February 2025 Imaging Case of the Month: A Wolf in Sheep’s Clothing

Mathew T. Stib MD and Michael B. Gotway MD

Department of Radiology

Mayo Clinic Arizona

Phoenix, AZ USA

Clinical History: A 72-year-old man presents to his physician with chest pain. The patient awoke 2 weeks earlier with right-sided chest pain, thought to be the result of a pulled muscle. However, the pain did not remit over the next 2 weeks. The patient also complained of a mild cough productive of white sputum and some mild intermittent shortness of breath improving with albuterol. The patient denied fever.

The patient’s past medical history was remarkable for seasonal allergies, especially dust exposure, treated with fluticasone, and occasional wheezing, treated as needed with an albuterol inhaler. The patient was also diabetic and had hypertension and a history of hypothyroidism. The patient’s past surgical history included right knee total arthroplasty and lithotripsy for renal stones. The patient denied allergies, smoking, and illicit drug use. His medications included fluticasone, albuterol, amlodipine, atorvastatin, ramipril, sitagliptin-metformin, levothyroxine, and probiotics.    

The patient’s vital signs included a blood pressure of 121/75 mmHg, a pulse rate of 78/minute, a respiratory rate of 18/minute and a temperature of 36.4°C. Pulse oximetry on room air was 96%. The patient’s weight was 89.kg, his body mass index 28.15 kg/m2. The physical examination was unremarkable. In particular, the breath sounds were normal.

A complete blood count showed a mildly elevated white blood cell count at 11.1 x 109/L (normal, 3.4 – 9.6 x 109/L), with a normal absolute neutrophil count of 3.36  x 109/L (normal, 1.56 – 6.45 x 109/L). His hemoglobin and hematocrit values were mildly decreased at 11.1 gm/dL (normal, 13.5 – 17.5 gm/dL) and 36.3% (normal, 38.8 – 50%). The platelet count was normal at 280 x 109/L (normal, 149 – 375 x 109/L). The patient’s serum chemistries and liver function studies were normal aside from an a mildly decreased serum calcium level of 8.6 mg/dL (normal, 8.8-10.2 mg/dL), an elevated glucose level of 186 mg/dL, (normal, 70-100 mg/dL), and a mildly elevated alkaline phosphatase level of 121 U/L (normal, 45-115 U/L). The urinary drug toxicity screen was negative, and coagulation parameters were normal. The thyroid stimulating hormone level was within the normal range. Frontal and lateral chest radiography (Figure 1) was performed.

Figure 1. Frontal and lateral chest radiography. To open figure 1 in a separate, enlarged window click here.

Which of the following statements regarding this chest radiograph is most accurate? (click on the correct answer to be directed to the second of eleven pages)

1. The frontal chest radiograph shows no abnormal findings

2. The frontal chest radiograph shows basal predominant fibrotic abnormalities

3. The frontal chest radiograph shows large lung volumes with a cystic appearance

4. The frontal chest radiograph shows a partially circumscribed opacity projected over the right thorax

5. The frontal chest radiograph shows abnormal mediastinal contours

Cite as: Stib MT, Gotway MB. February 2025 Imaging Case of the Month: A Wolf in Sheep’s Clothing. Southwest J Pulm Crit Care Sleep. 2025;30(2):14-25. doi:

https://doi.org/10.13175/swjpccs003-25

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January 2025 Medical Image of the Month: Psoriasis with Pulmonary Involvement

Figure 1. Axial lung-windowed CT reconstructions through the mid (A,B) and lower (C) lungs from a 58-year-old man with psoriasis presenting for evaluation of interstitial lung disease.  There is peripheral and lower lung predominant reticulation, ground glass, and traction bronchiolectasis with architectural distortion and atelectasis. To view Figure 1 in a separate enlarged window click here.  

Figure 2. Low-power (A) and high-power (B,C) hematoxylin & eosin-stained pathology slides from a surgical lung biopsy (left lower lobe) demonstrating scattered lymphoid aggregates with patchy granulomatous organizing pneumonia and scattered loosely formed nonnecrotizing granulomas, concern for underlying systemic connective tissue disease-related interstitial lung disease. To view Figure 2 in a separate enlarged window click here.

A 58-year-old man presented to our pulmonary service for a second opinion concerning his interstitial lung disease (ILD), which had been diagnosed as rheumatoid arthritis associated ILD. The patient had a positive rheumatoid factor (barely) at an outside institution, but no other test results or historical or physical exam findings to suggest rheumatoid arthritis. He was being treated with mycophenolate, but did not feel that he was improving. To the contrary, there had been a recent decline in his overall lung function. The only other relevant medical history is psoriasis. The patient is a lifelong nonsmoker. Resting pulse oximetry was 95% on room air with a brief desaturation to 88% during ambulation, which quickly recovered with rest. The patient’s vital signs were otherwise normal. Physical exam findings were normal aside from mild cutaneous findings of plaque psoriasis. Results from pulmonary function testing at an outside institution were available, revealing a forced vital capacity 40% of reference and DLCO 37% of reference. The overall picture was consistent with restrictive lung disease. Images from an outside CT (Figure 1) demonstrated patchy findings of ILD with peripheral and lower lobe predominant reticulation, ground glass, and architectural distortion without any significant honeycombing or air trapping. The pattern was felt to be pretty nonspecific, but most consistent with ILD in the setting of autoimmune disease, favoring an NSIP or OP pattern over UIP.

Slides from the patient’s outside surgical lung biopsy were reviewed by our pathology department, who have expertise regarding pulmonary manifestations of psoriasis (1). Pathology (Figure 2) showed randomly distributed lymphoid aggregates in association with mild patchy chronic inflammatory infiltrates and patchy areas of numerous macrophages filling airspaces. There were scattered foci of organizing pneumonia focally with nonnecrotizing granulomas. In addition, there were a few scattered very loosely formed nonnecrotizing granulomas. Rare eosinophils were also present. Rare foci of osseous metaplasia were also identified.  While the findings were felt to be nonspecific, they are most concerning for an underlying systemic connective tissue disease involving the lung. The case was discussed at our multidisciplinary ILD conference and a consensus diagnosis of ILD related to psoriasis was made. There is limited data suggesting possible improvement in psoriatic ILD with psoriasis treatment using secukinumab (2). However, there are also reports of secukinumab exacerbating ILD in the setting of psoriasis (3). Given the patient’s lack of improvement on mycophenolate, a trial of secukinumab is being considered.

Interstitial pneumonia is relatively rare in the setting of psoriasis, with a series of 392 psoriasis patients demonstrating an incidence of 2% (4). In this series, the most common imaging findings were lower lung predominate ground glass and reticulation, as was seen in this case. Interestingly, one case series (5) found that a UIP pattern of fibrosis was the most common pattern of ILD on CT in patients with plaque psoriasis; however, many of these patients were smokers. Concomitant smoking seems to predispose the patient towards a UIP pattern of ILD in the setting of psoriasis. In non-smokers, NSIP and OP patterns of ILD seemed more prevalent. Although rare, ILD in psoriasis is an important possibility to consider given that some patients treated with biologic agents for their psoriasis experienced improvements in their ILD (2,4).

Clint Jokerst, MD1, Yasmeen M. Butt, MD2

Departments of 1Radiology and 2Pathology

Mayo Clinic Arizona

Phoenix, AZ USA

References

1. Butt YM, Smith ML, Tazelaar HD, Roden AC, Mengoli MC, Larsen BT. Surgical Pathology of Diffuse Parenchymal Lung Disease in Patients With Psoriasis or Psoriatic Arthritis. Arch Pathol Lab Med. 2022 May 1;147(5):525-533. [CrossRef][PubMed]

2. Miyachi H, Nakamura Y, Nakamura Y, Matsue H. Improvement of the initial stage of interstitial lung disease during psoriasis treatment with secukinumab. J Dermatol. 2017 Dec;44(12):e328-e329. [CrossRef][PubMed]

3. Kajihara I, Yamada-Kanazawa S, Maeda-Otsuka S, Jinnin M, Akaike K, Ihn H. Secukinumab-induced interstitial pneumonia in a patient with psoriasis vulgaris. J Dermatol. 2017 Dec;44(12):e322-e323. [CrossRef][PubMed]

4. Kawamoto H, Hara H, Minagawa S, Numata T, Araya J, Kaneko Y, Umezawa Y, Asahina A, Nakagawa H, Kuwano K. Interstitial Pneumonia in Psoriasis. Mayo Clin Proc Innov Qual Outcomes. 2018 Sep 20;2(4):370-377. [CrossRef][PubMed]

5. Rizzetto G, Tagliati C, Fogante M, et al. CT Patterns of Interstitial Lung Disease in Patients with Plaque Psoriasis: A Retrospective Case Series Study. Medicina (Kaunas). 2023 Sep 12;59(9):1650. [CrossRef][PubMed]

Cite as: Jokerst C, Butt YM. January 2025 Medical Image of the Month: Psoriasis with Pulmonary Involvement. Southwest J Pulm Crit Care Sleep. 2025;30(1):5-7. doi:

https://doi.org/10.13175/swjpccs054-24

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December 2024 Medical Image of the Month: An Endobronchial Tumor

Figure 1. PA (A) and lateral (B) CXR from a woman with wheezing demonstrating a right perihilar nodule projecting within the lingula (circled) with associated atelectasis. To view Figure 1 in a separate, enlarged window click here.

Figure 2. Inspiratory (A) and expiratory (B) axial CT images demonstrating a mass obstructing the lingular bronchus (*) with post-obstructive mucus plugging (arrow) and air-trapping (circled). Axial image from an FDG PET-CT (C) demonstrates moderate FDG uptake within the nodule (arrowhead). No other areas of tracer uptake were seen to suggest nodal metastatic disease. To view Figure 2 in a separate, enlarged window click here.

Figure 3. Images from virtual bronchoscopic reconstructions from the patient’s CT (A) demonstrating a nodule obstructing the lingular bronchus. Image from bronchoscopy (B) obtained just prior to biopsy correlates nicely with virtual bronchoscopic findings. To view Figure 3 in a separate, enlarged window click here.

Figure 4. Low-power (A) and high-power (B,C) hematoxylin & eosin-stained pathology slides from the nodule demonstrating submucosal tumor adjacent to airway cartilage (*). The tumor contains some squamoid-appearing cells (B) as well as some mucinous cells (C, arrows) and intermediate-appearing cells (C, arrowhead). To view Figure 4 in a separate, enlarged window click here.

A 61-year-old woman was for wheezing. She reported that the symptoms were sudden in onset and persisted for 2 months without improvement. There was no infectious prodrome, no history of an aspiration event, and the symptoms had no exacerbating or relieving factors. The patient reported a past medical history of reflux (controlled on omeprazole), dyslipidemia, hypertension, and migraine headaches. Her past surgical history includes remote histories of breast augmentation, hysterectomy and salpingo-oophorectomy, cholecystectomy, and urethral sling. The patient was a never-smoker with no history of illicit drug use, travel, or exposures. Family history was non-contributory. The patient medications included Crestor, Thiazide, Imitrex, Losartan, and Omeprazole. No known drug allergies.

Her vital signs were normal. Physical exam demonstrated an inspiratory wheeze which was diffuse and best appreciated anteriorly. A PA and Lateral chest x-ray was done at the time of initial referral (Figure 1). A CT scan was subsequently obtained (Figure 2), the results of which led to a PET-CT (Figure 2) and, eventually, bronchoscopy with biopsy (Figure 3). Pathological results were consistent with a low-grade mucoepidermoid carcinoma (MEC) (Figure 4). The patient subsequently underwent left upper lobectomy with lymph node dissection. Surgical pathology demonstrated a 2.5 cm well-differentiated MEC with negative margins; all sampled lymph nodes were negative for malignancy.

