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Somatostatin analogs are recommended for pharmacotherapy of TSH-secreting pituitary adenoma (TSHoma). A multicenter clinical trial was conducted to evaluate the efficacy and safety of lanreotide autogel treatment for TSHoma. A total of 13 Japanese patients with TSHoma were enrolled from February to December 2018 and treated with lanreotide autogel 90 mg every 4 weeks, with dose adjustments to 60 mg or 120 mg. Analysis was performed on data from patients receiving preoperative treatment (n = 6) up to 24 weeks and from those receiving primary or postoperative treatment (n = 7) up to 52 weeks. The primary efficacy endpoints were serum concentrations of TSH, free triiodothyronine (FT3), and free thyroxine (FT4). The secondary efficacy endpoints were pituitary tumor size and clinical symptoms. The serum concentrations of TSH, FT3, and FT4 decreased with treatment, and euthyroid status was maintained until final assessment. FT4 at final assessment was within reference ranges in 10/13 patients. The median (interquartile range) percent change in pituitary tumor size from baseline at final assessment was -23.8% (-38.1, -19.8). The clinical symptoms were also improved. The patients receiving preoperative treatment did not develop perioperative thyroid storm. Regarding safety, adverse events were observed in 12/13 patients, but none discontinued treatment. The common adverse events were gastrointestinal disorders (12/13 patients) and administration site reactions (5/13 patients). Lanreotide autogel may be effective for controlling thyroid function and reducing the pituitary tumor size, and is tolerable in patients with TSHoma (Japic Clinical Trials Information; JapicCTI-173772).

Background The endoscopic endonasal approach (EEA) has been accepted as an alternative option for diseases at the craniovertebral junction. However, the inferior destination through the endoscopic endonasal approach is anatomically higher than that of the transoral approach. Therefore, preoperative assessment of accessibility is mandatory for appropriate selection of indication. Using a navigation system, we examined the inferior limit through the endonasal route and evaluated the relationships between surrounding anatomicl structures and the lowest point. Methods This study included patients who underwent endoscopic transsphenoidal surgery for intrasellar lesions at our hospital (N = 23). At the start of surgery, the lowest point (target point [TP]) was marked with a straight probe under guidance of the navigation system. We measured 4 parameters on preoperative computed tomography: nasal length, hard palate length, anterior-posterior diameter of the nasopharynx, and nasopalatine angle. Patients were classified into groups depending on whether the TP was at or above (group A) or below (group B) the hard palatine line. Results TPs were above the hard palatine line in 15 patients (group A) and below the hard palatine line in 8 patients (group B). No TPs reached the nasopalatine line. Nasal length (P = 0.03) and nasopalatine angle (P = 0.01) were larger in group B than in group A. There were no significant differences in anterior-posterior diameter of the nasopharynx or hard palate length. Conclusions The hard palatine line is a reliable parameter for assessing the inferior limit of the endoscopic endonasal approach. Nostril size affects accessibility with surgical instruments.

Central nervous system tumors are classified based on an integrated diagnosis combining histology and molecular characteristics, including IDH1/2 and H3‐K27M mutations, as well as 1p/19q codeletion. Here, we aimed to develop and assess the feasibility of a glioma‐tailored 48‐gene next‐generation sequencing (NGS) panel for integrated glioma diagnosis. We designed a glioma‐tailored 48‐gene NGS panel for detecting 1p/19q codeletion and mutations in IDH1/2, TP53, PTEN, PDGFRA, NF1, RB1, CDKN2A/B, CDK4, and the TERT promoter (TERTp). We analyzed 106 glioma patients (grade II: 19 cases, grade III: 23 cases, grade IV: 64 cases) using this system. The 1p/19q codeletion was detected precisely in oligodendroglial tumors using our NGS panel. In a cohort of 64 grade Ⅳ gliomas, we identified 56 IDH‐wildtype glioblastomas. Within these IDH‐wildtype glioblastomas, 33 samples (58.9%) showed a mutation in TERTp. Notably, PDGFRA mutations and their amplification were more commonly seen in TERTp‐wildtype glioblastomas (43%) than in TERTp‐mutant glioblastomas (6%) (P = .001). Hierarchical molecular classification of IDH‐wildtype glioblastomas revealed 3 distinct groups of IDH‐wildtype glioblastomas. One major cluster was characterized by mutations in PDGFRA, amplification of CDK4 and PDGFRA, homozygous deletion of CDKN2A/B, and absence of TERTp mutations. This cluster was significantly associated with older age (P = .021), higher Ki‐67 score (P = .007), poor prognosis (P = .012), and a periventricular tumor location. We report the development of a glioma‐tailored NGS panel for detecting 1p/19q codeletion and driver gene mutations on a single platform. Our panel identified distinct subtypes of IDH‐ and TERTp‐wildtype glioblastomas with frequent PDGFRA alterations., A glioma‐tailored 48‐gene next‐generation sequencing panel identified distinct subtypes of wildtype IDH and TERT promoter glioblastomas with PDGFRA alterations.

