Thoracic Lymphadenopathy Research Articles

Clinicopathological and radiographic features in 40 cats diagnosed with pulmonary and cutaneous Rhodococcus equi infection (2012-2018).

ObjectivesThis retrospective study aimed to describe clinical manifestations, diagnostic options, radiological features, therapeutic plans and outcomes for cats infected with Rhodococcus equi.MethodsForty cats aged between 2 months and 11 years old (median 6 months) that were definitively diagnosed with rhodococcosis between 2012 and 2018 were recruited in this study. Medical records were reviewed for information on signalment, history, clinical presentation, diagnostic testing, treatment plans and clinical outcomes.ResultsOf the 40 cats, 36 showed the pulmonary form of the disease, with 35 (87.5%) presented with dyspnoea, while four cats presented with only cutaneous lesions. Mean body temperature was 38.7 ± 0.2°C. Dyspnoea was noted in 87.5% of the cats. Leukocytosis (58.3%) with band neutrophilia (83.3%), monocytosis (58.3%) and thrombocytopenia (55.5%) were prominent findings in the haematology reports. Hyperproteinaemia (61.1%) with hypoalbuminaemia (22.2%) and hyperglobulinaemia (63.8%) with a low albumin to globulin ratio (38.9%) were prominent features of blood biochemistry reports. An alveolar–interstitial pattern was noted in 75% of pre-thoracocentesis radiographs. Pleural effusion, hepatomegaly, thoracic lymphadenopathy and atelectasis of any lung lobe were seen in 88.9%, 75%, 41.7% and 36.1% of cats, respectively. Overall, the mortality rate was 67.5% in both forms.Conclusions and relevanceClinicians should be aware that feline rhodococcosis manifests as a pulmonary disease at a much higher rate than previously reported. Further studies are required to address the epidemiology, pathophysiology, disease management and prognosis of feline rhodococcosis. The role of immunosuppression as a predisposing factor in feline rhodococcosis requires further investigation.

Angioimmunoblastic T-Cell Lymphoma: Molecular Characterization of Clonal T and B-Cells and a Patient Derived Xenograft Model of Coexisting T and B-Cell Proliferations

Introduction: Angioimmunoblastic T-cell lymphoma (AITL) is a rare and aggressive type of lymphoma that accounts for about 20% of peripheral T-cell lymphomas with a 5 year overall survival rate of 30%. As most patients relapse after anthracycline-containing regimens and newer agents such as histone deacetylase inhibitors, other novel therapeutic approaches are needed. Signaling lymphocytic activation molecule F7 (SLAMF7), a molecule expressed on a subset of T-cells, activated B cells and myeloma cells, is an attractive target to explore based on our previous studies showing SLAMF7 expression in a subset of AITL cases. The association of AITL with Epstein Barr virus (EBV) positive B-cells is nearly always present and the efficacy of treatment in such patients with significant EBV viral load is not well-understood. In this study, we performed the molecular characterization of an aggressive EBV+ AITL case, established a patient-derived xenograft (PDX) AITL model of coexisting T and B-cell proliferations and evaluated novel therapeutic strategies. Methods: Primary tumor cells were injected into a NSG mouse. Flow cytometry, immunohistochemistry (IHC), CISH-EBER and BIOMED 2 PCR based clonality studies were used to confirm the engraftment and compared the consistency of engrafted tumor cells with the primary sample. Genomic DNA extracted from sorted T and B cells and from paired normal neutrophils of the original patient were subjected to Whole Exome sequencing (WES). In vivo AITL PDX model trials were tested for the efficacy of romidepsin (Rom), elotuzumab (Elo), rituximab (Rit) and in combinations of these drugs. Results: A 53 year old woman with AITL was treated with 6 cycles of CHOEP followed by autologous stem cell transplantation. 3 months after transplantation (9 months after diagnosis) she developed progressive fatigue and arthralgias. PET-CT scan showed new cervical, thoracic, abdominal and pelvic lymphadenopathy. A cervical lymph node biopsy was performed to confirm relapse. IHC staining showed atypical T cells expressing CD2, CD3, CD4, CD5, CD7, CD10, BCL6, PD1, SLAMF7 and CXCL13. Scattered CD20+/EBER+ B-immunoblasts were present with focal large clusters/small sheets. Primary tumor cells engrafted in NSG mouse via tail vein injection caused splenomegaly. Flow cytometry assay demonstrated the engraftment of tumor cells in peripheral blood, bone marrow and spleen tissue. CD3+CD19- cells dominated the engrafted cells in all three tissues. Histologic examination and immunophenotyping (IHC and EBER staining) of spleen were consistent with primary tumor tissue. Engrafted tumor cells were capable of serial passage in NSG mice with an increasing malignant B cell percentage that mimics the situation in which the B-cell component masks an underlying T-cell lymphoma in humans. T-cell receptor gene rearrangement assay confirmed the clonal identity of engrafted T-cells matched the primary relapsed tumor. A clonal IGH rearrangement of engrafted B-cells was also detected, while no monoclonal B-cell population was detected in the relapsed AITL sample, possibly due to the low number of EBV+ B-cells present in that biopsy. WES of sorted malignant T-cells showed 33 mutants in 31genes, including RhoA G17V, TET2,STAT3 and VAV1, previously described in AITL or other T-cell lymphomas. In parallel WES assay, 9 mutations were found in 9 genes from sorted EBV+ B immunoblasts. A PDX model using cells harvested from the second passage showed single agent, Elo or Rit, extended the survival of mice compared to the control group (p < 0.05). Rom alone had no such effect (p = 0.27). Combination of Rit with either Elo or Rom further improved survival compared to each single agent exposed cohort (p < 0.05). There was no significant difference between Rit/Elo and Rit/Rom (p = 0.067). PARP cleavage by IHC was higher in the Rit/Rom and Rit/Elo groups compared to other cohorts. Expression of SLAMF7 in a subset of engrafted T and B cells of the control mouse were confirmed via flow cytometry assay. Conclusions: To date, this is the first molecular characterization of AITL tumor cells in comparison with associated EBV+ B cells and use of such a PDX model for therapeutic evaluation of agents targeting both malignant T and B cells simultaneously. The in vivo data support further clinical investigation of applying elotuzumab or romidepsin in combination with rituximab in AITL containing EBV-positive B-cell proliferations. Disclosures Maciejewski: Novartis: Consultancy; Alexion: Consultancy. Hsi:Abbvie: Research Funding; Eli Lilly: Research Funding; Jazz: Consultancy; Cleveland Clinic&Abbvie Biotherapeutics Inc: Patents & Royalties: US8,603,477 B2.

