The effects of prophylactic tadalafil use on VEGF expression in the rabbit model of steroid-induced femoral head avascular necrosis.

OBJECTIVE: The purpose of this study was to examine the effect of prophylactic tadalafil use on a steroid-induced femoral head avascular necrosis model in terms of microscopic, imaging, and molecular biological changes. METHODS: Twenty-four New Zealand rabbits were divided into 3 equal groups. Eight rabbits were designated as the control group and did not receive treatment. Rabbits in group 1 (G1) received 0.1 mg/kg Escherichia coli lipopolysaccharide (LPS) intravenously and 40 mg/ kg methylprednisolone sodium succinate (MP) was administered intramuscularly for 3 days consecutively. Rabbits in group 2 (G2) were given 5 mg/kg tadalafil orally for 10 consecutive days. Starting on the eighth day, 0.1 mg/kg LPS was given, and following this 40 mg/kg MP injections were administered for 3 days. All animals were sacrificed 3 weeks after the final MP injection. Magnetic resonance imaging was performed, and bilateral femora were harvested. Half of the femoral head was stored for Vascular Endothelial Growth Factor (VEGF) examination with Western blot analysis. The other half was examined microscopically for the presence of osteonecrosis. RESULTS: In G1, 15 out of 16 hips (93%) of the 8 rabbits had osteonecrosis compared to 8 out of 12 hips (67%) of 6 rabbits in G2 (P > .05). The VEGF expression in G2 was significantly higher than in the control group and G1 (P < .05 and P < .001, respectively). There was no significant difference in VEGF expression between the control group and G1 (P > .05). CONCLUSION: This study has shown us that femoral head osteonecrosis can be reliably induced with LPS and corticosteroid, as described in the literature. Prophylactic tadalafil use did not decrease the occurrence of osteonecrosis significantly. However, it significantly increased VEGF expression in the femoral head independent of the effects of steroids and LPS.

Diagnosis and management of tumor-induced osteomalacia: a single center experience.

PURPOSE: The aim of this study is to review the clinical and laboratory characteristics, diagnostic and treatment modalities of tumor-induced osteomalacia (TIO) cases managed in a single center. MATERIAL METHODS: Demographic and clinical features, biochemical findings, diagnostic procedures, treatment modalities, and outcomes of nine patients who had the diagnosis of TIO were reviewed retrospectively. RESULTS: Mean age of the study group (F/M: 4/5) was 45.8 ± 10.8 years, and mean time from the onset of symptoms to diagnosis was 4.7 ± 2.8 years. The clinical manifestations were muscle weakness and difficulty in walking (8/9), hip pain (3/9), multiple fractures (2/9), stress fracture (2/9). Mean plasma phosphorus concentration was 1.28 ± 0.4 mg/dl at presentation. We performed radionuclide imaging modalities (18F-FDG PET/CT, Ga68-DOTATATE PET/CT, octreotide scintigraphy) in seven of nine patients, and tumor was detected in all. Lower extremity (n = 6; %67), head region (n = 2; %22) and thorax (n = 1; %11) were the tumor locations of our cases. Eight patients underwent surgery and remission was achieved postoperatively in all of the operated patients and plasma phosphorus level normalized in 4 ± 2 days. Pathological examination revealed mesenchymal tumors with different subtypes. Recurrence occurred in three patients at 13 ± 10.5 months after the first surgery. Two patients were reoperated and radiotherapy was also performed in one of them. CONCLUSION: Hypophosphatemia necessitates careful evaluation for the etiology. TIO is one of the important causes of adult-onset hypophosphatemic osteomalacia. Diagnosis of TIO is essential because the laboratory and clinical findings resolve after appropriate treatment.

What is the Effect of Bevacizumab on Cartilage and Synovium in a Rabbit Model of Hemophilic Arthropathy?

