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Postgraduate Education Corner: Chest Imaging and Pathology for Clinicians |

A 79-Year-Old Woman With Bilateral Cavitating Lung NodulesCavitating Lung Nodules in an Elderly Woman FREE TO VIEW

Karan Madan, MD, DM; Suvendu Purkait, MD; Sudheer Arava, MD; Ashu S. Bhalla, MD; Rakesh Kumar, MD; Randeep Guleria, MD, DM
Author and Funding Information

From the Department of Pulmonary Medicine and Sleep Disorders (Drs Madan and Guleria), Department of Pathology (Drs Purkait and Arava), Department of Radiodiagnosis (Dr Bhalla), and Department of Nuclear Medicine (Dr Kumar), All India Institute of Medical Sciences, New Delhi, India.

Correspondence to: Karan Madan, MD, DM, FCCP, Department of Pulmonary Medicine and Sleep Disorders, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India 110029; e-mail: drkaranmadan@gmail.com


Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2014;145(6):1419-1424. doi:10.1378/chest.13-2081
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A 79-year-old woman presented with history of cough, shortness of breath, and fever of 3 months’ duration. Cough was associated with scant amount of mucoid expectoration, and fever was low grade in intensity. Shortness of breath was insidious in onset and had gradually progressed over 3 months. The patient, however, was able to carry out normal activities without any significant symptoms. There was no history of hemoptysis, chest pain, wheezing, joint pain, weight loss, skin rash, Raynaud phenomenon, epistaxis, nasal discharge, hematuria, or photosensitivity. There were no other urinary, abdominal, or neurologic complaints. Past and personal history was unremarkable. The patient was a homemaker and a lifetime nonsmoker. There were no other addictions, occupational exposure, or history of travel. The patient had been treated with broad-spectrum antibiotics and antitussives on an outpatient basis with no symptomatic improvement.

On physical examination, the patient’s pulse rate was 90 beats/min, BP was 110/78 mm Hg, and respiratory rate was 16 breaths/min without any use of accessory muscles of respiration. There was no peripheral lymph node enlargement. Examination of the respiratory system and abdomen revealed no abnormal findings. The rest of the systemic examination was normal. Routine hematologic investigations showed an elevated erythrocyte sedimentation rate (60 mm/h). Total and differential leukocyte counts, platelets, and hemoglobin levels were within normal limits. Results of liver functions and kidney function tests, including a urine microscopic examination, were normal. Blood and urine cultures were sent and were sterile. Three sputum smear examinations for acid-fast bacilli and sputum cultures (mycobacterial and fungal) were negative, and a tuberculin test was nonreactive.

Serial chest radiographs demonstrated progressively increasing bilateral variable-sized pulmonary nodules, some of which demonstrated central cavitation (Fig 1A). CT imaging examination of the thorax (Figs 1B, 1C) confirmed the presence of multiple variable-sized, randomly distributed pulmonary nodules predominantly in the lower lobes and many of them demonstrated central cavitation. Most nodules were thick-walled with irregular inner margins; lung parenchyma surrounding these nodules was normal. There was no surrounding halo around the nodules. There was no mediastinal lymph node enlargement or pleural or pericardial effusion.

Figure Jump LinkFigure 1. A, Chest radiograph demonstrating multiple bilateral variable-sized pulmonary nodules, some of which show central cavitation (arrows). B-C, CT scan of the thorax showing multiple variable-sized, randomly distributed pulmonary nodules predominantly in the lower lobes. Many show central cavitation. There is no halo surrounding the nodules.Grahic Jump Location

Antinuclear factor, rheumatoid factor, and antineutrophil cytoplasmic antibody titers were not elevated. Ultrasonographic examination of the abdomen and a transvaginal ultrasound were normal. Flexible bronchoscopy examination demonstrated normal bronchial anatomy with no endobronchial mucosal abnormality. Cytologic examination results of the BAL fluid were negative. Bronchoscopic lung and endobronchial biopsy specimens demonstrated no significant abnormality.

