An unusual case of glomerulonephritis in a patient with non-Hodgkin mucosal associated lymphoid tissue (MALT) B-cell lymphoma.

BACKGROUND: Kidney involvement in non-Hodgkin lymphoma is well recognized and glomerulonephritis, when present, has been commonly reported to be associated with a membranoproliferative pattern. CASE PRESENTATION: We report a case of a 58-year-old lady with a recurrence of non-Hodgkin MALT B-cell lymphoma, presenting with acute kidney injury, nephrotic range proteinuria and a cellular urinalysis. She underwent a renal biopsy that showed a severe diffuse proliferative and exudative lupus-like glomerulonephritis, which is likely paraneoplastic in nature. We discuss the differential diagnosis and possible pathogenesis of glomerular injury in lymphoma-related proliferative glomerulonephritis. CONCLUSION: Differentiating between true lupus nephritis and a paraneoplastic glomerulonephritis is important, as it would have significant implications on treatment and clinical course.

Metallosis Following Titanium Implant Use in the Hand: A Case Report and Review of Current Literature.

Adverse reaction to metal debris (ARMD) consists of a spectrum of changes ranging from pure metallosis to aseptic lymphocytic vasculitis-associated lesion and granulomatous inflammation. Currently described ARMD cases are mainly limited to arthroplasty, typically total hip and knee arthroplasties in the lower limb and total wrist arthroplasty in the upper limb. Hypersensitivity to a metallic implant in fracture fixation is rare, and a severe form of metallosis has not been reported so far. In this paper, we present a case of ARMD occurring 10 years after the use of titanium implants for fracture fixation in the hand. Intra-operative findings, histopathological results, and a literature review on ARMD are also described.

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, ERß rs1256049, ERß 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.

Concordance of Cytological Specimens with Histological Tissue for Detection of Epidermal Growth Factor Receptor Mutation in Non-Small Cell Lung Cancer: A Systematic Review.

INTRODUCTION: There is increasing need for more testing in non-small cell lung cancer given the introduction of newer targeted therapies. Cytological specimens including conventional smears (CS), cell blocks (CB), and liquid-based cytology (LBC) are an alternative to histologic tissue (HT) specimens in detecting EGFR mutations, but the concordance of these 2 specimens is yet to be determined. The aim of the present systematic review is to determine the concordance rates between different cytologic specimens with HT in detecting EGFR mutations. METHODS: PubMed, Cochrane Library, and Google Scholar were utilized in the primary search, along with reference lists of electronically retrieved full-text articles. Concordance rates were pooled together if 2 or more studies reporting the same type of cytologic specimen were available. RESULTS: Overall, 15 studies were included in this review, with 13 studies included in the pooled analysis. There was an overall concordance rate of 92.8% in 593 paired cytologic and HT specimens, with LBC having the highest concordance rate of 96.0%, followed by CS and CB, each with a concordance rate of 95.8%, although the concordance rate of CS and/or CB was lower at 90.6% with a larger pool of studies. LBC was found to have a significantly higher concordance rate than CS and/or CB. CONCLUSION: Cytological specimens have a high concordance rate in detecting EGFR mutations, when compared to HT. LBC has shown superior concordance rates compared to CS and CB. Cytological specimens should be considered as an additional and alternative source of diagnostic material for EGFR testing.

Multicenter Evaluation of the Idylla GeneFusion in Non-Small-Cell Lung Cancer.

