A 51-year-old female patient was admitted to our hospital on October 8, 2019. She had been diagnosed with pneumonia in a community hospital with 1 month of low-grade fever and an increased lymphocyte count (5.2 × 10
9/L) and ground-glass opacities on lung computed tomography (CT) scans in February 2019. The fever was relieved after oral antibiotic administration. Peripheral blood (PB) lymphocytosis was persistent and new ground-glass opacities on lung CT scans appeared at the 7-month follow-up (Fig.
1a, b). The patient was then referred to our hospital. A series of lung CT scans (October 10, 2019) suggested migratory pulmonary shadows with new ground-glass opacities in both of her lungs (Fig.
1c, d). The laboratory examination revealed an elevated white blood cell (WBC) count and lymphocyte count (WBC count, 17.43 × 10
9/L; lymphocyte count, 12.97 × 10
9/L). Renal and liver function were normal. The levels of inflammatory biomarkers, such as the erythrocyte sedimentation rate, C-reactive protein level, and procalcitonin level, were normal. The MycoDot test, an antiviral antibody series, an anti-
Mycoplasma pneumoniae antibody test, a legionella pneumonia antibody test, a rheumatic antibody series (except an antinuclear antibody titre of 1:100+), an immunoglobulin test, and a cytomegalovirus DNA test were all negative. Slight elevations in β2-microglobulin (2.73 mg/L, reference, 0.7–1.8 mg/L) and lactate dehydrogenase concentrations (245 U/L, reference, 135–225 U/L) were observed. The patient was positive for Epstein-Barr virus (EBV-DNA) in the PB, with a level of 1.15 × 10
4 copies/mL. Ultrasound indicated lymphadenopathy (the largest lymph node was 2.0 cm × 0.5 cm) with normal structures of the bilateral cervical, axillary and inguinal sites without hepatomegaly or splenomegaly. Due to the persistent lymphocytosis in the PB, flow cytometry immunophenotyping (FCI) of the PB was performed, and NK cells with an abnormal phenotype accounted for 66.6 % of the PB WBC population; this abnormal population mainly expressed CD56, CD7, CD2, and CD159a; partially expressed CD11c, CD38, and HLA-DR; and was negative for CD159c, CD158a, CD158b, CD158e, CD14, CD64, CD34, CD117, CD33, CD10, CD71, CD36, CD11b, CD3, CD8, CD4, cKappa, cLambda, CD94, CD161, CD57, CD1a, TCRαβ, TCRγδ, CD15, CD123, CD5, cKi67, cCD3, and CD16 (Fig.
2a). A PB smear showed large granular lymphocytes accounting for 90 % of the PB WBC cells. The aforementioned abnormal NK cells infiltrated the bone marrow (BM), as detected by a BM morphology examination and FCI, which showed 55.2 % and 59.0 % abnormal NK cells, respectively. The abnormal NK cells in the BM mainly expressed CD56, CD7, CD2, and CD45RO; partially expressed CD11b and CD94; and were negative for CD16, CD57, cKi67, cCD3, CD20, CD23, CD1a, CD3, TCRαβ, TCRγδ, Kappa, Lambda, CD19, CD5, CD45RA, CD161, CD4, and CD8 (Fig.
2b). Furthermore, a repeated examination of the chest CT results suggested that the bilateral pulmonary ground-glass opacities not only persisted but also exhibited an altered distribution (Fig.
1e,f). To clarify the nature of the lung lesions, bronchoalveolar lavage (BAL) was conducted, and FCI of the BAL fluid (BALF) revealed that abnormal NK cells accounted for 11.35 % and 12.41 % of the infiltrates in both lungs. The NK cells in the BALF mainly expressed CD56, CD7, CD2, and CD94; partially expressed CD16; and were negative for CD57 and CD161 (Fig.
2c, d). Results for T cell rearrangement and B cell rearrangement were all negative. Therefore, the patient was diagnosed with pulmonary infiltration in CLPD-NK. In our study, because this patient had an indolent clinical course without any symptoms or treatment indications, she did not receive any therapy and was monitored with a watch and wait approach. During the 13-month follow-up period, the patient has remained well without obvious symptoms, and the results of routine blood tests did not change significantly.