Liposarcoma of the pleural cavity.

Liposarcoma rarely occurs in the pleura or thoracic cavity, and few reports appear in the literature. We hypothesized that combining clinicopathologic, immunohistochemical, and fluorescence in situ hybridization methods would allow definite diagnoses. Using formalin-fixed, paraffin-embedded blocks, we examined 6 atypical lipomatous tumor/well-differentiated liposarcomas (ALT/WDLPS), 5 dedifferentiated liposarcomas (DDLPSs), 2 pleomorphic liposarcomas, and 1 myxoid liposarcoma (MLPS). We used the Kaplan-Meier method and the Wilcoxon test for survival analysis for prognostic factor evaluation. Histologically, ALT/WDLPS was composed of a relatively mature adipocytic proliferation, accompanied by some lipoblasts. DDLPS exhibited round-to-oval tumor cells with a high nucleus-to-cytoplasm ratio that had proliferated in nests, accompanied in case 10 by some giant cells but no fatty cells. The pleomorphic type contained a varying proportion of pleomorphic lipoblasts. MLPS displayed uniform round- to oval-shaped cells and small signet-ring lipoblasts in a myxoid stroma. Immunohistochemically, 11 (79%), 11 (79%), and 10 (71%) of 14 cases were positive for S-100, p16, and CDK4, respectively. Six of the 14 cases (43%) were positive for MDM2 and adipophilin. One case of ALT/WDLPS and 3 cases of DDLPS exhibited MDM2 amplification by fluorescence in situ hybridization (Vysis LSI MDM2 SpectrumGreen Probe plus Vysis CEP 12 SpectrumOrange probe). ALT/WDLPS was the most favorable type for survival, while adipophilin tended to be a negative prognostic factor for pleural liposarcoma. For a firm diagnosis of liposarcoma in the pleura, immunohistochemistry for CDK4, MDM2, and adipophilin together with MDM2 gene amplification by fluorescence in situ hybridization may be an important diagnostic tool.

From the archives of MD Anderson Cancer Center: Primary effusion lymphoma with simultaneous involvement of the retroperitoneum and pleural cavity.

Primary effusion lymphoma (PEL) is a rare neoplasm that arises in the context of severe immunosuppression. Acquired immunodeficiency syndrome (AIDS) as a result of human immunodeficiency virus (HIV) infection is the most common cause of immunodeficiency in patients who develop PEL. These neoplasms usually involve one or more body cavities, so-called classic PEL. The pleural cavity is most often involved, followed by the peritoneal and pericardial cavities. Involvement of the cerebrospinal fluid (CSF) and meninges is rare. A subset of patients can present with a tissue-based mass, known as the extracavitary variant. We encountered a patient with HIV infection and severe immunosuppression who presented initially with mediastinal, retroperitoneal mass and bilateral pleural effusions. He subsequently developed CSF involvement. Despite therapy, the patient relapsed with chest wall disease 6 months later and died shortly thereafter. Our literature review yielded about 400 cases of PEL reported previously. About 65 % of PEL patients have had AIDS, but a subset of patients had immunosuppression attributable to organ transplantation or physiological immunosenescence. CSF involvement has been reported in ~2 % of patients, and about 10 % of patients had both body cavity and extracavitary disease. The pathologic findings in this case were typical of extracavitary PEL. The neoplastic cells had features of plasmablasts and were positive for HHV-8, Epstein-Barr virus encoded RNA (EBER) and plasma cell associated markers, and were negative for B-cell antigens. The prognosis of patients with PEL is usually poor with a median survival less than one year in most studies. We use this patient's case as an illustration of PEL and we review the clinicopathologic findings and differential diagnosis of PEL.

Intrapleural nano-immunotherapy promotes innate and adaptive immune responses to enhance anti-PD-L1 therapy for malignant pleural effusion.

