Detection of global hypermethylation in well-differentiated thyroid neoplasms by immunohistochemical (5-methylcytidine) analysis.

PURPOSE: While global hypomethylation of DNA has been found in several malignancies, studies on thyroid tumours have shown controversial results using different techniques. To help resolve this issue, we assessed methylation status using two different techniques in papillary thyroid carcinomas (PTC) and follicular adenomas (FA) and carcinomas (FTC), comparing adjacent non-neoplastic thyroid tissue. METHODS: A series of 15 FA, 18 FTC and 17 PTC were assessed by: (1) measurement of methylation levels of long interspersed nuclear elements (LINE-1) using a combined bisulfite restriction analysis polymerase chain reaction protocol and (2) immunostaining with an anti-5-methylcytidine antibody that detects methylated DNA regardless of the DNA sequence. Immunostaining was scored by image analysis. RESULTS: Methylation levels of LINE-1 in FA, FTC and PTC were not significantly different from adjacent normal tissue. There was no significant difference in methylation levels of LINE-1 between FA, FTC and PTC (p = 0.44). By immunohistochemical staining for methylation, the 5-methylcytidine score was significantly higher in tumours than in normal tissue counterparts, for FA (p < 0.001), FTC (p = 0.04) and PTC (p = 0.02). PTC showed the highest 5-methylcytidine expression amongst all tumours which was significantly different from FTC (p = 0.015), but not FA (p = 0.09). There was no correlation in methylation level between LINE-1 and 5-methylcytidine scores for each group and overall. CONCLUSIONS: Well-differentiated thyroid neoplasms (FA, FTC and PTC) were not found by two independent methods to undergo global hypomethylation as part of an oncogenic sequence from normal tissue to carcinoma. Instead, hypermethylation was detected in all types of tumours, implying that this epigenetic event may contribute to oncogenic development of thyroid neoplasms (both benign and malignant).

TSH-Secreting Pituitary Macroadenoma in a Girl with Lingual Thyroid.

Patients with long-standing hypothyroid are, in some cases, reported to develop pituitary gland hyperplasia due to loss of feedback inhibition of thyroxine in hypothalamus-the condition of which typically regresses after thyroxine replacement. Herein, a 15-year-old girl-with long-standing untreated lingual hypothyroid-presents with a pathologically proven TSH pituitary macroadenoma and bilateral large ovarian cysts. Although MR imaging may differentiate between hyperplasia and macroadenoma of the pituitary gland, pathological examination is still a cornerstone to correct diagnosis.

Fatal Balamuthia amebic encephalitis in a healthy child: a case report with review of survival cases.

Balamuthia mandrillaris is one of the 4 amebas in fresh water and soil that cause diseases in humans. Granulomatous amebic encephalitis (GAE), caused by B. mandrillaris, is a rare but life-threatening condition. A 4-year-old, previously healthy, Thai girl presented with progressive headache and ataxia for over a month. Neuroimaging studies showed an infiltrative mass at the right cerebellar hemisphere mimicking a malignant cerebellar tumor. The pathological finding after total mass removal revealed severe necrotizing inflammation, with presence of scattered amebic trophozoites. Cerebrospinal fluid (CSF) obtained from lumbar puncture showed evidence of non-specific inflammation without identifiable organisms. A combination of pentamidine, sulfasalazine, fluconazole, and clarithromycin had been initiated promptly before PCR confirmed the diagnosis of Balamuthia amebic encephalitis (BAE). The patient showed initial improvement after the surgery and combined medical treatment, but gradually deteriorated and died of multiple organ failure within 46 days upon admission despite early diagnosis and treatment. In addition to the case, 10 survivors of BAE reported in the PubMed database were briefly reviewed in an attempt to identify the possible factors leading to survival of the patients diagnosed with this rare disease.

PCR detection of Mycobacterium tuberculosis in necrotising non-granulomatous lymphadenitis using formalin-fixed paraffin-embedded tissue: a study in Thai patients.

BACKGROUND: Necrotising non-granulomatous lymphadenitis can be observed in several conditions, most notably infection (including tuberculosis, yersiniosis and nocardiasis), Kikuchi-Fujimoto disease and systemic lupus erythematosus. AIMS: To evaluate the role of PCR in the detection of Mycobacterium tuberculosis in necrotising non-granulomatous lymphadenitis in Thai patients using formalin-fixed paraffin-embedded tissue. METHODS: 35 patient samples showing necrotising non-granulomatous lymphadenitis were subjected to PCR for detection of the IS6110 sequence of M tuberculosis. For comparison, sections were visually assessed for acid-fast bacilli using the Ziehl-Neelsen stain. RESULTS: Among 35 cases of necrotising non-granulomatous lymphadenitis, a conclusive diagnosis could be reached in 23 cases: 15 cases of Kikuchi-Fujimoto disease, 6 of tuberculosis and 2 of systemic lupus erythematosus. Of the 6 cases of tuberculous lymphadenitis, 4 (66.6%) were detected by PCR in formalin-fixed paraffin-embedded tissue samples. PCR was positive in 6/12 of the remaining cases (50%) in which a definitive diagnosis could not be reached by other methods. CONCLUSION: Using PCR, a significant percentage (28%) of cases of necrotising non-granulomatous lymphadenitis in this study could be attributed to M tuberculosis. PCR for identification of the organism can be extremely helpful in confirming a diagnosis of tuberculosis when Ziehl-Neelsen staining is negative.