Objective Pin-type head frame systems have become a worldwide standard procedure, but they can cause some complications on rare occasions. This study aimed to examine the incidence and associated risk factors of depressed skull fracture and related intracranial hematoma (DSFH) due to the use of head frames in our institute over the past 10 years. Methods This study included 1749 patients who underwent neurosurgical surgeries using pin-type head frames, including the Mayfield (Integra NeuroSciences, Plainsboro, NJ) skull clamp (721 cases) and the Sugita (Mizuho Ikakogyo Co., Ltd., Tokyo, Japan) head frame (1028 cases). We retrospectively reviewed hospital records of our institute to identify cases of DSFH, and documented the type of head frame used, as well as patient characteristics. Results The incidence of DSFH was 0.29% (5 of 1749 cases). All 5 cases had an associated epidural hematoma, with a single case having an additional dural laceration (without subdural damage). All perforation sites, located at the parietal bone near the pterion, occurred by the unilateral horizontal screw of the Sugita head frame. None of the patients experienced postoperative neurological decline. Conclusions Even in the adult population, the DSFH by the pin-type head frame can occur infrequently. Based on our results, we recommend that the following factors should be considered when the pin-type head frame is used for neurosurgical procedures: location of pin application, thickness and fragility of the skull, and adequate control of compressive forces exerted by the head frame.

The criteria for surgical cure of acromegaly have become more stringent during the past decades and a change from Cortina to new consensus criteria has recently been proposed. However, the superiority of the new consensus over Cortina criteria with respect to postoperative metabolic parameters remains to be ascertained. We retrospectively assessed metabolic parameters, the body habitus, and other health-related parameters of 48 patients with surgically controlled acromegaly who met the Cortina criteria [normalized insulin-like growth factor-1 (IGF-1) level and nadir growth hormone (GH) level

Given the anatomical proximity of tuberculum sellae meningioma (TSM) to the hypothalamo-pituitary system, pituitary function impairments are of great concern. We retrospectively investigated pituitary function changes following surgery in patients with TSM using pituitary provocation tests (PPTs). Thirty-one patients (27 females and 4 males) with TSM underwent initial transcranial surgery (29 patients) or transsphenoidal surgery (two patients); surgeries were performed carefully to avoid injuring the pituitary stalk. In 24 patients, the PPTs were performed via a triple bolus injection with regular insulin, thyrotropin-releasing hormone (TRH), and luteinizing hormone releasing hormone (LH-RH). Seven patients underwent a quadruple test (growth-hormone-releasing factor, corticotrophin-releasing hormone, TRH, and LH-RH). The preoperative and postoperative target hormone levels of the anterior pituitary were normal in 93.5% and 96.8% of patients, respectively. At least one hormonal axis demonstrated impaired PPT responses in two patients (6.5%) preoperatively and in one patient (3.2%) postoperatively. The growth hormone (GH) response was also well preserved. A compromised GH peak level was only observed in one patient (3.2%) preoperatively. Postoperatively, transient diabetes insipidus and transient hyponatremia were observed in four (12.9%) and eight (25.8%) patients, respectively. No patients needed permanent postoperative hormone replacement. The preoperative pituitary function was well preserved in most patients, including those with large tumors pushing against the pituitary stalk considerably or embedded in it. After careful surgery to avoid damaging the pituitary stalk, pituitary function was preserved. However, transient postoperative hyponatremia occurred in 25.8% of patients; thus, surgeons should pay careful attention to this issue.

Patients with acromegaly have a compromised quality of life (QOL). Modern surgical techniques have improved the surgical cure rate. However, there are no prospective studies reporting postoperative changes in QOL among patients cured solely by surgery. The aim of the present study was to determine the effect of surgery on QOL using the 36-item short form health survey (SF-36) questionnaire. SF-36 scores comprise 3 components: the physical component summary (PCS), the mental component summary (MCS) and role-social component summary (RCS). Included in this prospective cohort were 41 patients with acromegaly who underwent surgery alone and achieved postoperative normalization of insulin-like growth factor-1. All participants completed the SF-36 preoperatively and 1 year postoperatively. Preoperatively, RCS and 4 subscale scores (role physical, social functioning, role emotional, mental health) were below the set standards for the normal population. Postoperatively, the PCS and RCS scores did not change significantly, but the MCS score improved significantly (from 48.1 ± 11.3 to 51.7 ± 8.9, p=0.03). Further we compared the QOL of 26 patients whose nadir GH level was < 0.4 μg/L during postoperative oral glucose tolerance testing (complete remission group) with that of 15 patients whose nadir GH level was ≥ 0.4 μg/L (partial remission group). There were no significant differences between these groups in terms of PCS, MCS, RCS, or any subscale scores. In conclusion, surgical remission mostly improved the participants' mental condition. There was no difference in QOL between patients who achieved the new remission criteria and those who did not.

