Fine-needle aspiration cytology of periarticular nodule - Atypical presentation of gouty tophi: A report of two cases.

Gout is a chronic arthropathy caused due to the deposition of monosodium urate crystals. Gouty tophus can be the initial presenting feature of gout with or without any clinical symptoms. Demonstration of urate crystals in synovial fluid or biopsy helps in confirming the diagnosis of gout. However, fine-needle aspiration cytology (FNAC) of periarticular soft-tissue nodules is a valuable tool in the diagnosis of gout. We present two such cases of isolated soft-tissue lesions wherein the initial diagnosis of gouty tophus was made on FNAC and subsequently followed by a clinical and biochemical workup.

INTRODUCTION

Gout is arthritis caused due to the deposition of uric acid crystals. Periarticular nodules can be a challenge to both clinicians and radiologists. Various causes of periarticular soft-tissue nodules include rheumatoid nodules, ganglion cysts, pigmented villonodular synovitis, synovial chondromatosis, and synovial sarcoma.[ Gouty tophus is an important differential diagnosis of nodular swelling and it can be difficult to diagnose, especially in cases of atypical presentation or the absence of arthritis or hyperuricemia. In such cases, fine-needle aspiration cytology (FNAC) can help in diagnosing periarticular gouty tophi by the demonstration of urate crystals. We present two cases of gouty tophus with a review of the literature.

CASE REPORTS

Case 1

A 48-year-old male patient presented with a subcutaneous nodule and pain around the nodule on the posterior aspect of the left ankle for the past 2 years [Figure 1a]. Local examination revealed a soft-tissue nodule of 2 × 2 cm. It was firm, immobile, and non-tender. The overlying skin was ulcerated. The patient revealed that a recent incision and drainage procedure was done on the same site 15 days back by a medical practitioner treating it for an abscess. The patient had no other systemic complaints. Radiographs of the left feet (anterior-posterior view) showed a soft-tissue swelling overlying the posterior aspect of the ankle [Figure 1b]. No evidence of any calcification or lucency was seen within the swelling. Underlying bones and articular surfaces appeared normal. No definite clinical diagnosis was made and the patient was advised for FNAC. FNAC was performed and yielded whitish cellular aspirate. Light microscopy of air-dried smears was stained with Giemsa stain and wet smears were alcohol fixed in ethanol and Papanicolaou staining was performed. Fine-needle aspiration demonstrated slender needle-shaped urate crystals seen in stacks and sheave and singly dispersed which are negatively stained in Giemsa stain [Figure 1c and d]. Few multinucleated giant cells and synovial cells were also present in the background of blood. Diagnosis of gouty tophus was given. On further investigation, the patient’s uric acid levels were found to be 10.5 mg/dl. Hematological workup revealed hemoglobin (11.2 g/dL), leukocyte count (5900/mm3), and platelet count (180,000/µL). The patient was started on uricosuric drugs.

Figure 1:

(a) Clinical photograph showing an ulcerated nodule on the ankle. (b) Radiograph of the ankle anteroposterior view shows a lytic lesion in the ankle. (c and d) Photomicrograph shows negatively stained singly scattered and clusters of needle-shaped urate crystals in the background of blood; Giemsa stain ×100, c; ×400, d.

Case 2

A 48-year-old male patient presented with on and off pain and nodular swelling on the dorsal aspect of the left forearm around the elbow joint for 1 year. There was a firm immobile nodule measuring 1.5 × 1.5 cm [Figure 2a]. Hematological and biochemical examination revealed Hb of 9.1 gm/dL an elevated erythrocyte sedimentation rate of 70 mm in the 1st h. The liver function test and serum electrolytes were within normal limits. Serum urea was normal but serum creatinine was raised (2.3 g/dl). The patient also had raised serum uric acid level of 13.1 mg/dl. Ultrasonography of the swelling was performed which showed a soft-tissue lesion in the posterior aspect of the left upper arm near the elbow joint which was heterogeneously hyperechoic with liquefaction and necrosis. Underlying bone appeared normal and no conclusive diagnosis was made. The patient was advised of FNAC of the swelling for further confirmation. On FNAC, blood mixed whitish cellular material was aspirated. Air-dried smears were stained with Giemsa stain and wet smears were alcohol fixed in ethanol and Papanicolaou staining was performed. Microscopy showed many needles shaped crystals in aggregates and singly scattered, which are negatively stained in Giemsa and PAP stain, along with occasional multinucleated giant cells along with synovial cells and a few acute inflammatory infiltrates [Figure 2b-d]. A final diagnosis of gouty tophus was made. The patient was started on uricosuric drugs.

