High prevalence of TP53 mutations is associated with poor survival and an EMT signature in gliosarcoma patients

Gliosarcoma (GS) is a rare variant (2%) of glioblastoma (GBM) that poses clinical genomic challenges because of its poor prognosis and limited genomic information. To gain a comprehensive view of the genomic alterations in GS and to understand the molecular etiology of GS, we applied whole-exome sequencing analyses for 28 GS cases (6 blood-matched fresh-frozen tissues for the discovery set, 22 formalin-fixed paraffin-embedded tissues for the validation set) and copy-number variation microarrays for 5 blood-matched fresh-frozen tissues. TP53 mutations were more prevalent in the GS cases (20/28, 70%) compared to the GBM cases (29/90, 32%), and the GS patients with TP53 mutations showed a significantly shorter survival (multivariate Cox analysis, hazard ratio=23.9, 95% confidence interval, 2.87–199.63, P=0.003). A pathway analysis showed recurrent alterations in MAPK signaling (EGFR, RASGRF2 and TP53), phosphatidylinositol/calcium signaling (CACNA1s, PLCs and ITPRs) and focal adhesion/tight junction (PTEN and PAK3) pathways. Genomic profiling of the matched recurrent GS cases detected the occurrence of TP53 mutations in two recurrent GS cases, which suggests that TP53 mutations play a role in treatment resistance. Functionally, we found that TP53 mutations are associated with the epithelial–mesenchymal transition (EMT) process of sarcomatous components of GS. We provide the first comprehensive genome-wide genetic alternation profiling of GS, which suggests novel prognostic subgroups in GS patients based on their TP53 mutation status and provides new insight in the pathogenesis and targeted treatment of GS.

Diagnostic Significance of Cellular Neuroglial Tissue in Ovarian Immature Teratoma

BACKGROUND: Immature teratoma (IT) is a tumor containing immature neuroectodermal tissue, primarily in the form of neuroepithelial tubules. However, the diagnosis of tumors containing only cellular neuroglial tissue (CNT) without distinct neuroepithelial tubules is often difficult, since the histological characteristics of immature neuroectodermal tissues remain unclear. Here, we examined the significance of CNT and tried to define immature neuroectodermal tissues by comparing the histological features of neuroglial tissues between mature teratoma (MT) and IT. METHODS: The histological features of neuroglial tissue, including the cellularity, border between the neuroglial and adjacent tissues, cellular composition, mitotic index, Ki-67 proliferation rate, presence or absence of tissue necrosis, vascularity, and endothelial hyperplasia, were compared between 91 MT and 35 IT cases. RESULTS: CNTs with a cellularity grade of ≥ 2 were observed in 96% of IT cases and 4% of MT cases (p < .001); however, CNT with a cellularity grade of 3 in MT cases was confined to the histologically distinct granular layer of mature cerebellar tissue. Moreover, CNT in IT exhibited significantly higher rates of Ki-67 proliferation, mitoses, and necrosis than those in MT (p < .001). Furthermore, an infiltrative border of neuroglial tissue and glomeruloid endothelial hyperplasia were significantly more frequent in IT cases than in MT cases (p < .001). CONCLUSIONS: Our results suggest that if CNT with a cellularity grade of ≥ 2 is not a component of cerebellar tissue, such cases should be diagnosed as IT containing immature neuroectodermal tissue, particularly if they exhibit an infiltrative border, mitoses, necrosis, and increased Ki-67 proliferation.

Giant hypothalamic hamartoma associated with an intracranial cyst in a newborn

We report the case of a giant hypothalamic hamartoma with a large intracranial cyst in a neonate. On ultrasonography, the lesion presented as a lobulated, mass-like lesion with similar echogenicity to the adjacent brain parenchyma, located anterior to the underdeveloped and compressed left temporal lobe, and presenting as an intracranial cyst in the left cerebral convexity without definite internal echogenicity or septa. The presence of a hypothalamic hamartoma and intracranial neurenteric cyst were confirmed by surgical biopsy. The association of a giant hypothalamic hamartoma and a neurenteric cyst is rare. Due to the rarity of this association, the large size of the intracranial cyst, and the resulting distortion in the regional anatomy, the diagnosis of the solid mass was not made correctly on prenatal high-resolution ultrasonography.

