What is the significance of a PET scan showing metastasis to a single internal mammary lymph node and pericardial fat pad, with a Cancer Antigen (CA) 125 level of 48 in a patient with stage 4 ovarian cancer?

Significance of PET-Positive Internal Mammary Node and Pericardial Fat Pad in Stage 4 Ovarian Cancer

The PET-avid internal mammary lymph node and pericardial fat pad uptake represent distant metastatic disease consistent with your patient's stage 4 ovarian cancer, but the relatively low CA-125 of 48 U/mL suggests either early recurrence, low tumor burden, or a less chemosensitive tumor phenotype that warrants close surveillance and consideration of systemic therapy. 1, 2

Understanding the Clinical Context

Internal Mammary Node Metastasis

• Supradiaphragmatic lymph node involvement, including internal mammary nodes, is a documented but uncommon site of ovarian cancer metastasis. 3
• Internal mammary lymph node metastases from ovarian cancer have been reported in the literature, including cases discovered incidentally years after initial diagnosis. 3
• This finding confirms distant metastatic spread and is consistent with stage 4 disease classification. 1

Pericardial Fat Pad Involvement

• Pericardial involvement represents advanced disease with thoracic extension beyond typical peritoneal spread. 1
• PET/CT has superior accuracy for detecting distant metastases compared to CT alone, particularly in detecting small volume disease in unusual locations. 4, 1

Interpreting the CA-125 Level

The Discordance Between Imaging and Tumor Marker

• Your patient's CA-125 of 48 U/mL is only minimally elevated (normal <35 U/mL), which creates a clinically significant discordance with the PET findings. 2
• CA-125 has only 50% sensitivity for stage I disease but typically shows elevated levels in 80% of patients with stage II or greater disease. 2, 5
• This relatively low CA-125 in the setting of metastatic disease suggests one of three scenarios:
  • Low tumor burden with metabolically active but small volume disease 1
  • A tumor phenotype with poor CA-125 expression (occurs in approximately 3-4% of advanced ovarian cancers) 5
  • Potentially less chemosensitive disease, as CA-125 kinetics correlate with platinum sensitivity 1

CA-125 Dynamics and Prognosis

• The modeled CA-125 elimination rate constant (KELIM) during chemotherapy is a validated independent indicator of tumor platinum-based chemosensitivity. 1
• Serial CA-125 monitoring will be critical for this patient, as progressive elevation over time—even within the normal range—may indicate disease progression and warrants further evaluation. 6, 2

Clinical Implications and Management

Imaging Strategy

• CT of the chest, abdomen, and pelvis with IV contrast should be obtained to fully characterize the extent of disease beyond the PET findings. 4, 1
• PET/CT is particularly valuable when CT findings are indeterminate or when there is rising CA-125 with negative conventional imaging, which is relevant for future surveillance in this patient. 4, 1
• The combination of PET/CT with contrast-enhanced CT provides superior accuracy for staging compared to either modality alone. 1, 4

Treatment Considerations

• The presence of distant metastases (internal mammary node, pericardial involvement) in stage 4 disease typically indicates systemic chemotherapy as the primary treatment modality. 1
• The relatively low CA-125 may indicate a tumor with different biological behavior that could affect chemotherapy response. 1
• Close monitoring of CA-125 kinetics during the first 3-4 cycles of chemotherapy will provide prognostic information about tumor chemosensitivity. 1

Surveillance Strategy

• Serial CA-125 measurements every 3 months during active treatment and surveillance are recommended, particularly given the baseline elevation. 1, 2
• Imaging surveillance with CT chest/abdomen/pelvis should be performed when CA-125 rises or clinical symptoms develop. 1, 4
• PET/CT should be reserved for situations where conventional imaging is equivocal despite clinical or biochemical suspicion of progression. 1, 4

Important Caveats

Differential Diagnosis Considerations

• While ovarian cancer is the presumed primary given the stage 4 diagnosis, breast metastases to internal mammary nodes from a synchronous breast primary should be excluded if not already done, as this would fundamentally change management. 7, 8
• Immunohistochemical staining for CA-125, PAX8, and ER/PR can differentiate ovarian from breast primaries if tissue is available. 7, 8

Prognostic Implications

• Supradiaphragmatic metastases from ovarian cancer, including internal mammary node involvement, generally indicate advanced disease with guarded prognosis. 3, 9
• The low CA-125 relative to disease burden may indicate a less favorable tumor biology, as higher CA-125 levels typically correlate with more chemosensitive disease. 1, 5

Monitoring Pitfalls to Avoid

• Do not rely solely on CA-125 for surveillance in this patient—the discordance between imaging and tumor marker necessitates combined biochemical and radiographic monitoring. 1, 2
• False-negative PET/CT can occur with mucinous or borderline tumors, but false-positive results can occur with inflammatory conditions. 4
• Progressive CA-125 elevation, even if remaining below 70 U/mL (twice the upper limit of normal), should prompt imaging evaluation. 2