Eosinophilic Bodies Research Articles

Infecção mista de Bartonella e Eperythrozoon em um cão - relato de caso

ABSTRACT A March male Golden, weighing 7.6kg, presented with gradual weight loss, high body temperature, depression, poor appetite and thirst, and vomiting before consultation. The results showed that the erythrocytes, hematocrit, hemoglobin, and platelets were lower than the reference values. The diagnosis of mixed infection with haematocrit and eosinophilic bodies was confirmed by real-time fluorescence PCR of whole blood, which was positive for haematocrit and eosinophilic bodies. The dog was treated with doxycycline and ceftriaxone, and the dog fully recovered after 2 weeks with blood transfusion, symptomatic treatment, and supportive therapy. This indicates that the disease can be treated well by a comprehensive treatment approach.

A lower motor neuron disease in takahē (Porphyrio hochstetteri) is an endoplasmic reticulum storage disease

Aims: To investigate the pathogenesis of a disease in takahē with intracytoplasmic inclusion bodies in lower motor neurons. Methods: Four cases aged between 5 and 12 years, from three different wildlife sanctuaries in New Zealand were examined. Of these, only one had signs of spinal dysfunction in the form of paresis. Stained paraffin sections of tissues were examined by light microscopy and immunostained sections of the ventral horn of the spinal cord by confocal microscopy. Epoxy resin sections of the bird with spinal dysfunction were examined by electron microscopy. Results: Two types of inclusion bodies were noted, but only in motor neurons of the ventral spinal cord and brain stem. These were large globoid eosinophilic bodies up to 5 µm in diameter, and yellow/brown granular inclusions mostly at the pole of the cell. The globoid bodies stained with Luxol fast blue but not with periodic acid Schiff (PAS), or Sudan black. The granular inclusions stained with Luxol fast blue, PAS and Sudan black. Both bodies were slightly autofluorescent. On electron microscopy the globoid bodies had an even electron-dense texture and were bound by a membrane. Beneath the membrane were large numbers of small intraluminal vesicles. The smaller granular bodies were more heterogeneous, irregularly rounded and membrane-bound accumulations of granular electron-dense material, often with electron-lucent vacuoles. Others were more vesicular but contained varying amounts of electron-dense material. The large globoid bodies did not immunostain for lysosomal markers lysosomal associated protein 1 (LAMP1) or cathepsin D so they were not lysosomal. The small granular bodies stained for cathepsin D by a chromogenic method. A kindred matrix analysis showed two cases to be as closely related as first cousins, and another case was almost as closely related to one of them, but the fourth bird was unrelated to any other. Conclusions: It was concluded that this was an endoplasmic reticulum storage disease due to a specific protein misfolding within endoplasmic reticulum. It was rationalised that the two types of inclusions reflected the same aetiology, but that misfolded protein in the smaller granular bodies had entered the lysosomal system via endoplasmic reticulum autophagy. Although the cause was unclear, it most likely had a genetic aetiology or predisposition and, as such, has clinical relevance.

Identification and genomic characterization of Baculovirus penaei in Litopenaeus vannamei in Taiwan.

Baculovirus penaei (BP), the causative agent of tetrahedral baculovirosis, causes the death of penaeid genera at the larval and post-larval stages. BP has been reported in the Western Pacific, South-East Atlantic, and the State of Hawaii, but never in Asia. The clinical features of BP infection are non-specific, and diagnosis relies on histological and molecular methods. In the present study, we report the first identification of BP infection in a shrimp farm in Northern Taiwan in 2022. Histopathologically, several tetrahedral eosinophilic intranuclear occlusion bodies were observed in or budding out of the nuclei of the degenerative hepatopancreatic cells. In situ hybridization and polymerase chain reaction confirmed tetrahedral baculovirosis infection caused by BP. Sequence alignment of the TW BP-1 with the USA BP strain reported in 1995 revealed 94.81% identity in the partial gene. The possibility of the emergence of USA-like BP in Taiwan highlights the importance of further epidemiological investigations on the prevalence and impact of BP in Asia.

