Glycogen-rich pleomorphic xanthoastrocytoma with clear-cell features: confirmatory report of a rare variant with implications for differential diagnosis

Central nervous system space-occupying lesions with clear-cell features encompass a nosologically heterogeneous array, ranging from reactive histiocytic proliferations to neuroepithelial or meningothelial neoplasms of various grades and to metastases. In the face of such differential diagnostic breadth, recognizing cytoplasmic lucency as part of the morphological spectrum of some low grade gliomas will directly have an impact on patient care. We describe a prevailing clear-cell change in an epileptogenic left temporal pleomorphic xanthoastrocytoma surgically resected from a 36-year-old man. Mostly subarachnoid and focally calcified, the tumor was composed of fascicles of moderately atypical spindle cells with optically lucent cytoplasm that tended to intermingle with a desmoplastic mesh of reticulin fibers. Immunohistochemically, coexpression of S100 protein, vimentin, GFAP, and CD34 was noted. Conversely, neither punctate staining for EMA nor positivity for CD68 was seen. Mitotic activity was absent, and the MIB1 labeling index was 2-3% on average. Diastase-sensitive PAS-positive granula indicated clear-cell change to proceed from glycogen storage. Electron microscopy showed tumor cell cytoplasm to be largely obliterated by non-lysosomal-bound pools of glycogen, while hardly any fat vacuole was encountered. Neither ependymal-derived organelles nor annular lamellae suggesting oligodendroglial differentiation were detected. The latter differential diagnosis was further invalidated by lack of codeletion of chromosomal regions 1p36 and 19q13 on molecular genetic testing. By significantly interfering with pattern recognition as an implicit approach in histopathology, clear-cell change in pleomorphic xanthoastrocytoma is likely to suspend its status as a “classic”, and to prompt more deductive differential diagnostic strategies to exclude look-alikes, especially clear-cell ependymoma and oligodendroglioma.     

Oncocytic ependymoma: A new morphological variant of high-grade ependymal neoplasm composed of mitochondrion-rich epithelioid cells

Oncocytomas are defined as tumors containing in excess of 50% large mitochondrion-rich cells, irrespective of histogenesis and dignity. Along the central neuraxis, oncocytomas are distinctly uncommon but relevant to the differential diagnosis of neoplasia marked by prominent cytoplasmic granularity. We describe an anaplastic ependymoma (WHO grade III) with a prevailing oncocytic component that was surgically resected from the right fronto-insular region of a 43-year-old female. Preoperative imaging showed a fairly circumscribed, partly cystic, contrast-enhancing mass of 2 cm × 2 cm × 1.7 cm. Histology revealed a biphasic neoplasm wherein conventional ependymal features coexisted with plump epithelioid cells replete with brightly eosinophilic granules. Whereas both components displayed an overtly ependymal immunophenotype, including positivity for S100 protein and GFAP, as well as “dot-like” staining for EMA, the oncocytic population also tended to intensely react with the antimitochondrial antibody 113-1. Conversely, failure to bind CD68 indicated absence of significant lysosomal storage. Negative reactions for both pan-cytokeratin (MNF 116) and low molecular weight cytokeratin (CAM 5.2), as well as synaptophysin and thyroglobulin, further assisted in ruling out metastatic carcinoma. In addition to confirming the presence of “zipper-like” intercellular junctions and microvillus-bearing cytoplasmic microlumina, electron microscopy allowed for the pervasive accumulation of mitochondria in tumor cells to be directly visualized. A previously not documented variant, oncocytic ependymoma, is felt to add a reasonably relevant novel item to the differential diagnosis of granule-bearing central nervous system neoplasia, in particular oncocytic meningioma, granular cell astrocytoma, as well as metastatic deposits by oncocytic malignancies from extracranial sites.     

Paratesticular myxoid/round cell liposarcoma harboring type 3 DDIT3-FUS fusion gene: Report of a very rare case

Myxoid/round cell liposarcomas are rare mesenchymal neoplasms. They preferentially occur in the lower extremity, and most of them have type 1 or type 2 DDIT3-FUS fusion gene. We report here a very rare case of myxoid/round cell liposarcoma of the paratesticular region with type 3 DDIT3-FUS fusion gene. A 46-year-old Japanese man noticed a gradually enlarged intrascrotal mass without pain. Surgical resection of 3.4 cm × 2.1 cm oval mass was carried out, and it was located in the right paratesticular region apart from the spermatic cord and epididymis. Histological examination of the tumor revealed ovoid cell proliferation with anastomosing vascular network and scattered lipoblasts. Genetic analysis elucidated that the tumor had a chromosomal translocation, type 3 DDIT3-FUS chimeric gene. The tumor was definitely diagnosed as myxoid/round cell liposarcoma of the paratesticular region.     

