Pleural involvement of diffuse large B-cell lymphoma mimicking malignant pleural mesothelioma.

Diffuse large B-cell lymphoma (DLBCL) is a common cancer in haematology. We report a case of DLBCL mimicking malignant pleural mesothelioma (MPM). A 75-year-old man with a 1-week exacerbation of dyspnoea on exertion and right pleural effusion on chest radiography was admitted to our hospital. Positron emission tomography/computed tomography revealed diffuse pleural thick lesions and massive pleural effusion, and these lesions had accumulation of fluorodeoxyglucose. Because we suspected MPM or lung cancer, we performed a biopsy with thoracoscopy to confirm the diagnosis. A biopsy of the pleural effusion with thoracoscopy revealed DLBCL. Chemotherapy was immediately selected, and the diffuse thickened pleural wall and massive pleural effusion of the right chest were significantly improved after two cycles of chemotherapy.

Introduction

Malignant pleural mesothelioma (MPM) has one of the poorest prognoses among respiratory diseases [1,2]. MPM is still a major public health problem, as it is related to environmental and occupational asbestos exposure. Given the incubation periods, the incidence of MPM in Japan is gradually increasing, and the total number of patients will peak in 2030. Because the clinical manifestations of MPM are usually non-specific, physicians often need a differential diagnosis of lung cancer, tuberculous pleurisy, or synovial sarcoma [[3], [4], [5]]. In contrast, diffuse large B-cell lymphoma (DLBCL) can be treated by chemotherapy, and its imaging findings are generally different from those of MPM. DLBCL usually invades superficial lymph nodes, such as cervical, axillary, and inguinal lymph nodes. As it is an extranodal disease, the gastrointestinal tract and lung are also targeted [6]. Here, we present a very rare case of a patient with DLBCL who was initially suspected to have MPM due to characteristic findings on positron emission tomography/computed tomography (PET-CT).

Case presentation

A 75-year-old man with a 1-week exacerbation of dyspnoea on exertion and right pleural effusion on chest radiography was admitted to our hospital. He had no history of smoking or asbestos exposure. He had a paranasal sinus operation approximately 60 years previously. Chest radiography revealed a massive loculated pleural effusion in the right thorax (Fig. 1A). PET-CT revealed diffuse thick pleural lesions, massive pleural effusion, and enlarged mediastinal, left subclavicular and abdominal lymph nodes, and these lesions had accumulation of fluorodeoxyglucose (FDG) (Fig. 1B–D). Blood examination indicated a slight elevation of lactase dehydrogenase (336 U/L) and a normal albumin level (3.5 mg/dL). Tumor markers were almost within normal levels (carcinoembryonic antigen, 2.0 ng/mL; squamous cell carcinoma-related antigen, 1.6 ng/mL; sialyl Lewis-x antigen, 31.5 IU/mL; neuron-specific enolase, 25.2 ng/mL; cytokeratin-19 fragment, <1.0 ng/mL; pro-gastrin-releasing peptide, 35.7 pg/mL; soluble interleukin-2 receptor [sIL-2R], 455 U/mL). We also conducted an interferon-gamma release assay and human immunodeficiency virus (HIV) test, which turned out to be negative.

Fig. 1

Images of positron emission tomography/computed tomography (PET-CT).

CT showed a massive loculated pleural effusion in the right thorax (A). PET-CT showed an enlarged left subclavicular lymph node with accumulation of fluorodeoxyglucose (FDG) (B, D). PET-CT also showed diffuse thick wall lesions and accumulation of FDG along the edge of the pleura and in multiple mediastinal lymph nodes (C, D).

We punctured the pleural effusion of the right chest. A haemorrhagic pleural effusion was recovered. Cytology results of the pleural effusion showed malignancy which suggesting haematological tumor (Fig. 2A–B). The results of cytology were inadequate to make a precise diagnosis. Because we suspected MPM, lung cancer or lymphoma, we performed a biopsy with thoracoscopy to confirm the diagnosis. Thoracoscopy revealed diffuse rough and irregular mucosa of the pleura with redness and swelling (Fig. 3A–B). A biopsy of the pleura with thoracoscopy revealed DLBCL (Fig. 4A–B). We confirmed that the lesions with high integration of FDG along the entire circumference of the pleura were DLBCL lesions. Magnetic resonance imaging of the head with contrast revealed no evidence of brain metastasis. After a precise diagnosis, the patient consulted a haematologist. The patient underwent chemotherapy with a combination of rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisolone (R–CHOP). The diffuse thickened pleural wall and massive pleural effusion in the right chest significantly improved after two cycles of chemotherapy.

Fig. 2

Images of pleural effusion cytology.

Cytology of pleural effusion showed large atypical cell with poor connectivity and coarse chromatin aggregation. (A, haemotoxylin & eosin staining, B, Giemsa staining).

Fig. 3

Images from thoracoscopy.

Thoracoscopy revealed diffuse rough and irregular mucosa of the pleura with redness and swelling (A, B).

Fig. 4

Histopathology of pleural biopsy specimens.

Diffuse, large, atypical, naked nuclear cells infiltrated the centre of the tissues. (A, haemotoxylin & eosin staining, × 100). Lymphoma cells expressed CD20 on their cellular membrane, which suggested B-cell lymphoma (B, CD20 staining, × 100).

Discussion

In this case, we experienced a rare type of DLBCL mimicking MPM. We highlight two important clinical messages in this case. First, even if a chest CT scan suggests typical MPM, other differential diagnoses should be kept in mind. MPM is strongly related to asbestos, and it is rare in people that have never been exposed to asbestos [7]. Therefore, when we encounter patients with typical MPM imaging but lacking a history of asbestos exposure, we should consider other diseases and should closely examine all aspects of malignant disease.

Second, it is important to be familiar with the atypical features of malignant lymphoma. Malignant lymphoma sometimes invades pulmonary regions, but diffuse intrapleural invasions are very rare [6]. Primary effusion lymphoma, which is a rare type of HIV-related malignant lymphoma, can invade pleural lesions but not the left subclavicular, mediastinal or abdominal lymph nodes [8]. In this case, the existence of multiple mediastinal and abdominal lymphadenopathies was important in determining the differential diagnosis. Furthermore, this case showed negative result of HIV test.

Although we searched the literature, we could not find a case identical to this one, but we did find some similar case reports. While malignant lymphoma typically forms nodular lesions as an extranodal disease, the formation of diffuse thick pleural lesions in patients with multiple myeloma has been previously reported [9]. There was also a report of a patient with DLBCL forming thick local lesions [10]. As with the present case, we should keep in mind the pleural disease of malignant lymphoma. In the clinical setting, there were some difficulties in differentiating malignant lymphoma. sIL-2R is usually helpful when malignant lymphoma is suspected. However, this case lacked elevated sIL-2R levels. Furthermore, this patient did not have fever, body weight loss, or night sweats, known as B symptoms. Malignant lymphoma with atypical features may not present with typical clinical findings. Lacking a history of asbestos exposure suggested an atypical aspect of MPM. Obtaining an accurate medical history is also important for a precise diagnosis.

Conclusions

We encountered a rare case of pleural involvement of DLBCL mimicking MPM. Because both MPM and malignant lymphoma have poor prognoses without appropriate treatment, early diagnosis is important to improve survival. Clinicians should keep in mind the importance of differential diagnoses of MPM when they experience typical images compatible with MPM but lacking typical history or laboratory features.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.