EXTRAORDINARY EXTRA NODAL LYMPHOMA

SESSION TITLE: Monday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM INTRODUCTION: There are over 20 sub types of non-Hodgkin Lymphoma (NHL), marginal zone lymphoma being the 3rd most common. Mucosa-associated lymphoid tissue lymphoma is an extra nodal marginal zone lymphoma (EMZL). We present a case of indolent nodal marginal zone lymphoma progressing to pulmonary EMZL with diffuse tracheobronchial involvement. CASE PRESENTATION: An 86-year-old female was seen in her oncologist’s office for follow up of indolent abdominal nodal marginal zone B cell lymphoma which had been stable for the last 5 years. She reported dry cough, exertional dyspnea and intermittent wheezing for the last 2 weeks. Medical history was unremarkable otherwise. Vital signs and physical exam were within normal limits. Baseline labs including CBC, CMP and chest x-ray were unremarkable. The patient was evaluated with contrast enhanced CT scan of the chest, abdomen and pelvis which revealed endobronchial lesion in the right middle and lower lobes with post obstructive atelectasis of the right middle lobe, and mediastinal, bilateral hilar and axillary lymphadenopathy. These findings were new compared to the previous CT scans. An endoscopic bronchial ultrasound was done which revealed diffuse mucosal involvement of the tracheobronchial tree in the form of nodular mucosa, and narrowing of the bronchus intermedius. Biopsy of the abnormal mucosa and thoracic lymphadenopathy was done and was consistent with marginal zone B cell lymphoma. Our patient was recommended induction with RCVP (rituximab, cyclophosphamide, vincristine, and prednisone) for 1-2 cycles for followed by maintenance with rituximab, revlimid or both. DISCUSSION: Marginal zone lymphoma (MZL) is a group of indolent NHL B-cell lymphomas, which accounts for approximately 8% of all NHL cases. The average age at diagnosis is 60 years, and it is slightly more common in women than in men. The most common form is EMZL. Common sites for EMZL are stomach, small intestine, salivary gland, thyroid and lungs. When present, EMZL of the lung will present as single or multiple nodules or consolidations on imaging. Treatment depends on the extent of the disease. Options are radiation, surgical resection, immunotherapy (anti-CD 20 monoclonal antibody) alone or in combination with chemotherapy. CONCLUSIONS: EMZL shares clinical features with chronic infections and metastatic cancer. It should be high in the differential in patients with consolidation and thoracic lymphadenopathy. Diffuse involvement of the airways including the upper airways is extremely rare which was present in our case. Also, our patient did not have any underlying autoimmune or infectious etiology that is found in most of the cases of EMZL. Long term success with any therapy is limited requiring close observation. Reference #1: Borie R, Wislez M, Antoine M, Bergman CC, Thieblemont C, Cadranel J. Pulmonary mucosa-associated lymphoid tissue lymphoma revisited. Eur Respir J 47: 1244-1260, 2016. Reference #2: Kawaguchi T, Himeji D, Kawano N, Shimao Y, Marutsuka K. Internal Medicine. 2018 Mar 9; 57(15): 2233-2236. Reference #3: Zinzani PL. The many faces of marginal zone lymphoma. Hematology Am Soc Hematol Educ Program1: 426-432, 2012. DISCLOSURES: No relevant relationships by Shujaa Faryad, source=Web Response No relevant relationships by Rajamurugan Meenakshisundaram, source=Web Response

