Diagnostic Approach to Pulmonary B-Cell Lymphomas in Small Biopsies, with Practical Recommendations to Avoid Misinterpretation.

Pulmonary lymphomas are rare. With the current less invasive approaches used to obtain material for diagnosis, the diagnosis of pulmonary lymphoma is now frequently established in a small biopsy rather than in a resection. Therefore, the diagnosis has become more challenging and requires correlation with the clinico-radiologic presentation and with ancillary studies (immunohistochemistry, flow cytometry, cytogenetics, and/or molecular analysis). Due to the rarity of pulmonary lymphomas, clinical suspicion of a lymphomatous process is low at initial presentation, and material may be only submitted for histopathology. For this reason, herein, we provide recommendations to arrive at the correct diagnosis of the most common lung B-cell lymphomas (marginal zone lymphoma of mucosa-associated lymphoid tissue, diffuse large B-cell lymphoma, intravascular large B-cell lymphoma, lymphomatoid granulomatosis) in the setting of small biopsies, utilizing only immunohistochemistry. The differential diagnosis varies according to the lymphoma subtype and includes reactive conditions, solid tumors, and other hematolymphoid malignancies. Although morphology and immunohistochemistry may be sufficient to establish a diagnosis, in some cases, the best recommendation is to obtain additional tissue via a VATS biopsy/wedge resection with material submitted for flow cytometry, cytogenetics, and/or molecular studies to be able to properly classify a pulmonary lymphoid process.

Case Report: Nontuberculous mycobacterial infections in children with complete DiGeorge anomaly.

Children with complete DiGeorge anomaly (cDGA) have congenital athymia, resulting in severe T cell immunodeficiency and susceptibility to a broad range of infections. We report the clinical course, immunologic phenotypes, treatment, and outcomes of three cases of disseminated nontuberculous mycobacterial infections (NTM) in patients with cDGA who underwent cultured thymus tissue implantation (CTTI). Two patients were diagnosed with Mycobacterium avium complex (MAC) and one patient with Mycobacterium kansasii. All three patients required protracted therapy with multiple antimycobacterial agents. One patient, who was treated with steroids due to concern for immune reconstitution inflammatory syndrome (IRIS), died due to MAC infection. Two patients have completed therapy and are alive and well. T cell counts and cultured thymus tissue biopsies demonstrated good thymic function and thymopoiesis despite NTM infection. Based on our experience with these three patients, we recommend that providers strongly consider macrolide prophylaxis upon diagnosis of cDGA. We obtain mycobacterial blood cultures when cDGA patients have fevers without a localizing source. In cDGA patients with disseminated NTM, treatment should consist of at least two antimycobacterial medications and be provided in close consultation with an infectious diseases subspecialist. Therapy should be continued until T cell reconstitution is achieved.

T Cell Repertoire Maturation Induced by Persistent and Latent Viral Infection Is Insufficient to Induce Costimulation Blockade Resistant Organ Allograft Rejection in Mice.

CD28:CD80/86 pathway costimulation blockade (CoB) with the CD80/86-specific fusion protein CTLA4-Ig prevents T cell-mediated allograft rejection in mice. However, in humans, transplantation with CoB has been hampered by CoB-resistant rejection (CoBRR). CoBRR has been attributed in part to pathogen-driven T cell repertoire maturation and resultant heterologous alloreactive memory. This has been demonstrated experimentally in mice. However, prior murine models have used viral pathogens, CoB regimens, graft types, and/or antigen systems atypically encountered clinically. We therefore sought to explore whether CoBRR would emerge in a model of virus-induced memory differentiation designed to more closely mimic clinical conditions. Specifically, we examined mouse homologs of clinically prevalent viruses including murine polyomavirus, cytomegalovirus, and gammaherpesvirus 68 in the presence of clinically relevant maintenance CoB regimens using a fully MHC-mismatched, vascularized allograft model. Infected mice developed a significant, sustained increase in effector memory T cells consistent with that seen in humans, but neither developed heterologous alloreactivity nor rejected primarily vascularized heterotopic heart transplants at an increased rate compared with uninfected mice. These results indicate that memory acquisition alone is insufficient to provoke CoBRR and suggest that knowledge of prior latent or persistent viral infection may have limited utility in anticipating heterologous CoB-resistant alloimmunity.

Elevated Cardiac Troponin I in Preservation Solution Is Associated With Primary Graft Dysfunction.

