A 58-year-old woman presents to the clinic for a follow-up evaluation after routine laboratory studies showed a platelet count of 850,000/μL. She is asymptomatic except for occasional burning pain and redness in her fingertips, which is relieved by cooling and aspirin. She denies fever, weight loss, or easy bruising. Past medical history is negative, and she does not take any medications. Vital signs are within normal limits. Physical examination is unremarkable, with no palpable splenomegaly.
Laboratory studies show the following:
Hemoglobin: 13.8 g/dL
White blood cell count: 9,200/μL
Peripheral smear: Large, mature platelets with frequent clustering; no peripheral blasts.
Inflammatory markers (ESR/CRP): Normal
Iron studies: Normal
BCR-ABL1 fusion gene: Negative
JAK2 V617F mutation: Positive
Which of the following is the most likely additional finding in this patient?
The correct answer is:
C) Increased number of enlarged, mature megakaryocytes in the bone marrow
This patient is presenting with essential Thrombocythemia (ET), a chronic myeloproliferative neoplasm characterized by the autonomous overproduction of platelets. The burning pain and redness in her extremities describe erythromelalgia, a classic microvascular complication of ET caused by platelet-mediated inflammation and occlusion. The diagnosis of ET requires a sustained platelet count >450,000/μL, the presence of a driver mutation (JAK2 in 50–60%, CALR in 25%, or MPL in 5%), and the exclusion of other myeloproliferative disorders or reactive causes. Bone marrow biopsy typically shows a dramatic increase in large, mature-appearing megakaryocytes with deeply lobulated ("staghorn") nuclei, often occurring in clusters.
Answer choice A: Absence of the Philadelphia chromosome in myeloid precursors, is incorrect. While it is true that ET is Philadelphia chromosome-negative, the absence of a translocation is an exclusion criterion rather than a characteristic finding found upon further diagnostic testing of the bone marrow.
Answer choice B: Erythropoietin (EPO) level below the reference range, is incorrect. A low erythropoietin level is a major diagnostic criterion for polycythemia vera (PV). In ET, the hemoglobin and EPO levels are typically within the normal range.
Answer choice D: Markedly increased reticulin fibrosis on bone marrow biopsy, is incorrect. This is the hallmark of primary myelofibrosis (PMF). While ET can eventually progress to a fibrotic phase, markedly increased fibrosis at presentation points toward PMF, which would also typically feature teardrop-shaped red cells (dacrocytes) and splenomegaly.
Answer choice E: Presence of "starry sky" macrophages in the lymph nodes, is incorrect. This is the classic histological description of Burkitt Lymphoma, an aggressive B-cell malignancy that does not present with isolated thrombocytosis.
Key Learning Point
Essential thrombocythemia (ET) is a diagnosis of exclusion that presents with extreme thrombocytosis and a risk of both thrombosis and hemorrhage. The most common driver mutation is JAK2 V617F. Bone marrow biopsy shows a proliferation of large, mature megakaryocytes. Treatment for high-risk patients (age >60 years or history of thrombosis) involves hydroxyurea and low-dose aspirin.
