Case Report | Open Access
Benjamin Sephton, Francesco Folli, "Bone Non-Hodgkin’s Lymphoma: Mimicking Deep Vein Thrombosis", Case Reports in Orthopedics, vol. 2019, Article ID 7179380, 4 pages, 2019. https://doi.org/10.1155/2019/7179380
Bone Non-Hodgkin’s Lymphoma: Mimicking Deep Vein Thrombosis
The incidence of deep vein thrombosis (DVT) in the general population is around 1 in 1000 people. Clinical features are often nonspecific presenting most often with leg pain and swelling. Accurate diagnosis and treatment of DVT are important to prevent a potentially fatal complication of pulmonary embolism (PE). Primary non-Hodgkin’s lymphoma of bone (PLB) is a rare disease that accounts for fewer than 5% of all primary bone tumours. Patients most commonly present with localized bone pain, and in about one-half of cases, a soft tissue swelling or a palpable mass. Constitutional “B” symptoms including fever, weight loss, and night sweats may also be present at the time of diagnosis. Imaging involves radiographs, CT, and MRI combined with PET CT to examine for lymph node involvement and staging. PLB is difficult to diagnose by radiographs alone—the diagnosis depends on further imaging and histopathological assessment of biopsy specimens. Further to this, the indolent course of disease and nonspecific symptoms can delay the diagnosis. At present, multiagent chemotherapy (±RT) is the modality of choice; a common regime is CHOP. This may be further combined with monoclonal antibody rituximab (RCHOP) which targets CD20-positive tumours. This case report details an unusual presentation of non-Hodgkin’s lymphoma of bone mimicking a deep vein thrombosis, leading to an interesting diagnostic sequence in a 65-year-old female.
The incidence of deep vein thrombosis (DVT) in the general population is around 1 in 1000 people . Clinical features are often nonspecific presenting most often with leg pain and swelling . Accurate diagnosis and treatment of DVT are important to prevent a potentially fatal complication of pulmonary embolism (PE). Primary non-Hodgkin’s lymphoma (NHL) of bone is a rare disease accounting for 3-7% of all bone tumours [3, 4] and less than 2% of all lymphomas in adults . The femur has been cited as the most common site in several studies, around 28% of all primary NHL bone tumours [4, 5]. The vast majority of these patients present with either long-standing bone pain, a palpable mass, or the presence of “B” symptoms (fever, weight loss, and night sweats) [5, 6]. This case report details an unusual presentation of repeated knee effusions and lower limb swelling leading to an interesting diagnostic sequence in a 65-year-old female.
2. Case Presentation
A 65-year-old English female initially presented to the emergency department with a history of a painful and swollen left knee and lower limb. She had a background of long-standing osteoarthritis (of right knee), osteoporosis, and varicose veins. Her drug history consisted of Calcichew and vitamin D supplementation and nil other medication. The onset of symptoms and lower limb swelling occurred on return from Spain 3 weeks previously; however, the patient had previously reported to her GP 6 months earlier with worsening knee pain. On initial examination, the whole leg was swollen and tender with slight erythema; a left knee effusion was evident with full range of motion at the joint.
Her vital signs were within normal limits as were haematological and biochemical markers. An initial Doppler ultrasound (US) showed a ruptured Baker’s cyst measuring cm, and no evidence of DVT was seen (Figure 1). Left knee radiographs at the time showed an effusion of the knee joint; no osteoarthritic or erosive changes were seen (Figure 2). Two further Doppler US were performed throughout the investigative course for repeated swelling+pain in the lower limb, confirming the ruptured Baker’s cyst. The final US showed that the distal femoral vein and popliteal veins were not compressible and contained echogenic debris, in keeping with a deep vein thrombosis.
Following development of shortness of breath and chest pain, a computed tomography pulmonary angiogram (CTPA) was performed to exclude pulmonary embolism (PE); CTPA was negative for a PE; however, it demonstrated an abnormally enlarged left hilar node measuring 2 cm in the short axis which required further investigation. A whole-body PET CT scan was then performed; this identified a large soft tissue mass around the left distal femur with minimal related cortical irregularity and increased bone density. Although a significantly infected haematoma was a possible diagnosis, this was felt to more likely represent a malignant mass, possibly a sarcoma, and a biopsy was recommended (Figure 3).
Following this, a magnetic resonance imaging (MRI) scan was performed for further work-up and analysis of the leg mass. The MRI showed a heterogeneous large soft tissue mass around the left distal femur with mild related cortical irregularity with potential bone marrow deposits in the lesser trochanter and head of the femur (Figure 4), judged to likely represent a malignant mass, possibly a sarcoma.
The case was discussed with the specialist sarcoma unit, and a decision was made for the biopsy of the soft tissue mass. Four core soft tissue biopsies were taken and sent for histopathology and immunohistochemistry. The conclusion of the report was a B-cell lymphoma of the left femur (see Table 1 for the full report).
Once a diagnosis of B-cell lymphoma was made, she was transferred to the care of haematology. At present, she has been started on the R-CHOP (R-CHOP—rituximab, cyclophosphamide, hydroxydaunomycin (doxorubivin), Oncovin (vincristine), prednisolone) regime with intermittent methotrexate weekly, after having received 5 days of 100 mg OD prednisolone.
