Second Known Case of Concurrent ET, WM Raises Questions About Their Coexistence

In a rare medical finding, physicians have documented the second known case worldwide of concurrent essential thrombocythemia (ET) and Waldenström macroglobulinemia (WM).1 The case, recently documented in Case Reports in Hematology, is underscoring the clinical challenges and unanswered questions surrounding the coexistence of myeloproliferative and lymphoplasmacytic malignancies.

ET, a chronic myeloproliferative neoplasm (MPN), is characterized by overproduction of platelets, often linked to mutations in JAK2, CALR, or MPL gene, while WM is a B-cell lymphoproliferative disorder defined by infiltration of bone marrow with lymphoplasmacytic cells and secretion of monoclonal IgM protein.

The similarities between the 2 reported cases raise questions about whether these malignancies share environmental or genetic triggers. | Image credit: keetazalay - stock.adobe.com

In this new patient case, ET was managed successfully with cytoreduction, though the smoldering WM required ongoing surveillance. As the researchers noted, the rarity of such cases underscores the need for broader studies to explore shared genetic and environmental mechanisms and to guide treatment strategies when patients face more than one hematologic malignancy.

“Both WM and ET are rare diseases. Their co-occurrence in a single patient raises the possibility of a shared mechanism in the process of neoplastic transformation,” wrote the researchers. The group noted that the mutations responsible for predisposing patients to myeloproliferative diseases are the same as those for MPNs. These include JAK2, MPL, and CALR.

The patient, a 64-year-old Caucasian man, presented with headaches, noncardiac chest pain, and fatigue. His medical history included atrial fibrillation and autoimmune thyroiditis. Notably, his family history revealed multiple cases of WM and multiple myeloma across several paternal relatives, suggesting a strong inherited predisposition.

Initial bloodwork showed elevated platelets (743×10⁹/L), leading to testing for JAK2 mutation, which was positive and confirmed a diagnosis of ET. However, given the family history, clinicians also ordered serum protein electrophoresis, which revealed an IgM “M spike,” prompting further evaluation for WM. Bone marrow biopsies confirmed both disorders: ET driven by JAK2 V617F mutation and WM characterized by MYD88 L265P mutation. Genetic testing suggested these arose independently, rather than from a shared malignant clone.

The distinct genetic drivers seen in this patient suggest independent neoplastic events rather than a shared transformation, explained the researchers. However, the clustering of plasma cell malignancies in his family points to inherited risk factors that may predispose them to multiple hematologic cancers. Environmental exposures, including the patient’s history of herbicide and pesticide contact, may also have contributed.

“Given our patient’s documented multigenerational family history of WM and MM, a common exposure or genetic predisposition is possible,” explained the researchers. “Some, but not all, studies have found an association between pesticide exposure and MPNs, but we did not identify consistent common exposures within the family cohort; three of the six family members with plasma cell malignancies had heavy farm chemical exposures, but the other 3 had no such pesticide history.”

The patient was treated with hydroxyurea and aspirin to control platelet counts and symptoms related to ET, normalizing platelet levels and improving symptoms. WM remained smoldering, marked by rising IgM levels but without symptoms requiring treatment. Clinicians opted for observation, consistent with guidelines to avoid early exposure to potentially toxic therapies in indolent WM.

Over 5 years of follow-up, the patient’s hemoglobin declined modestly and IgM levels rose from 500 mg/dL to nearly 2800 mg/dL. Despite progression, the patient has not developed anemia severe enough or clinical symptoms to warrant WM-directed therapy.

The only previously published case involved a 55-year-old Chinese man diagnosed with both ET and WM, also harboring JAK2 V617F and MYD88 L265P mutations.2 That patient responded to pegylated interferon, which is known to have activity in both MPNs and WM. The similarities between the two cases, including the mutational profile, absence of organomegaly, and dual diagnoses, raise questions about whether these malignancies share environmental or genetic triggers, noted the researchers.1

References

1. Wallace M, Mathey B, Yeung CCS, Appelbaum JS, Wallace M. Coexistence of essential thrombocythemia and Waldenström macroglobulinemia: a case report. Case Rep Hematol. Published online August 28, 2025. doi:10.1155/crh/3390770

2. Lu N, Neoh CL, Ruan Z, et al. Essential thrombocythaemia with concomitant Waldenström macroglobulinemia: case report and literature review. Onco Targets Ther. 2020;12:3431-3435. doi:10.2147/OTT.S245950