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Dyspnea With Unilateral Pulmonary Ground Glass Opacities and Cavitary Lesions

      Case Presentation

      A 62-year-old man presented with a 3-month history of shortness of breath and a dry cough. He had a medical history of hypertension (without use of angiotensin-converting enzyme inhibitors), hyperlipidemia, depression, and 10-pack-years of cigarette smoking several decades ago. He was a limousine driver and denied any history of occupational high-risk exposures. The patient denied significant weight gain or weight loss, night sweats, fevers, hemoptysis, chest pain, or palpitations. He had a normal physical examination. Pulmonary function studies with a hemoglobin level of 12.9 gm/dL revealed normal spirometry, normal lung volumes, and moderately low diffusion capacity (56% of predicted). A 6-minute walk test showed mild desaturation (97% to 92% after 432 m). Stress echo revealed ejection fraction of 60% with no regional wall motion abnormalities, no evidence of impaired diastolic filling, estimated peak pulmonary artery pressure 35 to 40 mm Hg, and no valvular abnormalities with desaturation to 87% during the test. Extensive rheumatologic, infectious disease, and hypercoagulability workup were unremarkable. BAL was negative for malignancy, infection, or eosinophilic lung disease.
      Initial chest radiograph showed small right lung volume with reticular opacities (Fig 1). Subsequent chest CT scanning revealed diffuse right lung ground glass opacities (GGO) and a 1.5-cm solid nodule with spiculated margins in the superior segment of left lower lobe (LLL) (Fig 2). Repeat chest CT scanning after 3 months revealed development of new large cavitary lesions in the right lung, worsening GGOs, mediastinal lymphadenopathy, and the stable left lung nodule (Fig 3). Three months later (6 months since presentation), a third chest CT scan revealed a 10-cm mass in his mediastinum with complete obstruction of the right main pulmonary artery and partially collapsed superior vena cava (SVC) (Fig 4).
      Figure thumbnail gr1
      Figure 1Posterior-anterior chest radiograph on initial presentation shows right basilar patchy opacity and scattered regions of pulmonary scarring.
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      Figure 2Initial chest CT scan shows unilateral right-sided ground glass opacities with subpleural consolidation and a 1.5-cm solid lung nodule with speculated margins in the superior segment of the left lower lobe.
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      Figure 3Subsequent chest CT scan (3 months after presentation) shows unilateral right-sided ground glass opacities with interval development of multiple large cavitary lesions,
      Figure thumbnail gr4
      Figure 4Final chest CT angiography (6 months after presentation) shows complete obstruction on the main right pulmonary artery, compression of the superior vena cava, and a large right-sided mass whose epicenter is at the proximal right hilum.
      Bronchoscopy with BAL did not show eosinophilia that would suggest a diagnosis of eosinophilic pneumonia or interstitial lung disease associated with high BAL eosinophilia (connective tissue disease, drug-induced pneumonitis, sarcoidosis, or pulmonary Langerhans cell histiocytosis). Additionally, BAL was negative for infectious and malignant causes. Open right lung biopsy showed organizing acute lung injury, accompanied by organizing fibrinous pleuritis and patchy parenchymal infarcts with numerous intravascular organizing thrombi with no evidence of malignancy (Fig 5). Endobronchial ultrasound scanning was performed and showed necrotic subcarinal lymph nodes negative for granulomas, infectious, and malignant causes. Finally, the LLL nodule was biopsied and revealed malignant spindle cell tumor (Fig 6A).
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      Figure 5A, Acute infarction is present in the lower half of this picture. Active fibroplasia, interstitial edema, and acute inflammatory infiltration are present in the adjacent intact parenchyma. B, Intra-alveolar fibrin, septal edema, type II pneumocyte hyperplasia, subpleural vascular congestion, and mild fibroplasia represent the histology of the diffuse ground glass changes present throughout the right lung. (Hematoxylin and eosin stain; original, ×400.)
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      Figure 6A diagnosis of pulmonary artery intimal sarcoma in this case is strongly supported by A, the pulmonary arterial location of this tumor, the characteristic malignant spindle cell morphology, and the markedly amplified transcriptional proteins, B, MDM2 marker, and C, HMGA2 marker. (Hematoxylin and eosin stain; original magnification ×400.)
      What is the diagnosis?
      Diagnosis: Primary pulmonary arterial intimal sarcoma

