Mediastinal Adenopathy Research Articles

‘Destroyed Lung’: A Marker of Sequel of ‘Far Advanced’ Radiological Type of Pulmonary Tuberculosis’

Pulmonary Tuberculosis is caused by bacilli mycobacterium tuberculosis and known to infect human race since the dawn of history and archaeological evidence has traced its association in neolithic times. Tuberculosis is the most common infectious lung disease in India with significant mortality and morbidity. Tuberculosis can cause diverse thoracic presentations ranging from nodules, consolidations& cavitation, mediastinal adenopathy, pleural effusion to diffuse endobronchial disease presenting like bronchial asthma. Due to diverse presentations, diagnosis is many times delayed due to lack of suspicion by treating general physicians and rational treatment not offered in time. In spite of awareness by government organizations and considered as a ‘global health issue of concern’ by the World Health organization, tuberculosis is still considered as a social stigma. Destroyed lung is described in literature and known as a complication of pulmonary tuberculosis. Destroyed lung is defined as combination of pleural and parenchymal lung destruction with cavitation, bronchiectasis, loss of lung volume and mediastinal herniation to diseased side. In this case series, we have reported two cases with history of pulmonary tuberculosis in the past and received adequate anti-tuberculosis treatment. Both were having residual chronic lung disease and symptoms causing significant impact on quality of life with recurrent hospitalization, hospital visits and cost of care. One patient has a history of delayed diagnosis and ATT was started after maximum lung destruction due to a tuberculous process that has already occurred. In this patient tuberculosis was cured but residual lung damage or sequel presenting as destroyed lung. In the second case, tuberculosis was diagnosed in adequate time but the patient has defaulted due to adverse events of ATT and he has taken medications as per his own tolerance. Neither adherence nor compliance was acceptable in the second case and resulted in a partially treated case of pulmonary tuberculosis. Ongoing lung destruction in the second case would be the cause for destroyed lungs in absence of irrational medicines in today’s era of good quality ATT. Destroyed lung is preventable with early diagnosis, prompt evaluation with microscopy and nucleic acid amplification tests and treatment with universally available, acceptable and affordable free ATT as National guidelines. 'Destroyed lung' are having a significant impact on quality of life and health expenditure and are considered as ‘radiological stigma’ of Tuberculosis. Radiological classifications of tuberculosis are less used now, and, it can be justified in grading of disease severity and aggressive treatment planning. Radiological classifications also help in predicting complications such as ‘destroyed lung’ during evolution of advanced pulmonary tuberculosis disease which can be prevented with timely diagnosis and use of rational treatment with good clinical and radiological outcome.

Clinical Approach to Advanced Mantle Cell Lymphoma: A Detailed Case Analysis

Mantle cell lymphoma (MCL) is a rare and aggressive subtype of non-Hodgkin lymphoma (NHL) originating from cells in the mantle zone. Herein, we present a case report of a 49-year-old male patient diagnosed with stage VI MCL, illustrating various diagnostic methods and procedures utilized in his evaluation. The patient presented with progressively enlarging cervical lymph nodes, fatigue, weight loss, anorexia, chronic diarrhea, abdominal pain, and rectal bleeding. Clinical examination revealed cutaneomucosal pallor, tachycardia, expiratory polypnea, bilateral jugulocarotid adenopathies, and splenomegaly. Laboratory investigations showed normocytic normochromic anemia, hyperleukocytosis, lymphocytic predominance, and thrombocytopenia. Peripheral blood smear analysis indicated a lymphoproliferative disorder, confirmed by flow cytometry revealing monotypic lymphoid cells. Bone marrow biopsy showed hypoplastic marrow with atypical cells. Immunohistochemistry confirmed mantle cell lymphoma localization. Subsequent thoraco-abdomino-pelvic CT scan revealed mediastinal and abdominal adenopathy with splenomegaly, leading to a diagnosis of stage IV MCL. The case highlights the importance of early and comprehensive diagnostic approaches in MCL management.

Anicteric Cholestasis Syndrome with Pruritus Revealing Systemic Sarcoidosis

Introduction: Sarcoidosis is a systemic granulomatosis of unknown aetiology characterised by the formation of non-caseating granulomas in organs. Hepatic involvement can be difficult to diagnose. Material and method: We report the case of a 30-year-old female patient with a long history of intractable pruritus revealing systemic sarcoidosis. Case report: A 30-year-old female patient presented with a persistent pruritus without jaundice or fever. Examination revealed tender hepatomegaly and scratch lesions. Laboratory tests revealed elevated liver enzymes with cholestasis, and serum protein electrophoresis showed an inflammatory profile. The different viral hepatitis tests were non-contributory. Alpha fetoprotein was normal. Abdominal ultrasound and CT scans revealed a heteronodular hepatomegaly. The first liver biopsy was consistent with autoimmune hepatitis lesions. The disease improved with general corticosteroid therapy and azathioprine. Two years later, with the persistence of the pruritus, blood calcium levels and angiotensin-converting enzyme tests were found to be elevated. A new liver biopsy showed epitheliogigantocellular granulomas without caseous necrosis. A thoracic CT scan revealed mediastinal adenopathy. This suggested systemic sarcoidosis. The patient progressed well clinically and radiologically on general corticosteroids with adjuvant therapy and azathioprine. Conclusion: Sarcoidosis is a systemic disease that can affect most tissues and organs. Hepatic involvement is frequent and more often difficult to diagnose.

