March 2024 Pulmonary Case of the Month: A Nodule of a Different Color

Lewis J. Wesselius MD

Pulmonary Department

Mayo Clinic Arizona

Scottsdale, AZ USA

History of Present Illness

The patient is a 73-year-old woman from Wisconsin seen in January 2024 for lung nodules.  She had been followed by her physician in Wisconsin for lung nodules but had never had a biopsy or specific diagnosis. She reported that the nodules “waxed and waned.” Her Wisconsin physician suggested she be evaluated in Arizona.

She has occasional cough attributed to paroxysmal nocturnal dyspnea, but denies sputum production, fever, chills or shortness of breath

Past Medical History, Family History and Social History

• Rheumatoid arthritis diagnosed in her 30s, although not currently on any treatment.
• Breast cancer 2006, treated with chemoradiation
• Osteoporosis
• Family history:  negative for lung cancer or other lung disorders
• Social History: Lifelong nonsmoker

Medications

• None

Physical Examination

• Unremarkable

Laboratory

• Normal CBC
• Cocci serology: negative
• Rheumatoid factor: elevated 61 U/ml (normal < 15)
• Anti-cyclic citrullinated peptide antibody: negative
• Erythrocyte Sedimentation Rate: normal

Radiology

A thoracic CT of the chest done in Wisconsin in November 2023 showed an 18 mm nodule in medial right lower lobe (RLL, Figure 1A) and several other smaller nodules noted, largest other nodule in left lower lobe (LLL, Figure 1B, blue arrow).

Figure 1. Selected images from thoracic CT done November 2023 showing RLL mass (A, red arrow) and LLL mass (B, blue arrow).

What is the next appropriate step in her evaluation? (Click on the correct answer to be directed to the second of six pages)

1. Repeat the thoracic CT scan
2. Bronchoscopy
3. Positron emission tomography (PET) scan
4. 1 and 3
5. All of the above

Cite as: Wesselius LJ. March 2024 Pulmonary Case of the Month: A Nodule of a Different Color. Southwest J Pulm Crit Care Sleep. 2024;28(3):26-29. doi: https://doi.org/10.13175/swjpccs010-24 PDF

June 2019 Pulmonary Case of the Month: Try, Try Again

Lewis J. Wesselius, MD

Department of Pulmonary Medicine

Mayo Clinic Arizona

Scottsdale, AZ USA

History of Present Illness

A 53-year-old woman from presented with a 3-year history of shortness of breath. She was diagnosed with pneumonia in 2016, but even after treatment with antibiotics, continued to require supplemental oxygen. A CT-guided biopsy of a lung nodule was performed but there were no diagnostic findings. A surgical lung biopsy at another hospital was done but the report is unavailable. She had been diagnosed with possible scleroderma and treated with mycophenolate for 3 months and then azathioprine. 

Past Medical History, Social History and Family History

Aside from her history as in the HPI she has a remarkably negative past medical history. She does not smoke. Family history is noncontributory.

Physical Examination

• HEENT:  negative
• Chest:  Fine crackles at both lung bases
• Cardiovascular: regular rhythm, no murmur
• Skin:  skin thickening on fingers and distal forearms, but not elsewhere.  No pitting, ulcerations or calcinosis

Radiology

A chest x-ray was performed (Figure 1).

Figure 1. PA chest radiography done on presentation.

Which of the following should be done? (Click on the correct answer to be directed to the second of six pages)

1. Obtain previous radiography and biopsy reports
2. Pulmonary function testing
3. Thoracic CT scan
4. 1 and 3
5. All of the above

Cite as: Wesselius LJ. June 2019 pulmonary case of the month: Try, try again. Southwest J Pulm Crit Care. 2019;18(6):144-51. doi: https://doi.org/10.13175/swjpcc026-19 PDF

Treatment of Lymphoma and Cardiac Monitoring during Pregnancy

Stella Pak, MD

Yan Yatsynovich, MD 

Damian Valencia, MD

Calvert Busch, MD

Emily Vannorsdall, MD

Department of Medicine

Kettering Medical Center

Kettering, OH USA

Abstract

Limited data is available regarding fetal-maternal outcomes with chemotherapy during pregnancy, including cardiovascular toxicity and evaluation thereof. Early cardiovascular evaluation and initiation of cardioprotective therapies should be considered. Herein, we report a case of a 33-year-old woman treated with R-CHOP chemotherapy for large B-cell lymphoma found to have some degree of reversible cardiac strain.

