July 2019
Volume 60, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2019
Incidence of Perineural Invasion with Hedgehog Pathway Inhibitors in Orbital and Periorbital Basal Cell Carcinoma
Author Affiliations & Notes
  • Arthika Chandramohan
    Ophthalmology, Stanford Eye Institute, California, United States
  • Archana Appukuttan Nair
    Ophthalmology, New York University, New York, United States
  • Anne Chang
    Dermatology, Stanford University, California, United States
  • Andrea L Kossler
    Ophthalmology, Stanford Eye Institute, California, United States
  • Footnotes
    Commercial Relationships   Arthika Chandramohan, None; Archana Nair, None; Anne Chang, None; Andrea Kossler, None
  • Footnotes
    Support  none
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 3585. doi:
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      Arthika Chandramohan, Archana Appukuttan Nair, Anne Chang, Andrea L Kossler; Incidence of Perineural Invasion with Hedgehog Pathway Inhibitors in Orbital and Periorbital Basal Cell Carcinoma. Invest. Ophthalmol. Vis. Sci. 2019;60(9):3585.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : To report our incidence of malignant perineural invasion (PNI) noted following the use of neoadjuvant Hedgehog Pathway Inhibitors (HPI) for orbital and periorbital basal cell carcinoma (BCC).

Methods : This retrospective cohort study examined all patients who received neoadjuvant HPI therapy at Stanford Hospital from 2009 to 2018. Data were abstracted via clinical study data, imaging files, and photographs. Dermatopathology specimens were evaluated for large nerve (>0.1mm diameter) invasion guided by pre-surgical imaging. The study was granted IRB exemption from the university’s institutional review board.

Results : Twenty-two patients were treated with neo/adjuvant HPIs. Two patients (9.1%) treated with vismodegib had histopathologic evidence of large nerve PNI. Both received vismodegib as neoadjuvant therapy for >6 months and showed secondary resistance by RECIST criteria. The first was a 48-year-old female with initial complete clinical response but who developed recurrence three months after stopping therapy. Moh’s excision with negative margins was performed and the patient was disease free for two and half years until she presented with brow numbness and an enlarged superior orbital nerve on MRI. Repeat biopsy confirmed BCC with newly noted perineural invasion of the superior orbital nerve. The other was a 76-year-old male maintained on vismodegib with stable orbital disease and moderate regression from treatment for 30 months. Three months after treatment cessation, an orbital MRI revealed enlargement of the infraorbital nerve and biopsy confirmed BCC. Both patients developed concurrent facial squamous cell carcinomas while on HPI treatment and stopped the HPIs due to intolerable side effects.

Conclusions : Reported incidence of large nerve invasion by cancerous cells in basal cell carcinoma (BCC) is rare, approximately 3% in examined orbital cases. We report a 9.1% incidence in cases receiving neoadjuvant hedgehog pathway inhibitor (HPI) therapy, an over threefold increase compared to orbital cases not treated with HPIs. Though limited by sample size and retrospective design, our data supports further investigation of the cellular changes that occur in the tumor beds of regressed BCC, which may harbor lingering disease or resistant cells with de novo mutations--perhaps with an affinity for proximate large caliber nerves--perpetuating carcinomatous disease.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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