MEC in the lungs is rare, accounting for 0.1%-0.2% of pulmonary malignancies (1). These tumors are thought to arise from minor salivary glands in the tracheobronchial tree (2). They are classified as low grade or high grade based on histological criteria (3). On imaging, these tumors are more common in lobar or segmental airways and tend to be round or lobular with well-circumscribed margins. They tend to be vascular and demonstrate heterogeneous enhancement on contrast-enhanced CT. Because they arise from the lining of the airways, they are often associated with post-obstructive findings like mucus plugging, air-trapping, atelectasis, and pneumonia. Patients usually present with symptoms related to endoluminal growth, including persistent cough/sputum, wheezing, dyspnea, hemoptysis, and/or recurrent pneumonias. Patients are often initially mis-diagnosed with asthma, bronchitis, or COPD. The patients frequently do not have a smoking history, which can be helpful when ordering a differential diagnosis. The lesions often demonstrate submucosal growth so bronchial washings/brushings are often negative, as was the case for this patient. This case is a good reminder of the “other” endobronchial tumors, which also include carcinoid tumors (well-circumscribed, vascular, more common in bronchi as opposed to trachea), adenoid cystic carcinoma (usually involve the trachea as a “cylindroma”, have submucosal and perineural growth), sarcomas (chondrosarcoma, sarcoma metastases), hamartomas (often contain fat and/or popcorn calcifications), and tracheobronchial papillomatosis (younger patients, multiple cavitary lesions) (4).

Clinton E. Jokerst MD, Matthew T. Stib MD, Carlos Rojas MD, Michael B. Gotway MD

Department of Radiology

Mayo Clinic Arizona

Phoenix, AZ USA

References

1. Miller DL, Allen MS. Rare pulmonary neoplasms. Mayo Clin Proc. 1993 May;68(5):492-8. doi: [CrossRef] [PubMed]
2. Ishizumi T, Tateishi U, Watanabe S, Maeda T, Arai Y. F-18 FDG PET/CT imaging of low-grade mucoepidermoid carcinoma of the bronchus. Ann Nucl Med. 2007 Jul;21(5):299-302. [CrossRef][PubMed]
3. Yousem SA, Hochholzer L. Mucoepidermoid tumors of the lung. Cancer. 1987 Sep 15;60(6):1346-52. [CrossRef] [PubMed]
4. Park CM, Goo JM, Lee HJ, Kim MA, Lee CH, Kang MJ. Tumors in the tracheobronchial tree: CT and FDG PET features. Radiographics. 2009 Jan-Feb;29(1):55-71. [CrossRef] [PubMed]

Cite as: Jokerst CE, Stib MT, Rojas C, Gotway MB. December 2024 Image of the Month: An Endobronchial Tumor. Southwest J Pulm Crit Care Sleep. 2024;29(6):57-59. doi: https://doi.org/10.13175/swjpccs051-24 PDF

November 2024 Medical Image of the Month: A Case of Short Telomeres

Figure 1. PA (A) and lateral (B) CXR demonstrating small lung volumes with peripheral reticulonodular opacities. The findings are highly suggestive of pulmonary fibrosis. To view Figure 1 in a separate, enlarged window click here.

Figure 2. Axial CT images from the upper (A), mid (B), and lower lungs (C). Images demonstrate a rather nonspecific pattern of fibrosis consisting of patchy areas of reticulation, ground glass, and septal line thickening. The findings are peripheral-predominant, but there was no predilection for the lung bases vs. apices. No subpleural honeycombing was seen. To view Figure 2 in a separate, enlarged window click here.

Figure 3. Results from telomere length testing of lymphocytes (A) and granulocytes (B). The results of both tests put the patient below the 10th percentile with the granulocyte telomere length being below the 1st percentile. To view Figure 3 in a separate, enlarged window click here.

A 50-year-old woman was referred to our institution for further evaluation of her ILD. Her history of present illness began during the COVID-19 pandemic, when she noticed that she had trouble climbing stairs while wearing a mask. She also had a slowly progressive cough which, at first, she attributed to seasonal allergies. Eventually her symptoms prompted pulmonary function testing at an outside institution, which showed moderately severe restriction with a DLco 40% of predicted. Chest x-ray (Figure 1) and chest CT (Figure 2) demonstrated findings of pulmonary fibrosis. The patient worked as an accountant and was a life-long nonsmoker. No concerning exposure history and no history of any medications associated with pulmonary fibrosis. Her family history is remarkable for a brother diagnosed with IPF at age 49, currently status post lung transplant. Her sister and father were both diagnosed with alpha-1-antitrypsin (both died in their 50’s). The patient also reports premature graying of her hair, at age 17. The combination of family history, gray hair, and pulmonary fibrosis prompted further testing for short telomeres, which was positive (Figure 3). The patient was diagnosed with interstitial lung disease secondary to short telomere syndrome.

Telomeres are short repeating nucleotides that the end of chromosomes that protect them from gradual degradation during aging (1). Short telomere syndromes (STSs) are accelerated-aging syndromes often caused by heritable gene mutations that result in decreased telomere length. Organ systems with increased cell turnover, such as skin, lungs, bone marrow, and GI tract, are most commonly affected (2). The relationship between telomere length and interstitial lung disease is complicated. The first association between genetically determined telomere abnormalities and lung fibrosis was observed for the telomeropathy dyskeratosis congenital (DC), an entity characterized by skin abnormalities, bone marrow failure, and pulmonary fibrosis, which was observed in 19% of patients (3). Mutations in other telomere related genes have subsequently been identified in familial and sporadic idiopathic interestitial pneumonias (4-6). Short telomeres have been identified in about 25 percent of sporadic cases of IPF (7) and should be suspected in patients with familial pulmonary fibrosis and/or early onset IPF in patients with signs of premature aging, such as developing gray hair at a young age.

Clinton E. Jokerst MD, Matthew T. Stib MD, Carlos A. Rojas MD, Michael B. Gotway MD

Department of Radiology

Mayo Clinic Arizona

Phoenix, AZ USA

References

1. Martínez P, Blasco MA. Telomere-driven diseases and telomere-targeting therapies. J Cell Biol. 2017 Apr 3;216(4):875-887. [CrossRef] [PubMed]
2. Mangaonkar AA, Patnaik MM. Short Telomere Syndromes in Clinical Practice: Bridging Bench and Bedside. Mayo Clin Proc. 2018 Jul;93(7):904-916. [CrossRef] [PubMed]
3. Knight S, Vulliamy T, Copplestone A, Gluckman E, Mason P, Dokal I. Dyskeratosis Congenita (DC) Registry: identification of new features of DC. Br J Haematol. 1998 Dec;103(4):990-6. [CrossRef] [PubMed]
4. Cronkhite JT, Xing C, Raghu G, Chin KM, Torres F, Rosenblatt RL, Garcia CK. Telomere shortening in familial and sporadic pulmonary fibrosis. Am J Respir Crit Care Med. 2008 Oct 1;178(7):729-37. [CrossRef] [PubMed]
5. Diaz de Leon A, Cronkhite JT, Katzenstein AL, et al. Telomere lengths, pulmonary fibrosis and telomerase (TERT) mutations. PLoS One. 2010 May 19;5(5):e10680. [CrossRef] [PubMed]
6. Newton CA, Batra K, Torrealba J, et al. Telomere-related lung fibrosis is diagnostically heterogeneous but uniformly progressive. Eur Respir J. 2016 Dec;48(6):1710-1720. [CrossRef] [PubMed]
7. Armanios MY, Chen JJ, Cogan JD, et al. Telomerase mutations in families with idiopathic pulmonary fibrosis. N Engl J Med. 2007 Mar 29;356(13):1317-26. [CrossRef] [PubMed]

Cite as: Jokerst CE, Stib MT, Rojas CA, Gotway MB. November 2024 Medical Image of the Month: A Case of Short Telomeres. Southwest J Pulm Crit Care Sleep. 2024;29(5):45-47. doi: https://doi.org/10.13175/swjpccs049-24 PDF

November 2024 Imaging Case of the Month: A Recurring Issue

Michael B. Gotway MD

Department of Radiology

Mayo Clinic, Arizona

Phoenix, Arizona USA

Clinical History: A 65-year-old woman with a history of orthotopic liver transplantation 2 years earlier for non-alcoholic steatohepatitis presented to the Emergency Room for chronic fatigue, malaise, nausea and vomiting, and generalized weakness. She denies shortness of breath, hemoptysis, or productive cough. Her post liver transplant course was complicated by wound infection, biliary stricture requiring ERCP with stent placement, and Clostridium difficile colitis. Prior to her liver transplant the patient had chronic renal insufficiency which has been slowly progressing (creatinine of 2.8 mg/dL, estimated GFR of 17.6 mL) and she was currently undergoing renal transplant evaluation. The patient also has a past medical history of coronary artery disease requiring bypass grafting surgery, hypothyroidism requiring hormone replacement, and type II diabetes not requiring specific therapy. Her past surgical history included cholecystectomy and hysterectomy.

The patient is a lifelong non-smoker, she reports an allergy to penicillin and amoxicillin (hives), and she does not drink alcohol, and denies illicit drug use. Her medications include tacrolimus, mycophenolic acid, allopurinol, calcium, vitamin D, levothyroxine, pantoprazole, sertraline, fluconazole, sulfamethoxazole and trimethoprim, and prednisone.

On physical examination the patient was febrile (39.2º C). Her blood pressure was initially 97/53 mmHg; however, during her stay in the Emergency Department went as low as 71/41 mmHg. Her heart rate remained in the low to mid 90s, her respiratory rate was 12-14 breaths per minute, and her oxygen saturations were 99% on room air. The patient had uniformly decreased breath sounds bilaterally but the lungs were otherwise clear. Her cardiac examination was normal aside from trace bilateral pedal edema. Her abdominal examination was normal. She was neurologically intact.

A complete blood count showed a normal white blood cell count at 6.2 x 10⁹/L (normal, 3.4 – 9.6 x 10⁹/L), with a normal absolute neutrophil count of 3.65 x 10⁹/L (normal, 1.4 – 6.6 x 10⁹/L); the percent distribution of lymphocytes, monocytes, and eosinophils was normal. Her hemoglobin and hematocrit values were 10 gm/dL (normal, 13.2 – 16.6 gm/dL) and 33.7% (normal, 34.9 – 44.5%). The platelet count was normal at 134 x 10⁹/L (normal, 149 – 375 x 10⁹/L). The patient’s serum chemistries and liver function studies were normal, including an albumin level at 4.3 gm/dL (normal, 3.5 – 5 gm/dL), with normal alanine aminotransferase at 42 U/L (normal, 7-45 U/L) and aspartate aminotransferase of 40 U/L (normal, 8-43 U/L); alkaline phosphatase levels, bilirubin, and coagulation studies were normal. SARS-CoV-2 PCR testing was negative.

Frontal chest radiography (Figure 1) was performed.

Figure 1. Frontal (A) and lateral (B) chest radiography obtained in the Emergency Room. To view Figure 1 in a separate enlarged window, click here.

Which of the following statements regarding this chest radiograph is accurate? (Click on the correct answer to be directed to the second of twelve pages)

1. Frontal chest radiography shows unremarkable findings
2. Frontal chest radiography shows a moderate-to-large right pleural effusion
3. Frontal chest radiography shows mediastinal lymphadenopathy
4. Frontal chest radiography shows pneumothorax
5. Frontal chest radiography shows numerous small nodules

Cite as: Gotway MB. November 2024 Imaging Case of the Month: A Recurring Issue. Southwest J Pulm Crit Care Sleep. 2024;29(6):36-44. doi: https://doi.org/10.13175/swjpccs047-24 PDF

October 2024 Medical Image of the Month: Lofgren syndrome with Erythema Nodosum

Figure 1. 3 photographs of the patient’s lower extremities demonstrating bilateral ankle swelling with erythema and warmth and an erythematous nodule over the medial right knee (middle image). To view Figure 1 in a separate, enlarged window click here.

Figure 2. Contrast-enhanced chest CT with lung (A) and soft tissue(B) windows demonstrating small scattered pulmonary nodules (arrows) and mediastinal and hilar lymphadenopathy (*). To view Figure 2 in a separate, enlarged window click here.

A 33-year-old man with a past medical history of non-metastatic right sided testicular cancer status post radical orchiectomy 10 years prior presented to the emergency department for 1 week of bilateral lower extremity swelling and pain. He had associated shortness of breath, right sided chest pain, fatigue, and night sweats. Physical exam revealed bilateral ankle swelling with erythema and warmth and there was noted an erythematous nodule over the medial right knee and anterior right thigh (Figure 1). He was tachycardic to a rate of 110 bpm, but otherwise had an unremarkable physical exam and review of systems. 