To evaluate the usefulness of high-temporal-resolution dynamic contrast-enhanced (DCE) MRI and quantitative pharmacokinetic analysis to differentiate the normal-appearing pituitary gland from a pituitary macroadenoma. Twenty-seven patients with macroadenomas underwent preoperative DCE-MRI with a temporal resolution of 5 s using compressed sensing to obtain pharmacokinetic parameters. Two independent observers localized the normal-appearing pituitary gland on post-contrast T1-weighted images before and after referring to the corresponding Ktrans maps. Agreements between the localizations and intraoperative findings were evaluated using the kappa statistics. The Mann–Whitney U test was used to compare the pharmacokinetic parameters of the normal-appearing pituitary gland and adenoma. For both observers, the agreement between the MRI-based localization and the intraoperative findings increased after referring to the Ktrans maps (observer 1, 0.930–1; observer 2, 0.636–0.855). The normal-appearing pituitary gland had significantly higher Ktrans [/min] (1.50 ± 0.80 vs 0.58 ± 0.49, P

To evaluate the feasibility of assessment of microvessel perfusion of pituitary adenomas with intravoxel incoherent motion (IVIM) imaging using single-shot turbo spin-echo-based diffusion-weighted imaging (SS-TSE-DWI). We examined 51 consecutive patients with pituitary adenomas (35 non-functioning and 16 functioning) and 32 patients with normal pituitary glands using SS-TSE-DWI IVIM. The diffusion coefficient (D), the perfusion fraction (f), and the pseudo-diffusion coefficient (D*) were calculated pixel-by-pixel for each adenoma and normal pituitary gland. We also obtained the pathological microvessel area (MVA) of each adenoma. The IVIM parameters in adenomas were compared with those in normal pituitary glands using the Mann–Whitney U test. The correlation between the MVA and IVIM f of adenomas was analyzed using Spearman’s rank correlation coefficient. The mean D (× 10−3 mm2/s) in adenomas was 0.723 ± 0.253, which was significantly lower than that in normal pituitary glands (0.862 ± 0.128; p

Background Xanthogranuloma is a chronic inflammatory mass characterized by cholesterol crystal deposition, which is rarely seen in the sellar region. The objective of this study is to identify the clinical features and cause of sellar xanthogranulomas. Methods We retrospectively analyzed manifestation, radiographic, and endocrinologic presentation in 9 patients (7 women and 2 men) whom we had previously treated. Results The patients were between 26 and 73 years of age (median, 56 years). The chief symptoms were visual symptoms in 3, polyuria in 3, headache in 4, and tiredness in 4 patients. Perimetry found visual field deficit in 6 patients. Anterior pituitary provocation tests disclosed impairment of ≥1 hormone in all patients: growth hormone in 8 patients and adrenocorticotropic hormone–cortisol axis in 8 patients. The lesions were suprasellar in 2 patients, intrasellar in 2 patients, and intrasuprasellar region in 5 patients. Three of the lesions were solid and 6 were single cystic to multicystic. Very low intensity area on T2-weighted magnetic resonance imaging was observed in 4 lesions. Postcontrast study performed in 7 lesions showed enhancement in solid parts or cyst walls. Surgical decompression improved visual disturbance in half of the patients but rarely improved hormonal deficits. Follow-up (median, 47 months) found no recurrence of the lesion. In addition to these 9 cases, we found 2 xanthogranulomatous lesions pathologically associated with ciliated epithelia, which also presented with severe hypopituitarism. Conclusions Xanthogranuloma seems to be the last stage of the chronic inflammation affecting Rathke cleft cyst or craniopharyngioma presenting with severe anterior pituitary insufficiency.