Spinal Trauma Revealing a Metastatic Medullary Lesion: A Case Report

Introduction and Importance: Intramedullary spinal cord metastases (ISCM) are a rare and devastating complication of malignant disease with a poor prognosis. Prompt and accurate diagnosis is necessary for effective treatment, and magnetic resonance imaging (MRI) is the preferred imaging technique. In this article, a rare case of an ISCM presenting with motor weakness after trauma is described. Case Presentation: The patient showed progressive severe paraplegia and urinary retention, and a thoraco-abdomino-pelvic scan showed a mediastinal pulmonary process and mediastinal adenopathies with adrenal lesions. He was admitted and a total resection of the processus was performed. After surgery, the patient showed partial neurological improvement, but two weeks later, he had a consciousness impairment. A cerebral CT scan showed multiple round lesions, with perilesional edema, and the patient died one month later. Discussion: The article discusses the pathogenic mechanisms of ISCM and its diagnosis, treatment, and management, which are controversial due to the multitude of clinical circumstances and the lack of controlled studies on the efficacy of the different therapeutic approaches. Conclusion: In conclusion, this rare case of Intramedullary Spinal Cord Metastases (ISCM) offers several important take-away lessons for clinicians and researchers alike.

Abstract PO1-05-04: CDK4/6 inhibitor-induced Interstitial Lung Disease (ILD) - A Case Series

Abstract Introduction: CDK4/6 inhibitors interrupt cell cycle by inhibiting intracellular and hormonal signals responsible for proliferation of malignant cells, making them an effective treatment for patients with HR+ advanced breast cancer. Pre-clinical data demonstrates that CDK4/6 inhibitors allow for inflammatory cell recruitment, inducing pulmonary inflammation and thereby increasing the risk of ILD. The overall risk of ILD was 1.6% in a meta-analysis of over 16,000 patients treated with CDK4/6 inhibitors while individual reported risk was 1%, 1.6% and 3% for palbociclib, ribociclib, and abemaciclib respectively. Objective: The aim of this case series is to add to the body of literature about this rare but possibly serious side effect of CDK4/6 inhibitor associated ILD. Early detection and prompt management are essential for improved patient outcomes. Case 1 A 61 year-old female was diagnosed with metastatic breast cancer to brain and bones after being admitted for evaluation of acute vision loss. She started on palbociclib and letrozole and subsequently had 2 hospitalizations for acute hypoxemic respiratory failure with unremarkable infectious workup. CT scan was significant for bilateral pulmonary infiltrates raising suspicion for CDK4/6 inhibitor-induced pneumonitis; subsequently palbociclib was discontinued and the patient was started on steroid taper resulting in improvement of her respiratory status. Case 2 A 71 year-old female with a remote history of left breast cancer and sarcoidosis presented with respiratory symptoms. She was found to have metastatic breast cancer with CT scan revealing hilar and mediastinal adenopathy. The patient initially received taxol with near resolution of disease on imaging. The patient was subsequently started on palbociclib + letrozole. After 9 months of treatment, the patient was admitted for pneumonia and discharged home with oxygen. PFTs at the time were suggestive of restrictive pathology related to obesity hypoventilation. Six months later, the patient was admitted for worsening respiratory failure; CT scan revealed interstitial changes likely due to multifactorial etiologies including palbociclib-induced pneumonitis. The patient subsequently passed away. Case 3 An 81 year-old female diagnosed with remote history of L. breast cancer presented with shortness of breath and weakness. CT scan revealed a nodule and lymphadenopathy; biopsy of nodule was consistent with breast primary. The patient was initially started on ribociclib which was discontinued after 4 cycles due to transaminitis. She was switched to palbociclib, however 2 months after initiation, the patient presented with flu-like symptoms. CT revealed scattered subpleural ground-glass opacities. Infectious workup was negative; pulmonary consultation believed this was likely due to drug-induced pneumonitis and palbociclib was discontinued and she was treated with a steroid taper. Patient was switched to fulvestrant; and after 9 months she was diagnosed with stage IV tongue cancer and her breast cancer therapy was discontinued. Discussion CDK4/6 inhibitors have improved survival in patients with metastatic breast cancer, however they are associated with rare but serious adverse effects like ILD. ILD is a challenging clinical diagnosis as it refers to a cluster of disorders of varying presentation and pathophysiology, and as a result can be missed. Conclusion This case series demonstrates that CDK4/6 inhibitor-associated ILD may be more prevalent than originally reported. It is important to identify early by performing a thorough workup, including a detailed history and physical exam, medication list review, infectious work-up, chest imaging, PFTs and pulmonology consultation. Publishing a set of standardized guidelines to diagnose and treat CDK4/6 inhibitor-induced ILD is necessary as more cases are identified. Citation Format: Ami Chitalia, Krishna Shah. CDK4/6 inhibitor-induced Interstitial Lung Disease (ILD) - A Case Series [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-05-04.

An Atypical Etiology for Granulomatous Mediastinal Lymphadenopathy in an Immunocompetent Adult Male

Abstract Nontuberculous mycobacteria (NTM) are widely distributed microorganisms that have the potential to cause severe illness in humans, especially those with compromised immune systems. In adults, the disease mainly manifests as chronic pulmonary disease. Few case reports are available on lymphadenopathy caused by nontubercular mycobacterium in children, primarily affecting the cervical lymph nodes. However, it is exceptionally rare for an immunocompetent adult to develop mediastinal lymphadenopathy due to NTM infection. We present a case of posttubercular fibrocavitary lung disease with mediastinal adenopathy in an immunocompetent male. The initial clinical suspicion was the reactivation of tuberculosis. However, the cultures from the mediastinal node aspirate obtained by Endo Bronchial Ultra Sound guided Trans Bronchial Needle Aspiration (EBUS-TBNA) and the bronchoalveolar lavage showed growth of nontubercular mycobacterium. Our literature search only revealed a case report discussing mediastinal lymphadenopathy associated with NTM in an immunocompetent individual.

