Periocular Squamous Cell Carcinoma Research Articles

Immunotherapy for local/regional control of locally advanced orbital and periocular squamous cell carcinoma.

e18034 Background: Periocular squamous cell carcinoma can be of eyelid skin, ocular surface (bulbar) or palpebral conjunctival, or of lacrimal sac/nasolacrimal duct mucosal origin, is relatively rare, and presents unique anatomic considerations due to proximity to the eye and inherent risk to ocular structures associated with high dose radiation therapy. We herein report on 17 patients with orbital or periocular SCC who were treated with immunotherapy (IO) to decrease surgical morbidity or to avoid high dose radiation therapy. Methods: Retrospective review of all previously unreported patients with orbital, conjunctival, or periocular SCC who were treated with IO either in the neoadjuvant setting prior to surgery or for treatment of periocular SCC with perineural spread into the orbit and skull base. Results: 17 patients, 12 men and 5 women (Age range: 44-92; median=70 years old) with orbital (n=6), conjunctival (n=5), or lacrimal sac/duct (n=2) squamous cell carcinoma (SCC), or periocular SCC with perineural spread into the orbit and skull base (n=4) who were treated with IO either as single drug (n= 11) or in combination with chemotherapy (n= 6 ). In all patients either cemiplimab or pembolizumab was used. In 13 patients IO was used in the neoadjuvant setting prior to planned surgery. In 4 patients with perineural spread as they had non surgically resectable disease, IO was used to avoid high dose radiation therapy with its inherent significant risk of ocular toxicity. Overall, 3 patients achieved complete response, 10 patients achieved partial response, and 4 patients had stable disease, using RECIST criteria. One of 5 patients with conjunctival SCC also had nodal metastasis at presentation and achieved a dramatic complete response of both the conjunctival tumor and the nodal metastasis and managed to avoid surgery altogether. This patient had a very high tumor mutation burden (TMB). One patient developed diabetic ketoacidosis as a side effect of IO; otherwise the adverse effects were low grade. Conclusions: IO either as single drug or in combination with chemotherapy has a fairly high response rate in patients with ocular adnexal, conjunctival or orbital SCC and in patients with periocular SCC with perineural spread in the orbit and skull base. Future prospective trails using IO for orbital and ocular adnexal SCC should be planned and should aim to correlate molecular data such as TMB with response.

Intralesional interferon alpha-2b as a novel treatment for periocular squamous cell carcinoma in horses.

To determine the safety and efficacy of perilesional human recombinant interferon alpha-2b (IFNα2b) for treatment of periocular squamous cell carcinoma (PSCC) in horses. Eleven horses (12 eyes) with PSCC were enrolled in this prospective clinical study with owner consent. Systemically healthy horses were included in the study following confirmation of PSCC via biopsy. Every two weeks for a maximum of six treatments, horses were sedated and perilesional injection of IFNα2b (10 million IU) was performed. Tumors were measured prior to each injection and at one, three, and 12 months after treatment completion. A greater than 50% reduction in tumor size was considered positive response to treatment (i.e., partial or complete response). Development of anti-IFNα2b antibodies was assessed using serum samples obtained after treatment initiation and compared with treatment responses. Antibody concentrations were analyzed using a mixed model. Statistical significance was considered p < 0.05. Each horse received four to six perilesional injections of IFNα2b. Five of 12 eyes (4/11 horses) responded to treatment. Two of five eyes showed complete resolution of gross PSCC. No systemic adverse effects were seen. Local swelling occurred during treatment protocol in 6/11 horses but resolved without intervention. All horses developed serum anti-IFNα2b antibodies. There was no evidence of statistical difference in antibody concentration between responders and non-responders. Perilesional administration of IFNα2b was found to be well-tolerated in horses with PSCC, and induced tumor regression in 42% of treated eyes. Treatment failure appears unrelated to the development of IFNα2b antibodies.

Outcomes of Mohs micrographic surgery for periocular squamous cell carcinoma.