BACKGROUND: Hemophilic arthropathy can cause recurrent hemarthroses and severe damage to the synovium and articular cartilage. Previous studies have shown that vascular endothelial growth factor (VEGF) plays an essential role in neoangiogenesis. Bevacizumab, a monoclonal VEGF inhibitor, is used clinically to prevent angiogenesis. However, its effects on hemophilic arthropathy are unknown. QUESTIONS/PURPOSES: Using a hemophilic arthropathy rabbit model, we asked: Does an intra-articular injection of bevacizumab (1) inhibit VEGF, (2) decrease signal intensity in dynamic contrast-enhanced MRI (DCE-MRI) as an assessment of capillary permeability and neoangiogenesis, (3) reduce cartilage damage, (4) reduce synovial changes, and (5) affect macroscopic changes during the development of hemophilic arthropathy? METHODS: Twenty-five male New Zealand rabbits were divided into four groups. Eight knees from four rabbits were used as the control group. We used an established animal model for hemophilic arthropathy in the remaining 21 rabbits. Animals were assigned randomly to three groups with seven rabbits in each group. One group was used to establish mild arthropathy, and the other two were used to establish severe arthropathy. Autologous blood from the rabbits' ears was injected into the right and left knees twice per week for 8 weeks to represent mild arthropathy and for 16 weeks to represent severe arthropathy. In the mild arthropathy group, bevacizumab was injected into the right knee once every 2 weeks. Bevacizumab was injected into the right knee of rabbits in one of the severe arthropathy groups once every 2 weeks for 16 weeks, and intra-articular bevacizumab injections were administered to the right knees of rabbits in the other severe arthropathy group once every 2 weeks after the eighth week. An equal volume of 0.9% saline was injected into the left knee of rabbits in all arthropathy groups. To explore the efficacy of bevacizumab, joint diameters were quantitatively measured, and cartilage and synovial changes were examined. Degeneration of articular cartilage was evaluated with the semiquantitative Osteoarthritis Research Society International grading system. Synovial damage was analyzed with a semiquantitative microscopic scoring system. In addition, we evaluated perfusion and angiogenesis using DCE-MRI (quantitative signal intensity changes). Immunohistochemical testing was used to measure VEGF levels (analyzed by Western blotting). RESULTS: Intra-articular bevacizumab treatment inhibited VEGF in our rabbit model of hemophilic arthropathy. VEGF protein expression levels were lower in the mild arthropathy group that received intra-articular bevacizumab (0.89 ± 0.45) than the mild arthropathy control group (1.41 ± 0.61) (mean difference -0.52 [95% CI -0.898 to -0.143]; p = 0.02). VEGF levels were lower in the severe arthropathy group that received treatment for 16 weeks (0.94 ± 0.27) than in the control knees (1.49 ± 0.36) (mean difference -0.55 [95% CI -0.935 to -0.161]; p = 0.01). In the severe arthropathy group, the Osteoarthritis Research Society International score indicating cartilage damage was lower in the group that received intra-articular bevacizumab treatment from the beginning than in the control group (median 17 [range 13 to 18] versus 18 [range 17 to 20]; difference of medians 1; p = 0.02). Additionally, the scores indicated synovial damage was lower in the group that received intra-articular bevacizumab treatment from the beginning than the control group (median 5 [range 4 to 9] versus 9 [range 8 to 12]; difference of medians 4; p = 0.02). The mean of mean values for signal intensity changes was higher in the nontreated severe groups than in the group of healthy knees. The signal intensity changes were higher in the severe arthropathy control groups (Groups BC and CC) (median 311.6 [range 301.4 to 361.2] and 315.1 [range 269.7 to 460.4]) than in the mild arthropathy control group (Group AC) (median 234.1 [range 212.5 to 304.2]; difference of medians 77.5 and 81, respectively; p = 0.02 and p = 0.04, respectively). In the severe arthropathy group, discoloration caused by hemosiderin deposition in the cartilage and synovium was more pronounced than in the mild arthropathy group. In the severe arthropathy group treated with intra-articular bevacizumab, joint diameters were smaller than in the control group (Group BT median 12.7 mm [range 12.3 to 14.0] versus Group BC median 14.0 mm [range 13.1 to 14.5]; difference of medians 1.3 mm; p = 0.02). CONCLUSION: Hemarthrosis damages the synovial tissues and cartilage in the knees of rabbits, regardless of whether they are treated with intra-articular bevacizumab. However, intra-articular injection of bevacizumab may reduce cartilage and synovial damage in rabbits when treatment is initiated early during the development of hemophilic arthropathy. CLINICAL RELEVANCE: If the findings in this study are replicated in larger-animal models that consider the limitations of our work, then a trial in humans might be appropriate to ascertain whether intra-articular injection of bevacizumab could reduce cartilage damage and synovial changes in patients with hemophilia whose hemarthroses cannot otherwise be controlled.

