Indian Journal of Pathology and Microbiology
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Year : 2018  |  Volume : 61  |  Issue : 4  |  Page : 623-625
Bone marrow edema mimicking amyloid

Department of Pathology, University College of Medical Sciences and Guru Teg Bahadur Hospital, New Delhi, India

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Date of Web Publication10-Oct-2018

How to cite this article:
Garg N, Bansal D, Mangla G, Kotru M. Bone marrow edema mimicking amyloid. Indian J Pathol Microbiol 2018;61:623-5

How to cite this URL:
Garg N, Bansal D, Mangla G, Kotru M. Bone marrow edema mimicking amyloid. Indian J Pathol Microbiol [serial online] 2018 [cited 2021 Feb 26];61:623-5. Available from: https://www.ijpmonline.org/text.asp?2018/61/4/623/243008

Bone marrow edema (BME) has been a topic of increasing interest among radiologists as it serves as an early indicator of numerous pathologies on imaging.[1] In histopathology, it is recognized as an eosinophilic material deposition in the BM biopsies (BMB). This case highlights the importance of recognition of BME (eosinophilic material), its differential diagnosis, and an approach to diagnosis.

A 55-year-old male, hypertensive, presented with swelling all over the body for 2½ months, associated with decreased urine output, backache, and abdominal pain. There was no organomegaly. His blood urea was 177 mg/dL, serum creatinine 5.2 mg/L, and ultrasonography kidneys, ureters, and bladder was normal. Gross ascites and bilateral pleural effusion were present. Hyperkalemia (serum potassium = 5.3 meq/L) and hypocalcemia (serum calcium = 7.5 mg/dL), total protein (6.5 g/dL), and albumin (3.2 g/dL) were normal. Hematological investigations including BM were done to rule out multiple myeloma (MM). Hemogram and peripheral smear (PS) revealed severe normocytic normochromic anemia (Hb = 5.8 g/dL) with a normal leukocyte (5.6 × 109/L) and platelet count (2.65 × 109/L). BM aspirates were particulate and normocellular. Erythroid showed normoblastic maturation, myeloid showed all stages of maturation, and megakaryocytes were normal. M:E ratio was 1.4:1. Plasma cells were not increased. Abundant extracellular eosinophilic material was seen in [Figure 1]a. BMB was normocellular for age and showed deposition of similar acellular eosinophilic material in extracellular spaces. However, there was no deposition in vessel wall, no fat atrophy, or necrosis of adjacent bone [Figure 1]b. Special stains for amyloid, crystal violet, and Congo red [Figure 1]c and Alcian blue were negative [Figure 1]d. Serum electrophoresis showed the presence of a polyclonal M band ruling out MM. An impression of cellular reactive BM with BME was given. BME could be attributed to underlying volume overload. This has resulted in increased blood flow to the marrow with increased intravascular pressures leading to capillary leakage and subsequent development of BME.
Figure 1: (a) Bone marrow aspirate, ×100, Giemsa (INSET, ×200); (b) bone marrow biopsy, ×200, H/E: Showing deposition of abundant extracellular amorphous acellular eosinophilic material; (c) Congo red, ×100: negative; (d) Alcian blue stain at pH 2.5; ×40 (INSET, ×200): negative

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BME is defined as the excess of interstitial fluid in the BM. Causes of BME include primary BME syndrome, trauma, osteoarthritis, sickle cell disease, osteomyelitis, neoplastic, iatrogenic, metabolic, and neurological.[1] Local ischemia along with inflammatory cytokines seems to play an important role in the development of BME.[1]

Histologically, BME is seen as acellular extracellular eosinophilic material.[2] Histological finding of BME tends to be incidental with very few studies in the literature. Before making a diagnosis of BME, other causes of eosinophilic material in BM should be ruled out. These include amyloid, gelatinous transformation of marrow (GMT), and myelonecrosis. [Figure 2] shows the approach to diagnose the nature of eosinophilic material in BM.
Figure 2: Approach to identify the nature of eosinophilic material in bone marrow