Sarcoidosis with esophageal involvement: an uncommon clinical enigma.

We present the case of a 46-year-old male, a former smoker, with a medical history significant for morbid obesity grade III, hypothyroidism, hyperuricemia, and dyslipidemia. Four months ago, he was diagnosed with sarcoidosis involving mediastinal lymph nodes and is currently undergoing treatment with corticosteroids. The patient presented to the emergency department with persistent epigastric and thoracic pain lasting one week, accompanied by dysphagia and odynophagia intermittently. Laboratory tests showed elevated acute-phase reactants, with no other notable abnormalities. Chest X-ray revealed pre-existing mediastinal adenopathy. Despite an abdominal CT scan with contrast showing no significant findings, esophagogastroduodenoscopy revealed marked extrinsic compression of the esophagus between 25 and 32 cm from the dental arch, with less intensity distally. Although passage of the endoscope through this area caused significant pain, it did not hinder its advancement. A chest CT scan with oral contrast demonstrated filamentous narrowing of the esophagus in the middle third, along with concentric thickening of its walls and multiple paratracheal, parahilar, and periesophageal lymphadenopathies. Following a tapering regimen of corticosteroids, the patient was discharged with a clinical diagnosis of sarcoidosis with mediastinal and esophageal involvement secondary to extrinsic compression. Due to clinical improvement with the prescribed treatment, endoscopic ultrasound and biopsies to assess esophageal wall involvement were deemed unnecessary.

Local management of unresectable lung atypical carcinoid tumor: a case report and review of literature

Neuroendocrine tumors comprise a rare but increasing heterogeneous group of malignancies arising from neuroendocrine cells, most commonly from the lung and gastrointestinal tract. Due to the vast histopathological differentiation of each subtype and the scarce clinical data published, choosing the most effective therapy can be challenging. Radiotherapy can play a significant role in the treatment of locally advanced metastatic tumors, however there is a lack of randomized clinical trials in this setting. This article reviews the current knowledge on the classification and treatment of unresectable lung atypical carcinoids. We present a clinical case of a ULAC treated with systemic therapy and RT in different settings of the disease. The subject is a 48 years old male, diagnosed with a well differentiated pulmonary NET, classified as cT4N3M1b (supraclavicular and mediastinal adenopathies and an adrenal metastatic lesion) with disease progression after systemic treatment, and with superior vena cava compression. The primary tumor and involved nodal areas were treated to 54Gy/30 fractions using VMAT. SBRT was given to the metastatic left adrenal gland. Five months after RT, CT showed a volumetric reduction of <25% of the thoracic disease and adrenal gland’s lesion stability. The disease remained stable for the next year and a half, when local and distant progression occurred, starting systemic treatment. A year and a half later, the patient presented with brain metastasis and underwent radiosurgery. At last follow-up, 5 years after diagnosis, the patient maintains treatment with capecitabine and temozolomide and is clinically stable. Definitive RT should be considered in the management of ULAC to improve local control.

Validation of Childhood Hodgkin International Prognostic Score (CHIPS) for Predicting Event-Free Survival in Intermediate and High-Risk Hodgkin Lymphoma

Background: Improving risk stratification of patients with Hodgkin lymphoma (HL) allows for optimization of treatment allocation and minimization of late effects when possible. The Childhood Hodgkin International Prognostic Score (CHIPS) was developed as a predictive model for event-free survival (EFS) in pediatric and adolescent HL using clinical data at diagnosis from patients with intermediate-risk HL treated on Children's Oncology Group protocol AHOD0031 (NCT00025259) with doxorubicin, bleomycin, vincristine, etoposide, prednisone, cyclophosphamide (ABVE-PC) chemotherapy and response-adapted radiation. Stage IV, large mediastinal mass, albumin <3.5 g/deciliter, and fever were identified as independent predictors of EFS and assigned one point each, resulting in CHIPS ranging from 0 to 4. CHIPS was highly predictive of EFS in this patient cohort, but has not been validated in high-risk patients or in patients treated with other therapeutic regimens. We aim to validate the CHIPS as a risk stratification tool for patients with intermediate or high-risk HL treated with Stanford V chemotherapy by the Pediatric Hodgkin Consortium (PHC). Methods: The PHC trial HOD99 (NCT00145600) enrolled patients on the high-risk arm with stage IIB, IIIB, or IV disease <22 years (n=123). HOD05 (NCT00352027) enrolled patients with intermediate-risk HL with stage IB, IA or IIA with “E” lesions, ≥3 nodal sites, or bulky mediastinal adenopathy, or IIIA disease <22 years (n=49). All patients received 12 weeks of Stanford V chemotherapy with doxorubicin, vinblastine, mechlorethamine, vincristine, bleomycin, etoposide, and prednisone followed by low-dose, response-adapted radiation therapy. All patients with absent B symptoms were deemed afebrile; patients missing documentation of any elements of CHIPS were excluded from the analysis. Results: Our final analysis included a total of 164 patients, 116 with high-risk HL from HOD99 and 48 with intermediate-risk HL from HOD05. One patient was excluded for missing fever data and 7 were excluded due to missing albumin values. Patients were classified into 2 groups based on their CHIPS value: CHIPS 0-1 (n=88, 53.7%) and CHIPS 2-4 (n=76, 46.3%). The EFS for patients in the CHIPS 0-1 and CHIPS 2-4 groups was analyzed using Kaplan-Meier curves (Figure 1). The 2-year EFS estimates for patients with CHIPS 0-1 and CHIPS 2-4 were 95.5% (95% confidence interval (CI) 91.2%-99.9%) and 80.3% (95% CI 71.8%-89.7%), respectively, with a log-rank p-value of 0.003. Similarly, the 4-year EFS estimates for patients with CHIPS 0-1 and CHIPS 2-4 were 93.2% (95% CI 88.0%-98.6%) and 77.6% (95% CI 68.7%-87.6%), respectively, with a log-rank p-value of 0.004. The reduced EFS in patients with higher CHIPS is consistent across different stages and early response assessment (Table 1). Conclusions: CHIPS is highly predictive of EFS in pediatric and adolescent patients with intermediate and high-risk HL treated with Stanford V chemotherapy, as it identifies a subset (CHIPS 2-4) with significantly lower EFS compared to the other subset (CHIPS 0-1). Assessment of CHIPS alongside novel approaches such as circulating tumor DNA and total metabolic tumor volume should be analyzed across trials to allow for further enhancements to risk stratification for pediatric, adolescent and young adult HL.