Introduction

There are no guidelines specific for cardiotoxicity monitoring in pregnant patients undergoing chemotherapy. Pregnant patients are more vulnerable to cardiovascular complications, such as congestive heart failure, from chemotherapy as their cardiovascular system is under considerable stress from increasing physiological demands in pregnancy. With elevated cardiac output and circulatory volume from baseline, these patients do not have much cardiopulmonary reserve to compensate for cardiac strains from chemotherapy side effects (1). Therefore, it would be critical for clinicians to be aware of increased risk of cardiovascular adverse effect from chemotherapeutic agents in pregnant patients. Herein, we report a case of a 33-year-old woman treated with R-CHOP chemotherapy for large B-cell lymphoma found to have some degree of reversible cardiac strain.

Case Presentation

An otherwise healthy 33-year-old Caucasian female, G2P1 at 24 weeks gestation presented with a chief complaint of cough, chest pressure, and swelling in the neck and face. Physical exam was notable for a negative Pemberton’s sign, two lymph nodes in the right supraclavicular region measuring approximately 2 cm without axillary or groin lymphadenopathy. Cardiac exam demonstrated distant heart sounds with a faint I-II/VI systolic murmur in the left second intercostal space, without presence of bruits or lower extremity edema. Lung exam was positive for occasional wheezing in the left lower lobe. Breast exam was normal. Initial chest x-ray (Figure 1) and computed tomography (CT) scan (Figure 2) of the chest revealed a mediastinal mass (11 x 9.2 x 8.7 cm) and a moderate sized pericardial effusion.

Figure 1. Roentgenogram of chest demonstrating a large mass on left lower lobe and pericardial effusion.

Figure 2. Computerized tomography of chest revealing a large homogeneous left mediastinal mass (92.1 mm X 87.1 mm).

Follow up CT-guided biopsy yielded a diagnosis of large B-cell lymphoma. Bronchoscopy done at that time demonstrated diffuse tracheal and bronchial involvement, likely pointing to primary mediastinal derivation of the tumor. Interestingly, the patient had a history of lymph node biopsy of two areas on her right lateral neck and right medial supraclavicular node; pathology reports were consistent with granulomatous disease at that time. Due to pregnancy, baseline positron emission tomography (PET)/CT was not performed, however, the patient did undergo staging with a CT scan of the chest and abdominal/pelvic and magnetic resonance imaging (MRI), both of which were negative for metastatic disease. Bone marrow biopsy obtained was negative for malignancy as well. Dose-adjusted R-EPOCH (rituximab, etoposide, prednisone, oncovin, cyclophosphamide, hydroxydaunorubicin) was replaced with R-CHOP (rituximab, cyclophosphamide, hydroxydaunomycin, oncovin, prednisolone) due to the teratogenic effects of etoposide. Embryologic toxicity has previously been observed with etoposide including skeletal abnormalities, exencephaly, encephalocele and anophthalmia. Monitoring of cardiac function was performed before, during and after treatment. Initial echocardiogram demonstrated preserved ejection fraction (EF) of 60% with a large pericardial effusion and early signs of tamponade. No strain studies were done prior to initiation of chemotherapy. The patient had undergone a total of six cycles with a good response. Upon treatment completion fluoro-D-glucose (FDG)-PET/CT did show persistent uptake mostly in the manubrium as well as a persistent mediastinal mass with a low standardized uptake values (SUV).