Whole-body fluorodeoxyglucose (FDG) PET-CT scan examination was performed. Scan findings demonstrated multiple cavitating nodules in both lungs with increased FDG uptake (Fig 2). Multiple small FDG avid lymph nodes were observed in the cervical, axillary, and inguinal locations, and focal uptake was noted around the area of duodeno-jejunal flexure. CT scan-guided fine-needle aspiration cytology examination from one of the lung nodules showed occasional atypical cells that could not be exactly characterized. As the patient was unwilling to undergo a surgical lung biopsy, CT scan-guided biopsy of the pulmonary nodule was performed. Histopathologic examination of the biopsy specimen (Fig 3) demonstrated diffuse infiltration of pulmonary parenchyma by monomorphic large-sized atypical mononuclear cells with marked destruction of the pulmonary parenchyma. The neoplastic cells had vesicular nuclei, coarse chromatin, and scant cytoplasm. There was no evidence of angiocentricity, angiodestruction, or necrosis. The neoplastic lymphoid cells were immunopositive for CD20 and multiple myeloma oncogene while negative for CD3, CD 10, Bcl-6, and Epstein-Barr virus latent membrane protein.

Figure Jump LinkFigure 2. Fluorodeoxyglucose (FDG)-PET/CT imaging findings demonstrating multiple FDG avid cavitating pulmonary nodules. The corresponding CT scan images are also shown.Grahic Jump Location
Figure Jump LinkFigure 3. Histopathologic examination findings from the CT scan-guided lung biopsy. A, Diffuse infiltration of lung parenchyma by medium- to large-sized atypical lymphoid cells with destruction of alveolar architecture (hematoxylin & eosin, magnification × 400). B, Membranous/cytoplasmic immunopositivity for CD20 (magnification × 400). C, Immunonegativity for CD3 (magnification × 400). D, Nuclear immunopositivity for MUM1 (× 400).Grahic Jump Location
What is the diagnosis?
Diagnosis: Primary pulmonary diffuse large B-cell lymphoma
Clinical Discussion

Primary pulmonary lymphoma (PPL) is defined as an extranodal clonal lymphoid neoplasm involving one or both lungs (parenchyma and/or bronchi) in a patient with no detectable extrapulmonary involvement at diagnosis or during the subsequent 3 months.1 It is a rare clinical entity which accounts for 0.4% of all malignant lymphomas and < 1% of all pulmonary tumors.2,3 The commonest histologic subtype of PPL (70%-90% of all cases) is the mucosa-associated lymphoid tissue type (MALT) lymphoma (low-grade lymphoma).3,4 The primary pulmonary diffuse large B-cell lymphoma (PBL) (high-grade lymphoma), as was diagnosed in the patient, is uncommon and is seen in up to 10% patients with PPL.5 Most patients with PPL usually present in the sixth decade of life, and there is a slight male predominance.6 Clinically, most patients are asymptomatic. Symptomatic disease presentations (more common in high-grade lymphomas) may include dyspnea, cough, fever, loss of weight, and/or appetite and other systemic symptoms. The treatment strategy and risk stratification for primary pulmonary non-Hodgkin’s lymphoma is not clearly established. Treatment strategies include a wait-and-watch approach with mild forms of disease with minimal symptoms, surgery, chemotherapy, and chemotherapy followed by radiotherapy. In the PBL subtype, anthracycline-based chemotherapy with anti-CD20 monoclonal antibody has been proposed as the optimal therapeutic strategy.5 Isolated pulmonary involvement is classified as stage I, according to the Ann Arbor lymphoma staging system.7 MALT lymphoma may transform into PBL.5 Accurate diagnosis of PPL is often difficult and delayed owing to nonspecific clinical and radiologic features. Prognosis for high-grade or PBL is worse than low-grade lymphomas and they are more likely to present with respiratory and systemic symptoms as in the index patient. PBL is more common in patients who are immune-suppressed or have underlying autoimmune disorders, and occurrence in the absence of these risk factors is rare.8 None of these risk factors was present in the index patient. The patient presented with nonspecific respiratory symptoms and bilateral cavitating lung nodules leading us to clinically consider the possibility of metastatic malignancy or pulmonary vasculitis (granulomatosis with polyangitis) as the first differential diagnosis.