Rapid spontaneous malignant progression of supratentorial tanycytic ependymoma with sarcomatous features – “Ependymosarcoma”

By analogy to gliosarcoma, the term “ependymosarcoma” has recently been coined to thematize the rare phenomenon of a malignant mesenchymal component arising within an ependymoma. We report on an example of this paradigm, involving tanycytic ependymoma as the host tumor in a 40-year-old female who underwent two tumor extirpation procedures at one-year interval. She first presented with severe headaches, and was seen by imaging to harbor a moderately enhancing mass 2.5 cm in diameter at the rostral septum pellucidum accompanied by occlusive hydrocephalus. Microscopically, the tumor consisted of solid, wavy fascicles of elongated cells that were occasionally interrupted by vague perivascular pseudorosettes. Mitotic activity was absent, and less than 1% of nuclei immunoreacted for MIB-1. A histological diagnosis of tanycytic ependymoma (WHO grade II) was rendered, and no adjuvant therapy given. At recurrence, the lesion was 3.5 cm in diameter, intensely enhancing, and had already seeded into the subarachnoid space. Histology showed a biphasic glial–sarcomatous architecture with remnants of the original ependymoma now displaying hypercellularity and atypical – yet not frankly anaplastic – features. The sarcomatous moiety consisted of spindle and epithelioid cells densely interwoven with reticulin fibers. While the ependymal component was GFAP and S100 protein positive, and featured punctate staining for EMA, none of these markers was expressed in the adjacent sarcoma. Instead, the latter reacted for vimentin and smooth muscle actin. To the best of our knowledge, this is the first documentation of tanycytic ependymoma undergoing malignant transformation, one driven by a highly anaplastic mesenchymal component, corresponding to “ependymosarcoma”.     

FISH analyses for 1p and 19q status on gliomas: Reporting an 8 years' experience from a tertiary care center in the Middle East

Diffuse gliomas are the most common primary malignancies of the central nervous system (CNS). The 2016 edition of the World Health Organization (WHO) classification of CNS tumors opted to integrate current molecular data with the traditional histologic diagnosis in the definition of the disease. This integrated diagnosis offers a greater level of objectivity and helps in establishing more definitive diagnoses for tumors that may have been controversial on histology alone. The classification of gliomas may require FISH technique to identify chromosomal abnormalities. FISH is commonly used to identify 1p/19q codeletion, but many challenges are encountered in the process. In this study, we review the FISH results for 1p/19q codeletion of n = 85 diffuse glioma samples examined at a tertiary care center in the Middle East over a period of 8 years. We also conduct a literature review to study the potential role of DNA-microarray in the identification of 1p/19q deletions. Glioblastoma (GBM), WHO grade IV is the most common glioma type identified (n = 24; 29%). All oligodendrogliomas show 1p/19q codeletion (26/26) while 12.5% of GBMs have 1p/19q codeletion (3/24). Isolated 1p deletions are only identified in one case of diffuse astrocytoma, WHO grade II. Isolated 19q deletions are identified in oligoastrocytoma, anaplastic astrocytoma, and glioblastoma. FISH is the most commonly used technique to diagnose oligodendroglioma because it is a simple, effective, and accessible technique in settings with limited resources. However, the optimization process remains highly variable between laboratories. Microarray is a more objective technique that can provide more information about the genetic alterations of the tumor for better diagnosis and sub-classification of diffuse glioma types.     

Role of estradiol withdrawal in ‘anhedonic’ sucrose consumption: A model of postpartum depression