The patient had initially considered radiotherapy in her post-delivery course, but given her most recent PET scan with a Deauville score of less than 4, the patient decided to avoid radiation and opted for close follow-up with repeat imaging. The Deauville 5-point scoring system is an internationally accepted point based scale used to characterize fluorodeoxyglucose (FDG) avidity of malignant tumor mass as seen on FDG positron emission tomography (PET) scan. Scores between 1 and 2 are considered negative, a score of 3 is typically paired with other studies and clinical signs to determine progression of disease, a score of 4 and 5 are considered positive for malignancy progression. Her pericardial effusion had resolved with chemotherapy.

Echocardiographic cardiac strain evaluation performed during follow-up evidenced a drop in her longitudinal strains from 22.8 to -15% just prior to delivery. Ejection fraction remained preserved at >60%. Low-dose carvedilol was considered during treatment however patient was not agreeable. The patient had an uneventful delivery and strain studies post-delivery showed a stable -15% strain. Echocardiogram performed 6 months post-chemotherapy demonstrated an ejection fraction of 72% and normalization of longitudinal strain. In the light of chemotherapy with known cardiotoxic adverse effects, as well as pregnancy strain on cardiac function, the patient did well and underwent an uneventful course.

Discussion 

The majority of data on maternal and fetal cardiotoxic effects of chemotherapy during pregnancy is based on case reports and retrospective data collection (2).

Registry data seems to suggest that the incidence of toxic side effects is not significantly increased during pregnancy and in the current literature there is no mention of an increased frequency of heart failure or left ventricular dysfunction during pregnancy (3-5). A study by Van Calsteren et al. (6), suggested that serum levels of chemotherapy, including anthracyclines, measured in pregnant women, were lower compared with those in nonpregnant women although the differences were not statistically significant. Despite the lower serum levels, cardiotoxicity might have a more significant impact on the maternal cardiovascular system in a context of increased hemodynamic loading. The use of cardiotoxic medications during pregnancy requires further attention, however no standard cardiac follow-up protocols are currently in place (7).

There may be a need for clinical cardiac assessments and an echocardiographic functional evaluation, including cardiac strain monitoring, prior to starting chemotherapy and repeat echocardiographic evaluation prior to every dose. If changes in cardiac function are observed, less cardiotoxic treatments might be considered or cardioprotective agents could be used. In this particular patient population, baseline echocardiography with strain study is crucial. Evidence of abnormal strain study during any part of the treatment should prompt initiation of cardioprotective therapy as per standards of the current heart failure guidelines. In addition, we suggest consideration for close cardiac follow-up monitoring, including a repeat echocardiogram study at 12 months post completion of chemotherapy/radiotherapy treatment. It is still unclear whether prophylactic therapy with cardioprotective agents would be safe and beneficial in these patients. Though we may be able to extrapolate data from trials performed on non-pregnant patients undergoing therapy and apply it to this particular niche of patients. The 2013 ACC/AHA heart failure guidelines state that it may be reasonable to evaluate those who are receiving (or who have received) cardiotoxic chemotherapy agents for left ventricular dysfunction as well as use echocardiographic techniques or biomarkers to identify increased heart failure risk in those receiving chemotherapy (8). In addition, the 2012 European Society of Medical Oncology (ESMO) guidelines stress on importance of serials cardiac function monitoring at baseline, 3, 6 and 9 months during treatment and then at 12 and 18 months after initiation of treatment (9).

Today, there is still no clear consensus with regards to cardioprotective therapy in patients exposed to cardiotoxic agents. As of 2016, the ACC/AHA guidelines did not reflect any change in recommendations in this particular field. Risk-stratification and prophylactic cardioprotective therapy remain an ultimate goal in pregnant patients undergoing chemotherapy, but how that should be done is still being studied. Early cardiology involvement and possible early initiation of prophylactic heart failure therapy should be considered.