BACKGROUND: Although primary graft dysfunction (PGD) is a leading cause of mortality and morbidity early post-heart transplant, relatively little is known regarding mechanisms involved in PGD development. METHODS AND RESULTS: We examined the relationship between cardiac troponin I (cTnI) concentrations in the preservation solution from 43 heart transplant procedures and the development of PGD. Donor hearts were flushed with cold preservation solution (University of Wisconsin [UW] or Custodiol) and stored in the same solution. cTnI concentrations were measured utilizing the i-STAT System and normalized to left ventricular mass. Recipient medical records were reviewed to determine PGD according to the 2014 ISHLT consensus conference. Nineteen patients developed PGD following cardiac transplantation. For both UW and Custodiol, normalized cTnI levels were significantly increased (P = .031 and .034, respectively) for those cases that developed PGD versus no PGD. cTnI levels correlated with duration of ischemic time in the UW group, but not for the Custodiol group. Donor age and donor cTnI (obtained prior to organ procurement) did not correlate with preservation cTnI levels in either UW or Custodiol. CONCLUSIONS: Increased preservation solution cTnI is associated with the development of PGD suggesting preservation injury may be a dominant mechanism for the development of PGD.

Repair of Bicuspid Aortic Valve Syndrome with Anomalous Right Coronary Artery in Osteogenesis Imperfecta.

Osteogenesis imperfecta (OI) is an inherited connective tissue disorder caused by the defective synthesis of type I collagen. The clinical phenotype is dominated by bone fragility, but cardiovascular tissue involvement has also been reported. Here, the case is described of a 37-year-old man with OI who presented with aortic insufficiency, bicuspid aortic valve, dilated aortic root, and anomalous right coronary artery. The patient was treated successfully with a mechanical valved conduit aortic root replacement and anomalous coronary artery unroofing and reimplantation. This case highlights the feasibility of complex surgical repairs in this population, as well as challenges surrounding the choice of valve prosthesis given the congenital bone fragility and predilection for fractures.

Surgical treatment of a cavernous haemangioma of the heart.

Cardiac haemangioma is an extremely rare, benign vascular tumour. A 42-year-old female patient who was previously very active presented with complaints of exertional chest pain as well as lower extremity oedema. Computed tomography and magnetic resonance imaging showed a large mass in the anterior mediastinum originating from the right atrioventricular groove and abutting the superior vena cava, right atrium, right ventricular outflow tract and aortic root. Open biopsy via right mini-thoracotomy revealed cavernous haemangioma. After the biopsy, the patient was treated with three doses of bevacizumab but symptoms worsened and the mass did not regress. Therefore, the patient underwent median sternotomy and resection of the large tumour that encroached upon the right coronary artery. Final histopathological examination revealed cavernous haemangioma. The patient made an uneventful recovery.

Myocardial scar in sarcoidosis by 12-lead ECG and pathology.

This case demonstrates the use of QRS scoring to quantify myocardial scar in a patient with cardiac sarcoidosis and left bundle branch block who progressively received an implantable defibrillator, cardiac resynchronization therapy (CRT), left ventricular assist device and cardiac transplantation. QRS scoring has been shown to correlate with magnetic resonance imaging measurements of scar, identify arrhythmogenic substrate and predict response to CRT, but had not previously been compared to pathology-documented scar in nonischemic cardiomyopathies. Further study is warranted to assess the ability of QRS scoring to guide therapy for individual patients.

Reproducibility of left atrial ablation with high-intensity focused ultrasound energy in a calf model.

OBJECTIVE: Achieving transmural tissue ablation might be necessary for successful treatment of atrial fibrillation. The purpose of this study was to evaluate the reproducibility of transmural left atrial ablation using a high-intensity focused ultrasound energy system in a calf model. METHODS: Nine heparinized bovines underwent a beating-heart left atrial ablation with a single application of the high-intensity focused ultrasound device. All animals were acutely killed, and the left atrium was fixed in formalin. Protocolized histological sections (5 µm) were obtained throughout each lesion and prepared with Masson trichrome and hematoxylin and eosin staining. Measurements were performed on a total of 359 slides from the 9 lesions. In addition, fresh left atrial tissues from 18 unused human donor hearts that did not meet the criteria for cardiac transplantation were measured at the site where the high-intensity focused ultrasound device is normally applied. RESULTS: Calf left atrial thickness ranged between 2.5 and 20.1 mm, with a mean of 9.10 mm. High-intensity focused ultrasound ablation consistently produced a 100% transmural lesion in left atrial thickness up to 6 mm. In addition, a transmural lesion was observed in 91% of tissues that were up to 10 mm thick and in 85% that were up to 15 mm thick. Human left atrial thickness ranged between 1.2 to 6 mm, with a mean of 3.7 mm. CONCLUSIONS: Calf left atrial thickness in this study was greater than human left atrial thickness. Human left atrial thickness is generally less than 6 mm, and in this range high-intensity focused ultrasound ablation achieved 100% transmurality. These histological results might correlate with a high success rate of atrial fibrillation ablation by using the high-intensity focused ultrasound system.

