What is the clinical significance and management of the Castle sign?

Castle Sign: Clinical Significance and Management

The Castle sign, also known as the reversed halo sign or atoll sign, is a radiographic finding on CT imaging characterized by an area of ground glass opacity surrounded by a ring of consolidation, which is highly suggestive of mucormycosis infection and requires urgent diagnostic confirmation and treatment.

Radiographic Characteristics and Diagnostic Value

• The Castle sign (reversed halo sign) appears as an area of ground glass opacity surrounded by a ring of consolidation on CT imaging, particularly in pulmonary infections 1
• This sign was present in 19% of patients with mucormycosis, but in less than 1% of patients with invasive aspergillosis and in no patients with fusariosis, making it relatively specific for mucormycosis in the appropriate clinical context 1
• The diagnostic value of this finding depends on the pre-test probability, as a wide range of infectious and non-infectious diseases may present with a reversed halo sign 1

Clinical Significance

• When the Castle sign is identified in immunocompromised patients, particularly those with hematological malignancies, it should raise high suspicion for invasive mucormycosis 1
• The majority of patients with a reversed halo sign had undergone hematopoietic stem cell transplantation for acute myelogenous or chronic lymphatic leukemia 1
• Other radiographic findings that may support mucormycosis diagnosis include:
  • Pleural effusion, which independently predicted mucormycosis in comparative studies 1
  • Multiple nodular infiltrates (more than ten) may be associated with mucormycosis, though findings are inconsistent across studies 1

Management Approach

Diagnostic Confirmation

• When the Castle sign is identified, histological proof is urgently needed to confirm the diagnosis 1
• CT-guided needle biopsy has been successfully used to diagnose mucormycosis in patients with pulmonary nodular infiltrates, with a diagnostic yield of 11-21% 1
• A minimum platelet count of 50,000/μL is recommended for biopsy procedures, which can be achieved through platelet transfusion if necessary 1

Imaging Considerations

• KDOQI guidelines recommend using the smallest volume of iodinated contrast or non-iodinated contrast agents (e.g., CO2 gas) to preserve residual kidney function in patients with CKD 1
• In patients with suspected disseminated disease (approximately 20% of cases), cranial, thoracic, and abdominal imaging studies are warranted 1

Treatment Approach

• Once mucormycosis is confirmed, prompt treatment is essential due to its high mortality rate 1
• Surgical debulking or resection of infected tissue is often necessary 2
• Antifungal therapy with amphotericin B formulations is the mainstay of treatment 1
• For patients with extrathyroidal extension or nodal metastases in CASTLE tumors (a rare thyroid malignancy that can present with a similar radiographic appearance), curative surgery followed by adjuvant radiotherapy should be considered 2

Differential Diagnosis

• While the Castle sign is highly suggestive of mucormycosis in immunocompromised patients, it can also be seen in:
  • Other fungal infections (though less commonly in aspergillosis and not in fusariosis) 1
  • CASTLE tumors (Carcinoma showing thymus-like differentiation), which are rare thyroid malignancies accounting for 0.1-0.15% of all thyroid cancers 2, 3
  • Other infectious and non-infectious pulmonary conditions 1

Prognostic Implications

• Early identification and management of the Castle sign, particularly when associated with mucormycosis, is critical for improving survival 1
• In CASTLE tumors, nodal involvement and extrathyroidal extension are the main prognostic factors that influence patient survival 2
• Complete resection of CASTLE tumors is vital to reduce local recurrence rates and improve long-term survival 2

Pitfalls and Caveats

• The Castle sign is not pathognomonic for any single condition and must be interpreted in the appropriate clinical context 1
• Delay in diagnosis and treatment of mucormycosis can significantly increase mortality 1
• Percutaneous core needle biopsy may not be helpful in diagnosing some conditions that present with the Castle sign, such as Castleman's disease 4
• Significant CT enhancement with intravenous contrast in vascular lesions may indicate increased vascularity, which could cause surgical complications during resection 4