Beta-2 Microglobulin As a Seric Marker for Diagnosis of Hematologic Neoplasms in First Contact Consultation with the Hematologist
Authors: Landeros Perez Aldo Aldair , Padilla Ortega José Alejandro , Lupercio Ramírez Miriam de Jesús , Arias Garcia Francisco Ivan Ivan , Ron Magaña Ana Lucia , Villalobos Laura Olivia , Vargas Carretero Cesar J. , Chamorro Morales Norma Hilda 
Published: December 2023

Introduction
Beta-2 microglobulin is a protein component of the Major histocompatibility complex I. Its concentration in blood has been long used as prognostic marker in some hematologic neoplasms, and even used as a tool for surveillance of relapse in other neoplasms. It is frequently elevated in non-Hodgkin lymphoma (NHL), Myelodysplastic syndrome (MDS), myeloma multiple (MM), chronic lymphocytic leukemia (CLL) and other Lymphoproliferative disorders. Although its utility as a diagnostic tool has been poorly described.
Aim
Describe the blood levels of Beta-2 Microglobulin in patients who are sent without established diagnosis to be evaluated by hematology department and its association with the different definitive diagnosis.
Methods
We captured information from outpatients who were evaluated in the first consultation at hematology department because of any citopenia or clinical suspicion of any hematologic neoplasm from September 2022 to July 2023. If the patient consented, we recorded it in database and measured blood levels of beta-2 microglobulin on first consultation, and then followed until definitive diagnosis was established. Analysis of data was made with IBM SPSS Statistics for Windows, Version 27.0. Armonk, NY: IBM Corp; we used Mann Whitney U Test for quantitative variable comparison, and Fisher exact test to determine differences between groups. Statistical significances were calculates using p&lt;0.05.
Results
We captured a total of 87 patients, but 11 had to be excluded because of lack of information. Of the 76 patients included for analysis, 34 were male (44.7%) and 42 were female (55.3%). The medium age was 45.1 years (Range: 15-95 years). After the first consultation, 30 patients (39.5%) were suspected to have a neoplasm, and in follow-up, 35 (46.05%) ended up with a definitive diagnosis of hematologic neoplasm. Only one patient with initial suspected neoplasm ended up with benign disease, but 6 patients in which a bening condition was suspected ended up with a neoplasm diagnosis. There was a total of 35 (46.05%) patients with definitive neoplastic diagnostic, being the most frequent: NHL (n=15, 19.7%), Myeloproliferative neoplasm (MPNs) (n=6, 7.8%), and MM (4, 5.2%). In the no neoplastic pathology, the most frequent diagnosis was iron-deficit anemia (n=17; 22.36%), followed by megaloblastic anemia (n=4, 5.26%) and infectious disease (n=4, 26%).
Beta-2 microglobulin was higher in the group with definitive neoplastic diagnosis (5.4mg/L vs 2.4mg/L, x 2=0.053), and was also, significatively higher in the NHL (4.94mg/L, x 2=0.005), MM (13.43mg/L, x 2=0.008), CLL (6.3mg/L, x 2=0.02) and MDS (8.05mg/L, x 2=0.034) subgroups. The sensibility for any hematologic neoplasm was 48.5% and specificity was 82.93%, with a positive LR of 2.84 and a Negative LR of 0.62. The subgroups with higher sensibility were MM (75%), CLL (66.6%), MPNs (66.6%) and MDS (100%), being the Positive LR of 4.3 for MM, 3.9 for CLL, 3.9 for MPNs and 5.86 for MDS. Groups with the lowest correlation were Hodgkin lymphoma (HL) with sensibility of 33.3%, and isolated plasmacytoma (PC) with sensibility of 0%.
In the group with benign diagnosis, only 6 (7.89%) presented levels above upper normal limit of blood Beta-2 microglobulin, 4 (5.26%) with iron-deficit anemia, 1 (1.31%) with liver disease, 1 (1.31%) with Pulmonary tuberculosis and 1 (1.31%) with systemic lupus erythematosus; being the highest levels in pulmonary tuberculosis (14.9mg/L).
Conclusions
The blood levels of beta-2 microglobulin in our work were in concordance with other previous described papers, in which is frequently elevated in NHL, MM, and CCL. But in our case, it showed a marked elevation in MPNs, and MDS (higher correlation). It should be noted, no tumor burden was recorded in our study, which could directly affect beta-2 microglobulin levels.
In conclusion, although not a strong correlation as an expert hematologist clinical evaluation, beta-2microglobulin could be of use to strengthen clinical suspicion of those hematologic neoplasms or reassess cases in which MDS/MPNs are a possible differential diagnosis.