The occurrence of monoclonal gammopathy of undetermined significance (MGUS) and essential thrombocytopenia (ET) in the same patient is quite rare [1-3], usually manifesting as an incidental finding. In addition, the coexistence of multiple myeloma (MM) with ET has also been rarely reported [4-8]. Moreover, the evolution of MGUS to MM simultaneously with blastic transformation of ET in the form of acute biphenotypic leukemia, as observed in this report, represents an exceptionally rare occurrence. With an anecdotal purpose, we herein report the long-term clinical history of a patient who presented with concomitant evolution of MGUS to MM and from ET to acute biphenotypic leukemia, with the original diagnosis of MGUS and ET occurring 37 years prior.

In 2010, a 77-year-old man presented to our center with increasing thrombocytosis and monoclonal paraproteinemia (IgG lambda). In 1975, at another center, he was diagnosed with MGUS associated with ET. The patient was managed according to the prevalent clinical guidelines and received low-dose acetylsalicylic acid (LD-ASA). Upon presentation to our clinic (35 years after original diagnosis and treatment), he reported that for several years he had not been followed up by periodic laboratory evaluations and hematologic examinations. Therefore, a comprehensive work-up, including a bone marrow (BM) aspirate and trephine biopsy, was performed. Megakaryocytic hyperplasia and clustering consistent with ET, along with an infiltration of IgG kappa clonally mature plasma cells (PC) consistent with MGUS, was noted. Janus kinase 2 (JAK 2) V617F, P190, and P210 mutation analyses revealed no abnormalities. In addition, no defining features potentially associated with POEMS syndrome [9], which may be suspected on the basis of the coexistence of a JAK 2-negative thrombocytosis with a monoclonal component, were found by comprehensive work-up; in particular, no organomegalies, skin changes, peripheral nerve abnormalities, or endocrinopathy were present. The radiological evaluation of his skeleton ruled out both lytic and sclerotic bone changes. Human immunodeficiency virus, hepatitis C virus, and hepatitis B virus infections were ruled out by serological evaluations. Therefore, the patient was diagnosed with IgG lambda MGUS concomitant with JAK 2-negative ET. Given the remarkable thrombocytosis (platelet count, >1,000×10⁹/L), hydroxyurea was added to LD-ASA. Thereafter, the patient was regularly followed up until 2 years later when his hemogram showed pancytopenia concomitant with an increase in monoclonal protein concentration higher than 4 g/dL. At that time, examination of a BM aspirate revealed a 30% proportion of clonal IgG kappa PC along with 20% blasts; the latter cells, showed coexpression of lymphoid and myeloid markers, being positive for CD34, CD13, CD33, HLA-DR, CD19, and CD22. BM trephine biopsy (Fig. 1) confirmed BM infiltration by PC and blasts. Conventional cytogenetic and fluorescence in situ hybridization revealed a normal karyotype; negative JAK 2 V617F, P190, and P210 mutation analyses were confirmed. Unfortunately, no other molecular studies were performed. Physical examination revealed no remarkable findings; in particular, neither upper abdominal organomegalies nor superficial adenomegalies was palpable. Laboratory and radiologic evaluations revealed moderate Bence Jones proteinuria (lambda type) and mild pancytopenia but no other abnormalities were found. In particular, serum calcium and comprehensive metabolic, renal, hepatic, and coagulative panel results were normal. In addition, skeletal survey showed neither lytic nor sclerotic lesions throughout the axial and appendicular skeleton. The diagnosis of MM coexisting with secondary acute biphenotypic phenotype was made. The patient was evaluated as a possible candidate for treatment with hypomethylating agents, but his condition suddenly deteriorated and he died of pneumonia.

This case lacks practical therapeutic implications and reliable indications for the management of this uncommon occurrence, and our report has only anecdotal value. However, the overlapping occurrence of acute biphenotypic leukemia transformed from ET and MM is extremely rare. We speculate that the synchronous evolution of ET and MGUS along with coexpression of lymphoid antigens by blastic cells could suggest a common origin of these 2 malignancies, potentially evolving from a common precursor by progressive transformation to more aggressive disorders [5]. However, this hypothesis remains to be investigated.