Lung adenocarcinoma metastasis within a pituitary neuroendocrine tumor: a case report with review of literature.

Collision tumors involving the metastasis of malignant neoplasms to pituitary neuroendocrine tumors (PitNETs) are extremely rare. We herein report a case involving a patient with lung adenocarcinoma metastasis within a PitNET who exhibited relatively rapid progression of neurological symptoms. A 75-year-old man who underwent tumor resection 36 and 18 years prior to presentation for bladder and colon cancer, respectively, without recurrence presented with bitemporal hemianopsia, ptosis, and diplopia of the right eye. Subsequent magnetic resonance imaging (MRI) revealed a tumor 3.2 cm in diameter that extended from the anterior pituitary gland to the suprasellar region. Gadolinium-enhanced MRI of the tumor showed heterogeneous contrast enhancement. Considering the relatively rapid progression of neurological symptoms, semi-emergency endoscopic endonasal transsphenoidal surgery was performed. Histopathological examination revealed a group of thyroid transcription factor-1- and napsin A-positive papillary proliferating cells intermingled with α-subunit- and steroidogenic factor-1-positive PitNET cells. Thus, the patient was diagnosed with lung adenocarcinoma metastasis within a gonadotroph PitNET. Genetic testing revealed the presence of an EGFR (Ex-19del) mutation, after which chemotherapy was initiated. Additional stereotactic radiotherapy was performed for the residual tumor in the sella turcica. With continued chemotherapy, good control of both the primary and metastatic tumors was noted after 24 months after surgery. Cases of malignant neoplasm metastasis within a PitNET are difficult to diagnose. In the case of a sella turcica tumor with relatively rapid progression of neurological symptoms, early surgical intervention is recommended given the possibility of a highly proliferative tumor and the need to obtain pathologic specimens.

Concurrent IgG4-related hypophysitis and clinically nonfunctioning gonadotroph pituitary neuroendocrine tumor.

BACKGROUND: Some patients develop immunoglobulin G4 (IgG4)-related hypophysitis associated with systemic diseases. More than 30 cases of IgG4-related hypophysitis have been reported. However, biopsy has rarely been performed in these patients, and none have had an associated pituitary neuroendocrine tumor (PitNET). We present a case of concurrent IgG4-related hypophysitis and PitNET. CASE PRESENTATION: A 56-year-old Japanese man arrived at the hospital with visual impairment, bitemporal hemianopia, and right abducens nerve palsy. Magnetic resonance imaging revealed pituitary body and stalk swelling as well as a small poorly enhanced right anterior lobe mass. Laboratory and loading test results suggested hypopituitarism. Because IgG4 level was elevated, a systemic examination was performed; multiple nodules were found in both lung fields. The diagnosis was based on an endoscopic transnasal biopsy of the pituitary gland. A histopathological examination revealed a marked infiltration of plasma cells into the pituitary gland, which was strongly positive for IgG4. The histological features of the resected tumor were consistent with those of gonadotroph PitNET, which was immunohistochemically positive for follicle-stimulating hormone-ß and steroidogenic factor-1, and no plasma cell infiltration was observed. Based on the histopathological examination results, steroid therapy was initiated, which reduced pituitary gland size and serum IgG4 levels. DISCUSSION AND CONCLUSIONS: This is the first reported case of IgG4-related hypophysitis with PitNET. Although no pathological findings indicating a relationship between the two conditions were found, we were able to preoperatively differentiate multiple lesions via detailed diagnostic imaging.

A case of pituitary adenoma with infiltration into the sphenoid sinus accompanied by melanocyte proliferation.