Clinical course and features of soft tissue sarcomas in geriatric patients: a single-center experience.

OBJECTIVE: This study was performed to examine the disease course in geriatric patients with soft tissue sarcoma and determine the risk factors for mortality. METHODS: We retrospectively analyzed patients who were treated at Istanbul University Oncology Institute from January 2000 to August 2021. RESULTS: Eighty patients were included in the study. The patients' median age was 69 years (range, 65-88 years). The median overall survival of patients diagnosed between the ages of 65 and 74 years was 70 months, and that of patients diagnosed at the age of ≤75 years was significantly lower at 46 months. The median survival of patients who did and did not undergo surgical resection was 66 and 11 months, respectively, with a significant difference. The median overall survival of patients with positive and negative surgical margins was 58 and 96 months, respectively, also with a significant difference. Age at diagnosis and recurrence/metastasis significantly affected mortality. A 1-year increase in the age at diagnosis increased mortality by 1.147 times. CONCLUSION: Age of >75 years, inability to undergo surgery, positive surgical margins, and head and neck location may be associated with a poor prognosis in geriatric patients with soft tissue sarcoma.

Effect of Cabergoline Treatment on Disease Control in Acromegaly Patients.

The aim of this study was to evaluate the efficacy of cabergoline in normalizing plasma IGF-I levels in acromegaly patients with elevated IGF-I levels after surgery and/or SRL therapy. Acromegaly patients (n: 143) were evaluated retrospectively. Patients with elevated IGF-I levels after surgery and/or SRLs therapy and a fixed dose of SRLs treatment for the last six months with no history of radiotherapy in the last three years were included in the study (n: 12). Previous treatment regimens, baseline PRL and IGF-I levels (ULNR), sella MRI, and immunohistochemical findings were evaluated. Cabergoline was used as an add on (n: 11) or single medical treatment (n: 1). The median duration of treatment with SRL alone was 12 months (range 6-48 months). The mean IGF-I value before cabergoline therapy was 1.45±0.4 ULNR. The mean cabergoline dose and duration of treatment were 1.55±0.75 mg/week and 9±6.3 months, respectively. IGF-I normalization was only achieved in patients with serum IGF-I concentration<1.5×ULNR before the onset of cabergoline treatment (n: 9). In some of the patients with IGF-I normalization, baseline prolactin levels were normal (n: 3). Immunopositivity for prolactin in adenoma tissue was found in three patients with IGF-I normalization. Cabergoline therapy is effective in the normalization of IGF-I levels even in normoprolactinemic acromegaly patients when IGF-I levels are mildly or moderately elevated during SRL therapy.

Focal cortical dysplasia pathology: diagnostic difficulty, classification, and utility for pathogenesis.

OBJECTIVE: In the histopathological examination of treatment-resistant epilepsy, focal cortical dysplasia (FCD) is the most common diagnosis in the pediatric group. FCD is classified histopathologically according to the International League Against Epilepsy (ILAE) classification. In the last decade since the ILAE classification has been released, molecular genetic studies have revealed mTOR pathway-related mutations as a major etiology. The objective of this study was to determine the incidence of FCD in treatment-resistant epilepsy patients, explore histomorphological and immunohistochemical features, examine clinicopathological correlation, demonstrate mTOR pathway activation using a pS6 antibody immunohistochemically, and try to introduce a candidate for possible targeted therapies. METHODS: Paraffin blocks and slides of tissue from patients with treatment-resistant epilepsy were reexamined retrospectively. Histopathological subtypes of FCD were determined according to the ILAE classification. NeuN and neurofilament H (NF-H) staining were performed, and additionally a pS6 antibody was used to demonstrate mTOR pathway activation. RESULTS: In 32 cases diagnosed with FCD, or 17.5% of 183 surgical epilepsy materials, there were no significant differences in the statistical analysis of clinical variables between the ILAE FCD subtypes. Recommended antibody NeuN revealed microcolumnar alignment in the FCD type Ia and IIIa groups and the loss of lamination in the type Ib group. Another recommended antibody, NF-H, was not found to be useful in discriminating between normal and dysmorphic neurons. pS6 expression, showing mTOR pathway activation, was observed in dysmorphic neurons and balloon cells in all FCD type II cases. CONCLUSIONS: Significant pS6 expression in FCD type II represents the genomic nature of the disease noted in the literature. Nevertheless, the known MTOR gene and mTOR pathway-related mutations remain behind proportionally to explain the mTOR pathway activation in all FCD type II cases. Clinicopathologically and genetically integrated classification and usage of mTOR pathway inhibitors in treatment are expected as a recent evolution.