Progressive meningiomas that have failed surgery and radiation have a poor prognosis and no standard therapy. While meningiomas are more common in females overall, progressive meningiomas are enriched in males. We performed a comprehensive molecular characterization of 169 meningiomas from 53 patients with progressive/high-grade tumors, including matched primary and recurrent samples. Exome sequencing in an initial cohort (n = 24) detected frequent alterations in genes residing on the X chromosome, with somatic intragenic deletions of the dystrophin-encoding and muscular dystrophy-associated DMD gene as the most common alteration (n = 5, 20.8%), along with alterations of other known X-linked cancer-related genes KDM6A (n =2, 8.3%), DDX3X, RBM10 and STAG2 (n = 1, 4.1% each). DMD inactivation (by genomic deletion or loss of protein expression) was ultimately detected in 17/53 progressive meningioma patients (32%). Importantly, patients with tumors harboring DMD inactivation had a shorter overall survival (OS) than their wild-type counterparts [5.1 years (95% CI 1.3–9.0) vs. median not reached (95% CI 2.9–not reached, p = 0.006)]. Given the known poor prognostic association of TERT alterations in these tumors, we also assessed for these events, and found seven patients with TERT promoter mutations and three with TERT rearrangements in this cohort (n = 10, 18.8%), including a recurrent novel RETREG1–TERT rearrangement that was present in two patients. In a multivariate model, DMD inactivation (p = 0.033, HR = 2.6, 95% CI 1.0–6.6) and TERT alterations (p = 0.005, HR = 3.8, 95% CI 1.5–9.9) were mutually independent in predicting unfavorable outcomes. Thus, DMD alterations identify a subset of progressive/high-grade meningiomas with worse outcomes.

Choroid plexus tumors (CPTs) are rare intraventricular neoplasms accounting for about 0.3–0.6% of all intracranial tumors. This retrospective study on CPTs presents clinico-pathological features and management strategies based on a 20-year single-institutional experience. This series included 10 consecutive patients with pathologically proven CPTs; 5 choroid plexus papillomas (CPPs), 3 atypical CPPs (ACPPs), and 2 choroid plexus carcinomas (CPCs). Their clinical, radiological, and histopathological features as well as management including follow-up studies were reviewed. The patients included five males and five females, aging from 0 years to 61 years with median of 28 years. The affected site was lateral ventricle in two adults and fourth ventricle in eight patients; four children and four adults. The most common symptoms were gait disturbance and memory disturbance. All the patients underwent craniotomy with total, subtotal, and partial removals achieved in 50%, 40%, and 10% of the patients, respectively. The occurrence of the high grade subtypes was 50% in both the adult and pediatric groups. The Ki-67/MIB-1 index increased across the three histological subtypes, from CPP to ACPP and then to CPC. Adjuvant therapy was administered in three patients. The two patients (one adult and one child) with CPC died of whole central nervous system dissemination. At a median of 62-month follow-up, the other eight patients were alive, with only one patient having recurrence and reoperation. The results demonstrate that gross total resection is usually curative for CPP and ACPP, and adjuvant chemoradiotherapy would be required for CPC and incompletely resected ACPP.

The purpose of this study is to elucidate the trend of glioblastoma outcome and scrutinize the factors contributing to better outcome over three decades.Survival time and the influencing factors were retrospectively analyzed in 223 newly diagnosed primary glioblastoma patients during 1980-2010. Appraised factors included age, sex, tumor site, year of surgery, extent of resections, use of surgery supporting system, Karnofsky Performance Status (KPS), chemotherapy, conventional external beam radiotherapy (EBRT), and CyberKnife stereotactic radiotherapy (CK-SRT) use.The median survival time (MST) in all patients was 13.6 months. The MSTs for 4 periods were 9.8 (1980-1990), 13.7 (1991-2000), 12.9 (2001-2005), and 15.8 months (2006-2010), respectively (p=0.0047). Total resection, subtotal resection, partial resection, and biopsy had MSTs of 31.8, 13.9, 11.4, and 7.0 months, respectively (p0.0001). Regarding chemotherapy, MSTs of the temozolomide base group and nimustine hydrochloride (ACNU) base group were 16.9 and 14.6 months, respectively, whereas the MST of patients without chemotherapy was only 9.8 months (p0.0001). The MSTs for 40-Gy EBRT plus CK-SRT and 60-Gy EBRT were 19.1 and 10.7 months, respectively (p0.0001). But in sub-selected patients, treated during 2001-2010, whose resection rate was total resection or subtotal resection, EBRT was completed and postoperative KPS was greater than or equal to 70, the MST with and without CK-SRT was 26.6 and 18.3 months, respectively (p=0.1529). According to the Cox proportional hazards model, degree of resection, KPS, ACNU use, temozolomide use, bevacizumab use, EBRT dose, and CK-SRT use were good prognostic factors. Use of neuronavigation and use of intraoperative magnetic resonance imaging were related to higher resection rate, but not determined as prognostic factors.We observed a gradual improvement in glioblastoma outcome, presumably because of improvements in therapeutic modalities for surgery, anticancer agents, and radiation, but the efficacy of CK-SRT remains unclear.

