MR Imaging Criteria for the Detection of Nasopharyngeal Carcinoma: Discrimination of Early-Stage Primary Tumors from Benign Hyperplasia.

BACKGROUND AND PURPOSE: MR imaging can detect nasopharyngeal carcinoma that is hidden from endoscopic view, but for accurate detection carcinoma confined within the nasopharynx (stage T1) must be distinguished from benign hyperplasia of the nasopharynx. This study aimed to document the MR imaging features of stage T1 nasopharyngeal carcinoma and to attempt to identify features distinguishing it from benign hyperplasia. MATERIALS AND METHODS: MR images of 189 patients with nasopharyngeal carcinoma confined to the nasopharynx and those of 144 patients with benign hyperplasia were reviewed and compared in this retrospective study. The center, volume, size asymmetry (maximum percentage difference in area between the right and left nasopharyngeal halves), signal intensity asymmetry, deep mucosal white line (greater contrast enhancement along the deep tumor margin), and absence/distortion of the adenoidal septa were evaluated. Differences were assessed with logistic regression and the χ2 test. RESULTS: The nasopharyngeal carcinoma center was lateral, central, or diffuse in 134/189 (70.9%), 25/189 (13.2%), and 30/189 (15.9%) cases, respectively. Nasopharyngeal carcinomas involving the walls showed that a deep mucosal white line was present in 180/183 (98.4%), with a focal loss of this line in 153/180 (85%) cases. Adenoidal septa were absent or distorted in 111/111 (100%) nasopharyngeal carcinomas involving the adenoid. Compared with benign hyperplasia, nasopharyngeal carcinoma had a significantly greater volume, size asymmetry, signal asymmetry, focal loss of the deep mucosal white line, and absence/distortion of the adenoidal septa (P < .001). Although size asymmetry was the most accurate criterion (89.5%) for nasopharyngeal carcinoma detection, use of this parameter alone would have missed 11.9% of early-stage T1 nasopharyngeal carcinomas. CONCLUSIONS: MR imaging features can help distinguish stage T1 nasopharyngeal carcinoma from benign hyperplasia in most cases.

JAK-STAT and G-protein-coupled receptor signaling pathways are frequently altered in epitheliotropic intestinal T-cell lymphoma.

Epitheliotropic intestinal T-cell lymphoma (EITL, also known as type II enteropathy-associated T-cell lymphoma) is an aggressive intestinal disease with poor prognosis and its molecular alterations have not been comprehensively characterized. We aimed to identify actionable easy-to-screen alterations that would allow better diagnostics and/or treatment of this deadly disease. By performing whole-exome sequencing of four EITL tumor-normal pairs, followed by amplicon deep sequencing of 42 tumor samples, frequent alterations of the JAK-STAT and G-protein-coupled receptor (GPCR) signaling pathways were discovered in a large portion of samples. Specifically, STAT5B was mutated in a remarkable 63% of cases, JAK3 in 35% and GNAI2 in 24%, with the majority occurring at known activating hotspots in key functional domains. Moreover, STAT5B locus carried copy-neutral loss of heterozygosity resulting in the duplication of the mutant copy, suggesting the importance of mutant STAT5B dosage for the development of EITL. Dysregulation of the JAK-STAT and GPCR pathways was also supported by gene expression profiling and further verified in patient tumor samples. In vitro overexpression of GNAI2 mutants led to the upregulation of pERK1/2, a member of MEK-ERK pathway. Notably, inhibitors of both JAK-STAT and MEK-ERK pathways effectively reduced viability of patient-derived primary EITL cells, indicating potential therapeutic strategies for this neoplasm with no effective treatment currently available.

Type II EATL (epitheliotropic intestinal T-cell lymphoma): a neoplasm of intra-epithelial T-cells with predominant CD8αα phenotype.

