine cistern: case report.

Rathke's cleft cyst is a cystic disease that occurs in the sella turcica or, occasionally, in the suprasellar area. An ectopic Rathke's cleft cyst is extremely rare, and its nature is less well understood. The authors report the case of a 14-year-old girl who presented with a growing cystic lesion in the prepontine cistern, immediately behind the dorsum sellae. Preoperative imaging and intraoperative investigation showed part of the cyst wall continuing into the dorsum sellae, to the pituitary gland. The cisternal portion of the cyst wall was totally resected via a right subtemporal approach. Histopathological examination of the cyst wall showed a monolayer of ciliated cells, identical to those of Rathke's cleft cyst. To the best of the authors' knowledge, this represents the first pediatric case of Rathke's cleft cyst occurring in the prepontine cistern.

Detection of genetic and chromosomal aberrations in medulloblastomas and primitive neuroectodermal tumors with DNA microarrays.

Medulloblastoma (MB) is the most frequent infratentorial malignant brain tumor in children. In contrast, primitive neuroectodermal tumor (PNET) is defined as a supratentorial malignant tumor generated from the cerebral hemisphere. These tumors have considerable histological overlap but have different clinical outcomes including overall survival period, recurrence rate, and chemosensitivity. We investigated the amplification and/or deletion of genes and the chromosomal gain and/or loss in 10 MBs and 3 PNETs with a genomic DNA microarray system. Genes that are frequently amplified in these both these tumors include MSH2, N-myc, AKT3, and EGFR. Amplifications of SNRPN, MYB, and PTEN are observed only in MB. The genes associated with Wnt/APC and Shh/PTCH pathways also have some aberrations. Common chromosomal aberrations include gains at 17q and 7q and losses at 17p. Minor chromosomal losses were also detected at 1p, 8p + q, 11p, 10p + q, 13q, 16q, and Xp + q in MB. SPNETs tend to contain fewer chromosomal and genetic abnormalities than MBs. In conclusion, there are gene expression and chromosomal differences between MBs and SPNETs. These differences may correlate with the prognosis.

Scoring radiologic characteristics to predict proliferative potential in meningiomas.

We investigated the feasibility of using radiologic characteristics to predict the proliferative potential in meningiomas. Our statistical analysis revealed that the presence of peritumoral edema, an ambiguous brain-tumor border, and irregular tumor shape were significantly correlated with a higher MIB-1 staining index (SI) value. We developed the following scoring system for specific features in each tumor: peritumoral edema (tumor with edema = 1, tumor without edema = 0); brain-tumor border (tumor with any ambiguous border = 1, tumor circumscribed by a distinct rim = 0); and tumor shape (tumor with irregular shape = 1, tumor with smooth shape = 0). Using Spearman's correlation coefficient analysis, we found a significant correlation (P < 0.005) between total score calculated for each patient and SI value. Our findings suggest that the proliferative potential of meningiomas can be predicted using a less invasive preoperative examination focusing on the presence of peritumoral edema, ambiguous brain-tumor border, and irregular tumor shape.

Skull metastasis from papillary thyroid carcinoma accompanied by neurofibromatosis type 1 and pheochromocytoma: report of a case.

We report here a 74-year-old woman with a skull metastasis from papillary thyroid carcinoma (PTC). In her medical history, she was diagnosed with neurofibromatosis type 1 (NF1) at age 28 years, and she underwent thyroidectomy for PTC at age 52 years and adrenectomy for pheochromocytoma (PC) at age 58 years. She was admitted to our hospital with an increased mass in the forehead. Head computed tomography (CT) showed an expansive, osteolytic, and solid tumor extending from the dura mater into the subcutis, destroying part of the frontal bone. Head magnetic resonance imaging (MRI) revealed that the tumor was chiefly extradural but partially invaded the dura mater. Cerebral angiography showed that the tumor was fed from a branch of the external carotid artery. She underwent surgery, and histological examination revealed that the skull tumor was a metastasis from PTC, indicating that skull metastasis occurred 23 years after curative surgery for PTC. The patient also underwent adjuvant radioiodine therapy. As little is known about skull metastases from PTC, we discuss its characteristics and the extremely rare combined occurrence of PC and PTC in an NF1 patient.