Hemophagocytic Lymphohistiocytosis (HLH): A Clinical and Pathological Grading System Based on the Presence of Hemophagocytosis

Abstract Introduction/Objective Hemophagocytic lymphohistiocytosis (HLH) is a heterogeneous group of disorders resulting from uncontrolled immune activation leading to severe hyperinflammation. The syndrome can be primary (genetic) or secondary to infections, malignancies, or autoimmune diseases. The diagnosis of HLH is challenging due to its nonspecific clinical presentation and the overlap with other conditions. This study aims to establish a reliable diagnostic approach for HLH by evaluating the accuracy of bone marrow histomorphological criteria in diagnosing the disease. Methods/Case Report We conducted a retrospective analysis of clinical and pathological data from patients diagnosed with HLH over a 12year period and included 38 patients with suspected HLH. A grading system for hemophagocytosis was developed based on the extent and frequency of hemophagocytic activity observed in bone marrow biopsies. Hemophagocytosis is categorized into four grades: Grade 0 indicates its absence, Grade 1 describes mild hemophagocytosis with less than 2 histiocytes containing hemophagocytosis per slide, Grade 2 denotes moderate hemophagocytosis with 3 to 5 histiocytes per slide, and Grade 3 signifies severe hemophagocytosis with more than 5 histiocytes per slide. Clinical data, comprising laboratory parameters and treatment outcomes, were analyzed in relation to the histologic grading of hemophagocytosis. Results (if a Case Study enter NA) Among the cases, grade 1 had 1 resolved case, 4 cases meeting 2 criteria all resolved, and 13 cases meeting 4 or more criteria resulted in 5 deaths and 8 resolutions. Grade 2 included 10 cases, with 2 meeting 2 criteria and resolving, and 8 meeting 4 or more criteria resulting in 5 deaths and 3 resolutions. Grade 3 comprised 10 cases, with 3 meeting 3 criteria and resolving, 3 meeting 5 or 7 criteria resulting in 1 death and 2 resolutions each, and 4 meeting 6 or 8 criteria resulting in 2 deaths and 2 resolutions each. Conclusion In our retrospective analysis of bone marrow biopsies from 38 patients with suspected HLH, our results indicate that the presence and extent of hemophagocytosis strongly suggest HLH. Implementing these criteria significantly improved diagnostic accuracy, reducing misdiagnosis rates and enabling timely therapy initiation. This study underscores the value of bone marrow histomorphological criteria in diagnosing HLH and stresses their importance in the standard diagnostic process for suspected HLH cases.