Upper Labial Mucosa Schwannoma: A Rare Case Report

An upper lip swelling, asymptomatic, and benign-looking lesion may be attributed to numerous aetiologies. About 25% to 45% of Schwannomas/Neurilemmomas occur in the head and neck region and are seldom seen in oral sites, accounting form only 1% of cases. Herein, the authors presented a case report of a 36-year-old female patient with a clinical appearance of upper labial mucosa swelling is mentioned, which mimicked a mucocele. It was a single, smooth, oval, fluctuant, and non tender swelling. Complete surgical excision was performed following proper protocol, and histological diagnosis revealed a well-outlined lesion enclosed within a fibrous capsule. The connective tissue mass of the tumour consisted predominantly of neural tissue arranged in Antoni A structures, characterised by a palisaded nuclear arrangement and the presence of distinctive eosinophilic Verocay bodies. Another area with a myxoid appearance, representing Antoni B structure, was also present, suggesting a Schwannoma/Neurilemmoma. During follow-up, complete healing with no recurrence of swelling was observed. Schwannomas/Neurilemmomas in the head and neck region are less common, particularly in the oral cavity. According to various studies, the occurrence of neurilemmomas in the intraoral aspect accounts for only 19.24% of cases, specifically involving the mucosa of the lip. Practitioners should consider this rare entity of Schwannoma/Neurilemmoma when evaluating an upper lip swelling routinely.

Diffuse leptomeningeal glioneuronal tumor in a child masquerading as an intramedullary spinal pilocytic astrocytoma.

Diffuse leptomeningeal glioneuronal tumor (DLGNT) occurs predominantly in children and is typically characterized by diffuse leptomeningeal lesions throughout the neuroaxis with focal segments of parenchymal involvement. Recent reports have identified cases without diffuse leptomeningeal involvement that retain classic glioneuronal features on histology. In this report, we present a case of a 4-year-old boy with a large cystic-solid intramedullary spinal cord lesion that on surgical biopsy revealed a biphasic astrocytic tumor with sparsely distributed eosinophilic granular bodies and Rosenthal fibers. Next-generation sequencing revealed a KIAA1549-BRAF fusion, 1p/19q codeletion, and lack of an IDH1 mutation. Methylation profiling demonstrated a calibrated class score of 0.98 for DLGNT and copy number loss of 1p. Despite the morphologic similarities to pilocytic astrocytoma and the lack of oligodendroglial/neuronal components or leptomeningeal dissemination, the molecular profile was definitive in classifying the tumor as DLGNT. This case highlights the importance of molecular and genetic testing in the characterization of pediatric central nervous system tumors.

A 90-day repeated oral dose toxicity study of 2-Butylbenzo[d]isothiazol-3(2H)-one in rats

2-Butylbenzo[d]isothiazol-3(2H)-one (BBIT, CAS No. 4299-07-4) is widely used as an industrial antiseptic and antifungal agent. To investigate its toxicological properties and determine the no-observed-adverse-effect level (NOAEL), a 90-day repeated oral toxicological study of BBIT was conducted in Crl:CD (SD) rats at doses of 0 (vehicle control, corn oil), 30, 90, or 270 mg/kg/day. There was no mortality or abnormal clinical signs related to treatment in any group. Slightly decreased body weight and food consumption were observed in the 270 mg/kg group in females. Increased urine volume and kidney weight, increased liver weight, and thickening of the forestomach mucosa in autopsy were observed in both sexes in the 270 mg/kg group. Histopathological examination revealed that hyperplasia of the squamous epithelium of the forestomach with parakeratosis and/or hyperkeratosis was observed in both sexes in all the BBIT-treated groups. Moreover, centrilobular hypertrophy of hepatocytes was observed in both sexes of the 270 mg/kg group. Similarly, increased depositions of eosinophilic bodies and/or hyaline droplets in the proximal tubules of the kidney were observed among the male in the 270 mg/kg group. Based on the forestomach changes, NOAEL was judged to be less than 30 mg/kg/day in both sexes under this study’s conditions.