References

1. Fadol AP, Lech T, Bickford C, Yusuf SW. Pregnancy in a patient with cancer and heart failure: challenges and complexities. J Adv Pract Oncol. 2012 Mar;3(2):85-93. [PubMed]
2. Gziri MM, Amant F, Debiève F, Van Calsteren K, De Catte L, Mertens L. Effects of chemotherapy during pregnancy on the maternal and fetal heart. Prenat Diagn. 2012 Jul;32(7):614-9. [CrossRef] [PubMed]
3. Cardonick E, Dougherty R, Grana G, Gilmandyar D, Ghaffar S, Usmani A. Breast cancer during pregnancy: maternal and fetal outcomes. Cancer J. 2010;16(1):76-82. [CrossRef] [PubMed]
4. Van Calsteren K, Heyns L, De Smet F, et al. Cancer during pregnancy: an analysis of 215 patients emphasizing the obstetrical and the neonatal outcomes. J Clin Oncol. 2010 Feb 1;28(4):683-9. [CrossRef] [PubMed]
5. Cardonick E, Iacobucci A. Use of chemotherapy during human pregnancy. Lancet Oncol. 2004 May;5(5):283-91. [CrossRef] [PubMed]
6. Van Calsteren K, Verbesselt R, Ottevanger N, et al. Pharmacokinetics of chemotherapeutic agents in pregnancy: a preclinical and clinical study. Acta Obstet Gynecol Scand. 2010 Oct;89(10):1338-45. [CrossRef] [PubMed]
7. Ewer MS, Ewer SM. Cardiotoxicity of anticancer treatments: what the cardiologist needs to know. Nat Rev Cardiol. 2010 Oct;7(10):564-75. [CrossRef] [PubMed]
8. Yancy CW, Jessup M, Bozkurt B, et al. 2013 2013 ACCF/AHA guideline for the management of heart failure: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation. 2013 Oct 15;128(16):1810-52. [CrossRef] [PubMed]
9. Curigliano G, Cardinale D, Suter T, et al. Cardiovascular toxicity induced by chemotherapy, targeted agents and radiotherapy: ESMO Clinical Practice Guidelines. Ann Oncol. 2012 Oct;23 Suppl 7:vii155-66. [CrossRef] [PubMed]

Cite as: Pak S, Yatsynovich Y, Valencia D, Bushch C, Vannorsdall E. Treatment of lymphoma and cardiac monitoring during pregnancy. Southwest J Pulm Crit Care. 2017;15(4):154-8. doi: https://doi.org/10.13175/swjpcc106-17 PDF 

October 2016 Pulmonary Case of the Month

Coya T Lindberg, BS¹

Ryan R Nahapetian, MD²

F Zahra Aly, MD, PhD, FRCPath³

¹University of Arizona College of Medicine Tucson, Tucson, AZ

²Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, University of Arizona, Tucson, AZ

³Brody School of Medicine at East Carolina University, NC

Pulmonary Case of the Month CME Information

Members of the Arizona, New Mexico, Colorado and California Thoracic Societies and the Mayo Clinic are able to receive 0.25 AMA PRA Category 1 Credits™ for each case they complete. Completion of an evaluation form is required to receive credit and a link is provided on the last panel of the activity. 

0.25 AMA PRA Category 1 Credit(s)™

Estimated time to complete this activity: 0.25 hours

Lead Author(s): Coya Lindberg, BS.  All Faculty, CME Planning Committee Members, and the CME Office Reviewers have disclosed that they do not have any relevant financial relationships with commercial interests that would constitute a conflict of interest concerning this CME activity.

Learning Objectives:
As a result of this activity I will be better able to:

1. Correctly interpret and identify clinical practices supported by the highest quality available evidence.
2. Will be better able to establsh the optimal evaluation leading to a correct diagnosis for patients with pulmonary, critical care and sleep disorders.
3. Will improve the translation of the most current clinical information into the delivery of high quality care for patients.
4. Will integrate new treatment options in discussing available treatment alternatives for patients with pulmonary, critical care and sleep related disorders.