Epstein-Barr virus-associated smooth muscle tumor presenting as a vulvar mass in an acquired immunodeficiency syndrome patient: a case report.

Smooth muscle tumors in immunocompromised patients have a strong association with Epstein-Barr virus (EBV) infection. EBV-associated smooth muscle tumors (EBV-SMT) are considered as a distinct group of smooth muscle tumors with different clinicopathologic features from conventional smooth muscle tumors. A 31-year-old female patient presented with a 2-cm mass at the left labium majus, the clinical diagnosis of which was a Bartholin lesion. She had acquired immunodeficiency syndrome diagnosed 29 months before. Excisional biopsy revealed a cellular tumor composed of round- to spindle-shaped cells with mild to moderate nuclear atypia. The tumor cells were immunoreactive for smooth muscle actin and muscle actin (HHF-35). Evidence of EBV infection was confirmed by in situ hybridization for EBV-encoded small RNA-1. To our knowledge, this is the first case of EBV-SMT presenting as a vulvar mass. EBV-SMT should be included in the differential diagnoses of mesenchymal tumor in patients with immunosuppression and in the differential diagnoses of smooth muscle tumor in uncommon sites, including the vulva.

Primary intracranial peripheral primitive neuroectodermal tumor/Ewing's sarcoma presenting with acute intracerebral hemorrhage.

OBJECTIVE: To report two cases of intracerebral hemorrhage due to primary intracranial peripheral primitive neuroectodermal tumor (pPNET)/Ewing's sarcoma (ES) and review of related literatures. MATERIAL: Two cases of 17-year-old patients presented with acute increased intracranial pressure one of which also had left hemiparesis. METHOD: On neuroimaging studies, the first patient had an intraparenchymal hematoma with a size of 4 cm at the right fronto-parietal junction adjacent to tumor infiltrating the superior sagittal sinus. The second patient had a large left temporal tumor with intraventricular hemorrhage. Both patients underwent craniotomy with complete removal of tumor and hematoma. RESULTS: Pathological examination in both cases revealed numerous small round tumor cells with stippled chromatin pattern and scanty cytoplasm. Tumor cells strongly expressed CD99. Vimentin immunoreactivity was observed. The final diagnosis of pPNET/ES was rendered. There was no evidence of extracranial disease in both cases. Both patients were doing well without evidence of recurrent disease at 12 and 24-month follow-up respectively. CONCLUSIONS: Peripheral primitive neuroectodermal tumor (pPNET)/Ewing's sarcoma (ES) is a malignant small round cell tumor, commonly arising in soft tissue of the trunk and lower extremity. Those occurring in the intracranium are rare, and most patients present with progressively increased intracranial pressure and/or cranial nerve deficit. The occurrence of intracerebral hemorrhage due to primary intracranial pPNET/ES is exceedingly rare. The role of adjuvant therapy in this condition is yet to be investigated.

Concurrence of multiple sclerosis and intracranial glioma. Report of a case and review of the literature.

We report a 39-year-old female patient known to have multiple sclerosis (MS), who later developed cerebral glioblastoma. The tumor was documented on the brain-magnetic resonance imaging (MRI) during the work-up for an apparent relapsing MS, and was subsequently confirmed pathologically by stereotactic biopsy and the postmortem brain examination. Our case, as well as others, re-emphasizes the need to evaluate the symptoms and brain MRI carefully, even in well-documented MS subjects. The concurrence of MS and intracranial glioma is uncommon. The possible relationship between the 2 diseases was discussed, and related literature reviewed.

Salivary gland choristoma of the middle ear: case treated with KTP laser.