A 90-day dose toxicity study of 2-(2H-benzotriazol-2-yl)-6-dodecyl-4-methylphenol in rats

2-(2H-benzotriazol-2-yl)-6-dodecyl-4-methylphenol (BTMLP, CAS No. 125304-04-3) is widely used as a liquid ultraviolet absorber that prevents deterioration of synthetic resins and so on. To investigate its toxicological properties and determine the no-observed-adverse-effect level (NOAEL), a 90-day repeated oral toxicological study of BTMLP was conducted in Crl:CD (SD) rats at doses of 0 (vehicle control, corn oil), 100, 300, and 1000 mg/kg/day. There was no observed mortality or abnormal clinical signs related to the treatment of any group. Body weight and food consumption were not affected by BTMLP treatment. In males, significant prolongations of prothrombin time and activated partial thrombin time were observed in the BTMLP-treated groups. Histopathological examination revealed a slight increase of the eosinophilic bodies and hyaline droplets in the renal cortical tubules in the 1000 mg/kg group in males. As mentioned above, the toxic effect of the BTMLP was noted in the blood coagulation system and kidneys only in males. Based on these findings, the NOAEL was judged to be less than 100 mg/kg/day in males and 1000 mg/kg/day in females under this study’s condition.

Eosinophilic imprints

Eosinophilic bodies are frequently used as a diagnostic aid in determining the underlying disease. The purpose of this article is to collate various eosinophilic entities seen histopathologically in various disorders.

S2182 A Case of Colonic Malakoplakia

Introduction: Malakoplakia is a rare histiocytic inflammatory response that is usually found in the urinary tract. Gastrointestinal involvement is considered the second most common location affected and is a result of dysfunctional macrophages. Histopathology is characterized by granular histiocytes with Micahelis-Gutmann bodies. Although usually an incidental finding, Malakoplakia is associated with immunosuppressive therapy, colorectal carcinoma and infectious diseases. Case Description/Methods: A 54-year-old man with a pmhx of alcohol use disorder was referred to clinic for acute, asymptomatic liver enzyme abnormalities. Laboratory findings were significant for AST of 270 U/L, ALT of 63 U/L, ALP of 65 U/L, and total bilirubin of 0.3 mg/dL. Further workup showed positive hepatitis B surface antigen, reactive hepatitis B core antibody and hepatitis B DNA by PCR was 172K IU/mL. Patient underwent screening colonoscopy which revealed a 2 mm sessile polyp in the cecum (Figure A). Histological examination of the polyp showed von-Hansemann cells containing Michaelis-Gutmann bodies, which is diagnostic for malakoplakia (Figure B). Discussion: The first report of colonic malakoplakia was described by Terner and Lattes in 1965 and usually involves the ascending colon, sigmoid colon and rectum. Clinical manifestations of colonic involvement range from asymptomatic to abdominal pain, fever, diarrhea and rectal bleeding. The lesion is characterized by von-Hansemann cells which are aggregates of histiocytes with eosinophilic cytoplasm and intracytoplasmic Michaelis-Gutmann bodies. Pathogenic mechanisms include a causative organism, altered immune response and phagocyte disfunction. Escherichia coli is the most common isolated pathogen found in 90% of patients with malakoplakia. These chronic bacterial infections are due to suspected abnormal macrophage function resulting in the inability to break down bacteria. The most susceptible include immunosuppressed patients who are post-transplant or have an untreated systemic disease such as chronic hepatitis. Antibiotic therapy, immunotherapy modification and surgical resection are the mainstay of management. While most cases of malakoplakia are diagnosed as incidental findings on screening colonoscopy, there does exist an associate with colorectal adenocarcinoma. Given the potential for significant morbidity if left untreated, malakoplakia diagnosed on incidental screening should prompt a work up for systemic infections, immune compromising diseases and malignancy.Figure 1.: A: Two mm cecum polyp denoted by yellow arrows. Figure B: High-power view of Malakoplakia (60x). Macrophages containing basophilic targetoid structures, known as Michaelis-Gutmann bodies.

Brain and spinal cord lesions in 28 inbred strains of aging mice.

