TABLE 1.
Pt | Sex/Agea/Race | Smoker | Other PMHx | Laterality/Location | # Prior Biopsies/Partial Excisions | Treatment | IFN Prior to Excisionb | HPV+c | Diff/Kerd | PD-L1: O/T/S/Ee | PD-L2: O/T/S/Ee | CD-8: O/T/Sf | Recurrence (Y/N)/Time to Recur | Follow-up |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
1 | F/61/W | Y | Asthma, HTN | L/Inf fornix | 2 | Excision, with margins to frozen section. Hughes flap, sentinel node bx. No cryo. | N | N | WD/+ | 3/4/3/1 | 2/0/2/1 | 3/1/3 | N | 11 mo |
2 | F/68/W | Y | DM, CKD, Gout, HTN, CVA, Bell’s Palsy, obese | R/Inf fornix | 2 | Excision, cryo, map biopsies. Postop IFN QID × 2 months | N | N | MD/+ | 2/2/2/1 | 2/0/1/0 | 2/0/2 | Y; 2 mo; repeat excision, cryo, margins to frozen sections, sentinel node bx; no further recurrence | 11 mo |
3 | F/82/A | N | HCV (untreated); cervical CA; HLD; HTN | R/Superior conj and cornea | 1 | Subtotal exenteration; margins to frozen section | N | N | PD/+ | 4/5/4/1 | 4/1/1/1 | 3/3/3 | Y; 7 mo; presented with headache, recurrent orbital mass, with bone erosion at the orbital apex and an enlarged parotid lymph node found; pt refuses further testing; died 2 months after recurrence with “fungating mass extending from orbit”; cause of death uncertain | 9 mo |
4 | M/62/W | Y | Bladder CA; pancreatic CA; | L/Diffuse inferior fornix, inferior palpebral conj and inferior bulbar conj | 0 | IFN QID × 2 mo without initial confirmatory biopsy | Y (1 mo) | N | WD/+ | 3/4/3/0 | 2/0/1/1 | 3/1/3 | Y; 2 mo; lateral canthal mass; biopsied; then IFN QID restarted × 1 mo; excision with cryotherapy, margins to frozen section; no further recurrence | 42 mo |
5 | M/49/W | Y | HTN; pheochromocytoma | R/superonasal palpebral and forniceal conj | 1 | Excision; cryo 2 months postop owing to in situ carcinoma on 1 margin from excision | Unknown | Y | MD/+ | 2/2/1/1 | 1/1/0/0 | 3/1/3 | Y; 54 mo; treated with eyelid wedge excision and map biopsies, followed by another excision 1 week later for positive margins; 4 subsequent excisions over subsequent years for carcinoma in situ, as well as multiple courses of interferon | 87 mo |
6 | M/58/W | N; but history of sun exposure | HTN; HLD | R/temporal limbus | 0 | Excision, cryo, EtOH, and corneal epithelial debridement | N | N | MD/+ | 1/2/1/0 | 1/0/1/0 | 1/0/2 | N; only 3 months of ophthalmic follow-up available, although patient alive at 36 mo and without recurrence per his nonophthalmic physicians | 3 mo |
7 | F/62/W | Y | Facial BCC; HLD | L/Inf fornix and inf bulbar | 0 | Excision and cryo; postop IFN QID ×2 months, stopped for 2 months, then resumed 2 more months | N | N | MD/+ | 4/5/3/0 | 2/1/2/1 | 3/1/3 | N | 18 mo |
8 | M/58/A | Y | Waldenstrom macroglobulinemia | L/Lower eyelid palpebral conj and fornix | Unknown | Excision, without cryo. | Y (1 mo) | N | MD/− | 2/2/2/1 | 1/1/1/0 | 2/1/2 | Y; 89 mo; inferior palpebral, bulbar, and forniceal conj; IFN QID ×1 mo without response, then excision, cryo and map biopsies. Margins positive, so treated with MMC 0.04% QID ×2 weeks. No recurrence since. | 116 mo |
9 | M/65/B | Y | Skull fracture; seizures; gastric CA; enucleation | R/eyelid margin and conj of anophthalmic socket (enucleated 40 years earlier for open globe injury) | 1 | Mohs surgery; 4 stages until margins cleared (whole lower eyelid, lateral canthus, all conjunctiva and most upper eyelid removed); first stage of reconstruction | N | N | MD/+ | 4/5/3/1 | 2/1/1/0 | 3/3/3 | N; postoperative radiation recommended, but pt refused; further reconstruction planned, but pt found to have advanced gastric CA and surgery not advised; underwent radiation for gastric CA, but refused chemo or surgery | 21 mo |
10 | F/71/W | Y | Breast CA; renal CA; ovarian CA; HTN; HLD; COPD | R/superior bulbar, forniceal and palpebral conjunctiva | 1 | IFN QID × 2 months to shrink tumor, then excision and cryo | Y (2 mo) | Y | MD/− | 5/5/3/1 | 2/1/1/0 | 3/3/3 | Y; 4 mo; nodule near lateral orbital rim, excised, positive for tumor, but with clear margins; 1 mo later 2 nodules above upper eyelid crease, biopsy positive for tumor; treated with 66 Gy photon radiation in 6 fractions with weekly carboplatin ×3 (last 3 doses not given owing to allergy); died 7 mo later from influenza | 16 mo |