Radiologic Discussion

The causes of multiple cavitating lung nodules can be broadly divided into infectious and noninfectious etiologies. Noninfective conditions include granulomatosis with polyangitis, pulmonary metastases, lung malignancies (bronchogenic carcinoma, Kaposi sarcoma in individuals infected with HIV), lymphomatoid granulomatosis, sarcoidosis, rheumatoid arthritis, and pulmonary amyloidosis. Rarer causes of cavitating pulmonary lesions include pulmonary infarction following pulmonary embolism, bronchiolitis obliterans with organizing pneumonia, and pulmonary Langerhans cell histiocytosis. Infective causes include necrotizing pneumonias with/without lung abscess, septic pulmonary embolism, actinomycosis, nocardiosis, melioidosis, Rhodococcus equi, Mycobacterium tuberculosis, nontuberculous mycobacteria and fungal infections, and parasitic lung diseases (echinococcus and paragonimiasis).9 The presence of a pulmonary cavitary lesion allows the clinician to perform a more focused evaluation as some clinical entities are more commonly associated with cavitating lung nodular lesions. In some settings, like lung cancer, the presence of cavitation in the pulmonary lesion has been shown to have possible negative association with overall survival.10 The usual radiographic features of common etiologies for cavitating pulmonary nodules are shown in Table 1.

Table Graphic Jump Location
Table 1 —Common Differential Diagnoses of Cavitating Lung Nodules With Their Characteristic Features

PPL presenting as multiple cavitating pulmonary nodules is rare but has been reported previously. Cavitation in the setting of PPL has been reported more frequently in the setting of HIV infection.11 It has been proposed that pulmonary involvement by lymphoma should be considered in the differential diagnosis of multiple cavitating pulmonary nodules.12 PBL has also been rarely reported to present as a pulmonary mass with cavitation.8

FDG-PET CT scanning is a useful and accurate noninvasive imaging modality in the evaluation of solitary/multiple lung nodules but there are limitations due to the possibility of false-positive and false-negative results. In patients with malignant nodules, it provides additional information regarding disease stage.13

Pathologic Discussion

According to the World Health Organization classification system, PPL can be divided into the B-cell primary pulmonary non-Hodgkin’s lymphoma (subdivided into low-grade type, high-grade type, primary pulmonary plasmacytoma, and intravascular pulmonary lymphomas) and lymphomatoid granulomatosis.14 Low-grade B-cell type is the most common histopathologic subtype, and 90% of those are composed of MALT or bronchus-associated lymphoid tissue. It is proposed that the low incidence of high-grade type is likely an underestimate as they can spread rapidly to extrathoracic locations. In many cases, high-grade PPL can coexist with MALT-type low-grade lymphoma.8

The diagnosis of PPL is often established with relatively smaller endobronchial, transbronchial, or transthoracic biopsy specimens (CT scan-guided transthoracic lung biopsy in the index patient). On microscopic examination in patients with large B-cell-type lymphoma, the tumor characteristically shows sheet-like infiltration of large atypical lymphoid cells, with centroblastic and/or immunoblastic morphology and destruction of pulmonary parenchyma. Immunohistochemically, the tumor cells express pan-B-cell antigens (CD19, CD20, and CD79a), along with either germinal (Bcl-6, CD10) or non-germinal center B-cell markers (multiple myeloma oncogene). The present case showed histomorphologic and immunophenotypic features of PBL, non-germinal center type. However, based on clinical and histologic features, lymphomatoid granulomatosis is one close differential diagnosis which was ruled out on the basis of lack of angiocentricity/angiodestructive architecture, polymorphous background cell population, and Epstein-Barr virus-latent membrane protein immunopositivity.