The aim of this study was to determine the influence of Wnt5a and its receptors on the survival of glioblastoma patients and to determine reliable evaluation methods for immunohistochemistry. Diagnostic specimens from 41 histopathologically confirmed primary glioblastoma patients whose Gd-enhanced tumors had been totally removed were immunohistochemically stained for Wnt5a, Fzd2, Fzd6, and Ryk. The immunoreactivity was evaluated using the following methods: (A) grayscale optical density after color deconvolution, (B) percentage of stained cells, (C) density of stained cells, (D) staining amount (multiplication product of B and C), and (E) staining rank. The data sets of A to E were statistically evaluated by correlation matrix analysis and regression analysis. The influence of the expression of the markers on survival was analyzed using a proportional hazard model. The results of color deconvolution (A) were well correlated with the results of the staining rank (E). In the semiquantitative results (B, C, and D), the staining amount (D) tended to show a better correlation with results of color deconvolution (A). Among all data sets, color deconvolution (A) demonstrated the most preferable fit in a proportional hazard model, and the expression of Fzd2 and Fzd6 was associated with poor prognosis in glioblastoma patients.

Temozolomide (TMZ) is an alkylating agent and was a first-line chemotherapeutic agent for malignant gliomas. Recently, TMZ has been documented to be effective against atypical pituitary adenomas (APAs) and pituitary carcinomas (PCs).The clinical and pathological characteristics of APAs and PCs treated with TMZ in Japan were surveyed and analyzed retrospectively.Members of the Japan Society of Hypothalamic and Pituitary Tumors were surveyed regarding the clinical characteristics of APAs and PCs treated with TMZ. Stored tumor samples were gathered from the responders and were assessed by the immunohistochemistry of Ki-67, O(6)-methyl-guanine-DNA methyltransferase, p53, MSH6, and anterior pituitary hormones. Responses to TMZ treatment were defined as complete response (CR), partial response (PR), progressive disease (PD), and stable disease (SD) according to RECIST (Response Evaluation Criteria in Solid Tumors) version 2.0.Three samples from 3 subjects with APA and 11 samples from 10 subjects with PC were available.The 13 subjects had APAs and PCs consisting of 5 prolactin-producing tumors, 5 ACTH-producing tumors, and 3 null cell adenomas. The clinical response to TMZ treatment was as follows: 4 cases of CR and PR (31%), 2 cases of SD (15%), 6 cases of recurrence after CR and PR (46%), and 1 case of PD (8%). However, considerable subjects had recurrent disease after a response to TMZ. The immunohistochemical findings of Ki-67, O(6)-methyl-guanine-DNA methyltransferase, and p53 did not show any significant correlation with the efficacy of TMZ. However, the immunopositivity of MSH6 was positively correlated with TMZ response (P = .015, Fisher's exact test).This study showed that preserving MSH6 function was contributory to the effectiveness of TMZ in malignant pituitary neoplasms. It is necessary to survey more cases and evaluate multifactor analyses.

ObjectiveThe glomerular filtration rate (GFR) is increased in patients with active acromegaly. The aim of this study is to elucidate whether renal function deteriorates in patients with acromegaly and whether this deterioration is reversible after surgical remission.Design/methodsA case–control study of 48 acromegalic patients who were surgically cured (cases) and 48 patients with nonfunctioning pituitary adenomas (NFomas, controls) was conducted. We performed clinical and biochemical examinations before surgery and 3months post-surgery. The GFR of each patient was estimated (estimated GFR, eGFR) using their serum creatinine, age, sex, and body surface area, and postoperative changes in the eGFR were assessed.ResultsThe preoperative eGFR was significantly higher in patients with acromegaly than in those with NFoma (99.8 vs 75.1mL/min respectively,PPP=0.12). Among the acromegalic patients, the postoperative decreases in the eGFR were more prominent in patients with a preoperatively high or normal vs low eGFR.ConclusionsOur data demonstrated a significant post-surgical eGFR decrease in patients with acromegaly, but not in patients with NFomas. This change in the eGFR was reversible in acromegalic patients with a high/normal preoperative eGFR, but not in those with a low preoperative eGFR. This suggests that the reversible pathophysiological change in some patients is functional but not organic.

Langerhans cell histiocytosis (LCH) is a proliferation of Langerhans cells intermixed with inflammatory cells, in particular eosinophils, that may manifest as a unisystem (unifocal or multifocal) or multisystem disease. We describe the clinical and histologic spectrum of LCH of the orbit and skull in our two cases. Both cases had unifocal erosive skull lesions with a history of trauma. Typical histologic features included numerous histiocytes with varying degrees of giant cell formation and scattered eosinophilic granulocytes. The presence of Langerhans cells was confirmed by CD1a and S100 immunohistochemistry. LCH has an excellent prognosis when treated with surgical resection, steroids and radiotherapy or chemotherapy. One of our patients is disease free at 7 year follow-up and one patient had regression of lesion on follow-up.

