MR imaging characteristics in primary lymphoma of bone with emphasis on non-aggressive appearance

Primary non-Hodgkin’s lymphoma of bone (PLB) is a rare entity among musculoskeletal tumors, and it is also uncommon among extra-nodal sites of NHL. The morphology of these lymphomas is identical to that of lymphomas at other sites, but the clinical course is often more protracted. Prognosis of PLB depends mainly on staging and on histological classification, but, generally, the clinical outcome, after treatment with combined chemo- and radiation therapy, is favorable, with a 5-year overall survival rate rising to 88% [1‐5, 9‐11, 18, 20]. On the other hand, Lewis et al. reported a 5-year survival rate of 58% and no statistically significant difference between PLB and systemic bone lymphoma [6]. With regard to histological subtype, tumor localization and clinical presentation, patients with PLB display homogeneous clinicopathological features [4, 5]. Almost all tumors are localized in long bones (particularly the femur, tibia, pelvis and humerus), and patients present with pain and/or a palpable mass. The literature describes a significant male preponderance, which is not confirmed in this present study. Although PLB presents in a wide age range of patients, evenly distributed among the second through eighth decades of life, in general, it is more frequently encountered in patients over 30 years of age, with a peak incidence in the fifth decade, in contrast to that of Ewing’s sarcoma and osteosarcoma [6, 8, 10, 11, 13, 14, 18]. In the latter patient group, a significant decrease in incidence is found beyond the third decade. In our study group of 29 patients a broad range of ages at presentation was also found (19–81 years); the median age was 40 years.

Plain radiographs of PLB often show destructive bone lesions, generally with periosteal layering and cortical disruption. On the other hand, plain radiographs of PLB may appear virtually normal or non-specific and can be overlooked as being normal. As such, there is no specific conventional radiographic pattern, and the radiographic differential diagnosis of PLB includes a broad spectrum of both benign (including osteomyelitis) and malignant (such as osteosarcoma, Ewing’s sarcoma) lesions [8, 16‐19]. These tumors and tumor-like lesions may demonstrate similar radiographic features but warrant different types of therapy. In this respect PLB is associated with a better prognostic outcome than that for other small round cell tumors. Literature on the presentation of MR imaging features of PLB is relatively scarce and contradictory. These studies, frequently with limited numbers of patients, mainly focused on the appearance of the cortical bone, relative to associated soft-tissue abnormalities, and on SI characteristics [13‐16, 18, 19, 21, 22]. Low SI on T2-weighted sequences has been mentioned as a feature of PLB, probably due to a high content of fibrous tissue [15]. We could not confirm this feature to a great extent in our population. Low SI on T1- or T2-weighted sequences was present in only one patient each. Almost all tumors showed a non-specific combination of intermediate (equal to that of muscle) SI on T1-weighted sequences and high SI on T2-weighted sequences.

Several studies on PLB and MR imaging focused on the pattern of cortical destruction in order to use it as a differentiating criterion. It was stated that a tumor with a normal (appearing) cortex and a substantial soft-tissue mass is likely to be lymphoma [13, 14]. MR imaging may show small linear foci of intermediate or high SI on T2-weighted sequences, penetrating the cortical bone. This MR pattern of permeative cortical destruction is, however, not specific to lymphoma. It can be seen in other small round cell tumors (in the younger age group) as well as in different metabolic and inflammatory processes, including hyperparathyroidism and osteomyelitis and, for instance, myeloma or metastatic carcinoma (in the older age group) [13, 14]. In our study, cortical abnormalities were present in 93% of patients, and extension into the soft tissue was found in 76%, but various types of destruction and combinations with or without such extension were recognized (Table 1). A pattern of permeative cortical destruction with linear foci of abnormal SI was noticed in 15 of the 29 (52%) patients. Ten of these 15 patients had a definite soft-tissue mass. In five patients, however, this was minimal or even absent. In 28% of our patient population complete cortical disruption could be appreciated; in all but one patient it was accompanied by a large soft-tissue mass. In another two patients, the cortical bone appeared to be completely normal, and in these patients there was no associated soft-tissue mass. In one patient with histologically confirmed PLB the tumor was selectively located within the cortical bone, without further extension into the soft tissue and/or bone marrow involvement. In one patient the cortical bone was homogeneously thickened, a feature that can also be encountered in reactive processes (after trauma or infection). Peri-osteal or cortical lymphoma without medullary involvement is a very rare manifestation of NHL, but it has been previously described [23]. In this respect, it can be concluded that in patients with PLB the pattern of cortical destruction is heterogeneous and non-specific.

MR imaging is the optimal modality to demonstrate the extent of bone marrow replacement by PLB, particularly using T1-weighted sequences [14, 24]. Multi-centric bone marrow disease is likely to be detected by longitudinal series with a large field of view. Signal intensities of the bone marrow component were non-specific in the present series, being intermediate on T1-weighted sequences and high on T2-weighted sequences in almost all patients. In only three patients a combination of intermediate and low signal intensity was found. Demarcation in the longitudinal extent was scored as sharp in 11 and unsharp in nine patients. The SI of the bone marrow tumor component was homogeneous in 13 of 28 patients (46%); however, it was inhomogeneous in 15 patients (54%), which can be explained by the intermingling of normal bone marrow between areas of tumor. Contrast-enhanced images of the bone marrow showed a similar distribution; enhancement was diffuse and homogeneous in 41% and heterogeneous in 59% of the patients whose condition was eligible for evaluation. Opposed to the bone marrow component, the soft- tissue component, if present, was far more homogeneous, both on T1-weighted contrast-enhanced images (82%) and as high SI on T2-weighted images (82%).

The data obtained in this retrospective study demonstrate that, in contrast to the relatively homogeneous clinical and pathological presentation, the MR imaging features are not uniform in patients with PLB. Although the majority of our patients displayed a combination of definite cortical abnormalities (either permeative destruction or complete disruption) and extension into soft-tissue, lymphoma may show different appearances. Particularly, intra-osseous lesions with linear cortical signal abnormalities without substantial soft-tissue mass, or even normal-appearing or thickened cortical bone without soft-tissue mass, may look non-aggressive and even benign. In the present study no fewer than nine of 29 patients (31%) with PLB presented in that manner. Radiologists should thus be aware of that in the right clinical context.

There are several limitations concerning this retrospective and largely descriptive study. The data obtained were collected from various institutions that had used different MR imaging systems, field strengths and protocols. In order to collect a larger number of patients, given the rarity of PLB, we could not avoid this. The assessment of heterogeneity or homogeneity of signal characteristics is quite subjective; however, for the goal of this study it was of minor importance. Fast dynamic contrast-enhanced sequences were used only incidentally. Nowadays, these acquisitions are widely used to assess the biologic behavior of primary bone and soft-tissue tumors and to determine the response to chemo- and/or radiation therapy. With regard to PLB, the rapid decrease of tumor volume and the complete disappearance of the soft-tissue component on MR imaging has been described as a significant indicator of good response to treatment [24]. In this respect, MR imaging has a direct impact on individual patient care, which is however, outside the scope of this study. We could not determine how MR imaging had caused any change in clinical approach in the patients with PLB described here. Differentiating PLB from other malignant small round cell tumors, on the one hand, or reactive processes, on the other hand, based on (MR) imaging criteria only, is, in our opinion, not possible and not useful, which stresses the need for accurate core biopsy, which is definitely crucial for both diagnosis and staging purposes.