Longitudinal Differences By Treatment Arm in Health-Related Quality of Life Among High Risk Pediatric Hodgkin's Lymphoma Patients Treated on the Children's Oncology Group Ahod 1331 Study

Introduction: Brentuximab vendotin (BV) with AVE-PC demonstrated superior efficacy to ABVE-PC for pediatric patients with high-risk HL in the AHOD 1331 trial. However, there are no data regarding the impact on health-related quality of life (HRQoL) with the addition of BV into the treatment of pediatric HL. Methods: Eligibility for AHOD 1331 (NCT 02166463) included previously untreated HL with high risk disease, defined as stage IIB +bulk, IIIB, IVA, or IVB classic HL. Participants were randomized to either BV-AVE-PC (“BV” arm) or ABVE-PC (standard arm). Among the first 309 participants enrolled in a prespecified longitudinal patient-reported outcomes sub study, 280 were age 11+ years and eligible to self-report HRQoL using the seven-item Child Health Ratings Inventories (CHRIs)-Global scale. HRQoL was assessed prior to treatment (T1), at cycle 2 (T2), at cycle 5 (T3), and at the end of treatment (T4). A clinically meaningful increase in HRQoL was considered a change of 7 points in the CHRIs-Global score (CHRIs), translating to a 1/3 standard deviation. Multivariable linear regression estimated the association between demographic/clinical variables and HRQoL at T1. Linear mixed models estimated the change in HRQoL relative to T1 with a time*treatment arm interaction to estimate differences in the change in HRQoL across treatment arm. This model was adjusted for age, sex, race/ethnicity, stage, large mediastinal adenopathy (LMA), B-symptoms at diagnosis, and a time-varying covariate for involved site radiation prior to T4. Results: Participant and disease characteristics were balanced by treatment arm; mean age at enrollment was 15.6 years (SD= 1.9), 52% were female, 60.4% had LMA, and 58% were stage IV. 93% of participants completed the CHRIs at T1, 92% at T2, 89% at T3, and 74% at T4. At T1, female sex (mean (SD) 64.1 (20.2) vs 71.3 (23.3) p=0.004) and fever (60.8 (23.0) vs. 71.9 (20.4) p=0.024) were associated with worse HRQoL. At each time point after pre-treatment (T1), HRQoL was higher, on average, in the BV arm compared to the standard arm (Figure 1). By T2, participants in the BV arm experienced a statistically and clinically significant increase in HRQoL compared to pre-treatment (T1) (Table 1; β=7.3 95%CI 3.2, 11.4; p≤0.001), which was greater than the change experienced in the standard arm (difference in change β=5.1 95%CI -0.2, 10.3; p=0.057). At T3 and T4 the BV arm continued to experience statistically significant improvements in HRQoL relative to T1 (T3 β=5.3 95%CI 0.8, 9.9; p=0.022; T4 β=14.6 95%CI 10.3, 18.9; p≤0.001). The standard arm did not experience a statistically or clinically significant increase in HRQoL from T1 until T4 (β=9.3 95%CI 4.7, 11.5; p<0.001). Conclusion: Patients with high-risk pediatric HL treated with BV-AVE-PC experienced more rapid and sustained improvement in HRQoL compared to patients treated with ABVE-PC. These data also demonstrate the feasibility and importance of incorporating HRQoL assessments into pediatric clinical trials.

Thoracic SMARCA4-Deficient Undifferentiated Tumors With Unusual Presentations: A Case Series.

Thoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT) is a recently described aggressive neoplasm of young smokers defined by SMARCA4 inactivating mutations and characterized by cells with rhabdoid morphology, high mitotic activity, and abundant necrosis. Describe and compare 3 unusual presentations of SMARCA4-UT in older adults, including one presenting as a metastatic lesion mimicking a primary bone sarcoma. Discuss the molecular characteristics of SMARCA4-UT and their relationship to nonsmall-cell lung carcinomas with SMARCA4. Three patients with SMARCA4-UTs were identified utilizing a natural language search in CoPath. hematoxylin and eosin sections from all patients as well as Papanicolaou-stained slides and Diff-Quik-stained slides for the first patient were examined. A broad range of immunostains, including BRG1/SMARCA4, were evaluated. Molecular testing was performed via next-generation sequencing. The 3 patients were aged 58, 70, and 70 years. All had a significant smoking history. The first patient presented with an iliac bone mass and mediastinal lymphadenopathy, the second with mediastinal adenopathy, and the third with a paratracheal mass. All 3 tumors showed a diffuse proliferation of pleomorphic, rhabdoid cells with high mitotic activity and tumor necrosis. SMARCA4 was lost in all 3 tumors by immunohistochemistry. Molecular testing revealed SMARCA4 alterations in the first 2. Thoracic SMARCA4-UT should be considered in the differential diagnosis of pleomorphic rhabdoid tumors in older adults with a smoking history. Although most present as lung and/or mediastinal masses, they may occasionally present as a metastasis and mimic an undifferentiated sarcoma, representing a potential diagnostic pitfall.