Periocular cutaneous squamous cell carcinoma (cSCC) accounts for 5-10% of all eyelid malignancies. Periocular cSCC carries a low mortality rate but can be destructive to local tissues. Due to the unique function and anatomy of the eyelids, Mohs micrographic surgery (MMS) is gold standard for treating cSCC to preserve healthy tissue and reduce rates of local recurrence. In this study, we describe the success and outcomes of MMS and subsequent oculoplastic reconstruction for periocular cSCC in the North East of England. Retrospective analysis of 34 patients who underwent MMS for periocular cSCC in the North of England between 2013 and 2020. Primary outcome measure of success is defined as no recurrence of cSCC after minimum 24 months' time elapsed post-MMS. Secondary outcome measures included analysis of disease characteristics, describing the surgical techniques utilised for oculoplastic reconstruction following MMS and surgical complications should they occur. Two patients (5.9%) had local recurrence of periocular cSCC. Median time elapsed since MMS was 60 months. A variety of oculoplastic surgical techniques were utilised in the repair of the Mohs defect. One patient (2.9%) developed a significant post-operative reconstruction complication. Periocular cSCC recurrence following MMS in the North of England is 5.9%, which is comparable to the literature. Significant post-operative complications following oculoplastic reconstruction of periocular MMS are very low, occurring in 2.9% of cases in this study.

Solving an eye condition by looking to the rear

Solving an eye condition by looking to the rear

Transorbital drillout to the cavernous sinus: an approach for squamous cell carcinoma with perineural spread. Illustrative cases

This study describes a transorbital apical approach to the cavernous sinus, where the greater wing of sphenoid (GWS) and superior orbital fissure (SOF) are drilled out to access the interdural incision zone and lateral wall of the cavernous sinus. This was a retrospective series of 3 patients with periocular squamous cell carcinoma (SCC) and radiological evidence of perineural spread to the cavernous sinus. Following an orbital exenteration, the GWS was drilled to reach the lateral border of the SOF. The meningo-orbital band, a periosteal transition between the frontotemporal basal dura and periorbita, was incised to enter the lateral wall of the cavernous sinus. The relevant cranial nerves were biopsied to provide an accurate zonal classification of disease. The transorbital apical approach via the SOF provides a corridor of access to the cranial nerves within the lateral wall of the cavernous sinus. This technique was successfully performed on 3 patients with periocular SCC. One case had radiological evidence of intracavernous oculomotor nerve involvement, 1 patient demonstrated nasociliary nerve enlargement at the SOF, and another had frontal nerve involvement extending into the cavernous sinus. Cerebrospinal fluid leak occurred in 1 case addressed with fat packing and fascial closure.

Novel MSH6 mutation predicted metastasis in eyelid and periocular squamous cell carcinoma.

Our previous research revealed the relative local aggressiveness of eyelid and periocular squamous cell carcinoma (EPSCC), but its distinct genetic characteristics involved remain unknown. We conducted this study based on next-generation sequencing to identify the genetic distinctiveness of EPSCC and damaging mutations for possible aetiology and poor prognosis. We performed sequencing using a 556-gene panel (SmartOnco) in 48 EPSCCs. Cox hazards model was applied to explore mutated genes that increase the risk of metastasis and death. Pathogenesis of the mutations was predicted by sequence alignment algorithms. The most commonly mutated genes were KMT2C (N = 17, 35%), LRP1B (N = 14, 29%), KMT2D (N = 12, 25%), PTCH1 (N = 10, 21%) and TP53 (N = 10, 21%). DNA mismatch repair (MMR) genes (42%) like MSH6 (19%) and MLH3 (12%) were among the most frequently mutated genes. Cell cycle regulators including TP53 (21%) and CDKN2A (10%) were less frequently mutated than in other squamous cell carcinomas (SCCs). Ultraviolet exposure, MMR deficiency and ageing were the main aetiology. Of note, KMT2C has a deleterious mutation hotspot. Patients burdened with MSH6 mutation has a higher risk of overall metastasis (P = 0.045, HR = 5.165) and nodal metastasis (P = 0.022, HR = 14.038). Moreover, a hotspot mutation MSH6E52A brought an even higher risk of nodal metastasis (P = 0.011, HR = 18.745). EPSCCs displayed a unique mutation profile from cutaneous SCCs and mucosal SCCs. We have identified novel damaging mutations in epigenetic regulators like KMT2C boosted early onset of EPSCCs in addition to UVR, ageing or MMR deficiency. And malfunction of MMR genes worsened prognosis.