The lower extremity lesions were consistent with erythema nodosum. Sarcoidosis was an amounting differential but as this is a diagnosis of exclusion, alternate causes needed to be ruled out. Deep vein thrombosis was excluded. CT angiogram did not show pulmonary embolus but it did show diffuse multifocal sub centimeter pulmonary nodules measuring up to 8 mm with mediastinal and hilar lymphadenopathy (Figure 2). Coccidioides serologies were negative. Bronchoscopy with EBUS-TBNA showed granulomatous inflammation, and no malignancy. After exclusion of other causes, multidisciplinary discussion concluded Lofgren syndrome in the setting of sarcoidosis.

Lofgren syndrome is characterized by erythema nodosum, shortness of breath, and bilateral hilar lymphadenopathy and is a clinical syndrome of sarcoidosis. It is highly specific for sarcoidosis, and in many cases, it can be diagnostic and tissue sampling is not recommended for diagnosis unless to rule out other causes such as malignancy or infection (1).  Lofgren syndrome is typically self-limiting and does not require chronic treatment, however, in the acute phase, patients can be very symptomatic and may require a short course of glucocorticoids.

Mary Jamison, NP-C

Department of Medicine

Banner University Medical Center, Tucson

Tucson, AZ USA

Reference

1. Crouser ED, Maier LA, Wilson KC, et al. Diagnosis and Detection of Sarcoidosis. An Official American Thoracic Society Clinical Practice Guideline. Am J Respir Crit Care Med. 2020 Apr 15;201(8):e26-e51. [CrossRef] [PubMed]

Cite as: Jamison M. October 2024 Medical Image of the Month: Lofgren syndrome with Erythema Nodosum. Southwest J Pulm Crit Care & Sleep. 2024;29(4):34-35. doi: https://doi.org/10.13175/swjpccs043-24 PDF

September 2024 Medical Image of the Month: A Curious Case of Nasal Congestion

Figure 1. (A) and lateral (B) views from a chest radiograph demonstrates subtle narrowing of the upper to mid trachea.  A sagittal reconstruction from a contrast-enhanced CT (C) demonstrates circumferential tracheal wall thickening with surrounding fat stranding suggesting tracheal inflammation. (Click here to view Figure 1 in a separate, enlarged window)

Figure 2. Initial contrast-enhanced CT with axial reconstructions through the trachea (A) show tracheitis with involvement of the posterior membrane.  On this CT the right bronchus intermedius (B) appears normal. On a 5-year follow-up contrast-enhanced CT, the tracheal inflammation has resolved (C) and there is new thickening and inflammation of the bronchus intermedius (D, arrow). Findings are consistent with a waxing and waning inflammatory process impacting the large airways, in this case granulomatosis with polyangiitis. (Click here to view Figure 2 in a separate, enlarged window)

Figure 3. Soft tissue neck CT with coronal reconstructions through the maxillary sinuses (A) and trachea (B) demonstrates significant mucosal thickening of the sinuses and also acute inflammatory changes along the trachea. (Click here to view Figure 3 in a separate, enlarged window)

A 79-year-old man presented to our institution for evaluation of intermittent fevers, profound nasal pain with congestion, cough, sore throat, voice changes, fatigue, generalized weakness, and loose stools which had been progressively affecting the patient for the last 6 months.  The patient has a past medical history of ulcerative colitis, hypothyroidism, atrial fibrillation, and hypertension. Just preceding the onset of symptoms, the patient had gone on a month-long trip through Africa and Asia. His symptoms were presumed infectious in the outpatient setting and had responded somewhat to an extended course of ciprofloxacin and metronidazole.

The patient had an outpatient head and neck CT that demonstrated significant mucosal thickening of the maxillary sinuses (Figure 4A). An outside hospital CT of the abdomen/pelvis was unremarkable aside from sigmoid diverticulosis. The patient’s significant nasal pain and congestion along with the fevers was suggestive of granulomatosis with polyangiitis (GPA). The differential also included hematologic malignancy and malaria (with travel history) which were ruled out with bone marrow biopsy and blood smears, respectively. Laboratory testing at this point was notable for leukocytosis of 12.6 and C-reactive protein elevated at 10. Rheumatologic testing was positive for ANA and proteinase-3 ANCA. Imaging findings of paranasal sinus mucosal thickening and tracheobronchial thickening (Figure 1, 2A) without sparing of the posterior membrane also supported GPA. Nasal endoscopy revealed mucosal inflammation and thickening. Biopsy was deemed unnecessary in this case. With the clinical history in addition to congruent laboratory, imaging, and endoscopic findings, the patient was diagnosed with GPA and started on oral prednisone for treatment.

This case demonstrates that, although many organ systems can be involved in GPA, not all need to be involved to make the diagnosis. Paranasal sinus thickening (Figure 3) is a common, non-specific finding on CT head that only found significance in this case when combined with the clinical history. The pattern of tracheitis seen was more specific. Involvement of the posterior membrane (see image 1C, 2A) can be seen in GPA, sarcoidosis, or amyloidosis, but importantly not with relapsing polychondritis. Waxing and waning through time is classic for GPA and illustrated in Figure 2. Pulmonary nodules, often with cavitation, are frequently described with GPA but not seen in this case. Renal involvement was lacking in this case, although there are not typically renal findings on imaging and the diagnosis of renal involvement is usually made with biopsy and lab findings.

Granulomatosis with polyangiitis (GPA) is an ANCA (antineutrophil cytoplasmic antibody) associated small to medium blood vessel vasculitis that can affect the tracheobronchial tree. The multisystem imaging and clinical disease manifestations of GPA are the consequence of underlying necrotizing granulomatous inflammation. Most patients with GPA are seropositive for proteinase 3-ANCA (PR3) rather than myeloperoxidase-ANCA (MPO), however ANCA immunoassays have been shown to be negative in 5-15% of patients with GPA (1,2). GPA is a rare disease with an estimated prevalence of 3 cases per 100,000 individuals in the United States, most commonly occurring in white people (90% of cases) and often in the sixth and seventh decade of life (3).

Although pulmonary involvement is common, affecting approximately two thirds of patients with GPA, tracheobronchial involvement is not a frequent disease manifestation (1,2). However, a striking majority (>70%) of patients who exhibit tracheobronchial involvement, particularly related to subglottic inflammation, are women (2,4). The large airway mucosal inflammation that these patients endure can be seen as smooth or nodular circumferential mucosal or submucosal thickening on CT (1,5). The most common tracheobronchial manifestation of GPA, subglottic stenosis, is the debilitating culmination of prolonged uncontrolled tracheal inflammation (6). Acute large airway manifestations of GPA can be similarly devastating as in the case of a 43yo woman with biopsy proven GPA (negative CRP and PR3-ANCA) found to have acute mainstem bronchus occlusion resulting in severe atelectasis (7).

The histopathologic changes of GPA include the following characteristic features: vasculitis with fibrinoid necrosis and occasionally intramural granulomatous inflammation of small to medium blood vessels as well as a pattern of “geographical” necrosis with giant cells, palisading histiocytes, neutrophilic microabscesses, and polymorphic granuloma (2,8). Given the often protracted disease course of tracheobronchial GPA and limited patient seropositivity, the presence of multisystem disease manifestations including concomitant pulmonary nodules, cavitary masses, renal disease, and/or sinonasal disease is integral to ascertaining the correct diagnosis (6).  Ultimately, histopathologic evidence remains the gold standard for diagnosis and first line treatment involves glucocorticoids with immunomodulatory adjuncts such as methotrexate and rituximab (2,8).

Gabriel Swenson MD, Steven Herber MD, Clinton Jokerst MD

Department of Radiology

Mayo Clinic Arizona, Scottsdale, AZ USA

References

1. Jalaber C, Puéchal X, Saab I, Canniff E, Terrier B, Mouthon L, Cabanne E, Mghaieth S, Revel MP, Chassagnon G. Differentiating tracheobronchial involvement in granulomatosis with polyangiitis and relapsing polychondritis on chest CT: a cohort study. Arthritis Res Ther. 2022 Oct 28;24(1):241. [CrossRef]  [PubMed]
2. Thompson GE, Specks U. Update on the Management of Respiratory Manifestations of the Antineutrophil Cytoplasmic Antibodies-Associated Vasculitides. Clin Chest Med. 2019 Sep;40(3):573-582. [CrossRef] [PubMed]
3. Carnevale C, Arancibia-Tagle D, Sarría-Echegaray P, Til-Pérez G, Tomás-Barberán M. Head and Neck Manifestations of Granulomatosis with Polyangiitis: A Retrospective analysis of 19 Patients and Review of the Literature. Int Arch Otorhinolaryngol. 2019 Apr;23(2):165-171. [CrossRef] [PubMed]
4. Quinn KA, Gelbard A, Sibley C, et al. Subglottic stenosis and endobronchial disease in granulomatosis with polyangiitis. Rheumatology (Oxford). 2019 Dec 1;58(12):2203-2211. [CrossRef] [PubMed]
5. Mayberry JP, Primack SL, Müller NL. Thoracic manifestations of systemic autoimmune diseases: radiographic and high-resolution CT findings. Radiographics. 2000 Nov-Dec;20(6):1623-35. [CrossRef] [PubMed]
6. Pakalniskis MG, Berg AD, Policeni BA, Gentry LR, Sato Y, Moritani T, Smoker WR. The Many Faces of Granulomatosis With Polyangiitis: A Review of the Head and Neck Imaging Manifestations. AJR Am J Roentgenol. 2015 Dec;205(6):W619-29. [CrossRef] [PubMed]
7. Kuwata R, Shirota Y, Ishii T. Severe Acute Atelectasis Caused by Complete Obstruction of Left Main Stem Bronchus Associated with Granulomatosis with Polyangiitis. J Rheumatol. 2020 Aug 1;47(8):1293-1294. [CrossRef] [PubMed]
8. Masiak A, Zdrojewski Z, Pęksa R, Smoleńska Ż, Czuszyńska Z, Siemińska A, Kowalska B, Stankiewicz C, Rutkowski B, Bułło-Piontecka B. The usefulness of histopathological examinations of non-renal biopsies in the diagnosis of granulomatosis with polyangiitis. Reumatologia. 2017;55(5):230-236. [CrossRef] [PubMed] 

Cite as: Swenson G, Herber S, Jokerst C. September 2024 Medical Image of the Month: A Curious Case of Nasal Congestion. Southwest J Pulm Crit Care Sleep. 2024;29(3):26-29. doi: https://doi.org/10.13175/swjpccs040-24 PDF

August 2024 Image of the Month: Lymphomatoid Granulomatosis

Figure 1. Multiple bilateral pulmonary nodules and masses demonstrating a waxing and waning behavior when compared to an older outside CT scan.  Some of the lesions demonstrate partial cavitation or contain air bronchograms. To view Figure 1 in a separate enlarged window click here.

Figure 2. FDG PET/CT MIP (A) and coronal fused (B) reconstructions highlighting extensive disease involvement including both visceral and soft tissue lesions. Coronal images from abdominal (C) and chest (D) contrast-enhanced CT scans demonstrate somewhat ill-defined hypoattenuating masses in the tail of the pancreas, spleen, left kidney, and a partially cavitary right superior lower lobe nodule. To view Figure 2 in a separate enlarged window click here.

Figure 3. Histopathologic evaluation demonstrated extensive coagulative necrosis with surrounding giant cells. Within the viable tissue, sheets of histiocytes and heterogeneous populations of lymphoid cells with prominent perivascular lymphohistiocytic infiltration were demonstrated. To view Figure 3 in a separate enlarged window click here.

Figure 4. Immunohistochemistry showed most lymphoid cells to be CD3 positive T-cells.   Both individually scattered large B cells and a thick perivascular cuff of CD20 positive large B-cells were also noted throughout the lymphohistiocytic proliferation. Ebstein Barr Encoding Region (EBER) in situ hybridization showed that most of the large B-cells, both in the perivascular and diffuse distribution, were positive for Epstein-Barr virus (EBV) To view Figure 4 in a separate enlarged window click here.

