Tophaceous calcium pyrophosphate dihydrate deposition disease of the knee mimicking an aggressive soft tissue tumour

Abstract

Calcium pyrophosphate crystal deposition disease (CPPD), previously pseudogout, is the second most common crystal arthropathy after gout. There is increased radiographic prevalence associated with age, trauma and several metabolic disorders. Tophaceous CPPD (T-CPPD) is a rare form of CPPD which, though non-neoplastic, mimics a bone or soft tissue malignancy. T-CPPD usually presents as a mass in the temporomandibular joint and occasionally in the paraspinal tissues, but rarely in the joints of the extremities. We present an exceptionally rare case of T-CPPD that was subtle on plain radiography, presenting as a soft tissue mass in the knee joint.

Background

Calcium pyrophosphate crystal deposition disease (CPPD), previously pseudogout, is the second most common crystal arthropathy after gout.¹ The prevalence of CPPD is unknown, though there is increased radiographic prevalence associated with age, trauma and several metabolic disorders. The knee is the most commonly involved joint, followed by the wrist, ankle, elbow, toe, shoulder and hip.² The disease is usually limited to articular cartilage (chondrocalcinosis); although, less commonly it occurs in the meniscus, ligamentum flavum and intervertebral disc.³ Tophaceous CPPD (T-CPPD), also known as tumoural CPPD, is a rare form of CPPD which although non-neoplastic, may mimic a bone or soft tissue tumour.⁴ T-CPPD usually presents as a mass in the temporomandibular joint or occasionally in the paraspinal tissues, but rarely in the joints of the extremities.^{2 3 5–7} We describe an exceptionally rare case of T-CPPD in the knee with a subtle appearance on plain radiography which did not detect calcifications.

Case presentation

A 50-year-old man presented to his general practitioner with a 2-year history of left lateral knee pain, swelling and decreased range of motion. He denied any history of trauma and was otherwise healthy. On physical examination, there was a firm, non-tender, 4×4 cm mass in the lateral aspect of the popliteal fossa.

Investigations

Plain radiographs were performed and a non-calcified soft tissue mass was seen at the posterior aspect of the left knee (figure 1). MRI demonstrated a heterogeneous soft tissue mass measuring 4.5×4×2.6 cm arising in the lateral subgastrocnemius recess of the posterior capsule (figure 2A–C). There was associated scalloping of the lateral femoral condyle, bone marrow oedema-like signal in the middle and posterior thirds of the lateral femoral condyle and a small joint effusion. A radial tear of the lateral meniscus and mild patellar chondromalacia were also noted. The differential diagnoses from the referral centre included a complex ganglion or synovial mass. The patient was recalled for gadolinium-enhanced MRI, which confirmed the findings of the previous investigation and showed marked heterogeneous enhancement of the mass (figure 2D). Differential diagnosis now included an aggressive soft tissue lesion and referral to a specialist soft tissue tumour centre was advised.

Figure 1.

Lateral plain radiograph of the knee demonstrating a small soft tissue mass (arrows) posterior to the lateral femoral condyle.

Figure 2.

MR images (A) and (B) showing a well-defined intermediate soft tissue mass (arrows) measuring 4.5×4×2.6 cm (mediolateral ×  superoinferior ×  anteroposterior) in the lateral subgastrocnemius recess of the right knee, (C) showing the associated cortical erosion (arrow) and marrow oedema-like signal and (D) demonstrating heterogeneous enhancement of the mass (arrows) postcontrast. (A) Sagittal T1-weighted spin echo (T1W SE), (B) axial fat suppressed protein density weighted fast spin echo (PDW FSE), (C) sagittal fat suppressed PDW FSE and (D) postcontrast fat suppressed sagittal T1W SE.

The favoured diagnosis at the Specialist Centre was nodular pigmented villonodular synovitis (PVNS) and the patient underwent ultrasound guided needle biopsy for confirmation of this. Histological examination of the biopsy sample demonstrated cores of ligament/tendon-type tissue covered by hyperplastic synovium. There were diffuse deposits of amorphous calcified material containing rhomboid-shaped crystals on polarised light compatible with T-CPPD (figure 3).

Figure 3.

H&E, ×4 magnification, (A) synovial tissue with amorphous deposits of coarsely calcified material and (B) rhomboid-shaped crystals seen under polarised light.

A subsequent CT study showed tiny focal areas of calcification (figure 4), consistent with the histological diagnosis of T-CPPD.

Figure 4.