Brain and spinal cord histopathology findings in male and female 20-month-old mice in a large-scale aging study of 28 inbred Jackson Laboratory mouse strains from 7 genetic families are described. Brain sections from selected strains at 12 and 24 months of age or older were also reviewed. Common lesions include axonal dystrophy in the gracile and/or cuneate nucleus in the sensory tract of the dorsal medulla and in the spinal cord in all strains. Hirano-like bodies were seen in 24/28 strains, and mineralization was observed in the thalamus of 9/28 strains. Less common lesions were also seen in the cerebellum, cerebral cortex, and other brain areas. No brain or spinal cord tumors were found. Evidence of an impairment of the ubiquitin-proteasome system (UPS) and/or suspected autophagy was manifested as medullary axonal dystrophy with intra-axonal granular eosinophilic bodies and LC3B immunohistochemistry in most strains. RIIIS/J, the most severely affected strain, showed moderate axonal dystrophy at 12 months, which progressed to severe lesions at 20 months. Comparative pathology in various species is discussed.

Giant Size Pilocytic Astrocytoma in Pediatric Patient : A Case Report

Introduction: Pilocytic astrocytomas are the most common primary tumor in children and adolescents, accounting for approximately 15.6% of all brain tumors and 5.4% of all gliomas. The incidence of tumors substantially decreases with age and diagnosis in patients older than 50 years is less common. According to the Central Brain Tumor Registry of the United States (CBTRUS), its development is more common in the first two decades of life and there are few reports in the age group over 18 years.
 Case Report: An 8-year-old girl was brought by her parents with complaints of loss of consciousness. This happened 2 days before admission to the hospital. The patient was prepared for craniotomy tumor removal. During the operation, the tumor specimen was sent to Anatomical Pathology for histopathological examination. The examination revealed calcified Rosenthal Fibers and eosinophilic granular bodies.
 Discussion : Astrocytic tumors originate from neuroepithelial tissue and are grade I because of their well-defined and slow-growing nature. They are mostly found in infratentorial structures such as the cerebellum and in the midline of brain structures such as the optic nerve, hypothalamus, and brainstem. However, it can be found anywhere on the neuroaxis. Considered relatively rare in adults, there are few publications on the most efficient treatment methods and subsequent patient outcomes.
 Conclusion: Pilocytic astrocytoma (PA) treated with complete or near complete tumor resection tends to have a better prognosis, recent studies recommend aggressive tumor resection without neurologic deficits.

Anaplastic Pleomorphic Xanthoastrocytoma versus Pleomorphic Xanthoastrocytoma

Pleomorphic xanthoastrocytoma (PXA), WHO grade II, is a rare entity accounting for <1% of all astrocytic tumors. It affects children and young adults and is commonly found in the temporal lobe. Anaplastic PXA (APXA) has a similar location and clinical manifestation as that of PXA but has a significantly worse prognosis than the latter. WHO 2016 defined PXA as having >5/10 HPF mitosis and with or without necrosis as APXA (grade III). Herein, we present two such cases with unusual locations and ages: (1) APXA inside lateral ventricle, in a 10-year-old female child and (2) PXA in a 39-year adult male. Histologically, both cases revealed a tumor comprised a highly pleomorphic heterogeneous population of cells, eosinophilic granular bodies, and psammoma bodies, however, necrosis and increased mitosis (>5/10 HPF) were appreciated only in the first case. Immunohistochemistry is supported by strongly positive glial fibrillary acidic protein, vimentin, and synaptophysin. This study analyzed all the characteristics of both these entities with their unusual presentations to prevent future misdiagnoses.

Renal epitheliotropism of feline morbillivirus in two cats.

The association of feline morbillivirus (FeMV) with kidney disease in cats is controversial. Two cats with a history of severe hematuria had eosinophilic inclusion-like bodies in the renal tubular epithelial cells, without any inflammatory cellular reaction. Ultrastructurally, aggregations of electron-dense viral-like particles were found where the inclusion-like bodies were located. Immunohistochemistry (IHC) using antibodies against FeMV matrix protein labeled these inclusion-like bodies, and also labeled the cytoplasm of tracheal and bronchiolar epithelial cells, and lymphocytes and macrophages in spleen and mesenteric lymph node. Using double IHC, FeMV antigen was detected in astroglia and oligodendroglia but not in microglia. Phylogenetic characterization of the fusion and hemagglutinin gene sequences revealed FeMV-1A genotypes in both cats. These findings indicated an active viral infection with FeMV. We propose that FeMV is a renal epitheliotropic virus and also localizes in various other tissues.