A 71-year-old woman presenting with headache and nausea was admitted to hospital. Magnetic resonance imaging revealed a tumorous lesion that surrounded the sella turcica and infiltrated the sphenoid sinus with bone destruction. The tumor was removed by nasal endoscopy. The histology was consistent with pituitary adenoma; immunohistochemistry indicated silent corticotroph adenoma with melanocyte proliferation. The possibility that melanocytes were incorporated into the tumor mass in the sphenoid sinus and underwent proliferation was evaluated by investigating the mechanisms of melanocyte proliferation associated with basic fibroblast growth factor (bFGF) and α melanocyte-stimulating hormone (αMSH). In the normal tissue, the pars intermedia and adrenocorticotropic hormone (ACTH)-producing cells were positive for αMSH. None of the control adenoma tissues were positive for bFGF or αMSH by immunostaining. In the present case, bFGF-positive cells and αMSHpositive cells were observed, suggesting that both may have been involved in melanocyte proliferation. The expression of bFGF has been linked to aggressive disease. Pituitary adenoma with melanocyte proliferation has not been previously reported. Careful follow-up is deemed necessary in the future.

Scoring system for intraoperative diagnosis of intracranial schwannoma by squash cytology.

OBJECTIVE: To assess the utility of a newly developed squash cytology (SC)-based scoring system for accurate intraoperative diagnosis of schwannoma. METHODS: We first compared SC-based and frozen section (FS) diagnoses with final pathological diagnoses of schwannoma (16 cases), meningioma (39 cases) and low-grade astrocytoma (16 cases). Then, by logistic regression modeling, we identified features of SC preparations that were independently predictive of schwannoma. To develop a diagnostic scoring system, we assigned one point to each feature, and performed receiver operating characteristic analysis to determine the score cut-off value that was most discriminatory for differentiating schwannoma from the other tumour types. We then compared accuracy, sensitivity, and specificity of diagnosis before and after the application of the scoring system. RESULTS: Overall diagnostic concordance rates for SC and FS were almost the same, at 73.2% (52/71) and 77.5% (55/71 cases), respectively. Of the 16 SC features entered into the analysis, the following nine were found to independently predict schwannoma, and were thus incorporated into the scoring system: smooth cluster margins, few or no isolated tumour cells, fibrillary stroma, spindle-shaped nuclei, parallel arrangement of stroma, parallel arrangement of nuclei, presence of anisonucleosis, absence of nucleoli, and hemosiderin deposition. A cut-off score of four items yielded the best sensitivity, specificity and predictive values for prediction of schwannoma. Use of the scoring system improved accuracy of intraoperative diagnosis from 80.3% to 94.4%, sensitivity from 56.2% to 93.8%, and specificity from 87.3% to 94.5%. CONCLUSION: Our proposed SC-based scoring system will increase accuracy of intraoperative diagnosis of schwannoma vs non-schwannoma tumours.

A case of aggressive pituitary neuroendocrine tumour with extremely rapid progression: possible diagnostic value of TERT promoter methylation.

Most pituitary adenoma/neuroendocrine tumours (PitNET) are histologically benign and grow slowly; however, a subset of these tumours exhibit a more aggressive clinical course characterized by local invasiveness and early recurrence. These high-risk PitNETs often require multiple surgeries and radiation over several years and may eventually acquire carcinomatous characteristics, such as metastasis in some cases. Herein, we report a rare case of PitNET causing oculomotor paresis with extremely rapid recurrence only 3 months after initial surgery, followed by lethal liver metastasis. Preoperative magnetic resonance imaging and intraoperative findings were consistent with typical PitNETs, other than moderate invasion of the cavernous sinus. Pathological examination of the specimen obtained from the initial transsphenoidal surgery revealed increased mitosis and elevated rates of cells positive for Ki-67 and p53. Based on the immunohistochemical assessment for transcription factors and pituitary hormones, the diagnosis was determined to be a silent sparsely granulated corticotroph PitNET with focal malignant transformation. Aggressive features represented by Ki-67 and p53 positivity were more robust in recurrent and metastatic specimens, but hormone immunostaining was decreased. Epigenetic analysis revealed methylation of the telomerase reverse transcriptase (TERT) promoter in the tumour, resulting in TERT upregulation. Despite extensive research, markers for distinguishing extremely aggressive PitNETs have not been determined. Although further analysis is needed, our case demonstrates the possible usefulness of assessing TERT promoter methylation status in the stratification of recurrence risk in extremely high-risk variants of PitNET.

