Non-neoplastic respiratory fluid cytology including cell differential counts for interstitial lung disease.

Bronchioloalveolar lavage (BAL) is a non-invasive and well-tolerated procedure that plays a key role in the diagnosis of a variety of non-neoplastic pulmonary diseases, including acute respiratory failure, infection, diffuse parenchymal lung disease (DLPD), paediatric and occupational lung disease, and in the evaluation of the lung allograft. A variety of analytic techniques are commonly performed on BAL fluid, including cytology, cell differential count, microbiology and virology, as well as a number of additional techniques in specific circumstances.

Alveolar proteinosis with hypersensitivity pneumonitis: a new clinical phenotype.

BACKGROUND AND OBJECTIVE: The aim of the present study was to report the features of five patients with concurrent histopathological features of pulmonary alveolar proteinosis (PAP) and hypersensitivity pneumonitis (HP) and their high-resolution CT (HRCT) appearances. METHODS: Patients with histopathological features of both HP and PAP on surgical lung biopsy referred for tertiary review were retrospectively identified. The pathology and HRCT images were semi-quantitatively scored to evaluate the relative contribution to HP and PAP. RESULTS: Five patients had histopathological features of HP and PAP but had varied HRCT appearances. All had imaging features of PAP to a varying degree with two patients also showing characteristics of HP but three patients had ill-defined thickened interlobular septa, not typical of either disease. CONCLUSIONS: We describe the coexistence of PAP and HP in five patients and discuss possible linkages between these two distinct pathologies.

Baseline Results of the West London lung cancer screening pilot study - Impact of mobile scanners and dual risk model utilisation.

OBJECTIVES: The West London lung screening pilot aimed to identify early-stage lung cancer by targeting low-dose CT (LDCT) to high risk participants. Successful implementation of screening requires maximising participant uptake and identifying those at highest risk. As well as reporting pre-specified baseline screening metrics, additional objectives were to 1) compare participant uptake between a mobile and hospital-based CT scanner and 2) evaluate the impact on cancer detection using two lung cancer risk models. METHODS: From primary care records, ever-smokers aged 60-75 were invited to a lung health check at a hospital or mobile site. Participants with PLCOM2012 6-yr risk ≥1.51 % and/or LLPv2 5-yr risk ≥2.0 % were offered a LDCT. Lung cancer detection rate, stage, and recall rates are reported. Participant uptake was compared at both sites (chi-squared test). LDCT eligibility and cancer detection rate were compared between those recruited under each risk model. RESULTS: Of 8366 potential participants invited, 1047/5135 (20.4 %) invitees responded to an invitation to the hospital site, and 702/3231 (21.7 %) to the mobile site (p = 0.14). The median distance travelled to the hospital site was less than to the mobile site (3.3 km vs 6.4 km, p < 0.01). Of 1159 participants eligible for a scan, 451/1159 (38.9 %) had a LLPv2 ≥2.0 % only, 71/1159 (6.1 %) had a PLCOM2012 ≥1.5 % only; 637/1159 (55.0 %) met both risk thresholds. Recall rate was 15.9 %. Lung cancer was detected in 29/1145 (2.5 %) participants scanned (stage 1, 58.6 %); 5/29 participants with lung cancer did not meet a PLCOM2012 threshold of ≥1.51 %; all had a LLPv2 ≥2.0 %. CONCLUSION: Targeted screening is effective in detecting early-stage lung cancer. Similar levels of participant uptake at a mobile and fixed site scanner were demonstrated, indicating that uptake was driven by factors in addition to scanner location. The LLPv2 model was more permissive; recruitment with PLCOM2012 alone would have missed several cancers.

Early histological changes of pulmonary arterial hypertension disclosed by invasive cardiopulmonary exercise testing.

Early diagnosis of pulmonary artery hypertension (PAH) is diagnostically challenging given the extent of pulmonary vascular remodeling required to bring about clinical signs and symptoms. Exercise testing can be invaluable in this setting, as stressing the cardiopulmonary system may unmask early disease. This report describes a young patient with a positive family history of PAH in whom contemporaneous invasive cardiopulmonary exercise testing and surgical lung biopsy reveal the novel association between exercise pulmonary hypertension (ePH) and early histological changes of PAH. Exercise PH currently carries no pathological correlates which means the hemodynamic effects of early pulmonary vascular remodeling remain unknown. Following the recent proceedings from the World Symposium in Pulmonary Hypertension 2018, which broaden the hemodynamic definition of PAH, this report suggests an important association between ePH and early pulmonary vascular remodeling supporting a role for exercise hemodynamic evaluation in patients at increased familial risk of PAH.