Figure 2:

(a) Clinical photograph shows a nodule in the shin. (b) Photomicrograph demonstrates slender needle-shaped urate crystals seen in stacks and sheave and singly dispersed needle-shaped urate crystals along with a few acute and chronic inflammatory cells and reactive giant cells; Giemsa stain ×100 (c and d) photomicrograph shows singly scattered and clusters of needle-shaped urate crystals Giemsa stain ×400, c; pap stain ×400, d.

DISCUSSION

Gout is a metabolic condition caused by persistent hyperuricemia which can occur as a result of inborn errors of purine metabolism or diminished renal excretion of uric acid. It can also be found in systemic conditions with extensive cell turnover. This disease more commonly occurs in men than in women and usually occurs during the 5th and 6th decades of life.[ It usually manifests as acute arthritis but can also present in the form of the asymptomatic nodule. The first metatarsophalangeal joint is the most common site for gouty deposition. Ankles, knees, wrists, and the interphalangeal joints of hands and shoulder can also be affected by uric acid deposition. It usually takes around 5 years between arthritis and the development of tophi.[ Tophi are commonly located in the olecranon bursa, the infrapatellar and Achilles tendons, and also in the subcutaneous tissue of the extensor surfaces of forearms.[ Gout generally manifests through four stages in its evolution: Asymptomatic hyperuricemia, acute gout, interval gout, and tophaceous gout. However, they can develop without concomitant arthritis. The diagnosis of gout becomes difficult when the presentation is atypical with no preceding history of gouty arthritis or when the serum uric acid levels are not raised. Sometimes, presentation as periarticular tophaceous nodules could be the first manifestation of gout.[

Soft-tissue tophi can be mistaken for neoplasm clinically and radiologically. The radiological features of gouty arthritis such as soft-tissue swelling, bone erosion, and solid soft-tissue masses (tophi) are not specific and can be seen in various benign and malignant disorders.[ The differential diagnosis of periarticular nodules includes rheumatoid nodule, ganglion cyst, pigmented villonodular synovitis, tumoral calcinosis, synovial chondromatosis, and synovial sarcoma.[ Pseudogout poses a further diagnostic challenge. It is characterized by the deposition of calcium pyrophosphate dehydrate (CPPD) crystals which are shorter, rhomboid, or needle shaped with weakly positive birefringence. In contrast, urate crystals are longer, slender needle shaped and scattered singly or in sheaves and stacks and have strong negative birefringence.[ On histopathology, tophi typically have a characteristic feathery appearance along with the presence of foreign body giant cells around aggregates of needle-shaped empty spaces in a basophilic matrix formed by washed urate crystals.[ Urate crystals can be readily demonstrated in both Giemsa and Papanicolaou stains. Nasser et al. mentioned the utility of Diff-Quick stain in the evaluation of gouty tophi and recommended the use of air-dried smears stained with Diff-Quick Romanowsky stain.[ FNA smears can also be stained by Papanicolaou stain after alcohol fixation to highlight the golden brown needle-shaped gouty crystal as well.[ Alcohol fixation is preferred over formalin fixation.[ On histopathology, few lesions do not show characteristic histologic features due to minimal crystal deposits, smaller biopsy, or foreign body giant cell response. There can be an abundance of a basophilic matrix with scant crystals or palisading granuloma-like formation. Special techniques can be helpful to demonstrate the presence of urate crystals in such cases. The different staining methods used to demonstrate urate crystals in tissue consist of Gomori methenamine silver stain and deGalantha stain. They are non-specific like routine hematoxylin-eosin (HE) stains without any specific advantage.[

Shidham et al. did a study of seven cases of pseudogout and eight cases of gout to ascertain the application of a special stain in the evaluation of the birefringence property of the gouty crystal. They observed that birefringence in the sections stained with the NAES method was H and E-stained sections failed to demonstrate the birefringent crystals by polarizing microscopy. They concluded that polarizing microscopy of sections stained with the NAES gave positive birefringence in CPPD crystals pseudogout, negative birefringence in MSU crystals in gout, and calcium hydroxyapatite crystals without birefringence in tumoral calcinosis which might not polarize in the routine H&E-stained sections. Therefore, NAES method can be used to supplement routine H&E stain for proper evaluation of the crystals under the polarizing microscope in cases where H and E do not give definitive results.[

SUMMARY

Periarticular nodules when subjected to FNAC may provide diagnostic material in patients presenting with gouty tophus. FNAC diagnosis thus may prove reliable even in the absence of biochemical findings and provide an early clinical diagnosis.