Synchronous metastatic lung adenocarcinoma and marginal B-cell lymphoma presenting as pleural nodules

Abstract

In this report, we present a 73 year old woman with synchronous metastatic lung adenocarcinoma and marginal B-cell lymphoma determined on histopathology of a parietal pleural biopsy. This case demonstrates radiological demonstration of pleural disease, procedural investigations and striking histopathology, along with a discussion around synchronous malignancy.

Background

Synchronous malignancy is an uncommonly seen presentation and even more so manifesting as metastatic pleural disease. Advances in pleural disease research have allowed for more accurate diagnosis and management, demonstrated best by this complex case.

Case presentation

A 73 year old woman patient who was referred to the outpatient procedural clinic for right-sided pleural effusion. She presented with a 3 month history of progressive dyspnoea on exertion that was accompanied by pleuritic chest pain radiating to her back and right shoulder. Her family physician ordered a chest X-ray for her that demonstrated a large right-sided pleural effusion, leading to her referral to our clinic (figure 1).

Figure 1.

Radiographical investigations of the patient’s pleural effusion. (A) Initial chest X-ray demonstrating large right pleural effusion. (B) CT thorax demonstrating mild right inferior pleural nodularity and thickening on the posterior hemithorax. (C) Positron Emission Tomography (PET)/CT scan showing avid areas of pleural nodularity.

The patient had multiple comorbidities in medical history. Of note, she suffered from systemic lupus erythematosus which had been quiescent for over 20 years and maintained on hydroxychloroquine; however, she gave a vague history of previous pleuritis related to her lupus for which she had a chest tube inserted (15-20 years ago). She also had a history of chronic obstructive pulmonary disease (COPD), symptomatically controlled on fluticasone furoate and vilanterol inhaler. She had a history of malignancy with colorectal cancer post resection over 30 years ago. She was a current smoker with a 30 pack year history.

Thoracentesis was performed on initial appointment, draining 1.1 L of straw coloured fluid. Results of the pleural fluid analysis demonstrated 85% lymphocytes with a negative culture and cytology. In follow-up a week later, the patient had a repeat thoracentesis for recurrence of her effusion and was once again sent for cytology. At the time, it was felt this may be due to lupus pleuritis given her history and she was started on prednisone 25 mg for 3 weeks to be tapered after reassessment.

After another week, the patient’s pleural effusion had once again reaccumulated despite steroid therapy. The cytology on the previous thoracentesis returned with numerous small mature lymphocytes with subsequent flow cytometry suggesting a B-cell lymphoproliferative neoplasm. Prednisone was stopped, a third repeat thoracentesis was deferred due to the patient’s stable condition, and a Computed Tomography (CT) of the chest, abdomen and pelvis were ordered to assess for malignancy. The CT demonstrated the large right pleural effusion with mild inferior right pleural thickening and nodularity with no evidence of mass or lymphadenopathy (figure 1). As such, the patient underwent a right-sided medical pleuroscopy.

Investigations

On pleuroscopy, patchy parietal pleural thickening with significant nodularity in the posterior hemithorax was noted. There were several nodules that were hyperemic seen anteriorly as well. The diaphragm was coated with this infiltrative tissue and was also quite nodular. The visceral pleura appeared anthracotic with some nodularity in the lower lobe. There was no significant pleural peel identified. Biopsies of the parietal pleura were taken with an overall impression of malignant involvement (figure 2). A right-sided indwelling pleural catheter (IPC) was inserted at the time of the procedure as well for symptomatic relief. Entrapped lung physiology was present.

Figure 2.

Pleuroscopy of the right pleural space demonstrating profound nodularity of the lower right posterior pleura concerning malignancy.

The parietal pleura biopsies returned with remarkable pathology (figure 3). There was a demonstration of metastatic, moderately differentiated, acinar type adenocarcinoma, positive for pan cytokeratin, moc31, BerEP4 and TTF1; overall, this favoured lung primary. Surrounding the adenocarcinoma was an extensive infiltrate of mature and atypical lymphocytes. Immunohistochemistry of these cells was positive for CD20, Bcl2 and focally CD43. Flow cytometry revealed 23% of leucocytes positive for CD19 and CD20, favouring B-cell lymphoproliferation. The lung adenocarcinoma was negative for endothelial-derived growth factor (EGFR), anaplastic lymphoma kinase (ALK), ROS proto-oncogene 1 and Program Death Ligand-1 (PD-L1) expression was <1%. Overall, impression by the pathologists was a metastatic, moderately differentiated lung adenocarcinoma synchronous with a marginal zone B-cell lymphoma.