Cavernous angiomas or hemangiomas and malignant lymphomas rarely involve the cavernous sinus. We report the case of a 72-year-old man with right circumorbital pain and right oculomotor nerve dysfunction because of a mass in the right cavernous sinus. It was removed via a transsphenoidal approach and histological examination revealed the mass was a cavernous hemangioma containing atypical large B cells in some sinusoidal vessels; no other evidence of lymphoma was detected on (18)F-2-fluoro-2-deoxy-D-glucose positron-emission tomography or bone marrow biopsy. The patient underwent gamma knife radiosurgery (GKS) of the right cavernous sinus, but no systemic chemotherapy was administered. Although good local control was achieved, the patient developed a systemic diffuse large B-cell lymphoma (DLBCL) 1.5 years after the GKS. The atypical lymphocytes of the cavernous hemangioma and biopsied lymph nodes expressed multiple myeloma oncogene-1 protein. This is a rare case of DLBCL occurring within a cavernous sinus that was diagnosed as hemangioma of the cavernous sinus by neuroimaging, surgical findings, and rapid-freezing histological diagnosis. The case indicates a importance of surgical sampling and detailed histopathological analysis.

To know the longitudinal shift of blood IGF-1 of cured acromegaly, we conducted retrospective survey of changes in blood IGF-1 over two years, which has not been previously investigated. Blood IGF-1 levels were measured for longer than 2 years after TSS in 37 patients whose nadir GH during postoperative oral glucose tolerance test (OGTt) was under 1 ng/mL. Blood IGF-1 very gradually declined after three months; 230.6 (mean) ng/mL at 3-12 months, 202.3 ng/mL at 12-24 months, and 198.6 ng/mL at 24-36 months. Their SD values, calculated based on standard IGF-1 values of age- and sex-matched Japanese population, also slowly decreased after three months; 1.69 (mean) at 3-12 months, 1.23 at 12-24 months, and 1.12 at 24-36 months. Very slow decrease of the IGF-1 levels continued beyond the first several months and even the first year after TSS. The declination of values is greater than that associated with aging. This declination may be at least partially a reflection of the slow decrease and late normalization of GH secretion.

ObjectiveSomatotropinomae are classified as densely and sparsely granulated adenomae, which typically exhibit a perinuclear pattern (PP) and a dot pattern (DP) in cytokeratin (CK) immunostaining respectively. Some exhibit a mixed pattern (MP). We studied the relationship between these somatotropinoma subtypes and their clinico-pathological features.MethodsThe study population consisted of 141 Japanese acromegalic patients. We evaluated their clinical presentation and their response to provocation tests with TRH and LHRH and to suppression (octreotide) test. Tumour tissues were subjected to immunostaining for CAM-5.2, MIB-1, CD34, E-cadherin (CDH1) and p53 (TP53). In 43 cases (30 non-DP and 13 DP), we analysedgspmutations (constitutively activating mutations of the Gsα protein that is encoded byGNASgene).ResultsThe 141 adenomae were categorised into three subtypes based on their CK staining patterns; 30 (21.3%) exhibited DP, 83 (58.9%) exhibited PP, and 28 (19.9%) exhibited MP. Compared with the other subtypes, DP adenomae were significantly larger, and their E-cadherin expression and response to TRH, LHRH and octreotide challenge were lower. The postoperative cure rate tended to be lower in DP adenomae.gspmutations were detected in 25 of 43 cases examined (58.1%); 20 of the 30 non-DP (66.7%) and 5 of the 13 DP tumours (38.5%) were affected by the mutation.ConclusionDP somatotropinomae exhibit characteristic features. Compared with the non-DP subtypes, DP adenomae manifested a larger tumour size, a lower incidence of abnormal responses to TRH and LHRH challenge, a poor response to octreotide test and a lower expression of E-cadherin.gspmutation was not exclusive for non-DP somatotropinomae.

Apart from the radiologic features regarding size and invasiveness, we had noticed some differences in morphology among types of pituitary adenomas. We conducted this study to verify the differences in radiologic morphology between growth hormone producing pituitary adenomas (GHoma) and nonfunctioning pituitary adenomas (NFoma). Pre-surgical magnetic resonance images (MRIs) were assessed in 50 cases of GHoma and 50 cases of NFoma. Geometric parameters on MRI were set in accordance with sellar anatomy. Intensity of T1-weighted image was not different between the two groups, but hypo-intensity of T2-weighted image was more frequently seen in GHoma. Predominant inferior extension of tumor was seen mostly in GHoma (88 vs. 38%). Extension of the tumor to the superior compartment of cavernous sinus was more frequent in NFoma. Pituitary gland was generally located superior to GHoma and postero-superior to NFoma. Growth characteristics of pituitary adenoma were confirmed to differ between GHoma and NFoma.