Previously, a hormone-simulated pregnancy (HSP), and the subsequent ‘postpartum’ withdrawal in estradiol has been shown to precipitate depressive-like behaviours in the forced swim test in female rats. In this study, we used the HSP and ‘postpartum’ withdrawal to investigate the impact on sucrose consumption, a model of anhedonia. Rats were assigned to “postpartum”, “postpartum” + EB (estradiol benzoate), “postpartum” + IMI (imipramine; a tricyclic antidepressant), “postpartum” + DPN (diarylpropionitrile; an ERβ agonist), or ovariectomized (OVX) controls and OVX + IMI treatments. All “postpartum” groups received daily hormone injections (estradiol and progesterone) over 23 days to simulate pregnancy, while IMI groups also received daily injections of imipramine. After Day 23, “postpartum” rats were withdrawn from the hormone regimen (mimicking the postpartum decrease in gonadal hormones), and then received daily injections of compounds indicated (DPN, EB, IMI). Rats were tested for consumption of, and preference for, sucrose weekly at baseline, during ‘pregnancy’ and on ‘Postpartum’ Days 2-3. During the ‘postpartum’ period rats in the “postpartum” group had lower sucrose consumption and preference compared to during late-‘pregnancy’, but no decrease in ‘postpartum’ consumption or preference was seen in any other groups except “postpartum” + IMI and a decrease in sucrose preference only in the postpartum + EB group from mid-‘pregnancy’ to ‘postpartum’. The OVX  + IMI group had decreased sucrose consumption relative to OVX controls, suggesting a negative effect of imipramine on sucrose consumption. Together, these results suggest an important, though complex, role for gonadal hormones in the behavioral changes accompanying this model of depression.     

Meningial perineurioma: a benign peripheral nerve sheath tumor in a previously unrecognized central nervous system location, mimicking meningioma

Perineurioma is an uncommon, mostly benign, spindle-cell tumor of peripheral nerve sheath origin with a predilection for the soft tissues. Although increasing awareness points to the sites of involvement by perineurioma possibly being as ubiquitous as those frequented by schwannian tumors, only one intracerebral example has been described to date. We report on a surgically resected perineurioma of the falx cerebri in an 86-year-old woman. Preoperative imaging showed an enhancing extraaxial mass of 6 cm × 5.7 cm × 3.7 cm. Histologically, the tumor consisted of a proliferation of spindle cells interwoven by a lattice of basal lamina. Alongside a prevailing soft tissue perineurioma pattern, sclerosing and reticular areas were seen as well. Tumor cells coexpressed EMA and GLUT-1, and a minority immunoreacted for smooth muscle actin. Pericellular basal lamina was decorated with collagen type IV. No staining for S100 protein was detected. Mitotic activity was virtually absent, and the MIB1 labeling index averaged 2%. Ultrastructural examination revealed abundant pinocytotic vesicles within and conspicuous tight junctions between slender cytoplasmic processes which, in turn, were encased by discontinuous basal lamina. FISH analysis confirmed loss of at least part of one chromosome 22q. This observation calls attention to perineurioma as a novel item in the repertoire of low-grade meningial spindle cell neoplasms, in the differential diagnostic context of which it is apt to being misconstrued as either meningioma, solitary fibrous tumor, or neurofibroma. Confusion with the latter bears the risk of overgrading innocuous features of perineurioma as criteria for malignancy.     

Cardiovascular responses after brisk finger movement and their dependency on the “eigenfrequency” of the baroreflex loop

The baroreflex is mainly involved in short-term blood pressure regulation and strongly influenced by activations of medullary circulation centres in the brain stem and higher brain centres. One important feature of the baroreflex is its strong preference for oscillations around 0.1 Hz, which can be seen as resonance or “eigenfrequency” (EF) of the control loop (so-called Mayer waves). In the present study we investigated beat-to-beat heart rate intervals (RRI) and arterial blood pressure (BP) changes after brisk finger movement and their relationship to the “eigenfrequency” determined by cross spectral analysis between RRI and arterial blood pressure time series of 17 healthy subjects. The analyses revealed significant correlations between BP response magnitude (r = 0.63, p < 0.01) respectively RRI response magnitude (r = 0.59, p < 0.05) and EF. This can be interpreted in such a way that subjects with a “high” EF (>0.10 Hz) elicit larger BP responses as well as larger RRI responses when compared to subjects with a “low” EF (<0.10 Hz).     

Pyogenic granuloma of the large intestine: Case report and review of reported cases in the adult

Pyogenic granuloma (PG) is a polypoid lobular capillary hemangioma rarely described in the large bowel. We describe the case of a 72-year-old man with recent weight loss, anemia, and change in bowel habit. A 3 cm × 2 cm polypoid lesion in the right flexure of the colon was observed and treated with extended right hemicolectomy. A review of the English-language literature on PG of the large bowel in adults yielded eight previously reported cases. The age of the patients ranged from 26 to 80 years with a mean of 54.8 years. The lesions were all solitary, except one case of multiple lesions in the colon. Another case was associated with satellite lesions. Seven cases were located in the colon and two in the rectum. The mean maximum diameter of the lesions was 1.6 cm (range 0.5–3 cm). Colorectal bleeding was the most common clinical symptom. Due to its unusual appearance, PG can be misdiagnosed and mistreated as colon carcinoma with extensive surgery. Polypectomy or endoscopy mucosal resection is the optimal treatment. In large or deep lesions, a surgical excision may be necessary. Pathologists should be familiar with this condition so as to avoid overdiagnosis as a malignant vascular tumor.     