Terminal diffuse alveolar damage in relation to interstitial pneumonias. An autopsy study.

Acute exacerbations of idiopathic pulmonary fibrosis/cryptogenic fibrosing alveolitis (IPF/CFA) are rare and typically terminal events, but their relationship to underlying patterns of idiopathic interstitial pneumonias is unknown. We reviewed autopsy material from patients who died of diffuse alveolar damage in the clinical setting of pulmonary fibrosis, both idiopathic and with background fibrosing alveolitis with connective tissue disorders (FA-CTDs), and compared them with cases of acute interstitial pneumonia. Of 15 patients with acute exacerbations of IPF/CFA (n = 12) or FA-CTD (n = 3), 12 had a background pattern of usual interstitial pneumonia and 3 had fibrotic nonspecific interstitial pneumonia. All cases of fibrotic nonspecific interstitial pneumonia were seen in association with FA-CTD. The cause of acute exacerbations is unknown, but our data suggest that toxic effects of oxygen and triggering infection are unlikely causes. In patients with CTDs, it remains uncertain whether the acute exacerbation is related to the fibrosis, the associated CTD, or a combination of these factors. Acute exacerbations of IPF/CFA may be a more common terminal event than previously thought.

Data set for reporting of lung carcinomas: recommendations from International Collaboration on Cancer Reporting.

CONTEXT: The International Collaboration on Cancer Reporting (ICCR) is a quadripartite alliance formed by the Royal College of Pathologists of Australasia, the Royal College of Pathologists of the United Kingdom, the College of American Pathologists, and the Canadian Partnership Against Cancer. The ICCR was formed with a view to reducing the global burden of cancer data set development and reduplication of effort by different international institutions that commission, publish, and maintain standardized cancer-reporting data sets. The resultant standardization of cancer reporting would be expected to benefit not only those countries directly involved in the collaboration but also others not in a position to develop their own data sets. OBJECTIVES: To develop an evidence-based reporting data set for each cancer site. DESIGN: A project to develop data sets for prostate, endometrium, and lung cancers and malignant melanoma was piloted by the quadripartite group. RESULTS: A set of required and recommended data elements and appropriate responses for each element were agreed upon for the reporting of lung cancer. CONCLUSIONS: This review describes the process of development of the lung cancer data set.

Late antibody-mediated rejection after heart transplantation following the development of de novo donor-specific human leukocyte antigen antibody.

BACKGROUND: Antibody-mediated rejection (AMR) is an important problem after heart transplantation. Most cases seem to occur in sensitized recipients with preformed donor-specific human leukocyte antigen antibody (DSA) early after transplantation. Few data exist on AMR in patients who form de novo DSA. We describe the clinical features and treatment outcome for late AMR secondary to de novo DSA. METHODS: This was a retrospective, observational cohort study. All heart transplant patients treated for symptomatic AMR secondary to de novo DSA between November 2005 and August 2011. RESULTS: Fifteen patients were treated for AMR giving an incidence of 3.1 cases per 1000 person years and a prevalence of 1.4%. All had evidence of heart failure on presentation and de novo DSA at diagnosis. There was a spectrum of histologic and immunohistochemical findings. Despite treatment with immunepheresis, intravenous immunoglobulin, and rituximab, and in some cases total lymph node irradiation (n=3) and bortezomib (n=2), clinical outcomes were poor. DSA antibody levels, measured using Labscreen single antigen kits, were reduced by a mean of 76% with a median of 77% and a range of 35% to 99%, but were not eliminated. Forty-six percent had persistent cardiac allograft dysfunction. Mean and median survival was 1.3 and 0.8 years after diagnosis of AMR. Only 40% were alive at the end of the study period. CONCLUSION: Late cardiac AMR caused by de novo DSA was an uncommon but serious problem. Despite treatment consistent with current best practice, 46% of patients developed persistent cardiac dysfunction and their medium-term survival was poor.

ALK translocation is associated with ALK immunoreactivity and extensive signet-ring morphology in primary lung adenocarcinoma.