SAT576 Change Is Not Always For The Best! A Transformation of Papillary Into Metastatic Anaplastic Thyroid Carcinoma

Abstract Disclosure: J. Syeda: None. R. Zafar: None. K. Rajamani: None. INTRODUCTION: Anaplastic thyroid carcinoma (ATC) can occur de-novo or from preexisting well-differentiated thyroid carcinoma (1). The presence or absence of certain driver mutations can help predict the likelihood of this transformation process. We present a case of an elderly female with an initial diagnosis of well-differentiated papillary thyroid cancer (PTC) with a transformation into metastatic anaplastic thyroid carcinoma (ATC). CASE PRESENTATION: An 81-year-old female patient was initially seen 8 years ago with a 35-year history of goiter. At the initial presentation, she felt well and did not have any symptoms. Physical examination revealed an enlarged thyroid gland with left lobe nodularity. A thyroid ultrasound showed a multinodular thyroid gland including a 2x1.7x1.2 cm solid nodule with macro calcifications in the right lobe, 2.8x2.6x2.5 cm solid nodule, and 1.6x1.3x1.6 cm heterogeneous solid nodule with calcifications and irregular margins in the left lobe. She had a fine needle aspiration of these three nodules. The right nodule was non-diagnostic and both left nodules were positive for PTC. She underwent a total thyroidectomy and central lymph node dissection. Radioactive iodine treatment with 163mCi was administered after surgery. One and a half years after surgery, her thyroglobulin levels started trending upward. This led to a further workup including a PET/CT scan, which showed a hyper metabolic 6 mm left supraclavicular lymph node. Needle biopsy of this lymph node disclosed metastatic PTC. The pathologic diagnosis following surgical resection was positive for metastatic poorly differentiated thyroid carcinoma. A subsequent PET/CT scan and a thyroid ultrasound showed an abnormal uptake of the left neck lymph node and additional metastatic nodes in the left neck respectively. A core needle biopsy of these lesions was positive for ATC. Foundation One CDx testing was positive for BRAF V600E, TP53, and TERT promoter mutations. Cellblock from the initial thyroidectomy was reevaluated by pathology and confirmed no evidence of ATC. Foundation One CDx testing of the thyroidectomy specimen was positive for BRAF V600E and TERT promoter mutations. Surveillance imaging shows mediastinal adenopathy, left pleural thickening, and bone and liver metastases. DISCUSSION: Anaplastic transformation is not uncommon (1). This case supports the evidence that TERT promoter mutations may not trigger anaplastic transformation but may predispose to the aggressive PTC phenotype prone to conversion to ATC when one of the ATC-related “second hit” genetic events occurs (2). This case suggests that the “second hit” event is a TP53 mutation. The detection of a TP53 mutation in PTC with an aggressive phenotype may help predict anaplastic transformation. REFERENCES: 1-Endocrine Pathology. 2021 Mar; 32(3):347-356. 2- Semin Cancer Biol. 2020 Apr; 61: 23-29. Presentation: Saturday, June 17, 2023

Radiotherapy Utilization and Outcomes on a Contemporary Trial for Pediatric High-Risk Hodgkin Lymphoma Study

Contemporary trials in pediatric Hodgkin lymphoma (cHL) evaluate strategies to reduce radiotherapy (RT) utilization while maintaining excellent progression-free survival (PFS). An alternative strategy is to irradiate selective sites at higher risk of relapse, and/or use proton therapy (PT) to minimize exposure to healthy tissue. We investigated the use of PT and photon therapy (XRT) and associated early outcomes among patients receiving involved site RT (ISRT) to high-risk sites on the Children's Oncology Group (COG) trial AHOD1331 (NCT021664643). This multicenter randomized, open-label phase 3 study enrolled patients 2-21 years (yrs) with previously untreated cHL: stages IIB + bulk, IIIB, IVA, IVB. Patients were randomized to 5 cycles of either ABVE-PC (doxorubicin, bleomycin, vincristine, etoposide, prednisone, cyclophosphamide) or the brentuximab vedotin (BV) containing regimen BV-AVE-PC given every 21 days. ISRT to 21 Gy was given to bulky mediastinal adenopathy and slow responding lesions (SRL) defined by 5-point score 4 or 5 on PET-CT after 2 cycles. ISRT could be delivered as 3D conformal XRT (3D), intensity modulated XRT (IMRT), or proton therapy (PT). Utilization of RT was compared by mode and by study enrollment midpoint among irradiated patients. Severe acute toxicity assessment included any incident grade 3 or higher toxicity during the ISRT period, except for neuropathy. Among 587 eligible patients who were enrolled across 153 institutions between March 2015 and August 2019 with a median follow up of 43.1 months, the 3-yr PFS was 82.5% (90% CI, 78.3%-85.9%) with ABVE-PC and 92.5% (90% CI 89.5%-94.6%) with BV-AVE-PC (p = 0.0002). There was no difference in ISRT receipt or modality by study arm (p = 0.33). Among those who received RT 69.7% received it due to bulky mediastinal adenopathy, 6.6% due to SRL, and 23.7% for both. Overall, 317 (54.0%) patients received protocol RT of which 28.7% received 3D, 44.8% received IMRT, and 26.5% received PT. PT utilization increased over the course of the study from 21.5% among the first 50% of irradiated patients to 31.5% in the second half of irradiated patients (p = 0.045). The 3-yr progression-free survival rates overall by RT were comparable: PT (88.0%, 90% CI 80.6% - 92.7%%); XRT (87.1%, 90% CI 82.9%-90.4%) (p = 0.85). No difference in PFS was observed between 3D versus IMRT (p = 0.65). No differences were observed in severe acute toxicities (8.33% vs. 8.15%, p = 0.96) between PT and XRT. Selective use of RT results in excellent outcomes for pediatric patients with high-risk HL and combination chemotherapy inclusive of the novel agent BV. Over the course of the study, PT utilization increased as an RT modality. Early results suggest that PT does not compromise disease control and has similar acute toxicity as XRT. Long term follow-up (>10 years) is needed to evaluate for secondary malignancies and cardiac toxicity among the different RT modalities.

