Louise Burke

Well-differentiated papillary mesothelioma of the pleura: a series of 24 cases.

Well-differentiated papillary mesothelioma (WDPM) of the pleura represents a distinct mesothelial tumor presenting with unilateral pleural effusion and superficial spreading of stout papillary formations with myxoid cores, lined by bland, flattened, or epithelioid cells, without or with limited invasion of the submesothelial layer. The majority of cases have been reported in the peritoneum in women of reproductive age with no history of asbestos exposure and also in the tunica vaginalis of men. We report 24 cases of pleural WDPM and compared their histologic, epidemiologic, and clinical features with those of classic mesothelioma. Men and women were equally affected, with a mean age of 60 years. Half of the patients had a history of occupational asbestos exposure. In 11 patients with a minimal follow-up period of 24 months, the survival ranged from 36 to 180 months with an average of 74 months as compared with 9.89 months for 1248 paired patients with diffuse malignant mesothelioma. Ten-year survival was 30.8%. We conclude that WDPM is a rare and unusual mesothelial tumor, characterized by a lack of deep invasion and associated with an indolent clinical course and long survival. For these reasons, WDPM is best considered as a specific clinico-pathologic entity distinct from conventional diffuse malignant mesothelioma.

SYT-SSX fusion is absent in sarcomatoid mesothelioma allowing its distinction from synovial sarcoma of the pleura

The diagnosis of sarcomatoid mesothelioma is still a worldwide challenge and it is often difficult, both clinically and by morphological analysis, to differentiate sarcomatoid mesothelioma from synovial sarcoma, the most frequent intrathoracic sarcoma. To confirm the absence of the synovial sarcoma translocation t(X; 18) (SYT-SSX) in sarcomatoid mesothelioma, and to test its usefulness differentiating sarcomatoid mesothelioma from synovial sarcoma, 28 tumours were examined using the reverse transcriptase-polymerase chain reaction. RNA was extracted from paraffin blocks using standard methods, reverse-transcribed and PCR performed. Molecular analysis completed in two independent laboratories showed that sarcomatoid mesothelioma samples were negative for the t(X-18). This result confirms the usefulness of this analysis in differentiating sarcomatoid mesothelioma from synovial sarcoma.

Increasing the accuracy of 18F-FDG PET/CT interpretation of “mildly positive” mediastinal nodes in the staging of non-small cell lung cancer

INTRODUCTIONnThe aim of this study was to identify radiological factors that may reduce false-positive results and increase diagnostic accuracy when staging the mediastinum of patients with non-small cell lung carcinoma (NSCLC).nnnMETHODSnThis was a retrospective, interdisciplinary, per-node analysis study. We included patients with NSCLC and mediastinal nodes with an SUV max in the range of 2.5-4.0 on PET-CT. We hypothesized that the greatest number of false positive cases would occur in this cohort of patients.nnnRESULTSnA total of 92 mediastinal lymph nodes were analyzed in 44 patients. Mediastinal disease (N2/N3) was histologically confirmed in 15 of 44 patients and in 34 of 92 lymph nodes; positive predictive value of 37% and false positive rate of 63%. Lymph node SUV max, tumor size, ratio of node SUV max to tumor SUV max (SUVn/SUVp), and ratio of node SUV max to node size (SUV n/SADn) were significantly higher in true positive cases. Using a threshold of 0.3 for SUV node/tumor and 3 for SUV node/size yielded sensitivities of 91% and 71% and specificities of 71% and 69% respectively for the detection of mediastinal disease. Using both ratios in combination resulted in a sensitivity of 65% and a specificity of 88%. Concurrent benign lung disease was observed significantly more frequently in false-positive cases.nnnCONCLUSIONnSUVn/SUVpt and SUVn/SADn may be complimentary to conventional visual interpretation and SUV max measurement in the assessment of mediastinal disease in patients with NSCLC.

Upregulation of neurokinin-1 receptor expression in the lungs of patients with sarcoidosis.