An Investigation into the Correlation of Scalp Electrophysiological Findings with Preoperative Clinical and Imaging Findings in Patients with Focal Cortical Dysplasia.

AIM: To evaluate the patients who had epilepsy surgery and pathologically proven focal cortical dysplasia (FCD) in order to further classify and discuss electroencephalography (EEG) findings in different pathological subtypes. MATERIAL AND METHODS: This study included 19 refractory epilepsy patients who underwent surgery between 1999 and 2017 in the Istanbul Faculty of Medicine. Demographic data, preoperative examinations, scalp video EEGs, and postoperative outcomes were evaluated retrospectively. RESULTS: In this study, 36.8% of the patients were female. The mean age was 21.89 ± 14.64 years. Rhythmic epileptiform discharges (RED) were observed in 31.6%. 37.5% of the patients with isolated intermittent spike/sharp waves were type I, 50% were type II, and 12.5% were type III. 100% of the patients with normal background activity were FCD type II. 67% of the patients with asymmetric slowing were FCD type I, 22% was FCD type II, 11% were FCD type III. 71% of the patients with symmetrical slowing were FCD type I, 29% were FCD type II. One patient had Frontal Intermittent Rhythmic Activity, one patient had Electrical Status Epilepticus in Slow Sleep, two patients had "burst suppression," and one patient had a "switch of" sign. The frequency of focal epileptogenic activity was higher when there was an FCD lesion on magnetic resonance imaging. CONCLUSION: The findings obtained in this study did not reveal any distinctive electrophysiological features in FCD and subgroups of FCD. The incidence of REDs did not differ between types. The frequency of isolated intermittent sharp/spike waves was higher in type II than I. Intermittent and continuous EEG slowing was more commonly seen among FCD Type I patients.

Long-term results of different surgical options in the management of solitary enchondroma.

BACKGROUNDS: We aimed to compare the average 10-year results of patients treated with three different surgical methods, that is, extended curettage, extended curettage with grafting and extended curettage with cementation for the management of solitary enchondromas. METHODS: Two hundreds and three patients with a solitary enchondroma who underwent surgery at our department between 1990 and 2015 were evaluated retrospectively. Only extended curettage was performed in Group A (n: 75), extended curettage with grafting with autologous bone graft from the iliac crest in Group B (n: 58), and extended curettage with bone cement in Group C (n: 70). Surgical complications and recurrence were analysed and compared between these groups. RESULTS: No significant differences were noted among the groups in terms of gender (P = 0.654), age (P = 0.264) and follow-up duration (P = 0.919). The mean follow-up period in all groups was 122.9 ± 39 (range: 60-271) months. In addition to curettage and cementation, three patients received mechanical support with plate screws because of fracture risk. One patient in the extended curettage with grafting group had surgical site infection that was treated with simple debridement and antibiotherapy. One patient in the extended curettage group had lost motions of the proximal interphalangeal joint, which was treated with aggressive physiotherapy. CONCLUSION: We compared the average 10-year results of patients treated with three surgical options, namely, extended curettage, extended curettage with grafting, and extended curettage with cementation and no difference was found among the groups in local control of solitary enchondromas.

Femoral artery aneurysm developed on intimal sarcoma: Case report.

