진성 적혈구 증가증. Polycythemia vera (PV)

다양한 혈액종양질환을 정리하고 있습니다.

 

오늘은 골수증식성 종양 (Myeloproiferative neoplasm, MPN) 중 

진성 적혈구 증가증. (Polycythemia vera, PV)에 대해 알아보겠습니다.

 

귀여운 라이언이 Polycythemia vera, 진성적혈구증가증을 가리키고 있어요!

 

1. Definition

Polycythemia vera(PV) is a chronic MPN characterized by increased RBC production independent of the mechanisms that normally regulate erythropoiesis.

Almost all patients carry somatic JAK2 V617F gain-of-function mutation or another functionally similar JAK2 exon12 mutation that results in proliferation not only of the erythroid lineage, but also of granulocytes and megakaryocytes (i.e. panmyelosis).

진성적혈구 증가증에는 3가지 phase가 있다. 뒤에서 좀 더 자세히 설명할 예정!

1) Polycythemic phase

2) Post-polycythemic myelofibrosis phase (= post-PV MF phase)

3) Balst phase

 

 

Q. 진성 적혈구 증가증에서 골수 검사가 필요한 이유는 무엇일까?

Hb, Hematocrit 상승과 JAK2-related mutation만 증명되면 진단 내릴 수 있는 것 아닌가?

 

A. 일부 JAK2(+) PV에서는 혈소판 증가증을 보이고 Hb level이 낮은 값을 보이는 경우가 있어 ET와 감별이 필요하다. 즉, JAK2 mutation은 PV에 특이적인 유전적 변이가 아니고 MPN에서 모두 나타날 수 있다. 따라서, 확실한 진단을 하기 위해서는 반드시 골수 검사를 통해 모든 lineage의 cell들이 증가되어 있는지(panmyelosis) 확인하고 Reticulin/MT stain을 통해 fibrosis 정도를 파악하는 과정 등이 필요하다.

+ JAK2 mutation의 variant allele frequencey(VAF)가 50% 이상으로 높으면 ET보다는 PV, PMF을 우선적으로 고려할 수 있다.

 

2. Localization

The peripheral blood and bone marrow are the major sites of involvement, but the spleen and liver are also affected and are the major sites of extramedullary hematopoiesis in later stages.

However, any organ can be damaged as a result of the vascular consequences of the increased RBC mass.

 

3. Clinical features

The major Sx of PV are related to HTN or vascular abnormalities caused by the increased RBC mass and increased visocity of blood.

- Venous/Arterial thrombosis : DVT, MI, Stroke, Mesenteric/Portal/Splenic vein thrombosis, Budd-Chiari syndrome

- Headache

- Dizziness

- Visual disturbances

- Paresthesia

- Other minor Sx : pruritus, erythromelalgia, gout

- 신체 진찰 시, plethora, palpable splenomegaly, hepatomegaly가 발견될 수 있다.

 

4. Microscopy

1) Polycythemic Phase

Peripheral Blood

- Mild to overt excess of normochromic, normocytic RBCs

- Immature granulocyte may be detectable, but myeloblasts are generally not observed, unless on blast phase.

 

Bone Marrow

- Age-adjusted cellularity is increased.

- Hypercellularity is especially noteworthy in the subcortical marrow space, which is normally hypocellular.

- Panmyelosis is prominent, especially on Erythroid and Megakaryocytic lineage.

 

2) Post-polycythemic myelofibrosis Phase

- Polycythemic phase에서 RBC를 과도하게 많이 생산하다보면 골수 내 Iron이 소진되고 IDA(Iron deficiency anemia)에서처럼 MCV, MCH가 감소하여 microcytic hypochromic anemia 로 이어진다.

- During the later phases of PV, erythropoiesis progressively decreases.

- As a result, the RBC mass normalizes and then decreases, and the spleen further enlarges.

- The splenic enlargement is a consequence of extramedullary hematopoiesis, which is characterized by the trilineage elements in the splenic sinuses and cords of Billroth.

3) Blast Phase

- Cases with ≥20% blasts are considered to be blast-phase post-PV MF.

 

5. Genetic Profile

The most common genetic abnormality in PV is the somatic gain-of-function mutation JAK2 V617F.

Although this muatation occurs >95% of patients with PV, it is not specific for this entity; it is found in other MPNs and is also seen in a small subset(<5%) of cases of AML/MDS/CMML etc.

At diagnosis, chromosomal abnormalities are detectable only in 20% cases. The frequency of chr abnormalities increases with disease progression; 80~90% are seen in cases of post-PV myelofibrosis.

 

 

Ref)

The WHO Classification of Tumours of Haematopoietic and LymphoidTissues, IARC 2017