Teaching Case

A 9-year-old boy presented with intermittent joint pain and morning stiffness involving the feet and shoulders of one year of evolution. Laboratory tests show a slightly elevated ESR without other remarkable findings. With a suspected diagnosis of juvenile idiopathic arthritis, treatment with NSAIDs and corticosteroids was started without clear improvement.

A feet and ankles MRI revealed symmetrical bone marrow signal abnormalities, with decreased signal intensity areas on T1-weighted images, increased signal intensity areas on T2-weighted images and gadolinium enhancement involving all tarsal bones and tibial and fibular distal metaphysis (Fig. 1a, 1b, 1c).

In addition, isolated foci of no enhancement in the tibial epiphysis and navicular and cuneiform bones were identified on post-gadolinium T1-weighted sequences (Fig. 1c) consistent with bone marrow necrosis.

Neither synovitis nor joint effusion was observed.

Given these findings a whole-body MRI was requested showing bone marrow signal abnormalities, similar to those on ankle MRI, with restricted diffusion (not shown), involving axial and appendicular skeleton (Fig. 2a, 2b, 2c, 2d, 2e, 2f).

The above-mentioned MRI findings suggested the possibility of an infiltrative haematological malignancy, despite the fact that the laboratory tests were unremarkable. A bone marrow biopsy was performed, and it revealed atypical lymphoid infiltrate with immunohistochemical, cytological and molecular biological features consistent with acute B lymphoblastic leukaemia.

Leukaemia represents a group of malignant hematologic neoplasms characterized by the clonal overproduction of immature or abnormally differentiated lymphoid precursors in the bone marrow. These abnormal cells proliferate and replace normal cells and may spread to the peripheral blood involving multiple organs [1]. It is the most common childhood cancer, being acute lymphoblastic leukaemia the most prevalent subtype [1, 2].

Usually, the clinical suspicion diagnosis of a malignant haematological disease is based on a series of systemic symptoms and signs (lymphadenopathy, hepatosplenomegaly, mediastinal mass…) that are supported by abnormal blood tests (anaemia, thrombocytopenia peripheral blood blasts…) and confirmed with a biopsy or a bone marrow aspirate [3,4]. However, some children can present with non-specific musculoskeletal symptoms, such as bone pain, that can be easily misdiagnosed as an inflammatory or infection disorder if the laboratory findings are unremarkable. All this implies a potential delay in the correct diagnosis and treatment [4].

The increasing use of MRI to evaluate musculoskeletal symptoms can lead to the incidental detection of an abnormal marrow signal pattern, nonspecific but suggestive of an infiltrative hematologic malignancy, and be useful to reach an early diagnosis, even when there are no abnormal cells in peripheral blood or other laboratory abnormalities.

The bone marrow is an organ that contains a combination of red and yellow fatty marrow, which determines its signal on the MRI.  At birth nearly all bone marrow in the skeleton is red marrow, which is rich in water and shows high signal intensity on T2-weighted images and low signal intensity on T1-weighted images. Throughout growth, the red marrow is progressively replaced by fatty marrow showing high MRI signal intensity on T1-weighted sequences and low on fat-suppressed T2-weighted sequences [2,6, 8, 9,10].

MRI of pathological conditions that cause replacement of bone marrow shows lower signal intensity than muscle on T1- weighted images, higher signal intensity on STIR or fat-suppressed T2-weighted images (“flip-flop sign”) and gadolinium enhancement, usually in a diffuse pattern. Bone infarct or bone marrow necrosis can also be present, showing a non-enhanced geographic area on postcontrast images [2,4,7,10]

Treatment options for leukaemia include chemotherapy regimens, bone marrow or peripheral blood stem cell transplant, and antibody-mediated medications [2].

The onset of isolated non-specific musculoskeletal symptoms without laboratory test abnormalities is a rare form of acute leukaemia debut, where MRI plays an important role in characterizing bone marrow infiltration and avoiding a delay in correct diagnosis.

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