A 64-year-old Caucasian male presented to the emergency room complaining of progressive fatigue, light-headedness, shortness of breath, and an intermittent cough. He reported waking up with extreme malaise and inability to ambulate on the day of presentation. However, upon further questioning, it became evident that his symptoms had started 3 months prior and had gradually progressed in severity. He had been on a camping trip in the Rocky Mountains of Colorado and stayed in a yurt for one and half months before presentation; the trip was cut short due to his shortness of breath and decreased exercise tolerance. He had seen his primary care provider for these symptoms and a chest X-ray showed bilateral upper and lower lobe alveolar infiltrates. He was treated for atypical pneumonia with a 5-day course of azithromycin. His cough resolved but there was no improvement in the rest of his symptoms. Review of systems was significant for unintentional weight loss of 8–10 pounds over a period of 2 years; he denied nausea, vomiting, diarrhea, and/or melena.\nHis medical history included hypertension, glaucoma, and hyperlipidemia. He was a former smoker, having quit about 20 years prior. He drank alcohol occasionally. Family history was significant for leukemia in his father.\nPhysical examination was significant for pale skin and conjunctiva and a 3/6 systolic murmur best heard at the left sternal border.\nLaboratory investigations showed hematocrit of 11.3% and hemoglobin of 3.7 gm/dl, and the stool guaiac test was positive. Computed tomography (CT) of the chest with intravenous contrast showed bilateral pulmonary opacities and mediastinal lymphadenopathy in the perivascular and posterior mediastinum (). CT of the abdomen and pelvis with contrast showed severe gastric wall thickening involving the proximal body and fundus with surrounding inflammatory changes (). Esophagogastroduodenoscopy with biopsy was performed. Gastric pathology showed an intense infiltrate of small, mature lymphocytes extending to the epithelium and obliteration of normal glandular architecture; immune-histochemical staining showed CD20+ and abnormal dim CD43 co-expression ( and ) and BCL2+ and low to moderate Ki-67 proliferation index suggestive of extra-nodal marginal zone B-cell lymphoma of mucosal-associated lymphoid tissue. Helicobacter pylori was not identified on immunohistochemical staining and a serological analysis of IgG antibodies was negative ruling out previous exposure. A HLA-DQ pattern analysis for celiac disease was inconclusive. Serological analysis to rule out chronic infective etiology for immune stimulation from blastomyces, coccidioides, histoplasma, legionella, mycoplasma, aspergillus, and hepatitis B or C was negative. Subsequently, he also underwent bronchoscopy with transbronchial biopsy of the right upper and middle lobes, which showed atypical lymphoid infiltrate consistent with involvement from known MALT lymphoma with CD20+ and dim CD43 co-expression ( and ). He was treated symptomatically for anemia with blood transfusion and intravenous iron administration. He underwent radiation therapy for MALT lymphoma of the stomach due to gastric bleeding and severe anemia requiring multiple transfusions. Radiation treatment was given with 15 MV photons with an AP/PA treatment technique using MLC shaping with CT based three-dimensional treatment and planning. He received a total dose of 36.0Gy in 20 fractions over 27 elapsed days. Immunotherapy with rituximab was considered. However, since the only symptomatic manifestations were related to his severe anemia secondary to the gastric involvement of his lymphoma, he was treated as localized disease. He is been closely followed by his oncologist and has been undergoing surveillance CT-scan of his chest/abdomen every 6 months and yearly PET scan. He has not required any chemotherapy or further radiation therapy and his lymphoma has remained stable.
A 65-year-old man with a progressive lung GGN in the left upper lobe for six and a half years and no symptoms presented to our hospital. The patient had a past clinical diagnosis of tuberculosis in the right upper lobe, and the pGGN (14 × 13 mm) was found on 25 February 2013 (Fig. , A2). Right upper lung lesion was partly absorbed after anti-tuberculosis treatment for nine months. Unfortunately, the shadow on the right upper lobe increased and was found on repeated chest CT on 21 June 2015 (Fig. , B2), and was diagnosed as squamous cell carcinoma through CT-guided lung biopsy. The patient underwent right upper lobe resection and lymph node dissection on 20 July 2015. The post-operative diagnosis was moderately differentiated squamous cell carcinoma, T2aN0M0 Ib. No recurrence of lung cancer in whole body was confirmed based on the results of 11 repeated CT scans taken from 23 October 2015 to 4 December 2019, but the size of pGGN gradually increased and the density progressively became solid without any change after antibiotic treatment (Fig. ). This increased shadow was considered as adenocarcinoma without any positive finding by bronchoscope. Eventually, the ground-glass shadow on the left upper lobe was diagnosed as extranodal marginal zone lymphoma of the MALT by CT-guided needle biopsy on 13 December 2019 with pathological immunohistochemistry showing CD20 (+), CD3 cells (+), CD10 (−), bcl-6 (−), bcl-2 (+), CD21, CD23 cells (+), mum-1 (+), CK epithelial cells (+), Ki-67 5% (+), Pax-5 (+), CyclinD1 (−), sox-11 (−), and CD5 few (+) (Fig. ). After reviewing his medical history again, the patient underwent three gastroscopies due to intermittent abdominal pain and melaena from 6 June 2017 to 19 September 2018. Finally, he was diagnosed with MALT lymphoma with immune phenotype showing CD3 (−), CD5 (−), CD10 (−), Ki-67 (3% +), CD20 (+ + +), and CyclinD1 (−) (Fig. ; note: low-grade malignant). But, he had no further therapy and follow-up after anti-HP treatment for one month. The patient was diagnosed with coexisting lung squamous cell carcinoma combined with pulmonary MALT lymphoma and was transferred to the Department of Hematology in our hospital for further treatment after the pGGN was first discovered more than six years ago.