Diversity of Radiological Imaging and Clinical Course in Pulmonary MALT Lymphoma: A Case Report by Gülfidan Aras in Journal of Clinical Case Reports Medical Images and Health Sciences

 Diversity of Radiological Imaging and Clinical Course in Pulmonary MALT Lymphoma: A Case Report  by Gülfidan Aras in Journal of Clinical Case Reports Medical Images and Health Sciences

Abstract

 A 59-year-old male patient was admitted to the emergency department with a three-month history of worsening dyspnea, fatigue, and cough. His vital signs were recorded as follows: blood pressure 138/88 mmHg, heart rate 98 beats/min, respiratory rate 25 breaths/min, temperature 37.8°C, and oxygen saturation 91%. During the lung auscultation, breath sounds were absent in the lower left lung, while crepitant rales were audible in the upper zone and the right lung. CT scan of the chest showed 1 cm lymph nodes, pleural effusion, fibrotic changes, varicose-cystic bronchiectasis, as well as consolidations and atelectasis with air bronchograms in both lungs. Furthermore, thoracic ultrasonography revealed a large effusion in the left hemithorax, measuring 11 cm. He was hospitalized after the placement of a pleural catheter. Radiological diversity and the clinical course of the patient posed challenges for establishing a differential diagnosis. TL; DR: In this paper; we aimed to present a case of MALT lymphoma that manifested in the lung and caused diagnostic confusion with radiological and clinical symptoms. 

Introduction 

MALT (Mucosa-Associated Lymphoid Tissue) is the lymphoid tissue that plays a role in mucosal defense. It includes functional memory B lymphocytes, which are essential for the immune response. They are not physiologically present in the lungs, but they become active there in response to infections and chronic antigenic stimulation. Marginal zone B-cell non-Hodgkin lymphoma (MALT Lymphoma) accounts for 8% of adult lymphomas. Although it is most commonly seen in the stomach, it can also be seen in the salivary glands, thyroid and lungs (1). It is the most common type of lymphoma in the lung. It presents common radiological, pathological, and clinical findings with infection and other granulomatous diseases, making differential diagnosis quite difficult for the clinician. In this paper, we aimed to present our case, which we had difficulty in diagnosing in the clinic. 

Case Presentation

A 59-year-old male patient was admitted to the emergency department with worsening dyspnea, fatigue, and cough over the past three months. The chest X-ray of the patient showed a consolidation extending from the center to the periphery in the left upper zone near the aortic arch, an increased density indicative of pleural effusion with sinus obliteration on the left, and a consolidation extending from the hilum to the lower zone near the heart edgeon the right

During the lung auscultation, breath sounds were absent in the lower left lung, while crepitant rales were detected in the upper zone and on the right side. Blood pressure was 138/88 mmHg, pulse was 98 beats /min, respiratory rate was 34 breaths/min, and oxygen saturation was 91%. At the time of admission, the patient's biochemical analysis results were as follows: Glucose 77 mg/dL (normal range: 70-115), urea 31 mg/dL (normal range: 17-43), creatinine 0.77 mg/dL, protein 65.8 g/L (normal range: 66- 83), albumin 39.3 g/dL (normal range: 35-53), LDH 423 U/L (normal range: <247), CRP 21.6 mg/L, png/mL, and pro-BNP 8 pg/mL. The hemogram evaluation results were as follows: Leukocyte count 8.27 x 10³/µL, Erythrocyte count 5.16 x 10⁶/uL, Hemoglobin 15.6 g/ dL, Hematocrit (Hct) 48.3%, Platelet count 240,000/uL, Lymphocyte count 2.05 x 10³/uL, Eosinophils 3.4%, and Neutrophil/Lymphocyte ratio 2.47 x 10e3/uL. The patient’s chest CT scan showed 1 cm lymph nodes in the mediastinum, fibrotic changes extending to the pleura, varicose-cystic bronchiectasis, and consolidations and atelectasis with air bronchograms in both lungs. There was also a massive fluid of 11 cm in the left hemithorax. (Figure 2). A thoracentesis was conducted on the patient’s left side following the detection of 13 cm of pleural fluid on thoracic ultrasonography. Lymphocytes, polymorphonuclear leukocytes, and mesothelial cells were observed in the cytological examination of the pleural fluid, but no atypical cells were detected. There was 98%