Bronchoalveolar lavage in lung cancer: does it increase the positive yield of bronchoscopy?

Abstract Background Cells obtained from bronchoalveolar space can give a definite diagnosis in malignancies. The present study aimed to assess the diagnostic yield of bronchoalveolar lavage (BAL) in lung cancer and to assess the relationship of its yield with radiology, endoscopy, and pathological subtypes. Patients and methods A retrospective study with re-revision of saved bronchoscopic video, computed tomography (CT) films, and pathology slides was conducted on 101 patients with definite bronchogenic carcinoma diagnosed over 4 years. Results BAL positive yield was found in 42.4% of cases, and its yield coincided with other bronchoscopic sampling methods in 43.6% of cases. Regarding CT findings, the BAL positive yield was significantly higher in peripheral lesions (79.1%), mass size more than or equal to 3 cm (62.8%), CT bronchus sign (46.5%), hilar and/or mediastinal adenopathy (86.0%), and consolidation (51.2%). The most common bronchoscopic abnormality in patients with BAL positive yield was submucosal lesions (83.3%). The adenocarcinoma (48.8%) and bronchoalveolar carcinoma (11.6%) were the histopathological types having significant BAL positive yield. The most significant predictive factors for BAL positive yield were mediastinal adenopathy, endobronchial lesions, nonvisible lesions, adenocarcinoma type, submucosal lesions, CT bronchus sign, mass size more than or equal to 3 cm, peripheral lesions, and concomitant use of bronchial brushing. BAL had 40.3% sensitivity, 51.7% specificity, 67.4% positive predictive value, 25.9% negative predictive value, and 43.6% diagnostic accuracy in bronchogenic carcinoma. Conclusion BAL increases the positive yield of bronchoscopy by 13.9% with fair diagnostic performance, especially in peripherally locating nonvisible lesions. Although tissue biopsy remains the gold standard sampling, clinicians might rely on BAL cytology for diagnosis of lung cancer in some patients.

17th International Conference on Malignant Lymphoma, Palazzo dei Congressi, Lugano, Switzerland, 13 - 17 June, 2023.

Introduction: Outcomes for high-risk pediatric and adolescent and young adult (AYA) classic Hodgkin lymphoma (cHL) improved substantially with the addition of brentuximab vedotin (Bv) to AVEPC (adriamycin, vincristine, etoposide, prednisone, cyclophosphamide) chemotherapy. As patients with stage IV disease have poor outcomes, we evaluated the prognostic implications of sites contributing to stage IV disease. Methods: On AHOD1331 (NCT02166463), patients age 2–21 years with high-risk cHL (stage IIB with bulk, IIIB, IVA, and IVB) were randomized to 5 cycles of AB (bleomycin)VE-PC versus Bv-AVE-PC, and consolidative radiotherapy based on interim response and large mediastinal adenopathy at diagnosis. Patients with stage IV disease, as determined by protocol defined and centrally reviewed PET-CT, were identified. Stage IV was defined as disseminated involvement of ≥1 extralymphatic organ or tissues (with or without lymph node involvement) or isolated extralymphatic organ involvement with distant nodal involvement. E-lesions were distinguished from sites of stage IV involvement in the lung, but any liver and/or bone marrow involvement, regardless of contiguity, was considered stage IV. Central review was performed to confirm institutional classification of stage, upstaging 33 patients to stage IV and downstaging 17 among the 353 enrolled and stratified as Stage IV by the institution. Baseline characteristics and progression-free survival (PFS) were compared by pattern of metastatic involvement (lung only, bone only, bone marrow only, or multi-site, defined as >1 site of involvement). Results: 369 patients (median age 15 years, range 3–22) with stage IV disease treated on AHOD1331 were included, of which 183 (50%) were treated with ABVE-PC and 186 (50%) with Bv-AVE-PC. Patterns of disease included: isolated involvement of lung (185; 50%); bone marrow (5; 1%); or bone (8; 2%), and 171 (46%) had multi-site involvement. B symptoms were present in 80% and 88% with bone marrow or bone involvement respectively, 50% of those with lung, and 57% with multi-site disease. The 3 year-PFS (95% CI) by site of involvement was: 88.0% (82.3, 91.9) for lung, 100% for isolated bone marrow or bone, and 82.5% (75.8, 87.5) for multi-site (p = 0.21). Bv-AVE-PC significantly improved PFS among stage IV patients compared to ABVE-PC (3-year PFS 90.2% vs. 81.5%, p = 0.01). Among those with isolated lung involvement, there was a non-significant increased PFS with Bv (3-year PFS 91.2% vs. 84.7%, p = 0.16), while those with multi-site metastatic disease experienced significantly improved PFS with Bv (3 year-PFS 88.1% vs. 77.1%, p = 0.05). Conclusions: Among pediatric and AYA patients with stage IV cHL, PFS was notably improved with Bv among patients with multi-site metastatic involvement. These results will help guide future efforts to understand strategies to improve outcomes among children with stage IV disease. The research was funded by: Supported in part by grants from the National Institutes of Health (U10CA098543, U10CA180899, and U10CA180886; all to the Children’s Oncology Group), the Quality Assurance Review Center (U10CA29511), Imaging and Radiology Oncology Core Rhode Island (U24CA180803), and St. Baldrick’s Foundation (to the Children’s Oncology Group) Keywords: Hodgkin lymphoma, molecular targeted therapies, Lymphoid Cancers - Other No conflicts of interests pertinent to the abstract.