Intimal angiosarcoma is a rare vascular malignancy, and diagnosis is very difficult due to nonspecific symptoms. There are controversial points regarding the diagnosis, treatment and follow-up of intimal angiosarcomas. The purpose of this case report was to evaluate the diagnosis and treatment process of a patient diagnosed with femoral artery intimal angiosarcoma. Furthermore, in line with previous studies, it was aimed to illuminate controversial points. A 33-year-old male patient, who had been operated on due to ruptured femoral artery aneurysm, was diagnosed with intimal angiosarcoma with the pathology result. Recurrence was observed during clinical follow-up, and the patient was treated with chemotherapy and radiotherapy. Since there was no response to treatment, the patient underwent aggressive surgery including the surrounding tissues. No recurrence or metastasis was observed in the patient's 10th month follow-up. Although intimal angiosarcoma is rare, it should be considered in differential diagnosis when femoral artery aneurysm is detected. The most important step in treatment is aggressive surgery, but adding chemo-radiotherapy to the treatment should be considered.

A single-center experience of transsphenoidal endoscopic surgery for acromegaly in 73 patients: results and predictive factors for remission.

BACKGROUND: Transsphenoidal endoscopic surgery is the first-line treatment for growth hormone-secreting adenomas. OBJECTIVE: To analyse the results of the transsphenoidal endoscopic approach for acromegaly and to determine the predictive factors of remission. METHODS: A single-centre retrospective review was performed in patients who underwent endoscopic transsphenoidal surgery for acromegaly between January 2009 and January 2019. Demographic features, clinical presentation, histopathology records, complications and pre- and postoperative radiologic and endocrinological assessments were evaluated. The factors that influenced the remission rates were investigated. RESULTS: A total of 73 patients underwent surgery via the transsphenoidal endoscopic approach. Cavernous sinus invasion was detected in 32 patients (43.8%); and macroadenoma, in 57 (78%). The pathology specimens of the 27 patients (36.9%) showed dual-staining adenomas with prolactin. A total of 51 patients (69.8%) attained biochemical remission 1 year after surgery. A second operation was performed in 10 patients (13.6%) with residual tumours without biochemical remission in the first year. Six (60%) of the patients attained remission at the last follow-up. Transient diabetes insipidus was observed in 18 patients (24.6%); and rhinorrhoea, which was resolved with conservative treatment, in 4 (5.4%). None of the patients developed panhypopituitarism. The presence of cavernous sinus invasion and preoperative IGF-1, immediate postoperative GH and third-month IGF-1 levels were predictive of remission. CONCLUSION: Transsphenoidal endoscopic surgery is a safe and effective treatment for acromegaly. Reoperation should be considered in patients with residual tumours without remission.

Relation Between ILAE Hippocampal Sclerosis Classification and Clinical Findings in Temporal Lobe Epilepsy.

AIM: To investigate the relationship between clinical features and prognosis of the hippocampal sclerosis (HS) cases and International League Against Epilepsy (ILAE) histopathology classification. MATERIAL AND METHODS: A hundred patients with refractory epilepsy who were operated with the diagnosis of the Mesial Temporal Lobe Epilepsy were included in the study. Socio-demographic characteristics, clinical and family histories, post-operative ILAE and Engel epilepsy scores and diagnostic tests were recorded. At the same time, all of the pathological specimens were classified according to the new semi-quantitative ILAE classification. A significant statistical relationship was investigated between clinical data and HS-ILAE groups. RESULTS: There were 36 male 64 female patients. The mean follow-up period was 6.5 years. 75% of the cases were HS-ILAE type 1, 19% HS-ILAE type 2, 6% were unidentifiable. FCD3A was detected in 3 patients. The HS-ILAE Type 2 ratio was high on the rightsided cases. In addition, HS-ILAE Type 1 ratio was high in patients with early seizure onset and long duration of epilepsy. There was no significant relationship between long-term ILAE and Engel epilepsy outcome scores and HS-ILAE types. CONCLUSION: Resection of mesiotemporal structures in hippocampal sclerosis provides seizure control in at least two-thirds of cases. Histopathological findings may help us understand the epileptogenicity-prognosis of HS. The relationship between ILAE histopathology classification and clinical factors will become more obvious in the future. According to our study, there was a relationship between onset age of epilepsy, epilepsy duration, lesion side and HS-ILAE types. The reinforcement of these relationships with larger series will benefit clinicians.

