Department of Respiratory Medicine, Kyorin University School of Medicine, Mitaka City, Tokyo, JapanJapan
Department of General Surgery, Kyorin University School of Medicine, Mitaka City, Tokyo, JapanJapan
Department of Pathology, Kyorin University School of Medicine, Mitaka City, Tokyo, JapanJapan
Department of Radiology, Kyorin University School of Medicine, Mitaka City, Tokyo, JapanJapan
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A 72-year-old man was referred to our hospital because of persistent right chest pain and an abnormal shadow on chest X-ray. Thoracic computed tomography showed a right upper pleural nodule and massive right pleural thickening with an ipsilateral pleural effusion, which partially extended to the left pleura. The pleural tumor showed an intense standardized uptake value of 28.5 on fluorodeoxyglucose positron emission tomography/computed tomography. After performing a thoracic pleural biopsy, a diagnosis of primary pleural lymphoma, diffuse large B cell type, was made. Primary tumors account for about 5-10% of pleural neoplasms, which of 2.4% accounts for primary pleural lymphoma. Although, primary pleural lymphoma is an extremely rare tumor, it should be considered in the differential diagnosis of pleural thickening in the costophrenic recess with pleural effusion even if the patient has no apparent history of pyothorax associated with Epstein-Barr virus infection.
Keywords: Primary pleural lymphoma; Diffuse large B cell lymphoma; Pleural thickening; Thoracic computed tomography
Primary pleural lymphoma is an extremely rare disorder, accounting for 2.4% of pri- 1,2 mary chest wall tumors.1,2 The clinical manifestations and characteristic pleural thickening on
thoracic computed tomography are clinical clues to the diagnosis. A case of primary pleural
lymphoma, diffuse large B cell type, with thickened pleura and ipsilateral pleural effusion as
the initial presentation, is reported.
A 72-year-old man was referred to our hospital because of a 1-month history of persis-
tent right chest pain. He had been in good health except for normal pressure hydrocephalus two
examination, he appeared well, and vital signs and physical ex-
amination were normal. Chest X-ray showed a solitary nodule measuring 15 mm in size with an
thoracic CT (Figure 1C) and Fluorodeoxyglucose (FDG) Positron Emission Tomography/Com-
puted Tomography (PET/CT) (Figure 2) showed that the right pleural mass partially extended
Figure 1. Chest X-ray shows a solitary nodule, 15 mm in size, with an extrapleural sign in the right upper lung field, together with blunting of the right costophrenic angle (A). On thoracic CT, no abnormal lesion is noted in the lung parenchyma (B), but a massive right pleural mass with pleural effusion is seen, which partially extends to the left pleura and spinal canal through the right intervertebral foramen (C).
to the left pleura and invaded to the spinal canal through the right
intervertebral foramen, which showed an intense Standardized
Uptake Value (SUV) of 28.5, suggesting malignancy. Serum
laboratory examinations were normal except for mild anemia,
mild elevation of Lactase Dehydrogenase (LDH) (230 IU/L), C-
reactive protein (1.3 mg/dL), and soluble interleukin-2 receptor
(956 U/mL). Furthermore, no elevation of serum tumor markers
such as Carcinoembryonic antigen (CEA) (1.8 ng/mL, normal
range <5.0 ng/mL), carbohydrate antigen 19-9 (5.7 U/mL, nor-
mal range <37.0 U/mL), squamous cell carcinoma antigen (1.4
ng/mL, normal range <1.5 mg/mL), and neuron-specific enolase
(8.6 ng/mL, normal range<10.0 ng/mL) were noted. Thoracen-
tesis demonstrated elevation of the total cell count (4,200 /mL;
with lymphocytes 87%, neutrophils 6%, monocytes 6%), total
proteins of 4.3 g/dL, and LDH of 200 IU/L, suggesting a chronic
exudative pleural effusion. The values of CEA (0.8 ng/mL), ad-
enosine aminhydrolase (25.1 IU/L), and hyaluronic acid (43,900
ng/mL) in the pleural fluid were normal, and the cytological as-
sessment was class II.