Prognostic value of chest x-ray- and CT-defined large mediastinal adenopathy in high-risk pediatric Hodgkin lymphoma: A report from the Children's Oncology Group Study AHOD0831.

We compared the prognostic value of chest radiograph (CXR)- and computed tomography (CT)-derived definition of large mediastinal adenopathy (LMA) in pediatric Hodgkin lymphoma (HL). Total 143 patients treated for stage IIIB/IVB HL on COG AHOD0831 were included in this study. Six definitions of LMA were investigated: (i) mediastinal mass ratio on CXR (MRCXR )>1/3; (ii) mediastinal mass ratio on CT (MRCT )>1/3; (iii) mediastinal mass volume on CT (MVCT )>200mL; (iv) normalized mediastinal mass volume (MVCT /thoracic diameter [TD])>1mL/mm; (v) mediastinal mass diameter on CT (MDCT )>10cm; and (vi) normalized mediastinal mass diameter (MDCT /TD)>1/3. Median age at diagnosis was 15.8years (range: 5.2-21.3years). In patients with a slow early response (SER) to chemotherapy, MVCT >200mL, MDCT >10cm, and MDCT /TD>1/3 were associated with worse relapse-free survival (RFS) on MVA, while MRCXR >1/3, MRCT >1/3, and MVCT /TD>1mL/mm trended toward worse RFS; MDCT /TD was the most strongly prognostic for inferior RFS, with a hazard ratio of 6.41 for MDCT /TD>1/3 versus ≤1/3 on MVA (p=.02). LMA according to MVCT >200mL, MDCT >10cm, and MDCT /TD>1/3 is associated with poor prognosis in advanced-stage HL patients with SER. The normalized mediastinal diameter, MDCT /TD>1/3 appears to be the strongest predictor of inferior RFS.

AIUM Practice Parameter for the Performance and Interpretation of Diagnostic Ultrasound of the Thyroid and Extracranial Head and Neck.

AIUM Practice Parameter for the Performance and Interpretation of Diagnostic Ultrasound of the Thyroid and Extracranial Head and Neck.

An Atypical Presentation of X-linked Lymphoproliferative Disease type 1 Presenting with Seronegative Coccidioidomycosis

X-linked lymphoproliferative disease (XLP-1), an inborn error of immunity (IEI) caused by pathogenic variants in SH2D1A encoding signaling lymphocyte activation molecule-associated protein (SAP), is characterized by hemophagocytic lymphohistiocytosis (HLH), lymphoma, and hypogammaglobulinemia. We report the first known case of XLP-1 presenting with seronegative coccidioidomycosis. CaseA 13-year-old boy with persistent asthma, recurrent otitis media requiring four sets of tympanostomy tubes, chronic sinusitis, and Common Variable Immunodeficiency (CVID) presented with acute-on-chronic hypoxic respiratory failure. He had been off subcutaneous immunoglobulin (SCIg) replacement for 2 years. Sputum culture was positive for H. influenzae, treated with cefepime and azithromycin and supplemental oxygen for acute hypoxic respiratory failure. Fever persisted despite 48 hours of antibiotics. CT chest showed bronchiectasis with mediastinal, subcarinal and hilar adenopathy. Coccidioides immitis IgG and IgM were negative, but urine antigen was positive. There was no radiologic or cerebrospinal fluid evidence of disseminated coccidioidomycosis.Immunologic workup revealed undetectable IgG, IgA, IgM, and IgE (table 1). Lymphocyte subsets showed severe T and NK cell lymphopenia. Total B cell count was normal, but he had decreased CD19+27+ and transitional B cells, with absent switched memory B cells and no plasmablasts (table 1). Lymphocyte proliferation to mitogens/antigens was decreased. Serum ferritin was normal, and EBV PCR was negative. A targeted 429-gene panel identified a hemizygous variant of uncertain significance (VUS) in SH2D1A, c.82_102dup (p.Ser28_Ser34dup). SAP expression was absent in CD4+ T cells and NK cells with a bimodal expression in CD8+ T cells, suggesting possible mosaicism in this subset. He was diagnosed with X-linked lymphoproliferative disease 1 (XLP-1) and treated with fluconazole, trimethoprim-sulfamethoxazole prophylaxis, and IgG replacement (1 g/kg intravenous initially, then transitioned to weekly SCIg targeting an IgG >1000 mg/dL), with clinical improvement, resolution of fevers and acute hypoxia. He was referred for hematopoietic cell transplant evaluation.Coccidioidomycosis has not been described in a new diagnosis of XLP-1 and should be considered in this IEI. Coccidioidomycosis susceptibility has been reported in other IEIs including impaired interleukin-12/interferon-gamma axis signaling, STAT3 loss of function, chronic granulomatous disease, and recently cytidine triphosphate synthase 1 (CTPS1) deficiency.Table 1Patient’s immunologic variables compared to reference range. Absolute values are shownImmunologic VariablePatient ValuesReference RangeIgG<70 (L)<70 mg/dLIgA<15 (L)<15 mg/dLIgM<8 (L)<8 mg/dLIgE<1.5 (L)<1.5 IU/uLTotal CD4+ T Cells11 (L)570–2400 cells/uLTotal CD8+ T Cells63 (L)210–1200 cells/uLTotal CD19+ B cells173165–1154 cells/uLCD19+ CD24++ CD38++ (Transitional B Cells)0 (L)8–392 cells/uLCD19+CD24+CD38+ (Naïve B Cells)12159–1146 cells/uLCD19+CD27-(Naïve B cells)169140–2269 cells/uLCD19+ CD27+ CD38+ IgM- (Plasmablasts)0<30 cells/uLCD19+CD27+IgD-IgM- (Switched-memory B cells)0 (L)6–190 cells/uLCD16+ CD56+ (NK Cells)32 (L)78–470 cells/uLL – low