Substance P (SP) is a proinflammatory neuropeptide that is secreted by sensory nerves and inflammatory cells. Increased levels of SP are found in sarcoid bronchoalveolar lavage fluid. SP acts by binding to the neurokinin-1 receptor and increases secretion of tumor necrosis factor-α in many cell types. We sought to determine neurokinin-1 receptor expression in patients with sarcoidosis compared with normal controls. Neurokinin-1 receptor messenger RNA and protein expression were below the limits of detection by reverse transcriptase-polymerase chain reaction and immunohistochemistry in peripheral blood mononuclear cells of healthy volunteers (n = 9) or patients with stage 1 or 2 pulmonary sarcoidosis (n = 10), but were detected in 1/9 bronchoalveolar lavage cells of controls compared with 8/10 patients with sarcoidosis (p = 0.012) and 2/9 biopsies of controls compared with 9/10 patients with sarcoidosis (p = 0.013). Immunohistochemistry localized upregulated neurokinin-1 receptor expression to bronchial and alveolar epithelial cells, macrophages, lymphocytes, and sarcoid granulomas. The patient in whom neurokinin-1 receptor was not detected was taking corticosteroids. Incubation of the type II alveolar and bronchial epithelial cell lines A549 and SK-LU 1 with dexamethasone downregulated neurokinin-1 receptor expression. Upregulated neurokinin-1 receptor expression in patients with sarcoidosis may potentiate substance P-induced proinflammatory cytokine production in patients with sarcoidosis.

Development and progress of Ireland's biobank network: Ethical, legal, and social implications (ELSI), standardized documentation, sample and data release, and international perspective.

Biobank Ireland Trust (BIT) was established in 2004 to promote and develop an Irish biobank network to benefit patients, researchers, industry, and the economy. The network commenced in 2008 with two hospital biobanks and currently consists of biobanks in the four main cancer hospitals in Ireland. The St. Jamess Hospital (SJH) Biobank coordinates the network. Procedures, based on ISBER and NCI guidelines, are standardized across the network. Policies and documents-Patient Consent Policy, Patient Information Sheet, Biobank Consent Form, Sample and Data Access Policy (SAP), and Sample Application Form have been agreed upon (after robust discussion) for use in each hospital. An optimum sequence for document preparation and submission for review is outlined. Once consensus is reached among the participating biobanks, the SJH biobank liaises with the Research and Ethics Committees, the Office of the Data Protection Commissioner, The National Cancer Registry (NCR), patient advocate groups, researchers, and other stakeholders. The NCR provides de-identified data from its database for researchers via unique biobank codes. ELSI issues discussed include the introduction of prospective consent across the network and the return of significant research results to patients. Only 4 of 363 patients opted to be re-contacted and re-consented on each occasion that their samples are included in a new project. It was decided, after multidisciplinary discussion, that results will not be returned to patients. The SAP is modeled on those of several international networks. Biobank Ireland is affiliated with international biobanking groups-Marble Arch International Working Group, ISBER, and ESBB. The Irish government continues to deliberate on how to fund and implement biobanking nationally. Meanwhile BIT uses every opportunity to promote awareness of the benefits of biobanking in events and in the media.

Thoracic vasculitis presenting as surgical problems

We present four patients with vasculitis manifesting with unusual clinical or pathological features, generating surgical problems. Two cases presented with pulmonary hypertension, with investigations and radiological evidence prompting clinical suspicion of pulmonary thrombo-embolic disease. First case, with an antecedant history of Wegeners granulomatosis (WG), demonstrated following “embolectomy”, WG involving the large pulmonary elastic arteries. The second case of inoperable “pulmonary thrombo-embolic disease” was subsequently found at limited post mortem to have giant cell arteritis, which affected widespread small peripheral pulmonary arterial vessels. The other two cases were of aortitis occurring in the background of immune-mediated disease, which had been treated with aggressive immunosuppression regimens. The first of these was a case of Cogans syndrome complicated by descending aortitis, a rarely reported phenomenon, with co-existent acute endocarditis of the aortic valve leaflets. Most cases of endocarditis in this context occur secondary to and in continuity with ascending aortitis. That this case, and a case of ascending aortitis occurring in the context of relapsing polychondritis occurred in the face of aggressive immunosuppression with an apparent clinical response, underscores the need to not accept a clinical picture at face value. This has implications for clinical management, particularly in the follow-up of surgical prosthetic devices such as grafts which may be used in these cases. All four cases emphasise the continued importance of histology and the post-mortem examination in elucidating previously undetected or unsuspected disease.