Loss of nectin-3 expression as a marker of tumor aggressiveness in pancreatic neuroendocrine tumor.

Pancreatic neuroendocrine tumors (PanNETs) are rare, and prediction of aggressive characteristics, such as recurrence and metastasis and prognosis of PanNETs remain difficult. Nectins are cell adhesion molecules that regulate the formation of adherens and tight junctions. In this study, we investigated the clinicopathological significance of nectin-3 expression in patients with PanNETs. Immunohistochemical analysis of nectin-3 expression was performed on 78 cases of PanNET. Low nectin-3 expression in the membrane (positive ratio ≤25%) was observed in 62 cases (79.5%) and was significantly correlated with larger tumor size (>20 mm; P = 0.003), G2/G3 tumors (P = 0.025), higher Ki67 labeling index (≥3%; P = 0.009), lymphatic involvement (P = 0.047), advanced pT-factor (T2-T4; P = 0.003), lymph node metastasis (P = 0.006), advanced Union for International Cancer Control/American Joint Committee on Cancer-stage (Stage II-IV; P = 0.001), advanced ENETS stage (Stage IIa-IV; P = 0.001), nonfunctioning tumors (P = 0.002), and a shorter disease-free survival (P = 0.019). However, there was no significant correlation between nectin-3 expression in the membrane and/or cytoplasm and the clinicopathological parameters. The present results suggest that decreased nectin-3 expression in the membrane is associated with increased tumor aggressiveness of PanNETs. Clinically, immunohistochemical analysis of nectin-3 may help predict tumor aggressiveness for PanNETs.

Mutations in the Mitochondrial ND1 Gene Are Associated with Postoperative Prognosis of Localized Renal Cell Carcinoma.

We analyzed mutations in the mitochondrial ND1 gene to determine their association with clinicopathological parameters and postoperative recurrence of renal cell carcinoma (RCC) in Japanese patients. Among 62 RCC cases for which tumor pathology was confirmed by histopathology, ND1 sequencing revealed the presence of 30 mutation sites in 19 cases. Most mutations were heteroplasmic, with 16 of 19 cases harboring one or more heteroplasmic sites. Additionally, 12 sites had amino acid mutations, which were frequent in 10 of the cases. The 5-year recurrence-free survival (RFS) rate was significantly worse in patients with tumors >40 mm in diameter (p = 0.0091), pathological T (pT) stage ≥3 (p = 0.0122), Fuhrman nuclear atypia grade ≥III (p = 0.0070), and ND1 mutations (p = 0.0006). Multivariate analysis using these factors revealed that mutations in ND1 were significantly associated with the 5-year RFS rate (p = 0.0044). These results suggest a strong correlation between the presence of ND1 mutations in cancer tissue and postoperative recurrence of localized RCC in Japanese patients.

A method for estimating spatial resolution of real image in the Fourier domain.

Spatial resolution is a fundamental parameter in structural sciences. In crystallography, the resolution is determined from the detection limit of high-angle diffraction in reciprocal space. In electron microscopy, correlation in the Fourier domain is used for estimating the resolution. In this paper, we report a method for estimating the spatial resolution of real images from a logarithmic intensity plot in the Fourier domain. The logarithmic intensity plots of test images indicated that the full width at half maximum of a Gaussian point spread function can be estimated from the images. The spatial resolution of imaging X-ray microtomography using Fresnel zone-plate optics was also estimated with this method. A cross section of a test object visualized with the imaging microtomography indicated that square-wave patterns up to 120-nm pitch were resolved. The logarithmic intensity plot was calculated from a tomographic cross section of brain tissue. The full width at half maximum of the point spread function estimated from the plot coincided with the resolution determined from the test object. These results indicated that the logarithmic intensity plot in the Fourier domain provides an alternative measure of the spatial resolution without explicitly defining a noise criterion.