lymphocyte dominance in the cell count. In the biochemical analysis, the pH was 7.440, lactate dehydrogenase (LDH) was 206 U/L, total protein was 39.40 g/dL, albumin was 25 g/dL, glucose was 60 mg/dL, and adenosine deaminase (ADA) was 34.4 U/L. Gram staining of the fluid, bacterial, fungal, and acid-fast bacilli growth were all negative. The patient's fluid was drained by aspiration. An intrapleural catheter was placed due to the high amount of fluid and increased dyspnea. The patient was admitted to the ward and initiated on oxygen therapy, bronchodilators, and antibiotics. The pleural fluid sent for cytological analysis two more times during the patient's hospitalization was found to be serohemorrhagic. Upon reevaluating his microbiological results, no growth was observed. Although many lymphoid cells were seen in the cytopathological examination of the patient's second pleural fluid, no atypical features were monitored. The patient's condition stabilized during clinical follow-up, and the pleural catheter was removed. However, after a while, the patient's dyspnea complaint recurred and the catheter was placed again because of the increase in fluid on the radiograph (Figure 3). There was no change in the infection markers of the patient, who also had fever from time to time, and CRP ranged between 20 and 16 mg/dL during follow-up. There was no growth in his small amount of sputum and blood cultures taken during the fever. The patient underwent fiberoptic bronchoscopy and no endobronchial lesions were detected. Wang fine needle aspiration and bronchial lavage were applied to mediastinal lymphadenomegaly Wang IA revealed lymphoid cells, but a definitive diagnosis could not be obtained. No findings were found in the lavage other than bronchial epithelial cells and polymorphonuclear leukocytes. 

No FDG uptake was detected in the pleural fluid during the patient's whole-body positron emission tomography (PET-CT) scan, though minimal FDG uptake was observed in certain pleural areas. Consolidated/ground glass foci with the focal lepidic appearance in places were detected with left lung lingular, lower lobe central SUVmax 9.14, and right lung lower lobe SUVmax 6.55 and were evaluated to be in favor of malignant processes. Abdominal ultrasonography was unremarkable. No extrapulmonary findings were monitored in PET-CT scan either. When Wang IA did not yield any results, endoscopic ultrasonographic bronchoscopy (EBUS) was performed. The pathological interpretation was in favor of granulomatous inflammation, as mature transformed lymphocytes, polymorphonuclear leukocytes, epithelioid histiocytes, and loose granuloma-like structures formed by epithelioid histiocyte clusters and multinucleated giant cells were observed in the materials obtained. Alveolar sarcoidosis was taken into account, but the serum angiotensin converting enzyme level was also found to be normal at 39.1 U/L (8- 52.0). The patient was discharged due to the clinical stability of the patient with CRP 3.2 and procalcitonin <0.01 and was called for a follow-up at a later date. In the meantime, the patient was discussed at the surgical council. A decision was made to perform video-assisted thoracoscopy due to the fluid not regressing, increased dyspnea, and malignant involvement in PET-CT. During the procedure conducted under general anesthesia, 400 cc of fluid was aspirated. Biopsies were obtained from two distinct areas of the pleura and from a nodular region on the diaphragm, followed bytalc pleurodesis. Samples were sent to microbiology and pathology. The patient, having experienced no complications, was discharged following the procedure

Pathology:

 Samples taken from the parietal pleura and the nodule on the diaphragm were evaluated as low-grade non-Hodgkin Lymphoma and interpreted as extra-nodal marginal zone lymphoma (MALT) by the pathologist (Figure 5). Discussion Clinical: The patient, who had been admitted to the emergency room with symptoms of dyspnea, hypoxia, and fever, was hospitalized after pleural fluid was exudate and consolidation was detected. Although the patient's clinical symptoms were severe, CRP was moderately high, and the occasional fever despite antibiotic therapy during hospitalization suggested diagnoses such as malignancy and tuberculosis, in addition to non-specific infection. Lymphomatous proliferation can involve the lung in various ways. Non-Hodgkin or Hodgkin lymphoma can present in the lung through hematogenous spread or by invading from adjacent mediastinal lymph nodes. However, primary involvement of the lung is also possible. Primary lymphomas should not have extra-pulmonary organ involvement for at least 3 months after diagnosis. The most common are MALT and effusion lymphomas (2). Effusion lymphomas may involve the pericardial and peritoneal cavities, with the most common primary involvement being the pleura, without solid organ involvement. Human-Herpes-8 infection and EBV may be accompanied by fever and lymphocytic-exudative fluid. HHV-8 negative cases have a better prognosis (3). In this case, there was also an exudative pleural effusion. However, although pleural involvement was not detected in the fluid cytological examination, pleural involvement was detected in biopsies. However, it is not possible to say that the patient only has effusion lymphoma (PEL). MALT (Mucosa-associated Lymphoid Tissue) lymphoma is the type of lymphoma that most commonly involves pulmonary tissue, is often asymptomatic, and shows radiological alveolar opacities. Although it is more commonly affected in people aged 50-60, it can rarely be seen under the age of 30. It constitutes 60% of pulmonary lymphomas. Weight loss and fever are especially prominent during the aggressive phase, though the condition may initially be asymptomatic. Autoimmune disease may be the basis in 16% of cases (1,4). The prognosis of MALT lymphomas is good; 5–10-year survival is more than 80% (5).