Targeted therapy in lung cancer requires the assessment of multiple oncogenic driver alterations, including fusion genes. This retrospective study evaluated the Idylla GeneFusion prototype, an automated and ease-of-use (<2 minutes) test, with a short turnaround time (3 hours) to detect fusions involving ALK, ROS1, RET, and NTRK1/2/3 genes and MET exon 14 skipping. This multicenter study (18 centers) included 313 tissue samples from lung cancer patients with 97 ALK, 44 ROS1, 20 RET, and 5 NTRKs fusions, 32 MET exon 14 skipping, and 115 wild-type samples, previously identified with reference methods (RNA-based next-generation sequencing/fluorescence in situ hybridization/quantitative PCR). Valid results were obtained for 306 cases (98%), overall concordance between Idylla and the reference methods was 89% (273/306); overall sensitivity and specificity were 85% (165/193) and 96% (108/113), respectively. Discordances were observed in 28 samples, where Idylla did not detect the alteration identified by the reference methods; and 5 samples where Idylla identified an alteration not detected by the reference methods. All of the ALK-, ROS1-, and RET-specific fusions and MET exon 14 skipping identified by Idylla GeneFusion were confirmed by reference method. To conclude, Idylla GeneFusion is a clinically valuable test that does not require a specific infrastructure, allowing a rapid result. The absence of alteration or the detection of expression imbalance only requires additional testing by orthogonal methods.

Polymorphisms in inflammatory pathway genes, host factors and lung cancer risk in Chinese female never-smokers.

Inflammation appears to be important in lung carcinogenesis among smokers, but its role among never-smokers is not well established. We hypothesized that inflammatory medical conditions and gene polymorphisms interact to increase lung cancer risk in never-smokers. We interviewed 433 Singaporean female never-smoker lung cancer patients and 1375 hospital controls, and evaluated six polymorphisms in the interleukin 1-ß, interleukin 6 (IL6), cyclooxygenase-2, peroxisome proliferator-activated receptor-γ and interleukin 1-ß receptor antagonist (IL1RN) genes. Tuberculosis was associated with a non-significant elevated risk of lung cancer [odds ratio (OR) 1.58, 95% confidence interval (CI) 0.95-2.62]. There was no effect of asthma, atopy or chronic productive cough individually. However, the presence of one or more of these conditions (asthma, cough or atopy) increased risk (OR 2.24, 95%CI 1.15-4.38) in individuals possessing the T/T genotype at interleukin 1-ß -31T/C, but not in those possessing the C/T (OR 0.87, 95%CI 0.51-1.57) or C/C genotypes (OR 0.58, 95%CI 0.27-1.27), and in individuals having the *2 variable number of tandem repeat allele of IL1RN [OR 5.09 (1.39-18.67)], but not in those without (OR 0.93, 95%CI 0.63-1.35). The IL6-634 G allele increased the risk of lung cancer (OR 1.44, 95%CI 1.07-1.94). Lung cancer risk also increased with the number of polymorphism sites where at least 1 'risk' allele was present [interleukin 1-ß -31T/C (T allele), IL1RN (*2 allele) and IL6-634C/G (G allele)] among those with asthma, cough or atopy (Ptrend 0.001) but not in those without (Ptrend 0.47). Our results suggest that the effect of inflammatory medical conditions on lung cancer in never-smokers is modulated by host genetic susceptibility and will need to be confirmed in other studies conducted in similar populations.

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.

Paraneoplastic Secretion of Multiple Phosphatonins From a Deep Fibrous Histiocytoma Causing Oncogenic Osteomalacia.