Primary periocular squamous cell carcinoma in central Spain: Factors related to recurrence.

To describe the characteristics and recurrence rates of primary periocular squamous cell carcinoma (SCC) in Spain. This retrospective study investigates the characteristics of primary periocular SCC at two tertiary centers in Spain from 2000 to 2020. Data were collected on demographics, skin phenotype, location, clinical and histological diagnosis, the commitment of surgical margins, recurrence, and risk factors. Multivariate analysis and risk factors were used to investigate recurrence rates, considering p < 0.05 as statistically significant. Over the 20-year studied period, 107 patients with primary periocular SCC were assessed. The mean age of SCC was 76.8 ± 12.8 years, 55 (50.9%) were females, and 105 (98.1%) had Fitzpatrick skin phenotype type II or III. SCC lesions affected less than 1/3 of the eyelid (56/52.3% cases), mainly the lower lid (42/39.3% lesions). Sixty (56.1%) cases were SCC differentiated, 76 (71%) had clear margins. Clinical diagnosis of SCC corroborated with histological in 84 (78.5%) cases and orbital involvement occurred in 18 (16.8%) cases. Recurrence was observed in 13 (12.1%) cases, occurring more in large tumors and undifferentiated subtype (53.8%), with committed margins (69.2%) (p = 0.001), being the commitment of margins a significant predictor for recurrence, although thickness was an independent predictor. Periocular SCC in Spain showed a similar pattern as in the world. The risk of recurrence is increased in undifferentiated and large periocular SCC, partially removed with committed margins.

Clinical and pathological risk factors for worse stage and mortality of eyelid and periocular squamous cell carcinoma

BackgroundThe clinical and pathological risk factors for worse T stage and prognosis in eyelid and periocular squamous cell carcinomas (SCCs) remain unclear. P63 was reported to predict a worse prognosis...

Dramatic invasion of the orbit by periocular cutaneous squamous cell carcinoma

The periocular skin is susceptible to numerous benign and malignant neoplasms. Malignant skin tumors of the periocular area are very particular; they can present differently, are rapidly aggressive and pose a real therapeutic challenge. Aggressive forms occur mostly in immunocompromised individuals. A complete destruction of the orbit is rare and the initial seat is most often the eyelid. We report the case of an immunocompetent 70-year-old patient with destruction of the entire orbital region including the eyeball secondary to the extension of squamous cell carcinoma of the internal canthus.

Use of the Intratumoural Anticancer Drug Tigilanol Tiglate in Two Horses

Tigilanol tiglate is a novel small molecule approved as a veterinary pharmaceutical in Europe for intratumoural treatment of non-metastatic, non-resectable canine mast cell tumors. The drug has a “tumor agnostic” mode of action associated with induction of an acute inflammatory response at the treatment site, immune cell recruitment, and disruption of tumor vasculature. Consequently, tigilanol tiglate has potential in treating a range of tumor types in humans and companion animals. However, it is likely that species-specific dosing and concomitant medication protocols will be required, especially to manage the drug-induced acute inflammatory response at the treatment site. As an initial step in evaluating tigilanol tiglate for treating cutaneous tumors in horses, we developed an equine-specific protocol involving (a) a 30% reduction in intratumoural tigilanol tiglate dose rate compared to that used in dogs, and (b) a regime of concomitant medications to manage the drug-induced acute inflammatory response at the treatment site. Here we report a preliminary study in two horses using the protocol to treat (i) an aggressive fibroblastic sarcoid that had recurred following surgical excision and (ii) a fast-growing peri-ocular squamous cell carcinoma. Clinical response to tigilanol tiglate treatment in these cases was similar to that observed in canine and human patients. Localized inflammation and bruising developed rapidly at the treatment site with haemorrhagic necrosis of the tumor evident within 24 h. Slough of necrotic tumor mass occurred within 6–16 days followed by infill of the tissue defect and full re-epithelialisation of the treatment site with good functional outcome. Drug-induced inflammation and oedema at the treatment site were well controlled by the concomitant medications and largely resolved within 3 days, while the wound that formed following tumor slough healed uneventfully. Both patients displayed minor lethargy during the first 36 h after treatment and localized treatment-site discomfort was apparent over the first 3–5 days. There was no evidence of recurrence of the sarcoid at 93 days, or the squamous cell carcinoma at 189 days. The results from this study support continued development and evaluation of tigilanol tiglate as a potential future treatment option for cutaneous equine tumors.