Upfront Stereotactic Radiosurgery for Pineal Parenchymal Tumors in Adults

OBJECTIVE: Pineal parenchymal tumors (PPTs) in adults are rare, and knowledge regarding their optimal management and treatment outcome is limited. Herein, we present the clinical results of our series of PPTs other than pineoblastomas managed by stereotactic radiosurgery (SRS) at upfront setting. METHODS: Between 1997 and 2014, nine consecutive adult patients with the diagnosis of PPTs, either pineocytoma or pineal parenchymal tumor of intermediate differentiation, were treated with SRS. There were 6 men and 3 women. The median age was 39 years (range, 31-53 years). All of the patients presented with symptoms of hydrocephalus. Endoscopic third ventriculostomy and biopsy was done for initial management. After histologic diagnosis, patients were treated with Gamma Knife with the mean dose of 13.3 Gy (n=3) or fractionated Cyberknife with 32 Gy (n=6). RESULTS: After a mean follow-up of 78.6 months (range, 14-223 months), all patients were alive and all of their tumors were locally controlled except for one instance of cerebrospinal fluid seeding metastasis. On magnetic resonance images, tumor size decreased in all patients, resulting in complete response in 3 patients and partial response in 6. One patient had experienced temporary memory impairment after SRS, which improved spontaneously. CONCLUSION: SRS is effective and safe for PPTs in adults and can be considered as a useful alternative to surgical resection at upfront setting.

Primary Histiocytic Sarcoma of the Central Nervous System / Journal of the Korean Cancer Association, 대한암학회지

Histiocytic sarcoma is a type of lymphoma that rarely involves the central nervous system (CNS). Its rarity can easily lead to a misdiagnosis. We describe a patient with primary CNS histocytic sarcoma involving the cerebral hemisphere and spinal cord, who had been initially misdiagnosed as demyelinating disease. Two biopsies were necessary before a correct diagnosis was made. A histologic examination showed bizarre shaped histiocytes with larger nuclei and nuclear atypia. The cells were positive for CD68, CD163, and S-100 protein. As a resection was not feasible due to multifocality, he was treated with highdose methotrexate, but showed no response. As a result, he was switched to high dose cytarabine; but again, showed no response. The patient died 2 months from the start of chemotherapy and 8 months from the onset of symptoms. Since few patients with this condition have been described and histopathology is difficult to diagnose, suspicion of the disease is essential.

Intramedullary Spinal Cysticercosis: A Case Report and Review of Literature

To report a case of spinal intramedullary cysticercosis in thoracic spine. A 47-year old man living in Korea referred to our hospital with both feet tingling sensation for about a year. Laboratory evaluations, including serologic tests were not helpful. Magnetic resonance imaging revealed a 1.7 cm intramedullary mass at T10-11 level, which believed to be a tumor instead, rather than a cysticercosis preoperatively. Successful operation was done with a histopathological result confirmed it as cysticercosis. Even though the prevalence of intramedullary spinal cysticercosis is extremely rare, and radiologic exams mimic other common tumors like ependymoma or astrocytoma, the disease should be considered as differential diagnosis.

Significant Symptom Relief with Hepatic Artery Embolization in a VIPoma with Liver Metastases / 대한내과학회지

Vasoactive intestinal polypeptide-secreting tumors (VIPomas) cause VIPoma syndrome, which is characterized by watery diarrhea, hypokalemia, and achlorhydria. The treatment options for metastatic VIPomas include somatostatin analogs, cytoreductive surgery, and chemotherapy. We report the case of a 54-year-old male who presented with a peripancreatic mass with multiple hepatic metastases on computed tomography. After resection, the peripancreatic mass was demonstrated pathologically to be a neuroendocrine tumor. Although the patient received systemic chemotherapy and somatostatin analogs for the hepatic metastatic masses, the tumor increased in size. The patient then experienced severe diarrhea, despite treatment with the somatostatin analogs. Elevated serum VIP levels (3,260 pg/mL) and typical symptoms confirmed the diagnosis of VIPoma. We performed hepatic artery embolization (HAE) to reduce the tumor volume and control his symptoms, which led to a very rapid symptomatic response. The patient has remained symptom-free for 18 months with repeated HAE.