Salivary gland choristoma of the middle ear is rare. It consists of non-malignant, non-growing, normal salivary gland tissue in the middle ear. It is a developmental abnormality that occurs around the proximal part of the second branchial arch before the fourth month of intrauterine life. The authors found the 25th recorded case in our centre and another 24 reported cases from a review of the literature between 1961 and 1999. Intratympanic salivary gland choristoma frequently occurs during the first and second decades of life and with a female preponderance (56 per cent). Nearly all the patients (96 per cent) in our review presented with a hearing loss, that had begun since birth, in infancy, or during childhood. Tinnitus (28 per cent), and serous otitis media (24 per cent) were also commonly present. One case complained of otorrhoea. Intratympanic and extratympanic anomalies were found in 96.2 per cent and 34.6 per cent of cases respectively. Of these anomalies, ossicular chain (88.5 per cent), facial nerve (65.4 per cent), middle-ear muscles (30.8 per cent) and labyrinthine windows (23 per cent) were the four most common sites. Therefore, salivary gland choristoma may represent a manifestation of a congenital ear anomaly. Diagnosis of salivary gland choristoma is generally not documented pre-operatively, but is based on surgical biopsy and histopathological investigations. Treatment of this rare lesion depends on the size, location and extent of the mass, degree of anatomical abnormality and expertise of the surgeon. In difficult cases where the mass is attached to the dehiscent or inferiorly placed facial nerve, only biopsy is recommended. However, complete surgical removal is advocated for a mass that is easy to remove. KTP laser use via a 200 micron fibre-optic light carrier can facilitate removal especially in cases with ossicular chain involvement.

Ganglioglioma of the optic chiasm: case report and review of the literature.

We report a case of a hypothalamic chiasmatic ganglioglioma in a 21-year-old woman who presented with hyperprolactinemia and developed visual field defects. This circumscribed cystic lesion with an enhancing mural nodule was radiologically indistinguishable from a pilocytic astrocytoma. Although rare, gangliogliomas should be included in the differential diagnosis of lesions occurring in this area of the brain.

Primary mucoepidermoid carcinoma of the intrahepatic bile duct: a case report with review of literature.

A 64-year-old Thai man had a primary mucoepidermoid carcinoma, a variant of the cholangiocarcinoma, of the left lobe of the liver. A 5 x 4 x 3 cm tumor metastasized within the liver and to the porta hepatic and parapancreatic lymph nodes with compression of the head of pancreas and distal part of the common bile duct resulting in obstructive janudice. The patient died within 7 months from massive hemorrhage of a chronic peptic ulcer of the duodenum. Review of the medical literature in the English language disclosed 11 primary mucoepidermoid carcinomas of the bile ducts, including the present instance. Nine tumors were intrahepatic; three were in the right lobe and six in the left lobe. Two neoplasms were extrahepatic; they arose in the common hepatic ducts. There were 6 men and 5 women of 44 to 78 years old; the mean age was 60 years. The size of the tumor ranged from 1.5 to 18 cm in greatest dimension; the average size was 8.4 cm. The tumor metastasized frequently to the regional lymph nodes. Invasion of the portal vein and hepatic artery has also occurred. Ten patients having primary mucoepidermoid carcinoma of the bile duct died within 11 months regardless of treatments. Only one patient was well, 10 months after extensive resection of a 1.5 cm tumor of the common hepatic duct. It is concluded that the prognosis is generally poor for the patient having primary mucoepidermoid carcinoma of the bile duct.

Astroblastoma: report of a case with microsatellite analysis.

A 5-year-old girl who developed progressive headache, vomiting, and left hemiparesis was found to have a cystic tumor with an enhanced mural nodule in the right frontoparietal region on a computed tomography examination. The lesion was histologically and ultrastructurally verified as an astroblastoma, an uncommon neuroepithelial tumor of uncertain origin. Molecular analysis using 17 microsatellite markers on chromosomes 9, 10, 11, 17, 19, and 22 showed loss of heterozygosity at the D19S412 locus on the long arm of chromsome 19. This observation suggests that there is a tumor suppressor gene in this chromosomal region, which plays a role in the pathogenesis of astroblastoma.

Extensive ossification in a craniopharyngioma.

A rare extensive ossification occurred in a suprasellar craniopharyngioma of a man who died at 21 years of age. The tumor produced headache, retarded physical and mental development, visual disturbances, and increased intracranial pressure. The neoplasm recurred after surgical and roentgenological treatments. Differentiation of multipotential mesenchymal cells or mesenchymal type cells within the tumor has been suggested as the mode of occurrence of bone in this craniopharyngioma.

Genetic heterogeneity and progression in different areas within high-grade diffuse astrocytoma.

The primary objective of this study was to determine loss of heterozygosity (LOH) in various portions of 9 high-grade diffuse astrocytomas, 8 glioblastomas and 1 anaplastic astrocytoma. LOH was observed on chromosomes 9, 10, 17 and 19 in 8, 3, 4 and 2 cases, respectively. Genetic heterogeneity and a multistep process were identified in 4 glioblastomas explaining the diverse morphological characteristics, a common feature of diffuse astrocytomas. In 2, 2, 3 and 1 cases, the allele losses were found within part of grade IV astrocytomas but not grades II or II/III, on chromosomes 9, 10, 17 and 19, respectively. In one of these, while genetic heterogeneity was observed on chromosome 17 between the area of grade II and grade IV, 9pLOH was found within both areas and occurred on the same allele. The other 5 cases did not demonstrate genetic heterogeneity and the LOH was on the same allele, irrespective of grade, suggesting clonal origin. In conclusion, at the molecular level, the diverse morphological features of astrocytoma develops by a multistep mechanism of genetic alterations from one cell via low-grade and more malignant tumors towards glioblastoma.