Malignant pleural effusion (MPE) is indicative of terminal malignancy with a uniformly fatal prognosis. Often, two distinct compartments of tumour microenvironment, the effusion and disseminated pleural tumours, co-exist in the pleural cavity, presenting a major challenge for therapeutic interventions and drug delivery. Clinical evidence suggests that MPE comprises abundant tumour-associated myeloid cells with the tumour-promoting phenotype, impairing antitumour immunity. Here we developed a liposomal nanoparticle loaded with cyclic dinucleotide (LNP-CDN) for targeted activation of stimulators of interferon genes signalling in macrophages and dendritic cells and showed that, on intrapleural administration, they induce drastic changes in the transcriptional landscape in MPE, mitigating the immune cold MPE in both effusion and pleural tumours. Moreover, combination immunotherapy with blockade of programmed death ligand 1 potently reduced MPE volume and inhibited tumour growth not only in the pleural cavity but also in the lung parenchyma, conferring significantly prolonged survival of MPE-bearing mice. Furthermore, the LNP-CDN-induced immunological effects were also observed with clinical MPE samples, suggesting the potential of intrapleural LNP-CDN for clinical MPE immunotherapy.

Thigh mass in a patient with malignant pleural mesothelioma: Metastasis at an unusual site.

Soft tissue tumors are a highly heterogeneous group of lesions with varied clinical presentation. The majority is primary tumors and metastatic tumors are very rare. Malignant pleural mesothelioma presenting as a soft tissue mass at a distant site is even rarer and can cause diagnostic challenges both clinically and pathologically. We report a case of malignant pleural mesothelioma presenting as a soft tissue mass in the left thigh. A 59-year-old man, non-smoker, working in a cement factory since 30 years presented with complains of difficulty in walking since 1½ months. Review of his previous medical records revealed malignant pleural mesothelioma, which was diagnosed 9 months before. He had denied chemotherapy and was on Ayurvedic medication. The lesion involved the adjacent intercostal muscles. Few enlarged lymph nodes were noted in mediastinal and cervical regions. Biopsy of left supraclavicular and right cervical lymph nodes showed metastases. Metastasis from malignant pleural mesothelioma to the thigh was confirmed by immunohistochemistry. The tumor was positive for CK5/6, CK7, Calretinin and vimentin and immunonegative for CEA, Napsin A and TTF 1.

A rare case of chest wall lipoma growing into the pleural cavity: a case report.

BACKGROUND: Several cases of lipoma in unusual locations in the thorax have been reported. Appropriate surgical treatment depending on the location and shape is often required. CASE PRESENTATION: We herein report an extremely rare case of a chest wall lipoma growing into the pleural cavity. The tumor was successfully removed without damaging the capsule by a combination of direct and thoracoscopic approaches. CONCLUSIONS: Chest wall lipomas growing into pleural cavity can be successfully treated by a combination of direct and thoracoscopic approaches.

Machine learning applied to near-infrared spectra for clinical pleural effusion classification.

Lung cancer patients with malignant pleural effusions (MPE) have a particular poor prognosis. It is crucial to distinguish MPE from benign pleural effusion (BPE). The present study aims to develop a rapid, convenient and economical diagnostic method based on FTIR near-infrared spectroscopy (NIRS) combined with machine learning strategy for clinical pleural effusion classification. NIRS spectra were recorded for 47 MPE samples and 35 BPE samples. The sample data were randomly divided into train set (n = 62) and test set (n = 20). Partial least squares, random forest, support vector machine (SVM), and gradient boosting machine models were trained, and subsequent predictive performance were predicted on the test set. Besides the whole spectra used in modeling, selected features using SVM recursive feature elimination algorithm were also investigated in modeling. Among those models, NIRS combined with SVM showed the best predictive performance (accuracy: 1.0, kappa: 1.0, and AUCROC: 1.0). SVM with the top 50 feature wavenumbers also displayed a high predictive performance (accuracy: 0.95, kappa: 0.89, AUCROC: 0.99). Our study revealed that the combination of NIRS and machine learning is an innovative, rapid, and convenient method for clinical pleural effusion classification, and worth further evaluation.