Roles of α‑synuclein in gastrointestinal microbiome dysbiosis‑related Parkinson's disease progression (Review).

Parkinson's disease (PD) is the second most common neurodegenerative disease amongst the middle-aged and elderly populations. Several studies have confirmed that the microbiota-gut-brain axis (MGBA) serves a key role in the pathogenesis of PD. Changes to the gastrointestinal microbiome (GM) cause misfolding and abnormal aggregation of α-synuclein (α-syn) in the intestine. Abnormal α-syn is not eliminated via physiological mechanisms and is transported into the central nervous system (CNS) via the vagus nerve. The abnormal levels of α-syn aggregate in the substantia nigra pars compacta, not only leading to the formation of eosinophilic Lewis Bodies in the cytoplasm and mitochondrial dysfunction in dopaminergic (DA) neurons, but also leading to the stimulation of an inflammatory response in the microglia. These pathological changes result in an increase in oxidative stress (OS), which triggers nerve cell apoptosis, a characteristic of PD. This increase in OS further oxidizes and intensifies abnormal aggregation of α-syn, eventually forming a positive feedback loop. The present review discusses the abnormal accumulation of α-syn in the intestine caused by the GM changes and the increased levels of α-syn transport to the CNS via the MGBA, resulting in the loss of DA neurons and an increase in the inflammatory response of microglial cells in the brain of patients with PD. In addition, relevant clinical therapeutic strategies for improving the GM and reducing α-syn accumulation to relieve the symptoms and progression of PD are described.

Efficacy and safety of body-insulated acupuncture needle for electrical stimulation at rabbit scia-tic nerve trunk

To evaluate the efficacy and safety of electrical stimulation at the rabbit sciatic nerve trunk with the body-insulated acupuncture needle whose body is painted with insulating material. Eighteen male New Zealand rabbits were randomized into the body-insulated acupuncture needle (BIAN), the general acupuncture needle (GAN), and the blank control groups，with 6 rabbits in each group. The rats'sciatic nerve trunks in BIAN and GAN groups were stimulated by electroacupuncture with the body-insulated acupuncture needle (only allowing the uncoated needle handle and tip to conduct electricity) and the general acupuncture needle, separately. The current intensity was recorded when regular plantarflexion reflexes (sciatic nerve effector reflexes) were observed in the rabbit's foot. The pathological changes of the sciatic nerve at the acupuncture site were observed by H.E. staining, and the ultrastructural changes of the sciatic nerve trunk were observed by transmission electron microscope. The intensity of the current causing the regular plantar flexion reflection in BIAN group (［0.29±0.07］ mA) was significantly lower than that in the GAN group(［0.86±0.08］ mA, P<0.01). H.E. staining revealed nerve axon degeneration, forming eosinophilic bodies, nerve fiber edema, and focal loss of myelin sheath in the GAN group. While the nerve fiber damage was not obvious, and axons were only degenerated in a few areas in the BIAN group. Transmission electron microscopy observations showed that the nerve myelin sheath structure was separated, the layers were arranged disorderly and bubbled in the GAN group. while the nerve myelin sheath structure of the BIAN group was normal, and it presents a concentric circle-like light and dark lamellar structure, with fewer myelin vacuoles and fissures, only a small part of the mitochondria, microfilaments, and microtubules of the nerve axons were abnormal, and the overall vacuole-like degeneration was significantly reduced, with few of the myelinated fibers were slightly degenerated, and axonal disease was not obvious. Insulated acupuncture needle is more accurate and safer than ordinary acupuncture needle for electrical stimulation of rabbit sciatic nerve trunk, and the required electric current intensity is smaller.