The deformation of the skull base in patients with unilateral frontal plagiocephaly (UFP) is well known, but the mechanism is not still clear. We analyzed the skull base in the patients with UFP who underwent fronto-orbital advancement (FOA) in the early life during the last decade. We assessed the treatment results and outcome of FOA performed in six patients, four girls and two boys younger than 2 years, in the last decade. Also, the basal cranium’s angles were measured by 3D reconstruction images on computed tomography (CT) scan. The mean patients’ age at FOAs was 11 months. Two cases were classified as grade 2A, two cases as grade 2B, and two cases as grade 3 (the classification of Di Rocco and Velardi). The ethmoidal axis was deviated a mean of 8.2° to the affected side. The mean angle between the petrosal pyramids and the midline (anterior-petrosal-sagittal angle, APSA) was 75.3° on the affected side and 66.2° on the normal side. The mean difference of APSA was 9.2°. On the follow-up CT images 5 years after surgery, the deviations of the ethmoidal axis clearly decreased, 5.7°, but the differences of APSA did not change, 8.8°. The midline distortion of anterior skull base should be considered to be spontaneously corrected during the follow-up periods in patients with all types of UFP who underwent FOA, unlike posterior skull base in the patients with grades 2B and 3 classification.

To know the clinical characteristics of pituitary adenomas in the elderly patients aged 80 years or older who were surgically treated. From 1995 through 2012, 907 patients underwent surgery for the pituitary adenomas at Kagoshima- and Hiroshima University hospitals in Japan. Ten (1.1 %) patients were aged 80 years or older. We retrospectively assessed the clinical characteristics including preoperative comorbidities, manifestations, neuroimaging findings, and endocrinologic features of these ten patients. The subjects included eight males and two females. Their ages ranged from 80 to 86 with mean of 83.1 years. Of these, besides one case of growth hormone-producing adenoma, others were clinically nonfunctioning adenoma. Six patients had modest comorbidities such as hypertension, cardiovascular diseases, diabetes mellitus, or chronic kidney dysfunction, and all patients were classified into grade 2–3 on American Society of Anesthesiologists’ Physical Status grading. Transsphenoidal surgery was performed in all due to visual disturbance in eight, diabetes mellitus as an intercurrent illness of acromegaly in one, and for the purpose of preventing visual disturbance in one patient who had an adenoma impinging optic chiasm but still had normal visual field. The surgeries provided sufficient decompression of the optic pathways and improved visual disorder in all. In an acromegalic male, his comorbidities considerably improved. No permanent surgical morbidity ensued. More than three axes of anterior pituitary hormones were preoperatively impaired in all, which were rarely recovered. Transsphenoidal surgery is safe and efficient treatment way for patients aged 80 years or older with pituitary adenomas with chiasmatic symptoms when the patients’ general condition is well preserved and pituitary hormonal deficiency is adequately replaced.

Growth hormone deficiency (GHD) in surgically-cured acromegalics has been reported to negatively affect their metabolic condition and quality of life (QOL). The incidence of GHD, its causes, and its effects on their physio-psychological condition remain to be examined in detail. We performed a retrospective study to investigate GH secretory function in surgically-cured acromegalics, prognostic factors of GHD, and its impact on QOL. The study population consisted of 72 acromegalics who were determined to be surgically cured according to the Cortina consensus criteria. We recorded the incidence of impaired GH secretory function based on the peak GH level during postoperative insulin tolerance test (ITT) which lowered their nadir blood sugar to under 50 mg/dL. Their QOL was evaluated by SF-36. In surgically-cured acromegalics, the incidence of severe GHD (peak GH during ITT ≦ 3.0 μg/L) was 12.5 % (9/72). The preoperative tumor size was significantly larger in patients with severe GHD than without severe GHD (21.9 ± 9.0 vs. 15.5 ± 7.1 mm, p = 0.017). The peak GH levels during postoperative ITT were statistically correlated with the physical but not the mental component summary of the SF-36 score. The incidence of GHD was 12.5 % in our surgically-cured acromegalics. As some QOL aspects are positively related with peak GH levels during postoperative ITT, efforts should be made to preserve pituitary function in acromegalic patients undergoing adenomectomy.