Cytological Evaluation and REBA HPV-ID HPV Testing of Newly Developed Liquid-Based Cytology, EASYPREP: Comparison with SurePath

BACKGROUND: The objective of this study was to evaluate a newly-developed EASYPREP liquid-based cytology method in cervicovaginal specimens and compare it with SurePath. METHODS: Cervicovaginal specimens were prospectively collected from 1,000 patients with EASYPREP and SurePath. The specimens were first collected by brushing for SurePath and second for EASYPREP. The specimens of both methods were diagnosed according to the Bethesda System. Additionally, we performed to REBA HPV-ID genotyping and sequencing analysis for human papillomavirus (HPV) on 249 specimens. RESULTS: EASYPREP and SurePath showed even distribution of cells and were equal in cellularity and staining quality. The diagnostic agreement between the two methods was 96.5%. Based on the standard of SurePath, the sensitivity, specificity, positive predictive value, and negative predictive value of EASYPREP were 90.7%, 99.2%, 94.8%, and 98.5%, respectively. The positivity of REBA HPV-ID was 49.4% and 95.1% in normal and abnormal cytological samples, respectively. The result of REBA HPV-ID had high concordance with sequencing analysis. CONCLUSIONS: EASYPREP provided comparable results to SurePath in the diagnosis and staining quality of cytology examinations and in HPV testing with REBA HPV-ID. EASYPREP could be another LBC method choice for the cervicovaginal specimens. Additionally, REBA HPV-ID may be a useful method for HPV genotyping.

Intracranial Fibromatosis: A Case Report

Fibromatosis can occur at various sites, but intracranial fibromatosis is exceptionally rare. Here, we report a case of intracranial fibromatosis arising in the suprasellar area of a 52-year-old woman who had undergone a surgery at that site. A computed tomography scan revealed a heavily calcified, highly enhancing, poorly demarcated mass in the left sellar area that extended into the left suprasellar, parasellar areas, and orbital apex and completely encased the left distal inferior cerebral artery. Histologic and immunohistochemical features were compatible with those of fibromatosis, although the cellularity was focally higher than usual. The etiology of extra-abdominal fibromatosis is unknown, but physical injuries such as trauma and irradiation have been reported to be associated with its occurrence. Although fibromatosis is rare in the intracranial area, it should be considered as a differential diagnosis when an intracranial mass occurs at a previously injured site.

Intracranial Fibromatosis: A Case Report

Fibromatosis can occur at various sites, but intracranial fibromatosis is exceptionally rare. Here, we report a case of intracranial fibromatosis arising in the suprasellar area of a 52-year-old woman who had undergone a surgery at that site. A computed tomography scan revealed a heavily calcified, highly enhancing, poorly demarcated mass in the left sellar area that extended into the left suprasellar, parasellar areas, and orbital apex and completely encased the left distal inferior cerebral artery. Histologic and immunohistochemical features were compatible with those of fibromatosis, although the cellularity was focally higher than usual. The etiology of extra-abdominal fibromatosis is unknown, but physical injuries such as trauma and irradiation have been reported to be associated with its occurrence. Although fibromatosis is rare in the intracranial area, it should be considered as a differential diagnosis when an intracranial mass occurs at a previously injured site.

Neoplastic Stromal Cells of Intracranial Hemangioblastomas Disclose Pericyte-derived Mesenchymal Stromal Cells-like Phenotype

BACKGROUND: Stromal cells (SCs) of hemangioblastomas (HBs) have been regarded as true neoplastic components, but their ontogeny remains unclear. Convincing evidence suggests that embryonic mesenchymal cells may be the cells of origin of HBs. The aim of the present study was to investigate the immunophenotypic characteristics of neoplastic SCs using a set of markers against endothelial cells (ECs), vascular smooth muscle cells (vSMCs), mesenchymal stromal cells (MSCs), and pericytes. METHODS: Intracranial HBs (n=46), angiolipoma (n=9), and pyogenic granuloma (n=11) were retrieved and the immunophenotypic profile of SCs was determined by immune stainings. RESULTS: The MIB-1 labeling index was significantly higher in SCs compared to that of ECs and vSMCs, regardless of the type of lesion. The neoplastic SCs of HBs consistently expressed both MSC and pericyte markers, but did not express markers of ECs and vSMCs. Double immunofluorescent staining demonstrated that the neoplastic SCs of HBs expressing MSC or pericyte markers directly abutted onto the ECs of capillaries/venules. CONCLUSIONS: The results suggest that the neoplastic SCs of HBs share the immunophenotypic profile and distribution with those of pericyte-derived MSCs. Thus, HBs might originate from a distinctive population of pericyte-derived MSCs in the central nervous system.