Axial CT study demonstrating faint calcification within the lesion (arrow).

Differential diagnosis

The nodular form of PVNS is the commonest focal intra-articular soft tissue mass of the knee, but almost invariably does not calcify. Only two cases of atypical PVNS containing calcifications have been reported.^{8 9} The demonstration of calcification, either radiographically, or as in this case by CT, therefore has an impact on differential diagnosis. Recognised causes of calcified intra-articular soft tissue masses include synovial chondroma, synovial chondromatosis,¹⁰ synovial chondrosarcoma,¹¹ synovial sarcoma,¹² tophaceous gout and chronic Hoffa's disease.^13–15 Imaging appearances of differential diagnoses are described in table 1. The possibility of a calcified mass being sarcomatous emphasises the importance of diagnostic needle biopsy. However, there remains challenges for the diagnosing pathologists, particularly when calcifications are in the context of a mass lesion with hypertrophic chondrocytes. Noting the overall features including presence of characteristic crystals and absence of bone permeation is important to prevent the overdiagnosis of chondrosarcoma and subsequent overtreatment.¹⁶

Table 1.

Imaging appearances of differentials in cases of non-radiographic tophaceous calcium pyrophosphate crystal deposition disease (T-CPPD) at the knee

	X-ray	Ultrasound	MRI	CT
T-CPPD	Normal or areas of calcification. May be soft tissue swelling	Heterogeneous soft tissue mass	Lobular soft tissue mass. Intermediate T1 signal, heterogeneously bright on proton density fat saturation sequences. Gadolinium enhancement	Lobular soft tissue mass with random focal or marginal areas of calcification7
Pigmented villonodular synovitis8	May be normal or show joint effusion. Bone erosions on both sides of the joint	Hypoechoic or heterogeneous soft tissue mass	Characteristically low-signal intensity on all image sequences including T1 and T2. ‘Blooming’ artifact from haemosiderin on gradient echo images. Variable gadolinium enhancement	Hypertrophic synovium and soft tissue mass. May be an effusion, and hyperdensity due to haemosiderin
Ganglion cyst	Usually normal. May be a soft tissue swelling	Hypoechoic (fluid density) cyst. May vary in shape, for example, discreet or lobulated. May have acoustic enhancement9	Cyst with fluid signal characteristics. High signal on T2 and low signal on T110	May be difficult to visualise. Low-density (fluid density) cyst. Low Hounsfield units
Malignant soft tissue tumour	Usually normal. May be a soft tissue swelling and bone destruction	Mixed echogenicity, may be solid and cystic components	Variable signal characteristics, tumour can be solid and cystic components. May enhance with gadolinium	Variable density, may be mixed solid and cystic components
Meniscal cyst	Usually normal. May be soft tissue swelling	May be normal if intra-articular. Hypoechoic cyst demonstrated if extra-articular	Imaging modality of choice. Cyst with fluid signal characteristics. High signal on T2 and low signal on T1	Usually normal. Low-density (fluid density) cyst if large

Treatment

It was explained to the patient that this is a benign disease. His condition was medically managed and anti-inflammatories were prescribed.

Outcome and follow-up

The patient was reviewed in clinic after 6 months. He reported a reduction in problems during activities of daily living and surgical intervention was deemed unnecessary.

Discussion

To our knowledge, there is only one case of T-CPPD without radiographic calcification in the existing literature.⁶ At the time of writing, only 30 cases in the joints of the extremities have been described in the literature. Most previous cases of T-CPPD in the extremities were radiographically misdiagnosed as bone or soft tissue tumours.^{7 17} Two cases have been previously reported in the knee joint.^{6 7} Only one of which was subtle on plain radiography,⁶ as was the case we present with also a similar clinical presentation and no history of trauma. In both cases, although plain radiographs did not demonstrate calcification in the mass, CT showed scattered focal areas of increased density compatible with calcification, demonstrating the potential value of carrying out CT. In the previous case, an excisional biopsy was performed and rhomboid-shaped, positively birefringent polarised light crystals compatible with CPPD were found.⁶ However, in our case the mass was much smaller and ultrasound guided needle biopsy was performed to confirm the histological diagnosis.

Learning points.

• Tophaceous-calcium pyrophosphate crystal deposition is especially rare in the joints of the extremities.

• Nonetheless, this diagnosis should be considered in the case of an intra-articular calcifying soft tissue mass.

• Needle biopsy should be undertaken to confirm or exclude the presence of rhomboid crystals typical of calcium pyrophosphate.