The clinical characteristics, diagnosis and treatment of lymphoma of lung origin were investigated to improve the diagnosis rate. METHODS: We retrospectively summarized three cases of lymphoma of primary origin in the lung admitted to our hospital from January 1, 2002 to June 1, 2008, and analyzed their clinical manifestations, imaging features, bronchoscopic manifestations, diagnosis and treatment methods in the light of literature. Results: Lymphoma originating from the lung is a rare lymphoma with no specific clinical manifestations, and it is difficult to confirm the diagnosis. The main symptoms of lymphoma in the lung are cough, fever, chest tightness and shortness of breath. The imaging may show a single or multiple nodules or masses, solid shadow, etc. There is no enlargement of hilar and mediastinal lymph nodes in the early stage. Bronchoscopy may reveal bronchial stenosis, chronic inflammation or general normality.
The final diagnosis is made by bronchoscopy, percutaneous lung puncture, open-heart surgery and thoracoscopy, combined with pathological and immunohistochemical examination. The main treatment options are surgery and chemotherapy. The prognosis depends on the malignancy of the lymphoma, the patient’s age, general condition, stage and LDH. conclusion: the clinical manifestations of lymphoma originating from the lung are atypical and easy to be misdiagnosed.
Non-Hodgkin’s lymphoma; lung; diagnosis; treatment; prognosis Malignant lymphoma mostly occurs in the lymph nodes first. Those originating in extra-nodal organs are less common and account for 14% to 25% of malignant lymphomas [1,2], with non-Hodgkin’s lymphomas significantly more common than Hodgkin’s disease. Primary pulmonary lymphoma is a malignant lymphoma that originates from the lymphoid tissue within the lung and is a rather rare extranodal lymphoma, with an incidence of less than 1%, accounting for approximately 3.6% of extranodal lymphomas [3], and therefore is often misdiagnosed clinically. This data set reports one case admitted by the authors on December 7, 2006, plus two other cases of pathologically confirmed primary pulmonary non-Hodgkin’s lymphoma registered in our hospital from 2002 to 2008, and analyzes its clinical manifestations, imaging features, bronchoscopic manifestations, diagnosis and treatment methods in the context of literature.
Clinical data
Case 1, female, 62 years old. She was admitted to the hospital on May 4, 2003, with cough and wheezing for six months. There were no obvious positive signs of tumor on admission examination. Post-admission chest radiography revealed a large dense shadow in the left middle and lower lung fields, obscured by the diaphragm and rib-diaphragm angle with superior irregularity, patchy right lower lung field with small stripes of blurred shadow, and no significant displacement of mediastinum or cardiac shadow. The tomography showed that the left and right main bronchi were patent, and there were no obvious enlarged lymph nodes in the mediastinum and hilum. Ultrasound examination of the abdomen showed no occupying lesions in the liver, gallbladder, spleen and both kidneys, and no masses in the abdominal aorta.
Pathological diagnosis of mucosa-associated malignant lymphoma was made by bronchofibroscopic biopsy, and immunohistochemistry showed CD20(+) and CD45(-). After diagnosis, chemotherapy was given on CHOP regimen. Pre-chemotherapy laboratory tests showed normal LDH and an ECOG score of 1. After 4 cycles of CHOP regimen chemotherapy, the lung mass was significantly reduced. The patient discontinued chemotherapy because of the combination of herniated disc and the worsening of her corresponding symptoms. He died in January 2005 due to tumor progression.
Case 2, female, 59 years old. Recurrent cough, fever and shortness of breath for 3+ months. On August 5, 2006, a CT scan of the chest showed a soft tissue density shadow in the right hilar and right mediastinum, narrowing of the bronchi in the upper lobe of the right lung; no significant abnormality in the left lung; a large soft tissue density shadow in the interstitial space in front of the mediastinal vessels, a shadow of enlarged lymph nodes in the mediastinum, a shadow of pericardial effusion; and a shadow of pleural fluid in the right.
On August 9, 2006, a percutaneous lung mass biopsy was performed and the lung lymphoid tissue was found to be proliferative; on September 16, 2006, the right middle and lower lobes of the lung were found to be in a state of dysplasia, and the mass in the hilar region was widely adherent to the mediastinum and could not be removed. The mouth was unclear, and two pieces of tissue were taken for pathological examination. Pathology report: one piece showed granulomatous inflammation; one piece saw diffuse lymphocytic hyperplasia, which was diagnosed as pulmonary non-Hodgkin’s lymphoma stage IV according to its immunohistochemistry, with LCA(+), CD79(+), CD20(+), CD43(+), CD3(+).
The patient had no superficial lymph nodes, abdominal ultrasound showed no occupying lesions in the liver, bile, spleen, or both kidneys, no masses in the para-aortic abdomen, LDH 295.0 U/L (normal reference value is 114.0-240.0 U/L), and ECOG score of 2. CHOP regimen chemotherapy from October 17, 2006 to December 8, 2006 for 3 cycle, changed to 2 cycles of chemotherapy with EP regimen due to disease progression, still ineffective, died on March 5, 2007.
Case 3, male, 62 years old. The patient was admitted to our department on December 7, 2006 due to chest tightness and shortness of breath for 2+ months and intermittent fever for 4 days (T 38.7-39.4°C). The patient’s MR in 1999 suggested left pulmonary atelectasis. right upper lung mass, left pleural effusion, and solid left lingual lobe were found on CT examination on September 16, 2006. The pleural fluid was bloody and no cancer cells were found in the cytological examination of pleural fluid several times.
