Bone marrow - nonneoplastic
Benign changes
Necrosis

Author: Xiangrong (Alex) Zhao, M.D., Ph.D. (see Authors page)

Revised: 11 July 2017, last major update December 2013

Copyright: (c) 2002-2017, PathologyOutlines.com, Inc.

PubMed Search: Bone marrow necrosis [title]

Cite this page: Necrosis. PathologyOutlines.com website. http://pathologyoutlines.com/topic/bonemarrownecrosis.html. Accessed July 25th, 2017.
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
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
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

Images hosted on other servers:

Necrotic and nonnecrotic areas

Disruption of normal bone marrow architecture

With TTP and colon carcinoma

Antiphospholipid syndrome

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

Images hosted on other servers:

Nuclear features associated with necrosis

Ghost-like hematopoietic cells

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