Cerebral transplantation of encapsulated mesenchymal stem cells improves cellular pathology after experimental traumatic brain injury

Purpose: “Naked” human mesenchymal stem cells (MSC) are neuro-protective in experimental brain injury (TBI). In a controlled cortical impact (CCI) rat model, we investigated whether encapsulated MSC (eMSC) act similarly, and whether efficacy is augmented using cells transfected to produce the neuro-protective substance glucagon-like peptide-1 (GLP-1). Methods: Thirty two Sprague–Dawley rats were randomized to five groups: controls (no CCI), CCI-only, CCI + eMSC, CCI + GLP-1 eMSC, and CCI + empty capsules. On day 14, cisternal cerebro-spinal fluid (CSF) was sampled for measurement of GLP-1 concentration. Brains were immuno-histochemically assessed using specific antibody staining for NeuN, MAP-2 and GFAP. In another nine healthy rats, in vitroResults: GLP-1 production rates were measured from cells explanted after 2, 7 and 14 days. GLP-1 production rate in transfected cells, before implantation, was 7.03 fmol/capsule/h. Cells were still secreting GLP-1 at a rate of 3.68 ± 0.49, 2.85 ± 0.45 and 3.53 ± 0.55 after 2, 7 and 14 days, respectively. In both of the stem cell treated CCI groups, hippocampal cell loss was reduced, along with an attenuation of cortical neuronal and glial abnormalities, as measured by MAP-2 and GFAP expression. The effects were more pronounced in animals treated with GLP-1 secreting eMSC. This group displayed an increased CSF level of GLP-1 (17.3 ± 3.4 pM). Conclusions: Hippocampal neuronal cell loss, and cortical glial and neuronal cyto-skeletal abnormalities, after CCI are reduced following transplantation of encapsulated eMSC. These effects were augmented by GLP-1 transfected eMSC.     

Reduced serum non-enzymatic antioxidant defense and increased lipid peroxidation in schizophrenic patients on a hypocaloric diet

This study aimed to affirm the use of functional near-infrared spectroscopy (fNIR) in examining frontal lobe role during automatic (i.e., requires retrieval from long-term memory) and method-based (i.e., requires calculation) arithmetic processing. Adult university students (math difficulties [MD] and control) performed simple arithmetic calculations while monitored using an fNIR system designed to image regions within the frontal cortices. Addition and subtraction problems presented on a computer screen belonged to one of three categories: triples “under 10” (e.g., 2 + 3 = ?, 5 − 3 = ?), triples that “break 10” (e.g., 5 + 8 = ?, 13 − 5 = ?), or triples “including 10” (e.g., 10 + 7 = ?, 17 − 10 = ?). fNIR recordings indicated significant interactions between type of triple, operation, and group over left frontal lobe, and between type of triple and group over right frontal lobe.Within-group differences among controls were found in the “break 10” triples with higher DeOxyHb level recorded during subtraction processing. Between-group differences were found in the “break 10” and “including 10” triples for subtraction with higher levels of DeOxyHb recorded among controls. Results imply that among adults frontal lobe is still involved during simple mathematical processing and fNIR recordings can differentiate its role in adults of varying mathematical ability.     

Influence of 5 Hz repetitive transcranial magnetic stimulation on motor learning

The aim of our study was to assess a possible improvement in motor learning induced by 5 Hz repetitive transcranial magnetic stimulation (rTMS) of human motor cortex. The same stimulation protocol previously enhanced perceptual learning as assessed by tactile discrimination performance when applied to the human primary somatosensory cortex. We applied 1250 pulses of 5 Hz “real” rTMS at 90% of resting motor threshold to the motor hotspot of the abductor pollicis brevis (APB) muscle in 15 healthy subjects before 1 h of motor training. Furthermore, 15 subjects received 5 Hz “sham” rTMS and served as control group. The motor task consisted of a synchronized co-contraction of the right APB and deltoid muscle. The latency between the onsets of muscle contractions was measured during training and served as a parameter for motor learning. MEP amplitudes were assessed in a subgroup of 10 subjects before and after rTMS as a parameter of corticospinal excitability. We found a significant learning effect in both groups as indicated by a reduction of latencies between the onsets of muscle contractions in the course of the training. Corticospinal excitability increased after “real”, but not after “sham” rTMS. However, “real” rTMS did not significantly influence motor learning as compared to “sham” rTMS. We conclude that 5 Hz rTMS of human primary motor cortex is not able to improve motor learning in healthy subjects, which might be due to the higher complexity of motor learning as compared to perceptual learning in the tactile domain.     