P031 Montelukast antagonising underlying systemic illness

Abstract Background/Aims Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare, multisystemic, autoimmune vasculitis involving small to medium-sized blood vessels. It has a well-established affiliation with atopic syndromes, typically adult-onset asthma and sinusitis. More rare associations are linked with drug side effects such as Montelukast. According to the ‘American College of Rheumatology 1990’, the following criteria yield a sensitivity of 84% in identifying a patient with EGPA. The criteria include: asthma, eosinophilia &amp;gt;10% on differential white cell count, mononeuropathy or polyneuropathy, transient pulmonary infiltrates on chest radiography, paranasal sinus abnormality, and blood vessel biopsy demonstrating extravascular eosinophilia, in a patient with symptoms of systemic vasculitis. The multisystemic involvement of EGPA makes both diagnosis and management difficult as presentations can vary. Methods We report the complex case of a 61 year-old gentleman diagnosed with EGPA. His relevant past medical history includes a diagnosis of Asthma in 2002 (managed with inhaled bronchodilators, corticosteroids, and montelukast), recurrent sinusitis, and lower respiratory tract infections. The patient presented with a one month history of abdominal cramping and bloating. This was associated with nausea, constipation, anorexia, and a week of ‘drenching’ night sweats. His full physical examination during this time was unremarkable. Results He had a normal CT Abdomen Pelvis and colonoscopy. His admission chest radiograph demonstrated bilateral parenchymal lung changes. This was followed by a CT Thorax showing bilateral upper and lower lobe bronchiectasis. Mediastinal and hilar adenopathy consistent with a diagnosis of allergic bronchopulmonary aspergillosis with associated reactive adenopathy. His laboratory investigations showed eosinophilia (21.68) and leucocytosis (32.7). In view of these results, an autoantibody screen was sent showing positive ANCA and positive anti-Myeloperoxidase antibodies(MPO titre 55). Two days into his admission he developed pain and paralysis of his right upper limb. He reported marked fatigue followed by a petechial, non-blanching, vasculitic rash on both ankles. Neurological examination reflected a subacute symmetrical sensory and motor polyneuropathy predominantly involving the right side with bilateral foot drop. MRI Brain demonstrated an established infarct in the left external capsule. He was commenced on high dose aspirin. Due to high suspicion for EGPA, methylprednisolone was commenced for 5 days, followed by tapering oral corticosteroid therapy and Rituximab therapy. A skin punch biopsy showed ‘ a vasculopathic type reaction with small vessel vasculitis, associated mixed inflammatory infiltrate which includes some eosinophils’ confirmed his diagnosis. Conclusion A topic of particular relevance to this case is the association between EGPA and montelukast. It has been hypothesised that there may be a relationship between Leukotriene Receptor Antagonist Therapy, specifically Montelukast, with the pathogenesis of EGPA. Some research suggests that treatment with Montelukast permits the decreased need for oral corticosteroids for asthma control. Therefore, suggesting that EGPA could have been masked by corticosteroid therapy. Disclosure Á. Connerton: None.

‘Stepladder Lung Cavities’ with ‘Starry Sky Pattern’ in HRCT Thorax with Constitutional Symptoms: A Strong Predictor of Active Pulmonary Tuberculosis

Pulmonary Tuberculosis is most common diseases in India with significant mortality and morbidity. Tuberculosis can cause diverse thoracic presentations ranging from nodules, consolidations &amp; cavitation, mediastinal adenopathy, pleural effusion to diffuse endobronchial disease presenting like bronchial asthma. In this case report, 29- year male, presented with constitutional symptoms for 4 months duration with partial response to medical treatment received according to their knowledge and experience towards bronchial asthma, enteric fever and jaundice. Radiological investigations documented only prominent hilum left side of thorax which was underestimated due to presence of wheeze. Recurrent, progressive and partially responding constitutional symptoms was the reason for referral to our center. We have also noted prominent hilum with inhomogeneous infiltrates left lung field and localized wheeze and crepitations on left side of thoracic cavity in mammary and interscapular region. We have further evaluated with HRCT thorax and observed thick-walled cavities in left upper lobe posterior segment. ‘Stepladder Lung Cavities’ in HRCT is defined as multiple cavities adjacent with each other partially communicating to noncommunicating of variable size and shape unilaterally or bilaterally in stepladder fashion. ‘Starry sky pattern’ in HRCT Thorax is defined as randomly placed nodular opacities presenting as discrete or conglomerated, interstitial and acinonodular opacities unilateral or bilateral adjacent to pulmonary cavities usually reported as satellite nodules. Satellite nodules are defined as nodular opacities adjacent to pulmonary primary caviatary lung disease and indicator lymphatic local spread and active pulmonary tuberculosis. We have done sputum examination and documented acid-fast bacilli in sputum smear and MTB genome with rifampicin sensitivity in cartridge based nucleic acid amplification test. Treatment initiated with anti-tuberculosis (ATT) and recorded near complete radiological resolution, bacteriological cure after six months with good compliance. High index of suspicion is must while managing these cases with constitutional symptoms with typical ‘Stepladder Lung Cavities’ with ‘starry sky pattern’ in HRCT Thorax to have successful treatment outcome.