Myeloid sarcoma as the only manifestation in a rare mixed lineage leukemia-fusion-driven acute myeloid leukemia: A case report

Abstract

BACKGROUND

The mixed lineage leukemia (MLL)-eleven-nineteen lysine-rich leukemia (ELL) fusion gene is a rare occurrence among the various MLL fusion genes. We present the first case in which myeloid sarcoma (MS) was the only manifestation of adult MLL-ELL-positive acute myeloid leukemia (AML).

CASE SUMMARY

We report a case of a 33-year-old male patient who was admitted in June 2022 with a right occipital area mass measuring approximately 7 cm × 8 cm. Blood work was normal. The patient underwent right occipital giant subscalp mass excision and incisional flap grafting. Immunohistochemistry was positive for myeloperoxidase, CD43 and CD45 and negative for CD3, CD20, CD34, and CD56. The bone marrow aspirate showed hypercellularity with 20% myeloblasts. Flow cytometry showed that myeloblasts accounted for 27.21% of the nucleated cells, which expressed CD33, CD38, and CD117. The karyotype was 46, XY, t (11, 19) (q23; p13.1), -12, + mar/46, XY. Next-generation sequencing showed a fusion of MLL exon 7 to exon 2 of ELL. A diagnosis of MLL-ELL-positive AML (M2 subtype) with subcutaneous MS was made.

CONCLUSION

MLL-ELL-positive AML with MS is a rare clinical entity. Additional research is needed to elucidate the molecular mechanisms of the pathogenesis of MS.

Key Words: Myeloid sarcoma, Acute myeloid leukemia, Mixed lineage leukemia-eleven-nineteen lysine-rich leukemia, Transplantation, Case report

Core Tip: This study described myeloid sarcoma as the first and only manifestation in an adult patient with mixed lineage leukemia-eleven-nineteen lysine-rich leukemia-positive acute myeloid leukemia. Based on our findings and information from a few previous reports, we speculate that our patient had (1): Transformation of preleukemia cells in the marrow followed by spread to extramedullary sites; or (2) homing of preleukemia cells to extramedullary sites, followed by spreading back to bone marrow. The current study helps increase the awareness of this particular disease and reduce the clinical underdiagnosis rate.

INTRODUCTION

Myeloid sarcoma (MS) is a rare disease characterized by an extramedullary tumor composed of immature myeloid cells. When differentiating any extramedullary lesion infiltrated by heterogeneous cells, clinicians should consider the possibility of MS[1]. Mixed lineage leukemia (MLL) gene rearrangements define a unique leukemia with distinctive pathophysiology and phenotype. The MLL gene encodes a large histone methyltransferase that directly binds and actively regulates gene transcription. In MLL rearrangement leukemia, menin acts as an oncogenic cofactor leading to leukemogenesis by mediating aberrant gene expression through the HOX gene and cofactor meis homeobox 1[2]. A chromosomal translocation t (11; 19) (q23; P13), with breakpoints mainly located within the 19p13.1 subband, generates the MLL-eleven-nineteen lysine-rich leukemia (ELL) fusion gene and is predominantly found in acute myeloid leukemia (AML)[3]. We present a rare case in which MS was the only manifestation of adult MLL-ELL-positive AML.

CASE PRESENTATION

Chief complaints

A 33-year-old male patient was admitted in June 2022 with a right occipital area mass measuring approximately 7 cm × 8 cm.

History of present illness

The patient had scalp swelling for 4 mo prior to this presentation.

History of past illness

The patient had no history of chronic conditions.

Personal and family history

The patients’ personal and family histories were not significant.

Physical examination

A hard, immobile mass measuring approximately 7 cm × 8 cm was observed in the right occipital region of the skull. The local scalp color appeared dark brown with no abnormalities in the surrounding area.

Laboratory examinations

Blood work was normal. No malignant cells were seen in the cerebrospinal fluid.

Imaging examinations

No bone erosion or abnormalities were detected in the brain parenchyma by computed tomography scan (Figure 1). The cranial magnetic resonance imaging also showed no significant abnormalities.

Figure 1 Head computed tomography. Anomalous density shadow of the right occipital subcutaneous region.

Further diagnostic work-up

The patient underwent right occipital giant subscalp mass excision and incisional flap grafting (Figure 2). Resection tissue staining showed a small round-cell tumor, which was suspected to be lymphoma. Immunohistochemistry was positive for myeloperoxidase, CD43 and CD45 and negative for CD3, CD20, CD34, and CD56. The bone marrow (BM) aspirate showed hypercellularity with 20% myeloblasts. Flow cytometry showed that myeloblasts accounted for 27.21% of the nucleated cells, which expressed CD33, CD38, and CD117 (Figure 3). The karyotype was 46, XY, t (11, 19) (q23; p13.1), -12, + mar[4]/46, XY[5]. Next-generation sequencing showed a fusion of MLL exon 12 to exon 1 of ELL.

Figure 2 Skin grafting after myeloid sarcoma resection.

Figure 3 Flow cytometric analysis of the bone marrow aspirate. A: Expression of CD45 of all cell populations; B: Increase of CD117 positive cells was demonstrated; C: Increase of CD117/HLA-DR positive cells was demonstrated; D: Increase of CD117/CD33 positive cells was demonstrated.

FINAL DIAGNOSIS

A diagnosis of MLL-ELL-positive AML (M2 subtype) with subcutaneous MS was made.

TREATMENT

Complete remission (CR) was achieved after the first course of standard 7  +  3 (idarubicin and cytarabine) induction chemotherapy. He then received 2 cycles of high-dose cytarabine-based consolidation therapy followed by a myeloablative, allogeneic, matched, unrelated-donor hematopoietic stem cell transplant.

OUTCOME AND FOLLOW-UP

When last seen in May 2023, he was still in CR.

DISCUSSION

To our knowledge, we present the first case in which MS was the only manifestation of adult MLL-ELL-positive AML. The molecular mechanisms underlying extramedullary involvement remain unknown, but 70% of MS cases have concurrent AML. “extramedullary AML tumor” may be a more accurate term for MS[6].

The MLL-ELL fusion gene is a rare occurrence among the various MLL fusion genes. It is associated with the genesis of AML in a mouse model[7]. MLL-ELL fusions are present in 12% of adult AML patients, 7% of pediatric AML patients and 15% of infant AML patients[8]. No concurrent MLL-ELL-positive MS cases have been mentioned in the literature, although two cases of MLL-ELL-positive MS with no evidence of AML have been reported[9,10]. Based on our findings and information from a few previous reports, we speculate that our patient had (1): Transformation of preleukemia cells in the marrow followed by spread to extramedullary sites; or and (2) homing of preleukemia cells to extramedullary sites, followed by spreading back to BM. This hypothesis has been proven in the development of blastic plasmacytoid dendritic cell neoplasm[4].

MLL-ELL-positive AML is associated with high response rates to conventional chemotherapy, but relapse is common, and some patients may benefit from allogeneic hematopoietic stem cell transplantation (allo-HSCT)[11]. Our patient achieved BM minimal residual disease-negative CR, and concurrently, 10% hematogones[5] existed in his BM, which may imply longer overall survival and a lower rate of acute graft-versus-host disease after HSCT.

CONCLUSION

In conclusion, MLL-ELL-positive AML with MS is a rare clinical entity. Additional research is needed to elucidate the molecular mechanisms of the pathogenesis of MS.