In this multicentre study, we examined 60 cases of Type II enteropathy-associated T-cell lymphoma (EATL) from the Asia-Pacific region by histological review, immunohistochemistry and molecular techniques. Patients were mostly adult males (median age: 58 years, male:female 2.6:1), presenting with abdominal pain (60%), intestinal perforation (40%) and weight loss (28%). None had a history of coeliac disease and the median survival was only 7 months. Histologically, these tumours could be divided into (i) central tumour zone comprising a monotonous population of neoplastic lymphocytes, (ii) peripheral zone featuring stunted villi and morphologically atypical lymphocytes showing epitheliotropism, and (iii) distant mucosa with normal villous architecture and cytologically normal intra-epithelial lymphocytes (IELs). Characterized by extensive nuclear expression of Megakaryocyte-associated tyrosine kinase (MATK) (87%) and usually a CD8(+)CD56(+) (88%) cytotoxic phenotype, there was frequent aberrant expression of CD20 (24%). T-cell receptor (TCR) expression was silent or not evaluable in 40% but of the remainder, there was predominant expression of TCRαß over TCRγδ (1.6:1). In keeping with the normal ratio of IEL subsets, CD8(+) cases showed predominant CD8αα homodimer expression (77%), regardless of TCR lineage. These tumours constitute a distinct entity from classical EATL, and the pathology may reflect tumour progression from IEL precursors, remnants of which are often seen in the distant mucosa.

EBV-associated smooth muscle tumour presenting as a parapharyngeal mass--a rare presentation.

The Epstein-Barr virus-associated smooth muscle tumour (EBV-SMT) is a rare entity that has only recently been recognised. Since its first description in 1993, it has been reported only in immunocompromised patients, and generally presents as one or more non-specific mass lesions which may arise almost anywhere within the body. Because of its sporadic occurrence, non-specific presenting features and frequently unusual sites of occurrence, it often presents a diagnostic challenge for the clinician. We describe an interesting patient with an EBV-SMT which masqueraded as nasopharyngeal carcinoma, presenting with serous otitis media, nasopharyngeal mass and raised Epstein-Barr virus (EBV) serology.

Malignant perivascular epithelioid cell tumour of the fibula: a report and a short review of bone perivascular epithelioid cell tumour.

Perivascular epithelioid cell tumour (PEComa) is a term applied to a family of mesenchymal tumours composed of varying proportions of spindle and epithelioid cell components associated with HMB-45 expression. PEComa rarely arises in the soft tissue, visceral organs, skin and bone. This report details an instance when a purely epithelioid PEComa arose from the right fibula of a 52-year-old Chinese woman without features of tuberous sclerosis complex. The excision specimen disclosed an epithelioid tumour with a nested pattern associated with areas of nuclear pleomorphism, mitotic activity, necrosis and vascular invasion in addition to HMB-45 expression on immunohistochemistry. To the best of the authors' knowledge, this represents the first case of a histologically malignant PEComa of the bone. A short review of primary bone PEComas and potential problems in diagnosis is presented.

Epstein-Barr virus-associated smooth muscle tumour mimicking bilateral vocal process granuloma.

A case is presented of a 36-year-old Chinese woman with a renal transplant for end-stage renal failure due to Goodpasture's syndrome. She presented with a year's history of throat discomfort and acid regurgitation into her throat. Videolaryngoscopy revealed bilateral vocal process granuloma, presumed to be due to gastroesophageal reflux. A four-week course of high dose omeprazole was prescribed. On follow up a month later, the granulomas had enlarged, and laser excision was undertaken. Histological and immunohistochemical staining was consistent with Epstein-Barr virus-associated smooth muscle tumour. This is believed to be the first reported case in the English literature of such a tumour affecting the vocal process. The aim of this paper is to present the pathogenesis, clinical behaviour and treatment of Epstein-Barr virus-associated smooth muscle tumour, and to review the literature concerning the differential diagnosis of polypoid vocal process lesions.

Unusual presentation of abdominal Castleman's disease.

Castleman's disease is a rare lymphoproliferative disorder of uncertain origin. We report an unusual presentation of Castleman's disease in the transverse mesocolon that mimicked a vascular gastrointestinal stromal tumour and review the literature surrounding this peculiar entity.

Pathologic, radiologic and PET scan response of gastrointestinal stromal tumors after neoadjuvant treatment with imatinib mesylate.

