Prognosis of multiple myeloma patients based on histopathological evaluation of bone marrow

Abstract

Background: Multiple myeloma is still one of deadliest malignancies known. Although many attempts to prognosticate the disease have been done like the International Staging System (ISS), most of the proposed prognostic tools are based merely on laboratory tests and hence prone to analytical errors in large and high-volume centers. This study aims to evaluate the prognostic effectiveness of histopathologic components of bone marrow and compare it to the results of laboratory-based prognostic tools.

Methods: This cross-sectional study, bone marrow specimens of 93 multiple myeloma patients underwent aspiration and biopsy evaluated. The primary outcome was overall survival (OS) based on plasma cell percentage. The secondary outcomes were also OS based on angiogenesis using IHC marker CD34, nuclear atypia level, BM involvement pattern and the presence of fibrosis in bone marrow specimens. All biopsy specimens assessed using light microscopy on Hematoxylin and Eosin and IHC staining. Giemsa staining assessed for aspirate specimens.

Results: Of 93 patients, 63.4% were dead. Median survival was 34.0 months (95% CI [24.6; 43.3]) and the average age at diagnosis was 65 years (highest 84 and lowest 40). Patients with bone marrow plasma cell count of over 70%, had a hazard ratio (HR) of death of 4.7 times more than those with plasma cell count between 10-25%. Similarly, diffuse infiltration pattern (HR 4.67) and blastic morphology (HR 4.17) associated with a significant worse prognosis (p=0.03).

Conclusion: Comparing to laboratory-based ISS, wider HR of death spectrum in this study proposes a potential more precise, robust and easy-to-use prognostication tool.

Keywords: Histopathological prognosis; International staging system; Multiple myeloma.

Figure 1

CD34 IHC stained Bone marrow specimens showing different staining patterns. A: BM infiltrated with MM cells. A high and crazy pattern of angiogenesis is seen. B: control 1 containing Normal BM and normal vasculature. C: control 2. IHC, immunohistochemistry; BM, bone marrow; MM, multiple myeloma.

Figure 2

Kaplan-Meier survival curve of patients according to their bone marrow plasma cell percent. Blue line represents group 1 patients (10-25% plasma cells) with the best median survival and red line represents group 4 patients (>70% plasma cells) with worst (not reached vs. 23 months (95% CI [19.3;26.7]); log-rank, p= 0.01)).