The Terrible Triad of Checkpoint Inhibition: A Case Report of Myasthenia Gravis, Myocarditis, and Myositis Induced by Cemiplimab in a Patient with Metastatic Cutaneous Squamous Cell Carcinoma

Background We report a case of a patient with squamous cell carcinoma (SCC) who developed myasthenia gravis (MG), myositis, and myocarditis after receiving cemiplimab, an anti-PD-1 immune checkpoint inhibitor (ICI). Case Presentation. An 86-year-old man with metastatic periocular SCC presented with decreased vision in the left eye, severe fatigue, and lower back and bilateral hip pain 3 weeks after receiving cemiplimab. Within hours, he developed dysphonia, pharyngeal secretions, and dysphagia, necessitating intubation. Endomyocardial biopsy revealed active lymphocyte-mediated necrosis consistent with ICI-induced myocarditis. Anti-striated muscle and anti-acetylcholine receptor antibodies were elevated, consistent with myositis and myasthenia gravis. Despite plasma exchange therapy, steroids, and intravenous immunoglobulin, he died from cardiac arrest. Conclusions The presence of myasthenia gravis, myocarditis, or myositis should prompt evaluation for all three toxicities as they may represent an overlap syndrome. The severity of these immunotoxicities highlights the need for clinicians to suspect multiple simultaneous adverse effects of ICIs.

Nomogram for Preoperative Estimation of Orbit Invasion Risk in Periocular Squamous Cell Carcinoma.

Importance: Orbital invasion occurs in some periocular squamous cell carcinoma (SCC), compromising surgical outcomes, and prognoses of patients. To date, however, there are no validation studies on the clinical features related to orbital invasion in patients with periocular SCC.Objective: To explore clinical features that may be associated with orbital invasion and build a model for predicting the risk of orbital invasion.Design, Setting, and Participants: In this retrospective mono-center case-control study, 90 patients with periocular SCC were treated at the Ninth People's Hospital Shanghai Jiao Tong University School of Medicine from January 2005 to August 2019. “Case” is defined as a SCC patient with orbit invasion prior to operation. “Exposure” is defined as the different sites of lesion.Main Outcomes and Measures: Clinical features, including “time to relapse after surgery,” were collected. Multivariate logistic regression analysis was applied to identify the independent risk clinical features associated with orbital invasion, which was then incorporated into a nomogram.Results: Of the 90 patients included in this study, 33 patients (36.7%) had orbital invasion. 14 of the 33 orbit-invasive patients had local recurrence, while 11 of 57 orbit non-invasive patients had local recurrence, suggesting that orbital invasion is a risk factor for local recurrence. The multivariate binary logistic regression indicated that the lesions at the medial canthus [odds ratio (OR), 5.024, 95% CI, 1.409–17.912, P = 0.013], the age at diagnosis (10-years intervals; OR, 0.590, 95% CI, 0.412–0.844, P = 0.004), and bleeding in the lesion (OR, 3.480, 95% CI, 1.254–9.660, P = 0.017) were three preoperative clinical features significantly associated with orbital invasion.Conclusion: For periocular SCC, lesions at the medial canthus, the younger age of the patients at diagnosis, and bleeding in the lesion were the three main clinical features associated with orbital invasion. The risk score model for orbital invasion can act as a supportive tool for optimized clinical evaluation and treatment decisions.