Epidural Cavernous Hemangioma with Foraminal Extension

The increased use of magnetic resonance imaging (MRI) has increased the frequency of diagnosis of cavernous hemangioma, but its presentation of an epidural lesion with foraminal extension without intramedullary involvement is very rare. We describe a 31-year-old woman admitted to our department with pain in the left side of her neck and shoulder. Gadolinium enhanced cervical MRI revealed a brightly enhanced, extradural mass (112 cm sized) with widened neural foramen; after surgical excision, it was histologically confirmed as a cavernous hemangioma. Postoperatively, the patient has no neurological deficit or specific complication. Although this lesion mimicked an epidural- neurogenic tumor, its enhancement pattern indicated a cavernous hemangioma. Accurate preoperative diagnosis is necessary for treatment planning. Cavernous hemangioma must be included in the differential diagnosis of a brightly enhanced, extradural tumors.

Intradural Involvement of Multicentric Myxoid Liposarcoma

Liposarcomas are malignant tumors of the soft tissue, with myxoid liposarcoma being the second most common subtype, tending to occur in the limbs, particularly in the thighs. Myxoid liposarcomas have an intermediate prognosis between well-differentiated and pleomorphic tumors. Spinal metastasis is usual but intradural involvement is extremely rare. We present an unusual case of a multicentric myxoid liposarcoma with intradural involvement. A 41-year-old woman complained of tingling sensation on her left arm. Radiological evaluation revealed multiple masses in her cervical spine, abdominal wall, liver, heart and right thigh, all of which were resected. She was histologically diagnosed with small round cell myxoid sarcoma and underwent adjuvant chemotherapy. However, magnetic resonance imaging analysis after 1 year revealed a large metastatic mass with bony invasion at the C6-T1 level. This mass consisted of extradural and intradural components causing severe compression of the spinal cord. She underwent resection via a posterior facetectomy of C6-7 and an anterior C7 corpectomy. However, the patient died of multiple metastases 18 months after the first diagnosis.

Two Cases of Pheochromocytoma Presented with Hypertension and Weight Loss / 대한소아내분비학회지

Pheochromocytoma is a rare disease in children, arising from chromaffin cells of adrenal medullary or extra-adrenal paraganglionic tissues. Typical clinical features include hypertension, diaphoresis, headache, and weight loss. It should therefore be considered that patients associated with hypertension might have pheochromocytoma. The diagnostic approach is based on typical clinical manifestations and biochemical test. Pheochromocytoma is completely curable by surgical resection. Early diagnosis and total excision are the most important aspects of accurate treatment of pheochromocytoma in children. We report two patients with pheochromocytoma presented with hypertension and weight loss both of which were improved after tumor resection.

Lyn Expression in Osteoblastic Osteosarcoma Tissues and Its Correlation with Clinicopathologic Factors

BACKGROUND: The Src family kinases (SFKs) are involved in multiple aspects of tumorigenesis, such as, proliferation, migration, and angiogenesis, and are involved in the generation and progression of many types of tumors. Furthermore, dasatinib, a general SFKs inhibitor was recently approved for use in chronic myeloid leukemia. This study was performed to evaluate the expression of Lyn, a member of the SFKs, in osteosarcoma tissues. METHODS: One hundred and sixteen patients with osteoblastic osteosarcoma were selected for Lyn expression analysis. The correlation between Lyn expression in tumor sections and patients' clinicopathologic characteristics and the prognostic significance of Lyn expression were evaluated. RESULTS: Lyn was found to be expressed in 52 of the 116 patients (44.8%), and Lyn positive tumor was found to be significantly associated with a lytic tumor pattern on plain radiographs (p = 0.04). Furthermore, those positive for Lyn showed longer metastasis free survival (5-year metastasis free survival, 65.2% for Lyn positive and 46.8% for Lyn negative; p = 0.06), though this was only marginally significant. CONCLUSIONS: Lyn was found to be overexpressed in osteosarcoma tissues, and this overexpression was found to be correlated with osteolysis.

Tuberculous Meningoencephalitis Complicated by Subarachnoid Hemorrhage

Tuberculous meningoencephalitis (TBM) is often complicated by various neurologic manifestations including ischemic infarctions. However, intracerebral hemorrhage in TBM has rarely been described. We report a 30-year-old woman with TBM who developed subarachnoid, intraventricular, and intracerebral hemorrhage, and finally died in spite of treatment with antituberculous and steroid therapy. Autopsy findings revealed multifocal thrombotic occlusion of the arteries and thinning of the vessel walls secondary to tuberculous vasculitis.

