A 55-year-old female presented to the emergency department for evaluation of severe lower flank pain radiating to her lower abdomen and chest. Further review of symptoms revealed that she also had cough, night sweats, chills, and an unintentional weight loss of 31 pounds over 3 months. Clinical examination was significant for bilateral axillary lymphadenopathy. Subsequently, a computed tomography (CT) scan of her chest, abdomen, and pelvis was performed that revealed extensive bilateral lymphadenopathy (above and below the diaphragm) as well as a new right upper lobe (RUL) thin-walled cavitary lung lesion with spiculated margins (Figure 1a). A positron-emission tomography (PET)-CT scan showed highly metabolically active lymphadenopathy in the neck, chest, abdomen, and pelvis but minimal to no PET avidity within the RUL cavitary lesion (Figure 1b). Axillary lymph node sampling showed moderate-to-large B-lymphocytes (positive for CD5, CD20, and cyclin D1), with fluorescence in situ hybridization positive for t(11; 14), consistent with MCL. Although a bone marrow biopsy revealed low disease burden (<10% involvement), her lymphoma demonstrated a high proliferation rate (Ki67 proliferation index 30%), and she was diagnosed with stage IV-B MCL.
Prior to initiation of chemotherapy, she was referred to the pulmonary clinic for workup of the lung lesion, which was felt to have radiographic features atypical for lymphoma. She was an active, 30 pack-year smoker with symptoms of stable chronic bronchitis, sinusitis, and scant hemoptysis. Serum tuberculosis testing (TB-quantiferon) was negative. Although no prior self-history of cancer, she had a strong family history for cancer (lung cancer [father, paternal uncle, and paternal grandfather], cervical cancer [mother], and premenopausal breast cancer [paternal aunt]). Chest CT was significant for severe emphysema, multiple indeterminate pulmonary nodules, and a 1.7 x 1.1 cm, subpleural, thin-walled cavitary lesion with spiculated margins in the RUL (Figure 1a). Initial differential diagnosis included malignancy (primary/metastatic carcinoma and less likely lymphoma), subacute or chronic infections (such as tuberculosis and fungal infection), and vasculitis. Bronchoscopy was unremarkable, and bronchoalveolar lavage showed 87% macrophages, 10% neutrophils, and 2% lymphocytes, without malignant cells. Respiratory cultures grew 1+ Aspergillus flavus. Serum antineutrophil cytoplasmic antibodies and rheumatoid arthritis factor were negative. A short-interval (2 months) follow-up CT imaging showed stable pulmonary nodules but a persistent RUL cavitary lesion. A video-assisted thoracoscopic wedge resection was performed to exclude other diagnoses prior to initiation of chemotherapy for MCL. Pathological examination revealed a lepidic predominant, well-differentiated adenocarcinoma (pathological stage T1a), with coexistent foci of lymphoid infiltrates within and adjacent to adenocarcinoma (Figure 2a). The lymphoid infiltrate had histological features (convoluted irregular small nuclei; Figure 2b). By immunohistochemistry, the adenocarcinoma component was strongly positive with thyroid transcription factor-1, confirming pulmonary origin (Figure 2c) and discounting the possibility of metastasis from a possible mammary carcinoma. In addition, immunohistochemical profile (positive for B-cell markers CD20, pax5, and BCL1 [cyclin D1]; Figure 3a and b) was consistent with MCL. Multidisciplinary consensus was that no additional surgery, lymph node sampling, or adjuvant chemotherapy was needed. She was subsequently observed for both adenocarcinoma and lymphoma (high proliferation rate but with low disease burden), with surveillance imaging. A year later, however, she presented with dyspnea and a new right-sided pleural effusion (cytology positive for adenocarcinoma, negative for epithelial growth factor receptor/anaplastic lymphoma kinase). She received 6 cycles of carboplatin/pemetrexed/bevacizumab with good treatment response; however, she declined further maintenance therapy due to an intolerance of side effects. A few months later (a year ago), she presented with weight loss, chills, and night sweats, and CT imaging showed progressive lymphadenopathy concerning for MCL. She received ibrutinib and rituximab with good response initially; however, she could not complete the prescribed therapy due to side effects and was unfortunately lost to follow-up at the time of this writing.