Pitfalls in diagnostic myopathology of sporadic inclusion body myositis (SIBM).

Sporadic inclusion body myositis (SIBM) is the most common idiopathic inflammatory myopathy in Caucasians over the age of 50 years. The prevalence of SIBM in the Asian population was initially thought to be very low, although the recent study showed that the prevalence of SIBM in Japan is in fact similar to the prevalence in Australia and the USA. SIBM is a refractory myositis with associated myodegenerative features mimicking the neuropathology of Alzheimer’s disease. The diagnosis of definite SIBM requires the typical clinical features and the presence of an autoaggressive inflammatory reaction, rimmed vacuoles, and congophilic deposits or tubulofilamentous inclusions. About one-fourth of patients with the typical clinical features of SIBM did not fulfill the pathological criteria of the definite SIBM. These canonical biopsy features may be absent in the early stage of the disease. Here we review the typical findings and the diagnostic pitfalls of the muscle biopsy in SIBM.

Histopathological subtypes of medulloblastoma according to WHO classification (2007): An 8-year retrospective study.

Objective: To provide histopathological subtypes of medulloblastomas (according to 2007 WHO Classification of tumors of the central nervous system) that were previously diagnosed during 1998 to 2005 in Siriraj Hospital, and to characterize the immunophenotypic patterns of medulloblastomas in correlation with these subtypes. Methods: All diagnosed medulloblastomas collected during 1998 to 2005 in the Department of Pathology, Siriraj Hospital were reviewed and classified according to WHO classification (2007) by H&E staining. Furthermore, we performed immunohistochemical studies, including synaptophysin, glial fibrillary acidic protein (GFAP), neurofilament, and Ki-67 to characterize the immunophenotypical patterns of medulloblastoma correlated with morphological variants. Statistic analyses were Tukey HSD, Mann-Whitney test, and Fisher’s exact test. Results: Of 41 medulloblastomas, 32 cases were classic type (78.05%), 6 cases were large cell/anaplastic variant (14.63%), and 3 cases were desmoplastic variant (7.32%). This study showed significantly increased Ki-67 indices in the large cell/anaplastic variant compared to either classic medulloblastoma or desmoplastic/nodular variant (p <0.05). There is no statistical difference in immunophenotypes of synaptophysin, GFAP, or neurofilament between each subtype. Conclusion: According to 2007 WHO classification of tumor of the central nervous system 2007, in our study, the majority was medulloblastoma classic type, followed by large cell/anaplastic and desmoplastic/nodular variants, respectively. Statistical significance of Ki-67 indices suggests its applicable adjuvant diagnostic tool to distinguish the large cell/anaplastic variant from others.

Predictive value of MRI and CT findings in childhood medulloblastoma studied in Thai patients.

Objective: To evaluate the prognostic value of CT and MRI findings in patients with medulloblastoma. Methods: From 1998 to 2007, the MRI and CT of fourteen patients with medulloblastoma were retrospectively reviewed. The findings of cyst or necrotic portion, composition of calcification, hemorrhage and residual tumor after surgical removal were evaluated. Histopathologic findings were classified as large cell and non-large cell type. Outcomes of the disease were indicated by evidence of leptomeningeal seeding, a recurrence event and survival time after diagnosis. Results: Only the large cell type of medulloblastoma was statistically significant in decreasing survival time. No other MRI or CT findings were statistically significant to predict outcomes of the disease. Conclusion: The histologic type of medulloblastoma is a predictive indicator of the outcome of treatment regardless of imaging findings. However, the limitation of this study due to small sample size was considered.

Diagnostic accuracy of perfusion CT in differentiating brain abscess from necrotic tumor.

OBJECTIVE: To evaluate the diagnostic accuracy of perfusion computed tomography (CTP) in differentiating between brain abscess and necrotic tumor. MATERIAL AND METHOD: Prospective study was performed in patients suspected of a space taking lesion in the brain. CTP was done at the suspected levels and post-processing measurement of cerebral blood volume (CBV), cerebral blood flow (CBF), mean transit time (MTT), and permeability surface index (PS) were evaluated at ring enhanced area, central non-enhanced area, edema and contralateral normal brain. RESULTS: Seventeen patients with 21 lesions were studied. Of the 21 lesions, 12 were abscess and nine were tumors. By comparing means, only MTT at the ring enhanced area showed statistically significant difference between brain abscess and tumor (p = 0.009, 95% CI = 1.403 to 4.900). When ratio of CBV, CBF and MTT of the ring enhanced area and contralateral normal brain were analyzed (CBVr, CBFr, MTTr respectively), there were significant differences of CBVr and CBFr between the two groups (p = 0.003, 95% CI = -4.266 to -1.051 and p = 0.006, 95% CI = -9.934 to -1.969 respectively). With the threshold of CBVr more than or equal to 1.5 and CBFr more than or equal to 1, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for diagnosis of tumor were 100%, 75%, 75%, 100%, and 85.7% respectively. CONCLUSION: The CTP was shown to be useful in differentiating brain abscess from tumor. With CBVr less than 1.5, tumor can be excluded.

