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Research Letters |

Durable Response to Chemotherapy for Recurrent Squamous Cell Carcinoma of the Cheek With Perineural Spread FREE

Robert Phan, BS; Laura Phan, MD; Lawrence E. Ginsberg, MD; George Blumenschein, MD; Michelle D. Williams, MD; Bita Esmaeli, MD
Arch Ophthalmol. 2009;127(8):1074-1075. doi:10.1001/archophthalmol.2009.170.
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Published online

Squamous cell carcinoma (SCC) in the periocular region can invade the orbit and intracranial cavity.1 One route of such spread, known as perineural spread (PNS), involves the contiguous spread of the tumor along the potential space between a nerve and its sheath.26 Perineural spread is associated with a high rate of recurrence, metastasis, and poor prognosis. The usual treatment for SCC with PNS is surgical resection followed by wide-field radiation therapy (RT).4 We herein report a case of recurrent SCC with PNS treated with intravenous chemotherapy as a single modality with complete and sustained resolution of clinical and radiographic signs of PNS.

A 70-year-old man had undergone excision of an invasive SCC (<1 cm wide) of the right cheek with positive excision margins 2 years before the referral. He developed right facial paralysis and lower eyelid ectropion a few weeks after excision. He underwent surgical repair of paralytic ectropion presumed to be due to idiopathic Bell's palsy. The ectropion recurred after 8 months. Magnetic resonance imaging revealed an infraorbital right cheek mass that extended into the masticator space. The patient was referred to the M. D. Anderson Cancer Center for further management. The histologic sections of the original lesion on the cheek were reviewed at our institution and the diagnosis of SCC was confirmed (Figure 1). No perineural invasion was noted on the representative section of the original outside specimen.

Place holder to copy figure label and caption
Figure 1.

Histologic section of the lesion on the cheek shows squamous cell carcinoma (hematoxylin-eosin, original magnification ×10).

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Extraocular motility examination suggested a right abduction deficit and right esotropia (Figure 2A). Ocular adnexal examination results were significant for right eyebrow ptosis and hypesthesia of the right cheek and cornea. The patient had 11 mm of lagophthalmos, right lower eyelid paralytic ectropion, and an associated corneal ulcer. The patient denied significant pain or paresthesias.

Place holder to copy figure label and caption
Figure 2.

Clinical photographs. A, Right esotropia and paralytic ectropion of the right lower eyelid with associated corneal ulceration due to exposure and corneal hypesthesia. B, These clinical findings resolved almost completely with the exception of some residual lower-face weakness after 2 cycles of chemotherapy.

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A diagnosis of recurrent SCC of the cheek with extensive PNS and resultant multiple cranial neuropathies was made. Repeated magnetic resonance imaging again revealed a right premaxillary soft tissue tumor with extensive PNS along the right infraorbital nerve with extension to the right pterygopalatine fossa, the right cavernous sinus, and the right Meckel cave (Figure 3A and C).

Place holder to copy figure label and caption
Figure 3.

Magnetic resonance images. A, An axial fat-suppressed contrast-enhanced T1-weighted magnetic resonance image shows the tumor in the right pterygopalatine fossa (small arrow) representing posterior spread from the primary premaxillary lesion along the infraorbital branch of cranial nerve V, second division (V2). Also note excessive, abnormal enhancement in the right foramen ovale (large arrow), representing downhill, antegrade perineural extension from the Meckel cave. B, A corresponding image following treatment shows that the previously seen enhancement is largely absent. C, A coronal fat-suppressed contrast-enhanced T1-weighted magnetic resonance image shows the enhancing tumor in the right Meckel cave (arrow). D, A coronal fat-suppressed contrast-enhanced T1-weighted magnetic resonance image performed after therapy shows much-decreased enhancement in the Meckel cave (arrow).

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Given the extensive skull base spread, it was felt that the lesion was not surgically resectable. Because the patient had no significant pain, RT was deferred. Intravenous chemotherapy consisting of 736 mg of carboplatin and 380 mg of paclitaxel was administered every 3 weeks for 4 cycles. After 2 cycles of chemotherapy, the patient experienced significant resolution of clinical (Figure 2B) and radiographic (Figure 3B and D) signs of PNS. Three years after completion of chemotherapy, the patient remains without clinical or radiographic evidence of disease recurrence.

We report here an impressive durable response to systemic cytotoxic chemotherapy delivered as single-modality treatment for advanced recurrent SCC with PNS. Chemotherapy for head and neck SCC is usually delivered as induction neoadjuvant chemotherapy before surgery or RT or concurrently with RT. We were unable to find any other example in the literature of the use of systemic chemotherapy as single-modality treatment for SCC with PNS.

