February 2024 Medical Image of the Month: Pulmonary Alveolar Proteinosis in Myelodysplastic Syndrome

Figure 1.  Axial CT images from a contrast-enhanced chest CT performed on the patient at time of admission (A,B) demonstrate a combination of smooth septal line thickening and superimposed ground glass, resulting in a “crazy paving” appearance.  A noncontrast chest CT performed at an outside hospital 2 months earlier also demonstrates “crazy paving”; however, the findings have progressed significantly during the 2 intervening months.

A 56-year-old man presented to our institution with weight loss, fatigue, and worsening dyspnea. A chest CT (Figure 1A,B) showed a patchy, mostly central crazy-paving pattern. An outside hospital CT performed 2 months earlier was also made available for comparison (Figure 1C,D) demonstrating interval progression of these findings. The patient also had mediastinal and hilar adenopathy.  Past workup had primarily focused on the lymphadenopathy with considerations of possible lymphoma, sarcoidosis or coccidiomycosis infection. A past lymph node biopsy had revealed non-caseating granulomas and serum titers were positive for coccidiomycosis. Lymphadenopathy decreased after initiation of coccidiomycosis treatment, but symptoms and crazy paving findings continued to worsen. Further workup revealed a new diagnosis of myelodysplastic syndrome (MDS) and subsequent bronchoalveolar lavage (BAL) and histology results were consistent with secondary PAP, likely due to patient’s underlying hematologic disease.

Pulmonary alveolar proteinosis (PAP) is a rare disease characterized by the accumulation of lipoproteinaceous material in the lung alveoli. There are two types of PAP that occur in adults: Idiopathic/autoimmune and Secondary PAP. Idiopathic/autoimmune PAP is more common and is thought to result from antibody production against granulocyte-macrophage-colony-stimulating factor (GM-CSF) that regulates surfactant homeostasis. Secondary PAP results from a precipitating condition, often inhalation exposure, underlying malignancy, or immunocompromise.

The clinical manifestations of PAP are nonspecific and includes dyspnea, nonproductive cough, fatigue, and weight loss. CT may show nonspecific findings of smooth, bilateral interlobular septal thickening superimposed on a background of ground-glass opacification (crazy-paving). Diagnosis is confirmed with BAL and lung biopsy showing accumulation of eosinophilic and periodic acid-Schiff stain (PAS) positive lipoproteinaceous material within alveoli. Treatment involves pulmonary lavage for idiopathic/autoimmune PAP and treating the underlying condition for secondary PAP.

Parker Brown MD, Clint Jokerst MD, Michael Gotway MD, Matthew Stib MD

Department of Radiology

Mayo Clinic Arizona, Scottsdale, AZ

References

1. Frazier AA, Franks TJ, Cooke EO, Mohammed TL, Pugatch RD, Galvin JR. From the archives of the AFIP: pulmonary alveolar proteinosis. Radiographics. 2008 May-Jun;28(3):883-99; quiz 915. [CrossRef][PubMed]
2. Ioachimescu OC, Kavuru MS. Pulmonary alveolar proteinosis. Chron Respir Dis. 2006;3(3):149-59. [CrossRef] [PubMed]
3. Presneill JJ, Nakata K, Inoue Y, Seymour JF. Pulmonary alveolar proteinosis. Clin Chest Med. 2004 Sep;25(3):593-613, viii. [CrossRef] [PubMed]

Cite as: Brown P, Jokerst C, Gotway MB, Stib M. February 2024 Medical Image of the Month: Pulmonary Alveolar Proteinosis in Myelodysplastic Syndrome. Southwest J Pulm Crit Care Sleep. 2024;28(2):18-19. doi: https://doi.org/10.13175/swjpccs004-24 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

Medical Image of the Week: Diffuse Alveolar Hemorrhage in a Patient with ANCA Vasculitis and IgG4-Related Disease

Figure 1. Well-circumscribed, high-density, airspace opacities with a “crazy-paving” pattern in the upper and lower lobes with peripheral sparing (blue arrows) consistent with alveolar hemorrhage.

Figure 2. Well-circumscribed, high-density, airspace opacities with a “crazy-paving” pattern in the upper and lower lobes with peripheral sparing (blue arrows) consistent with alveolar hemorrhage.