Hepatic adrenal rest tumor: Diagnostic pitfall and proposed algorithms to prevent misdiagnosis as lipid-rich hepatocellular carcinoma.

We present a case of adrenal rest tumor of the liver in which differential diagnosis from lipid rich-hepatocellular carcinoma (HCC) was challenging. The patient was a 50-year-old woman in whom a 3-cm tumorous mass was discovered in segment 7 of the liver during computed tomography evaluation of a uterine leiomyoma. The preoperative diagnosis was HCC, and subsegmental liver resection was performed. The tumor appeared as a well-demarcated golden yellow nodule consisting of clear or partially eosinophilic cells arranged in a trabecular pattern. The initial impression of this lesion was that of clear cell type or lipid-rich type HCC because it stained positive for Hep Par1, but negative for arginase-1 and positive for CD56 which is one of the neuroendocrine markers. The lesion also stained positive for SF-1 and 3ß-HSD, both of which are markers of adrenocortical tissue. The final diagnosis was hepatic adrenal rest tumor. Hepatic adrenal rest tumor should be considered in the differential diagnosis of segment 7 tumor. A diagnostic algorithm that includes immunohistochemical staining for CD56 and arginase-1 is to rule out the possibility of lipid-rich HCC.

Intratumoral heterogeneity of HER2 protein and amplification of HER2 gene in salivary duct carcinoma.

Salivary duct carcinoma (SDC) is an aggressive adenocarcinoma of the salivary glands, and accounts for 1-3% of all malignant salivary gland tumors, resembling morphologically invasive ductal carcinoma (IDC) of the breast. In contrast to IDC of the breast and gastric carcinoma (GC), the study of human epidermal growth factor receptor 2 (HER2) in SDC has not progressed. Therefore, we investigated the relationship between HER2 protein expression and amplification of the HER2 gene, and compared them in terms of intratumoral heterogeneity (ITH) in 13 cases of SDC using immunohistochemistry and dual color in situ hybridization. We found seven cases with protein overexpression (53.8%) and five cases with gene amplification (38.5%) in accordance with ASCO/CAP guidelines. ITH of HER2 protein expression was seen in seven cases (53.8%). Interestingly, the ratio of the HER2 gene showed homogenous distribution with or without the presence of ITH of HER2 protein expression. SDC tends to have more ITH of HER2 protein similarly to GC, in contrast to IDC of the breast. ITH of HER2 protein in SDC has no heterogeneity of the HER2 gene amplification. The mechanism of HER2 protein expression in SDC might proceed through a more complex pathway relative to that of IDC of the breast.

Pathology of Crooke Cells in the Human Pituitaries: A Timely Review.

Crooke cell change was first found in the regressed and suppressed corticotroph (adrenocorticotropic hormone-producing) cells, and now is known to occur in pituitary tumors. The tumor cells of this type can be recognized by morphology with immunohistochemistry, and are well known to predict aggressive behavior such as invasion and rare metastases. This is one of the representative neuroendocrine tumors in the pituitary which is now considered to have malignant potential as proposed in the pancreas and gastrointestinal tracts. It is important to emphasize the pituitary tumor pathology such as Crooke cell change for prognostication and appropriate therapies. This review article describes the evolution from the Crooke cells to Crooke cell tumors which is timely along with the Fifth WHO classification 2022 published online.

Double pituitary neuroendocrine tumors in a patient with normal growth hormone level acromegaly: A case report and review of the literature.

