Khoon Leong Chuah

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 TCRαβ 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.

Female Reproductive Factors, Gene Polymorphisms in the Estrogen Metabolism Pathway, and Risk of Lung Cancer in Chinese Women

The authors examined relations between reproductive factors and 5 estrogen pathway gene polymorphisms (CYP17 rs743572, CYP19A1 rs10046, ERβ rs1256049, ERβ rs4986938, and COMT rs4680) among 702 Singapore Chinese female lung cancer cases and 1,578 hospital controls, of whom 433 cases (61.7%) and 1,375 controls (87.1%) were never smokers. Parity (per child, odds ratio (OR) = 0.92, 95% confidence interval (CI): 0.87, 0.97) and menstrual cycle length (for ≥30 days vs. <30 days, OR = 0.50, 95% CI: 0.32, 0.80) were inversely associated with lung cancer in never smokers, while age at first birth (for ages 21-25, 26-30, and ≥31 years vs. ≤20 years, ORs were 1.54, 2.17, and 1.30, respectively), age at menopause (for ages 49-51 and ≥52 years vs. ≤48 years, ORs were 1.37 and 1.59; P(trend) = 0.003), and reproductive period (for 31-33, 34-36, 37-39, and ≥40 years vs. ≤30 years, ORs were 1.06, 1.25, 1.45, and 1.47; P(trend) = 0.026) were positively associated. Among smokers, parity was inversely associated with lung cancer, but there was no association with other reproductive factors. The COMT rs4680 A allele was positively associated with lung cancer in never smokers (for G/A or A/A vs. G/G, OR = 1.46, 95% CI: 1.12, 1.90) but not in ever smokers. No associations were seen with other polymorphisms. These results support a risk-enhancing role of estrogens in lung carcinogenesis among never smokers.

Sarcoidosis in Singapore: Epidemiology, clinical presentation and ethnic differences

Background and objectives:  The aim of this study is to better understand the epidemiological and clinical features of patients with sarcoidosis in Singapore and to ascertain if ethnic differences exist.

Discovered on gastrointestinal stromal tumours 1 (DOG1) expression in non-gastrointestinal stromal tumour (non-GIST) neoplasms

Mertens F. FUS–CREB3 l2/l1-positive sarcomas show a specific gene expression profile with upregulation of CD24 and FOXL1. Clin. Cancer Res. 2011; 17; 2646–2656. 9. Doyle LA, Moller E, Dal Cin P, Fletcher CD, Mertens F, Hornick JL. MUC4 is a highly sensitive and specific marker for low-grade fibromyxoid sarcoma. Am. J. Surg. Pathol. 2011; 35; 733–741. 10. Doyle LA, Hornick JL. EWSR1 rearrangements in sclerosing epithelioid fibrosarcoma. Am. J. Surg. Pathol. 2013; 37; 1630– 1631. 11. Arbajian E, Puls F, Magnusson L et al. Recurrent EWSR1– CREB3 l1 gene fusions in sclerosing epithelioid fibrosarcoma. Am. J. Surg. Pathol. 2014; [Epub ahead of print].

Meat Consumption and Risk of Lung Cancer Among Never-Smoking Women

The relationship between diet and lung cancer, apart from the protective effect of fruit and vegetables, is poorly understood. Reports on the role of dietary components such as meat are inconsistent, and few studies include sufficient numbers of nonsmokers. We examined the relationship between meat consumption and never-smoking lung cancer in a hospital-based case–control study of Singapore Chinese women, a population with low smoking prevalence. Three hundred and ninety-nine cases and 815 controls were recruited, of whom 258 cases and 712 controls were never smokers. A standardized questionnaire (which included a food frequency questionnaire module) was administered by trained interviewers. Among these never smokers, fruit and vegetable intake were inversely associated with lung cancer risk. Seventy-two percent of meat consumed was white meat (chicken or fish). Meat consumption overall was inversely associated with lung cancer [adjusted odds ratio (OR), 0.88, 0.59 for second, third tertiles, P trend = .012]. An inverse relationship between fish consumption and lung cancer (adjusted OR, 0.81, 0.47 for 2nd, 3rd tertiles, P trend < .001) was observed. No association was seen between consumption of processed meats and lung cancer, nor between dietary heterocyclic amines and lung cancer. Our data suggest that fish consumption may be protective against lung cancer in never smokers.