A 72-year-old man with a history of hypertension and diabetes and a remote smoking history (10 pack-years) presented to our institution with approximately 1 year of poor appetite, night sweats, and progressive weakness as well as ~ 70 lb. weight loss over the past 6 months. He had also developed multiple intramuscular tumors within his extremities, with rapid growth of a right forearm tumor requiring fasciotomy and debridement. He denied recent foreign travel and his family history was significant for non-Hodgkin lymphoma in his father. Extensive prior clinical and laboratory investigation yielded a negative rheumatological workup, hypercalcemia and an elevated CRP, but was otherwise unremarkable.

Outside imaging studies had shown abdominal adenopathy with numerous intramuscular masses as well as several visceral masses involving the liver, pancreas, spleen and kidneys. Histopathology from several sources including his right forearm debridement surgical specimen and biopsy specimens from lesions in his lung, liver, and groin have all been nondiagnostic. Pathology reports from an outside institution describe the samples as demonstrating only granulomatous inflammation with necrotic debris. A chest CT was ordered to further characterize pulmonary nodules and masses seen on recent abdominal imaging. When compared to a prior outside CT scan, the lesions demonstrated some interval waxing and waning. Also, some of the lesions were cavitary and some contained air bronchograms (Figure 1). Given the waxing and waning behavior of the pulmonary nodules, the differential diagnosis included inflammatory pseudotumor, vasculitis, additional nonmalignant infiltrative processes, as well as hematologic malignancy. Many of the lesions scattered throughout the body were shown to be hypermetabolic on FDG PET-CT (Figure 2).

The patient came to our institution for multidisciplinary management. Surgical biopsy of a left thigh lesion was obtained. Histopathologic analysis showed extensive coagulative necrosis, however within the viable tissue there were sheets of histiocytes and heterogeneous populations of lymphoid cells. Immunohistochemistry staining showed most lymphoid cells to be CD3 positive T-cells with a thick perivascular cuff of CD20 positive large B-cells. Ebstein Barr Encoding Region (EBER) in situ hybridization showed the vast majority of the large B-cells to be positive for Epstein-Barr virus (EBV) (Figures 3 and 4). The histologic findings of extensive necrosis, granulomatous inflammation, and perivascular proliferation of EBV positive large B-cells was diagnostic of an EBV positive large B-cell lymphoma. In the clinical context of numerous mass like lesions involving multiple organs, including the lungs, soft tissue, kidney, spleen, and skeletal muscle, the findings were highly suggestive of  lymphomatoid granulomatosis, grade 3. Diagnostic lumbar puncture for staging revealed no evidence of CNS involvement and the patient was subsequently initiated on an R-CHOP chemotherapy regimen given his substantial tumor burden.

Lymphomatoid granulomatosis (LYG) is an uncommon Ebstein-Barr virus (EBV) related entity that characteristically causes pulmonary nodules and lymphocytic angioinvasion. It falls on the spectrum of EBV-driven B-cell lymphoproliferative disease. LYG is defined and graded pathologically by the amount and density of EBV+ atypical B-cells while also having angioinvasive EBV- T-cell infiltrates (1). Classic organ involvement includes skin, lungs, central nervous system, liver, and kidneys with bone marrow and lymph nodes less likely. The disease most often affects middle-aged adults with men twice as likely to be affected compared to women. LYG classically involves immunocompromised hosts. Importantly, LYG and posttransplant lymphoproliferative disorder (PTLD) have nearly identical pathologic features; thus, transplant recipients should be diagnosed with PTLD (2).

One of the earliest studies on LYG found that malignant lymphoma developed in 12% of patients (3). A subsequent case series found that despite only four of their seven patients showing proof of monoclonality or oligoclonality, all cases of LYG behaved aggressively (4). Grading the EBV+ density guides treatment recommendations with low-grade being treated with interferon-α2b while high-grade is treated with immunochemotherapy. Hematopoietic stem cell transplant is considered for primary refractory disease or multiple relapses (1). Overall, treatment has remained controversial for decades. The mortality rate of LYG ranges from 38-71% (2). LYG is unusual from an imaging standpoint as it appears as an aggressive malignancy, but areas of involvement can spontaneously regress without being treated.

Steven Herber MD, Gabriel Swenson MD, Clinton Jokerst MD

Department of Radiology

Mayo Clinic Arizona

Phoenix, AZ USA

References

1. Melani C, Jaffe ES, Wilson WH. Pathobiology and treatment of lymphomatoid granulomatosis, a rare EBV-driven disorder. Blood. 2020 Apr 16;135(16):1344-1352. [CrossRef] [PubMed]
2. Katzenstein AL, Doxtader E, Narendra S. Lymphomatoid granulomatosis: insights gained over 4 decades. Am J Surg Pathol. 2010 Dec;34(12):e35-48. [CrossRef] [PubMed]
3. Katzenstein AL, Carrington CB, Liebow AA. Lymphomatoid granulomatosis: a clinicopathologic study of 152 cases. Cancer. 1979 Jan;43(1):360-73. [CrossRef] [PubMed]
4. Nicholson AG, Wotherspoon AC, Diss TC, et al. Lymphomatoid granulomatosis: evidence that some cases represent Epstein-Barr virus-associated B-cell lymphoma. Histopathology. 1996 Oct;29(4):317-24. [CrossRef] [PubMed]

Cite as: Herber S, Swenson G, Jokerst C. August 2024 Image of the Month: Lymphatoid Granulomatosis. Southwest J Pulm Crit Care Sleep. 2024;(29(2):19-22. doi: https://doi.org/10.13175/swjpccs039-24 PDF

August 2024 Imaging Case of the Month: An Unexplained Pleural Effusion

Matthew T. Stib MD

Michael B. Gotway MD

Department of Radiology

Mayo Clinic, Arizona

Scottsdale, AZ USA

Clinical History: A 65-year-old woman with presents with intermittent right-sided chest pain and shortness of breath / dyspnea on exertion for several months’ duration.

The patient’s past medical history includes a history of myocardial infarction with stent placement and atrial fibrillation. She has no prior surgical history aside from carpal tunnel release and tonsillectomy.

The patient is a lifelong non-smoker, she reports no allergies and she drinks alcohol only socially and denies illicit drug use. Her medications include Xarelto (rivaroxaban) for her atrial fibrillation, alendronate, atorvastatin, metoprolol, and pantoprazole in addition to a multivitamin.

On physical examination the patient was obese but not in acute distress, with normal blood pressure, pulse rate, and respiratory rate. Her pulmonary and cardiovascular examination was unremarkable aside for dullness to percussion over the right posterior and lateral thorax, and her musculoskeletal examination did not disclose any abnormalities. She was neurologically intact. Oxygen saturation at rest on room air  95%, 93% with exercise.

A complete blood count showed a normal white blood cell count at 6.5 x 10⁹/L (normal, 3.4 – 9.6 x 10⁹/L), with a normal absolute neutrophil count of 3.65 x 10⁹/L (normal, 1.4 – 6.6 x 10⁹/L); the percent distribution of lymphocytes, monocytes, and eosinophils was normal. Her hemoglobin and hematocrit values were 13 gm/dL (normal, 13.2 – 16.6 gm/dL) and 39.7% (normal, 34.9 – 44.5%). The platelet count was normal at 274 x 10⁹/L (normal, 149 – 375 x 10⁹/L). The patient’s serum chemistries and liver function studies were largely normal, including an albumin level at 4.3 gm/dL (normal, 3.5 – 5 gm/dL), with mildly elevated alanine aminotransferase at 59 U/L (normal, 7-45 U/L) and aspartate aminotransferase of 68 U/L (normal, 8-43 U/L); alkaline phosphatase levels, bilirubin, and coagulation studies were normal. SARS-CoV-2 PCR testing was negative. The erythrocyte sedimentation rate was normal at 8 mm/hr (normal, 0-29 mm/hr), as was her C-reactive protein at <2 mg/L (normal, <2 mg/L).  

Frontal chest radiography (Figure 1) was performed.

Figure 1. Frontal and lateral chest radiography. To view Figure 1 in a separate, enlarged window click here.

Which of the following statements regarding this chest radiograph is accurate? (Click on the correct answer to be directed to the second of seventeen pages)

1. Frontal chest radiography shows normal findings
2. Frontal chest radiography shows a moderate-to-large right pleural effusion
3. Frontal chest radiography shows mediastinal lymphadenopathy
4. Frontal chest radiography shows pneumothorax
5. Frontal chest radiography shows numerous small nodules

Cite as: Stib MT, Gotway MB. August 2024 Imaging Case of the Month: An Unexplained Pleural Effusion. Southwest J Pulm Crit Care Sleep. 2024;29(2):9-18. doi: https://doi.org/10.13175/swjpccs038-24 PDF

July 2024 Medical Image of the Month: Vocal Cord Paralysis on PET-CT

Figure 1.  Axial image from a CT scan (A) showing a spiculated left upper lobe nodule.  An axial image from a more inferior slice, at the level of the left hilum (B), demonstrates prominent left hilar adenopathy filling the AP window/subaortic space (*).

Figure 2.  Axial images from an FDG-PET CT obtained shortly after the initial chest CT demonstrates focal hypermetabolic activity associated with the left upper lobe nodule (A) and pre-aortic adenopathy (arrowhead).  There is also hypermetabolism associated with the right (contralateral) vocal cord (B) (arrow).

A 60-year-old woman with a past medical history of hypertension, rheumatoid arthritis, and a significant smoking history (40+ pack-years) presented with a 3-month history of hoarseness of voice as well as a 10 lb weight loss over a 5-month period.  Chest CT revealed a spiculated left upper lobe nodule (Figure 1A). Additionally, there was evidence of bulky mediastinal and left hilar lymphadenopathy (Figure 1B). A subsequent 17-FDG PET-CT (Figure 2) demonstrated marked metabolic activity in the left upper lobe nodule with an SUV maximum of 9.1. Metabolically active mediastinal and left hilar lymphadenopathy was also noted with an SUV maximum of 5.9.

Interestingly, increased metabolic activity of the right vocal cord compared to the left was noted on the PET scan (Figure 2B). Direct laryngoscopy, performed during intubation for a diagnostic bronchoscopy and endobronchial ultrasound, confirmed left vocal cord paralysis. EBUS sampling of multiple mediastinal hilar lymph node stations, including 4L, and 7, confirmed malignant cells compatible with small cell lung carcinoma. Immunohistochemistry further supported the diagnosis, revealing positive staining for TTF-1, synaptophysin, CD56, and focal chromogranin negativity.

The false-positive PET scan of the larynx, correlated with laryngoscopic findings, points towards contralateral vocal cord paralysis. The asymmetrical FDG uptake in the right vocal cord is attributed to compensatory muscle activation due to left vocal cord paralysis. Vocal cord paralysis is almost twice as common on the left due to the longer anatomical pathway of the left recurrent laryngeal nerve and the fact that it passes through the aortopulmonary window [1]. In this case, PET/CT images demonstrated that the focal FDG uptake was localized in the right vocal cord muscles. This focal FDG uptake is a result of increased work of vocal cord muscles caused by contralateral (left) recurrent laryngeal nerve palsy due to direct nerve invasion by the metastatic adenopathy. Knowledge of this pitfall is important to avoid false-positive PET results [2].

Abdulmonam Ali, MD

Pulmonary & Critical Care

SSM Health

Mount Vernon, IL USA

References

1. Lee M, Ramaswamy MR, Lilien DL, Nathan CO. Unilateral vocal cord paralysis causes contralateral false-positive positron emission tomography scans of the larynx. Ann Otol Rhinol Laryngol. 2005 Mar;114(3):202-6. [CrossRef] [PubMed]
2. Oner AO, Boz A, Surer Budak E, Kaplan Kurt GH. Left Vocal Cord Paralysis Detected by PET/CT in a Case of Lung Cancer. Case Rep Oncol Med. 2015;2015:617294. [CrossRef] [PubMed]

Cite as: Ali A. July 2024 Medical Image of the Month: Vocal Cord Paralysis on PET-CT. Southwest J Pulm Crit Care Sleep. 2024;29(1):6-7. doi: https://doi.org/10.13175/swjpccs012-24 PDF

June 2024 Medical Image of the Month: A 76-year-old Man Presenting with Acute Hoarseness

Figure 1. Anterior-posterior chest x-ray (A) showing moderate elevation of left hemidiaphragm (arrow) and an ill-defined nodular opacity in the left perihilar region (*) suspicious for a hilar mass. Axial image from a contrast enhanced chest CT (B) showing central left upper lobe mass extending into the hilum resulting in narrowing of the vascular and bronchial structures of the left upper lobe.