      Clinical Discussion

      The patient presented with non- symptoms of dry cough and dyspnea on exertion. His initial workup, which included a normal spirometry with normal lung volumes and a largely normal echocardiogram, ruled out obstructive lung disease and heart failure. The lack of occupational exposure, weight loss, night sweats, fevers, hemoptysis, or chest pain at presentation decreased the suspicion for pulmonary malignancy as the cause of the patient’s symptoms. The 1.5-cm left-sided pulmonary nodule was not suspected to be related to the patient’s symptoms. The desaturations during the stress echocardiogram and 6-minute walk test along with the moderately low diffusion capacity in the setting of normal lung volumes on pulmonary function testing pointed towards underlying pulmonary vascular disease. The absence of more specific symptoms and negative comprehensive rheumatologic workup decreased the suspicion for connective tissue disease related interstitial lung disease. Negative initial bronchoscopy and diffuse GGOs on CT scanning raised the suspicion of cryptogenic organizing pneumonia (COP), which prompted starting treatment with 60 mg of prednisone daily. Lack of clinical response led to another chest CT scan that revealed increasing GGOs, new cavitary lesions, and lymphadenopathy that led to endobronchial ultrasound scanning. Sampling of lymph nodes showed necrotic subcarinal lymph node negative for granulomas and infectious and malignant causes. Finally, LLL nodule was biopsied and revealed pleomorphic spindle cell neoplasm that was diagnosed as pulmonary intimal sarcoma.
      Pulmonary artery intimal sarcoma (PAIS) is a rare and aggressive malignancy with a very poor prognosis. Since its discovery in 1923 by Mandelstamm, approximately 300 cases have been reported worldwide.
      • Mandelstamm M.
      Über primäre Neubildungen des Herzens.
      ,
      • García-Cabezas S.
      • Centeno-Haro M.
      • Espejo-Pérez S.
      • et al.
      Intimal sarcoma of the pulmonary artery with multiple lung metastases: long-term survival case.
      It has an estimated incidence of 0.001% to 0.003%, with a median survival of 17 months.
      • García-Cabezas S.
      • Centeno-Haro M.
      • Espejo-Pérez S.
      • et al.
      Intimal sarcoma of the pulmonary artery with multiple lung metastases: long-term survival case.
      PAIS largely occurs in the fifth or sixth decade of life with a modest female predominance.
      • Parish J.M.
      • Rosenow III, E.C.
      • Swensen S.J.
      • Crotty T.B.
      Pulmonary artery sarcoma: clinical features.
      • Yi C.A.
      • Lee K.S.
      • Choe Y.H.
      • et al.
      Computed tomography in pulmonary artery sarcoma: distinguishing features from pulmonary embolic disease.
      • Yi J.E.
      • Tazelaar H.D.
      • Burke A.
      • Manabe T.
      Pulmonary artery sarcoma.
      Symptoms include dyspnea, cough, hemoptysis, chest pain, and weight loss.
      • Parish J.M.
      • Rosenow III, E.C.
      • Swensen S.J.
      • Crotty T.B.
      Pulmonary artery sarcoma: clinical features.
      ,
      • Yi J.E.
      • Tazelaar H.D.
      • Burke A.
      • Manabe T.
      Pulmonary artery sarcoma.
      Clinical and radiologic findings often mimic pulmonary vascular diseases, leading to delayed diagnosis.
      • Jiang S.
      • Li J.
      • Zeng Q.
      • Liang J.
      Pulmonary artery intimal sarcoma misdiagnosed as pulmonary embolism: a case report.
      ,
      • El-Sayed Ahmed M.M.
      • Aftab M.
      • Al-Najjar R.M.
      • de la Cruz K.I.
      • Benjamin R.S.
      • Hallman C.H.
      Pulmonary artery sarcoma mimicking pulmonary embolism.
      Table 1 summarizes the criteria for PAIS diagnosis.
      Table 1Diagnostic Features of Pulmonary Arterial Intimal Sarcoma
      • Parish J.M.
      • Rosenow III, E.C.
      • Swensen S.J.
      • Crotty T.B.
      Pulmonary artery sarcoma: clinical features.
      • Yi C.A.
      • Lee K.S.
      • Choe Y.H.
      • et al.
      Computed tomography in pulmonary artery sarcoma: distinguishing features from pulmonary embolic disease.
      • Yi J.E.
      • Tazelaar H.D.
      • Burke A.
      • Manabe T.
      Pulmonary artery sarcoma.
      DefinitionPulmonary artery soft tissue tumor that displays an intraluminal polyploid growth pattern and fibroblastic or myofibroblastic differentiation
      LocalizationAnywhere in the pulmonary trunk; right and left pulmonary arteries are the most common sites
      Clinical featuresFever, dyspnea, cough, chest pain, back pain, weight loss, malaise, hemoptysis, syncope
      ImagingResembles findings of thromboembolic diseases. Solid-appearing enlargement of proximal pulmonary artery branches with pulmonary nodules is highly suggestive of pulmonary artery intimal sarcoma. Heterogeneous soft tissue density, smooth vascular tapering without abrupt narrowing and cutoffs, and unilateral central pulmonary emboli aids in differentiation of pulmonary artery intimal sarcoma from thrombi.
      HistopathologyAngiocentric pleomorphic malignant spindle cells forming intraluminal tumor thrombi and/or invasion of vessel walls and their surrounding stroma
      ImmunohistochemistryDiffuse avid staining for factors VIII, CD31, CD34 confirms the endothelial origin of the tumor cells; positive staining for MDM2 and HMGA2 markers are supportive surrogates of intimal (endothelial) malignancy.