AIM: The aim of this study is to review the radiologic, PET scan and pathologic response and the outcome of patients with advanced GIST treated with neoadjuvant IM followed by surgical resection. MATERIALS AND METHODS: We report a case and review 36 patients reported in MEDLINE with advanced GIST treated with neoadjuvant IM followed by surgical resection. RESULTS: Thirty-seven patients with a median age of 56 years (range, 32-76 years) at presentation were treated with neoadjuvant IM. Radiologic response accurately predicted pathological response in 31/36 patients, whereas PET scan was accurate in predicting treatment response in only 6/23 patients. CONCLUSION: This study demonstrates that the pathologic response of GIST to IM is usually incomplete and does not correlate with the complete response seen on PET scan. This finding suggests that surgical resection will continue to play a vital role in the treatment of patients with advanced disease responding to IM treatment.

An unusual cause of granulomatous inflammation: eosinophilic abscess in Langerhans cell histiocytosis.

Eosinophilic abscess inciting a granulomatous response has rarely been reported and appears not to have been described in the setting of a neoplasm. In this report, a case is described where a granulomatous response occurred around eosinophilic abscesses in a patient with Langerhans cell histiocytosis, an association which has not previously been documented. On histology, the excised lymph node showed the presence of eosinophilic abscess and necrosis surrounded by granulomas, which in turn were surrounded by Langerhans cells, a feature confirmed on immunohistochemistry. Although rare, this case highlights the importance of careful examination of eosinophilic abscess with granulomatous inflammation in order to exclude an underlying neoplasm.

Gefitinib is more effective in never-smokers with non-small-cell lung cancer: experience among Asian patients.

We retrospectively analysed the results of patients with advanced non-small-cell lung cancer treated with gefitinib to derive clinical factors predictive of response and a favourable survival outcome. Patients were treated with gefitinib 250 mg per day and re-evaluated 4-8 weeks later with repeat CT scan and every 8 weeks thereafter to assess response and the duration of response. Pathology review by a histopathologist was conducted, in particular to confirm a recently published result of bronchioloalveolar carcinoma histology or its components as predictive of response to gefitinib. Logistic regression and Cox regression analytical methods were applied to determine factors that could predict for response and improved overall survival. A total of 110 patients were treated. The overall response rate was 32% partial responses (PRs). Only never-smoking status was predictive of response in the logistic regression analysis, adjusted OR=6.1, 95% CI=1.7, 21.5. The presence of a PR and good performance status were predictive of a favourable survival outcome from the Cox regression modelling. Responders had an adjusted HR of 3.0, 95% CI=1.5-5.8 compared to nonresponders, while patients with ECOG status 0-1 had an adjusted HR of 0.42, 95% CI=0.25-0.72, compared with patients with ECOG status 2-4. Bronchioloalveolar carcinoma or its components were distinctly absent on pathology review. In conclusions, Never-smoking status is an important clinical predictor of a favourable response to gefitinib.

Littoral cell angioma of the spleen.

INTRODUCTION: Littoral cell angioma is a recently described vascular tumour of the spleen with an unknown aetiology. CLINICAL PICTURE: We present a case of a 36-year-old lady who had a successful living-related renal transplantation 13 years ago. On follow-up, she was investigated for pyrexia of unknown origin (PUO) and was found to have a large solitary hypodense splenic lesion. TREATMENT: Splenectomy was carried out because an underlying infective or neoplastic cause for this patient on long-term immunosuppression could not be excluded. The operation and subsequent clinical course was uneventful and the patient's fever settled postoperatively. The histological and immunohistochemical features of the tumour were consistent with a littoral cell angioma. CONCLUSION: Littoral cell angioma is a vascular tumour of the spleen. This case illustrates that it can be a cause of PUO and should be considered in the differential diagnosis of splenic hypodense lesions.

Pineal yolk sac tumour with a solid pattern: a case report in a Chinese adult man with Down's syndrome.

Intracranial germ cell tumours are rare. The incidence of primary intracranial yolk sac tumour is even more uncommon, with only two reported cases being associated with Down's syndrome in the English literature. This report details the findings of yolk sac tumour in the pineal region affecting a 22 year old Chinese man with Down's syndrome. Histology revealed yolk sac tumour with only a solid pattern, potentially mimicking the more common germinoma in the pineal region. No other germ cell components were identified. This is the third report of intracranial yolk sac tumour manifesting in a patient with trisomy 21. The pathology of this tumour and its differential diagnoses are discussed.

Monophasic, solitary tumefactive demyelinating lesion: neuroimaging features and neuropathological diagnosis.