Multiple colon ulcers in a patient with HIV: Do not forget amoebiasis

A 66-year-old man with no past medical history presented with 2 weeks of fever, abdominal pain and watery diarrhoea. He tested positive for human immunodeficiency virus (HIV), and the CD4+ T-cell count was 43.8/mL. Endoscopy revealed multiple circumferential ulcers in the ascending colon (Figure 1), transverse colon and caecum. Biopsies from the colonic ulcers showed numerous amoebic trophozoites (Figure 2, arrows) and eosinophilic intranuclear inclusion bodies (Figure 2, arrowheads). Immunohistochemistry for cytomegalovirus (CMV) (Dako mouse anti-CMV monoclonal antibody clone CCH2 + DDG9) was positive in the eosinophilic intranuclear bodies (Figure 3).

A novel histopathological grading system for ganglioglioma.

Gangliogliomas are central nervous system tumors located in the temporal lobe of young patients, frequently associated with epilepsy. In this paper, we propose a grading system based solely on histopathological criteria. We reevaluated all cases of ganglioglioma, atypical ganglioglioma, and anaplastic ganglioglioma diagnosed between 2011 and 2020 in the Pathology Department of the Emergency Clinical Hospital Bagdasar-Arseni, based on the type of glial mitoses, the number of neuronal and glial mitoses, presence of necrosis, microvascular proliferation, eosinophilic granular bodies, hypercellularity, presence and disposition of inflammatory infiltrate and atypical pleomorphism. Based on the proposed grading system, a score of 0–4 corresponded to a benign ganglioglioma, 5–9 to an atypical ganglioglioma, and 10–18 to an anaplastic ganglioglioma. The survival rates were 90% for benign ganglioglioma, 71.43% for atypical ganglioglioma, and 62.54% for anaplastic ganglioglioma. One case of benign ganglioglioma underwent a malignant transformation into anaplastic ganglioglioma, and recurrences were noticed in 28.57% of atypical ganglioglioma cases and 30.7% of all anaplastic gangliogliomas. The presence of rare glial mitoses and hypercellularity was correlated with mortality in cases of atypical ganglioglioma. We believe this histopathological scoring system could be used as a three-tier system to identify atypical ganglioglioma cases that are bound to have an aggressive course of evolution and require close follow-up. The other option would be to convert it to a two-tier grading system that can separate low-grade gangliogliomas from high-grade ones. The latter category can encompass both atypical and anaplastic ganglioglioma due to the high mortality of both entities.

PATH-05. A CASE OF PILOCYTIC ASTROCYTOMA HARBORING THE FGFR1 GENE MUTATION WITH A PREDOMINANT OLIGODENDROGLIOMA-LIKE COMPONENT

Pilocytic astrocytomas rarely present with oligodendroglioma-like morphological features, which gives rise to a diagnostic challenge. In this report we present a case of pilocytic astrocytoma harboring the FGFR1 mutation, accompanied with a predominant oligodendroglioma-like component, thus initially diagnosed as oligodendroglioma. A 14-year-old female presented with syncope and simple partial seizure involving her right upper limb. Contrast-enhanced MRI revealed an enhancing lesion with substantial cystic portion and perifocal edema in the left parietal lobe. Open surgery was performed and a gross total resection of the tumor was achieved. On initial histopathological diagnosis, tumor cells with monotonous round nuclei and perinuclear halo predominated with branching capillaries, which were strongly suggestive for oligodendroglioma. Immunohistochemically, IDH1 R132H was negative, and Ki-67 index was around 5%. The patient was thus initially diagnosed as oligodendroglioma, WHO grade II, based on the 2007 WHO classification criteria. However, histopathological re-review revealed a minor astrocytic component with Rosenthal fibers and rare eosinophilic granular bodies, thus the diagnosis was changed as pilocytic astrocytoma. FGFR1 K654E mutation was confirmed by Sanger sequencing. Although she postoperatively developed mild sensory disturbance in her right hands, finger agnosia, and left-right disorientation, her symptoms had gradually improved, and she was discharged on day 17 with a Karnofsky performance status (KPS) of 90 and no cognitive decline. Without any adjuvant therapies, she has remained recurrence-free for 85 months. While the diagnosis of pilocytic astrocytoma with predominant oligodendroglioma-like component can be challenging, analysis of IDH1 and FGFR1 mutations can be beneficial in certain cases.