5. Outcome and Follow-Up
The patient is currently an inpatient at the specialist local haematology centre and is awaiting outcome of the multidisciplinary team meeting and results of the bone marrow aspirate and trephine (BMAT) biopsy.
A painful swollen leg is a common clinical scenario for a wide range of pathologies. The initial management in the majority is to start anticoagulation and arrange a venous duplex scan, as the priority is to rule out a DVT. Only one-third of patients with their first DVT are of a spontaneous origin , therefore stressing the importance of further investigation for an underlying precipitant or causative factor. Tumours are a rare but an important differential diagnosis in such patients. Sixty percent of soft tissue sarcomas arise in the extremities; 70% occur in the lower limb and mostly in the thigh. As a rule of the thumb, any mass over 5 cm in size arising beneath the level of deep fascia in the lower limb should be considered a sarcoma unless proven otherwise .
On her first ED presentation, sarcoma was not considered as a differential diagnosis. The duplex scan was unable to detect a coexisting solid soft tissue swelling at the early stage of diagnosis work-up. Because malignancy is a strong risk factor for DVT, the issue of whether or not patients who present with idiopathic DVT are harbouring an occult malignancy has been well documented in the literature. Prandoni et al. found malignancy in 3.3% of idiopathic DVT patients and in 17.1% of patients with recurrent DVT . Despite this association, a malignancy work-up is not indicated for most patients presenting with DVT .
Primary non-Hodgkin’s lymphoma of bone (PLB) is a rare disease that accounts for fewer than 5% of all primary bone tumours . Patients most commonly present with localized bone pain, and in about one-half of cases, a soft tissue swelling or a palpable mass . Constitutional “B” symptoms including fever, weight loss, and night sweats may also be present at the time of diagnosis . As seen in this case, the indolent course of disease and nonspecific symptoms can delay the diagnosis, combined with the fact that symptoms may precede haematological abnormalities.
Imaging involves radiographs, CT, and MRI combined with PET CT to examine for lymph node involvement and staging. Radiographs have widespread variability in appearance; however, the typical finding is of diffuse medullary “mottled” or “moth-eaten” radiolucencies . In this case, normal radiographs of the bone were seen (Figure 2), and it is acknowledged in the literature that PLB is difficult to diagnose by radiographs alone—with the diagnosis dependent on further imaging and histopathological assessment of biopsy specimens .
Further imaging includes CT and MRI. A pattern of osteolysis is classically seen on CT imaging; however, osteosclerotic and mixed patterns are also reported . MRI allows assessment of bone marrow, cortex, and lymph node involvement. Bone marrow involvement is best seen on T1-weighted series evidenced as low signal intensity within the medullary space . On T2-weighted series, these reactive areas show up with high signal intensity. Soft tissue extension with minimal cortical destruction is often seen with high density on T2-weighted images . In the presented case, a large soft tissue mass was seen on MRI with mild cortical irregularity; this, however, was thought to be most likely sarcoma, emphasizing the importance of an accurate biopsy for confirmation. PET CT scanning can be further used to assess staging and has been shown to be accurate for this purpose . In our case, the PET CT was performed prior to MRI due to diagnostic work-up for an enlarged hilar lymph node.
For complete histological diagnosis, a biopsy is performed by a trained orthopaedic oncologist. A fine-needle aspiration biopsy may suffice for masses with soft tissue extension; however, if this is not the case, a bone marrow aspirate and trephine may be used to access the medullary canal . The vast majority (80%) of primary NHL of bone cases is diffuse large B-cell lymphoma, characterised by large cells that are classified as centroblastic, immunoblastic, or anaplastic at histology . Differential diagnoses at histology include neuroblastomas, small-cell round tumours, Ewing’s sarcomas, and Langerhans cell histiocytosis. Differentiating between Ewing’s sarcoma and primary NHL’s can prove a challenging task for histopathologists.
Malignancy should always be ruled out in patients with unexplained persevering bone pain. Despite a number of basic imaging modalities used in our case, a normal radiograph and ultrasound cannot be accurately relied upon to exclude a primary tumour of the bone. Primary NHLs of bone are an extremely rare cause of knee pain and swelling; however, with repeated presentations and no response to treatment, investigation for further underlying causes should take place.
Learning Points. (1) Non-Hodgkin’s lymphoma can present with musculoskeletal manifestations in a small number of patients. (2) Deep vein thrombosis may be a sign of underlying disease, and clinicians should consider searching for underlying causative factors. (3) Knee radiographs may demonstrate lytic or radiolucent lesions but may also be normal initially. If there is an index of suspicion of sarcoma/lymphoma, a more comprehensive MRI should be performed. (4) Full diagnostic work-up includes blood markers, radiographs, MRI, (PET) CT of the chest, abdomen, and pelvis, and histological diagnosis via a biopsy (FNA or BMAT). (5) Multiagent chemotherapy (CHOP) is the mainstay of treatment with consideration of addition of rituximab (RCHOP) in CD20-positive tumours.
Conflicts of Interest
The authors declare that there is no conflict of interest regarding the publication of this paper.
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Copyright © 2019 Benjamin Sephton and Francesco Folli. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.