원발성 골수섬유화증. Primary myelofibrosis (PMF)

다양한 혈액종양질환을 정리하고 있습니다.

 

오늘은 골수증식성 종양 (Myeloproiferative neoplasm, MPN) 중 

원발성 골수섬유화증 (Primary myelofibrosis, PMF)에 대해 알아보겠습니다.

 

귀여운 라이언이 원발성 골수섬유화증, Primary myelofibrosis를 가리키고 있네요!

 

1.  Definition

Primary myelofibrosis (PMF) is a clonal MPN characterized by a proliferation of predominantly abnormal megakaryocytes and granulocytes in the bone marrow, which in fully developed disease is associated with reactive deposition of fibrous connectie tissue and with extramedullary hematopoiesis.

 

PMF는 크게 2가지 stage가 있습니다.

1) Pre-fibrotic/early stage

- Hypercellular BM with absent/minimal fibrosis

Prefibrotic PMF의 진단기준

2) Overt fibrotic stage

- 골수가 섬유화되어 immature한 적혈구,백혈구들이 완전 성숙해지지 못한 채로 말초혈액으로 삐져나옵니다. 

- Marked BM fibrosis and often osteosclerosis

- Leukoerythroblastosis

- Anisopoikilocytosis, 특히 tear-drop cell이 관찰됩니다.

- Splenomegaly, Hepatomegaly

Overt PMF의 진단기준

 

2. Localization

The blood and bone marrow are always involved.

In the later stages of the disease, extramedullary hematopoiesis (= myeloid metaplasia) becomes prominent, particularly in the spleen. Increase in the number of circulating CD34+ cells is a phenomenon largely restricted to overt PMF.

 

3. Clinical features

As many as 30% of the cases are asymptomatic at the time of diagnosis, and are discovered by detection of splenomegaly or abnormal CBC(anemia, leukocytosis, leukoerythroblastic feature, thrombocytosis etc).

More than 50% of patients with PMF experience constitutional Sx, including,

- fatigue

- dyspnea

- weight loss

- night sweat

- low-grade fever

PMF의 진행 과정

4. Microscopy

Prefibrotic/early PMF

30~50% of PMF cases are first detected in the prefibrotic early stage, with no significant increase in reticulin and/or collagen fibers. (Grade MF-0 or 1)

- BM biopsy usually shows hypercellularity, with an increase in the number of neutrophils and atypical megakaryocytes.

- Erythropoiesis is reduced, with no dysplastic features.

- Megakaryocytes are markedly abnormal, and their morphological atypia and topographical distribution within the BM are critical for the recognition of pre-PMF and DDx with ET. They often form dense clusters, which are frequently adjacetn to the BM vascular sinuses and bone trabeculae. Size of megakaryocytes are variable. Overall, megakaryocytes in pre-PMF are more atypical than in any other type of MPN.

 

Overt primary myelofibrosis

Peripheral Blood

- Leukoerythroblastosis : Left-shifted maturation of granulocytic series + nRBCs

- Anisopoikilocytosis, typically with tear-drop cells

Bone Marrow

- Hypocellular BM with marked reticulin or collagen fibrosis. (Grade MF-2 or 3)

- Organomegaly caused by extramedullary hematopoiesis

 

Extramedullary hematopoiesis

The most common site of extramedullary hematopoiesis is spleen, followed by the liver. Possibility of a myeloid sarcoma should be considered and examined through IHC studies with CD34, CD117(KIT).

 

5. Genetic profile

지난번 게시물에서 말했듯이, MPN 관련 유전적 변이들(JAK2 V617F, JAK2 exon 12, MPL W515K/L, CALR)은 질환별로 특이적이지는 않습니다.

다만, JAK2 V617F 의 variant allele frequency(VAF)가 높을수록 PV 보다는 ET/PMF일 가능성이 높다고 밝혀져있습니다.

아래 그림은 관련 논문에서 따온 Figure입니다.

 

Ref 1)

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

Ref 2)

Park SH, Chi HS, Cho YU, Jang S, Park CJ. The allele burden of JAK2 V617F can aid in differential diagnosis of Philadelphia Chromosome-Negative Myeloproliferative Neoplasm. Blood Res. 2013 Jun;48(2):128-32.