Deep learning to detect acute respiratory distress syndrome on chest radiographs: a retrospective study with external validation.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a common, but under-recognised, critical illness syndrome associated with high mortality. An important factor in its under-recognition is the variability in chest radiograph interpretation for ARDS. We sought to train a deep convolutional neural network (CNN) to detect ARDS findings on chest radiographs. METHODS: CNNs were pretrained on 595 506 radiographs from two centres to identify common chest findings (eg, opacity and effusion), and then trained on 8072 radiographs annotated for ARDS by multiple physicians using various transfer learning approaches. The best performing CNN was tested on chest radiographs in an internal and external cohort, including a subset reviewed by six physicians, including a chest radiologist and physicians trained in intensive care medicine. Chest radiograph data were acquired from four US hospitals. FINDINGS: In an internal test set of 1560 chest radiographs from 455 patients with acute hypoxaemic respiratory failure, a CNN could detect ARDS with an area under the receiver operator characteristics curve (AUROC) of 0·92 (95% CI 0·89-0·94). In the subgroup of 413 images reviewed by at least six physicians, its AUROC was 0·93 (95% CI 0·88-0·96), sensitivity 83·0% (95% CI 74·0-91·1), and specificity 88·3% (95% CI 83·1-92·8). Among images with zero of six ARDS annotations (n=155), the median CNN probability was 11%, with six (4%) assigned a probability above 50%. Among images with six of six ARDS annotations (n=27), the median CNN probability was 91%, with two (7%) assigned a probability below 50%. In an external cohort of 958 chest radiographs from 431 patients with sepsis, the AUROC was 0·88 (95% CI 0·85-0·91). When radiographs annotated as equivocal were excluded, the AUROC was 0·93 (0·92-0·95). INTERPRETATION: A CNN can be trained to achieve expert physician-level performance in ARDS detection on chest radiographs. Further research is needed to evaluate the use of these algorithms to support real-time identification of ARDS patients to ensure fidelity with evidence-based care or to support ongoing ARDS research. FUNDING: National Institutes of Health, Department of Defense, and Department of Veterans Affairs.

Novel therapies for malignant pleural effusion: Anti­angiogenic therapy and immunotherapy (Review).

Patients with a variety of malignancies can develop malignant pleural effusion (MPE). MPE can cause significant symptoms and result in a marked decrease in quality of life and a poor prognosis. MPE is primarily considered as an immune and vascular manifestation of pleural metastases. In the present review, the existing evidence supporting the applicability of anti­angiogenic therapy and immunotherapy for the treatment of MPE was summarized. Patients with MPE have benefited from anti­angiogenic agents, including bevacizumab and endostar; however, no relevant prospective phase III trial has, thus far, specifically analyzed the benefit of anti­angiogenic therapy in MPE. Immunotherapy for MPE may be sufficient to turn a dire clinical situation into a therapeutic advantage. Similar to anti­angiogenic therapy, more clinical data on the efficiency and safety of immunotherapy for controlling MPE are urgently required. The combined use of anti­angiogenic therapy and immunotherapy may be a promising strategy for MPE, which requires to be further understood.

Adenoid cystic carcinoma of the labium oris with rare metastasis to the pleural cavity.

A 57-year-old Southeast Asian woman with a remote history of adenoid cystic carcinoma (ACC) of the right labium superius oris (upper lip) presented to the hospital with vague epigastric pain. On workup, she was found to have multiple pleural nodules. Histopathology confirmed the diagnosis of metastatic ACC. After 8 months of active surveillance, evidence of disease progression was found and the patient was started on pembrolizumab. Follow-up after starting pembrolizumab showed stable disease with no significant side effects.

Performance of Xpert® MTB/RIF in diagnosing tuberculous pleuritis using thoracoscopic pleural biopsy.

BACKGROUND: Etiological diagnosis of tuberculous pleuritis is challenging, owing to a paucity of Mycobacterium tuberculosis (MTB) in the affected region. Moreover, currently available methods, such as the detection of acid-fast bacilli and microbiological culture, are not always conducive to timely diagnosis and treatment. In this study, we evaluated the performance of Xpert® MTB/RIF assay (hereinafter referred to as "Xpert") in detecting MTB in difficult-to-diagnose patients using suspensions of pleural biopsy tissue specimens obtained under direct thoracoscopic guidance. METHODS: One hundred and sixty patients with an unexplained pleural effusion were included from the Shenyang Tenth People's Hospital and Shenyang Chest Hospital, China, between 2017 and 2018. The included patients underwent thoracoscopy under local anesthesia, with an intercostal incision of approximately 1.0 cm for biopsy. The biopsy specimens were used for pathological and etiological examinations. The Xpert test was evaluated for its sensitivity and specificity, as well as positive and negative predictive values (PPV and NPV, respectively), against data obtained using standards: the BACTEC™ MGIT™ 960 liquid culture system and a composite reference standard (CRS). RESULTS: The sensitivity and specificity of Xpert were 68.8 and 64.6%, respectively, against the MGIT 960 culture data. The PPV and NPV of Xpert were 56.4 and 75.6%, respectively. The sensitivity of Xpert was 69.0% against the CRS data, which was significantly higher than that of MGIT 960 culture (56.6%). The PPV and NPV of Xpert against the CRS data were 100.0 and 57.3%, respectively. CONCLUSIONS: Xpert is a good rule-in test but has limited value as a rule-out test for the diagnosis of tuberculosis pleuritis.