Pulmonary MALT Lymphoma has variable features on CT

Pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma is the most common primary pulmonary lymphoma. There are limited studies on imaging features of pulmonary MALT lymphoma. We present the computed tomography (CT) manifestations of pulmonary MALT lymphoma and the correlation between CT manifestations and clinical characteristics. Patients (n = 53) with histologically confirmed pulmonary MALT lymphoma who underwent chest CT scanning were retrospectively analyzed. Evaluated findings included distribution of pulmonary lesions, morphological pattern of appearance, contrast enhancement features, size, presence of thoracic lymphadenopathy, and secondary associated features. Pulmonary MALT lymphoma was observed in multiple (79%) and bilateral (66%) disease with random distribution (≥70%) of pulmonary lesions. The most frequent morphological pattern was consolidation (n = 33, 62%), followed by nodule (n = 23, 43%) and mass (n = 11, 21%). Common associated features were air bronchograms and bronchiectasis, especially cystic bronchiectasis and angiogram sign. Asymptomatic patients had less consolidation and bronchiectasis than did symptomatic patients. Cystic bronchiectasis was only observed in the symptomatic group. In conclusion, pulmonary MALT lymphoma manifests as diverse patterns on CT scans. Consolidation combined with cystic bronchiectasis was a characteristic late sign, which may assist in differential diagnosis. High-resolution CT images and multiplanar reconstruction techniques are helpful for accurately determining imaging manifestations.

Noncaseating granulomatous diseases in germ cell cancer patients–A single-center experience

ObjectivesIn patients with testicular Germ Cell Tumors (GCT) noncaseating granulomatous diseases such as Sarcoid Like Lesions (SLL) or Sarcoidosis can mimic metastasis due to hilar or mediastinal lymphadenopathy. Due to the clinical and prognostic impact, exclusion of malignant diseases is mandatory. Material and methodsRetrospectively, data from 636 GCT patients, who were seen in the course of tumor surveillance/follow-up were collected. Focus was put on the detection of tumor relapse vs. noncaseating granulomatous reactions. For the differential diagnosis of thoracic lymphadenopathy or pulmonary infiltrates either bronchoscopy (e.g., endobronchial ultrasound-guided transbronchial needle aspiration, endobronchial ultrasound-guided transbronchial needle aspiration) or thoracic surgery was performed. Both GCT patients with either tumor relapse or coexisting SLL were compared to GCT patients without SLL and tumor relapse. ResultsTwenty-nine patients suffered from suspected tumor relapse. Whereas thoracic relapses were suspected in 15 patients on chest computed tomography, thoracic relapse was confirmed in 5 cases by open surgery. In 2 cases open surgery yielded reactive lymphadenitis, and in 8 cases SLL was diagnosed either via EBUS-TBNA (n = 7) or thoracoscopic wedge resection plus lymphadenectomy (n = 1). With focus on overall survival, no relevant difference was found between all tested subgroups (P = 0.265; logrank test). ConclusionsIn GCT patients, the coexistence of noncaseating granulomatous disease is common. Minimal invasive bronchoscopic techniques can serve for the cytopathologic exclusion of malignant thoracic manifestations. In our monocenter patient group the coexistence of SLL did not have any prognostic impact on overall survival.

Rapid emergence of cryptococcal fungemia, Mycobacterium chelonae vertebral osteomyelitis and gastro intestinal stromal tumor in a young HIV late presenter: a case report

BackgroundHighly active antiretroviral therapy has significantly changed the natural history of HIV infection, leading to a dramatic reduction of HIV-related morbidity and mortality. Late Presenters, Very Late Presenters and AIDS presenters still represent, also in Europe, including Italy, a huge challenge in terms of diagnostic and therapeutic management.Case presentationA 35-year-old male with a history of fever and back pain. HIV test resulted positive with a high HIV Viral Load and a very low T-CD4 number of cells (5 cells/mm3). Imaging investigations revealed multiple vertebral and pulmonary lesions together with abdominal and thoracic lymphadenopathy. Blood cultures were positive for Cryptococcus neoformans and for Staphylococcus haemolyticus.Lymphnode biopsy resulted positive in PCR for Non-Tuberculosis Mycobacteria (Mycobacterium chelonae). A gastric biopsy also revealed a GIST. The patient also had CMV DNA positive. Although we performed antiretroviral therapy and specific-therapies for each disease, he was transferred to intensive care unit where he died due to an Acute Respiratory Distress Syndrome.ConclusionThe reported case is unusual due to the relevant number of opportunistic diseases (both infectious and tumoral) emerging not long after the HIV infection had been diagnosed.Late presenters HIV patients and AIDS presenters still represent a challenge, which is often too complex for clinicians to deal with. In spite of proper management, the risk of suboptimal results cannot be excluded.

