Name

Primary myelofibrosis

ICD-O-1 Morphology

9961/1: Myelosclerosis with myeloid metaplasia
9920/3: Megakaryoctyic myelosis
Effective 1978 - 1991

ICD-O-2 Morphology

9961/1: Myelosclerosis with myeloid metaplasia
9920/3: Megakaryocytic myelosis
Effective 1992 - 2000

ICD-O-3 Morphology

9961/3: Myelosclerosis with myeloid metaplasia
Effective 2001 and later

Reportable

for cases diagnosed 1978 and later

Primary Site(s)

C421
Primary site must be bone marrow (C421)

Grade

Not Applicable

Module Rule

None

Alternate Names

Chronic granulocytic-megakaryocytic myelosis
CIMF
Megakaryocytic myelosclerosis
MMM
Myelofibrosis-osteosclerosis
Myelofibrosis as a result of myeloproliferative disease
Myelosclerosis with myeloid metaplasia
PMF
Prefibrotic primary myelofibrosis
Primary myelofibrosis, prefibrotic/early stage
Primary myelofibrosis, overt fibrotic stage

Definition

Primary myelofibrosis (PMF) is a clonal myeloproliferative neoplasm (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 connective tissue and with extramedullary hematopoiesis.

There is a stepwise evolution from an initial pre/fibrotic early stage, characterized by hypercellular bone marrow with absent or minimal reticulin fibrosis, to an overt fibrotic stage with marked reticulin or collagen fibrosis in the bone marrow, and often osteosclerosis.

The fibrotic stage of PMF is clinically characterized by leukoerthroblastosis in the blood, hepatomegaly, and splenomegaly.

The diagnostic criteria for prefibrotic/early PMF (pre-PMF) are:

Major criteria
1. Megakaryocytic proliferation and atypia, without reticulin fibrosis .grade 1*, accompanied by increased age-adjusted BM cellularity, granulocytic proliferation, and often
decreased erythropoiesis
2. Not meeting the WHO criteria for BCR-ABL11 CML, PV, ET, myelodysplastic syndromes, or other myeloid neoplasms
3. Presence of JAK2, CALR, or MPL mutation or in the absence of these mutations, presence of another clonal marker,† or absence of minor reactive BM reticulin fibrosis

Minor criteria
Presence of at least 1 of the following, confirmed in 2 consecutive determinations:
a. Anemia not attributed to a comorbid condition
b. Leukocytosis $11 3 109/L
c. Palpable splenomegaly
d. LDH increased to above upper normal limit of institutional reference range
Diagnosis of pre-PMF requires meeting all 3 major criteria, and at least 1 minor criterion

Diagnosis of overt PMF requires meeting all 3 major criteria, and at least 1 minor criterion

Abstractor Notes

"Post essential thrombocythemia myelofibrosis" is not a diagnosis associated with 9961/3. It is a diagnosis associated with a progression of essential thrombocythemia (ET) (9962/3).

Radiation therapy and surgery (splenectomy) may be done for enlarged spleen.

Blood transfusions are given to correct anemia and should not be listed as treatment. Splenectomy may be done if the patient is symptomatic

Aspirin was previously documented as treatment for this disease. This was found to be incorrect. Treatment has been updated based on the NCI website (updated 6/12/15).

For more information, see the NCI website: https://www.cancer.gov/types/myeloproliferative/hp/chronic-treatment-pdq#section/_9

Definitive Diagnostic Methods

Clinical diagnosis
Genetic testing

Genetics Data

BCR-ABL1 fusion gene absent
CALR (~30% of cases)
del(13)(q12-22)
der(6)t(1;6)(q21-23;p21.3)
del(20q) and partial trisomy
Gains of chromosome 9 and/or 8
JAK2 V617F (~50% - 60% of cases)
MPL (~8% of cases)
Philadelphia (Ph) chromosome absent

Immunophenotyping

None

Treatments

Chemotherapy
Hematologic Transplant and/or Endocrine Procedures
Immunotherapy
Radiation therapy
Surgery

Transformations from

None

Corresponding ICD-9 Codes

238.76 Myelofibrosis with myeloid metaplasia

Corresponding ICD-10 Codes

D47.1 Chronic myeloproliferative disease

Corresponding ICD-10-CM Codes (U.S. only)

D47.4 Osteomyelofibrosis (effective October 01, 2015)

Signs and Symptoms

Bone pain
Early satiety
Night sweats
Thrombocytosis
Weight loss

Progression and Transformation

None

Epidemiology and Mortality

Age: 60-70's years median age
Incidence: 0.5-1.5 per 100,000 persons per year
Sex: no male or female predominance
Survival: 3-7 years for patients diagnosed in fibrotic stage; 10-15 years for patients diagnosed in early prefibrotic phase

Sources

Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J (Eds):
WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues (Revised 4th edition)
IARC: Lyon 2017
Section: Myeloproliferative neoplasms
Pages: 44-50

International Classification of Diseases for Oncology, Third Edition, First Revision. Geneva: World Health Organization, 2013.
Section: ICD-O-3.1 (2011) Morphological Codes
Pages: http://codes.iarc.fr/codegroup/2

National Cancer Institute
Section: General Information About Myeloproliferative Neoplasms
Pages: https://www.cancer.gov/types/myeloproliferative/hp/mds-mpd-treatment-pdq
Glossary