Acute myeloid leukemia with RAM immunophenotype presenting with extensive mesenteric and retroperitoneal lymphadenopathy: A case report and review of the literature

Abstract

Acute myeloid leukemia (AML) with RAM immunophenotype is a rare recently described AML subtype. It is defined by blasts with strong expression of CD56 and weak to absent expression of CD45, HLA-DR....., and CD38 and characterized by significantly worse outcome [1] . Little is known about the clinical presentation and this immunophenotype is not widely recognized in clinical practice. We describe a case of AML with RAM immunophenotype in a 5-year-old male patient with a unique presentation, including extensive mesenteric and retroperitoneal lymphadenopathy. Diagnostic studies included bilateral bone marrow and lymph node biopsies, flow cytometry, cytogenetics, fluorescence in-situ hybridization (FISH), and next generation sequencing. Bone marrow biopsy revealed >90% blasts, positive for CD34, CD117, and CD56 by flow cytometry and immunohistochemistry. Next generation sequencing revealed BCOR loss and CBFA2T3-GLIS2 fusion. Following induction chemotherapy, bone marrow biopsy showed residual disease and a stem cell transplant was performed. The patient relapsed three months after transplant and subsequently passed away eleven months after initial diagnosis. Limited literature is available describing this newly identified AML subset. The RAM immunophenotype has been identified as an independent prognostic factor for relapse rate and overall and disease-free survival [1] . Few case reports are available to characterize the genetic profile, typical presentation, and clinical course of patients with this unique immunophenotype.

Acute myeloid leukemia with RAM immunophenotype: A new underdiagnosed entity

“…This conundrum was resolved, however, by using stem cell myeloid markers such as CD34 and CD 117 9 . Our biopsy and IHC findings of the blasts being positive for CD34, CD117, and CD56 (diffuse and strong) are similar to the biopsy and IHC findings as reported by Wick et al 14 None of the previously reported cases have a prior history of myeloid sarcoma except for one of the twins as reported by Abu‐Arja et al, 10 in which the second twin had developed myeloid sarcoma after therapy and succumbed to it. Zangrando et al 18 observed similar CD56 expression and a diagnostic dilemma in AML RAM versus solid tumor metastasis on flow cytometry, where CD56 showed comparable expression in both cases, along with dim to negative CD45 and CD38.…”

“…On immunophenotyping, we observed a similar pattern of expression of markers as that reported previously 1,2,4,5,9–11,13–15,20 . All of the cases had dim to negative CD45 and CD38, along with negative HLA DR and bright CD56 expression.…”

“…Cytogenetics done using conventional karyotyping in our cohort showed a normal karyotype in 4/5 cases, indicating intermediate risk AML. One case showed 46,XY,add(19)(p13)[35]/46,XY 14 . There was no case of Down syndrome in our cohort.…”

“…Cytogenetic study was done in 5/7 patients using conventional karyotyping, of whomfour patient revealed no cytogenetic abnormality. One patient showed 46,XY,add(19)(p13)[35]/46,XY 14 . None of the cases showed any association to trisomy 21.…”

“…There is a high frequency of acute megakaryoblastic leukemia (AMKL) among the RAM phenotype 1,2,5,9,10 . A high prevalence of more than 60% of the CBFA2T3‐GLIS2 fusion gene, which may act as pathogenic driver in this group of patients, is also reported in the literature 1,2,5,10–15 . This phenotype is associated with a significantly worse outcome with a high induction failure rate and poor event free and overall survival 1,2,5,10,11 .…”