Incidental thoracic findings in computed tomography scans before transcatheter aortic valve implantation.

Preoperative computed tomography (CT) scans for transcatheter aortic valve implantation (TAVI) are used routinely. In elderly high-risk patients, incidental radiographic findings are frequently reported. The aim of this study was to investigate the impact of auxiliary findings on the patients' mid-term survival, which might affect the treatment strategy. Between March 2011 and April 2016, all radiological reports of contrast-enhanced CT scans of 976 patients scheduled for TAVI were analysed retrospectively for incidental thoracic findings including solitary pulmonary nodules (SPN) and thoracic lymphadenopathy (LAP). The minimum follow-up period was 1 year after TAVI. The median age of all patients was 79 years; 51.9% (n = 507) were women. Approximately 37% (n = 361) of patients showed 1 of the determined findings. An SPN ≥5 mm was diagnosed in 16.4% (n = 160) of patients. Four of them developed lung cancer and 2 nodules were identified as metastases during follow-up. In addition, 12% (n = 117) of the patients had thoracic LAP. Whereas SPN had no significant effect on the overall survival rate, evidence of LAP turned out to be a statistically significant factor regarding 4-year survival (P = 0.001; hazard ratio 1.66; 95% confidence internal 1.19-2.31). SPN ≥5 mm were detected in 16.4% of patients scheduled for TAVI. Nevertheless, the incidence of lung cancer was low and the effect on survival in this high-risk group of patients was statistically not significant. In contrast, thoracic LAP had a significant negative effect on survival. It needs to be proven if the outcome of this cohort can be enhanced by further diagnostics and therapy.

Comprehensive review of fetal adenocarcinoma of the lung.

Fetal adenocarcinoma of the lung (FLAC) is a rare tumor. It accounts for ~0.1%–0.5% of all pulmonary neoplasms. Due to its rarity, much of the world literature regarding FLAC comes from case reports and case series. FLAC is an adenocarcinoma resembling developing fetal lung in its pseudoglandular stage (8–16 weeks of gestation). It is distinguishable from pulmonary blastoma (PB) because it lacks the mesenchymal component which is a hallmark finding in PB. Due to differences in histopathology and clinical course, FLAC has been further categorized into low-grade (L-FLAC) and high-grade (H-FLAC) forms. L-FLAC displays low nuclear atypia and prominent morule formation and has a pure pattern. H-FLAC typically presents with at least 50% fetal morphology, and is often associated with other conventional types of lung adenocarcinoma. FLAC expresses neuroendocrine markers and thyroid transcription factor 1 in most cases. L-FLAC has an aberrant nuclear/cytoplasmic expression of β-catenin and presents mutations in this gene. H-FLAC overexpresses p53. These tumors have a very low frequency of mutations in KRAS and EGFR; it is thought that they are different from a molecular point of view to conventional lung adenocarcinomas. Approximately 25%–40% of patients are asymptomatic at presentation; most of them are incidental findings on chest radiographs. H-FLAC is more common in elderly male patients, with a heavy smoking history. L-FLAC tends to occur in young females. Patients with L-FLAC are usually diagnosed with stage I–II disease, while patients with H-FLAC usually present with a more advanced-stage disease. Poor prognostic factors for FLAC are thoracic lymphadenopathy, metastases at diagnosis, and tumor recurrence; however, the 10-year survival for FLAC is estimated at 75%.

Respiratory manifestations in LPS-responsive beige-like anchor (LRBA) protein-deficient patients.

Pulmonary manifestations are common in LRBA deficiency. Respiratory characteristics in LRBA-deficient patients should be investigated, monitored, and treated from the time of diagnosis. What is Known: • Lipopolysaccharide-responsive beige-like anchor (LRBA) deficiency is a syndrome of primary immune deficiency and immune dysregulation. • Studies concerning the pulmonary characteristics of LRBA-deficient patients are lacking. What is New: • Respiratory manifestations include infections, bronchiectasis, interstitial lung disease, thoracic lymphadenopathy, and clubbing. • Awareness to pulmonary morbidity in LRBA-deficient patients and involvement of a pulmonologist in the workup and clinical decision-making is important. • Respiratory characteristics in LRBA-deficient patients should be investigated, monitored, and treated from a young age.

Chest wall - underappreciated structure in sonography. Part II: Non-cancerous lesions.