Skeletal metastasis from a squamous cell carcinoma of the nictitating membrane in a Haflinger horse

SummaryA 12‐year‐old Haflinger gelding with a history of a persistent cough was referred for evaluation of a severe lameness of the left forelimb. An excision of the right nictitans had been performed 2 years prior to presentation, and a squamous cell carcinoma (SCC) with embolic neoplastic cells in several blood vessels had been confirmed by histopathology. The origin of the lameness could not be localised with regional analgesia; therefore, a nuclear scintigraphic examination was performed. This revealed an area of marked increased radiopharmaceutical uptake at the level of the caudodorsal border of the left scapula. Further examination, including ultrasound‐guided biopsy of the suspect region, confirmed the presence of SCC invading the scapula. Due to poor a prognosis, the horse was subjected to euthanasia. Prior to euthanasia, the gelding was tested homozygous for the missense variant in the damage‐specific DNA‐binding protein 2 (DDB2) gene, which is reported as a risk factor for the development of nictitans SCC in Haflinger horses. Post‐mortem evaluation revealed multiple SCC metastasis, affecting the scapula, the liver and the lungs. To the authors' knowledge, this is the first reported case of bone metastasis following a primary periocular SCC in a horse.

A Clinical Masquerader: Squamous Cell Carcinoma of the Eyelid Previously Diagnosed as an Eye Bump

Malignant eyelid tumors are often difficult to diagnose at early stage growth, and can be clinically challenging. Due to the high prevalence of periocular skin cancers, clinicians must be very attentive in their assessment of skin lesions amongst their patients. This case report highlights an early non-healing eyelid lesion transforming into squamous cell carcinoma. An 83-year-old male with no history of malignancy presented with a non-healing and rapidly growing lesion of the left lower eyelid. He first noticed this lesion one-month prior and was treated with oral antibiotics without improvement by his primary care provider. Our slit lamp examination of the left eyelid revealed a large ulcerated mass with white mucoid discharge draining from the center of the lesion. After an oculoplastics referral, the patient was diagnosed with squamous cell carcinoma confirmed by biopsy. Computed tomography(CT) showed no metastasis or invasion to deep layer tissue. The management decision in this case required exenteration of the left eye socket followed by radiation therapy. This case illustrates the clinical course and invasive nature of periocular squamous cell carcinoma. It can present in a variety of different appearances, but are mostly painless, hyperkeratotic lesions that progressively change and ulcerate. An extensive history and careful clinical examination are vital in order to detect malignancy in a timely manner.

Validation Study of the AJCC Cancer Staging Manual, Eighth Edition, Staging System for Eyelid and Periocular Squamous Cell Carcinoma

To our knowledge, there are no validation studies to date of the prognostic value of the AJCC Cancer Staging Manual, eighth edition (AJCC 8), criteria for eyelid and periocular squamous cell carcinoma. To determine the association of tumor (T) category in AJCC 8 with local recurrence, nodal metastasis, distant metastasis, and disease-specific survival (DSS) for eyelid and periocular squamous cell carcinoma. In this retrospective, single-center cohort study, 109 consecutive patients with eyelid and periocular squamous cell carcinoma treated from January 1999 to April 2018 were included. Patients with secondary involvement of the periocular region were excluded. Local recurrence, nodal metastasis, distance metastasis, and DSS. Of the 109 included patients, 81 (74.3%) were male, and the median (range) age was 66 (40-91) years. At presentation, 43 patients (39.4%) had recurrent tumor, 4 (3.7%) had nodal metastasis, and 1 (0.9%) had distant metastasis. The median (range) follow-up was 23 (1-161) months. During follow-up, 11 patients (10.1%) developed local recurrence, 7 (6.4%) developed nodal metastasis, 2 (1.8%) developed distant metastasis, and 9 (8.3%) died of disease. The 5-year DSS rate was 87.7% (95% CI, 79.5-96.9). Chronic immunosuppression (hazard ratio, 47.24; 95% CI, 7.33-304.30; P < .001) and presentation with recurrent squamous cell carcinoma (hazard ratio, 5.22; 95% CI, 1.12-24.31; P = .04) were associated with local recurrence during follow-up. Of the 11 patients with local recurrence during follow-up, 7 (64%) had perineural invasion. T category was associated with nodal metastasis; clinical stage of T2c or worse at presentation was associated with higher risk of nodal metastasis and death of disease but not with a higher risk of local recurrence. Distant metastasis was associated with nodal metastasis at presentation (hazard ratio, 32.50; 95% CI, 1.97-536.40; P = .02) and during follow-up. A total of 33 patients (30.3%) had different T categories depending on whether disease was staged according to the seventh or eighth edition of the AJCC Cancer Staging Manual. Compared with AJCC 7, AJCC 8 showed a better predictive value in terms of local recurrence (T3, 17% vs 14%; T4, 11% vs 16%) and DSS. These findings suggest that T category in AJCC 8 is associated with nodal metastasis and DSS. Immunosuppression and presentation with recurrent disease are associated with increased risk of future local recurrence. Patients with tumors of clinical stage T2c or worse at presentation are at increased risk of nodal metastasis and worse DSS and should undergo surveillance for nodal metastasis. Future studies, ideally prospective in design, could provide greater confidence in these findings.