BACKGROUND: ALK rearrangement is particularly observed in signet-ring sub-type adenocarcinoma. Since fluorescence in situ hybridization (FISH) is not suitable for mass screening, we aimed to characterize the predictive utility of tumour morphology and ALK immunoreactivity to identify ALK rearrangement, in a primary lung adenocarcinoma dataset enriched for signet-ring morphology, compared with that of other morphology. METHODS: 7 adenocarcinomas from diagnostic archives reported with signet-ring morphology were assessed and compared with 11 adenocarcinomas without signet-ring features over the same time period. Growth patterns were reviewed, ALK expression was assessed by standard immunohistochemistry using ALK1 clone and Envision detection (Dako), and ALK rearrangement was assessed by FISH (Abbott Molecular). Associations between groups and predictive utility of tumour morphology and ALK expression using FISH as gold standard were calculated. RESULTS: 2 excision lung biopsy cases with pure (100%) signet-ring morphology and solid patterns demonstrated diffuse moderate cytoplasmic ALK immunoreactivity (2+) and harboured ALK rearrangements (p=0.007), unlike 5 mixed-signet-ring and 11 non-signet-ring adenocarcinomas, which showed negative or 1+ immunoreactivity; and did not harbour ALK rearrangements (p>0.1). ALK expression was not associated with ALK copy number. 6 of 7 cases with signet ring morphology stained for TTF-1. Pure signet-ring morphology and moderate ALK expression were both associated with ALK rearranged tumours. CONCLUSION: ALK rearrangement is strongly associated with ALK immunoreactivity, and was seen only in tumours with pure signet-ring morphology and solid growth pattern. Tumour morphology, growth pattern and ALK immunoreactivity appear to be good indicators of ALK rearrangement, with TTF-1 positivity aiding in proving primary pulmonary origin.

Lymph nodes involved by multicentric Castleman disease among HIV-positive individuals are often involved by Kaposi sarcoma.

Multicentric Castleman disease (MCD), a lymphoproliferative disorder and Kaposi sarcoma (KS), a vascular tumor, both occur at a higher frequency among patients with human immunodeficiency virus (HIV) infection. Human herpes virus 8 (HHV8), with an ability to infect and persist in B-lymphoid cells and endothelial cells, is causally associated with both MCD and KS. The coexistence of these HHV8-associated diseases in the same tissue samples has hitherto not been investigated. In this report, we compile the histologic and immunohistochemical findings in 24 lymph node (LN) and 5 spleen samples from 26 patients documented to have HIV-associated MCD. In addition to MCD, 15 of 24 LN samples (63%) showed evidence of coexisting KS. The involvement by KS was typically "microscopic" and involved the LN capsule, trabeculae, or hilum. Examination of 5 spleens involved by MCD did not show any evidence of KS. These were compared with LN biopsies from HIV patients with neither granulomatous diseases, metastatic carcinomas nor lymphoproliferative disorders. Among 20 LN biopsies from 19 individuals without MCD, 5 LNs showed involvement by KS (25%); an association significantly lower than LNs with MCD (Pearson chi 2: 6.2, 2-sided significance: 0.013). Coexistence of MCD and KS in the same tissue sample is a common phenomenon and we hypothesise that the association is due to lytic HHV8 infection of B-lymphoid cells exposing susceptible endothelial cells at vulnerable subsites within the LNs to extremely high levels of HHV8 resulting in formation of KS tumorlets in MCD-LNs.

Diagnosis and management of male breast cancer.

BACKGROUND: Male breast cancer (MBC) is rare with an incidence of 1% of all breast cancers. The evidence about the treatment is derived from the data on the management of the female breast cancer because conduction of randomized, controlled trials is impossible due to the rarity of the disease. In this study, we review the special features, overall management, diagnosis, and treatment of patients with MBC managed under our care with a brief review of the current literature. METHODS: During the period 1998 to 2006, we managed 1103 new patients with breast cancer in St Mary's Hospital. Among these, 14 patients were men. We retrospectively reviewed the case notes, histology, and follow-up notes of all the newly diagnosed patients with MBC. RESULTS: In this series, 28.6% had only in situ disease. Moreover, in 78.6% there was an in situ component present. One patient was found to have a cancer on the microdochectomy specimen after an operation for single duct nipple discharge, and in a second patient the cancer was found in the gynecomastia operation specimen. All ten invasive tumors were estrogen receptor positive (ER +ve), whereas eight were progesterone receptor positive (PgR +ve). With a median follow-up of 35 months, there was one locoregional recurrence and one disease-associated death. CONCLUSIONS: In situ cancer may not be as rare as previously reported among patients with MBC. Increased patient awareness and early assessment by a specialist is a key to early diagnosis and improved outcomes.