The chest wall is a vast and complex structure, hence the wide range of pathological conditions that may affect it. The aim of this publication is to discuss the usefulness of ultrasound for the diagnosis of benign lesions involving the thoracic wall. The most commonly encountered conditions include sternal and costal injuries and thoracic lymphadenopathy. Ultrasound is very efficient in identifying the etiology of pain experienced in the anterior chest wall following CPR interventions. Both available literature and the authors’ own experience prompt us to propose ultrasound evaluation as the first step in the diagnostic workup of chest trauma, as it permits far superior visualization of the examined structures compared with conventional radiography. Sonographic evaluation allows correct diagnosis in the case of various costal and chondral defects suspicious for cancer. It also facilitates diagnosis of such conditions as degenerative lesions, subluxation of sternoclavicular joints (SCJs) and inflammatory lesions of various etiology and location. US may be used as the diagnostic modality of choice in conditions following thoracoscopy or thoracotomy. It may also visualize the fairly common sternal wound infection, including bone inflammation. Slipping rib syndrome, relatively little known among clinicians, has also been discussed in the study. A whole gamut of benign lesions of thoracic soft tissues, such as enlarged lymph nodes, torn muscles, hematomas, abscesses, fissures, scars or foreign bodies, are all easily identified on ultrasound, just like in other superficially located organs.

Analysis of chest computed tomography manifestations of non-Mycobacterium tuberculosis induced granulomatous lung diseases

PurposeTo analyze the chest computed tomography (CT) manifestations of non-Mycobacterium tuberculosis (TB) induced granulomatous lung disease (GLD) with their clinical presentations and laboratory test results. MethodsA total of 55 patients had chest CT scan during a period from June 2010 to January 2016. We retrospectively compared the location, morphology and other specific features of the lesions that were pathologically diagnosed as non-TB induced GLD. Clinical presentations and laboratory results were also documented. ResultsInfectious causes of GLD identified are mainly pulmonary cryptococcosis (n = 8, 14.5%) and pulmonary actinomycosis (n = 3, 5.5%). For non-infectious causes, the most common cause is pulmonary sarcoidosis (n = 27, 49.1%). Symptoms frequently observed include cough (n = 39, 70.9%) and expectoration (n = 30, 54.4%). Lesions due to GLD are mainly multiple and have bilateral distribution on chest CT. These findings are particularly prominent for non-infectious GLD. Lesions in non-TB induced infectious GLD are often unilateral. The morphology of lung lesions is mostly nodules, but lesions can also be masses, consolidations or ground-glass opacity based on the underlying etiology. Nodules are prominent in lungs affected by sarcoidosis along with thoracic lymphadenopathy. Nodules are also seen in non-TB induced infectious GLD, but they are rarely accompanied by hilar lymphadenopathy. ConclusionChest CT could be helpful in diagnosis of the underlying causes of the disease. Nevertheless, chest CT is still insufficient to provide a diagnosis alone due to its unsatisfactory specificity. Confirmation of the diagnosis still relies on histopathological exam of tissue samples.

Epstein-Barr Virus Mucocutaneous Colonic Ulcer in an Immunocompetent Patient

Epstein Barr virus (EBV) positive mucocutaneous ulcers (MCU) were first described in 2010 in immunosuppressed individuals. Lesions have been noted in the oral mucosa, skin, and gastrointestinal tract. Although these lesions are typically benign and will heal with conservative therapy with reversal of immunosuppression, rare reports have described progression to disseminated Hodgkin's lymphoma (HL). We report a case of EBVMCU in an immunocompetent patient during a period of active EBV infectious mononucleosis superimposed on campylobacter colitis. A 47-year-old, previously healthy male presented to the hospital for evaluation for a 1-month history of bloody diarrhea associated with recent development of pharyngitis and flu-like symptoms. Physical exam noted pharyngeal erythema, symmetrical bilateral cervical lymphadenopathy with diffuse abdominal tenderness to palpation. Initial labs noted normal hemoglobin and WBC with a lymphocyte predominance. Transaminases were elevated with an AST 202 U/L, ALT 410 U/L and an alkaline phosphatase of 870 U/L. CT of his abdomen and pelvis revealed circumferential thickening of the rectum with inflammatory stranding, diffuse pelvic, abdominal, and thoracic lymphadenopathy, splenomegaly, and multiple hepatic lesions: collectively concerning for malignancy. Serum AFP, CEA, CA 19-9, and HIV markers were normal. Fecal calprotectin was elevated over 830ug/g. Hepatic MRI noted presence of cysts. Stool cultures were positive for campylobacter. He was started on azithromycin and after several days of therapy, symptoms did not improve. Colonoscopy revealed several clean based ulcers in the rectum and sigmoid-colon (Figure 1) with biopsies positive for EBVMCU (Figure 2). Serum EBV IgM was positive. He was ultimately discharged in stable condition with instructions for close follow-up. To date, 51 cases of EBVMCU have been described in the literature, 5 of which developed within the colon. All reports describe a predisposing factor of immunosuppression by either medication or age-related immunosenescence in patients >60. We report a presumed novel case in which colonic EBVMCU developed in a young immunocompetent patient during active EBV infection superimposed with campylobacter colitis. It is imperative to keep a broad differential and investigate persistent symptoms despite a diagnosis. EBVMCU falls on a spectrum of EBV-associated proliferative disorders, including HL, thus close surveillance is needed to ensure disease resolution.Figure: Colonoscopy acquired images depicting several clean based rectal ulcers.Figure: (Left) H&E stain of rectal ulcer noting colonic mucosa with dense lymphoplasmacyctic infiltrate. (Right) EBV in situ hybridization indicating presence of EBV DNA within the nuclei of infected cells.