Figure 2. 400x magnification hematoxylin and eosin-stained endobronchial biopsy (A) demonstrating malignant cells with large hyperchromatic nuclei (circle) infiltrating through stromal tissue. Compare with the nuclear size of the nearby normal submucosal glands (arrows), 200x magnification image (B) demonstrating poorly differentiated carcinoma cells filling the subepithelial stroma. Normal ciliated mucosal cells are in the upper left of the image (arrowheads).

A 76-year-old man with a past medical history significant for coronary artery disease, diabetes mellitus, and 40-pack-year smoking history presented to the emergency department with 1 week of progressive hoarseness. Associated symptoms included a cough initially productive of green sputum that progressed to scant hemoptysis, as well as intermittent hiccups. Four days prior to presentation he sought treatment at a clinic in Mexico, where he was diagnosed with influenza and treated with Tamiflu and Moxifloxacin. His symptoms did not improve, prompting him to seek care at our hospital.

On interview, he denied fevers, chills, dysphagia, otalgia, odynophagia, dyspepsia, chest pain, dyspnea, or weight changes. His temperature was 36.3°C, heart rate 75 beats per minute, blood pressure 150/77 mmHg, respiratory rate 22 breaths per minute, and oxygen saturation 93% on room air. On physical examination, the patient was found to have a hoarse voice, with an otherwise normal oropharyngeal exam. Cardiopulmonary exam was notable for bowel sounds auscultated in the left lower lung fields. The remainder of the exam was unremarkable. Laboratory testing including CBC, CMP, and a respiratory pathogen PCR panel did not detect any viruses.

A chest X-ray was obtained (Figure 1A); imaging was significant for moderate elevation of left hemidiaphragm (A), an ill-defined nodular opacity in the left perihilar region, and suspicion for a hilar mass (B). Chest CT confirmed a large central left upper lobe hilar mass compressing regional vascular and bronchial structures (Figure 1B). The patient underwent Endobronchial ultrasound-guided fine needle aspiration (EBUS FNA) and endobronchial biopsy, which confirmed the diagnosis, recurrent laryngeal nerve injury secondary to left upper lobe non-small cell lung carcinoma (Figure 2).

Hoarseness can be caused by a diverse array of conditions, ranging from local inflammatory processes (e.g., laryngitis or benign vocal cord lesions), to more systemic, neurologic, or oncologic conditions. A systematic evaluation is therefore essential to create an appropriate differential and guide the diagnostic evaluation. This evaluation begins with a detailed history probing for any red flag symptoms: symptoms persisting greater than two weeks, dysphagia, odynophagia, weight loss, or hemoptysis, as was seen in the case above.

Recurrent laryngeal nerve injuries are a less common cause of hoarseness. An understanding of the anatomic course of the recurrent laryngeal nerve (RLN) aids in localizing pathology. The RLN branches off cranial nerve X, also known as the Vagus nerve, and supplies most of the laryngeal muscles. The left RLN extends inferiorly into the chest, and loops posteriorly under the aortic arch before returning superiorly through the neck. Similarly, the right RLN loops posteriorly around the right subclavian artery before traversing superiorly back through the neck. The majority of recurrent laryngeal nerve injuries are iatrogenic, secondary to thyroid or cardiothoracic surgery. However, in the absence of surgery, understanding the anatomy paired with further imaging can help localize the pathology.

The patient’s radiographic findings suggested an intrathoracic mass concerning for a primary lung malignancy. This mass was further characterized on chest CT, which confirmed a large central left upper lobe hilar mass compressing regional vascular and bronchial structures. In the setting of hoarseness, the malignancy was likely causing injury to the recurrent laryngeal nerve. Additionally, given the symptom of hiccups paired with image findings of an elevated hemidiaphragm, the phrenic nerve was also likely being compressed. A biopsy would then further identify the lung mass.

Bronchoscopy showed patent airways and extensive nodular mucosa and endobronchial tumor at the left upper lobe / lingula. Endobronchial biopsy of the left upper lobe revealed infiltrating malignant cells in the submucosal connective tissue. No keratin production or gland formation was seen. Further work-up with immunohistochemical preparations showed the tumor cells to be negative for TTF-1 and p40, markers indicative of pulmonary adenocarcinoma and squamous cell carcinoma, respectively. In light of these features, the most accurate diagnosis is non-small cell carcinoma, not otherwise specified (NOS).

The differential for dysphonia in an adult extends beyond the anatomic boundaries of the laryngopharynx, including an intrathoracic malignancy causing recurrent laryngeal nerve injury. Additionally, phrenic nerve palsy secondary to a mediastinal mass should be included in the differential for an elevated hemidiaphragm.

Alexandra Fuher MD¹, Carrie B. Marshall MD², William Aaron Manning MD³

¹Department of Internal Medicine, University of Colorado Anschutz Medical Campus

²Department of Pathology, University of Colorado Anschutz Medical Campus

³Department of Pediatrics, University of Colorado Anschutz Medical Campus

References

1. Culp JM, Patel G. Recurrent Laryngeal Nerve Injury. [Updated 2023 May 22]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK560832.
2. Reiter R, Hoffmann TK, Pickhard A, Brosch S. Hoarseness-causes and treatments. Dtsch Arztebl Int. 2015 May 8;112(19):329-37. [CrossRef] [PubMed]
3. Feierabend RH, Shahram MN. Hoarseness in adults. Am Fam Physician. 2009 Aug 15;80(4):363-70. [PubMed]
4. Travis WD, Brambilla E, Noguchi M, et al. Diagnosis of lung cancer in small biopsies and cytology: implications of the 2011 International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification. Arch Pathol Lab Med. 2013 May;137(5):668-84. [CrossRef] [PubMed]

Cite as: Fuher A, Marshall CB, Manning WA. June 2024 Medical Image of the Month: A 76-year-old Man Presenting with Acute Hoarseness. Southwest J Pulm Crit Care Sleep. 2024;28(6):78-80. doi: https://doi.org/10.13175/swjpccs002-24 PDF

May 2024 Imaging Case of the Month: Nothing Is Guaranteed

Michael B. Gotway MD

Department of Radiology

Mayo Clinic, Arizona

Phoenix, Arizona 85054

Clinical History: A 68-year-old man with mantle cell lymphoma diagnosed 5 years earlier presents with weight loss and abdominal distension. HIs lymphoma presented as lymphadenopathy in the neck, chest, and abdomen (Figure 1A), the diagnosis established by percutaneous needle biopsy of enlarged lymph nodes in the neck (Figure 1B); the lymph nodes showed CD5 positivity.

Figure 1. (A) Axial ¹⁸FDG – PET scan shows intense tracer uptake within left supraclavicular lymphadenopathy. (B) Percutaneous fine needle aspiration biopsy of the left supraclavicular lymphadenopathy. (C) Axial ¹⁸FDG – PET scan 3 month after diagnosis following hyper-CVAD therapy shows resolution of the tracer-avid left supraclavicular lymphadenopathy. To view Figure 1 in a separate, enlarged window click here.

Peripheral flow cytometry revealed leukemic involvement as well. The patient underwent hyper-CVAD therapy (cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride [aka, Adriamycin], and dexamethasone), with rituximab, with a good response (Figure 1C). Radiotherapy was also performed for the left neck and supraclavicular lymphadenopathy.

PMH, SH, FH: The patient’s past medical history was otherwise unremarkable and he had no previous surgical history. The patient had no known allergies and denied alcohol use. He was former smoker, having quit at a young age.

Physical Exam: The patient’s physical examination showed a blood pressure of 130 / 76 mmHg, pulse rate 67 / min, respiration rate of 16/min, and a temperature of 36.3° C. His pulmonary and cardiovascular examination was unremarkable, and his musculoskeletal examination did not disclose any abnormalities, and he was neurologically intact.

Laboratory Evaluation: A complete blood count showed a normal white blood cell count at 5.1 x 10⁹/L (normal, 3.4 – 9.6 x 10⁹/L), with a normal absolute neutrophil count of 2.8 x 10⁹/L (normal, 1.4 – 6.6 x 10⁹/L). His hemoglobin and hematocrit values were mildly decreased at 13.2 gm/dL (normal, 13.5 – 17.5 gm/dL) and 38.7% (normal, 38.8 – 50%). The platelet count was normal at 196 x 10⁹/L (normal, 149 – 375 x 10⁹/L). The patient’s serum chemistries and liver function studies were normal aside from an elevated lactate dehydrogenase level at 745 U/L (normal, 122-222 U/L). A urinary drug toxicity screen was negative, and coagulation parameters were normal. SARS-CoV-2 PCR testing was negative. Thyroid stimulating hormone level was within the normal range. Frontal and lateral chest radiography (Figure 2) was performed.

Figure 2. Frontal (A) and lateral (B) chest radiography at presentation. To view Figure 2 in a separate, enlarged window click here.

Which of the following statements regarding this chest radiograph is most accurate? (Click on the correct answer to be directed to the second of 12 pages)

1. Frontal chest radiography shows normal findings
2. Frontal chest radiography shows the “dense hilum” sign
3. Frontal chest radiography shows mediastinal lymphadenopathy
4. Frontal chest radiography shows pleural effusion
5. Frontal chest radiography shows numerous small nodules

Cite as: Gotway MB. May 2024 Imaging Case of the Month: Nothing Is Guaranteed. Southwest J Pulm Crit Care Sleep. 2024;28(5):59-67. doi: https://doi.org/10.13175/swjpccs018-24 PDF

March 2024 Medical Image of the Month: Sputum Cytology in Patients with Suspected Lung Malignancy Presenting with Acute Hypoxic Respiratory Failure

Figure 1. Axial image from a CT scan (A) showing masslike consolidation in the right lower lobe (*). Axial image from FDG-PET CT (B) showing the hypermetabolic center of the mass-like consolidation (arrow).

Figure 2. Sputum cytology low power (A) and high power (B) H&E stains showing clusters of malignant cells.

A 71-year-old woman presented with right-sided mass-like consolidation and pleural effusion on CT (Figure 1A), discovered incidentally after placement of a drug-eluting stent for coronary artery disease. The patient had a medical history significant for COPD, hypertension, hyperlipidemia, and coronary artery disease, status post a recent drug-eluting stent (less than 1 month ago). The patient received a presumptive diagnosis of pneumonia with parapneumonic effusion. Findings persisted despite multiple courses of empiric antibiotic therapy. She then underwent thoracentesis; pleural fluid was exudative; however, cytology was inconclusive. An FDG PET-CT (Figure 1B) revealed hypermetabolic activity in the right lower lobe with radiotracer activity up to 7.7 SUV concerning for malignancy. Diagnostic bronchoscopy was planned; however, her condition deteriorated suddenly the day before her planned procedure. EMS found the patient to be severely hypoxic, SpO2 in the 70s. Patient was taken by ambulance to the local emergency room.

Upon arrival, the patient was in mild respiratory distress which improved upon applying non-invasive positive-pressure ventilation. She had mild tachycardia and reduced air movement in the right lower third of the chest on physical exam. Repeat CT confirmed the persistence of the right lower lobe mass-like consolidation and moderate-sized pleural effusion. Empirical treatment for post-obstructive pneumonia was initiated. Right-sided thoracentesis again demonstrated exudative pleural fluid with negative cytology for malignancy and negative culture results. Due to concerns about her respiratory status, diagnostic bronchoscopy was abandoned. However, the patient was coughing up blood-tinged sputum which was sent for cytology (Figure 2) confirming a diagnosis of non-small cell lung cancer favoring adenocarcinoma. Immunostains performed on sections of the cell block showed malignant cells positive for CK7 and TTF1 and negative for P40 supporting the diagnosis of adenocarcinoma of lung.

