Introduction:

Table 1:

Figure 1: Moderately cellular aspirate showing predominant population ofblast cells (pointed by arrows).

Figure 2 (a): Multiple non-caseating granulomas (pointed by arrows) in the background of blast cells infiltration

Figure 2 (b): A focal collection of epitheloid macrophages forming  non-caseating granuloma.

Discussion:

The coexistence of B-cell acute lymphoblastic leukemia (B-ALL) and non-caseating granulomas in the bone marrow is exceptionally rare and poses significant diagnostic and therapeutic challenges. Acute lymphoblastic leukemia is primarily defined by clonal proliferation of immature lymphoblasts in bone marrow, yet granulomatous inflammation is not a typical histopathologic feature of this disease(2). Granulomas in bone marrow biopsies are described infrequently, with reported incidence ranging from 0.3% to 2.2% of all marrow specimens. While granulomas have been reported in association with Hodgkin lymphoma, non-Hodgkin lymphoma, and multiple myeloma, their occurrence with acute lymphoblastic leukemia is rarely documented. In the American Journal of Clinical Pathology case series, among ten patients with non-Hodgkin’s lymphoproliferative malignancies and marrow granulomas, only one case involved acute lymphoblastic leukemia, underscoring the exceptional nature of this finding(3). Mechanisms behind non-caseating granuloma formation associated with malignancies have been described as sarcoid-like reactions (SLRs). Such reactions are histologically indistinguishable from granulomas seen in systemic sarcoidosis but occur in the setting of neoplastic disease without fulfilling clinical criteria for sarcoidosis. The pathogenesis is believed to involve immune activation by tumor antigens or paraneoplastic immune responses, triggering T-lymphocyte and macrophage aggregation into granulomatous formations(4).The identification of granulomas within a leukemic marrow necessitates a thorough exclusion of infectious etiologies (especially mycobacterial and fungal infections) and true systemic sarcoidosis before attributing the findings to a sarcoid-like reaction. In regions with high tuberculosis prevalence, this distinction is particularly critical. Prior case reports emphasize the need for comprehensive microbiologic investigations, including Ziehl–Neelsen staining, PCR testing, and appropriate cultures, to avoid misdiagnosis and inappropriate therapy(2).  In our case,there was no clinical evidence of multisystem involvement, special stains for typical and atypical Mycobacterium and fungal infection (Ziehl Neelson , Modified Ziehl Neelson Stain and Grocott Methamine Silver) were negative , PCR for Mycobacterium infection tuberculosis (MTB by genexpert) was also negative. Based on these, infectious etiology and sarcoidosis were ruled out.

Furthermore, granulomatous reactions can sometimes overshadow or delay the recognition of leukemic infiltrates, especially if blast percentages are low or focal. Close correlation witimmunophenotyping, and cytogenetic analyses is therefore essential to confirm the diagnosis of B-ALL in the presence of granulomatous marrow changes.(2). In summary, non-caseating granulomas within the bone marrow in association with B-ALL, while exceedingly rare, represent a documented phenomenon that can complicate diagnosis and management. Clinicians should maintain a high index of suspicion for underlying hematologic malignancy in patients presenting with unexplained marrow granulomas, particularly after infectious and systemic granulomatous diseases have been excluded. A coordinated diagnostic strategy including morphology, immunophenotyping, microbiologic testing, and clinical correlation is essential to guide appropriate treatment.

Competing Interest: The authors declared no conflict of interest.