Robot-assisted minimally invasive thoraco-laparoscopic esophagectomy for esophageal cancer in the upper mediastinum

Background: Patients with upper third esophageal cancer or esophageal cancer with upper mediastinal paratracheal lymph node metastases are often precluded from surgery because of technical difficulties. With the aid of robotic surgery, an excellent overview and reach of the thoracic inlet can be accomplished. In this way, patients with upper mediastinal esophageal cancer are eligible for esophageal resection with curative intent. The aim of this study was to review the results of a consecutive series of patients who underwent robot-assisted minimally invasive esophagectomy (RAMIE) for tumors of the upper 1/3 of the esophagus or positive lymph nodes in the upper mediastinum. Methods: Between 2007–2016, 31 patients who underwent RAMIE in the UMC Utrecht for proximal esophageal cancer or proximal thoracic lymphadenopathy were identified from a prospective surgical database. Perioperative characteristics and oncologic outcomes were collected. Results: The majority of patients had a squamous cell carcinoma. Clinical tumor stage was cT3 or higher in 25 (81%) of patients. Clinically positive lymph nodes (cN1–3) were observed in 29 (94%) patients. Neoadjuvant treatment was administered in 27 (87%) patients. Median duration of the surgical procedure was 435 min (range 299–874 min). Pulmonary complications were most frequent and occurred in 13 (42%) patients. Median intensive care (ICU stay) was 1 day (range 1–65 days) and median overall postoperative hospital stay was 15 days (range 10–118 days). In hospital mortality was 10%. Causes of mortality were tracheo-neo-esophageal fistula, sepsis after abdominal wall drainage due to leakage of the jejunal fistula resulting in respiratory and kidney failure, after which refraining further treatment resulting in death, and irreversible ARDS in a patient with COPD Gold III needing extracorporeal life support. Radical resection was achieved in 30 (97%) of the patients. Median number of retrieved lymph nodes was 22 (range 9–57). Median time of follow up was 18 months (range 3–81 months). Median disease-free survival was 13 months (range 0–81 months) and median overall survival was 16 months (range 0–81 months). Tumor recurrence occurred in 15 patients (48%) and was locoregional only in 3 patients, systemic only in 5 patients and combined locoregional and systemic in 7 patients. Conclusions: Robot assisted thoraco-laparoscopic esophagectomy with curative intent in patients with upper mediastinal esophageal cancer is feasible, but associated with increased in hospital mortality. Short-term oncologic results are encouraging.

Internal Thoracic Lymphadenopathy in Breast Cancer

The internal thoracic (IT) nodal basin is a first-echelon drainage pathway in the breast, accounting for up to a quarter of its lymphatic drainage, primarily from the deep structures of the breast. The presence of internal thoracic node (ITN) metastases upstages the breast cancer (BC) patient to a minimum of clinical stage III disease. Medial tumors, deep tumors, young age, axillary nodal metastases, tumors of a high nuclear grade, lymphovascular invasion, and triple-negative hormone receptor status are predisposing factors for ITN metastases from primary BC. It has been observed that medial tumors carry a worse prognosis than lateral tumors when all other factors are equal, indicating that understaging of ITN has a significant impact on patient outcomes. Despite the established prognostic significance of IT adenopathy in BC, this nodal basin is not routinely staged due to the difficulty in accessing it and due to the controversy regarding its management. Since the initial ITN studies in the 1960s, improvement in imaging techniques and the availability of minimally invasive biopsy techniques have fueled renewed interest in ITNs and their clinical significance in BC. Radiologists who image and diagnose BC can offer more accurate staging assessments by consistently evaluating the IT nodal chain in the BC patient. In this article, the authors discuss current knowledge of the ITNs in BC and review ITN anatomy. The imaging appearance of pathologic ITNs using various modalities, potential mimics of IT adenopathy, and image-guided sampling techniques are described. A succinct discussion of the clinical management of ITN-positive BC and its challenges is also included. © RSNA, 2017.

Robot-assisted minimally invasive thoraco-laparoscopic esophagectomy for esophageal cancer in the upper mediastinum.