Differential diagnosis of multiple cavitating lung nodules is broad, including a variety of infectious and noninfectious etiologies, and it is imperative that a definitive diagnosis is established by performing appropriate and relevant radiologic and pathologic/microbiological investigations. After confirmation of the diagnosis, the patient was referred to the oncology services for initiation of chemotherapy. However, the patient opted for a wait-and-watch approach and was not willing to undergo chemotherapy. On last telephonic contact (5 months postdiagnosis), the patient had experienced no clinical deterioration. The present case highlights the fact that PPL can rarely present as multiple cavitating pulmonary nodules in immunocompetent individuals and a histopathologic confirmation of diagnosis is necessary for ensuring appropriate management.

Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Other contributions:CHEST worked with the authors to ensure that the Journal policies on patient consent to report information were met.

Cadranel J, Wislez M, Antoine M. Primary pulmonary lymphoma. Eur Respir J. 2002;20(3):750-762.
 
Wannesson L, Cavalli F, Zucca E. Primary pulmonary lymphoma: current status. Clin Lymphoma Myeloma. 2005;6(3):220-227.
 
Ferraro P, Trastek VF, Adlakha H, Deschamps C, Allen MS, Pairolero PC. Primary non-Hodgkin’s lymphoma of the lung. Ann Thorac Surg. 2000;69(4):993-997.
 
Habermann TM, Ryu JH, Inwards DJ, Kurtin PJ. Primary pulmonary lymphoma. Semin Oncol. 1999;26(3):307-315.
 
Wróbel T, Dzietczenia J, Prochorec-Sobieszek M, Mazur G, Piwkowski P. Primary pulmonary diffuse large B-cell lymphoma. Am J Hematol. 2012;87(1):107-108.
 
Cordier JF, Chailleux E, Lauque D, et al. Primary pulmonary lymphomas. A clinical study of 70 cases in nonimmunocompromised patients. Chest. 1993;103(1):201-208.
 
Carbone PP, Kaplan HS, Musshoff K, Smithers DW, Tubiana M. Report of the Committee on Hodgkin’s Disease Staging Classification. Cancer Res. 1971;31(11):1860-1861.
 
Martínez Rivera C, Bonnin Vilaplana M, Simón Adiego C, Palacín Forgué A, Puig Zuza J, Sampablo Lauro I. Primary pulmonary lymphoma presenting as a pulmonary mass with cavitation [in Spanish]. Arch Bronconeumol. 2004;40(2):94-96.
 
Gadkowski LB, Stout JE. Cavitary pulmonary disease. Clin Microbiol Rev. 2008;21(2):305-333.
 
Singh N, Mootha VK, Madan K, Aggarwal AN, Behera D. Tumor cavitation among lung cancer patients receiving first-line chemotherapy at a tertiary care centre in India: association with histology and overall survival. Med Oncol. 2013;30(3):602.
 
Ray P, Antoine M, Mary-Krause M, et al. AIDS-related primary pulmonary lymphoma. Am J Respir Crit Care Med. 1998;158(4):1221-1229.
 
Van Schoor J, Joos G, Pauwels R. Non-Hodgkin’s lymphoma presenting as multiple cavitating pulmonary nodules. Eur Respir J. 1993;6(8):1229-1231.
 
Gould MK, Donington J, Lynch WR, et al. Evaluation of individuals with pulmonary nodules: when is it lung cancer? Diagnosis and Management of Lung Cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2013;143(5_suppl):e93S-e120S.
 
Travis WD. Pathology & Genetics: Tumours of the Lung, Pleura, Thymus, and Heart. Lyon, France: IARC Press; 2004.
 