Non-infectious aortitis of the ascending aorta: a histological and clinical correlation of 71 cases including overlap with medial degeneration and atheroma—a challenge for the pathologist

Aims Aortitis is a rare but important cause of thoracic aortic disease. We describe its histopathological patterns and associations with other aortic pathologies and systemic inflammatory disease. Methods Database searches of thoracic specimens over 17 years from two centres yielded 71 cases of non-infectious aortitis. Histological verification of tunica media inflammation was required for inclusion. Clinical information and histopathological features were recorded. Results Three histological patterns emerged—necrotising aortitis with giant cells (53), diffuse band-like aortitis (16) and ‘other’ (2). 50/53 cases of necrotising aortitis with giant cells were isolated/idiopathic, while 9/16 cases of diffuse aortitis had a systemic inflammatory disease. Medial degeneration (MD) was prominent in 23/71 cases—all in the necrotising aortitis with giant cells category. Conclusions Non-infectious aortitis is predominantly idiopathic/isolated in nature, occurring in elderly females. Two patterns emerge—(1) necrotising aortitis with giant cells, which is more likely to be idiopathic and linked to MD, suggesting a possible aetiological relationship; and (2) diffuse aortitis, which is linked to an increased risk of systemic inflammatory disease. Knowledge, therefore, of histopathological patterns may guide patient management and follow-up.

A CF patient with progressive proteinuric renal disease: a CF-specific nodular glomerulosclerosis?

Cystic fibrosis (CF) is a multisystemic disease but without a classical disease-specific renal phenotype. A 32-year-old male patient with CF (ΔF508/ΔF508) presented with a nephrotic syndrome. Renal biopsy revealed nodular glomerulosclerosis (NGS) occurring in the absence of diabetes mellitus, amyloidosis and any other known common cause of NGS. He had a progressive decline in estimated glomerular filtration rate (eGFR) to chronic kidney disease stage V (eGFR <15 mL/min/1.73 m2) over a 3-year period despite optimal medical management. This is the fourth reported case of NGS in a patient with CF without diabetes and is the first to originate from a European country. This case supports the concept of a CF-related NGS.

Hypersensitivity Pneumonitis A Perspective From Members of the Pulmonary Pathology Society

CONTEXTn- Hypersensitivity pneumonitis (HP) is a lung disease that develops in susceptible individuals after inhalational exposure to an organic antigen or chemical compound. Pathogenesis is attributed to a combination of type III (immune complex-mediated) and type IV (delayed) hypersensitivity reactions to the inciting agent.nnnOBJECTIVEn- To provide an overview of the current status of the medical literature regarding hypersensitivity pneumonitis.nnnDATA SOURCESn- A literature search was performed using PubMed and Google search engines. The terms hypersensitivity pneumonitis and extrinsic allergic alveolitis were used, with the search starting on January 9, 2017, and concluding March 8, 2017.nnnCONCLUSIONSn- As a pathologist, it is important to consider hypersensitivity pneumonitis when examining lung specimens because it is often clinically and pathologically overlooked. Recognizing the often subtle findings and correlating them with the patients history or suggesting a thorough clinical investigation of potential exposures can be of help in identifying the underlying condition so that the patient can be appropriately managed.

A regional analysis of epidermal growth factor receptor ( EGFR ) mutated lung cancer for HSE South

BackgroundEGFR mutated lung cancer represents a subgroup with distinct clinical presentations, prognosis, and management requirements. We investigated the survival, prognostic factors, and real-world treatment of NSCLC patients with EGFR mutation in clinical practice.MethodsA retrospective review of all specimens sent for EGFR analysis from December 2009 to September 2015 was performed. Patient demographics, specimen type, EGFR mutation status/type, stage at diagnosis, treatment, response rate, and survival data were recorded.Results27/334 (8%) patient specimens sent for EGFR testing tested positive for a sensitising EGFR mutation. The median age was 65xa0years (40–85xa0years). Exon 19 deletion represented the most commonly detected alteration, accounting for 39% (nxa0=xa011). First-line treatment for those with Exon 18, 19, or 21 alterations (nxa0=xa024) was with an EGFR tyrosine kinase inhibitor (TKI) in 79% (nxa0=xa019). Objective response rate among these patients was 74% and median duration of response was 13xa0months (range 7–35xa0months).ConclusionThe incidence of EGFR mutation in our cohort of NSCLC is 9% which is consistent with mutation incidence reported in other countries. The rate of EGFR mutation in our population is slightly below that reported internationally, but treatment outcomes are consistent with published data. Real-world patient data have important contributions to make with regard to quality measurement, incorporating patient experience into guidelines and identifying safety signals.