Aspirin and non-aspirin non-steroidal anti-inflammatory drug use and risk of lung cancer

There is evidence that aspirin and non-aspirin non-steroidal anti-inflammatory drug (NSAID) have anti-carcinogenic properties, but their effect on lung cancer, in particular in never-smokers, is unclear. Information on past or current use of anti-inflammatory medication was obtained in 398 Chinese female primary lung cancer cases and 814 controls in a hospital-based study in Singapore. 65% of cases and 88% of controls were never-smokers. Controls were excluded if they had been admitted for conditions associated with aspirin or NSAID use (n=174). Regular aspirin use (twice a week or more, for a month or more) was associated with a reduced risk of lung cancer (adjusted odds ratio [OR] 0.50, 95% confidence intervals [95%CI] 0.31-0.81 in non-smokers; OR 0.38, 95%CI 0.16-0.93 in smokers). Regular use of non-aspirin NSAID, paracetamol, steroid creams and steroid pills was uncommon and no association with lung cancer was detected. Our results suggest that aspirin consumption may reduce lung cancer risk in Asian women and are consistent with current understanding of the role of cyclooxygenase in lung carcinogenesis.

Plasmablastic lymphoma affecting the lung and bone marrow with CD10 expression and t(8;14)(q24;q32) translocation.

Plasmablastic lymphoma is a rare variant of a diffuse, large B-cell lymphoma, which typically presents in the oral cavity in immunocompromised patients. In HIV positive patients, this tumor has a tendency to manifest in extramedullary sites. In this report, we document a rare instance in which this neoplasm besides affecting the bone marrow also involved the lung. In addition, the lymphoma in our case disclosed CD10 positivity on immunohistochemistry and t(8;14)(q24;q34) translocation on cytogenetic analysis, mimicking a Burkitt/atypical Burkitt lymphoma. The problems in diagnosis are discussed.

Tracheal carcinoma ex pleomorphic adenoma: a rare tumour with potential problems in diagnosis.

CLL with 17p deletion in our patient without EBV infection or prior fludarabine therapy. The pathogenesis in our patient is unclear and questions the use of the term Richter’s transformation for describing aggressive lymphomas arising in CLL ⁄ SLL that are molecularly distinct. The expression of CD5 in H-RS cells noted in our case has not been reported in previous cases of the HL variant of Richter’s transformation, although de novo HL has been known to express many T-cell antigens, CD2 and CD4 in particular. The B-cell genotype of H-RS cells and their clonal distinction from CLL ⁄ SLL cells suggest CD5 expression in the former is aberrant and cannot be used to infer a common clonal origin of the two neoplastic populations. In summary, our case adds to the literature on transformation of CLL ⁄ SLL to HL, which is a rare variant of Richter’s syndrome, and supports the hypothesis that the latter is a second neoplasm rather than clonal evolution of SLL.

Pleuroparenchymal Fibroelastosis of the Lung: A Review

Described in Japan by Amitani et al in 1992, the entity of idiopathic upper lobe fibrosis was subsequently given the name pleuroparenchymal fibroelastosis (PPFE) in the English-speaking world. Pleuroparenchymal fibroelastosis is believed to be a rare disease characterized by a fibrosing process affecting the pleura and the subpleural lung parenchyma, with a predilection for the upper lobes. Uniquely, the fibrosing process is elastotic in nature, being associated with intra-alveolar fibrosis. The etiology of PPFE is unclear at this juncture, with many cases being considered as idiopathic forms of the disease. Conditions associated with PPFE include infections, bone marrow transplantation, and autoimmunity. In this review, we explore the clinical, radiologic, and pathologic features associated with PPFE in light of current understanding of the disease. Recent studies implicated that PPFE may not be as uncommon as claimed. The various differential diagnoses and implications of diagnosing PPFE are discussed.

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.