Figures

Figure Jump LinkFigure 1. A, Chest radiograph demonstrating multiple bilateral variable-sized pulmonary nodules, some of which show central cavitation (arrows). B-C, CT scan of the thorax showing multiple variable-sized, randomly distributed pulmonary nodules predominantly in the lower lobes. Many show central cavitation. There is no halo surrounding the nodules.Grahic Jump Location
Figure Jump LinkFigure 2. Fluorodeoxyglucose (FDG)-PET/CT imaging findings demonstrating multiple FDG avid cavitating pulmonary nodules. The corresponding CT scan images are also shown.Grahic Jump Location
Figure Jump LinkFigure 3. Histopathologic examination findings from the CT scan-guided lung biopsy. A, Diffuse infiltration of lung parenchyma by medium- to large-sized atypical lymphoid cells with destruction of alveolar architecture (hematoxylin & eosin, magnification × 400). B, Membranous/cytoplasmic immunopositivity for CD20 (magnification × 400). C, Immunonegativity for CD3 (magnification × 400). D, Nuclear immunopositivity for MUM1 (× 400).Grahic Jump Location

Tables

Table Graphic Jump Location
Table 1 —Common Differential Diagnoses of Cavitating Lung Nodules With Their Characteristic Features

References

Cadranel J, Wislez M, Antoine M. Primary pulmonary lymphoma. Eur Respir J. 2002;20(3):750-762.
 
Wannesson L, Cavalli F, Zucca E. Primary pulmonary lymphoma: current status. Clin Lymphoma Myeloma. 2005;6(3):220-227.
 
Ferraro P, Trastek VF, Adlakha H, Deschamps C, Allen MS, Pairolero PC. Primary non-Hodgkin’s lymphoma of the lung. Ann Thorac Surg. 2000;69(4):993-997.
 
Habermann TM, Ryu JH, Inwards DJ, Kurtin PJ. Primary pulmonary lymphoma. Semin Oncol. 1999;26(3):307-315.
 
Wróbel T, Dzietczenia J, Prochorec-Sobieszek M, Mazur G, Piwkowski P. Primary pulmonary diffuse large B-cell lymphoma. Am J Hematol. 2012;87(1):107-108.
 
Cordier JF, Chailleux E, Lauque D, et al. Primary pulmonary lymphomas. A clinical study of 70 cases in nonimmunocompromised patients. Chest. 1993;103(1):201-208.
 
Carbone PP, Kaplan HS, Musshoff K, Smithers DW, Tubiana M. Report of the Committee on Hodgkin’s Disease Staging Classification. Cancer Res. 1971;31(11):1860-1861.
 
Martínez Rivera C, Bonnin Vilaplana M, Simón Adiego C, Palacín Forgué A, Puig Zuza J, Sampablo Lauro I. Primary pulmonary lymphoma presenting as a pulmonary mass with cavitation [in Spanish]. Arch Bronconeumol. 2004;40(2):94-96.
 
Gadkowski LB, Stout JE. Cavitary pulmonary disease. Clin Microbiol Rev. 2008;21(2):305-333.
 
Singh N, Mootha VK, Madan K, Aggarwal AN, Behera D. Tumor cavitation among lung cancer patients receiving first-line chemotherapy at a tertiary care centre in India: association with histology and overall survival. Med Oncol. 2013;30(3):602.
 
Ray P, Antoine M, Mary-Krause M, et al. AIDS-related primary pulmonary lymphoma. Am J Respir Crit Care Med. 1998;158(4):1221-1229.
 
Van Schoor J, Joos G, Pauwels R. Non-Hodgkin’s lymphoma presenting as multiple cavitating pulmonary nodules. Eur Respir J. 1993;6(8):1229-1231.
 
Gould MK, Donington J, Lynch WR, et al. Evaluation of individuals with pulmonary nodules: when is it lung cancer? Diagnosis and Management of Lung Cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2013;143(5_suppl):e93S-e120S.
 
Travis WD. Pathology & Genetics: Tumours of the Lung, Pleura, Thymus, and Heart. Lyon, France: IARC Press; 2004.
 
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