K and Ca dependence of inspiratory-related rhythm in novel “calibrated” mouse brainstem slices

Recently developed transversal newborn rat brainstem slices with “calibrated” rostrocaudal margins unraveled novel features of rhythmogenic inspiratory active pre-Bötzinger complex (preBötC) neural networks (Ballanyi and Ruangkittisakul, 2009). For example, slice rhythm in physiological (3 mM) superfusate K⁺ is depressed by modestly raised Ca²⁺ and restored by raised K⁺. Correspondingly, we generated here calibrated preBötC slices from commonly used newborn C57BL/6 mice in which rostrocaudal extents of respiratory marker structures, e.g., the inferior olive, turned out to be smaller than in newborn rats. Slices of 400–600 μm thickness with likely centered preBötC kernel (“m-preBötC slices”) generated rhythm in 3 mM K⁺ and 1 mM Ca²⁺ for several hours although its rate decreased to <5 bursts/min after >1 h. Rhythm was stable at 8–12 bursts/min in 6–7 mM K⁺, depressed by 2 mM Ca²⁺, and restored by 9 mM K⁺. Our findings provide the basis for future structure–function analyses of the mouse preBötC, whose activity depends critically on a “Ca⁺/K⁺ antagonism” as in rats.     

Gliomas: association of histology and molecular genetic analysis of chromosomes 1p, 10q, and 19q

The aim of our study was to evaluate the frequencies of loss of heterozygosity (LOH) on chromosomes 1p, 10q, and 19q in gliomas and to correlate them with the histological diagnosis and with patient age and gender. We found deletions within chromosome 1p to be significantly associated with the histological subtype of glial tumor (P < 0.05); frequency of 1p deletions increased from astrocytoma (0%) through glioblastoma (31%) and oligoastrocytoma (57%) to oligodendroglioma (63%). In patients with 1p LOH, the odds for having astrocytoma or glioblastoma were approximately 10-fold and 4-fold lower, respectively, than oligodendroglioma. The odds for having oligoastrocytoma were similar to oligodendroglioma (OR = 1.3). The frequency of 10q LOH in patients with glioblastoma was significantly higher than in patients with oligodendroglioma (89% vs. 36%; P < 0.005). In patients with oligodendroglioma, most cases with LOH on chromosome 1p also had LOH 19q (90%), one case of 1p LOH also had a deletion on 10q. Statistical analyses revealed a significant association between deletions on 1p and 19q (P < 0.05). Our data provide evidence that use of molecular genetic analyses of chromosomes 1p, 19q, and 10q might improve the diagnosis of gliomas.     

Variety enhances food intake in humans: Role of sensory-specific satiety

Twenty-one subjects were studied to evaluate the effect of renewal of sensory stimulations of previously eaten foods on sensory-specific satiety and intake. The subjects ate French fries then brownie cakes ad libitum in three situations: “monotonous” — fries then brownies were consumed alone; “simultaneous” — condiments (ketchup and mayonnaise for the fries, vanilla cream and whipped cream for the brownies) were added during intakes; “successive” — after intake of fries alone, ketchup then mayonnaise were available with fries and, after intake of brownies alone, vanilla cream then whipped cream were offered with brownies. The quantities eaten in the “simultaneous” and “successive” situations were higher (p < 0.001) than those in the “monotonous” one (1485 ± 582 and 1682 ± 777 kcal vs 1195 ± 552 kcal, respectively). In the “successive” situation, hedonic ratings for fries diminished during intake but increased after the introduction of ketchup, leading to additional intake of fries. Similarly, hedonic ratings for brownies diminished during intake and increased after the introduction of vanilla cream leading to additional brownie intake (mayonnaise and whipped cream had no significant effect). Food variety, obtained by adding condiments can increase food intake in the short term. The mechanism by which food consumption is increased after the addition of condiments is introduced is at least partly related to the attenuation of sensory-satiety for a given food.