On thoracoscopy, protrusion of the surface of the pa-
rietal pleura with white colored central necrosis together with
dilatation of the capillary vessels at the normal site (Figure 3)
was noted. On hematoxylin and eosin staining, the diagnostic
thoracoscopic pleural biopsy specimens demonstrated abundant
large atypical cells (Figure 4) that were immunohistochemically
positive for CD20 (Figure 4, inset), CD79a, CD10, and Bcl2, but
negative for cytokeratins and calretinin.
Based on these findings, he was diagnosed with prima-
ry pleural lymphoma, diffuse large B cell lymphoma (DLBCL),
Ann Arbor stage II. Thereafter, he was treated with 6 consecu-
tive courses of R-CHOP chemotherapy (R: rituximab (375 mg/ 2 2 m2 on day 1), C: cyclophosphamide (750 mg/m2 on day 2), H:
doxorubicin hydrochloride (50 mg/m2 on day 2), O: vincristine
sulfate (1.4 mg/m2 on day 2), and P: prednisone 100 mg/body on
days 2 to 6), which resulted in complete remission, and he was
discharged uneventfully.
Primary tumors account for about 5-10% of pleural
neoplasms such as malignant mesothelioma, localized fibrous
tumor, and pleural liposarcoma, in this order.3,4 Secondary tu-
mors, which account for approximately 90% of all pleural neo-
plasms, are metastatic disease, such as lung cancer (40%), breast
cancer (20%), lymphoma (10%), ovarian carcinoma, and gastric 3,4 carcinoma.3,4 In this regard, although approximately 16% of pa-
tients with Non-Hodgkin’s Lymphoma (NHL) present with or
subsequently develop pleural involvement during the course of
disease, primary pleural lymphoma is an extremely rare disor-
der, accounting for 2.4% of primary chest wall tumors. The
most frequent type of lymphoma involving the pleura is DL-
BCL, followed by follicular lymphoma, with rates of approxi-
mately 60% and 20%, respectively, as was the present case.
In general, clinical clues to the diagnosis of primary
pulmonary lymphoma are pleural effusion, pleural thickening,
and/or chest pain, as in the present case. Filly et al. reported
that pleural effusion was seen in 7% of patients with Hodgkin’s
lymphoma (HL) and 10% of patients with NHL who were previ-
ously untreated. The mechanisms of pleural effusion in primary
pleural lymphoma can be due either to impaired lymphatic drain-
age because of mediastinal adenopathy or pleural or pulmonary
infiltration, or to thoracic duct obstruction. The pleural effusion in NHL appears to be caused by impaired lymphatic drainage,
and that of HL was due to direct pleural infiltration of tumor
cells. The precise reason is unknown, but the mode of spread is rather lymphatic in HL, and contiguous and/or hematogenous in
10,11 NHL, which may explain the higher affinity to parietal pleura in NHL. Similarly, though the reason is unknown, pleural in-
volvement can be unilateral or bilateral and is more common on
the left side.
Regarding radiological findings, primary pleural lym-
phoma can present as an enhancing mass in the costophrenic re-
cess with pleural effusion, corresponding to pleural thickening
and/or nodular pleural infiltration, which needs differentiation
or other metastatic pleural diseases,14 as in the present case.
The tumor development mechanisms of malignant
lymphoma arising in the pleura have not yet been established,15
but Hirai et al. demonstrated that all of nine Japanese patients
with primary pleural lymphoma without a history of pyothorax
had no Epstein-Barr virus (EBV) infection, as in the present case
(figure not shown).
This case showed unique clinical presentation of pri-
mary pleural lymphoma in that 1) massive right pleural thicken-
ing with an ipsilateral pleural effusion, 2) no history of pyotho-
rax associated with EBV infection. Thus, this case reminds us
of the fact that we should be aware of the possibility of primary
pleural lymphoma as an extremely rare tumor if the patient has
pleural thickening with pleural effusion, even with no history of chronic pyothorax.