Pradnya D. Patil

Development of Squamous Cell Carcinoma After Pulmonary Aspergillosis in the Native Lung of a Lung Transplant Recipient: A Case Report

Lung transplant recipients have a significant incidence of posttransplant lung nodules. Such nodules can occur from various etiologies, both in the lung allograft or in the native lung. They most commonly originate from infections, such as Pseudomonas or Aspergillus species, or from posttransplant lymphoproliferative disorder. Lung cancer is challenging to diagnose in a native lung, especially with an underlying fibrotic disease. We present a case of a 75-year-old woman who presented with classic clinical features of pulmonary aspergillosis in the native right lung with idiopathic pulmonary fibrosis 5 years after left-sided single-lung transplant. She required a right lower lobectomy and antifungal treatment with isavuconazonium sulfate and inhaled amphotericin. A persistent right upper lobe lung nodule was noted during surveillance imaging and was initially presumed to be recurrent Aspergillus infection; however, growth of the nodule and change in its characteristics prompted additional examination. A navigational bronchoscopic biopsy was positive for squamous cell carcinoma. Her options for stage IIIA squamous cell carcinoma were limited to chemotherapy with paclitaxel and carboplatin plus radiation. Although initial surveillance scans showed adequate tumor response, metastatic squamous cell carcinoma was found in the liver 6 months later. She was eventually transitioned to palliative care. This case highlights the importance of a high index of suspicion for examination of nodules in the native lung of lung transplant recipients, even in cases of a known diagnosis, owing to the high morbidity and mortality associated with primary lung cancer in this population.

Incidental extensive adenocarcinoma in lungs explanted from a transplant recipient with an idiopathic pulmonary fibrosis flare-up: A clinical dilemma

Patients under consideration for lung transplantation as treatment for end-stage lung diseases such as idiopathic pulmonary fibrosis (IPF) often have risk factors such as a history of smoking or concomitant emphysema, both of which can predispose the patient to lung cancer. In fact, IPF itself increases the risk of lung cancer development by 6.8% to 20%. Solid organ malignancy (non-skin) is an established contraindication for lung transplantation. We encountered a clinical dilemma in a patient who presented with an IPF flare-up and underwent urgent evaluation for lung transplantation. After transplant, the patients explanted lungs showed extensive adenocarcinoma in situ, with the foci of invasion and metastatic adenocarcinoma in N1-level lymph nodes, as well as usual interstitial pneumonia. Retrospectively, we saw no evidence to suggest malignancy in addition to the IPF flare-up. Clinical diagnostic dilemmas such as this emphasize the need for new noninvasive testing that would facilitate malignancy diagnosis in patients too sick to undergo invasive tissue biopsy for diagnosis. Careful pathological examination of explanted lungs in patients with IPF is critical, as it can majorly influence immunosuppressive regimens, surveillance imaging, and overall prognosis after lung transplant.

RaPtomics: Integrating radiomic and pathomic features for predicting recurrence in early stage lung cancer

Non-small cell lung cancer (NSCLC) is the leading cause of cancer related deaths worldwide. The treatment of choice for early stage NSCLC is surgical resection followed by adjuvant chemotherapy for high risk patients. Currently, the decision to offer chemotherapy is primarily dependent on several clinical and visual radiographic factors as there is a lack of a biomarker which can accurately stratify and predict disease risk in these patients. Computer extracted image features from CT scans (radiomic) and (pathomic) from H&E tissue slides have already shown promising results in predicting recurrence free survival (RFS) in lung cancer patients. This paper presents new radiology-pathology fusion approach (RaPtomics) to combine radiomic and pathomic features for predicting recurrence in early stage NSCLC. Radiomic textural features (Gabor, Haralick, Law, Laplace and CoLlAGe) from within and outside lung nodules on CT scans and intranuclear pathology features (Shape, Cell Cluster Graph and Global Graph Features) were extracted from digitized whole slide H&E tissue images on an initial discovery set of 50 patients. The top most predictive radiomic and pathomic features were then combined and in conjunction with machine learning algorithms were used to predict classifier. The performance of the RaPtomic classifier was evaluated on a training set from the Cleveland Clinic (n=50) and independently validated on images from the publicly available cancer genome atlas (TCGA) dataset (n=43). The RaPtomic prognostic model using Linear Discriminant Analysis (LDA) classifier, in conjunction with two radiomic and two pathomic shape features, significantly predicted 5-year recurrence free survival (RFS) (AUC 0.78; p<0.005) as compared to radiomic (AUC 0.74; p<0.01) and pathomic (AUC 0.67; p<0.05) features alone.

