We presented characteristic MRI and CT findings of hematopoietic islands of the axial skeleton in a case series of ten patients. The awareness of this rare entity is important in order not to misdiagnose these lesions as osteoblastic metastases, which typically show similar signal intensities on MRI. Diagnostic difficulties particularly arise when an underlying malignancy is known.
MRI
Normal bone marrow shows intermediate signal intensity on T1w spin-echo images since it contains about 50% fat and 50% water in adults (14). In our patient cohort, all hematopoietic islands presented moderate hypointense signal on unenhanced T1w TSE MR images compared to surrounding marrow. This is explained by the fact that in hematopoietic islands a marked amount of fat is still preserved. Our finding is consistent with previous reported cases of focal hematopoietic islands (2, 9-11). They were also mild hypointense on T1w TSE images, which is helpful in differentiating these lesions from osteoblastic metastases, which usually show strong T1w signal drop iso- or hypointense compared to adjacent muscle or disk (15, 16).
Unenhanced T1w sequences are important in differentiating benign lesions with fat content (like benign bone marrow lesions or edema) from metastases, which normally show a significant reduction in fat component due to cellular replacement with marrow infiltration (17). In a previous study, Carroll et al. analyzed T1w images of 74 patients with both benign and malignant bone marrow signal alterations on MRI (51 biopsy-proven, 23 clinical follow-up) and compared relative signal intensity of bone marrow to adjacent skeletal muscle and/or nondegenerated intervertebral disk in order to establish standards on MRI differentiating infiltrative marrow pathology from hematopoietic marrow. It was summarized that marrow lesions that are relatively isointense or hypointense to muscle and/or disk on T1w spin-echo images should not be considered normal hematopoietic marrow (15).
Schweitzer et al. previously reported the “bull´s eye sign” as a specific indicator of normal hematopoietic marrow and the “halo sign” as a strong indicator of metastatic disease in 47 patients with osseous lesions of the pelvis evaluating T1w and T2w sequences (18). The “bull´s eye sign”, which describes a central T1w high signal intensity in an osseous lesion, could not be found in our cases of hematopoietic islands. Thus, T1w TSE images are important for the differentiation of sclerotic osteoblastic metastases with strong hypointense signal equal to adjacent disc or muscle and focal hematopoietic islands with only moderate signal drop.
Normal bone marrow shows intermediate signal intensity on T2w TSE images. In our cohort, all hematopoietic islands showed hypointense signals on T2w TSE images, which is similar to osteoblastic metastases. In contrast, osteolytic metastases show high signal intensity on T2w images (14, 19, 20). All previous reported hematopoietic islands as well showed hypointense T2w signals, which is in concordance with our findings (2, 9-11).
STIR sequences provide high tissue contrast by suppressing fat signals. Thus, all pathologic processes, such as metastases, edema, and inflammation show strong hyperintense signals. Normal bone marrow usually shows low signal intensity on STIR imaging (14, 20). Five out of 14 lesions in our cohort showed isointense signals on STIR sequences compared to adjacent bone marrow, while nine showed slightly hyperintense signals. In contrast, osteolytic metastases typically show strong hyperintense signals on STIR sequences, while osteoblastic metastases show similar signal behavior to hematopoietic islands due to a lack of water protons (14).
Thus, T2w TSE and STIR imaging are not helpful in differentiating focal hematopoietic islands from osteoblastic metastases.
After gadolinium administration normal bone marrow enhances to a certain extent (21). Osteoblastic metastases typically show also no or only slight enhancement, while osteolytic lesions strongly enhance (14, 19, 20). Hematopoietic islands in our cohort showed slight enhancement after contrast administration, which was more conspicuous on fat-saturated images. Thus, gadolinium cannot differentiate between osteoblastic metastases and focal hematopoietic islands but are helpful in differentiating them from osteolytic or mixed type metastases, which usually show strong enhancement. As of yet, there are no previous studies describing the signal behavior of hematopoietic islands after gadolinium administration. In general in uncertain bony lesions, contrast administration is highly recommended (22).