Myofibrillar myopathy with limb-girdle phenotype in a Thai patient.

Myofibrillar myopathy (MFM) encompasses a genetically and clinically heterogeneous group of inherited or sporadic skeletal muscle disorders characterized pathologically by the presence of myofibrillar dissolution associated with accumulation of myofibrillar degradation products and ectopic expression of multiple proteins especially Z-disk related proteins. Patients with MFM initially present with muscle weakness and commonly developed cardiomypathy in the advanced stage. To date, mutations of genes encoding Z-disk proteins or proteins maintaining myofibrillar integrity including ZASP, MYOT, DES, FLNC and CRYAB underlie MFM. The authors herein report a 29-year-old Thai woman with a clinical diagnosis of autosomal dominant limb-girdle muscular dystrophy (LGMD1) who has one affected grandmother. The patient was subsequently found to have MFM based on her myopathological findings. Analyses of all MFM-genes known to date revealed no mutations. The current case emphasizes the importance of muscle biopsy in LGMD1 patients and a wide range of phenotypic variations among patients with MFM. The causative genes underlying the majority of MFM remain uncovered. Close monitoring of the cardiac function is crucial to prevent mortality among these patients.

Floppy infant caused by MTM1 mutation: a first genetically-confirmed X-linked myotubular myopathy patient in Thailand.

Floppy infant syndrome (FIS) refers to a condition wherein an infant manifests generalized hypotonia since birth or in early life. It is heterogeneous and can be caused by various central nervous system disorders, neuromuscular diseases and genetic disorders. X-linked myotubular myopathy (XMTM) is a progressive congenital myopathy morphologically characterized by the presence of centrally placed nuclei in numerous muscle fibers without any other particular pathological abnormalities. Patients are frequently born with floppiness and respiratory distress. The vast majority of patients carry a truncating or missense mutation in MTM1. The authors report here a full term male baby with clinicopathological features of XMTM. The diagnosis is validated by the finding of a c. 141-144delAGAA mutation ofMTM1. To the best of the authors' knowledge, the present case is the first genetically confirmed XMTM in Thailand. A brief review of various neuromuscular disorders causing floppy infant syndrome is also included.

Dysembryoplastic neuroepithelial tumor : A case report.

We report on a classic case of dysembryoplastic neuroepithelial tumor (DNT) located in the right temporal lobe of a 12-years-old Thai boy presenting with visual, auditory and gustatory hallucinations for 4 years. DNT is an uncommon low-grade neuronal and mixed neuronal-glial tumor which has a characteristic clinical presentation, as well as characteristic radiological and histopathological finding. DNT has excellent prognosis and surgery is mainly curative treatment. Hence, it is important to recognize this entity in order to avoid unwarranted radio-or chemotherapy.

Pseudotrisomy 13 syndrome : A case report.

We report on a male baby with microcephaly, holoprosencephaly of alobar type with sigle ventricle, cyclopia, proboscis, poorly developed testes, and clenched hands without polydactyly, suggestive of trisomy 13 syndrome. However, the cytogenetic study disclosed 46,XY. The case presented here very well represents pseudotrisomy 13 syndrome and signifies the value of cytogenetic study and genetic counseling.

Myopathology, a 14-year Siriraj experience: What have we learned.

Neuromuscular laboratory, Department of Pathology Siriraj Hospital was established in 1989. Within fourteen years, 315 specimens from 304 patients were received. The patients’ age ranged from 22-week gestation to 76 years old. The ratio of males to female was 1.11:1. Muscular dystrophies comprised 26.63%, non-specific changes 25.66%, primary myopathies, including unclassified myopathy 13.82%, neurogenic muscle diseases 12.82% dysimmune and infectious myopathies 8.89%, mitochondrial myopathy 4.94% and others 7.24%. Summaries of our patients were described.

Reversal of marrow fibrosis in agnogenic myeloid metaplasia by allogeneic peripheral blood stem cell transplantation.

Agnogenic myeloid metaplasia (AMM) is a clonal hematopoietic stem cell disorder characterized by bone marrow fibrosis, extramedullary hemopoiesis, splenomegaly and a leukoerythroblastic blood picture. Current standard therapies using hydroxyurea, interferon, androgens or corticosteroids have not shown to prolong survival of patients with AMM. In this study, we performed a curative approach using an HLA-matched sibling as a donor for allogeneic peripheral blood stem cell transplantation (PBSCT) for a 45-year-old woman with AMM. Busulfan and cyclophosphamide were given as a conditioning regimen from day -7 to day -2 with cyclosporinA and methotrexate as post-transplant immunosuppressive therapy. Donor PBSCs were mobilized by G-CSF at 16 microg/kg/day for five days and transplantation was performed on March 2-3, 2000. The patient rapidly engrafted within 2 weeks after PBSC infusion without evidence of graft versus host disease. Her blood counts and bone marrow 2 years after transplantation were normal with full donor pattern by molecular analysis. In conclusion, marrow fibrosis can be reverted to normal by allogeneic PBSCT. Allogeneic PBSCT should thus be offered to AMM patients if an HLA-matched sibling is available. This report represents the first SCT for AMM in Thailand.