Background: Acromegaly is a rare disease caused by growth hormone (GH) hypersecretion caused by a pituitary neuroendocrine tumor (PitNET). However, some acromegaly patients show normal GH levels, and they can be a pitfall in clinical diagnosis. Moreover, rarely, synchronous true double or multiple PitNETs are encountered. Moreover, these PitNETs increase the risk of a left lesion during surgical exploration. Case Description: The patient, who was a 73-year-old female, was referred to our hospital with a chief complaint of headache. Assessment of basal anterior pituitary function revealed a slightly high level of insulin-like growth factor-1 (IGF-1) (standard deviation, 2.4), and her physical findings exhibited mild acromegalic features. The endocrine evaluation confirmed acromegaly and magnetic resonance imaging (MRI) showed a macro PitNET with suprasellar extension. Endoscopic endonasal surgery (EES) was performed to remove the macro PitNET. Although postoperative MRI showed complete removal of the macro PitNET, endocrinological testing indicated no improvement in GH or IGF-1 excess. Pathological examination of the surgical specimen revealed a gonadotropic PitNET. Therefore, we repeated the MRI scan and found a micro PitNET in the thin left normal pituitary gland. A second EES was successfully performed to remove the micro PitNET completely, and both endocrinological and pathological examinations confirmed that the disease was cured. Conclusion: Diagnosing acromegaly with low GH levels requires close monitoring. Double PitNETs are relatively rare and can cause incomplete remission of functional PitNETs.

Analysis of Insulinoma-Associated Protein 1 Expression in Pituitary Neuroendocrine Tumors.

Insulinoma-associated protein 1 (INSM1) is a representative diagnostic marker of neuroendocrine neoplasms (NENs); however, it has not yet been used to diagnose pituitary neuroendocrine tumors (PitNETs), according to the 2022 World Health Organization (WHO) classification of pituitary tumors. This study aimed to examine the expression of INSM1 using immunohistochemistry, in the various cell lineages of PitNET classified by hormone secretion and transcription factor expression. INSM1 expression in PitNETs (different subtypes) and normal pituitary tissues was immunohistochemically assessed. The results were interpreted as scores of 0 (negative), 1 (focally positive), or 2 (frankly positive), depending on the proportion of cell staining. Twenty-eight of 35 PitNET cases (80%) showed INSM1 positivity in their nuclei. The staining in each histological subtype of PitNETs was as follows: somatotroph tumors, score 0 = 3/5, score 1 = 1/5, score 2 = 1/5; lactotroph tumors, score 0 = 2/5, score 1 = 1/5, score 2 = 2/5; thyrotroph tumors, score 2 = 5/5; corticotroph tumors: score 1 = 1/9, score 2 = 8/9; gonadotroph tumors, score 0 = 2/10, score 1 = 0/10, score 2 = 8/10; and unclassifiable tumor, score 1 = 1/1. INSM1 expression in most PitNETs was obtained, similar to that in the normal pituitary gland; thus, INSM1 may maintain the characteristics of anterior pituitary cells and pituitary tumors.

Immunohistochemical Analyses of Mammalian Target of Rapamycin (mTOR) Expression in Pituitary Neuroendocrine Tumors (PitNETs): mTOR as a Therapeutic Target for Functional PitNETs.

Current therapeutic modalities for pituitary neuroendocrine tumors (PitNETs) include medication, surgery, and radiotherapy. Some patients have tumors that are refractory to current modalities. Therefore, novel treatment options are needed for patients with intractable diseases. Consequently, we examined the pathological data of PitNETs to study medical therapies. We retrospectively studied 120 patients with histologically diagnosed PitNETs. We used the data for the histopathological examination of hormones, such as growth hormone (GH), prolactin (PRL), adrenocorticotropic hormone, thyroid stimulating hormone, luteinizing hormone, follicle-stimulating hormone, and α-subunit, together with the immunohistochemical studies of the phospho-mammalian target of rapamycin (mTOR), cytokeratin (CAM5.2), somatostatin receptor (SSTR) type 2 and 5, Pit-1 (POU1F1/GHF-1), steroidogenic factor-1 (SF-1), and Tpit. GH-, PRL-, and SSTR5-immunopositive PitNETs had significantly higher percentage of mTOR-positivity, compared with GH-, PRL-, and SSTR5-immunonegative Pit NETs. Our results show that activation of the AKT/phosphatidylinositol-3-kinase pathway, including mTOR activation, might be related the development of PitNETs, especially GH- and PRL-producing PitNETs. Thus, mTOR is a potential target for treating functional PitNETs.