11 | M/80/W | Y | None | R/superior and nasal limbal bulbar conjunctiva | 0 | IFN QID × 1 mo, then excision, cryo, EtOH and corneal epithelial debridement | Y (1 mo) | N | WD/− | 2/2/1/1 | 0/0/0/0 | 2/3/1 | Y; 28 mo; 2 locations on bulbar conjunctiva; re-excision recommended, but patient preferred IFN; IFN QID ×6 mo, both lesions resolved | 40 mo |
12 | M/51/W | Y | Enucleation | R/conj of anophthalmic socket (enucleate 38 years earlier for open globe injury); parotid mass | 1; also FNA of periparotid lymph node positive | Orbital exenteration, right parotidectomy and neck dissection | N | Y | MD/− | 3/3/3/1 | 1/1/0/1 | 1/1/1 | Unknown; postop, treated with 60 Gy photon radiation; last seen at cancer center 1 week postradiation. Followed-up with PCP 14 months postsurgery, nonhealing wounds and granulation tissue noted in orbit; referred to ophthalmology and oncology, but was lost to follow-up | 14 mo |
13 | M/48/W | Y | Quadriplegia and brain injury after MVA | R/eyelid margin | 0 | Wedge resection of eyelid margin, margins to frozen section | N | N | MD/+ | 3/5/2/1 | 2/1/2/1 | 3/3/2 | N | 17 mo |
14 | F/94/unk | Unknown | CABG, HTN, advanced dementia, pacemaker | L/lower eyelid palpebral conj | 0 | Incisional biopsy; tumor extends to deep and later margins–no further surgery; treatment with IFN drops started | N | N | WD/− | 2/2/3/1 | 3/1/2/1 | 2/0/2 | N/A; tumor incompletely excised and not yet fully treated | 1 mo |
15 | F/66/W | N; but exposed to secondhand smoke | Benign breast tumor | L/nasal bulbar conj | 0 | Excisional biospy, cryo, AMT and IFN injection 8 million units | N | N | MD/− | 3/3/3/1 | 2/0/1/0 | 2/0/2 | N | 6 mo |
16 | F/67/W | N | HLD, squamous CA on leg and arm | L/nasal limbus | 0 | Excisional biopsy, alcohol, and cryo | N | N | WD/+ | 2/2/2/0 | 0/0/0/0 | 1/0/2 | N | 16 mo |
17 | M/78/W | N | Coronary artery disease and stent | L/upper eyelid conj of anophthalmic socket (enucleated owing to old trauma) | 1 | Posterior lamella excision with AMT and IFN injection; postoperatively 3 additional IFN injections (monthly) | N | N | MD/+ | 2/2/2/1 | 2/0/1/1 | 2/1/3 | N | 3 mo |
18 | M/53/unk | unknown | Unknown | R/inferotemporal limbus | 0 | Excisional biopsy with cryo and AMT | N | N | MD/+ | 2/3/2/0 | 1/0/1/0 | 2/1/3 | N | 16 mo |
A = Asian; AMT = amniotic membrane transfer; B = black; BCC = basal cell carcinoma; Bx = biopsy; CA = cancer; CABG = coronary artery bypass graft; CKD = chronic kidney disease; COPD = chronic obstructive pulmonary disease; Conj = conjunctiva; Cryo = cryotherapy; CVA = cerebrovascular accident; Diff = differentiation; DM = diabetes mellitus; E = endothelial; EtOH = ethanol; FNA = fine needle aspiration; HCV = hepatitis C virus; HLD = hyperlipidemia; HPV+ = human papilloma virus-positive (by p16 immunostaining); HTN = hypertension; IFN = interferon alpha 2b; Inf = inferior; Ker = keratinization; L = left; MD = moderately differentiated; MMC = mitomycin C; MVA = motor vehicle accident; O = overall; PD = poorly differentiated; PD-L1 = programmed cell death 1 ligand 1; PD-L2 = programmed cell death 1 ligand 2; PMHx = past medical history; Postop = postoperative; Pt = patient; QID = 4× per day; R = right; S = stroma; T = tumor; unk = unknown; W = white; WD = well-differentiated.
Age at presentation.
Interferon treatment prior to tumor excision was assessed as its effects may have altered tumor expression patterns of PD-L1 or PD-L2.
HPV positivity was assessed by >70% of tumor cells staining positively for p16.
Differentiation was graded as well-differentiated (WD), moderately differentiated (MD), or poorly differentiated (PD); keratinization was graded as keratinizing (+) or nonkeratinizing (−).
PD-L1 and PD-L2 expression levels were graded on a 0–5 scale (see Methods section for more detail). The 0–5 scale was used to grade overall expression of the marker, and also expression in tumor cells alone, stromal cells alone, and endothelial cells alone.
CD8-positive T lymphocytes were graded on a scale of 0–3 (see Methods section for more detail). This scale was used to grade overall expression of the marker, as well as expression in tumor cells alone and stromal cells alone.