[Show abstract][Hide abstract] ABSTRACT: Most of the squamous cell carcinomas (SCCs) of the skin and head and neck contain p53 mutations. The presence of p53 mutations in premalignant lesions suggests that they represent early events during tumor progression and additional alterations may be required for SCC development. Here we show that codeletion of the p53 and αv integrin genes in mouse stratified epithelia induced SCCs in 100% of the mice, more frequently and with much shorter latency than deletion of either gene alone. The SCCs that lacked p53 and αv in the epithelial tumor cells exhibited high Akt activity, lacked multiple types of infiltrating immune cells, contained a defective vasculature and grew slower than tumors that expressed p53 or αv. These results reveal that loss of αv in epithelial cells that lack p53 promotes SCC development, but also prevents remodeling of the tumor microenvironment and delays tumor growth. We observed that Akt inactivation in SCC cells that lack p53 and αv promoted anoikis. Thus, tumors may arise in these mice as a result of the increased cell survival induced by Akt activation triggered by loss of αv and p53, and by the defective recruitment of immune cells to these tumors, which may allow immune evasion. However, the defective vasculature and lack of a supportive stroma create a restrictive microenvironment in these SCCs that slows their growth. These mechanisms may underlie the rapid onset and slow growth of SCCs that lack p53 and αv.Oncogene advance online publication, 27 January 2014; doi:10.1038/onc.2013.585.
[Show abstract][Hide abstract] ABSTRACT: : To describe current indications, methods, and outcomes of sentinel lymph node (SLN) biopsy for eyelid and conjunctival tumors.
: Review of experience to date and relevant articles published in PubMed in English.
: The use of SLN biopsy for conjunctival and eyelid tumors has evolved greatly in the past decade, and positive SLNs have been reported for conjunctival and eyelid melanoma, eyelid Merkel cell carcinoma, eyelid sebaceous carcinoma, and eyelid squamous cell carcinoma. Current indications for SLN biopsy of eyelid and conjunctival malignancies are the presence of conjunctival melanomas ≥2 mm in histologic thickness and/or histologic ulceration; cutaneous eyelid melanomas ≥1 mm thick, those with >1 mitotic figures per high-power field, and/or those with histologic ulceration; sebaceous carcinomas ≥10 mm in width; and Merkel cell carcinomas of any size. The frequency of false-negative biopsy results seems to be decreasing as more experience is gained with the technical nuances of the procedure and with the complex lymphatic drainage of the head and neck region. Given the emerging data published on feasibility and reported cases of microscopically positive SLNs identified in patients with otherwise normal examination of the regional lymph nodes and normal imaging studies, it seems appropriate to continue to further evaluate SLN biopsy for selected ocular tumors in future prospective studies.
: SLN biopsy is feasible for eyelid and conjunctival tumors, and continued use of the procedure is recommended. Future multi-institutional trials are needed to expand on currently available data, fine-tune patient selection criteria, and elucidate the relationships between SLN status and patient survival and tumor recurrence.
Ophthalmic plastic and reconstructive surgery 01/2013; 29(1):57-62. DOI:10.1097/IOP.0b013e31827472c5 · 0.88 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Lymphoma of mucosa-associated lymphoid tissue (MALT) is the most common variety of lymphoma seen in the ocular adnexae. The authors present the case of a patient with MALT lymphoma refractory to treatment with rituximab. Subsequent treatment with 90Yttrium-Ibritumomab tiuxetan yielded a complete response.
Ophthalmic plastic and reconstructive surgery 07/2012; 28(6). DOI:10.1097/IOP.0b013e31824ab228 · 0.88 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Conjunctival melanoma is an uncommon malignancy with the potential for significant morbidity. Ulceration is known to be an indicator of more aggressive cutaneous melanoma. This factor has not been previously evaluated in conjunctival melanoma.
Twenty-six patients with conjunctival melanoma who underwent excision by a single surgeon at a cancer referral center treated between June 2003 and July 2008 were included. The medical records were reviewed for clinical and pathological data. Outcomes assessed included local recurrence, regional lymph node metastasis, distant metastasis, use of adjuvant topical chemotherapy or adjuvant radiation therapy, final visual acuity and death.