Subserosal Layer and/or Pancreatic Invasion Based on Anatomical Features as a Novel Prognostic Indicator in Patients with Distal Cholangiocarcinoma.

The American Joint Committee on Cancer (AJCC) 8th edition T-staging system for distal cholangiocarcinoma (DCC) proposes classification according to the depth of invasion (DOI); nevertheless, DOI measurement is complex and irreproducible. This study focused on the fibromuscular layer and evaluated whether the presence or absence of penetrating fibromuscular invasion of DCC contributes to recurrence and prognosis. In total, 55 patients pathologically diagnosed with DCC who underwent surgical resection from 2002 to 2022 were clinicopathologically examined. Subserosal layer and/or pancreatic (SS/Panc) invasion, defined as penetration of the fibromuscular layer and invasion of the subserosal layer or pancreas by the cancer, was assessed with other clinicopathological prognostic factors to investigate recurrence and prognostic factors. According to the AJCC 8th edition, there were 11 T1, 28 T2, and 16 T3 cases, with 44 (80%) cases of SS/Panc invasion. The DOI was not significantly different for both recurrence and prognostic factors. In the multivariate analysis, only SS/Panc was identified as an independent factor for prognosis (hazard ratio: 16.1; 95% confidence interval: 2.1-118.8, p = 0.006). In conclusion, while the determination of DOI in DCC does not accurately reflect recurrence and prognosis, the presence of SS/Panc invasion may contribute to the T-staging system.

Structural aging of human neurons is opposite of the changes in schizophrenia.

Human mentality develops with age and is altered in psychiatric disorders, though their underlying mechanism is unknown. In this study, we analyzed nanometer-scale three-dimensional structures of brain tissues of the anterior cingulate cortex from eight schizophrenia and eight control cases. The distribution profiles of neurite curvature of the control cases showed a trend depending on their age, resulting in an age-correlated decrease in the standard deviation of neurite curvature (Pearson's r = -0.80, p = 0.018). In contrast to the control cases, the schizophrenia cases deviate upward from this correlation, exhibiting a 60% higher neurite curvature compared with the controls (p = 7.8 × 10-4). The neurite curvature also showed a correlation with a hallucination score (Pearson's r = 0.80, p = 1.8 × 10-4), indicating that neurite structure is relevant to brain function. This report is based on our 3D analysis of human brain tissues over a decade and is unprecedented in terms of the number of cases. We suggest that neurite curvature plays a pivotal role in brain aging and can be used as a hallmark to exploit a novel treatment of schizophrenia.

Subtyping of hepatocellular adenoma: a machine learning-based approach.

Subtyping of hepatocellular adenoma (HCA) is an important task in practice as different subtypes may have different clinical outcomes and management algorithms. Definitive subtyping is currently dependent on immunohistochemical and molecular testing. The association between some morphologic/clinical features and HCA subtypes has been reported; however, the predictive performance of these features has been controversial. In this study, we attempted machine learning based methods to select an efficient and parsimonious set of morphologic/clinical features for differentiating a HCA subtype from the others, and then assessed the performance of the selected features in identifying the correct subtypes. We first examined 50 liver HCA resection specimens collected at the University of Washington and Kobe University/Kings College London, including HNF1α-mutated HCA (H-HCA) (n = 16), inflammatory HCA (I-HCA) (n = 20), beta-catenin activated HCA (ß-HCA) (n = 8), and unclassified HCA (U-HCA) (n = 6). Twenty-six morphologic/clinical features were assessed. We used LASSO (least absolute shrinkage and selection operator) to select key features that could differentiate a subtype from the others. We further performed SVM (support vector machine) analysis to assess the performance (sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy) of the selected features in HCA subtyping in an independent cohort of liver resection samples (n = 20) collected at the University of Wisconsin-Madison. With some overlap, different combinations of morphologic/clinical features were selected for each subtype. Based on SVM analysis, the selected features classified HCA into correct subtypes with an overall accuracy of at least 80%. Our findings are useful for initial diagnosis and subtyping of HCA, especially in clinical settings without access to immunohistochemical and molecular assays.