Microfilaria-dependent thoracic pathology associated with eosinophilic and fibrotic polyps in filaria-infected rodents.

BACKGROUND: Pulmonary manifestations are regularly reported in both human and animal filariasis. In human filariasis, the main known lung manifestations are the tropical pulmonary eosinophilia syndrome. Its duration and severity are correlated with the presence of microfilariae. Litomosoides sigmodontis is a filarial parasite residing in the pleural cavity of rodents. This model is widely used to understand the immune mechanisms that are established during infection and for the screening of therapeutic molecules. Some pulmonary manifestations during the patent phase of infection with L. sigmodontis have been described in different rodent hosts more or less permissive to infection. METHODS: Here, the permissive Mongolian gerbil (Meriones unguiculatus) was infected with L. sigmodontis. Prevalence and density of microfilariae and adult parasites were evaluated. Lungs were analyzed for pathological signatures using immunohistochemistry and 3D imaging techniques (two-photon and light sheet microscopy). RESULTS: Microfilaremia in gerbils was correlated with parasite load, as amicrofilaremic individuals had fewer parasites in their pleural cavities. Fibrotic polypoid structures were observed on both pleurae of infected gerbils. Polyps were of variable size and developed from the visceral mesothelium over the entire pleura. The larger polyps were vascularized and strongly infiltrated by immune cells such as eosinophils, macrophages or lymphocytes. The formation of these structures was induced by the presence of adult filariae since small and rare polyps were observed before patency, but they were exacerbated by the presence of gravid females and microfilariae. CONCLUSIONS: Altogether, these data emphasize the role of host-specific factors in the pathogenesis of filarial infections.

Video-assisted thoracic surgery in the primary management of advanced ovarian carcinoma with moderate to large pleural effusions: A Memorial Sloan Kettering Cancer Center Team Ovary Study.

OBJECTIVES: We assessed the utility of video-assisted thoracic surgery (VATS) in defining extent of intrathoracic disease in advanced ovarian carcinoma with moderate-to-large pleural effusions. METHODS: Beginning in 2001, VATS was performed on all patients with suspected advanced ovarian carcinoma and moderate-to-large pleural effusions, evaluating for macroscopic intrathoracic disease. The algorithm recommended primary debulking surgery (PDS) for ≤1 cm, neoadjuvant chemotherapy (NACT)/interval debulking surgery (IDS) for >1 cm intrathoracic disease. We reviewed records of patients undergoing VATS from 10/01-01/19. Differences between treatment groups were tested using standard statistical techniques. RESULTS: One-hundred patients met eligibility criteria (median age, 60; median CA-125 level, 1158 U/mL; medium serum albumin, 3.8 g/dL). Macroscopic pleural disease was found in 70 (70%). After VATS, 50 (50%) underwent attempted PDS (PDS group), 50 (50%) received NACT (NACT/IDS group). Forty-seven (94%) underwent IDS. Median overall survival (OS) for the entire cohort (n = 100) was 44.5 months (95% CI: 37.8-51.7). The PDS group had significantly longer survival than the NACT/IDS group [45.8 (95% CI: 40.5-87.8) vs. 37.4 months (95% CI: 33.3-45.2); p = .016]. On multivariable analysis, macroscopic intrathoracic disease (HR 2.18, 95% CI: 1.14-4.18; p = .019) and age ≥ 65 (HR 1.98, 95% CI: 1.16-3.40; p = .013) were independently associated with elevated death risk. Patients with the best outcome had no macroscopic disease at VATS and underwent PDS (median OS, 87.8 months). CONCLUSIONS: VATS is useful in therapeutic decision-making for PDS vs. NACT/IDS in advanced ovarian cancer with moderate-to-large pleural effusions.