The patient is a 47-year-old man with a history of bilateral orbital pseudotumor associated with immunoglobulin G4-related disease (IgG4-RD). He presented with progressively worsening exertional dyspnea evolving into multisystemic failure.  During the hospitalization, the patient was found to have pauci-immune ANCA-positive vasculitis and glomerulonephritis.

CT images (Figures 1 and 2) show relatively well-circumscribed and extensive upper lung predominant airspace opacities with high attenuation, in some cases with a patchy configuration. A background of interstitial prominence was also noted resulting in a "crazy paving" pattern”, consistent with diffuse alveolar hemorrhage.  This was confirmed with bronchoalveolar lavage.

Discussion

IgG4-RD (IgG4 related disease), is an autoimmune condition capable of causing inflammation and fibrosis of multiple organs, most classically the pancreas (1). IgG4 is the least abundant IgG in the serum and the least likely to stimulate immune activation due to its inability to activate complement (2).

The thoracic manifestations that have been described in cases of pure IgG4-RD include solid nodules, which can appear similar to malignant lesions. Interstitial changes have also been described in the form of non-specific interstitial pneumonia pattern, organizing pneumonia, bronchiolitis obliterans, acute interstitial pneumonitis and a sarcoid-like reaction. There may also be pleural involvement and thickening/irregularity of the central airways. The multiple varying presentations and their potential concomitance can lead to misinterpretation of findings (1-2).

This patient presented with the known history of IgG4-RD. The acute symptoms included hemoptysis/diffuse alveolar hemorrhage and renal failure. To the best of our knowledge, pulmonary hemorrhage has not been described as a potential manifestation of this IgG4-RD.   Therefore, the later diagnosed concomitant ANCA paucimmune vasculitis, likely explained the observed pulmonary findings. The coexistence of two different autoimmune vasculitides has been described before, both contributing to multiorgan-involvement (3).

Mariam Mostamandy BS and Diana Palacio MD

Department of Medical Imaging

The University of Arizona – Banner Medical Center

Tucson, AZ

References

1. Kurowecki D, Patlas MN, Haider EA, Alabousi A. Cross-sectional pictorial review of IgG4-related disease. Br J Radiol. July 2019:20190448. [CrossRef] [PubMed]
2. Campbell SN, Rubio E, Loschner AL. Clinical review of pulmonary manifestations of IgG4-related disease. Ann Am Thorac Soc. 2014;11(9):1466-75. [CrossRef] [PubMed]
3. Carruthers I, Shingare S, Khosroshahi A, et al. IgG4 plasma cell infiltration in granulomatosis with polyangiitis (formerly Wegener’s) lung biopsies. 2012 ACR/ARHP Annual Meeting. [Abstract 1534].

Cite as: Mostamandy M, Palacio D. Medical image of the week: diffuse alveolar hemorrhage in a patient with ANCA vasculitis and IgG4-related disease. Southwest J Pulm Crit Care. 2020;20(3):98-9. doi: https://doi.org/10.13175/swjpcc009-20 PDF 

Medical Image of the Week: Pulmonary Alveolar Proteinosis

Figure 1. Representative image from an axial CT scan showing “crazy paving”.

Pulmonary alveolar proteinosis (PAP) is a rare pulmonary disease characterized by alveolar accumulation of surfactant (1). It usually results from mutations in surfactant proteins or granulocyte macrophage-colony stimulating factor (GM-CSF) receptor genes. Other causes include toxic inhalation or hematological disorders, or it may be auto-immune, with anti-GM-CSF antibodies blocking activation of alveolar macrophages.

Auto-immune alveolar proteinosis is the most frequent form of PAP, representing 90% of cases. Although not specific, high-resolution computed tomography shows a characteristic diffuse ground-glass attenuation with superimposed interlobular septal thickening and intralobular lines which is called “crazy paving” (Figure 1). In most cases, bronchoalveolar lavage findings establish the diagnosis. Whole lung lavage is the most effective therapy, especially for auto-immune disease. Novel therapies targeting alveolar macrophages (recombinant GM-CSF therapy) or anti-GM-CSF antibodies (rituximab and plasmapheresis) are considered investigational. 

