Two Cases About Simultaneous Diagnosis Of Chronic Lymphocytic Leukemia And Solid Maligant Neoplasm And Literature Review

Objective:Chronic lymphocytic leukemia(CLL) is a kind of indolent lymphoma originated from B cell. Which is characterized by CD5+small B lymphocytes Widely gathered in peripheral blood, bone marrow, spleen and lymph nodes. In western countries, CLL is one of the most common type of adult leukemia, but in our country and other Asian regions,the incidence of CLL is relatively lower. What’s more,Been diagnosed with CLL and other non blood system solid malignant neoplasm at the same time is rare in clinic. Our hospital recently admitted 2 cases patients who has been diagnosed with CLL and malignant neoplasm at the same time, hereby report and review of the related literatures.Analyze the clinical features of leukemia superimposed with malignant neoplasm,in order to enhance clinicians’s awareness of this disease.Methods:Reported 2 cases about diagnosis of CLL and solid malignant neoplasm at the same time.Case 1 was admitted with"leukocytosis origin unknown, chronic lymphocytic leukemia?".Complete the physical examinations and related assistant examinations after admission.1, Blood routine and biochemical test.2, Bone marrow cell morphology, bone marrow biopsy,bone marrow flow cytology test, detection of p53(17 p13.1)gene,13q14gene,ATM(11q22.3)gene,RB1(13q14)gene and the number of chromosome 12, detection of IGHV gene rearrangement and IGH monoclonal V area mutation.3, Chest and abdomen CT.4, Neck lymph node biopsy, detection of TP53 gene mutation.5,Detection of EGFR mutation.Case 2 was admitted with" Esophageal placeholder, esophagus cancer?".Complete the physical examinations and related assistant examinations after admission.1, blood routine and biochemical test.2, Gastroscopy and esophageal placeholder biopsy.3, bone marrow cell morphology and bone marrow flow cytology test.Retrieved cases about leukemia superimposed with malignant neoplasm reported in the China National Knowledge Infrastructure(CNKI) and WANFANG DATA since 1996.Selected 105 cases with detailed informations,then combined with the two cases above, a total of 107 cases. Analyze the clinical features of those cases.Review of the literature,emphatically elaborate its pathogenesis.Results:Case 1,63 years old, Bilateral neck frequent, axillary, and inguinal lymph node enlargement,subcostal liver and spleen untouched.1, Blood routine showed that: WBC 17.22* 109/L, LYM 11.71* 109/L 68%, HGB 140 g/L, PLT 184* 109/L. 2, Bone marrow cell morphology imaged:bone marrow hyperplasia was obviously active. Lymphocyte hyperplasia was abnormal,and most of them were mature small lymphocytes(50%).Bone marrow flow cytology results suggested:abnormal mature B lymphocytes (48.7%), the immune phenotype:CD19+,CD20+,CD5+,CD10-,CD23+, FMC7-,CD38-(3.21%),ZAP70-(0.47%). The p53(17p13.1)gene and 13q14.3 gene deletion were detected. ATM (11 q22.3)gene and RBI (13q14) gene were not detected, the Increase of the number of chromosome 12 was not detected. IGHV gene monoclonal rearrangement was detected, but IGH monoclonal V area super mutation was not detected.3, CT showed right pulmonary placeholder, and mediastinum, bilateral axillary, abdomen and retroperitoneal lymph node enlargement. 4, Neck lymph node biopsy suggested metastatic cancer, immunohistochemistry: CK7+,TTF-1+, CK20-, P63+partly,Villin+little,CK5/6-,Napsin-A. Combined with immunohistochemistry,considering lung adenocarcinoma. TP53 mutation was not detected.5, EGFR gene mutation was not detected. Diagnosis:1, chronic lymphocytic leukemia (Rai I stage) 2, lung adenocarcinoma. This patient’s treatment strategy about CLL was follow-up observation. He has accepted nine courses of chemotherapy for lung cancer. After the second course of chemotherapy, reviewed the chest CT, the largest diameter of lung mass was decreased from 60mm to 35mm, compared with that before treatment. After the fourth, sixth, eighth course, reviewed the chest CT, there were no obvious changes. The patient in partial remission.Case 2,80 years old, ilateral neck frequent, axillary, and inguinal lymph node enlargement, subcostal liver untouched,and spleen touched.1, Blood routine showed that：WBC 26.5*109/L, LYM 21.28*109/L 80.3%, HGB 89 g/L, PLT 264*109/L. 2, Gastroscopy showed esophageal placeholder.The biopsy suggested esophageal squamous cell carcinoma,immunohistochemistry:CK5/6+,P63+,CK8/18-,Ki67(30%). 3, Bone marrow cell morphology imaged:bone marrow hyperplasia was obviously active. Lymphocyte hyperplasia was abnormal, most of them were mature small lymphocytes(80%).Bone marrow flow cytology results suggested:abnormal mature B lymphocytes (79.7%), the immune phenotype:CD19+,CD20+,CD5+,CD10-,sIgM+ very little, CD22+little,CD23+partly, FMC7+partly, cell membrane immunoglobulin Kappa light express restrictively. Diagnosis:1, chronic lymphocytic leukemia (Rai III stage) 2, esophageal squamous cell carcinomas. The patient refused treatment.Among the 107 cases,the male to female ratio was about 1:1.The age of second primary carcinomas ranged from 18 to 83 years old,with the mean age 51.7 years old.Among these cases,57 cases were initially diagnosed as solid malignant neoplasm, and major types are breast cancer, nasopharyngeal carcinoma, colon cancer, gastric cancer, lung cancer.31 cases as leukemia,and major types are CLL, CML.19 cases were synchronous. The Superimposing time ranged from 0 to 35 years. Conclusion:1. In the cases of leukemia superimposed with solid malignant neoplasm, synchronous neoplasm is rare than metachronousneoplasm.2. Combining with the cell morphology, immunology, molecular genetics and molecular biology to diagnose CLL, it can help clinicians estimate the prognosis better and make the tiered-therapy plan.3. The occurance of the second neoplasm in addition to be linked to the treatment of primary neoplasm (including chemotherapy and radiotherapy), it was also linked to biological factors, the body’s genetic background and immune abnormalities.4. when select treatment for primary tumor, clinicians should use less as far as possible mutagen, such as alkylating agents and antimetabolites, avoid excessive radiotherapy and chemotherapy, and regulate immune function of the organism,so that to prevent the occurrence and development of the second neoplasm. Clinicians should pay attention to the second neoplasm during the follow-up.5. The treatment principle of MPN is similar to the single primary tumors. There are two lines should be followed:comprehensive treatment and individualized treatment.