Radiological

 MALT lymphoma exhibits radiological variability, appearing as single or multiple bilateral lesions on both chest radiography and thoracic tomography. Chronic alveolar localized opacities smaller than 5 cm on radiography are accompanied by consolidation in 50% of cases. Diffuse reticulonodular opacity, atelectasis, and pleural effusion are detected in less than 10% of cases (1). In our case, there was also pleural fluid along with similar findings. Findings such as consolidation (60-77%) with air bronchogram and increased vascularity or multiple mass nodules, ground glass, halo sign, galaxy sign specific to tuberculosis and sarcoidosis have been reported in case series and reports. In addition, varicose cystic bronchiectasis secondary to consolidation can be detected. However, it is not possible to state that these findings are specific to MALT lymphoma. These radiological images are also observed in adenocarcinoma, pneumonia, metastases, sarcoidosis, and tuberculosis (6,7). In this case, chest X-ray revealed bilateral multifocal consolidation and densities indicative of pleural effusion. Consolidation, pleural effusion, varicose cystic bronchiectasis changes and mediastinal lymphadenomegaly were detected on thoracic tomography. None of these radiological findings were specific to lymphoma and diagnosis could not have been made without pathological examination. The partial alleviation of the patient's clinical symptoms compared to the beginning and the patient's relief with the drainage of the pleural fluid suggested possibilities such as infection, alveolar sarcoidosis, or adenocarcinoma when we did not have pathological data. Nevertheless, when intermittent fevers began to occur during the clinical course, it was obvious that lymphoma could not be excluded from the diagnosis. No endobronchial lesion was detected in the bronchoscopy performed on the patient; Wang fine needle aspiration and then endobronchial ultrasonographic biopsy were performed for mediastinal lymphadenomegaly. The sensitivity and specificity of positron emission tomography (PET-CT) in lymphoma varies according to organ involvement. It has been reported as 80-100% in lung involvement (8, 9). In our case, high SUVmax FDG uptake in consolidated foci in lepidic structure was monitored in PET-CT, and pleural uptake was minimal. The presence of clinical symptoms and high FDG uptake necessitated a video-assisted-thoracoscopic (VATS) procedure. Pathological: In the pleural fluid sample examined at the start of the treatment, abundant lymphoid cells were detected, but noatypical structures were observed. There were findings of granulomatous inflammation in the samples obtained from the mediastinal lymph nodes of the patient. In fact, in the biopsy samples taken by video-assisted thoracoscopy, lowgrade B-cell non-Hodgkin Lymphoma (CD20 positive (diffuse cells), anti-BCL-2 positive, anti Ki-67 low positive) and extranodal marginal zone lymphoma were detected in the parietal pleura. Pathologically, the lymphomatous infiltrate in MALT lymphoma exhibits heterogeneous features and consists of small lymphocytes, centrocyte-like cells, monocytoid B cells, rarely large transformed cells and plasma cells (10). Necrosis is rare. Neoplastic cells are expressed in CD 20 and CD 79. Ki67 index is lower than 20%. Lymphoma and sarcoidosis are similar in terms of clinical and radiological phenotype. Distinguishing lowgrade lymphomas from sarcoid lesions can be challenging; sarcoid granulomatous lesions may be accompanied by lymphoid cell infiltration. In addition, sarcoid-like reactions are frequently seen in malignant lymphomas. Moreover, sarcoidosis-lymphoma syndrome was first described in the study by Brincker et al. They reported that lymphoma was 5.5 times more common in sarcoidosis patients than in the general population, indicating the presence of sarcoidosis years before lymphoma (11, 12). Kokuho N et al reported MALT lymphoma in the lung for the first time in a ten-year-old sarcoidosis case with ocular, gastric and lung involvement (13). In this case, granulomatous inflammation was detected in mediastinal LAMs, but no findings of sarcoidosis were found in ocular, cardiac, renal examinations, angiotensinconverting enzyme, calcium, alkaline phosphatase, and 24- hour urine calcium analyses. There was also no abnormality in abdominal ultrasonography. We believe that the granulomatous inflammation in our case was reactive to immune deficiency

Conclusion 

The patient was started on Rituximab treatment by the hematology department. Clinical and radiological improvement was observed following treatment. In the follow-up PET-CT examination, regression in consolidated areas, decrease in FDG uptake, and metabolic partial regression were detected compared to the initial examination (Figure 6). Lymphomas, which do not have specific radiological and symptomatic features, can mimic most diseases of the respiratory system and do not present with a noisy picture, requiring the clinician to be persistent in making the diagnosis.

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