      Imaging Discussion

      We describe a case of PAIS that roentgenographically and clinically was suspected initially to be COP. On plain radiograph, COP often presents as unilateral or bilateral patchy areas of consolidation that may affect all lung zones.
      • Montesinos J.J.
      • Laguna M.A.
      Case 1: cryptogenic organizing pneumonia.
      CT scans of COP consist of GGOs, small or large lung nodules, and areas of patchy consolidation with a predominantly subpleural distribution.
      • Montesinos J.J.
      • Laguna M.A.
      Case 1: cryptogenic organizing pneumonia.
      The initial CT scan that showed exclusive right GGOs with subpleural consolidation raised the suspicion of COP. We were not sure whether the left lower lobe 1.5-cm lung nodule was related or not related to the presumptive diagnosis. Due to lack of clinical response to steroids, subsequent CT scans showed worsening GGOs and new cavitary lesions that are inconsistent with COP. The accelerated development of cavitary lesions is indicative of a necrotizing infectious process, vasculitis, or very aggressive cavitating malignancy. Because the patient continued to deteriorate clinically, we decided to sample the LLL lung nodule, which subsequently yielded the diagnosis. The patient then had CT angiogram of the chest to evaluate the pulmonary, which is usually the origin of this type of tumor. CT angiogram revealed a 10-cm mass in his mediastinum with complete obstruction of the right main pulmonary artery and partially collapsed SVC, which is a typical finding of aggressive advanced PAIS. The patient declined rapidly after the CT angiogram, and other imaging studies were difficult to obtain. He was hospitalized due to worsening shortness of breath and hypoxia, SVC syndrome, and new onset chest pain. He received one infusion of carboplatin and vinorelbine during his hospitalization. The patient further deteriorated during his hospitalization and subsequently elected for hospice and died 2 weeks later.

      Pathologic Discussion

      PAIS can mimic the clinical presentation of other pulmonary vascular diseases, especially pulmonary emboli, which can delay the prompt diagnosis of primary vascular malignancy.
      • García-Cabezas S.
      • Centeno-Haro M.
      • Espejo-Pérez S.
      • et al.
      Intimal sarcoma of the pulmonary artery with multiple lung metastases: long-term survival case.
      ,
      • Jiang S.
      • Li J.
      • Zeng Q.
      • Liang J.
      Pulmonary artery intimal sarcoma misdiagnosed as pulmonary embolism: a case report.
      ,
      • Bandyopadhyay D.
      • Panchabhai T.S.
      • Bajaj N.S.
      • Patil P.D.
      • Bunte M.C.
      Primary pulmonary artery sarcoma: a close associate of pulmonary embolism-20-year observational analysis.
      After a course of prednisone therapy for the suspected COP and worsening of the GGOs on repeat imaging, multiple wedge biopsies of the right lung were performed. Histopathologic results revealed extensive areas of acute lung injury and multifocal parenchymal infarctions. Also present were focal organizing fibrinous pleuritic and recent organizing thrombi within microscopic intraparenchymal veins and arteries. In all of the biopsies, there was no histologic evidence of malignancy or vasculitis. Organizing fibrinous pleuritis may be present in organizing pneumonia. The inexplicable arterial and venous thrombi were devoid of any histologic or cell marker evidence of malignancy. Cryptogenic pneumonia was considered clinically, but tissue findings are more consistent with organizing pneumonia. Thus, the case is not of COP. As the patient deteriorated, a core biopsy of the LLL nodule was performed that, for the first time, revealed a pleomorphic spindle cell malignancy. Extensive immunohistochemical analysis of the LLL nodule finally provided the diagnosis of a primary PAIS. The MDM2 and HMGA2 malignancy markers were notably positive (Fig 6B and C). Only in retrospect could the nondiagnostic thrombi within the right lung lesions be associated with the PAIS.

      Conclusions

      • PAIS is an extremely rare vascular malignancy and a challenging diagnosis.
      • The constellation of unilateral pulmonary cavitary lesions should raise the suspicion of ipsilateral pulmonary artery lesion.
      • Suspect malignancy in “atypical” cases with mixed and overlapping clinical picture.
      • Given the fact the patient’s left lung nodule was seen on his first chest CT scan, we can assume that his disease was metastatic at presentation.

      Acknowledgments

      Financial/nonfinancial disclosures: None declared.
      Other contributions: CHEST worked with the authors to ensure that the Journal policies on patient consent to report information were met.

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