P3.16-10 Radiomic Features on CT are Prognostic of Recurrence as well as Predictive of Added Benefit of Adjuvant Chemotherapy in ES-NSCLC

P3.16-10 Radiomic Features on CTare Prognostic of Recurrence as well as Predictive of Added Benefit of Adjuvant Chemotherapy in ES-NSCLC P. Vaidya, K. Bera, P. Fu, S. Ganesan, A. Khunger, P. Patil, V. Velcheti, A. Madabhushi Biomedical Engineering, Case Western Reserve University, Cleveland, OH/US, Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH/US, Biostatistics, Case Western Reserve University, Cleveland, OH/US, Rutgers Cancer Institute, New Jersey/US, Oncology, Cleveland Clinic, Cleveland, OH/US, Cleveland Clinic, Cleveland, OH/US, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH/US

Biomarkers for immune-related toxicities of checkpoint inhibitors: current progress and the road ahead

ABSTRACT Introduction: Immune checkpoint pathways are key immune regulatory pathways that play a physiologic role in maintaining immune-homeostasis and are often co-opted by cancer cells to evade the host immune system. Recent developments in cancer immunotherapy, mainly drugs blocking the immune checkpoint pathways, have revolutionized the treatment paradigm for many solid tumors. A wide spectrum of immune-related adverse events (irAEs) have been described with the use of these agents which necessitate treatment with immunosuppression, lead to disruption of therapy and can on occasion be life-threatening. There are currently no clinically validated biomarkers to predict the risk of irAEs. Areas covered: In this review, the authors describe the current progress in identifying biomarkers for irAEs and potential future directions. Literature search was conducted using PubMed-MEDLINE, Embase and Scopus. In addition, abstracts from major conference proceedings were reviewed for relevant content. Expert commentary: The discovery of biomarkers for irAEs is currently in its infancy, however there are a lot of promising candidate biomarkers that are currently being investigated. Biomarkers that can identify patients at a higher risk of developing irAEs or lead to early detection of autoimmune toxicities are crucial to optimize patient selection for immune-oncology agents and to minimize toxicity with their use.

A 68-Year-Old Lung Transplant Recipient With Shortness of Breath, Weight Loss, and Abnormal Chest CT

n n Case Presentationn A 68-year-old man presented to our ED with shortness of breath, weakness, and a 25-lb unintentional weight loss. He had undergone bilateral lung transplantation (cytomegalovirus [CMV]: donor+, recipient+; Epstein-Barr virus: donor+; recipient+) for idiopathic pulmonary fibrosis (IPF) 18xa0months prior. His posttransplant course was fairly unremarkable until 1xa0month earlier, when he was admitted for breathlessness and weakness. CT of the chest during that admission revealed mild intralobular and interlobular septal thickening. A bronchoscopy with BAL and transbronchial biopsies did not show acute cellular rejection, but the BAL fluid was positive for coronavirus. His cortisol level was undetectable; he was diagnosed with adrenal insufficiency and fludrocortisone was initiated. He was taking prednisone, tacrolimus, and everolimus for immunosuppression and valganciclovir, itraconazole, and trimethoprim-sulfamethoxazole for antimicrobial prophylaxis. His 25-lb weight loss occurred over the span of just one month.n n

A 47-Year-Old Man With Fever, Dry Cough, and a Lung Mass After Redo Lung Transplantation

CASE PRESENTATIONnA 47-year-old man who was a redo double lung transplant recipient (cytomegalovirus [CMV] status: donor positive/recipient positive; Epstein-Barr virus status: donor positive/recipient positive) presented to the hospital with 1xa0week of generalized malaise, low-grade fevers, and dry cough. His redo lung transplantation was necessitated by bronchiolitis obliterans syndrome, and his previous lung transplantation 5 years earlier was for silicosis-related progressive massive fibrosis. He denied any difficulty breathing or chest pain. There was no history of GI or urinary symptoms, and the patient had no anorexia, weight loss, night sweats, sick contacts, or history of travel. He had a history of 1 earlier episode of CMV viremia that was treated with valganciclovir. His immunosuppressive regimen included tacrolimus, mycophenolate mofetil, and prednisone, and his infection prophylaxis included trimethoprim-sulfamethoxazole, itraconazole, and valganciclovir. Results of a chest radiograph 8xa0weeks earlier were normal.