CONTEXT: Literature suggests that oncogenic osteomalacia is usually caused by a benign mesenchymal tumor secreting fibroblast growth factor subtype-23 (FGF-23), but the involvement of other phosphatonins has only been scarcely reported. We have previously published a seemingly typical case of oncogenic osteomalacia. Following curative neoplasm resection, we now report unique molecular characteristics and biology of this tumor. CASE DESCRIPTION: A 25-year-old man had been diagnosed with severe oncogenic osteomalacia that gradually crippled him over 6 years. 68Ga-DOTA-TATE positron emission tomography/computed tomography scan localized the culprit tumor to his left sole, which on resection revealed a deep fibrous histiocytoma displaying a proliferation of spindle cells with storiform pattern associated with multinucleated giant cells resembling osteoclasts. Circulating FGF-23, which was elevated more than 2-fold, declined to undetectable levels 24 h after surgery. Microarray analysis revealed increased tumor gene expression of the phosphatonins FGF-23, matrix extracellular phosphoglycoprotein (MEPE) and secreted frizzled-related protein subtype 4, with elevated levels of all 3 proteins confirmed through immunoblot analysis. Differential expression of genes involved in bone formation and bone mineralization were further identified. The patient made an astonishing recovery from being wheelchair bound to fully self-ambulant 2 months postoperatively. CONCLUSION: This report describes oncogenic osteomalacia due to a deep fibrous histiocytoma, which coincidentally has been found to induce profound muscle weakness via the overexpression of 3 phosphatonins, which resolved fully upon radical resection of the tumor. Additionally, genes involved in bone formation and bone remodeling contribute to the molecular signature of oncogenic osteomalacia.

A case of raised CA 19-9 in a patient with desmoplastic fibroblastoma of the upper limb.

Carbohydrate antigen 19-9 (CA 19-9) is a tumor marker widely accepted as the most useful blood test in diagnosing and monitoring pancreatic cancer. However, CA 19-9 may also be raised in other conditions such as colorectal, hepatic, lung, and ovarian carcinoma as well as benign conditions such as hepatobiliary and pulmonary diseases. CA 19-9 is rarely elevated above 200 U/ml in benign conditions with values exceeding 1000 U/ml being highly suggestive of malignancy. The mechanism of secretion in both malignant and benign conditions remains unclear. Desmoplastic fibroblastoma (DF) is a benign soft tissue tumor. CA 19-9 has not been reported in association with DF previously. We present a case of raised serum CA 19-9 in a 71-year-old male attributed solely to DF in his left cubital fossa. The patient's CA 19-9 level rose from 56 U/ml at the time of presentation to 3763.8 U/ml over a period of 9 months. Post-DF excision, the CA 19-9 level decreased to 1464 U/ml at 1 month, 162.3 U/ml at 2.5 months, and 24U/ml, within normal range, at 7 months post-surgery. CA 19-9 levels continued to remain at 24 U/ml 1.5 years post-tumor excision. The CA 19-9 level in this patient was highly elevated which is unusual in association with a benign tumor. The rate of decrease in CA 19-9 level post-excision was in keeping with that reported after pancreatic cancer resections. This is the first case of DF in association with raised CA 19-9.

Behind the Façade: Robotic-Assisted Resection of a Diaphragmatic Osteochondroma.

Neoplasms arising from the diaphragm are not typically seen in clinical practice, though they may inflict significant morbidity and mortality. In the realm of thoracic surgery, osteochondromas are only encountered at the thoracic wall or vertebra. In this study, we describe a case of an osteochondroma arising from the diaphragm masquerading as a malignant lesion. The tumor was resected via robotic-assisted means and the patient was discharged with no complications.

Malignant Pleural PEComa: A Previously Undocumented Site.

Perivascular epithelioid cell (PEC) tumors are rare tumors of mesenchymal origin and can affect many anatomic regions. Although these tumors are usually benign, malignant variants exist. We document for the first time a malignant PEComa arising from the pleura of a 43-year-old Malay woman. The pathology of the tumor as well as differential diagnoses is discussed.

Impact of an interstitial lung disease service in the diagnosis and management of interstitial lung disease in Singapore.