Molecular, functional, and histopathological classification of the pituitary neuroendocrine neoplasms.

In 2017, WHO published an updated classification of the pituitary adenomas according to the lineages defined by the transcription factors, PIT1, SF1 and TPIT. Nomenclature of the pituitary tumors follows the mature cell types such as somatotroph (GH), lactotroph (LH), thyrotroph, corticotroph, and gonadotroph (FSH, LH). Null cell adenomas are defined by the absence of expression of any hormones and transcription factors. Not infrequently, the pituitary adenomas are invasive to the adjacent structures and are designated as aggressive adenomas. Knosp grading is often used to define the aggressiveness of the tumor. Sparsely granulated somatotroph adenomas and Crooke cell corticotroph adenomas are representative aggressive adenomas. Recently, genomics regarding various adenomas have been clarified, such as GNAS for somatotrophs and USP8 for corticotrophs. Familial pituitary adenomas are another aspect which has been clarified such as MEN1, Carney's complex, familial isolated pituitary adenoma and McCune-Albright syndrome. The pituitary adenomas often produce GH or PRL, hormones of PIT1 transcription factor. It has been agreed that the pituitary adenomas share the characteristics of neuroendocrine neoplasms. The terminology of pituitary neuroendocrine tumor has been discussed. This review article covers various aspects of pituitary adenomas.

Adult Langerhans Cell Histiocytosis Diagnosed by Biopsy of the Skull Tumor Generated after Craniotomy.

Langerhans cell histiocytosis (LCH) is a disease characterized by the proliferation of Langerhans cells. Most cases of LCH occur in children, although it can be seen in adults as well. We encountered an adult case of LCH. A 44-year-old woman who was diagnosed as diabetes insipidus underwent a magnetic resonance imaging (MRI) of the head which revealed sellar and suprasellar gadolinium-enhanced mass. Prolactin level was high and cabergoline was prescribed. The size of this mass had reduced, so we supposed the tumor was prolactinoma. However, after 4 years of observation, it had increased once again. The biopsy of pituitary stalk lesion was performed via transcranial approach. The histological diagnosis was initially gangliocytoma. The patient complained of back pain after surgery. Three months after the biopsy, a computed tomography (CT) scan revealed multiple osteolytic lesions throughout the entire body. One of the osteolytic lesions of the skull was removed to determine the diagnosis. The pathological examination of the skull led to a diagnosis of LCH. We concluded retrospectively that the lesion of the pituitary stalk was LCH mimicking gangliocytoma though classical pathological findings were not obtained. In conclusion, LCH should be considered as a differential diagnosis in adult cases of diabetes insipidus with hypothalamic-pituitary lesion.

Brain capillary structures of schizophrenia cases and controls show a correlation with their neuron structures.

Brain blood vessels constitute a micrometer-scale vascular network responsible for supply of oxygen and nutrition. In this study, we analyzed cerebral tissues of the anterior cingulate cortex and superior temporal gyrus of schizophrenia cases and age/gender-matched controls by using synchrotron radiation microtomography or micro-CT in order to examine the three-dimensional structure of cerebral vessels. Over 1 m of cerebral blood vessels was traced to build Cartesian-coordinate models, which were then used for calculating structural parameters including the diameter and curvature of the vessels. The distribution of vessel outer diameters showed a peak at 7-9 µm, corresponding to the diameter of the capillaries. Mean curvatures of the capillary vessels showed a significant correlation to the mean curvatures of neurites, while the mean capillary diameter was almost constant, independent of the cases. Our previous studies indicated that the neurites of schizophrenia cases are thin and tortuous compared to controls. The curved capillaries with a constant diameter should occupy a nearly constant volume, while neurons suffering from neurite thinning should have reduced volumes, resulting in a volumetric imbalance between the neurons and the vessels. We suggest that the observed structural correlation between neurons and blood vessels is related to neurovascular abnormalities in schizophrenia.