Diffusion-weighted imaging
DWI is based on quantifying the motion of water molecules within tissue (23). Three patients of our cohort received DWI with obtaining SSFP sequences with relatively short acquisition time and insensitivity for patient movement. All examined hematopoietic islands presented as hypointense lesions when qualitatively compared to adjacent bone marrow. In previous studies, SSFP imaging was able to differentiate between malignant, depicted as hyperintense, and benign vertebral fractures, depicted as iso- or hypointense in comparison to normal bone marrow (23, 24). However, osteoblastic metastases may also present hypointensity on SSFP sequences due to sclerosis (25, 26). Thus, DWI is not of definite value in distinguishing these two entities.
Chemical Shift- imaging
Chemical shift imaging, which can be used to quantitatively assess the fat and water content of vertebral bone marrow on a voxel-by-voxel-basis, was done in two patients in our cohort (12). In a previous study of Zajick et al. on 221 marrow lesions in 92 patients a signal drop of more than 20% on out-of-phase images compared with in-phase images indicated benign lesions (13). In accordance with benign lesions, all hematopoietic islands in our patient cohort showed signal drops greater than this 20% threshold on out-of-phase images due to their fat content. In contrast, in malignant lesions normal fat-containing marrow is replaced with high cellular tumorous tissue, which has the effect that this increase in water protons is associated with a lack of suppression on the out-of-phase images (13, 27, 28). Thus, chemical shift imaging seems to be of value for the differentiation of hematopoietic islands of the axial skeleton and osteoblastic metastases.
CT Imaging
On CT none of the lesions showed sclerosis, which is in contrast to osteoblastic metastases. This is a strong and important imaging feature to make the correct diagnosis.
Hybrid Imaging Techniques
18F FDG PET-CT was done in two patients. No increased FDG uptake was found in both patients (cut-off value SUVmax > 3). This is in contrast to a previous case report of Bordalo-Rodrigues et al. He reported a case of a patient with lung carcinoma, who received 18F FDG PET-CT examination as pretherapeutic staging, where increased uptake was noted in a biopsy-proven hematopoietic island in the vertebral body of Th8 (9). Taking these findings into account, it has to be stated that focal areas of normal but hypercellular red marrow may show increased uptake on FDG PET-CT and therefore may be confused with neoplasm or infection. This may be due to upregulation of glucose transporters and metabolism in stimulated cells, also known from increased FDG-uptake in patients undergoing treatment with granulocyte-colony-stimulating-factor, which stimulated growth and differentiation of hematopoietic stem cells. However, in these cases- in contrast to hematopoietic islands- FDG-uptake is diffuse (7, 8).
Possibly, the hematopoietic activity in our lesions might have been too low to cause an increased FDG-uptake. It should be emphasized that hematopoietic islands may remain occult on FDG PET-CT. Therefore, FDG PET-CT is not of direct value for the differentiation of osteoblastic metastases and focal hematopoietic islands of the spine.
Skeletal scintigraphy
Tc 99m skeletal scintigraphy was performed in one patient in our cohort and was unremarkable. This is in contrast to a previous report of Lee et al., who described an increased radiotracer accumulation in a focal hematopoietic hyperplasia of the right third rib in a 24-year-old patient (11). Thus, skeletal scintigraphy is not of value in distinguishing hematopoietic islands from osteoblastic metastases.
Bone marrow biopsy
Five patients received CT-guided biopsy in order to confirm the diagnosis. All samples showed proportions of bone marrow with moderately increased hematopoiesis. The fat cell content was mildly reduced. There was no evidence of malignancy (Fig. 1f, Fig. 2g).
Limitations
A limitation of our study is the small number of patients. However, so far, there is little literature available on this topic. In addition, biopsy was obtained in only five patients, however osteoblastic metastases could be excluded by CT and follow-up MRI. Furthermore, not all patients received DWI, chemical shift and hybrid imaging. However, typical routine sequences (T1w TSE, T2w TSE and STIR) were available in all of the patients. In addition, gadolinium was applied in nine out of ten patients.