Childhood onset myasthenia gravis.

The authors share experiences in taking care of 27 cases of childhood onset myasthenia gravis (MGS). In all cases, the diagnosis was confirmed by a combination of clinical examination and Neostigmine test. The majority (92%) had localized ocular myasthenia with median onset of symptoms at 33 months of age. About 24 per cent of them progressed to generalized MGS. A few (8%) presented with respiratory failure that required ventilatory support with onset of symptoms at about 22 months. Thymectomy was performed in 10 cases. Complete and partial remissions were achieved in about 70 per cent and 26 per cent of cases respectively with the combination of an immunosuppressant (azathioprine) and a Cholinesterase inhibitor (pyridostigmine). None experienced a myasthenic crisis with proper management and good follow-up using the above combinations.

Radio-pathological conference, Siriraj Hospital wegener's granulomatosis.

A case report of male with history of headache, right eye swelling and blood-tinged nasal discharge was shown with typical findings of CT chest and MRI brain of the wegener's granulomatosis. The pathological finding was also shown and correlated.

Radiopathological conference of Siriraj Hospital pleomorphic Xanthoastrocytomas: A rare brain tumor.

A case report of female with long-standing history of seizure was shown with typical findings of CT and MRI brain of left temporal lobe pleomorphic xanthoastrocytomas. The pathological finding was also shown and correlated.

Expression of insulin-like growth factor I and II in various regionally important solid tumors.

Insulin-like growth factor I (IGF-I) may thwart a T cell response to several cancers, since suppression of IGF-I expression using an episome transcribing an antisense RNA into rat glioma and murine teratocarcinoma, which are known to actively express IGF-I, resulted in tumor regression and CD8+ T cell infiltration.1,2,3,4 This finding led to the gene therapy protocol for human glioblastoma multiforme, a known IGF-I over-expressing tumor, using the same strategy in 1993. The hypothesis that cancers which over-express IGF-I can be cured by this episome has led us to search for other cancers which actively produce IGF-I. Many cancers were reported to express IGF-I4, but most of the geographically important tumors in Thailand had not been studied for the expression of IGF-I. Our immediate goal was to survey the leading human cancers in the Tumor Registry of Siriraj Hospital (i.e., non-small cell lung cancer, cholangiocarcinoma, hepatocellular carcinoma, papillary thyroid carcinoma, nasopharyngeal carcinoma) including all stages of astrocytomas for the expression of IGF-I and IGF-II (a homologue of IGF-I). Tumor tissue collected from paraffin blocks deposited at the Department of Pathology, Siriraj Hospital was screened for the presence of the predominant form of IGF's (IGF-I or -II). Tumor tissues that express any specific form of IGF's more than adjacent wild-type cells are potential candidates for an antisense gene therapy against the expression of that specific form of IGF. Paraffin sections containing these cancer cells and adjacent wild-type cells were examined by immunohistochemical technique using mouse IgG-1 antihuman IGF-I, or antihuman IGF-II as primary antibodies. Normal liver tissue, known as the largest producer of both forms of IGF's, was used as a positive control. The staining pattern of both IGF-I and IGF-II in the liver was highest in the cytoplasm of normal hepatocytes. The majority of the tumors except for papillary thyroid carcinoma and nasopharyngeal carcinoma strongly expressed IGF-I. Only a few samples of the tissues studied expressed a low level of IGF-II, if any. This raises a further working proposal that the blockade of IGF-I synthesis in these tumors may help to delay the tumor progression so that an effective immune response can be established and destroy the tumor.

Mitochondrial genetics of mitochondrial diseases in Thailand.

Mitochondrial diseases are a heterogenous group of disorders with various biochemical defects in the oxidative phosphorylation system. They are included in the differential diagnosis of many cases of multisystem disease even though the neuromuscular and central nervous system are mainly involved. The complexity of the disease can make it difficult for the clinician to diagnose. The number of the patients suffered from Mitochondrial disease is expected to be increasingly found each year. We present here the mitochondrial diseases with their underlying molecular genetics in the mitochondrial DNA found in Thai patients.

Desmoplastic cerebral astrocytoma of infancy: A first case report in Thailand.

We report a new and rare entity of childhood brain tumor, desmoplastic cerebral astrocytoma of infancy. This neoplasm arises in the superficial cerebral cortex of infant under two-years of age. The tumor is voluminous size, partially cystic. It composes of astrocytes with massive desmoplasis, mimicking mesenchymal tumor. Despite their large size, the prognosis following successful surgical resection is quite favorable. To the best of our knowledge, this is the first case report in Thailand.