Answers

Short answers

1 Deep vein thrombosis, ruptured Baker’s cyst, venous insufficiency, cellulitis, trauma, reflex sympathetic dystrophy, lymphatic obstruction (for example, as a result of tumour, surgery, or trauma), tumour or fibrosis obstructing the iliac vein.¹

2 Extensive inguinal lymphadenopathy (predominantly right sided) that extends to surround the right internal and external iliac vessels (fig 2).

View larger version (61K): [in this window] [in a new window] [PowerPoint Slide for Teaching]   Fig 2 Computed tomogram showing extensive inguinal lymphadenopathy (mainly right sided) surrounding the right internal and external iliac vessels (arrow)

 

3 Lymph node biopsy.

4 Diffuse large B cell lymphoma with extensive right inguinal lymphadenopathy and iliac vein compression (causing severe unilateral oedema).

Long answers
1 Differential diagnoses
Several of the differential diagnoses can be excluded because of the patient’s history and examination. She has no history of trauma; no clinical evidence of cellulitis; no pain, tenderness, or skin changes to suggest reflex sympathetic dystrophy²; and no features of chronic venous insufficiency (lipodermatosclerosis, varicosities, history of deep vein thrombosis, or immobility).³ In addition, a ruptured Baker’s cyst usually causes swelling of the distal part of the limb. A proximal deep vein thrombosis was excluded by Doppler ultrasound imaging. This leaves obstruction of the lymphatic or iliac vein as the most likely cause.

Figure 3 shows an algorithm for establishing a diagnosis in chronic (>72 h) unilateral leg oedema.⁴ It highlights the importance of looking for enlarged inguinal lymph nodes and performing a pelvic or rectal examination, particularly if malignancy is suspected.

View larger version (51K): [in this window] [in a new window] [PowerPoint Slide for Teaching]   Fig 3 Algorithm for establishing a diagnosis in chronic unilateral leg oedema

 
Remember that although D-dimer assays are very sensitive, they are also highly non-specific. Not only is this marker increased in arterial thromboembolic disease (for example, stroke, myocardial infarction, acute limb ischaemia, and atrial fibrillation), but it is also raised in severe infection, sepsis, inflammation, malignancy, renal failure, pregnancy, and severe liver disease. It is also raised after surgery or trauma,⁵ and it increases with age, which reduces the clinical value of these assays in elderly people.⁶

2 Computed tomography
The coronal computed tomogram shows extensive inguinal lymphadenopathy surrounding the right internal and external iliac vessels (arrow). Axial images confirmed that the right external iliac vein was occluded, which explained the severity of the patient’s leg oedema. Staging computed tomography confirmed the presence of some right axillary lymphadenopathy, but no mediastinal or hilar lymphadenopathy. The patient was thought to have stage III lymphoma.

3 Definitive investigation
Lymph node biopsy is needed for a definitive diagnosis. Although the advent of immunohistochemical analytical techniques has increased the sensitivity and specificity of fine needle aspiration,^{7 8 9 10 11} excisional biopsy remains the diagnostic procedure of choice.¹² This is performed by a surgeon, and the type of surgeon will depend on the site of the lymph node (for example, an ear, nose, and throat surgeon for head and neck lymphadenopathy). Excisional biopsy has few complications, but these include vessel injury and the rare spinal accessory nerve injury.¹³

4 Unifying diagnosis
Diffuse large B cell lymphoma (DLBCL) is the most common lymphoma. It makes up 31% of all non-Hodgkin lymphomas and has an international incidence of 16 740 each year.¹⁴ These lymphomas can occur at any age, but they usually occur in middle aged and older people, with a male to female incidence ratio of 1.3:1.¹⁵

DLBCLs most commonly appear in lymphoreticuloendothelial tissues, including lymph nodes, spleen, and liver (bone marrow involvement is typically late). They often present as a single rapidly growing mass, which causes symptoms when it infiltrates tissues or obstructs organs. Around 30-40% are extranodal and are found in skin, bone, the gastrointestinal tract, genitourinary system, and central nervous system.¹⁶

Investigations include a full blood count, blood film, routine biochemistry, and lactate dehydrogenase, which is a prognostic marker. An excisional lymph node biopsy is needed to confirm the diagnosis. Chest radiography and computed tomography of the thorax, abdomen, and pelvis are performed for staging purposes, as is a bone marrow biopsy.¹⁵

DLBCL is fatal if untreated; chemotherapy achieves remission in 70% of patients and 50% are cured.¹⁶ The CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone) regimen was one of the first combinations to produce a complete remission and long term survivors. The addition of rituximab (a monoclonal antibody against CD20) to CHOP is the current standard treatment in patients with advanced disease.¹⁵

This case highlights the importance of making a diagnosis. Not uncommonly, we see patients who are diagnosed with "leg swelling, deep vein thrombosis excluded," which clearly is not a diagnosis and does not provide an explanation for the leg swelling.

Patient outcome

Once the diagnosis was made, the patient was referred to the haematologists and went on to receive chemotherapy, which reduced her leg oedema.

Cite this as: BMJ 2009;339:b3996