Rapidly Progressive Conjunctival Squamous Cell Carcinoma With Orbital Invasion

A 41-year-old HIV-negative man with a history of alcoholism and tobacco use presented with a painless right lower eyelid mass for 3 months (Fig. A). On examination, the lesion appeared to originate from the conjunctiva with intact eyelid epidermis (Fig. B). There was no lymphadenopathy. Biopsy revealed moderately differentiated squamous cell carcinoma with keratin pearls (Fig. C). The patient was lost to follow-up and returned 2 months later with a rapidly enlarged lesion of the eyelid and anterior orbit (Fig. D), with radiographic evidence of orbital invasion (Fig. E). After a negative systemic work-up, the patient underwent an orbital exenteration and subsequent radiotherapy. The patient remains free of disease 8 months following surgery.Right periocular squamous cell carcinoma. A, Clinical photograph depicting right lower eyelid mass. B, Visible mass and irregularity of the palpebral and bulbar conjunctiva upon lid eversion. C, Keratin pearl noted on biopsy (H&E, 400X). D, Clinical photograph showing rapid enlargement and extension of the mass into the entire right lower eyelid and anterior orbit. E, T2-weighted coronal orbital MRI confirming invasion into the extraconal inferior orbit.

Strontium‐90 plesiotherapy in the horse

SummaryStrontium‐90 plesiotherapy is a form of very superficial radiotherapy that is most commonly used as part of the management of ocular and periocular squamous cell carcinomas in the horse. Although it can be an extremely effective treatment, with the ability to deliver very high doses of radiation to the tumour without affecting the surrounding tissues, the penetration is only a few millimetres, which limits its use in equine medicine to very specific situations. In addition, the availability of strontium‐90 plesiotherapy is limited to specialist institutions due to the health and safety and security concerns of accessing a high activity sealed source.

Evaluation for High-risk HPV in Squamous Cell Carcinomas and Precursor Lesions Arising in the Conjunctiva and Lacrimal Sac.