This case emphasizes the importance of utilizing noninvasive testing like sputum cytology in patients with severe morbidity to help uncover underlying diagnoses. Studies and medical case reports highlighted the significance of sputum analysis in diagnosing lung cancer (1,2). Challenges posed by this case underscore the importance of considering alternative noninvasive measures to aid in making accurate diagnosis and help patient's and family understanding the underlying etiology of her persistent pneumonia )overall prognosis.

Abdulmonam Ali MD
Pulmonary & Critical Care
SSM Health
Danville, IL USA

References

1. Thunnissen FB. Sputum examination for early detection of lung cancer. J Clin Pathol. 2003 Nov;56(11):805-10. [CrossRef] [PubMed]
2. Ammanagi AS, Dombale VD, Miskin AT, Dandagi GL, Sangolli SS. Sputum cytology in suspected cases of carcinoma of lung (Sputum cytology a poor man's bronchoscopy!). Lung India. 2012 Jan;29(1):19-23. [CrossRef] [PubMed]

Cite as: Abdulmonam A. March 2024 Medical Image of the Month: Sputum Cytology in Patients with Suspected Lung Malignancy Presenting with Acute Hypoxic Respiratory Failure. Southwest J Pulm Crit Care Sleep. 2024;28:30-31. doi: https://doi.org/10.13175/swjpccs008-24 PDF

January 2024 Medical Image of the Month: Polyangiitis Overlap Syndrome (POS) Mimicking Fungal Pneumonia

Figure 1. PA chest radiographs obtained on 9/14/23 (A) and approximately 2.5 months later (B) demonstrates rapidly growing cavitary masses in the upper lungs (arrows). The rapid interval growth is more suggestive of an inflammatory as opposed to malignant process. To view Figure 1 in a separate, enlarged window click here.

Figure 2. Axial reconstructions from an unenhanced chest CT (A,B) demonstrate multiple areas of mass-like consolidation with some areas of cavitation and some internal air bronchograms. As was surmised from the CXRs, the appearance suggests an infections/inflammatory etiology. To view Figure 2 in a separate, enlarged window click here.

Figure 3. H&E (A) and GMS (B) stains of a specimen from biopsy of right upper lobe lesion. There is an organizing inflammatory process with extensive necrosis and no evidence of infectious organism. H&E staining of a renal biopsy (C) demonstrates chronic and active necrotizing and crescentic glomerulosclerosis with diffuse interstitial fibrosis and tubular atrophy. Taken in conjunction with the history and lack of any other findings to suggest infection, histopathological findings were deemed to be consistent with active granulomatosis with polyangiitis.  To view Figure 3 in a separate, enlarged window click here.

A 32-year-old woman with a history including hypertension, end-stage renal disease requiring dialysis, asthma, nonischemic cardiomyopathy, and migraines, was directly transferred to our hospital in November 2023 for the evaluation of hemoptysis. The patient reported a two-week history of a nonproductive cough, runny nose, muscle aches, subjective fevers, chills, fatigue, nausea, and decreased appetite. Within the past 2 days the patient had also developed hemoptysis, with 5-6 episodes per day.

Initial investigations, including chest X-ray and CT chest, revealed large biapical pulmonary consolidations with cavitation. Multiple nodular densities were observed throughout both lungs (Figures 1 and 2). The patient denied any recent sick contacts, travel history, and prior tuberculosis infection. She did, however, disclose a period of incarceration from 2011 to 2019.

Upon arrival at our hospital, the patient recounted a relatively normal state of health until January 2023 when she underwent a two-month hospitalization, culminating in the diagnosis of end-stage renal disease by biopsy at an outside facility. She attributed this to anautoimmune disease, for which she did not receive immunosuppressive therapy at the time. Subsequent hospitalization in September 2023 for rhinovirus pneumonia led to the diagnosis of heart failure with a reduced ejection fraction of 15-20%, determined to be of nonischemic origin.

In our ED vital signs revealed a heart rate of 110, blood pressure of 180/90 mmHg, normal respiratory rate, and no hypoxia on room air. Laboratory results were significant for leukocytosis 18.7x10⁹/L with high eosinophils count of 2.32x10⁹/L, elevated potassium 5.7 mmol/L, BUN 51 mg/dL, and creatinine 9.5 mg/dL. Chest X-ray depicted bilateral upper lung consolidations, notably worsened on the right with central cavitation (Figure 1B). Additional nodularity was observed in the left mid-lung, which was new in comparison to a prior chest x-ray done in September 2023 (Figure 1A).

Following her admission, an extensive infectious workup, including TB QuantiFERON testing, lumbar puncture, bronchoscopy with BAL, and blood cultures, was conducted. The results were unremarkable. Transbronchial biopsies from the right upper lobe cavity revealed an organizing inflammatory process with extensive necrosis, negative for neoplasm and infectious staining including GMS & acid-fast bacilli (Figure 3A,3B). An autoimmune panel revealed elevated ESR, CRP, PR3 antibody, and positive c-ANCA, leading to a diagnosis of Polyangiitis overlap syndrome. Treatment commenced with IV methylprednisone, transitioning to oral prednisone (60 mg daily) with a gradual taper over the next eight weeks. Inpatient administration of rituximab was initiated, with plans for three more infusions as part of her induction therapy.

According to the data from the French Vasculitis Study Group Registry (1), among the 795 patients with granulomatosis with polyangiitis (GPA), 354 individuals (44.5%) exhibited elevated blood eosinophil counts. Notably, hypereosinophilia, primarily of mild-to-moderate severity (ranging from 500 to 1500/mm³), was identified in approximately one-quarter of GPA patients at the time of diagnosis. In contrast, severe eosinophilia (>1500/mm3) was observed in only 28 patients (8%). Furthermore, this subset with severe eosinophilia was noted to have worse renal function at the time of presentation. Whereas in a retrospective European multicentre cohort published by Papo et al. (2), ANCA status was accessible for 734 EGPA patients with only 16 patients (2.2%) having PR3-ANCA. Notably, at baseline, PR3-ANCA positive patients, in comparison to those with MPO-ANCA and ANCA-negative individuals, exhibited a lower prevalence of active asthma and peripheral neuropathy. Conversely, they manifested a higher incidence of cutaneous manifestations and pulmonary nodules. Adding to the complexity, EGPA, characterized by peripheral blood eosinophilia, asthma, and chronic rhinosinusitis, contrasts with GPA, which manifests pulmonary nodules without eosinophilic infiltration and usually a more severe renal disease.

Polyangiitis overlap syndrome (POS), previously published by Leavitt and Fauci (3), was defined as systemic vasculitis that does not fit precisely into a single category of classical vasculitis or overlaps more than one subtype of vasculitis. Several polyangiitis overlap syndromes have been identified since 1986; however, less than 20 case reports of an overlap syndrome involving both GPA and EGPA have been published so far. As per the literature review performed by Bruno et al. (4), most of the reported POS cases had lung involvement with over half developed alveolar hemorrhage. They noted genetic and clinical heterogeneity in the pathogenesis of polyangiitis overlap syndrome suggesting distinct clinical phenotypes and outcomes to therapy. Notably, treatment strategies in polyangiitis overlap syndrome are usually tailored to the severity of the disease rather than the ANCA phenotype, leading to favorable outcomes in most cases.

John Fanous MD¹, Clint Jokerst MD², Rodrigo Cartin-Ceba MD¹

Division of Pulmonology¹and Department of Radiology²

Mayo Clinic Arizona, Scottsdale, AZ USA

References

1. Iudici M, Puéchal X, Pagnoux C, et al.; French Vasculitis Study Group. Significance of eosinophilia in granulomatosis with polyangiitis: data from the French Vasculitis Study Group Registry. Rheumatology (Oxford). 2022 Mar 2;61(3):1211-1216. [CrossRef] [PubMed]
2. Papo M, Sinico RA, Teixeira V, et al.; French Vasculitis Study Group and the EGPA European Study Group. Significance of PR3-ANCA positivity in eosinophilic granulomatosis with polyangiitis (Churg-Strauss). Rheumatology (Oxford). 2021 Sep 1;60(9):4355-4360. [CrossRef] [PubMed]
3. Leavitt RY, Fauci AS. Pulmonary vasculitis. Am Rev Respir Dis. 1986 Jul;134(1):149-66. [CrossRef] [PubMed]
4. Bruno L, Mandarano M, Bellezza G, Sidoni A, Gerli R, Bartoloni E, Perricone C. Polyangiitis overlap syndrome: a rare clinical entity. Rheumatol Int. 2023 Mar;43(3):537-543. [CrossRef] [PubMed]

Cite as: Fanous J, Jokerst C, Cartin-Ceba R. January 2024 Medical Image of the Month: Polyangiitis Overlap Syndrome (POS) Mimicking Fungal Pneumonia. Southwest J Pulm Crit Care Sleep. 2024;28(1):5-8. doi: https://doi.org/10.13175/swjpccs052-23 PDF

November 2023 Imaging Case of the Month: A Crazy Association

Parker J. Brown MD, Prasad M. Panse MD and Michael B. Gotway MD

Department of Radiology

Mayo Clinic, Arizona

Phoenix, Arizona

HPI: A 55-year-old man presents with a history of cough, poor appetite, low energy, and weight loss over the previous 6-10 months following COVID-19 infection 2 months earlier. 

PMH, SH, FH: The patient’s past medical history was positive for CVOID-19 infection 2 months earlier as well as pneumonia, not specified, in the previous year.

The patient’s past medical history was also remarkable for a 7-unit gastrointestinal hemorrhage approximately one year earlier following polypectomy for benign lesions in the transverse colon. During that hospital admission a complete blood count showed 1% blasts which prompted hematology consultation. The consulting oncologist felt the peripheral blasts were the result of a leukemoid reaction secondary to increased bone marrow stimulation owing to the patient’s acute anemia caused by the gastrointestinal hemorrhage. Macrocytosis and reticulocytosis was also noted and attributed to the same. Repeat complete blood count showed no blasts although some myelocytes, metamyelocytes, and polychromasia was noted for which follow up assessment was recommended. Serum B12 and folate levels were normal.

The patient had no prior surgeries.

The patient was not taking any prescription medications.

The patient is a non-smoker. He has no known allergies and drinks alcohol only socially and denied illicit drug use.

There was no significant family history.

Physical Examination: The patient’s physical examination showed his temperature to be 96.7°F with borderline elevated pulse rate of 95/min, a normal respiratory rate, and blood pressure of 118/67 mmHg. Room air oxygen saturation was 98%.

Initial Laboratory: A complete blood count showed a normal white blood cell count at 5.6 x10⁹/L (normal, 3.4 – 9.6 x10⁹/L), with 75% bands (normal, 50-75%). His hemoglobin and hematocrit values were 10.1 gm/dL (normal, 13.2 – 16.6 gm/dL) and 31.6% (normal, 38.3 – 48.6%). The platelet count was normal at 225 x 10⁹/L (normal, 135 – 317 x 10⁹/L). The patient’s serum chemistries and liver function studies were normal aside from mildly decreased total protein at 5.7 gm/dL (normal, 6.3-.9 gm/dL). The patient had an elevated anti-nuclear antibody titer at 1:320. SARS-CoV-2 PCR testing was positive.  

Radiography: Frontal chest radiography (Figure 1) was performed.

Figure 1. Frontal chest radiography at presentation.

Which of the following statements regarding this chest radiograph is accurate? (Click on the correct answer to be directed to the second of fourteen pages).

1. Frontal chest radiography shows normal findings
2. Frontal chest radiography shows marked cardiomegaly
3. Frontal chest radiography shows mediastinal lymphadenopathy
4. Frontal chest radiography shows pleural effusion
5. Frontal chest radiography shows multifocal consolidation

Cite as: Brown PJ, Panse PM, Gotway MB. November 2023 Imaging Case of the Month: A Crazy Association. Southwest J Pulm Crit Care Sleep. 2023;27(5):47-55. doi: https://doi.org/10.13175/swjpccs046-23 PDF

October 2023 Medical Image of the Month: Swyer-James-MacLeod Syndrome

Figure 1. Frontal (A) and lateral (B) topographic images from a non-contrast chest CT show a relative paucity of lung markings in the right hemithorax. There are at least 2 large, cystic-appearing lesions in the right lung, which appears somewhat hyperinflated. Axial (C) and sagittal (D) reconstructions from the CT confirm unilateral areas of emphysematous appearing hyperinflated lung with surrounding atelectasis. The left lung appears relatively normal. Click here to view Figure 1 in an enlarged, separate window.