Local recurrence was seen in three patients (12%). Regional lymph node metastasis and distant metastasis were each seen in four patients (15%). Tumors >2.0 mm thick were more likely to develop distant metastasis than those with a thickness of <2.0 mm (p = 0.0331). Ulceration was noted in 10 of 26 patients. Regional lymph node metastasis and distant metastasis were each seen in 4 of 10 patients with ulceration, and none of the patients without ulceration.
Ulceration in conjunctival melanoma may be an important histopathologic predictor of a more aggressive tumor. Globe-sparing multi-modality management of conjunctival melanoma can yield acceptable rates of local-regional recurrence.
[Show abstract][Hide abstract] ABSTRACT: Removal of an eye is sometimes necessary in the management of ocular malignancies. The most common intraocular malignancies
necessitating enucleation are uveal melanoma in adults and retinoblastoma in children. In patients with retinoblastoma, the
segment of optic nerve removed during enucleation must be long enough to ensure that the entire tumor has been removed. A
number of different types of orbital implants are available, each with advantages and disadvantages. Radiation can cause atrophy
and contraction of orbital tissues; thus, management of the socket in patients who have undergone radiation therapy is challenging.
There is considerable debate over the benefits of enucleation versus evisceration. Evisceration is not appropriate in patients
with intraocular tumors as it may leave tumor behind. Before evisceration is performed for an indication not related to cancer,
the eye should be carefully examined to rule out the presence of intraocular tumor.
[Show abstract][Hide abstract] ABSTRACT: A number of different cancers can affect the eyelid. Basal cell carcinoma is the most common; squamous cell carcinoma, melanoma,
and sebaceous cell carcinoma are less common. Management of these tumors is most commonly surgical, although chemotherapy
and radiation therapy play a role in some cases. Complex tumors require a multidisciplinary approach and long-term follow-up.
[Show abstract][Hide abstract] ABSTRACT: Nasolacrimal duct obstruction is often seen in patients with cancer. Iatrogenic causes such as surgery, radiation therapy,
and chemotherapy are among the most common causes. Primary lacrimal drainage tumors are less common causes. The evaluation
of patients with suspected nasolacrimal duct obstruction should include a thorough history and a comprehensive ophthalmic examination,
including probing and irrigation of the lacrimal drainage apparatus and a Schirmer’s test. Imaging studies may also be necessary.
Treatment depends on the degree and location of the obstruction and may consist of probing and irrigation alone; balloon dilation;
intubation of the drainage system with silicone stents; or dacryocystorhinostomy, usually with placement of silicone stents
to maintain duct patency during healing.
[Show abstract][Hide abstract] ABSTRACT: Eyelid malposition in cancer patients encompasses a variety of conditions, including ectropion, entropion, ptosis, eyelid
retraction, and eyelid malposition due to periorbital edema. Ectropion is by far the most commonly encountered form of eyelid
malposition in cancer patients. In some situations, the eyelid abnormality is the presenting sign of an underlying malignancy,
but most often, it is the result of therapeutic interventions for cancer.
[Show abstract][Hide abstract] ABSTRACT: Sebaceous carcinoma is a rare cutaneous malignancy that is most frequently found in the eyelids with an estimated risk of regional lymph node metastasis in the 8% to 14% range. The authors have previously reported the use of sentinel lymph node biopsy and microscopically positive sentinel lymph nodes in various eyelid and conjunctival cancers, including conjunctival and eyelid melanoma and Merkel cell carcinoma. The authors herein describe the first successful identification of a microscopically positive sentinel lymph node in a patient with sebaceous carcinoma of the eyelid, suggesting that sentinel lymph node biopsy for sebaceous carcinoma of the eyelid deserves further investigation.
Ophthalmic plastic and reconstructive surgery 10/2010; 27(1):e4-6. DOI:10.1097/IOP.0b013e3181ef7450 · 0.88 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To report a series of adults with orbital soft tissue sarcoma treated with various combinations of chemotherapy, radiation therapy, and surgery and to report on the efficacy of neoadjuvant therapy in these patients.
The medical records of adults who presented to our institution with orbital soft tissue sarcoma between 2003 and 2008 were reviewed. Outcome measures reviewed included response to chemotherapy, type of surgery, length of follow-up, visual acuity at last follow-up, local recurrence, distant metastasis, disease-free interval, and death.