Patients with upper third esophageal cancer or esophageal cancer with upper mediastinal paratracheal lymph node metastases are often precluded from surgery because of technical difficulties. With the aid of robotic surgery, an excellent overview and reach of the thoracic inlet can be accomplished. In this way, patients with upper mediastinal esophageal cancer are eligible for esophageal resection with curative intent. The aim of this study was to review the results of a consecutive series of patients who underwent robot-assisted minimally invasive esophagectomy (RAMIE) for tumors of the upper 1/3 of the esophagus or positive lymph nodes in the upper mediastinum. Between 2007-2016, 31 patients who underwent RAMIE in the UMC Utrecht for proximal esophageal cancer or proximal thoracic lymphadenopathy were identified from a prospective surgical database. Perioperative characteristics and oncologic outcomes were collected. The majority of patients had a squamous cell carcinoma. Clinical tumor stage was cT3 or higher in 25 (81%) of patients. Clinically positive lymph nodes (cN1-3) were observed in 29 (94%) patients. Neoadjuvant treatment was administered in 27 (87%) patients. Median duration of the surgical procedure was 435 min (range 299-874 min). Pulmonary complications were most frequent and occurred in 13 (42%) patients. Median intensive care (ICU stay) was 1 day (range 1-65 days) and median overall postoperative hospital stay was 15 days (range 10-118 days). In hospital mortality was 10%. Causes of mortality were tracheo-neo-esophageal fistula, sepsis after abdominal wall drainage due to leakage of the jejunal fistula resulting in respiratory and kidney failure, after which refraining further treatment resulting in death, and irreversible ARDS in a patient with COPD Gold III needing extracorporeal life support. Radical resection was achieved in 30 (97%) of the patients. Median number of retrieved lymph nodes was 22 (range 9-57). Median time of follow up was 18 months (range 3-81 months). Median disease-free survival was 13 months (range 0-81 months) and median overall survival was 16 months (range 0-81 months). Tumor recurrence occurred in 15 patients (48%) and was locoregional only in 3 patients, systemic only in 5 patients and combined locoregional and systemic in 7 patients. Robot assisted thoraco-laparoscopic esophagectomy with curative intent in patients with upper mediastinal esophageal cancer is feasible, but associated with increased in hospital mortality. Short-term oncologic results are encouraging.

No definite clinical features of immunoglobulin G4–related disease in patients with pulmonary nodular lymphoid hyperplasia

Pulmonary nodular lymphoid hyperplasia (PNLH) may show heavy lymphoplasmacytic infiltrates with increased immunoglobulin G4 (IgG4)-positive plasma cells as in IgG4-related disease (IgG4-RD). However, it is unclear whether PNLH could be a manifestation of IgG4-RD. A recent study reported the presence of Epstein-Barr virus (EBV) in IgG4-related lymphadenopathy. We postulated that a subset of PNLH might represent IgG4-related lung disease with EBV-positive lymphocytes as has been reported in IgG4-related lymphadenopathy. IgG and IgG4 immunohistochemistries were performed on 26 PNLH cases in our files (1994-2014) and on 9 controls including diffuse lymphoid hyperplasia of the lung without nodularity (n=2), usual interstitial pneumonia with increased lymphoplasmacytic infiltrates (n=5), and thoracic lymphadenopathy (n=2). EBV in situ hybridization was performed in the cases with the highest IgG4+ count (n=15). Median IgG4+ plasma cell count in PNLH was 36 cells per high-power field (interquartile range, 7-65) with median IgG4+/IgG+ ratio of 0.24 (interquartile range, 0.12-0.37). Three of 26 cases had a markedly increased IgG4+ count (range, 55-139) and IgG4+/IgG+ ratio (>0.4). Serum IgG4 level available in 1 of these cases was not elevated, and all 3 patients had alternate medical diagnoses. Absolute counts of IgG4+ plasma cells in PNLH did not significantly differ from the other control groups. Result of EBV in situ hybridization was negative in all cases tested. In conclusion, most PNLH cases had low IgG4+ cells, and there was no clinical evidence of IgG4-RD or EBV among those with increased IgG4+ cells.

Endobronchial Ultrasound-Guided Cautery-Assisted Transbronchial Forceps Biopsies: Safety and Sensitivity Relative to Transbronchial Needle Aspiration

Endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration (TBNA) is important in the evaluation of thoracic lymphadenopathy. Reliably providing excellent diagnostic yield for malignancy, its diagnosis of sarcoidosis is inconsistent. Furthermore, TBNA may not suffice when larger "core biopsy" samples of malignant tissue are required. The primary objective of this study was to determine if the sequential use of TBNA and a novel technique called cautery-assisted transbronchial forceps biopsy (ca-TBFB) was safe. Secondary outcomes included sensitivity and successful acquisition of tissue. The study prospectively enrolled 50 unselected patients undergoing convex-probe EBUS. All lymph nodes exceeding 1 cm were sequentially biopsied under EBUS guidance using TBNA and ca-TBFB. Safety and sensitivity were assessed at the nodal level for 111 nodes. Results of each technique were also reported for each patient. There were no significant adverse events. In nodes determined to be malignant, TBNA provided higher sensitivity (100%) than ca-TBFB (78%). However, among nodes with granulomatous inflammation, ca-TBFB exhibited higher sensitivity (90%) than TBNA (33%). On the one hand, for analysis based on patients rather than nodes, 6 of the 31 patients with malignancy would have been missed or understaged if the diagnosis were based on samples obtained by ca-TBFB. On the other hand, 3 of 8 patients with sarcoidosis would have been missed if analysis were based only on TBNA samples. In some patients, only ca-TBFB acquired sufficient tissue for the core samples needed in clinical trials of malignancy. The sequential use of TBNA and ca-TBFB appears to be safe. The larger samples obtained from ca-TBFB increased its sensitivity to detect granulomatous disease and provided adequate specimens for clinical trials of malignancy when specimens from needle biopsies were insufficient. For thoracic surgeons and advanced bronchoscopists, we advocate ca-TBFB as an alternative to TBNA in select clinical scenarios.