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Amyloid – Immunoglobulin light chain amyloidosis (AL) is characterized by a clonal population of BM plasma cells that produces a monoclonal light chain of j or k type. The light-chain protein misfolds into an insoluble β-pleated configuration which deposits in tissues interfering with organ function. In BMB, it is deposited in interstitium and vessel walls. These deposits are seen as blue-eosinophilic acellular, amorphous, extracellular congophilic material, displaying apple-green birefringence under polarized light, diagnostic of AL amyloidosis.[3]

GMT is a rare disease characterized by marrow hypoplasia, fat atrophy, and accumulation of extracellular gelatinous material. It is a morphologic sign of underlying severe systemic illness such as prolonged starvation, malabsorption, alcoholism, malignancy, and cytotoxic drugs.[3] Chronic malnutrition underlying these catabolic states results in fat cell utilization and replacement with hyaluronic acid.[3] The deposition of gelatinous material and subsequent alteration in marrow microenvironment is detrimental to hematopoiesis leading to peripheral cytopenias.[4] BMB is usually hypocellular with mild-to-marked hypoplasia of hematopoietic cells. There is atrophy of fat cells, which are both reduced in number and are of variable size. Both fat and hematopoietic cells are replaced by amorphous, finely granular, light blue to pale eosinophilic material, stained by alcian blue at pH 2.5.[3]

Myelonecrosis is defined as necrosis of hematopoietic cells in BM, usually accompanied by death of bone cells due to impairment of BM blood supply.[3] The most common causes include sickle-cell anemia, sickle-cell/Hb C disease, acute leukemias, metastatic carcinomas, and Caissons disease.[5] The PS shows leukoerythroblastic blood picture, but if necrosis is extensive, pancytopenia ensues.[5] BMB shows cells with granular cytoplasm, indistinct margins, and pyknotic nuclei in early stages and karyorrhectic nuclei with complete loss of cell margins in later stages.[5] Necrosis of adjacent trabeculae with the disappearance of osteocytes is seen.[3] Necrosis of small blood vessels results in extravasation of erythrocytes. The end result is amorphous eosinophilic debris.

To conclude, whenever abundant extracellular eosinophilic material is seen histologically, a systematic approach with special stains should be sought to reach a diagnosis. Histologically, BME is a diagnosis of exclusion. To the best of our knowledge, this is the first study reporting the approach to identify the nature of eosinophilic material in a BM and highlighting the importance of BME histologically.


The authors would like to acknowledge the Hematology Section of Pathology Department of UCMS and GTBH for their help in workup of the case.


The consent was obtained from the patient.

Declaration of patient consent

The authors would like to certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that name and initial will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.

   References Top

Patel S. Primary bone marrow Oedema syndromes. Rheumatology (Oxford) 2014;53:785-92.  Back to cited text no. 1
Thiryayi WA, Thiryayi SA, Freemont AJ. Histopathological perspective on bone marrow oedema, reactive bone change and haemorrhage. Eur J Radiol 2008;67:62-7.  Back to cited text no. 2
Das S, Mishra P, Kar R, Basu D. Gelatinous marrow transformation: A series of 11 cases from a tertiary care centre in South India. Turk J Haematol 2014;31:175-9.  Back to cited text no. 3
Nakanishi R, Ishida M, Hodohara K, Yoshida T, Yoshii M, Okuno H, et al. Prominent gelatinous bone marrow transformation presenting prior to myelodysplastic syndrome: A case report with review of the literature. Int J Clin Exp Pathol 2013;6:1677-82.  Back to cited text no. 4
Paydas S, Ergin M, Baslamisli F, Yavuz S, Zorludemir S, Sahin B, et al. Bone marrow necrosis: Clinicopathologic analysis of 20 cases and review of the literature. Am J Hematol 2002;70:300-5.  Back to cited text no. 5

Correspondence Address:
Mrinalini Kotru
Department of Pathology, University College of Medical Sciences and Guru Teg Bahadur Hospital, New Delhi - 110 095
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/IJPM.IJPM_89_18

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