Primary Nocardia Infection Causing a Fluorodeoxyglucose-Avid Right Renal Mass in a Redo Lung Transplant Recipient

Immunosuppression after lung transplantation may increase susceptibility to opportunistic infection and is associated with early and delayed deaths in lung transplant recipients. Factors that may predispose lung transplant recipients to opportunistic bacterial and fungal infections include prolonged corticosteroid use, renal impairment, treatment of acute rejection, and post-transplant diabetes mellitus. We present a unique case of a 63-year-old woman with diabetes mellitus who underwent redo lung transplantation. Three years after her right-sided single redo lung transplant, she presented with right-sided abdominal pain, nausea, and vomiting. Upon examination, computed tomography showed a 4.5 × 3.3u2009cm heterogeneous, enhancing right renal mass with a patent renal vein. Magnetic resonance imaging confirmed a T1/T2 hypointense, diffusion-restricting, right mid-renal mass that was fluorodeoxyglucose-avid on positron emission tomography. We initially suspected primary renal cell carcinoma. However, after a right nephrectomy, no evidence of neoplasia was observed; instead, a renal abscess containing filamentous bacteria was noted, raising suspicion for infection of the Nocardia species. Special stains confirmed a diagnosis of Nocardia renal abscess. Computed tomography of the chest and brain revealed no lesions consistent with infection. We initiated a long-term therapeutic regimen of anti-Nocardia therapy with imipenem and trimethoprim-sulfamethoxazole.

Pulmonary Artery Pseudoaneurysm: A Rare Cause of Fatal Massive Hemoptysis

Pulmonary artery pseudoaneurysm (PAPA), an uncommon complication of pyogenic bacterial and fungal infections and related septic emboli, is associated with high mortality. The pulmonary artery (PA) lacks an adventitial wall; therefore, repeated endovascular seeding of the PA with septic emboli creates saccular dilations that are more likely to rupture than systemic arterial aneurysms. The most common clinical presentation of PAPA is massive hemoptysis and resultant worsening hypoxemia. Computed tomography angiography is the preferred diagnostic modality for PAPA; typical imaging patterns include focal outpouchings of contrast adjacent to a branch of the PA following the same contrast density as the PA in all phases of the study. In mycotic PAPAs, multiple synchronous lesions are often seen in segmental and subsegmental PAs due to ongoing embolic phenomena. The recommended approach for a mycotic PAPA is prolonged antimicrobial therapy; for massive hemoptysis, endovascular treatment (e.g., coil embolization, stenting, or embolization of the feeding vessel) is preferred. PAPA resection and lobectomy are a last resort, generally reserved for patients with uncontrolled hemoptysis or pleural hemorrhage. We present a case of a 28-year-old woman with necrotizing pneumonia from intravenous drug use who ultimately died from massive hemoptysis and shock after a ruptured PAPA.

Coexistent Non–Small Cell Carcinoma and Small Cell Carcinoma in a Patient Presenting with Hyponatremia

Despite recent advances in screening methods, lung cancer remains the leading cause of cancer-related deaths worldwide. By the time lung cancer becomes symptomatic and patients seek treatment, it is often too advanced for curative measures. Low-dose computed tomography (CT) screening has been shown to reduce mortality in patients at high risk of lung cancer. We present a 66-year-old man with a 50-pack-year smoking history who had a right upper lobe (RUL) pulmonary nodule and left lower lobe (LLL) consolidation on a screening CT. He reported a weight loss of 45 pounds over 3 months, had recently been hospitalized for hyponatremia, and was notably cachectic. A CT of the chest showed a stable LLL mass-like consolidation and a 9 × 21u2009mm subsolid lesion in the RUL. Navigational bronchoscopy biopsy of the RUL lesion revealed squamous non–small cell lung cancer (NSCLC). Endobronchial ultrasound-guided transbronchial needle aspiration of the LLL lesion revealed small cell lung cancer (SCLC). The final diagnosis was a right-sided Stage I NSCLC (squamous) and a left-sided limited SCLC. The RUL NSCLC was treated with stereotactic radiation; the LLL SCLC was treated with concurrent chemotherapy and radiation. In patients with multiple lung nodules, a diagnosis of synchronous multiple primary lung cancers (MPLCs) is crucial, as inadvertent upstaging of patients with MPLC (to T3 and/or T4 tumors) can lead to erroneous staging, inaccurate prognosis, and improper treatment. Recent advances in the diagnosis of small pulmonary nodules via navigational bronchoscopy and management of these lesions dramatically affect a patients overall prognosis.