Figure 2. Hematoxylin and Eosin stained low-power pathological image from right upper lobectomy (A) demonstrates chronic bronchiolitis with features of subtotal obliterative bronchiolitis associated with mild septal fibrosis and prominent emphysematous/cystic change. Elastic trichrome stain of a small airway (B) demonstrates subtotal bronchiolitis obliterans. Click here to view Figure 2 in an enlarged, separate window.

Pathological slides from a right upper lobectomy specimen obtained at an outside institution were submitted to our Department of Pathology for review. A pre-operative noncontrast chest CT from the outside institution was submitted along with the path slides. The patient was a 27 y/o man who presented to the outside institution with exercise intolerance and increasing shortness of breath following a bout of COVID in early 2023. The patient also related a history of possible chronic myocarditis. A review of the CT demonstrated 2 distinct right-sided areas of hyperinflated, emphysematous lung with a relatively normal appearing left lung (Figure 1). Although congenital lobar emphysema was considered, the multifocal nature of the findings suggested against this, and a diagnosis of Swyer-James-MacLeod Syndrome was entertained. Histopathological analysis (Figure 2) confirmed this suspicion. When questioned further, the patient related a history of neonatal RSV infection requiring 3 weeks of hospitalization. The constellation of historical, radiological, and pathological findings was consistent with Swyer-James- MacLeod Syndrome.

This syndrome was first described in 1949 in a case report of a six-year-old boy from the UK by pediatrician Paul Swyer and radiologist George James (1). The pulmonologist William MacLeod published a review of nine cases in 1954 (2). Also known as “unilateral hyperlucent lung syndrome”, this is a postinfectious form of bronchiolitis obliterans. Severe infection early in life, while the lungs are still developing, is the proposed mechanism. Although different infections organisms are associated with this, respiratory syncytial virus is most implicated. Swyer-James-MacLeod Syndrome usually affects the lungs asymmetrically. On imaging, the most common pattern is that of a unilateral hyperlucent lung which may or may not be associated with hyperinflation and may or may not be associated with bronchiectasis (3). There is reduction in pulmonary blood flow and formation of septal fibrosis which leads to obstruction of pulmonary capillary beds. Alveolar hyperinflation leads to mechanical resistance to pulmonary blood flow and reduced ventilation leads to pulmonary vasoconstriction. Most patients asymptomatic, and many cases discovered incidentally. Treatment is usually conservative and preventative, focused on controlling pulmonary infections. Inhaled corticosteroids may have a limited role in treatment as well (4).

Samantha Moore, MD, PhD¹ and Clinton Jokerst MD²

Department of Laboratory Medicine and Pathology¹ and Department of Radiology²

Mayo Clinic Arizona, Scottsdale, AZ USA

References

1. Swyer PR, James GC. A case of unilateral pulmonary emphysema. Thorax. 1953 Jun;8(2):133-6. [CrossRef] [PubMed]
2. William Mathieson Macleod. Lancet. 1977 Oct 15;2(8042):833. [PubMed]
3. Lucaya J, Gartner S, García-Peña P, Cobos N, Roca I, Liñan S. Spectrum of manifestations of Swyer-James-MacLeod syndrome. J Comput Assist Tomogr. 1998 Jul-Aug;22(4):592-7. [CrossRef] [PubMed]
4. Mehra S, Basnayake T, Falhammar H, Heraganahally S, Tripathi S. Swyer-James-MacLeod syndrome-a rare diagnosis presented through two adult patients. Respirol Case Rep. 2017 Jun 16;5(5):e00245. [CrossRef] [PubMed]

Cite as: Moore S, Jokerst C. 2023 Medical Image of the Month: Swyer-James-MacLeod Syndrome. Southwest J Pulm Crit Care Sleep. 2023;27(4):45-46. doi: https://doi.org/10.13175/swjpccs042-23 PDF

September 2023 Medical Image of the Month: Aspergillus Presenting as a Pulmonary Nodule in an Immunocompetent Patient

Figure 1. Chest CT showing 11 x10 mm nodule in the anterior segment of the left upper lobe in the background of emphysematous and basal sub segmental atelectatic changes.

Figure 2. Lung biopsy low power (A) showing chronic inflammatory infiltrate in the interstitium along with a collection of fungus (arrow) (H&E: x40). Fungus with an area of necrosis (B) (H&E: x100). Numerous thin, narrow-angle, and branching hyphae with septa morphologically consistent with Aspergillus (C) (H&E: x400). Collection of Aspergillus (D). (Periodic acid–Schiff stain: x400).

A 32-year-old nonsmoking woman presented with complaints of recurrent hemoptysis for 5 months and dyspnea on exertion for 1 month. She denied any history of fever, cough, or COVID infection. She has hypothyroidism controlled on thyroxine 25mcg. During the evaluation, she was found to have an enhancing solitary pulmonary nodule (11 x 10 x 9mm) in the anterior segment of the left upper lobe (Figure 1). The patient was given a course of oral antibiotics (amoxicillin /clavulanic acid) and supportive treatment for hemoptysis. Sputum for Ziehl–Neelsen stain and cartridge based nucleic acid amplification test (CBNAAT) was negative. CT- guided biopsy of the nodule was performed. Histopathology showed fungal organisms which were thin, septate with acute angle branching and focal necrotic areas, morphologically consistent with Aspergillus (Figure 2). Serum-specific IgG against aspergillus antigen was normal. The patient was started on oral itraconazole 200mg BID. Follow-up after 1 month showed both symptomatic and radiological improvement. Repeat chest CT showed a significant decrease in size of the nodule.

There is a large spectrum of pulmonary aspergillosis. From this spectrum, pulmonary nodules are a less common manifestation of chronic pulmonary aspergillosis (CPA), especially in immunocompetent individuals. Aspergillus nodules are defined as small, round, discrete, and focal opacities on chest imaging. It can be further classified on basis of internal cavitation (i.e., non-cavitary nodules and cavitary nodules). Differentiating these nodules from other lung pathology may be difficult on CT findings alone and may demand further investigation like image-guided needle aspiration cytology or biopsy, blood investigations like serum Aspergillus precipitin IgG antibody and/or serum Aspergillus galactomannan. Delay in diagnoses may lead to persistence of pulmonary symptoms, and cavitation of the nodule. This entity has a favorable prognosis if managed accordingly. Although there is data regarding surgical management of aspergillus nodules, but data regarding the benefits of anti-fungal therapy in the same is limited.

Diagnosing aspergillus nodules in an immunocompetent individual is a challenge to all pulmonologists. Literature shows limited case reports and small case series on CPA presenting as non-cavitating SPN on radiology. Usually, in such cases, the diagnosis is made following removal or biopsy of the nodule(s), presuming it to be malignant. Patients diagnosed with Aspergillus nodules can’t be differentiated from lung malignant conditions based on demographics, which are usually similar. In the largest case series of Aspergillus nodules done by Muldoon EG et al. (6), 33 patients were reviewed constituting less than 10 % of the cohort of patients with CPA.  In a study done by Kang et al. (4) 77% of patients with aspergillus nodules were symptomatic and the most common symptom reported was hemoptysis. Similarly in our case hemoptysis was the chief complaint of the patient. Our patient is a woman and non-smoker similar to previous case reports and series.

In the current guidelines, the detection of serum Aspergillus precipitin IgG antibody is a key diagnostic criterion for CPA. Literature is unclear if the presence of Aspergillus IgG antibody could be considered a supportive finding in the making the diagnosis of Aspergillus nodules. Similarly, in our case also serum specific IgG against Aspergillus fumigatus was negative. Azoles are the primary treatment option in all subtypes of CPA including aspergillus nodule. Our patient also showed disease regression during itraconazole treatment. Another option for management is surgical, though it is associated with significant postoperative complications and recurrence of disease at other sites and must be reserved for selected patients.

Dr. Deependra Kumar Rai, Dr. Priya Sharma, Dr. Vatsal Bhushan Gupta

Department of Pulmonary, Critical Care, and Sleep Medicine

AIIMS Patna, Bihar, India

References

1. Kosmidis C, Denning DW. The clinical spectrum of pulmonary aspergillosis. Thorax. 2015 Mar;70(3):270-7. [CrossRef] [PubMed]
2. Hansell DM, Bankier AA, MacMahon H, McLoud TC, Müller NL, Remy J. Fleischner Society: glossary of terms for thoracic imaging. Radiology. 2008 Mar;246(3):697-722. [CrossRef] [PubMed]
3. Lee SH, Lee BJ, Jung DY, Kim JH, Sohn DS, Shin JW, Kim JY, Park IW, Choi BW. Clinical manifestations and treatment outcomes of pulmonary aspergilloma. Korean J Intern Med. 2004 Mar;19(1):38-42. [CrossRef] [PubMed]
4. Kang N, Park J, Jhun BW. Clinical Characteristics and Treatment Outcomes of Pathologically Confirmed Aspergillus Nodules. J Clin Med. 2020 Jul 10;9(7):2185. [CrossRef] [PubMed]
5. Yasuda M, Nagashima A, Haro A, Saitoh G. Aspergilloma mimicking a lung cancer. Int J Surg Case Rep. 2013;4(8):690-2. [CrossRef] [PubMed]
6. Muldoon EG, Sharman A, Page I, Bishop P, Denning DW. Aspergillus nodules; another presentation of Chronic Pulmonary Aspergillosis. BMC Pulm Med. 2016 Aug 18;16(1):123. [CrossRef] [PubMed]
7. Denning DW, Cadranel J, Beigelman-Aubry C, et al. Chronic pulmonary aspergillosis: rationale and clinical guidelines for diagnosis and management. Eur Respir J. 2016 Jan;47(1):45-68. [CrossRef] [PubMed]
8. Limper AH, Knox KS, Sarosi GA, et al. An official American Thoracic Society statement: Treatment of fungal infections in adult pulmonary and critical care patients. Am J Respir Crit Care Med. 2011 Jan 1;183(1):96-128. [CrossRef] [PubMed]
9. Godet C, Philippe B, Laurent F, Cadranel J. Chronic pulmonary aspergillosis: an update on diagnosis and treatment. Respiration. 2014;88(2):162-74. [CrossRef] [PubMed]
10. Kousha M, Tadi R, Soubani AO. Pulmonary aspergillosis: a clinical review. Eur Respir Rev. 2011 Sep 1;20(121):156-74. [CrossRef] [PubMed]

Cite as: Rai DK, Sharma P, Gupta VB. September 2023 Medical Image of the Month: Aspergillus Presenting as a Pulmonary Nodule in an Immunocompetent Patient. Southwest J Pulm Crit Care Sleep;27(3):30-32. doi: https://doi.org/10.13175/swjpccs035-23 PDF

August 2023 Medical Image of the Month: Cannonball Metastases from Metastatic Melanoma

Figure 1. Upright PA chest radiograph (A) demonstrates innumerable rounded nodules with a slight lower lung predilection. Coronal reconstruction from a subsequent chest CT with contrast (B) confirms innumerable round, solid and non-calcified pulmonary nodules most consistent with a “cannonball” pattern of pulmonary metastatic disease.

Figure 2. Axial susceptibility-weighted (A) and pre-contrast T1-weighted (B) images from a brain MRI centered on one (of many) intracranial lesions. This lesion in the posterior right cerebral hemisphere demonstrates a large amount of surrounding susceptibility artifact (A) consistent with blood product, indicating a hemorrhagic metastasis, common in metastatic melanoma which can be very vascular in nature.  There is elevated T1 signal surrounding the lesion (B), also consistent with hemorrhage. There is T1 signal in the center of the lesion as well (arrow), which could represent hemorrhage but could also represent melanin, which is T1 bright and can suggest the primary tumor histology (melanoma).