INTRODUCTION: The current gold standard for diagnosing interstitial lung disease (ILD) involves an ILD clinic evaluation, followed by discussion in a multidisciplinary meeting (MDM). However, there is a paucity of data on the impact of ILD MDMs on the diagnosis and management of ILDs in Southeast Asia. We studied the clinical impact of the ILD service on the diagnosis and management of ILDs at a university-affiliated tertiary hospital in Singapore. METHODS: A single-centre retrospective review was done on 97 consecutive patients referred for evaluation to the ILD service from March 2016 to August 2017. RESULTS: Mean age of the patients was 67 ± 11 years. Gender distribution was almost equal (52% male), with a majority of never-smokers (63%). Mean forced vital capacity (FVC) was 1.81 ± 0.66 L (66% ± 20% predicted). The three commonest referral diagnoses were ILD of uncertain classification (n = 38, 39%), connective tissue disease-associated ILD (CTD-ILD) (n = 24, 25%) and idiopathic pulmonary fibrosis (IPF) (n = 16, 17%). Following evaluation by the ILD service, there was a change of diagnosis in 60 (62%) patients and a change of management in 71 (73%) patients. The majority of consensus MDM diagnoses were IPF (n = 35, 36%), CTD-ILD (n = 30, 30%) and others (n = 15, 15%). There was a significant prognostic separation between the IPF and non-IPF diagnoses made following evaluation by the ILD service. CONCLUSION: The ILD service allowed for more precise subtyping of various ILDs. This is particularly useful for IPF patients, who can benefit from antifibrotic therapies.

Assessment of human papillomavirus and Epstein-Barr virus in lung adenocarcinoma.

The association of human papillomavirus (HPV) and Epstein-Barr virus (EBV) infection with non-small cell lung cancer is controversial. HPV and EBV prevalence in a uniform population of lung adenocarcinoma was investigated, hypothesizing that there would be differences seen between smokers and non-smokers and between sexes. Patients involved in this study were selected from a single institution database of lung cancer. In total 497 patients with adenocarcinoma were identified and 110 patients had sufficient tissue for analysis with an in situ hybridization method that probed for high-risk and low-risk HPV and EBV. There were 65 males and 45 females, 78 patients with stage I-IIIA disease and 32 patients with stage IIIB-IV disease. There were similar number of smokers and non-smokers. Across all stages HPV and EBV staining was absent from all tissues examined. It is unlikely that HPV or EBV is an important etiological agent in adenocarcinoma of the lung, even among the never-smokers.

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.

Extradural cervical spinal meningioma mimicking malignancy.

The vast majority of intraspinal meningiomas occur in an intradural extramedullary location. A meningioma in a purely extradural location in the cervical spine as reported here is quite exceptional. Extradural meningiomas tend to show more aggressive features than intradural meningiomas and are often confused with malignant neoplasms. We report an invasive extradural meningioma in the cervical spine with multi-segmental involvement, extension through the neural foramina and encasement of the subjacent vertebral artery, mimicking malignancies such as lymphoma and sarcoma. Although rare, meningiomas may demonstrate extradural multi-segmental growth and should be considered in the differential diagnosis of such lesions.

Diagnosis of adenoid cystic carcinoma of the lung by bronchial brushing: a case report.

BACKGROUND: A diagnosis of pulmonary adenoid cystic carcinoma on exfoliative cytology specimen is very uncommon. The diagnostic cytologic material typically is obtained following a tissue biopsy. No previous report of the diagnosis has been made on bronchial brushing cytologic material when the procedure preceded a tissue biopsy. CASE: A 44-year-old man who used to smoke cigarettes and was otherwise well complained of persistent cough for the past 6 months. A chest radiograph revealed a mass lesion in the left hilum. Computed tomography of the chest disclosed an irregular and spiculated soft tissue mass in the left apical anterior segment. Bronchial brushing via bronchoscope was performed, revealing carcinoma cells consistent with an adenoid cystic carcinoma on cytology. A bronchial biopsy and subsequent left upper lobectomy were performed, confirming the diagnosis of adenoid cystic carcinoma of the lung associated with tumor extension to the epithelial surface. CONCLUSION: A diagnosis of bronchial adenoid cystic carcinoma is possible on bronchial brushing. However, as a method in exfoliative cytology, the usefulness of bronchial brushing in diagnosing this tumor is limited by the neoplasm's proximity to the mucosal surface and whether the mucosa has been breached.