The characteristic clinicoradiological findings of multiple sclerosis and acute disseminated encephalomyelitis (ADEM), demonstrating a recurrent progressive course in the former and monophasicity in the latter associated with multiple discrete white matter lesions with variable enhancement on MRI, are not a diagnostic challenge. On the other hand, the less typical radiological presentation of a solitary tumefactive demyelinating lesion mimics a neoplasm, and often necessitates a biopsy. Nonetheless, histopathological examination is an imperfect gold standard and the recognition of certain imaging features may facilitate the correct diagnosis.

Giant cell arteritis (temporal arteritis, cranial arteritis) and a case from Singapore.

Giant cell arteritis as the underlying cause of blindness in the elderly is common in the West but is not seen except on rare occasions in South East Asia. We describe an 86-year-old Chinese man from Singapore who presented with a central retinal artery occlusion. Biopsy of a prominent superficial temporal artery established the underlying cause to be giant cell arteritis which was also the eventual cause of death as the condition resulted in rupture of a dissecting aneurysm of the aorta. Giant cell arteritis should be considered in all cases of ischaemic eye disease in the elderly. The importance of early diagnosis lies in the very high incidence of second eye involvement within days or at most weeks in untreated patients. A high index of suspicion is required for diagnosis of this condition which is likely under-diagnosed in our local context.

Tracheobronchial amyloidosis treated with rigid bronchoscopy and stenting.

Tracheobronchial amyloidosis (TBA) is an uncommon disease that can cause airway obstruction. We present a case of TBA in a 20-year-old man that was treated successfully with rigid bronchoscopy and stenting. The patient presented with progressive dyspnea despite having had a tracheostomy fashioned at another institution. Airway obstruction secondary to TBA was found distal to the tracheostomy. The amyloid protein subtype was AA, which is uncommon and is seldom of clinical significance in the respiratory tract. The patient underwent rigid bronchoscopy to remove the amyloid protein causing the airway obstruction. A Dumon silicone stent was then inserted to alleviate the obstruction. Thereafter, he recovered well and was discharged without a tracheostomy. This report shows that in patients with TBA causing airway obstruction, excellent results can be obtained with rigid bronchoscopy and stenting of the obstructing lesion.

Cost analysis of cataract surgery with intraocular lens implantation: a single blind randomised clinical trial comparing extracapsular cataract extraction and phacoemulsification.

A randomised single blinded clinical trial to compare the cost of cataract surgery between extracapsular cataract extraction (ECCE) and phacoemulsification (PEA) was conducted at Hospital Universiti Kebangsaan Malaysia (HUKM) between March and December 2000. A total of 60 patients were included in this study. The cost of a cataract surgery incurred by hospital, patients and households up to two months after discharge were included. The costs of training, loss of patients' income after discharge and intangible costs were excluded. Results showed that the average cost for one ECCE operation is RM1,664.46 (RM1,233.04-RM2,377.64) and for PEA is RM1,978.00 (RM1,557.87-RM3,334.50). During this short period of follow up, it can be concluded that ECCE is significantly cheaper than PEA by an average difference of RM 313.54 per patient (p < 0.001). Cost of equipment and low frequency of PEA technique done in HUKM were the two main reasons for the high unit cost of PEA as compared to ECCE.

Pseudodicentric (16;12)(q11;p11.2) in a type AB (mixed) thymoma.

Genetic alterations of thymomas are rarely described in the literature. In this study, a previously unreported instance of aberrant karyotypic change consisting of 45,XX,pseu dic(16;12) (q11;p11.2) [cp23]/87-90,idemx2[cp4] in a Masaoka Stage II mixed thymoma or type AB thymoma affecting a 56-year-old Chinese woman is detailed. Abnormalities involving 12p containing important tumor suppressor-like genes have been documented especially in hematological malignancies. Recently, recurrent losses involving 16q, a locus known to harbor several tumor suppressor genes, have been described in type C thymomas (squamous cell carcinoma), suggesting a possible relationship between type AB thymoma and type C thymoma. Whether these genes are involved in the pathogenesis of type AB thymoma remain to be clarified and it is currently unclear if cytogenetic studies may eventually play a role in the classification of thymic tumors.