What is the cause of recurrent squamous cell carcinoma in a patient with initial stage T2N0, who underwent surgery and had a subsequent PET (Positron Emission Tomography) scan showing no residual malignant disease, only to have the tumor recur after 4 months?

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Last updated: April 16, 2025View editorial policy

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From the Guidelines

The recurrence of squamous cell carcinoma after surgery despite a negative PET scan is not uncommon and can occur for several reasons, with the most likely explanation being microscopic cancer cells remaining after surgery that were too small to be detected by the PET scan, as supported by the study published in the Journal of the American College of Radiology in 2023 1. This phenomenon is called local recurrence and happens in a significant percentage of cases, depending on the original tumor location and characteristics. Other possibilities include incomplete surgical margins during the initial operation, particularly if the tumor was in a difficult anatomical location, or the aggressive biological nature of the particular cancer with a high propensity for recurrence. Some key factors that may contribute to the recurrence of squamous cell carcinoma include:

  • The presence of desmoplasia, which has been shown to pose a greatly increased risk of both recurrence and metastasis, as reported in studies from Germany 1
  • Invasion of squamous cell cancer into the deep reticular dermis or subcutaneous fat, which has been associated with aggressive behavior 1
  • Squamous cell tumor depth, as measured in millimeters, which may also have prognostic value 1 The management now typically involves a multidisciplinary approach, potentially including re-excision with wider margins, radiation therapy if not previously administered, and possibly systemic therapy depending on the extent of recurrence. Close surveillance will be necessary moving forward, with regular imaging and physical examinations every 3-6 months for at least the first two years, as this period carries the highest risk for additional recurrences, with up to 40% of patients suffering recurrence after therapy, and up to 25% of patients developing distant metastases, as stated in the study published in the Journal of the American College of Radiology in 2023 1.

From the Research

Tumor Recurrence in Squamous Cell Carcinoma

  • The recurrence of squamous cell carcinoma (SCC) after surgery and a PET scan showing no residual malignant tissue can be attributed to several factors, including the tumor's characteristics and the treatment approach 2, 3.
  • Studies have shown that the risk of recurrence increases with the number of risk factors (RFs) present in the tumor, such as diameter, poorly differentiated histology, tumor extension, and nerve invasion 4.
  • A retrospective cohort study found that the cumulative incidence of local recurrence, nodal metastasis, distant metastasis, and disease-specific death increased significantly as the number of RFs increased from 0 to 4 4.
  • Another study compared the risk of recurrence between Mohs micrographic surgery (MMS) and standard excision for cutaneous SCC of the head and neck, finding that MMS was associated with a lower rate of recurrence 5.

Risk Factors for Recurrence

  • Tumor size: A diameter of 2 cm or larger is considered a risk factor for recurrence 4.
  • Poorly differentiated histology: Tumors with poorly differentiated histology are more likely to recur 4.
  • Tumor extension: Tumors that extend beyond subcutaneous fat are at higher risk of recurrence 4.
  • Nerve invasion: Large caliber nerve invasion is a risk factor for recurrence 4.

Treatment Approaches

  • Surgery: The primary treatment for SCC, with the goal of removing the tumor and achieving clear margins 2, 5.
  • Radiation therapy: May be used as adjuvant or salvage treatment for high-risk tumors or in cases where surgery is not possible 3.
  • Mohs micrographic surgery: A surgical technique that involves removing the tumor layer by layer, with a lower rate of recurrence compared to standard excision 5.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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