Cutaneous Squamous Cell Carcinoma With Orbital Extension: JAMA Ophthalmology Clinical Challenge

A 72-year-old homeless man was referred for management of a recurrent cutaneous squamous cell carcinoma (SCC) of the right temple and brow. On review of history, maxillofacial magnetic resonance imaging (MRI) with and without contrast done 5 months prior to presentation showed a 5.9 × 5.3 × 3.7-cm mass centered at the right temple that tracked along the right lateral orbital wall as well as an enhancing right intraparotid lymph node.

The patient was lost to follow-up and re-presented 5 months later with an enlarged crusting and ulcerating lesion of the right temple/brow. On ocular examination, best corrected visual acuity was 20/100 OD and 20/125 OS due to cataracts, pupils reacted normally without afferent pupillary defect, and ocular motility was full. He had mild proptosis in the right eye and right lower eyelid retraction. Orbicularis strength was intact and symmetric in both eyes.

MRI of the orbits, face, and neck with and without contrast showed a 6.1 × 5.7 × 4.0-cm mass with erosion through the right sphenoid wing, involvement of the lacrimal gland, and abutment of the lateral rectus. In discussing treatment strategies for the orbital component of the disease, the patient was strongly against an orbital exenteration.

The patient was diagnosed as Stage T3N1M0 recurrent cutaneous SCC of the face. Neoadjuvant cemiplimab immunotherapy (anti–PD-L1 antibody), globe sparing orbitotomy, and surgical excision of the mass were the next line of treatment.

Advanced cutaneous SCC with orbital involvement has historically been difficult to treat with 10-year survival rates less than 20%. The standard treatment is exenteration, due to difficulty in obtaining clear margins in the orbit. Exenteration has been shown to provide better local control with clear margins obtained in 42.5% to 97% of cases and lower rates of local recurrence with overall survival of 83% and65% at 1 and 5 years, respectively. However, recently, the overall survival benefit of exenteration vs conservative surgeries has been questioned. In addition, exenteration causes facial disfigurement, loss of vision, psychological distress, and some, like this patient, may decline this surgery.

Recent reports have shown favorable outcomes with new immunotherapy treatments without exenteration in patients with locally advanced SCC with orbital extension. Cutaneous SCC has demonstrated excellent response to immunotherapy, with phase 1 and 2 trials demonstrating a 44% to 50% response rate. In 2018, the US Food and Drug Administration approved cemiplimab for the treatment of locally advanced and metastatic cutaneous SCC based on phase 1 and 2 trials.

The 2020 European interdisciplinary guidelines indicate cemiplimab as first-line treatment for advanced SCC not treatable with curative surgery or radiotherapy (grade A recommendation; level 2 evidence). A phase 2 study on the efficacy of neoadjuvant cemiplimab in head and neck SCC found complete pathologic response in 55% of patients, who ultimately did not receive radiotherapy after surgery. No guidelines exist on the duration of immunotherapy treatment, and clinical trials are underway to address the emerging role of cemiplimab in the neoadjuvant and adjuvant settings.

A 72-year-old homeless man was referred for management of a recurrent cutaneous squamous cell carcinoma (SCC) of the right temple and brow. On review of history, maxillofacial magnetic resonance imaging (MRI) with and without contrast done 5 months prior to presentation showed a 5.9 × 5.3 × 3.7-cm mass centered at the right temple that tracked along the right lateral orbital wall as well as an enhancing right intraparotid lymph node.

The patient was lost to follow-up and re-presented 5 months later with an enlarged crusting and ulcerating lesion of the right temple/brow. On ocular examination, best corrected visual acuity was 20/100 OD and 20/125 OS due to cataracts, pupils reacted normally without afferent pupillary defect, and ocular motility was full. He had mild proptosis in the right eye and right lower eyelid retraction. Orbicularis strength was intact and symmetric in both eyes.

MRI of the orbits, face, and neck with and without contrast showed a 6.1 × 5.7 × 4.0-cm mass with erosion through the right sphenoid wing, involvement of the lacrimal gland, and abutment of the lateral rectus. In discussing treatment strategies for the orbital component of the disease, the patient was strongly against an orbital exenteration.

The patient was diagnosed as Stage T3N1M0 recurrent cutaneous SCC of the face. Neoadjuvant cemiplimab immunotherapy (anti–PD-L1 antibody), globe sparing orbitotomy, and surgical excision of the mass were the next line of treatment.

Advanced cutaneous SCC with orbital involvement has historically been difficult to treat with 10-year survival rates less than 20%. The standard treatment is exenteration, due to difficulty in obtaining clear margins in the orbit. Exenteration has been shown to provide better local control with clear margins obtained in 42.5% to 97% of cases and lower rates of local recurrence with overall survival of 83% and65% at 1 and 5 years, respectively. However, recently, the overall survival benefit of exenteration vs conservative surgeries has been questioned. In addition, exenteration causes facial disfigurement, loss of vision, psychological distress, and some, like this patient, may decline this surgery.

Recent reports have shown favorable outcomes with new immunotherapy treatments without exenteration in patients with locally advanced SCC with orbital extension. Cutaneous SCC has demonstrated excellent response to immunotherapy, with phase 1 and 2 trials demonstrating a 44% to 50% response rate. In 2018, the US Food and Drug Administration approved cemiplimab for the treatment of locally advanced and metastatic cutaneous SCC based on phase 1 and 2 trials.

The 2020 European interdisciplinary guidelines indicate cemiplimab as first-line treatment for advanced SCC not treatable with curative surgery or radiotherapy (grade A recommendation; level 2 evidence). A phase 2 study on the efficacy of neoadjuvant cemiplimab in head and neck SCC found complete pathologic response in 55% of patients, who ultimately did not receive radiotherapy after surgery. No guidelines exist on the duration of immunotherapy treatment, and clinical trials are underway to address the emerging role of cemiplimab in the neoadjuvant and adjuvant settings.