Learning Format: Case-based, interactive online course, including mandatory assessment questions (number of questions varies by case). Please also read the Technical Requirements.

CME Sponsor: University of Arizona College of Medicine at Banner University Medical Center Tucson

Current Approval Period: January 1, 2015-December 31, 2016

Financial Support Received: None

A 49-year-old man presented with chest discomfort to an outside medical facility in Arizona. He was previously healthy and had no chronic medical diseases. Physical examination was unremarkable and he was afebrile. A chest X-ray was performed (Figure  1).

Figure 1. Initial chest x-ray

Which of the following is most likely? (Click on the correct answer to proceed to the second of five panels)

1. There is a large right chest mass
2. There is a loculated pleural effusion in the minor fissure
3. There is a right ventricular aneurysm
4. There is right lower lobe consolidation
5. There is right middle lobe consolidation

Cite as: Lindberg CT, Nahapetian RR, Aly FZ. October 2016 pulmonary case of the month. Southwest J Pulm Crit Care. 2016;13(4):152-8. doi: http://dx.doi.org/10.13175/swjpcc096-16 PDF

May 2013 Pulmonary Case of the Month: the Cure Can be Worse than the Disease

Lewis J. Wesselius, MD¹

Thomas V. Colby, MD²

Departments of Pulmonary Medicine¹ and Laboratory Medicine and Pathology²

Mayo Clinic Arizona

Scottsdale, AZ

History of Present Illness

A 65 year old man from Colorado presented for evaluation of “lung masses.” He had a prior diagnosis of dermatomyositis made in 2010 and had been with intravenous immunoglobulin (IVIG), prednisone and methotrexate. He had been previously seen in January, 2011 with a 5 mm left lower lobe nodule on thoracic CT which was unchanged compared to August, 2010. A thoracic CT scan done in July, 2011 in Colorado was interpreted as stable.

Over the prior month had been having chest discomfort.  He had a history of pulmonary embolism (PE) and felt the pain was similar in quality to his prior PE. This prompted a chest x-ray and he was told of “lung masses”. He had also experienced 20 pound weight loss.

His current medications included methotrexate 25 mg weekly, prednisone 3 mg every other day and warfarin 7 mg daily.

PMH, SH, FH

In addition to dermatomyositis, he has a history of a left lower extremity deep venous thrombosis with PE. At that time protein S deficiency, activated protein C resistance and factor V Leiden mutation were diagnosed and an inferior vena cava filter were placed. He also has a history of paroxysmal atrial fibrillation and the prior lung nodule noted above.

He was a prior smoker, quitting in 1991, but briefly resuming in 2010.  The patient had social alcohol use but no drug use. 

The patient’s father died at age 75 from prostate cancer; his mother died at age 89 with heart disease; and he had a sister living with throat cancer.

Physical Examination

Vital signs: Afebrile; Blood pressure 114/65 mm/Hg; Pulse 80 regular; Oxygen  Saturation  97% on room air at rest

HEENT: limited ability to open mouth

Chest:  few late exp wheezes

CV: Regular rhythm, no murmur

Skin: diffuse erythema, particularly on face. 

Neuro: muscle strength normal 

Radiography

His thoracic CT is shown in Figure 1.

Figure 1. Movies of the thoracic CT scan showing lung windows (Panel A, upper panel) and mediastinal windows (Panel B, lower panel).

Which of the following are pulmonary manifestations of dermatomyositis?

1. Lung cancer
2. Aspiration pneumonia
3. Interstitial lung disease
4. Metastatic cancer particularly from the cervix, pancreas, breasts, ovaries, gastrointestinal tract and lymph nodes
5. All of the above

Reference as: Wesselius LJ, Colby TV. May 2013 pulmonary case of the month: the cure can be worse than the disease. Southwest J Pulm Crit Care. 2013;6(5):199-208. PDF