Application of flow cytometry in the analysis of lymphoid disease in the lung and pleural space.

Various types of lymphoid neoplasms can occur in the lung. Lung parenchyma, the pleura or the pleural cavity can be the primary site of a lymphoid neoplasm or can be involved secondarily as a result of systemic dissemination from a separate primary site. Recognition of pulmonary lymphoid neoplasms (PLN) has increased secondary to technological advances in the medical field. Multiparameter flow cytometry (FC) is a one of the diagnostic tools that serves an essential role in the detecting and categorizing PLNs. FC allows for rapid identification and immunophenotypic characterization of PLN. In this article, we discuss the role of FC in the diagnosis of the most commonly encountered PLNs as well as their basic clinicopathologic features. We briefly discuss the role of FC in identifying non-hematolymphoid neoplasms in lung specimens as well.

Effect of puncture sites on pneumothorax after lung CT-guided biopsy.

To determine the influence of puncture site on aspiration in dealing with pneumothorax following CT-guided lung biopsy.Two hundred thirty-six pneumothorax patients after CT guided lung biopsies were retrospective analyzed from January 2013 to December 2018. Patients with minor asymptomatic pneumothorax were treated conservatively with monitoring of vital signs and follow-up CT to confirm stability. Ninety of the 236 pneumothorax patients, who underwent manual aspiration, were included in this analysis. In first manual aspiration, the needle from the lesion was retracted back into the pleural space after biopsy, and then aspiration treatment was performed. If the treatment is of unsatisfied result, a second attempt aspiration treatment, which puncture site away from initial biopsy one, was conducted. The efficacy of simple manual aspiration and the new method, changing puncture site for re-aspiration was observed.Immediate success was obtained in 62 out of the 90 patients in the first attempt. The effective rate and failure rate were 68.9% (62/90) and 31.1% (28/90), respectively. Twenty-eight patients in whom first attempt simple aspiration were unsuccessful underwent a second attempt aspiration, which puncture site away from initial biopsy one, was successful in 13 patients with 15 patients undergoing chest tube placement. The effective rate and failure rate were 46.4% (13/28) and 53.6% (15/28), respectively. Applying the modified procedure, total effective rate of aspiration elevated significantly from 68.9% (62/90) to 83.3% (75/90) (P < .05). No serious side effects were detected in the period of aspiration procedure.Manual aspiration with puncture site away from initial biopsy one is worth trying to deal with post-biopsy pneumothorax. This modified procedure improved the efficiency of treatment significantly, and reduced the rate of pneumothorax requiring chest tube placement.

Thoracoscopic surgery under local anesthesia for high-risk intractable secondary spontaneous pneumothorax.

OBJECTIVES: To evaluate the outcomes of thoracoscopic surgery for intractable secondary spontaneous pneumothorax (SSP) under local anesthesia in high-risk patients and report intraoperative findings useful for identifying air leakage points. METHODS: We analyzed outcomes of 14 consecutive thoracoscopic operations under local anesthesia for high-risk SSP from 2015 to 2019. Suspicious lesions were determined based on intraoperative direct or indirect detections. Direct detection involved identifying pleural fistulas or air bubbles. Indirect detection involved finding thin and transparent bullae without any other suspicious lesions. Identifications of culprit lesions were confirmed by arrest or significant decrease in air leakage after surgical repair. All surgical repairs were followed by immediate single pleurodesis for a definitive cure and prevention of recurrence. Success was defined as the removal of the thoracic tube by surgical repair combined with immediate postoperative single pleurodesis. RESULTS: The main underlying pulmonary diseases were emphysema (n = 7), carcinoma (n = 3), interstitial pneumonia (IP) (n = 3), and nontuberculous mycobacterial infection (n = 1). A leakage point was identified in 13 cases (six on direct and seven on indirect detections). Success was achieved in nine cases (four on direct and five on indirect detections). Adverse events included one case of acute exacerbation of IP and one case of carbon dioxide narcosis. CONCLUSION: Thoracoscopic surgery under local anesthesia can be the worthwhile definitive modality, among few remaining treatments, for highly fragile patients with SSP. Detecting air leakage directly and the presence of thin and transparent bullae without any other suspicious lesions can be clues for identifying culprit lesions.