Childhood Rhabdomyosarcoma of the Female Genital Tract: Association with Pathogenic DICER1 Variation, Clinicopathological Features, and Outcomes.

STUDY OBJECTIVE: Rhabdomyosarcomas (RMSs) of the female genital tract (FGT) have been recently shown to be associated with germline pathogenic variation in DICER1, which can underlie a tumor predisposition disorder. We sought to determine the incidence of a pathogenic variation in DICER1 in a cohort of RMSs of the FGT, as well as to evaluate the clinicopathological features and outcomes of the patients. DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: We retrospectively reviewed medical records of the patients diagnosed with RMS of the FGT between 1990 and 2019. Molecular genetic sequencing of the tumor to detect an RNase IIIb domain hot spot mutation in DICER1 samples was performed in 7 patients. Individuals with a missense mutation in the tumor were also screened for a loss of function germline mutation in DICER1. RESULTS: Of 210 cases of pediatric RMS, 11 arose from the FGT. Molecular genetic sequencing of the tumor samples revealed a somatic missense mutation in the RNase IIIb domain of DICER1 in a total of 3 patients, 2 patients with embryonal RMS of the cervix/uterus, and 1 patient with ovarian embryonal RMS. As a result of genetic testing for the loss of function germline mutation in DICER1, a heterozygous pathogenic variant was also found in 2 of these patients. CONCLUSION: Despite the limited number of patients, our findings suggest that it is important to be aware of the possible association between RMS of FGT and pathogenic germline DICER1 variants because the detection of this mutation in a patient or relatives can provide the opportunity for surveillance of related conditions that might improve long-term outcomes and survival.

The Relationship Between Clinico-Pathological Properties and p-Glycoprotein Expression in Hippocampal Sclerosis Among Patients with Mesial Temporal Lobe Epilepsy Who Undergo Selective Amygdalohippocampectomy Operation.

INTRODUCTION: The overproduction of the efflux transporters in the blood-brain barrier is considered to play a role in the development of drug resistance in mesial temporal lobe epilepsy (MTLE) patients. The aim of the present study was to investigate the relationship of clinical features of patients with MTLE accompanied by hippocampal sclerosis (HS) and the p-glycoprotein (p-gp) expression and neuronal loss in the hippocampus. METHODS: This study included a total of 33 patients who underwent selective amygdala-hippocampectomy operation. A detailed medical history of each patient, including age, side of HS, sex, age of habitual seizure onset, duration of habitual seizures, type and age of initial precipitating injury, presence and duration of latent period, presence and duration of silent period, monthly seizure frequency within 1 year prior to operation, mean age at the time of operation was evaluated retrospectively. RESULTS: The p-gp expression was significantly higher in the patient group with a seizure frequency of more than 15 days per month and a disease duration of more than 20 years. There was no significant difference between the p-gp expression and the clinical features of the MTLE-HS patients. CONCLUSION: These results suggest that p-gp expression is affected by disease duration and seizure frequency rather than a patient's clinical and pathological properties. In patients with HS-MTLE, potential use of the p-gp inhibitors as additional therapy and developing novel drugs not carried by multidrug carriers expressed in blood-brain barrier should be regarded as the new treatment targets.

Promoter region mutations of the telomerase reverse transcriptase (TERT) gene in head and neck squamous cell carcinoma.

OBJECTIVE: The aim of the present study was to assess the prevalence of TERT promoter region mutations in tumor samples of patients with squamous cell carcinoma at different sites of the head and neck region and correlate it with patients' clinicopathologic data. STUDY DESIGN: Mutations in promoter region of the TERT gene were analyzed with polymerase chain reaction-based direct sequencing method using formalin-fixed, paraffin-embedded tumor samples of 189 HNSCCs. TERT promoter region mutations were assessed in terms of age, gender, location, smoking, alcohol consumption, and overall survival. RESULTS: TERT promoter region mutations were detected in the oral cavity (75%); larynx (8.4%), hypopharynx (16.6%), and oropharynx (0%). TERT promoter region mutations are associated with younger age and female gender and have a reverse relationship with smoking and alcohol consumption. CONCLUSIONS: We found statistically significant higher rates of TERT promoter region mutations in tumor samples of patients with squamous cell carcinoma in the oral cavity compared with other locations in the head and neck region.

