A 60-year-old man, who was treated at our hospital for chronic obstructive pulmonary disease for five years, was admitted for the examination of ground glass opacity (GGO) in the lower lung field and mediastinal lymphadenopathy in the computed tomography (CT), which tended to be enlarged gradually. He was a former smoker (two packs a day for thirty-two years until fifty-one years of age) and had a history of surgery for inguinal hernia. He had dry cough and slight dyspnea (modified Medical Research Council [mMRC] grade I). Fine crackles were heard in the lower lung field upon chest auscultation. The superficial lymph nodes were not palpable. Laboratory data on admission are shown in Table 1.
Blood tests showed a white blood cell (WBC) count of 7400/muL without any significant abnormalities, hemoglobin level 14.5 g/dL, platelet count 25 x 104/muL, serum total protein 6.4 g/dL, albumin 3.7 g/dL, serum creatinine 1.09 mg/dL, lactate dehydrogenase 247 IU/L, serum beta2-microglobulin 2.4 mg/L (reference value < 2.0 mg/L), soluble interleukin 2 receptor 469 U/mL, sialylated carbohydrate antigen Krebs von den Lungen-6 (KL-6) 805 U/mL, angiotensin-converting enzyme (ACE) level 37.4 U/L, IgM level 791 mg/dL (reference value 33-183 mg/dL), IgG level 531 mg/dL (reference value 861-1747 mg/dL), IgA level 52 mg/dL (reference value 93-393 mg/dL), and IgE level 10 IU/mL (reference value < 170 IU/mL). In the urine test, kappa type Bence-Jones proteins (BJP) were detected. Pulmonary function tests showed obstructive ventilatory impairment, forced vital capacity (FVC) 3.94 L, FVC/predicted FVC 110.4%, forced expiratory volume in 1 s (FEV1) 2.41 L, and FEV1/FVC 61.17%. Electrocardiogram and ultrasonic cardiography were normal. An enhanced chest CT revealed emphysema dominant in the upper lung field, GGO in the lower lung field, interlobular septal thickening, mediastinal lymphadenopathy, and a soft tissue shadow in the paravertebral region (Fig. 1).
A fluorodeoxyglucose (FDG)-positron emission CT examination showed FDG accumulation in ill-defined soft tissue attenuation in the mediastinum and retroperitoneum (SUVmax = 2.5 and 2.4, respectively) (Fig. 2).
Bronchofiberscopy was performed. The recovery rate of bronchoalveolar lavage (BAL) from the right B5 was 60.0%. A BAL fluid (BALF) evaluation showed a total cell count of 4.26 x 105/mL and the differential WBC counts for macrophages, lymphocytes, neutrophils, and eosinophils were 95.0%, 3.8%, 0.9%, and 0.3%, respectively, showing normal proportion of the BALF. Among the T lymphocytes, the CD4/CD8 ratio was 1.8 and the proportion of CD1a was 1.3%, which was within the normal range. Bacterial, fungal, and acid-fast bacillus culture tests in BALF were negative. Transbronchial lung biopsy (TBLB) from the right S8 showed the infiltration of inflammatory cells, such as lymphocytes and plasma cells, in the alveolar wall.
Due to elevated serum IgM, urinary BJP and lymphadenopathy, our differential diagnoses included LPL, mucosa associated lymphoid tissue (MALT) lymphoma with plasma cell differentiation, and multiple myeloma. Bone marrow aspiration and biopsy were performed to assess bone marrow involvement. Normocellular marrow tissue with kappa predominant lymphocytes and plasma cells were obtained. The bone marrow smear showed 24.2% lymphocytes, 3.0% plasma cells, and some atypical cells. Flow cytometry suggested kappa-predominant B cells. These findings supported the diagnosis of LPL, but did not enable us to make a definitive diagnosis. To clarify the cause of the soft tissue shadow in the paravertebral region and GGO in the lower lung field, a surgical biopsy was performed from the right lower paratracheal lymph node and the right S8 of the lung. The lymph node specimen and the surrounding connective tissue revealed small lymphocytes and plasma cells between follicles (Fig. 3A). These cells were mostly positive for CD20, CD79a, and IgM, focally positive for CD138, and negative for CD3, CD5, CD10, and CD56. A few Dutcher bodies were also observed. In situ hybridization (ISH) revealed immunoglobulin light-chain restriction with an elevated kappa/lambda ratio of ten (Fig. 3B and C).
DNA was extracted from paraffin-embedded tissue and a mutation analysis using an allele-specific primer-polymerase chain reaction (PCR) confirmed MYD88 L265P mutation in lymph node specimens (a substitution of leucine with proline at amino acid position 265) (Fig. 4). G-banding was not available; fluorescence in situ hybridization (FISH) analysis of MALT lymphoma-specific translocation was negative.
In addition, eosinophilic amorphous deposits found in the lymph nodes and stroma of the fat connective tissue stained positively by Congo red, exhibited apple green color under polarized light, and were positive for AL kappa by immunohistochemistry (Fig. 5A-D).
In the lung specimens, mild emphysema and inflammatory fibrotic changes, including fibroblastic foci, were seen in the subpleural area. Besides these changes, amyloid deposition was also confirmed in the interlobular septa, and slight plasma cell infiltration was seen around amyloids. Thus, LPL with AL kappa amyloidosis was diagnosed, coexisting with interstitial pneumonia with usual interstitial pneumonia (UIP) like features.
During surgical biopsy, the lung tissue and fat connective tissue were fragile and bled easily. Due to massive bleeding, the operation was changed from video assisted thoracic surgery to thoracotomy. After surgery, the patient was moved to the respiratory care unit (RCU) with intubation for 16 days because of bleeding from the airways. After his condition improved, he was referred to another hospital.