We determined distribution of plasma cells and IgG4/IgG index and factors associated with the index in intracranial inflammatory lesions. Specimens of nine patients were analyzed immunohistochemically using antibodies against CD45, CD68, CD3, CD4, CD8, CD20, CD138, lambda chain, kappa chain, IgG, IgG4, IL-1α, IL-6, IL-18, toll-like receptor (TLR) 2, TLR4, high-mobility group box 1 (HMGB1), tumor necrosis factor-alpha (TNF-α), myeloid differentiation factor 88 (MyD88), and anaplastic lymphoma kinase (ALK). The relationship between all the factors was assessed using Spearman's rank correlation coefficient (ρ). Negative ALK staining was observed in all the patients. Plasma cells were detected in eight patients with varying degrees. The highest number of neutrophils, but no plasma cells, was observed in a patient with the shortest history of inflammation. IgG4/IgG index was independent of the number of plasma cells. The index was relatively highly correlated with IL-6 (ρ = 0.7271) and TLR4 expression (ρ = 0.7246). IL-6 expression was highly correlated with TLR4 expression (ρ = 0.8042). IL-18 was maximally expressed in all the patients. TLR4 expression was strong, but TRL2 expression was weak. Positive HMGB1 staining was observed in all the patients, predominantly in the nuclei, but also in the cytoplasm in four patients. The cytoplasmic expression strongly correlated with IL-1α expression (ρ = 0.9583). The cytoplasmic colocalization of HMGB1 and IL-1α was histologically confirmed in cells with collapsing nuclei by the double-staining method. The IgG4/IgG indexes varied case by case. IL-6 and TLR4 expressions may influence IgG4/IgG index. The nuclei of cells with both IL-1α and HMGB1 expressions in the cytoplasm collapse in the cell death stage. The cooperative high expression of TLR4, IL-6, IL-18, MyD88 and HMGB1 suggest their critical roles in the inflammation circuit.

A 53-year-old male presented with a case of prolactin-producing pituitary adenoma with abundant spherical amyloid depositions masquerading as extensive calcification and manifesting as visual disturbance. Computed tomography revealed a large high density mass suggesting calcified tumor in the intra- and supra-sellar regions. Magnetic resonance imaging revealed a heterogeneously enhanced large pituitary tumor reaching lateral ventricle. Blood prolactin level was elevated to 5971 ng/ml. Cabergoline treatment for 3 months provided considerable shrinkage of the tumor but failed to improve the visual symptoms. Transcranial surgery revealed that the tumor was fibrous and included abundant grayish translucent spherical granules with diameter of 0.5-1.5 mm. Immunohistochemically, the tumor was strongly positive for prolactin. Congo red stain and polarized light showed that these spherical bodies were amyloid depositions. No calcification was noted.

Choroid plexus papillomas are rare; they comprise less than 1% of all intracranial tumors. In children, most of these neoplasms arise in the lateral ventricle while in adults they are primarily located in the fourth ventricle. We report 3 children with choroid plexus papilloma in the fourth ventricle; they were one 5-month-old girl and 2 boys aged 8-and 15-years. The baby girl presented with macrocephaly and signs of raised intracranial pressure, the 2 boys exhibited cerebellar signs. On magnetic resonance imaging (MRI) the tumors were well-enhanced with a cauliflower-like contour and hydrocephalus. In one case, diffusion weighted images (DWIs) showed an isointense tumor signal clearly different from the well-known hyperintensity of medulloblastomas, Via suboccipital craniotomy we succeeded in the total or subtotal surgical resection of these tumors and there were no sequela. None of the tumors have recurred in the intervening 2-9 years. In conclusion, choroid plexus papilloma should be included as a differential diagnosis in children presenting with tumors in the fourth ventricle. The contour of the tumor on MRI and its intensity on DWI may be clues for a correct preoperative diagnosis.

We assessed the incidence of elderly patients in Japanese acromegalics and the characteristics of their clinical presentation. We also evaluated the safety and efficacy of transsphenoidal surgery (TSS) in this patient group. During the 28-year period from 1980 to 2007 we treated 290 patients with acromegaly at our hospitals. Of these, 9 (3.1%) were elderly, i.e. 70 years old or older. They comprised 0.7% of acromegalics treated during the first- and 4.5% of patients with acromegaly treated during the 2nd 14-year period. Before treatment, all manifested abnormal glucose tolerance; 6 had diabetes mellitus (DM), 6 presented with hypertension, and 2 had cardiovascular disease, malignant neoplasms, or hyperlipidemia. Of the 7 elderly acromegalics who underwent TSS none manifested surgical morbidity or new pituitary hormone deficiencies. Postoperatively, the nadir growth hormone (GH) level at the oral glucose tolerance test (OGTT) was under 1.0 ng/mL in 5 patients, insulin-like growth factor (IGF-1) levels normalized in 4. Glucose tolerance improved in all operated patients. Only 1 of 6 patients with preoperatively diagnosed DM continued to manifest DM post-treatment, anti-hypertensive drugs could be tapered in 3 of patients with preoperative hypertension. In conclusion, we found that there was a high incidence of abnormal glucose tolerance and hypertension in elderly acromegalics, that surgical treatment was effective and safe in this population, and that it was useful for the control of co-morbidities.