Table of Contents
Definition / general | Epidemiology | Pathophysiology | Etiology | Clinical features | Diagnosis | Laboratory | Radiology description | Prognostic factors | Case reports | Treatment | Gross description | Microscopic (histologic) description | Microscopic (histologic) images | Cytology description | Cytology images | Differential diagnosis | Additional referencesCite this page: Zhao X. Necrosis. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/bonemarrownecrosis.html. Accessed June 3rd, 2023.
Definition / general
- Definition: necrosis of myeloid tissue and medullary stroma in large areas of hematopoietic bone marrow (Cancer 2000;88:1769)
- Repeat biopsy may be needed for diagnosis (another site or after waiting for regeneration)
Epidemiology
- Rare, < 1% to 2% of bone marrow biopsies
- Often a severe complication of hematologic malignancies
- Seen in all age groups with no gender predilection
Pathophysiology
- Compromised microcirculation of oxygen and nutrients to bone marrow cells causes cell death
- Failure of microcirculation is due to inflammation related damage or mechanical obstruction (e.g. DIC, sickle cell disease, tumor emboli)
Etiology
- Associated with acute lymphoblastic leukemia (ALL) and is often discovered prior to its initial diagnosis or at time of recurrence of ALL
- May be associated with other lymphomas, solid tumor, myeloproliferative disorders or noncancerous conditions (Cancer 2000;88:1769):
- Infection
- Septic shock (Ann Fr Anesth Reanim 2004;23:501)
- Megaloblastic anemia
- Tuberculosis
- Drugs: e.g. fludarabine, imatinib mesylate, interferon alpha
- Sickle cell disease (Am J Med Sci 2000;320:342)
- Disseminated intravascular coagulation
- Hemolytic uremic syndrome
- Antiphospholipid syndrome
- Hyperparathyroidism
- Systemic lupus erythematosus (SLE)
Clinical features
- Bone pain in 75% (Cancer 2000;88:1769); may occur throughout body or localized to lower back / legs
- Fever in 69% (Cancer 2000;88:1769)
- Fatigue
- Jaundice
Diagnosis
- Bone marrow biopsy and aspirate demonstrate the histologic and cytologic features of necrosis and underlying diseases
- Should correlate with clinical and laboratory findings
Laboratory
- Anemia (91%), thrombocytopenia (78%), leukoerythroblastic findings (51%)
- Elevated lactic dehydrogenase (LDH) and alkaline phosphatase (ALP) in nearly 50% (Cancer 2000;88:1769)
Radiology description
- Bone marrow scanning
- Technetium 99m sulfur colloid and indium chloride localize selectively to reticuloendothelial elements of bone marrow, corresponding with areas of hematopoiesis
- Hematopoietic areas with changes greater than 2 cm can be visualized
- In bone marrow necrosis, there is little or no isotope uptake throughout the bone marrow cavity; bone marrow scintigraphy confirms the absence of hematopoiesis and also identifies the existence of residual bone marrow activity from which material can be obtained via guided aspiration or biopsy
- In recovery, reappearance of normal hematopoiesis is observed
- Nuclear magnetic resonance
- Noninvasive method to evaluate a large fraction of bone marrow
- Changes in bone marrow signal intensities reflect changes in proportions of fat and water contained in cellular elements
- Bone marrow necrosis is characterized by an increase of water content due to watery changes of bone marrow and replacement of fat by serous material
- While somewhat nondiagnostic, MRI can show the extent of necrosis and can serve as a guide to biopsy sites in which viable hematopoietic bone marrow is suspected; MRI can also document conversion from abnormal to normal bone marrow (Cancer 2000;88:1769)
Prognostic factors
- Greatly dependent on age of patient and nature of associated disease:
- Children with ALL and bone marrow necrosis appear to have the same prognosis as those without necrosis
- Adults with bone marrow necrosis associated with a noncancerous condition may have a better chance of complete recovery and long term survival than adults with bone marrow necrosis associated with a hematologic malignancy
- May be difficult to determine if necrosis is due to a drug or DIC versus an underlying malignancy; prognosis in these cases is difficult to predict
- Often short survival (Indian J Pathol Microbiol 2000;43:47)
Case reports
- 14 year old boy with idiopathic bone marrow necrosis (J Clin Diagn Res 2013;7:525)
- 66 year old man with G-CSF associated bone marrow necrosis in AML after induction chemotherapy (Case Rep Hematol 2012;2012:314278)
- Bone marrow necrosis associated with imatinib mesylate in patient with Philadelphia chromosome+ ALL (Ann Hematol 2006;85:542)
- Bone marrow necrosis as presenting feature of childhood ALL (Pediatr Blood Cancer 2007;49:367)
Treatment
- Treat underlying disease; provide supportive measures for associated anemia, pancytopenia, thrombocytopenia, embolic processes or other complications
- Corticosteroids for CREST syndrome (Eur J Haematol 2005;74:75)
Gross description
- Gelatinous aspirated specimen
Microscopic (histologic) description
- On trephine biopsy, disruption of normal bone marrow architecture with considerable loss of fat spaces
- Early: nuclear pyknosis and karyorrhexis
- Late: all cell outlines gone, serous transformation of marrow
Microscopic (histologic) images
Cytology description
- Amorphous proteinaceous material
- Enmeshed ghost-like hematopoietic cells with irregular or indistinct cell membranes
- Cytoplasm may shrink or be vacuolated
- Nuclear features are indicative of necrosis (pyknosis, karyorrhexis, karyolysis)
Cytology images
Differential diagnosis
- Avascular bone necrosis: may show destruction of spicular architecture
- Marrow aplasia: usually only a loss of myeloid components with no destruction of the reticular architecture
Additional references