Bhupinder Natt MD FACP

Division of Pulmonary, Allergy, Critical Care and Sleep

Banner University Medical Center, Tucson (AZ) USA

Reference

1. Borie R, Danel C, Debray MP, Taille C, Dombret MC, Aubier M, Epaud R, Crestani B. Pulmonary alveolar proteinosis. Eur Respir Rev. 2011 Jun;20(120):98-107. [CrossRef] [PubMed]

Cite as: Natt B. Medical image of the week: pulmonary alveolar proteinosis. Southwest J Pulm Crit Care. 2018;16(1):14. doi: https://doi.org/10.13175/swjpcc002-18 PDF 

October 2013 Imaging Case of the Month

Michael B. Gotway, MD

Department of Radiology

Mayo Clinic Arizona

Scottsdale, AZ 

Clinical History

A 67-year-old man with a history of hypertension and chronic lymphocytic leukemia (CLL), the latter diagnosed 10 years earlier, in remission until recently, presented with complaints of weight loss, not eating much, lethargy, and shortness of breath. His CLL had recurred and he was treated with rituximab, and bendamustine (a nitrogen mustard alkylating agent) and intravenous immunoglobulin. Frontal chest radiography (Figure 1) was performed.

Figure 1. Initial chest radiograph.

Which of the following statements regarding the chest radiograph is most accurate?

1. The chest radiograph shows basal predominant linear opacities suggesting fibrosis
2. The chest radiograph shows large lung volumes with cystic change
3. The chest radiograph shows multifocal ground-glass opacity and cavitary consolidation
4. The chest radiograph shows multifocal ground-glass opacity and consolidation associated with linear and reticular abnormalities
5. The chest radiograph shows multiple nodules

Reference as: Gotway MB. October 2013 imaging case of the month. Southwest J Pulm Crit Care. 2013;7(4):223-31. doi: http://dx.doi.org/10.13175/swjpcc133-13 PDF

March 2013 Imaging Case of the Month

Michael B. Gotway, MD*

Sudheer Penupolu, MD^‡

Jasminder Mand, MD^†

*Department of Radiology, Mayo Clinic, Arizona

^‡Fellow, Pulmonary Medicine, Mayo Clinic Arizona

^†Pulmonary and Critical Care Medicine, Maricopa Medical Center

Clinical History: A 54-year old Hispanic woman with no significant past medical history presented with complaints of cough and worsening dyspnea. She was in her usual state of health until 4-5 weeks prior to presentation when she started noticing gradually worsening dyspnea on exertion. She reported a dry cough initially which subsequently became productive of whitish, mucoid sputum. The patient denied chest pain, sore throat, sick contacts, or recent travel history. A chest x-ray was performed (Figure 1).

Figure 1. Frontal (A) and lateral (B) chest radiography.

Which of the following statements regarding the chest radiograph is most accurate?

1. The chest radiograph shows bilateral linear and reticular abnormalities
2. The chest radiograph shows nodular interstitial thickening
3. The chest radiograph shows multiple, bilateral circumscribed nodules
4. The chest radiograph shows mediastinal and hilar lymph node enlargement
5. The chest radiograph shows mediastinal widening

Reference as: Gotway MB, Penupolu S, Mand J. March 2013 imaging case of the month. Southwest J Pulm Crit Care. 2013;6(3):112-24. PDF

August 2012 Imaging Case of the Month

Michael B. Gotway, MD

Associate Editor, Imaging

Department of Radiology

Mayo Clinic Arizona

Scottsdale, Arizona 

Clinical History: A 48-year-old non-smoking man presented with a history of slowly progressive shortness of breath and recent onset of a headache. Frontal chest radiography (Figure 1) was performed. 

Figure 1: Frontal chest radiography shows normal cardiomediastinal contours with bilateral peri- and infrahilar predominant ground-glass opacity with a background of linear and reticular abnormalities.

Which of the differential diagnostic considerations listed below is the most likely consideration for the chest radiographic abnormality?

1. Pneumococcal pneumonia
2. Lung carcinoma
3. Idiopathic pulmonary fibrosis
4. Pulmonary alveolar proteinosis
5. Miliary tuberculosis

Reference as: Gotway MB. August 2012 imaging case of the month. Southwest J Pulm Crit Care 2012;5:74-81. (Click here for a PDF version of the case of the month)