Test riflessi nella diagnostica di laboratorio delle gammopatie monoclonali

AUTORI

ABSTRACT

Reflex tests for the laboratory diagnosis of monoclonal gammopathies

The reflex test is one of the most popular interventions for improving appropriateness in laboratory medicine;this tool adds valuable diagnostic information and is consistent with best medical practice. Reflex tests have been applied across a wide range of commonly encountered diagnostic scenarios, including the laboratory investigation of hyper- and hypothyroidism, hypovitaminosis D, prostate cancer, hypomagnesemia, antinuclear antibodies, and even molecular biology. The reflex test is less frequently applied for the diagnosis of monoclonal gammopathies. When a monoclonal spike is recognized on serum protein electrophoresis, it is appropriate to identify the spike by the confirmatory test immunotyping (immunofixation or immunosubtraction) to determine whether or not the spike corresponds to a monoclonal immunoglobulin. If the immunotyping confirms the presence of a monoclonal immunoglobulin, the measurement of serum free light chains should be considered as a second reflex test. The application of reflex test for diagnosing monoclonal gammopathies allows a rapid and complete laboratory report, improving the patient’s care and outcome and avoiding time loss and economic waste. In Italy, the reflex test for serum protein electrophoresis is still not included in the national nomenclature of outpatient specialist care, making the reimbursement system for this additional laboratory test impracticable. Some Italian regions have included the test in their reinbursement system; however, discrepancies between regions contribute to severe healthcare disparities among citizens. Therefore, there is an urgent need to include the reflex test for monoclonal gammopathies in the national nomenclature of outpatient specialist care.

BIBLIOGRAFIA

1. Plebani M, Lippi G, Zaninotto M, Ciaccio M. Ridurre l’inappropriatezza in medicina di laboratorio: come, quando e perchè. Biochim Clin 2019;43:42-9.
2. Elnenaei MO, Thoni A, Eissa M. Reflex and reflective laboratory interventions for adding value to test results; an integral part of laboratory stewardship. Clin Biochem 2022;105-106:16-22.
3. Murphy MJ. Reflex and reflective testing: progress, but much still to be done. Ann Clin Biochem 2021;58:75-7.
4. Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, et al. 2015 American thyroid association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: the american thyroid association guidelines task force on thyroid nodules and differentiated thyroid cancer. Thyroid 2016;26:1-133.
5. Haddad RI, Bischoff L, Ball D, Bernet V, Blomain E, Busaidy NL, et al. Thyroid carcinoma, version 2.2022, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw 2022;20:925-51.
6. Ferraro S, Caruso S, Panteghini M. Reflex Testing of free prostate-specific antigen as effective health care policy. Arch Pathol Lab Med 2019;143:1045.
7. Tonutti E, Bizzaro N, Morozzi G, Radice A, Cinquanta L, Villalta D, et al. The ANA-reflex test as a model for improving clinical appropriateness in autoimmune diagnostics. Auto Immun Highlights 2016;7:9.
8. Gosney JR, Paz-Ares L, Jänne P, Kerr KM, Leighl NB, Lozano MD, et al. Pathologist-initiated reflex testing for biomarkers in non-small-cell lung cancer: expert consensus on the rationale and considerations for implementation. ESMO Open 2023;8:101587.
9. Braxton DR, Huang Y, Darabi S, Chavez F, Das PM, Bowen TJ. Pathology molecular reflex testing improves turn-around-time and overall molecular testing rates in NSCLC. J Clin Oncol 2021;39 Suppl e13507
10. Burgos L, Tamariz-Amador LE, Puig N, Cedena MT, Guerrero C, Jelínek T, et al. Definition and clinical significance of the monoclonal gammopathy of undetermined significance-like phenotype in patients with monoclonal gammopathies. J Clin Oncol 2023;41:3019-31.
11. Rajkumar SV, Dimopoulos MA, Palumbo A, Blade J, Merlini G, Mateos MV, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol 2014;15:e538-48.
12. Tate JR, Smith JD, Wijeratne N, Mollee P. Proposed addendum to 2012 recommendations for standardised reporting of protein electrophoresis in Australia and New Zealand. Clin Biochem Rev 2019;40:23-30.
13. Dimopoulos MA, Moreau P, Terpos E, Mateos MV, Zweegman S, Cook G, et al. Multiple myeloma: EHA-ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2021;32:309-22.
14. Mollee P, Tate J. Monitoring of light chain myeloma – time for a change (Editorial). Br J Haematol 2017;178:177-8.
15. Salinas M, Flores E, Blasco A, Lopez-Garrigós M, Torreblanca R, Leiva-Salinas M, Gutierrez I, Leiva-Salinas C; PRIMary Care-LABoratory (PRIMLAB) working group. Laboratory reflex testing strategy for the early identification of primary care patients with multiple myeloma. Clin Biochem 2024;126:110730.
16. McDermott M, Dighe A, Szolovits P, Luo Y, Baron J. Using machine learning to develop smart reflex testing protocols. J Am Med Inform Assoc 2024;31:416-25.
17. Savoia M, Michetti L, Cigliana G, Turra F, Debbia D, Visconti V, et al. Indicazioni per l’armonizzazione del referto dell’elettroforesi delle sieroproteine e della tipizzazione delle componenti monoclonali. Biochim Clin 2024;48:88-100.