Radiation-Induced Meningiomas: A Series of Four Consecutive Patients and a Review of Literature.

AIM: To assess the clinical outcomes of treatment for radiation-induced meningiomas. MATERIAL AND METHODS: Medical records were retrospectively reviewed for all cranial meningioma cases that were diagnosed and/or underwent surgery at our hospital from 2009 to 2016. All radiation-associated meningioma patients constituted the core sample for this study. RESULTS: This series included one female and three male patients, with a mean age of 47.3 ± 16.3 years. The mean preoperative course was < 3 months. The most common symptom was headache (100%) and three patients had alopecia and thin scalp skin. The mean of the age at which they underwent radiotherapy was 18.5 ± 13.7 years. The mean latency period was 19.2 ± 7.4 years. Initial malignancies included two patients with desmoplastic medulloblastomas (13-year-old female, 65 Gy), (11-year-old male, 54 Gy) and a patient with grade II oligodendroglioma treated with 30 Gy. A male patient received low-dose radiotherapy for chronic otitis at 10 years old. Histopathological examinations revealed the following: 1) fibroblastic-grade I, Ki-67 2%-3%, 25.5 years latency; cerebellopontine angle, 2) atypical meningioma grade II, Ki-67 8%, 21 years, frontal; and 3) transitional grade I, Ki-67 3%-4%, 11 years, frontal. The fourth patient had three radiation-induced meningiomas and 27 radiation-induced cavernomas, and was treated using a gamma knife. The mean follow-up period was 34.8 ± 39.4 months. One patient had rhinorrhea and another experienced a cerebrospinal fluid fistula. Both underwent an additional operation. The former died because of meningitis on postoperative day 31. CONCLUSION: Most radiation-induced meningiomas are low-grade, but they have a high trend of recurrence. Close follow-up and yearly magnetic resonance imaging would minimize the morbidity rate. To reduce fatal complications, surgery should be planned in conjunction with plastic surgeons.

Neuroblastoma of the Iris in Children.

Neuroblastoma of the iris is an extremely rare clinical entity. An otherwise healthy 2-month-old male infant presented to the oncology clinic with a nodular whitish iris lesion in his right eye. The excisional tumor biopsy was consistent with a pathological diagnosis of neuroblastoma with differentiation and negative MYCN gene mutation. Further systemic evaluation revealed a right adrenal mass with no metastatic lesion. The biopsy of the adrenal lesion was also consistent with neuroblastoma. After four courses of chemotherapy, the adrenal mass was completely resected. The patient underwent two additional courses of postoperative chemotherapy and continued retinoic acid treatment. The patient is under regular follow-up with no evidence of recurrence 36 months after the initial diagnosis. This is the first case report to present a histopathological verification of neuroblastoma of the iris. The authors suggest that neonates and infants who are diagnosed as having neuroblastoma undergo an ophthalmologic examination after the initial diagnosis to investigate the true incidence of small iris lesions in neuroblastoma that may have been unrecognized. Neuroblastoma should be included in the differential diagnosis of amelanotic iris lesions in infants and young children. [J Pediatr Ophthalmol Strabismus. 2019;56:e12-e16.].

Clinical Significance of Granulation Pattern in Corticotroph Pituitary Adenomas.