Real-Time Detection of Hemothorax and Monitoring its Progression in a Piglet Model by Electrical Impedance Tomography: A Feasibility Study.

Hemothorax is a serious medical condition that can be life-threatening if left untreated. Early diagnosis and timely treatment are of great importance to produce favorable outcome. Although currently available diagnostic techniques, e.g., chest radiography, ultrasonography, and CT, can accurately detect hemothorax, delayed hemothorax cannot be identified early because these examinations are often performed on patients until noticeable symptoms manifest. Therefore, for early detection of delayed hemothorax, real-time monitoring by means of a portable and noninvasive imaging technique is needed. In this study, we employed electrical impedance tomography (EIT) to detect the onset of hemothorax in real time on eight piglet hemothorax models. The models were established by injection of 60 ml fresh autologous blood into the pleural cavity, and the subsequent development of hemothorax was monitored continuously. The results showed that EIT was able to sensitively detect hemothorax as small as 10 ml in volume, as well as its location. Also, the development of hemothorax over a range of 10 ml up to 60 ml was well monitored in real time, with a favorable linear relationship between the impedance change in EIT images and the volume of blood injected. These findings demonstrated that EIT has a unique potential for early diagnosis and continuous monitoring of hemothorax in clinical practice, providing medical staff valuable information for prompt identification and treatment of delayed hemothorax.

Alveolar rhabdomyosarcomas involving serous cavity fluid specimens exhibit diverse cytomorphologies: A case report and review of the literature.

Involvement of serous cavity specimens by alveolar rhabdomyosarcoma (ARMS) is a rare event and only a few case reports have been reported in the literature, with conflicting cytomorphologic patterns. Herein, we report on a 41-year-old man with no significant past medical history who presented with pancytopenia and shortness of breath and was found to have widely metastatic sinonasal alveolar rhabdomyosarcoma, including involvement of the pleura. The pleural fluid specimen was cellular and contained ARMS cells in small-to-medium sized three-dimensional fragments that resembled an adenocarcinoma or mesothelioma, and numerous single cells were seen in the background. The individual tumor cells demonstrated variable morphology; all were large, with varying degree of cytoplasm, and multinucleated cells were commonly seen in the background. The cells were negative for calretinin and claudin-4 and were positive for myogenin, confirming the diagnosis. Given the cytomorphologic diversity of ARMS seen in serous fluid specimens, patient history and the use of confirmatory immunostains are essential.

Usefulness of methylthioadenosine phosphorylase and BRCA-associated protein 1 immunohistochemistry in the diagnosis of malignant mesothelioma in effusion cytology specimens.

BACKGROUND: The separation of benign from malignant mesothelial proliferations on effusion cytology can be difficult. Loss of methylthioadenosine phosphorylase (MTAP) by immunohistochemistry is an established marker of malignancy in mesothelial proliferations, but to the authors' knowledge largely has been applied only to biopsies. The current study was conducted to determine the usefulness of MTAP immunohistochemistry in the diagnosis of malignant mesothelioma in effusion cytology specimens. METHODS: A total of 21 effusion cytology cases of malignant mesothelioma were stained for MTAP and BRCA-associated protein 1 (BAP1), with 15 reactive mesothelial cytology cases used as a control. Fourteen cases had a paired surgical specimen for comparison, and 7 cases were run for CDKN2A deletion by fluorescence in situ hybridization. RESULTS: Complete loss of MTAP cytoplasmic staining was noted in 7 of 21 effusion samples (33%), and no loss was observed in 11 effusion samples (52%); 11 of these cases had a matching surgical specimen and all 11 specimens demonstrated the same MTAP pattern. Partial loss was observed in 3 effusion specimens (80%, 40%, and 40% intact staining, respectively), but in all 3 the surgical specimen demonstrated 100% staining. None of the 15 reactive mesothelial cytology specimens demonstrated MTAP cytoplasmic loss. CDKN2A FISH demonstrated concordance in 5 of 7 cases (71%). MTAP immunohistochemistry had a sensitivity of 33% and a specificity of 100% for this differential diagnosis. CONCLUSIONS: MTAP staining demonstrated generally good concordance between the cytologic and surgical specimens and appears to be useful in the diagnosis of mesothelioma on effusion specimens. Complete loss of MTAP is a reliable marker of malignancy, but the significance of partial loss of MTAP staining is unclear.