Acute Myeloid Leukemia with a Glossal Mass

Introduction

Acute Myeloid Leukemia (AML) is an aggressive heterogeneous cancer of the bone marrow that stems from the unrestrained expansion of diseased hematopoietic cells coupled with a state of maturation arrest. Accounting for around 10% of cases, AML can manifest with extramedullary (EM) involvement. Common sites include soft tissues, skin, lymph nodes, and rarely the CNS. EM disease can be an additional risk for poor disease outcomes.

Case Presentation

A 37-year-old male was referred to our center as a case of acute leukemia. He had persistent fever, flu-like symptoms, and cervical lymphadenopathy three weeks prior. His initial leukocyte count was (150,000/microliter) with 90% peripheral blood blasts. He was started on oral cytoreductive therapy. Additionally, he was troubled by a slowly enlarging and painful lesion over the tip of his tongue (Figure 1a). Bone marrow examination revealed 90% myeloid blasts that were positive for CD33, CD13, CD117, HLA-DR, CD34, CD38, and cMPO (partial), confirming the AML diagnosis. The karyotype was normal, and the FLT3-ITD mutation was present by PCR. NGS-Myeloid confirmed the presence of FLT3-ITD mutation with variant allele frequency (VAF) of 17.4% and revealed WT1 with VAF of 44.8%.

MRI scan showed diffuse ill-defined signal abnormality of the anterior third of the tongue (Figure 1b) in intermediate signal T1, high signal STIR with post-contrast enhancement, measuring 2.8 x 2.1 x 2 cm. Premaxillary right-sided soft tissue thickening and enhancement, measuring 16 x 13 x 9 mm. Sub-centimetric submental lymph nodes (IA). Bilateral enlarged jugular lymph nodes at levels IIA, IIB, and III, the largest measuring 1.9 x 1.5 cm on the right side and 2.3 x 1.3 cm on the left.

Limited by the patient's refusal to undergo a biopsy of the tongue mass to confirm the likelihood of EM involvement, he received standard protocol for AML induction with the addition of Sorafenib. Despite the full resolution of the tongue mass clinically and radiologically, repeated bone marrow examination showed persistent disease at 45% myeloblasts infiltration. He was successfully salvaged with a combination of Gilteritinib, Azacitidine, and Venetoclax, which was followed by myeloablative allogeneic stem cell transplantation from a matched related donor. The patient has been in remission since then.

Discussion

The ongoing discoveries to untangle the molecular diversities in AML biology have and will continue to point out important pieces of the puzzle that can help further individualize therapies for patients. The collective findings of these studies drew a near complete picture of the current vast heterogeneity of AML biology; however, using a unified treatment strategy can only paint “less colorful” disease outcomes. Novel therapies continue to demonstrate their durability of response via their targeted hits and exhaustion of the cancer cells pool over conventional therapies aimed at undifferentiated cellular demise.

The presence of EM disease poses an additional challenge against favorable outcomes of AML treatment, necessitating the incorporation of more definitive interventions like stem cell transplantation to “contain” the disease and improve its outcomes whenever EM disease can be identified. In fact, molecular imaging can identify more cases of EM disease, increasing the estimation of its prevalence to around 20%. This may suggest looking for “occult” EM disease according to certain disease characteristics to inform our management for such unique cases. Molecularly, the risk for EM disease has been associated with certain mutations like FLT3-ITD and WT1, which were present in our patient, displaying EM involvement as an “early warning sign” for refractoriness to conventional therapy.

The threshold to use upfront novel strategies should be lower in the presence of additive risks, like EM disease with a less favorable molecular profile, toward achieving sustainable disease control in these patients. In fact, this can be the only strategy to offset these risks that are responsible for observed heterogeneity in treatment outcomes. The presence of EM involvement should call for “extra measures”. Notably, using a better-targeted therapy early on can ensure successful disease eradication and minimize the chance of fueling the emergence of more resistant clones that were inevitably selected using less novel and conventional therapy.

No relevant conflicts of interest to declare.