High-risk human papilloma virus (HR-HPV) is a well-established causative agent of oropharyngeal squamous cell carcinoma (SCC). In addition, HR-HPV has occasionally been reported to be present in dysplastic and malignant lesions of the conjunctiva and lacrimal sac, although its overall incidence and etiological role in periocular SCC are controversial. Sequential surgical samples of 52 combined cases of invasive SCC (I-SCC) and SCC in situ (SCCIS) from 2 periocular sites (conjunctiva and lacrimal sac) diagnosed over a 14-year period (2000 to 2014) were selected for evaluation, and relevant patient characteristics were documented. p16 immunohistochemistry was performed as a screening test. All p16-positive cases were further evaluated for HR-HPV using DNA in situ hybridization (DNA ISH), and a subset was also analyzed by polymerase chain reaction (PCR). Of 43 ocular surface squamous neoplasias (OSSNs), 30% (n=13; 8 SCCIS and 5 I-SCC cases) were positive for HR-HPV. HPV-positive OSSNs occurred in 8 men and 5 women with a mean age of 60 years (range, 39 to 94 y). HPV type-16 was detected in all conjunctival cases evaluated by PCR. All 5 conjunctival I-SCCs were nonkeratinizing (n=4) or partially keratinizing (n=1) and managed by simple excision. In contrast, HPV-negative conjunctival I-SCCs were predominantly keratinizing (11 keratinizing and 2 nonkeratinizing). Of 9 lacrimal sac I-SCCs (LSSCCs), 66.7% (n=6) were positive for HR-HPV by p16 and DNA ISH; HPV subtypes were HPV-16 (n=5) and HPV-58 (n=1). In addition, 2 p16-positive cases with negative DNA ISH results were HR-HPV positive (HPV-16 and HPV-33) when evaluated by PCR, suggesting that the rate of HR-HPV positivity among the LSSCCs may be as high as 89% (n=8). The combined group of HR-HPV-positive LSSCCs was seen in 4 men and 4 women with a mean age of 60 years (range, 34 to 71 y). Seven of the 8 HPV-positive LSSCCs (87.5%) had a nonkeratinizing or partially keratinizing histomorphology, whereas 1 case (12.5%) was predominantly keratinizing. The presence of HR-HPV in 30% of OSSNs and at least 66.7% of LSSCCs suggests the possibility of an etiologic role for HR-HPV at these sites.

Periorbital squamous cell carcinoma with orbital invasion

Periocular squamous cell carcinoma is an aggressive tumor with incidence for eyelid SCC has been reported to be between 0.09 and 2.42 cases per 100 000 population. SCC is the second most common eyelid malignancy, accounting less than 5% of malignant eyelid neoplasms. Orbital invasion is a serious complication of aggressive or neglected lesions, which has been reported to occur in 2.5% of all eyelid basal and squamous cell carcinomas. The aim of our study is to report a case of a 58-year male with periorbital squamous cell carcinoma referred to our clinic because of non-healing ulcer over the left frontal region. This case study reports a complication of orbital invasion with emphasis on the review of literature.

Periocular Squamous Cell Carcinoma: TNM Staging and Recurrence

To analyze the TNM stage, management, and recurrence rates of patients with histologically confirmed squamous cell carcinoma (SCC) of the eyelid. Retrospective case series from 3 Australian centers. A total of 254 cases of eyelid SCC from 254 patients (median age, 73 years; range, 28-102 years; 159 were male). Tumors were staged according to The American Joint Committee on Cancer 7th edition TNM criteria for eyelid carcinoma. Outcomes and recurrence rates according to TNM stage at presentation. A total of 25 cases (9.8%) were recurrent tumors. TNM classifications were as follows: T1N0M0, 74 patients (29.1%); T2aN0M0, 92 patients (36.2%); T2bN0M0, 50 patients (19.7%); T3aN0M0, 31 patients (12.2%); T3bN0M0, 5 patients (2.0%); T2bN0M1, 1 patient (0.4%); and T3bN1M1, 1 patient (0.4%). Perineural invasion (PNI) was present histologically in 8.3% of cases. Treatment modalities included Mohs microsurgery (31.1%), wide local excision (WLE) with paraffin section control (21.7%), WLE with frozen-section control (19.3%), and excision without margin control (24.4%). Three cases did not receive treatment. Median follow-up was 40 months (range, <1-132 months). Local recurrence occurred in 17 treated patients (6.8%). The recurrence rate was 5.3% (12/226 patients) for primary tumors and 20% (5/25 patients) for recurrent tumors (P = 0.019). Four patients (1.6%) died of their disease during follow-up. Higher T stage was significantly associated with both PNI (P = 0.035) and local recurrence (P < 0.001). We could not identify a T-stage threshold below which there was no risk of recurrence, as evidenced by 3 T1 primary tumors that recurred. Higher T stage was significantly associated with local recurrence, and recurrent tumors had a 4-fold increased risk of further recurrence compared with primary tumors. Therefore, it may be reasonable to consider sentinel lymph node biopsy or close nodal surveillance and follow-up for patients with recurrent or high T-stage tumors. Of note, we could not identify a T-stage threshold below which there was no risk of recurrences; therefore, clinicians should be aware of the potential for low T-stage tumors to recur.