These abnormal cells ( which could be either cancer cells, granulomas or fibrosis) result in disturbed hematopoiesis due to the following reasons:
- By physically replacing the native marrow cells
- By disturbing the bone marrow architecture
- By causing reactive fibrosis
The end result is that the ability of the bone marrow to produce blood cells is reduced resulting in pancytopenia.
The word myelo refers to bone marrow, and the word phthysis means shrinkage or atrophy.
- Metastatic cancer: cancers of breast, prostate, kidney, lung, adrenal, thyroid, etc
- Lymphoproliferative malignancy: lymphomas
- Granulomatous infectious diseases: miliary tuberculosis, fungal infections
- Necrosis in sickle cell disease and septicemia
- Bone disease in congenital osteopetrosis
- Lipid storage diseases such as Gaucher’s disease
- Primary and secondary myelofibrosis
- Evolution from polycythemia vera or essential thrombocythemia
Epidemiology and Prognosis
Myelophthisis shows a higher incidence in countries where healthcare access is limited and diseases are allowed to progress to advanced stages. In developed countries, it occurs in less than 10% of metastatic cancer patients.
Prognosis depends on the underlying condition. Patients with end-stage metastatic cancer have an extremely poor prognosis. On the other hand, infectious causes like tuberculosis, etc are completely amenable to treatment.
These depend on the underlying disease.
Anemia may cause skin pallor, weakness, fatigue, general malaise, poor concentration and shortness of breath. Patients with reduced leucocytes or severe neutropenia may show signs of infection and present with fever. Severe reduction in platelet count may result in bleeding from various sites, petechiae or ecchymoses.
Patients may present with pancytopenia that is, a reduced number of all the formed elements of the blood. The resultant anemia, neutropenia, and thrombocytopenia may be of mild, moderate or severe degree.
The characteristic feature is a leukoerythroblastic blood picture which is defined by the presence of immature erythroid (nucleated red blood cells) and myeloid (neutrophil) precursor cells in peripheral blood. This occurs due to extramedullary hematopoiesis or disruption of the marrow sinusoids which causes the release of immature cells into the peripheral circulation.
The following features are seen on blood film:
- Red cells exhibit variation in size and shape (anisocytosis and poikilocytosis) with the presence of teardrop forms (dacrocytes). Red cells are usually normocytic normochromic but occasionally may be slightly macrocytic. Nucleated red blood cells may also be seen.
- Immature white blood cells (myelocytes, metamyelocytes, occasionally promyelocytes and myeloblasts) are usually present in variable numbers.
- The platelet count is often low. Platelets are often bizarre in shape and large in size (giant platelets).
Read more about Abnormal RBC Types and Shapes
Bone Marrow Aspiration and Biopsy
Although peripheral blood smear findings are suggestive, definitive diagnosis requires bone marrow examination.
Bone marrow aspiration usually yields a dry tap, because myelofibrosis makes it difficult to aspirate the marrow particles.
Bone marrow biopsy shows replacement of the normal bone marrow by fibrosis, malignancy, granuloma or other infiltrative processes. Groups or sheets of malignant cells may be seen replacing the bone marrow in case of underlying malignancy. In tuberculosis, caseating granulomas are seen along with Langhans-type giant cells. Zeihl Neelsen stain may demonstrate the presence of acid-fast bacilli.
There may be evidence of splenomegaly and /or hepatomegaly due to extramedullary hematopoiesis in these organs.
They are not required per se for diagnosis. If obtained incidentally, they may reveal characteristic features that may suggest the underlying lesion.
Myelosclerosis may be seen in long-standing myelofibrosis. Osteoblastic or osteolytic lesions of the bone may be seen in specific tumors.
They are quite sensitive for detecting bony abnormalities found in myelophthisic anemia. They can also detect bone metastases.
Magnetic Resonance Imaging (MRI) Scans
MRI scan of a particular area can detect infiltration of the bone marrow by tumor or any space-occupying lesion.
The presence of immature blood cell precursors helps to differentiate myelophthisic anemia from other causes of pancytopenia, like aplastic anemia. As hematopoietic cells are damaged in aplastic anemia, immature blood cells are not seen in the peripheral blood.
Differentiation of myelophthisic process from a primary myeloproliferative syndrome requires molecular testing including cytogenetic evaluation and fluorescent in situ hybridization (FISH) to prove clonality of the stem cells.
- Treatment of the underlying disorder
- Transfusions as needed
The mainstay of treatment is treating the underlying disorder. Supportive treatment is provided for symptomatic patients.
Anemia is treated with blood transfusions (packed red blood cells) or in rare cases by supplemental erythropoietin therapy.
Patients with low levels of white cells or platelets generally do not need treatment unless bleeding or infection is present.