Clinicopathologic Characteristics of Endometrial Adenocarcinomas in Young Women

BACKGROUND: Despite an increased incidence of endometrial carcinomas in young Korean women, clinicopathologic characteristics and treatment outcomes have not been analyzed. METHODS: We investigated clinicopathologic characteristics of endometrial carcinoma in 48 women who were under the age of 40 in order to determine treatment guideline. RESULTS: According To The Criteria Of The Korean Society For Obesity, 70.8% Of Study Patients Were Overweight Or Obese, With An Average Body Mass Index (Bmi) Of 26.0 kg/m2. Twelve Patients Received Progesterone Treatment Only, And 6 Of Them Later Had Successful Pregnancies. The Histologic Subtype Was Endometrioid Adenocarcinoma In All Patients. Figo Stages Were 1A(41.7%), 1B(47.1%), II (2.8%), IIB2.8%), IIIA(2.8%), And IIIC (2.8%). Figo Grades Were Grade 1 (79%) Or 2 (21%). The Average Depth Of Invasion, Excluding Stage 1a, Was 4.6 Mm In The Hysterectomy Specimens. Two Patients Were Given Post-operative Radiation Treatment And 4 Were Treated With Chemotherapy. All But One Case Had An Uneventful Postoperative Course During Follow-up. CONCLUSIONS: A majority of endometrial carcinomas in young Korean women were associated with an early FIGO stage, favorable histologic subtype and grades, and a good prognosis. Progesterone treatment with close observation was a successful treatment option in a selected group of young patients.

Second Opinion Diagnoses of Cytologic Specimens on Consultation : Asan Medical Center Experience / 대한세포병리학회지

BACKGROUND: Second opinion diagnosis of outside pathology slides is a common practice for efficient and proper patient management. We analyzed cytology slides from outside hospitals submitted for a second opinion diagnosis to determine whether the second opinion diagnosis had any influence on patient care. METHODS: We reviewed 1,153 outside cytology slides referred to Asan Medical Center for second opinions from January, 2007, to December, 2007. All cases were categorized into three groups; no diagnostic discrepancy, minor diagnostic discrepancies (no impact on the management), and major diagnostic discrepancies (significant impact on the management and subsequent follow-up). RESULTS: The thyroid was the most common organ system (933 cases, 80.9%). Forty cases (3.6%) belonged to the major diagnostic discrepancy group and 149 cases (12.8%) to the minor discrepancy group. For validation of second opinion diagnoses in major discrepancy cases, subsequent biopsy or surgical resection specimens and clinical information were reviewed, which were available in 29 cases. The second opinion diagnoses resulted in alteration of clinical management in 21 of 29 cases. CONCLUSION: For all referred patients, second opinion diagnosis is important and mandatory for appropriate patient care.

Quality Control Program and Its Results of Korean Society for Cytopathologists / 대한세포병리학회지

In Korea, the quality control(QC) program forcytopathology was introduced in 1995. The program consists of a checklist for the cytolopathology departments, analysis data on all the participating institutions' QC data, including the annual data on cytologic examinations, the distribution of the gynecological cytologic diagnoses, as based on The Bethesda System 2001, and the data on cytologic-histolgical correlation of the gynecological field, and an evaluation for diagnostic accuracy. The diagnostic accuracy program has been performed 3 times per year with using gynecological, body fluid and fine needle aspiration cytologic slides. We report here on the institutional QC data and the evaluation for diagnostic accuracy since 2004, and also on the new strategy for quality control and assurance in the cytologic field. The diagnostic accuracy results of both the participating institutions and the QC committee were as follows; Category 0 and A: about 94%, Category B: 4~5%, Category C: less than 2%. As a whole, the cytologic daignostic accuracy is relatively satisfactory. In 2008, on site evaluation for pathology and cytology laboratories, as based on the "Quality Assurance Program for Pathology Services" is now going on, and a new method using virtual slides or image files for determining the diagnostic accuracy will be performed in November 2008.

Diagnostic accuracy of conventional Pap test, liquid-based cytology and human papillomavirus DNA testing in cervical cancer screening in Korea: a meta-analysis / 한국역학회지

No abstract available.