Single-port cholecystectomy with the TransEnterix SPIDER: simple and safe.

INTRODUCTION: Single-port or single-incision cholecystectomy with current rigid laparoscopic devices is limited by in-line visualization, restricting the ability to approach the surgical site with proper angles and instrumentation. A single-port access system with articulating arms and strong instrumentation should minimize these issues. The TransEnterix system may facilitate safe and straightforward single-port surgery. METHODS: The TransEnterix single-port surgery system was used in both survival and nonsurvival porcine laparoscopic cholecystectomies under animal use committee approval. Nonsurvival procedures compared four standard laparoscopic with four single-port cholecystectomies from a histologic perspective. Five single-port swine laparoscopic cholecystectomy procedures were completed in sterile conditions, and all animals survived for 1 week postoperatively. Standard surgical clips were used for both cystic duct and artery ligation. At sacrifice, both gross and microscopic histology were obtained for assessment of surgical complications. RESULTS: All cholecystectomies were successfully completed with the TransEnterix single-port system. Operative time for the survival procedures averaged 39.4 (range 18-66) min. Histology of the acute specimens showed less inflammation at the single-port site compared with the trocar sites from the standard cholecystectomy. At sacrifice, no complications were identified. CONCLUSIONS: The TransEnterix system is safe and straightforward for completing single-port cholecystectomy in this limited porcine series. Port site inflammation is reduced compared with standard laparoscopic trocars.

Systolic contraction within aneurysmal rabbit myocardium following transplantation of autologous skeletal myoblasts.

OBJECTIVE: Transplantation of autologous skeletal myoblasts (SKMB) into infarcted heart (or cellular cardiomyoplasty, CCM) augments myocardial performance in animal models of myocardial infarction. However, the effect of CCM in the setting of ventricular aneurysm has not been evaluated. This study analyzes the effects of transplanted SKMB on regional wall motion in a rabbit model of postinfarct ventricular aneurysm. We hypothesize that CCM, performed early after myocardial infarction, prevents the progression of dyskinetic wall motion. METHODS: Twenty-six rabbits underwent apical left ventricular cryoinfarction and soleus muscle biopsy for in vitro isolation of skeletal myoblasts. At 2 weeks postinfarct, the presence of ventricular aneurysm was detected in 23/26 animals by sonomicrometry and micromanometry. Seventeen of 23 animals were randomized to receive either 108 autologous myoblasts (CCM) or vehicle. Regional stroke work, percent systolic shortening, and synchronicity of regional wall motion were determined prior to, and four weeks following, injection (CCM; n = 9; vehicle, n = 8). Wall motion was evaluated under baseline and stress (dobutamine, 10 (g/kg/min) conditions. Six animals did not undergo randomization, but their hearts were used to measure the size of infarction. RESULTS: Four weeks following treatment of animals with ventricular aneurysm, systolic contractile activity was present in most animals treated with myoblasts but in none treated with vehicle (5/7 versus 0/6, respectively, P < 0.05). Dobutamine tended to accentuate the differences seen at baseline between the groups. CONCLUSIONS: This study demonstrates a high incidence of systolic contractile activity in a previously aneurysmal region of myocardium following CCM and may represent a novel therapy for the prevention and treatment of postinfarct aneurysm.

Histopathology and transmurality of acute microwave lesions on the beating human atrium.

Microwave energy allows thoracoscopic beating-heart ablation for the treatment of atrial fibrillation. However, there is a paucity of data on the histologic effects of microwave energy on the beating human heart. This study aims to histopathologically characterize microwave lesions on the beating human atrium. Microwave energy was applied prior to cardiectomy on the beating native right atrium in eight patients undergoing heart transplantation and as a circumferential left atrial 'box' lesion in one patient undergoing heart-lung transplantation. Lesions were applied following heparinization and cannulation, but before initiation of cardiopulmonary bypass. Following cardiectomy, specimens were resected, fixed and subjected to histologic preparation. Grossly, all atrial lesions were 'comma-shaped' with an area of maximum injury on the surface. Microscopically, myocyte injury manifested as acute coagulation necrosis with hypereosinophilic myocytes with both nuclear loss and pyknosis. Contraction bands were noted at the periphery of lesions. The injury was transmural in all right atrial lesions. The left atrial sample contained a circumferential lesion ranging from 0.1 to 0.8 cm in width. The cut edge demonstrated lesion depths of 0.2-0.6 cm, maximum (transmural) in the inferior margin. Microwave ablation represents an acceptable energy source to create characteristic lesions on the beating human atrium.