PATH-13. PLEOMORPHIC XANTHOASTROCYTOMA INTEGRATED GENOMIC CHARACTERIZATION - WHAT HAVE WE LEARNED?

Pleomorphic xanthoastrocytoma (PXA) is a rare astrocytoma occurring predominantly in children and young adults. It is characterized histologically by large pleomorphic, spindled and lipidized cells with frequent eosinophilic granular bodies and pericellular reticulin deposition. BRAF p.V600E mutation and CKDN2A/B deletion are the most common genetic alterations. We report the integrated genomic characterization of a cohort of 67 patients (37 F, 30 M; median age 20.3 years (interquartile 13.4–32.9) with histologically defined PXA (52, 78%) or anaplastic PXA (A-PXA) (15, 22%), using genome-wide cytogenetic (ThermoFisher Oncoscan, n=67), methylation profiling (Illumina EPIC array, n=43), and targeted next generation sequencing (n=32). BRAF p.V600E mutation (n=51, 76.1%) and CDKN2A/B deletion (n=63; 94%) were the most frequent alterations. Of 16 BRAF p.V600E negative cases, 7 showed an alternative BRAF activating mutation (n=2), NF1 (n=3) mutation or ATG7-RAF1 fusion (n=2). Targeted TERT analysis found promoter mutations in 3 (of 58) cases, but TERT amplification was absent. Supervised and unsupervised methylation profiling against a comprehensive reference cohort demonstrated consensus grouping with the PXA class in 36 of 43 cases; while the minority grouped with a ganglioglioma class (n=3), with reactive brain or had no resolvable subgroup (n=4). Follow-up was available in 61 patients (91.0%) (median 63 months). Overall survival was significantly different between PXA and A-PXA (5-year:80.4% vs. 55.1%; p=0.001), but not progression-free survival (5-year:61.7% vs. 39.8%; p=0.128). Our data confirm the high frequency of MAP-K abnormalities and CDKN2A/B deletion in PXA. WHO grade remains a strong predictor of patient overall survival.

CS-01 Rapid Recurrence and Anaplastic Transformation of a Pilocytic Astrocytoma in an Elderly Patient

BACKGROUND: Rapid recurrence of a pilocytic astrocytoma with anaplastic transformation is extremely rare. The case of an elderly patient with a cerebellar pilocytic astrocytoma with anaplastic transformation during short-term follow-up is reported. CASE DESCRIPTION: An 83-year-old woman presented initially with dizziness and a gait deviation to the right. Magnetic resonance imaging (MRI) demonstrated a homogeneously enhanced mass in the right cerebellar hemisphere, and the tumor was subtotally removed by right suboccipital craniotomy. Histological examination showed that the tumor cells contained eosinophilic cytoplasm and spindle-shaped processes with Rosenthal fibers and eosinophilic granular bodies, diagnosed as a typical pilocytic astrocytoma (PA). The MIB-1 index was less than 1%. The patient did not receive postoperative adjuvant radiation and chemotherapy. Two months after surgery, MRI showed growth of the residual tumor adjacent to the fourth ventricle, causing obstructive hydrocephalus. She underwent surgery again, and the tumor was totally removed. Histological findings showed mitotic cells and increased cellularity compared with the primary tumor, which was compatible with anaplastic transformation of PA with a MIB-1 index of 50%. Postoperatively, she was observed with best supportive care without postoperative adjuvant therapy. Nine months after the second operation, she died due to tonsillar herniation and obstructive hydrocephalus caused by a recurrent tumor. An autopsy was performed. CONCLUSION: It is extremely rare, as in the present case, that a cerebellar PA in an elderly patient recurs rapidly with anaplastic transformation, despite deferred postoperative adjuvant therapy including radiation and chemotherapy A novel molecular-targeted therapy is needed for anaplastic PA showing aggressive biological behavior.