OBJECTIVE: The granulation pattern of pituitary tumors may be important to predict tumor behavior, treatment outcomes, and recurrences. Therefore, we compared densely granulated corticotroph tumor (DGCT) and sparsely granulated corticotroph tumor (SGCT) in terms of clinicopathologic findings. MATERIAL AND METHOD: A total of 41 patients (31 females/10 males) were assessed in the study. The granulation patterns were detected by Periodic Acid-Schiff (PAS) and adrenocorticotropic hormone (ACTH) immunoreactivity. Diffuse and strong staining by PAS and ACTH were identified as DGCT, whereas faint staining by PAS and focal, weak staining by ACTH were identified as SGCT. Perinuclear ring-like patterns with low molecular weight keratin were identified as Crooke's cell tumors. DGCTs and SGCTs were compared in terms of clinical findings and treatment outcomes. RESULTS: The majority of the patients (71%) had DGCTs (n=29); whereas 24% of the patients had SGCTs (n=10) and 5% of the patients had Crooke's cell tumors (n=2). DGCTs and SGCTs were similar in terms of age, sex, estimated duration of disease, baseline cortisol and ACTH levels. SGCTs were larger than DGCTs (p=0.034). The remissions with surgery rates were similar between the groups; however, hypothalamic-pituitaryadrenal axis recovery time was longer in SGCTs (p=0.033). Persistent disease after surgery was slightly higher in DGCTs and recurrences were frequent in SGCTs; however, the differences were not statistically significant. CONCLUSION: DGCTs are often small microadenomas, while SGCTs are larger. Recurrences were slightly more common in SGCTs; however, further studies including larger series are needed to be able to obtain more significant results.

Granulomatous amebic encephalitis caused by Acanthamoeba in an immuncompetent child.

Sütçü M, Aktürk H, Gülümser-Sisko S, Acar M, Erol OB, Somer A, Bilgiç B, Salman N. Granulomatous amebic encephalitis caused by Acanthamoeba in an immuncompetent child. Turk J Pediatr 2018; 60: 340-343. Acanthamoeba may lead to granulomatous amebic encephalitis (GAE) with high mortality rates generally in patients with immunosupression and/or chronic disease. Here, we present a rare GAE case, who was a previously healthy child. A Georgian 9 year old boy presented with focal seizure on his left arm and confusion. Since computed tomography (CT) demonstrated hypodense lesion on right occipital lobe, brain biopsy was performed. Histopathological examination of the biopsy material revealed Acanthamoeba cysts and trophozoites together with granulomatous inflammation. The patient, who had no clinical and laboratory findings consistent with immunedeficiency, was diagnosed as GAE. He was treated with a combination drug therapy. Even if it is very rare, amebic meningoencephalitis may also be seen in immunocompetent children, as in our case. Definitive diagnosis is made by microbiological and histopathological examination of brain biopsy material.

Screening of AIP Gene Variations in a Cohort of Turkish Patients with Young-Onset Sporadic Hormone-Secreting Pituitary Adenomas.

Aims: Aryl hydrocarbon receptor-interacting protein (AIP) gene mutations have long been associated with apparently sporadic pituitary adenomas (PAs) with a prevalence range of 0-12%. The aim of this study was to evaluate the frequency of germline AIP variations in a large cohort of apparently sporadic PAs diagnosed before the age of 40 years, who did not exhibit hypercalcemia and/or MEN1 syndrome components during long-term follow-up. Materials and Methods: A total of 97 patients, diagnosed with functional PAs ≤40 years old, composed of somatotropinoma (n = 55), prolactinoma (n = 25), and corticotrophinoma (n = 17), were recruited for this study. Fifty-one of these patients [somatotropinoma (n = 30), prolactinoma (n = 15), and corticotrophinoma (n = 11)] were previously reported as AIP mutation-negative by Sanger sequencing. The entire coding sequence of the AIP gene, along with exon/intron boundaries and the untranslated regions of 41 newly recruited patients, were sequenced for germline variations. In addition, all patients were subjected to multiplex ligation-dependent probe amplification to detect copy number variations in the AIP gene. Results: The AIP c.911G>A: p.Arg304Gln (rs104894190) variant was detected in only two patients with functional PA: one with somatotropinoma [in 1/55 (1.8%)] and one with prolactinoma [in 1/25 (4%)]. None of the corticotrophinomas revealed AIP gene alterations. Thus, the overall prevalence of AIP variation was 2.1% in our cohort. Conclusions: Germline AIP gene variations among Turkish patients with apparently sporadic PAs are relatively rare among patients ≤40 years old. None of the patients in our cohort revealed any obviously pathogenic AIP variants.