Coinfection by Ureaplasma spp., Photobacterium damselae and an Actinomyces-like microorganism in a bottlenose dolphin (Tursiops truncatus) with pleuropneumonia stranded along the Adriatic coast of Italy

A case of pleuropneumonia is reported in an adult male bottlenose dolphin (Tursiops truncatus) found stranded in 2014 along the Central Adriatic coast of Italy. A severe pyogranulomatous pneumonia and thoracic lymphadenopathy were present at necropsy. Numerous Splendore-Hoeppli bodies were found microscopically scattered throughout the lung. Histochemical evidence of Actinomyces-like organisms was obtained from the pulmonary parenchyma, with a strain of Photobacterium damselae subsp. piscicida and Ureaplasma spp. being also isolated from the same tissue. For the latter, a genome fragment of approximately 1400bp from the 16s rDNA was amplified and sequenced. BLAST analysis revealed 100% identity with an uncultured Ureaplasma spp. (JQ193826.1).

57-Year-Old Man With Hip Pain and Lytic Bone Lesions

57-year-old man presented to his primary care physician with a 2-year history of progressive right hip pain. His medical history was notable for hyperlipidemia. He was up-to-date on sex- and agespecific cancer screening. The patient had no history of chest pain, palpitations, shortness of breath, cough, or other cardiac, respiratory, neurologic, or visual symptoms. He had no recent travel history or occupational or social contact with persons who were ill. Physical examination revealed an obese man (body mass index [calculated as weight in kilograms divided by height in meters squared], 40.34 kg/m 2 ) with normal vital signs and unremarkable findings on cardiac, respiratory, abdominal, neurologic, and lymphatic examination. No pain or tenderness was elicited on examination. He was treated initially with nonopioid pain medications. Sacroiliac corticosteroid injections were minimally beneficial. Results of a complete blood cell count (CBC) and electrolyte panel were normal with the exception of an elevated serum calcium level of 11.7 mg/dL (reference range, 8.9-10.1 mg/dL). Ultimately, magnetic resonance imaging (MRI) of his lumbar spine revealed numerous punched-out lytic lesions in the lumbar vertebra and pelvis. He underwent computed tomography (CT) of his chest, abdomen, and pelvis that identified further lytic lesions as well as multiple splenic lesions concerning for metastases. Two separate CT-guided bone biopsy samples of the lytic lesions in the lumbar vertebra did not elicit an etiology of the lesions.

Clinical Features and Gene Mutations of Lung Cancer Patients 30 Years of Age or Younger.

PurposeFew studies examining the clinical features and gene mutations in lung cancer patients 30 years of age or younger have been published. A trend towards increasing morbidity has been noted in young patients; thus, an urgent need exists to explore this subgroup of patients.MethodsPatients aged ≤30 years with pathologically diagnosed lung cancer were retrospectively evaluated. We reviewed the clinical features, gene mutations and prognosis of each patient.ResultsForty-one patients were included in this study. The mean age was 26.4±3.5 years. Cough, tightness/dyspnea and chest pain were common symptoms, and 58.5% of patients presented with advanced stages of lung cancer. Adenocarcinoma was the predominant histologic type noted in these young patients. Masses and nodules were the dominant imaging features observed upon lung computed tomography (CT). Thoracic lymphadenopathy occurred very frequently in these patients. Five of 6 patients with echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) gene fusions presented solid masses with no ground-glass opacity (GGO) and thoracic multifocal lymphadenopathy. Six of 22 (27.2%) cases contained EML4-ALK gene fusions. In addition, 5 of 22 (22.7%) patients harbored epidermal growth factor receptor (EGFR) mutations, and 2 of 17 patients exhibited KRAS and ROS1 gene mutations. The median survival times were 44.2 months for patients with early stage disease and 8 months for patients with advanced NSCLC disease. The one-year and 5-year survival rates were 56.6% and 38.6%, respectively.ConclusionsIncreased gene mutation frequencies are noted in these very young lung cancer patients. This finding indicates that the detection of gene mutations in these patients is important and will help to determine the appropriate targeted therapy.