On Dec. 14, 2006, electronic bronchoscopy showed no obvious masses in the bronchial orifices of both lungs, and on Dec. 20, 2006, CT scan + enhancement scan of the chest again showed a soft tissue density shadow of 5.4×4.4 cm in the right upper lung mediastinum, with uneven internal density, poorly defined margins, and burr shadows of varying lengths, and irregular solid areas in the middle lobe of the right lung and left lingual lobe. CT diagnosis: multiple foci in both lungs, consider the possibility of infectious lesions, and do not exclude pulmonary artery embolism.
On December 26, 2006, a CT-guided percutaneous right upper lung mass was biopsied and pathologically diagnosed as diffuse large B-cell lymphoma with immunohistochemistry of LCA(+), CD20(+), CD56(-), CD3(+). The patient’s LDH was 373.0 U/L (normal reference value is 114.0-240.0 U/L) and ECOG score was 1. 2 cycles of chemotherapy with CHOP regimen from December 30, 2006 to January 29, 2007, and a repeat CT showed significant reduction in both lung lesions and LDH decreased to normal. The sixth cycle of chemotherapy was completed on May 9, 2007. No special treatment has been administered since then. At press time, the patient remains free of disease progression and is alive and healthy.
DISCUSSION
The definition of primary extranodal NHL has been controversial. Briefly, the following general definition can be used, namely: after conventional staging, the tumor is clinically predominantly extra-nodal with no or only a small amount of intra-nodal involvement (≤25% of the tumor load).
The current clinical diagnosis of primary pulmonary lymphoma is based on the diagnostic criteria of Cordier [4] and others: (1) clear pathologic histologic diagnosis; (2) lesions confined to the lung with or without hilar and mediastinal lymph node involvement; and (3) no lymphoma of extra-pulmonary and bronchial tissues or organs within 3 months after diagnosis.
The current pathological staging of primary pulmonary lymphoma is based on the Ferraro et al[5] criteria. Stage IE: involvement of the lung or bronchi only (unilateral or bilateral); Stage II1E: involvement of the lung and hilar lymph nodes; Stage II2E: involvement of the lung and mediastinal lymph nodes; Stage II2E W: involvement of the lung and adjacent chest wall or diaphragm; Stage III: involvement of the lung and lymph nodes at the thorax; Stage IV: extensive involvement of the lung and other tissues or organs.
Most malignant lymphomas occur first in the lymph nodes. Those originating from extra-nodal organs are less common and account for 14%-25% of malignant lymphomas[1,2] . Primary pulmonary lymphomas account for about 3.6% of extra-lymph node lymphomas, 0.4% of all lymphomas, and only 0.5% of primary malignant tumors of the lung[6] From January 1, 2002 to June 1, 2008, a total of 1058 cases of malignant lymphomas were admitted to our hospital, of which 240 cases (23%) originated from outside the nodes. The incidence of malignant lymphoma originating from the lung was less than 0.3% of the total malignant lymphoma and 1.6% of the extra-nodal malignant lymphoma, which were lower than those reported in the domestic and international literature[3,6] .
In the past 20 years, only 180 cases of lymphoma originating from the lung have been reported in China, excluding 86 cases with repeated reports and incomplete data[7] , plus 3 cases reported by the authors, a total of 97 cases have been diagnosed. Data showed that primary pulmonary lymphoma in China was mainly seen in patients >18 years old, with a mean age of 52.7 years and a male-to-female ratio of 1.8:1. 5.3% of these patients had a long-term smoking history, suggesting that the disease may not be related to smoking.
The clinical manifestations of primary pulmonary lymphoma were non-specific. The three cases in this group mainly presented with cough, fever, chest tightness and shortness of breath. Imaging examination performance. In case 1, the diagnosis was confirmed by electronic bronchoscopic biopsy; in case 2, lung mass puncture and open chest exploration were performed successively without pathological diagnosis, and finally the diagnosis was confirmed by electronic bronchoscopic biopsy; in case 3, no mass cells were seen in multiple pleural fluid cytology examinations, and then the diagnosis was confirmed by CT-guided percutaneous lung mass puncture biopsy. The time from discovery of the lesion to diagnosis was 15 days, 70 days, and 100 days, respectively.
The treatment options available for primary pulmonary non-Hodgkin’s lymphoma include surgery, chemotherapy, or combined postoperative chemotherapy. Malignant lymphomas are very sensitive to chemotherapy, and lymphomas of primary origin in the lung are no exception. Traditional chemotherapy options commonly used are CHOP or COP regimens, and for patients with CD20(+), the application of Rituximab has become a new pathway for the treatment of NHL. Radiotherapy is less commonly used both at home and abroad, mainly considering the occurrence of radiation lung injury after radiotherapy.
Ferraro et al[5] reported 1-year survival rate of 89.0% and 5-year survival rate of 67.0% in 48 cases of primary pulmonary non-Hodgkin’s lymphoma. The overall survival rate at 2.5 years was 81.6% as reported by Shangguan Zongzheng et al. in China. Three patients in our group were given chemotherapy with CHOP regimen immediately after diagnosis.
Case 1 of this group survived for 1 year and 8 months, case 2 survived for 7 months, and case 3 admitted by the authors is now alive and well, with a survival time of >1.5 years.
Primary pulmonary lymphoma is a rare disease with non-specific clinical presentation, and its diagnosis depends on pathological histological examination and immunohistochemistry. Bronchofiberscopic biopsy, CT-guided percutaneous lung mass aspiration biopsy and VATS techniques are recognized as highly safe and less invasive examination methods that can improve early diagnosis and reduce misdiagnosis.