Identification of distinct regions of allelic loss on chromosome 13q in nasopharyngeal cancer from paraffin embedded tissues.

Our main purpose was to identify tumor suppressor gene loci on chromosome 13 responsible for nasopharyngeal cancer (NPC) development by analyzing loss of heterozygosity (LOH) and RB protein expression in paraffin embedded tissues. Normal and tumor DNA were extracted from microdissected samples, and their whole genomes were amplified using degenerate oligonucleotide primers. The polymerase chain reaction (PCR) products were analyzed by repeated amplification using primers derived from 16 microsatellite regions spanning the long arm of this chromosome. Among 50 informative cases, LOH was observed in 44 tumors. Thirty-one tumors displayed partial loss and provided an informative basis for detailed deletion mapping. Three minimal regions of loss were delineated; the first flanked by D13S120 and D13S219, the second by D13S126 and D13S119, and the third by D13S137 and 13qter. These 3 regions were linked to BRCA2 on 13q12, RB1 on 13q14, and 13q14.3-ter, respectively. Seven and 4 cases showed LOH either on 13q12 or 13q14, respectively. Nineteen cases showed LOH of both loci separately. One NPC displayed 13q12 and 13q14.3-ter LOH. RB protein expression was detectable in 76% of the cases. Ten out of 15 cases with the allelic losses limited to 13q14 showed RB protein expression. Contrasting that, 6 out of 7 cases devoid of RB protein expressions showed 13q14LOH. In conclusion, 13qLOH, involving 3 tumor suppressor gene loci, appears to be a frequent genetic event occurring during NPC development. However, other tumor suppressor genes besides RB1, may be responsible for the majority of 13q14LOH.

Traumatic neuroma as a cause of obstructive jaundice.

A 70-year-old man with previous cholecystectomy developed progressive obstructive jaundice, 3 months before hospitalization. Intraoperatively, a 2 x 2 x 1.5-cm mass in the distal part of the right hepatic duct was excised to release complete obstruction. It was verified as traumatic (amputation) neuroma. Despite rarity, traumatic neuroma of the bile duct should be considered in patients who have antecedent surgical procedure of the biliary tract with subsequent occurrence of extrahepatic biliary obstruction.

Solitary schwannoma of the tympanic membrane: a case report.

The external ear canal may be occluded by a rare tumor of the tympanic membrane. We reported herein a case of solid schwannoma arising from the tympanic membrane of a 29-year-old man. It presented as a circumscribed and encapsulated tumor of the external ear canal. The definite diagnosis was based on a careful microscopic examination and pathological findings. A precise excision of the tumor together with part of the tympanic membrane, followed by a myringoplasty was performed. To the best of our knowledge, our case should be the first reported case of this entity in the world literature.

Atypical granular cell tumor of the neurohypophysis: a case report with review of the literature.

A 76-year-old man had an atypical granular cell tumor of the neurohypophysis which showed pleomorphic nuclei, mitotic figures, and spindle-shaped cells, extremely rare findings to be encountered. Review of 45 patients with neurohypophyseal granular cell tumor revealed a ratio of 1:2 between male and female with the peak occurrence (31%) in the fifth decade, and with the mean age of 50 years. There were no patients below 20 years of age. The common clinical presentations included visual disturbances and endocrinopathies relating to sex hormones. Surgical removal was the treatment of choice. If it is possible, total extirpation should be attempted. Because of uncertain cellular origin, the lesion should be descriptively diagnosed as granular cell tumor although multiple terms have been proposed.

Epithelial-myoepithelial carcinoma of parotid gland: a case report with immunohistochemical and ultrastructural studies.

A 66-year-old man presented with a painless mass of the parotid gland. Light and electron microscopic studies verified the basic nature of the tumor as epithelial-myoepithelial carcinoma, a low-grade malignant neoplasm of the salivary gland. Pathologically, there were two types of cells; the inner eosinophilic epithelial cells lining the ducts and the outer clear cells. The former cells displayed immunoreactivity for cytokeratin and ultrastructural features of apical microvilli and desmosome. The latter cells were positive for actin, S-100 protein, vimentin and the cytoplasm contained actin microfilaments. Such pathological findings were characteristic features of this rare tumor. To our knowledge, this is the first reported case of EMC in Thailand.