A 48-year-old man with a significant smoking history presented with progressive dyspnea, a mildly productive cough with brown-tinged sputum, headache, weight loss, and progressive back pain over a period of 8 weeks. The patient had no known history of lung conditions. As part of their initial evaluation, the patient received a frontal CXR and was found to have innumerable rounded pulmonary nodules throughout the lungs, which were consistent with a “cannonball” pattern of pulmonary metastatic disease (Figure 1A). A subsequent CT confirmed innumerable pulmonary metastases (Figure 1B). An MRI of the brain and spine revealed hemorrhagic brain metastases (Figure 2), spinal metastases, and bone metastases. A biopsy of a lesion in the left iliac bone confirmed the diagnosis of metastatic melanoma.

This case highlights the so-called “cannonball” pattern of pulmonary metastatic disease with innumerable round nodules throughout the lungs with a slight lower lung predilection, consistent with a hematogenous spread of disease to the lungs. Classically, this pattern consists of numerous well-circumscribed relatively large lesions in the lungs with a pattern resembling multiple small "cannonballs". The distribution of nodules is random, and the factors that distinguish a cannonball pattern from a miliary pattern of pulmonary metastatic disease are that cannonball metastases are larger and less numerous compared to a miliary pattern of pulmonary metastatic disease (1,2). Although cannonball pattern of pulmonary metastatic disease is classically described in the setting of metastatic renal cell carcinoma, prostate cancer, choriocarcinoma, and sarcoma, it has been reported for a variety of other primary cancers, including melanoma. Similar cases of late-stage metastatic melanoma presenting as widely metastatic disease of unknown origin has also been reported (3).

Melanoma spreads to the lungs through hematogenous dissemination, resulting in the cannonball (or miliary) lesions observed on imaging. Specifically, when these lesions are small and distributed throughout the lung, they commonly indicate metastatic melanoma. While this classical presentation can be pathognomonic, it is important to consider other potential diagnoses, including malignancy, infectious diseases, and rheumatologic conditions. Malignant causes encompass metastatic colorectal cancer, breast cancer, renal cell carcinoma, choriocarcinoma, prostate carcinoma, and adrenal carcinoma. Additionally, non-cancerous causes include infectious etiologies such as septic emboli, coccidiomycosis, histoplasmosis, miliary tuberculosis, and nocardiosis. It is also important to note that rheumatologic conditions like granulomatosis with polyangiitis (Wegener's granulomatosis) can present with the cannonball sign; however, they typically involve both the upper and lower lungs. In this case, the lesions were determined to be due to metastatic melanoma, which had spread to the lungs via hematogenous dissemination.

For this patient, an oncologist was consulted, who recommended that the patient undergo treatment with ipilimumab and nivolumab. The response rate for this treatment regimen generally exceeds 50%, and more than 50% of individuals continue to survive after 5 years. Frequently, when extensive metastases are observed on imaging, healthcare providers often assume a limited life expectancy and tend to lean towards discussions of hospice care. However, it is important to keep in mind that even in cases of extensive metastatic disease, many cancers can be effectively treated with novel and highly effective immunologic anticancer medications.

Andrew Barsoum MD, Mueez Hussain MD, Ranjit Sivanandham MD, and Sina Bagheri MD.

Southwest Healthcare System

Murrieta, California 

References

1. Ammannagari N, Polu V. 'Cannon ball' pulmonary metastases. BMJ Case Rep. 2013 Jan 8;2013:bcr2012008158. [CrossRef][PubMed]
2. Andreu J, Mauleón S, Pallisa E, Majó J, Martinez-Rodriguez M, Cáceres J. Miliary lung disease revisited. Curr Probl Diagn Radiol. 2002 Sep-Oct;31(5):189-97. [PubMed]
3. Lowe A, Bray JJH. Late-stage melanoma presenting with cannonball metastases. BMJ Case Rep. 2020 Dec 12;13(12):e237969. [CrossRef][PubMed]

Cite as: Barsoum A, Hussain M, Sivanandham R, Bagheri S. August 2023 Medical Image of the Month: Cannonball Metastases from Metastatic Melanoma. Southwest J Pulm Crit Care Sleep. 2023;27(2):23-25. doi: https://doi.org/10.13175/swjpccs025-23 PDF

August 2023 Imaging Case of the Month: Chew Your Food Carefully

Michael B Gotway MD¹ and Yasmeen M Butt MD²

¹Departments of Radiology and ²Laboratory Medicine, Division of Anatomic Pathology

Mayo Clinic-Arizona

Scottsdale, Arizona USA

History of Present Illness

A 50-year-old woman presents with a history of chronic dyspnea and cough, becoming particularly problematic following COVID-19 infection 4 months prior to presentation. While she did experience significant periodic oxygen desaturations during her COVID-19 infection, she was not hospitalized for this illness. The patient also reported wheezing in the previous few weeks. 

Past Medical History, Family History and Social History

The patient’s past medical history was also notable for gastroesophageal reflux disease as well as both Coombs positive and iron deficiency anemia. She reports a history of asthma, well controlled with inhaler use.

The patient’s past surgical history included adenoidectomy, cholecystectomy, and gastric laparoscopic band placement.

Her medications included prednisone (20 mg daily), dextroamphetamine-amphetamine, furosemide, omeprazole, fluoxetine, zolpidem (Ambien), daily Bactrim, occasional Loratadine (Claritin). She also utilized an albuterol inhaler and Fluticasone-based (both Flonase and Breo Ellipta) inhalers.

The patient is a former smoker, ½ pack-per day for 26 years, having quit 11 years prior to presentation. She also reported a history of vaping (agent inhaled unclear) for 8 years, quitting 3 years earlier. She has no known allergies. She drinks alcohol socially and denied illicit drug use.

Physical Examination

The patient’s physical examination showed her temperature to be 99°F with normal pulse and respiratory rate but her blood pressure elevated at 160/90 mmHg. She was obese (263 lbs., BMI= 41). Bilateral basal rales were noted at her examination, but no other abnormal physical examination findings were detected.

Laboratory Evaluation

The patient’s room air pulse oximetry was 85%. A complete blood count showed an upper normal white blood cell count at 1.9 x10⁹/L (normal, 4.5 – 11 x10⁹/L). Her hemoglobin and hematocrit values were 10.7 gm/dL (normal, 12 – 16 gm/dL) and 37.1% (normal, 36 – 46%). The patient’s serum chemistries and liver function studies were entirely normal. The patient had an elevated anti-nuclear antibody titer at 1:320. An echocardiogram noted diastolic dysfunction but normal left ventricular contractility.

Frontal chest radiography (Figure 1) was performed.

Figure 1. Frontal chest radiography.

Which of the following statements regarding this chest radiograph is accurate? (Click on the correct answer to be directed to the second of 11 pages)

1. Frontal chest radiography shows normal findings
2. Frontal chest radiography shows marked cardiomegaly
3. Frontal chest radiography shows mediastinal lymphadenopathy
4. Frontal chest radiography shows pleural effusion
5. Frontal chest radiography shows multifocal peribronchial consolidation

Cite as: Gotway MB, Butt YM. August 2023 Imaging Case of the Month: Chew Your Food Carefully. Southwest J Pulm Crit Care Sleep. 2023;27(2):15-22. doi: https://doi.org/10.13175/swjpccs034-23 PDF

July 2023 Medical Image of the Month: Primary Tracheal Lymphoma

Figure 1. Frontal (A) and lateral (B) x-rays demonstrate a large density disrupting the tracheal air column (arrows), a reminder of how important it can be to evaluate the trachea on radiographs. The finding arises from the left aspect of the mid trachea, causing severe narrowing (arrowheads). To view Figure 1 in a separate, enlarged window click here.

Figure 2. Axial reconstruction from a contrast-enhanced chest CT (A) demonstrates an exophytic mass arising from the left aspect of the upper to mid trachea, causing severe tracheal stenosis. Centerline (B) and 3D Volume-rendered (C) reconstructions from a subsequent pre-bronchoscopy planning noncontrast CT scan demonstrate a mass arising from the left lateral wall of the trachea (arrows) involving slightly more than 5 cm of tracheal length. To view Figure 2 in a separate, enlarge window click here.

Figure 3. Bronchoscopic images of the trachea prior to (A) and following (B) piecemeal electrocautery for de-bulking of a fungating exophytic mass in the mid trachea. The procedure was performed to alleviate the patient’s severe symptoms related to severe tracheal stenosis. To view Figure 3 in a separate, enlarged window click here.

A 72-year-old woman was referred to our practice from an outside hospital with a history of tracheal mass with impending airway compromise. She originally presented with several days of dyspnea, stridor, and an increasingly muffled voice. She also provided a history of severe shortness of breath, but only when eating. Interestingly, she had no trouble swallowing. CXR findings at the outside hospital (Figure 1) prompted a CT (Figure 2A), which further prompted transfer of patient to our facility. The patient had a history of hypertension, hyperlipidemia, type 2 diabetes and obstructive sleep apnea. Her past surgical history included C-section and hysterectomy. The patient was a never-smoker with no significant drinking or drug usage history. The patient had no recent travel or exposure history. Review of symptoms otherwise negative. Although the patient had no formal diagnosis of asthma, she was on Mometasone/formoterol, 2 puffs bid and also had an albuterol rescue inhaler. The patient was on various other medications for seasonal allergies, hyperlipidemia, hypertension, and diabetes. No significant allergy history.

Vital signs upon presentation were normal, aside from tachycardia, heart rate was 103 bpm. No fever, normal oxygen saturation. On physical exam, the patient had obvious stridor heard throughout the lungs. Physical exam was otherwise unremarkable. Initial lab testing consisted of a basic metabolic panel and a complete blood count, both of which were normal. A repeat CT scan was obtained at our institution for pre-procedural planning. That CT demonstrated an endotracheal mass with a significant intraluminal component causing near-complete obstruction (Figure 2B,C). Of note, slightly more than 5 cm of the tracheal length was involved with tumor. In order to obtain a tissue diagnosis and also due to impending airway compromise, ridged bronchoscopy was performed (Figure 3). A combination of suction and electrocautery were used to debulk the tumor in order to relieve airway obstruction. Histopathology was consistent with diffuse large B-cell lymphoma. A bone marrow biopsy was negative for any marrow involvement. A diagnosis of primary tracheal lymphoma was made. The patient was started on the appropriate chemotherapy and had a good response.

Primary tumors of the trachea are rare and make up less than 0.4% of all tumors, producing 0.1% of cancer deaths worldwide. Primary malignant tumors typically arise from surface epithelium or salivary glands (1). As such, squamous cell carcinoma and adenoid cystic carcinoma account for the 1st and 2nd most common primary malignant tumors of the trachea. Mucoepidermoid carcinoma, a salivary gland type tumor, also occurs in the trachea. Given the presence of APUD cells in the trachea, carcinoid tumors can also occur, although these are rare in the central airways, and more common in the segmental and subsegmental bronchi. Given the presence of cartilage in the wall of the trachea, chondrosarcoma of the trachea can also occur. While most of these tumor histologies have a relatively nonspecific appearance, chondrosarcomas can produce chondroid matrix, which, when present, allows for some specificity when imaged with CT. Malignant involvement of the trachea can also result from direct invasion by tumors arising from adjacent structures such as the thyroid, lung, esophagus, and larynx, or by hematogenous metastasis from distant organs such as kidney, breast, colon, and melanoma (1).

Non-Hodgkin lymphoma (NHL) involving the central airway is uncommon, even though the disease frequently involves extranodal organs. Primary tracheobronchial NHL occurs in less than 1% of all NHL patients (2). Involvement of central airways in NHL can cause respiratory failure (3). A case very similar to our own was reported recently (4). In that case a patient with primary tracheobronchial NHL suffered rare, life-threatening obstruction of the central airway that prevented chemotherapy. To alleviate the airway obstruction, interventional bronchoscopy involving cryotherapy, electrocautery and argon plasma coagulation was performed, allowing administration of chemotherapy.

Clinton Jokerst MD, Matthew Stib MD, Carlos Rojas MD, Prasad Panse MD, Kris Cummings MD, Eric Jensen MD and Michael Gotway MD

Department of Radiology

Mayo Clinic Arizona, Scottsdale, AZ USA

References

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Cite as: Jokerst C, Stib M, Rojas C, Panse P, Cummings K, Jensen E, Gotway MB. July 2023 Medical Image of the Month: Primary Tracheal Lymphoma. Southwest J Pulm Crit Care. 2023;27(1):4-6. doi: https://doi.org/10.13175/swjpccs026-23 PDF