Figure 3.

Pathology of pleural nodule biopsies demonstrating metastatic adenocarcinoma surrounding by mature, atypical lymphocytes determined to be B-cell predominant on flow cytometry. (A) H&E slide of the adenocarcinoma component in the pleura. (B) immunohistochemical stain (TTF1) of the adenocarcinoma, confirming lung primary. (C) H&E slide of the lymphoma component. (D) immunohistochemical stain (CD20) of the lymphoma, confirming marginal zone type.

Outcome and follow-up

Unfortunately, therapeutic target biomarkers for the lung adenocarcinoma (EGFR, ALK, PD-L1) were all negative. Positron Emission Tomography (PET)/CT scan was performed for lymphoma staging and redemonstrated pleural nodularity and right hilar and mediastinal lymphadenopathy (figure 1). There was no extra-thoracic disease identified on PET. The patient was seen by medical oncology for her metastatic lung adenocarcinoma and started on pemetrexed and carboplatin for palliative intent, which she is currently receiving. Haematology also assessed the patient for the marginal zone lymphoma and elected to observe for the time being.

The patient had immediate and sustained symptomatic improvement following pleuroscopy and indwelling pleural catheter insertion for her pleural effusion. With thrice-weekly home drainages, she achieved spontaneous pleurodesis without talc administration at 63 days and had her IPC removed. There has been no clinical or radiographical recurrence of her effusion.

Discussion

There are few case reports describing the rare occurrence of synchronous primary lung malignancy and lymphoma presenting as a pleural disease.^1–4 Review of literature does reveal a fair number of synchronous colorectal malignancy and marginal zone lymphoma, likely owed to increased mucosa-associated lymphoid tissue in the GI tract.^5–7 This case, in particular, demonstrates pitfalls of pleural fluid cytology as a poorly sensitive diagnostic test and highlights the importance of tissue biopsy, particularly with the use of pleuroscopy.⁸ A diagnostic challenge was posed by the confounding history of lupus pleuritis as well, which was excluded by lack of treatment response and pleural biopsies.

The pathophysiology of synchronous cancer can be due to genetic or extrinsic risk factors (ie, smoking) or simply coincidental. Lymphoma and lung adenocarcinoma arise from different progenitor cells. Marginal zone lymphoma arises from a B-cell population within lymph nodes, the spleen, and mucosa-associated lymphoid tissue found in the lung and GI tract. Conversely, lung adenocarcinoma arises from alveolar epithelial cells. Furthermore, there are no known shared genetic driver mutations between lymphoma and lung adenocarcinoma.^{9 10} The patient’s smoking history and autoimmune disease history are risk factors for the development of her lung adenocarcinoma and marginal zone lymphoma, respectively.^{11 12}

The treatment modality of choice is unclear for synchronous lymphomas and lung primary malignancy. Marginal zone lymphomas take a rather indolent course and active surveillance with imaging is a reasonable option. Indications for treatment include rapid progression, deep invasion, impending end-organ damage and patient preference; the backbone of treatment, in this case, is rituximab.¹¹ However, metastatic lung adenocarcinoma carries a more grim prognosis, as low as 10% 2 year survival, especially without biomarkers for targeted treatment in this patient’s case.¹³ Understandably, prioritising treatment of the adenocarcinoma should take precedence in synchronous cases.

This case report highlights the malignant pleural disease diagnostic pathway through an interesting presentation of synchronous metastatic lung adenocarcinoma and marginal zone lymphoma. Although uncommon, it does present diagnostic and therapeutic challenges and emphasises the importance of tissue diagnosis. This report will add to the growing literature around these cases and provide some guidance should another clinician encounter this intriguing clinical dilemma.

Learning points.

• Synchronous malignancy is a rare and complicated presentation requiring thorough diagnostic work-up.

• Pleuroscopy is the gold standard for evaulation of undiagnosed pleural effusion or thickening.

• Further research into the underlying immunology of malignancy can shed light on the development of synchronous malignancies.

Ethics statements

Patient consent for publication

Consent obtained directly from patient(s).