Perineural spread occurs in 2.5% to 14% of head and neck SCCs4,5 and 1% to 8% of periocular SCCs.1 Of those cases, only 30% to 40% are symptomatic.2 Patients who develop symptoms may have facial paresthesia, facial paralysis, exposure keratopathy, facial pain, diplopia, and hearing loss. Perineural spread is often missed until advanced stages; thus, the prognosis for patients with PNS is often poor. McNab et al3 reported that of 21 patients with PNS of SCC in the periorbital region, 13 (62%) had died of disease by the 3-year follow-up.

In our patient, the likely route of PNS was along the infraorbital nerve to the right pterygopalatine fossa, right cavernous sinus, and right Meckel cave. It is important for oculoplastic and orbital surgeons to consider PNS as a possible underlying mechanism for facial nerve palsy and other cranial neuropathies so that the diagnosis of PNS is not delayed. Our case underscores the importance of individualizing the treatment plan for patients with PNS; treatment options may include surgery, RT, or systemic chemotherapy followed by close observation.

Correspondence: Dr Esmaeli, Section of Ophthalmology, Department of Head and Neck Surgery, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1445, Houston, TX 77030 (besmaeli@mdanderson.org).

Financial Disclosure: None reported.

Malhotra  RHuilgol  SCHuynh  NTSelva  D The Australian Mohs database: periocular squamous cell carcinoma. Ophthalmology 2004;111 (4) 617- 623
PubMed Link to Article
Veness  MJBiankin  S Perineural spread leading to orbital invasion from skin cancer. Australas Radiol 2000;44 (3) 296- 302
PubMed Link to Article
McNab  AAFrancis  ICBenger  RCrompton  JL Perineural spread of cutaneous squamous cell carcinoma via the orbit: clinical features and outcome in 21 cases. Ophthalmology 1997;104 (9) 1457- 1462
PubMed Link to Article
Goepfert  HDichtel  WJMedina  JELindberg  RDLuna  MD Perineural invasion in squamous cell skin carcinoma of the head and neck. Am J Surg 1984;148 (4) 542- 547
PubMed Link to Article
Ginsberg  LE Imaging of perineural tumor spread in head and neck cancer. Semin Ultrasound CT MR 1999;20 (3) 175- 186
PubMed Link to Article
Luxenberg  MNGuthrie  TH  Jr Chemotherapy of basal cell and squamous cell carcinoma of the eyelids and periorbital tissues. Ophthalmology 1986;93 (4) 504- 510
PubMed Link to Article

Figures

Place holder to copy figure label and caption
Figure 1.

Histologic section of the lesion on the cheek shows squamous cell carcinoma (hematoxylin-eosin, original magnification ×10).

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Place holder to copy figure label and caption
Figure 2.

Clinical photographs. A, Right esotropia and paralytic ectropion of the right lower eyelid with associated corneal ulceration due to exposure and corneal hypesthesia. B, These clinical findings resolved almost completely with the exception of some residual lower-face weakness after 2 cycles of chemotherapy.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 3.

Magnetic resonance images. A, An axial fat-suppressed contrast-enhanced T1-weighted magnetic resonance image shows the tumor in the right pterygopalatine fossa (small arrow) representing posterior spread from the primary premaxillary lesion along the infraorbital branch of cranial nerve V, second division (V2). Also note excessive, abnormal enhancement in the right foramen ovale (large arrow), representing downhill, antegrade perineural extension from the Meckel cave. B, A corresponding image following treatment shows that the previously seen enhancement is largely absent. C, A coronal fat-suppressed contrast-enhanced T1-weighted magnetic resonance image shows the enhancing tumor in the right Meckel cave (arrow). D, A coronal fat-suppressed contrast-enhanced T1-weighted magnetic resonance image performed after therapy shows much-decreased enhancement in the Meckel cave (arrow).

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Tables

References

Malhotra  RHuilgol  SCHuynh  NTSelva  D The Australian Mohs database: periocular squamous cell carcinoma. Ophthalmology 2004;111 (4) 617- 623
PubMed Link to Article
Veness  MJBiankin  S Perineural spread leading to orbital invasion from skin cancer. Australas Radiol 2000;44 (3) 296- 302
PubMed Link to Article
McNab  AAFrancis  ICBenger  RCrompton  JL Perineural spread of cutaneous squamous cell carcinoma via the orbit: clinical features and outcome in 21 cases. Ophthalmology 1997;104 (9) 1457- 1462
PubMed Link to Article
Goepfert  HDichtel  WJMedina  JELindberg  RDLuna  MD Perineural invasion in squamous cell skin carcinoma of the head and neck. Am J Surg 1984;148 (4) 542- 547
PubMed Link to Article
Ginsberg  LE Imaging of perineural tumor spread in head and neck cancer. Semin Ultrasound CT MR 1999;20 (3) 175- 186
PubMed Link to Article
Luxenberg  MNGuthrie  TH  Jr Chemotherapy of basal cell and squamous cell carcinoma of the eyelids and periorbital tissues. Ophthalmology 1986;93 (4) 504- 510
PubMed Link to Article

Correspondence

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