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

Written By : Dr Ishan Kataria |Medically Reviewed By : Dr. Kamal Kant Kohli Published On 2022-11-02T20:00:01+05:30  |  Updated On 2 Nov 2022 8:00 PM IST
Cutaneous Squamous Cell Carcinoma With Orbital Extension: JAMA Ophthalmology Clinical Challenge
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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.


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.

Adverse effects from immune checkpoint inhibitors are common, including fatigue, diarrhea, pruritus, nausea, and cough. Cemiplimab is generally well tolerated with a discontinuation rate of 8% in a phase 2 study. Serious autoimmune-related adverse effects can be fatal and require prompt management. In this patient, cemiplimab treatment was started until definitive surgical resection was performed. Palliative radiotherapy can preserve vision but is noncurative. Traditional chemotherapy and cetuximab treatment have low efficacy and durability in patients with advanced SCC.

The patient started cemiplimab treatment. After 3 months of immunotherapy, the mass decreased significantly to 2.5 cm. Right lateral orbitotomy with globe-sparing debulking of the tumor, lacrimal gland resection, right reconstruction of the orbital rim with bone graft, and canthoplasty were performed. Parotidectomy, neck dissection, and radial forearm free flap reconstruction were also performed. Pathology showed complete response to immunotherapy with no residual tumor at the primary site and 0/33 lymph nodes. No additional adjuvant treatment was recommended given complete pathologic response. With new treatment available for advanced cutaneous SCC, traditional periorbital treatment paradigms should be reevaluated. Further studies are needed to determine patient selection, the longterm efficacy, optimal duration of treatment, and the role of neoadjuvant use. Goals of treatment should be discussed with patients when formulating a treatment plan.

Source: Kathryn S. Park, BA; Theresa Guo, MD; Catherine Y. Liu; JAMA Ophthalmology Clinical Challenge

Published Online: October 6, 2022. doi:10.1001/jamaophthalmol.2022.3919


squamous cell carcinoma
Source : JAMA Ophthalmology Clinical Challenge
Dr Ishan Kataria
Dr Ishan Kataria

    Dr Ishan Kataria has done his MBBS from Medical College Bijapur and MS in Ophthalmology from Dr Vasant Rao Pawar Medical College, Nasik. Post completing MD, he pursuid Anterior Segment Fellowship from Sankara Eye Hospital and worked as a competent phaco and anterior segment consultant surgeon in a trust hospital in Bathinda for 2 years.He is currently pursuing Fellowship in Vitreo-Retina at Dr Sohan Singh Eye hospital Amritsar and is actively involved in various research activities under the guidance of the faculty.

    Dr. Kamal Kant Kohli
    Dr. Kamal Kant Kohli

    Dr Kamal Kant Kohli-MBBS, DTCD- a chest specialist with more than 30 years of practice and a flair for writing clinical articles, Dr Kamal Kant Kohli joined Medical Dialogues as a Chief Editor of Medical News. Besides writing articles, as an editor, he proofreads and verifies all the medical content published on Medical Dialogues including those coming from journals, studies,medical conferences,guidelines etc. Email: drkohli@medicaldialogues.in. Contact no. 011-43720751

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