Thirteen patients were identified. Nine had primary orbital lesions, 1 had a locally recurrent orbital lesion, 1 had a secondary tumor extending from the paranasal sinuses, and 2 had metastases in the orbit from primary tumors at other sites. Six patients (46%) had chemotherapy, and 10 (77%) had external-beam radiation therapy; 12 patients (92%) underwent surgical resection. The mean follow-up time for all patients was 26 months (range, 2 months -7 years). Three patients (23%) received preoperative chemotherapy with or without radiation therapy. Two of these patients underwent globe-preserving surgery, and 1 required an orbital exenteration due to the extent of disease even after chemoreduction.
Adults with orbital sarcomas may benefit from preoperative chemotherapy with or without radiation therapy. Multidisciplinary care with involvement of medical oncologists and radiation oncologists who are familiar with sarcoma chemotherapy and radiation may benefit these patients.
Ophthalmic plastic and reconstructive surgery 04/2010; 26(3):185-9. DOI:10.1097/IOP.0b013e3181ba75e6 · 0.88 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To report the clinical and histopathologic features in 6 patients with cutaneous melanoma metastatic to the eyelid and periocular skin.
Clinical records and radiographic features of all consecutive patients treated by the principal investigator between January 2005 and October 2007 with the diagnosis of cutaneous melanoma metastatic to the eyelid and periocular skin.
Six patients ranged in age from 26 to 84 years old (median, 55 years). Five patients had their metastatic lesion in the upper eyelid and 1 in the lower eyelid. The mean survival after the diagnosis of melanoma metastatic to the eyelid was 5.3 months. All patients had metastases at other sites detected prior to the diagnosis of the eyelid metastasis. The mean interval from initial primary tumor diagnosis to metastasis to the eyelid was 121 months. In all 6 patients, palliative surgical resection of the metastatic eyelid lesions was carried out.
Melanoma metastatic to the eyelid is not uncommon in advanced stage cutaneous melanoma. Palliative surgical management of these metastatic lesions should be considered to improve the patient's quality of life.
Ophthalmic plastic and reconstructive surgery 02/2010; 26(2):88-94. DOI:10.1097/IOP.0b013e3181b8e06f · 0.88 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A 17-year-old boy presented with a painless, right superotemporal orbital mass. Imaging demonstrated a lacrimal gland mass extending into the temporalis muscle through the lateral orbital wall. The patient underwent an orbital exenteration. Histopathology revealed malignant mixed tumor (carcinoma ex-pleomorphic adenoma) of the lacrimal gland with perineural and vascular invasion.
[Show abstract][Hide abstract] ABSTRACT: Eyelid contour abnormalities after ptosis surgery can be a challenge to manage. The authors present a method of surgically correcting such abnormalities via horizontal eyelid tightening.
Ophthalmic plastic and reconstructive surgery 01/2010; 27(2):e34-5. DOI:10.1097/IOP.0b013e3181c75794 · 0.88 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Benign lymphoid hyperplasia is a disorder characterized by polyclonal lymphocytic infiltration of orbital tissues, predominantly with B-cells. Rituximab is a monoclonal antibody directed against CD20, a B-cell marker. Two patients with recurrent orbital masses involving the lacrimal glands were treated with rituximab. The diagnosis of benign lymphoid hyperplasia with predominance of CD20 cells was confirmed in both cases based on a surgical biopsy. Both patients had been previously treated with standard therapies, including high-dose steroids, and one patient had failed external-beam radiation therapy. They both responded well to treatment with intravenous rituximab. Neither patient experienced any side effects associated with rituximab.
Ophthalmic plastic and reconstructive surgery 01/2010; 26(1):11-3. DOI:10.1097/IOP.0b013e3181b8e056 · 0.88 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Both Endotines and Ultratines are made of polymers of polylactic acid and polyglycolic acid and are used in brow elevation procedures. Ultratines appear to be much more likely to break during loading and insertion than Endotines. The authors report our experience with these devices and offer suggestions to decrease the likelihood of breakage.
Ophthalmic plastic and reconstructive surgery 01/2010; 26(1):63-4. DOI:10.1097/IOP.0b013e3181b8c869 · 0.88 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To report the findings on sentinel lymph node biopsy (SLNB) in 30 patients with ocular adnexal (conjunctival or eyelid) melanomas.
Prospective nonrandomized clinical trial.
Thirty patients with diagnosis of eyelid or conjunctival melanoma.
All patients with ocular adnexal melanoma who underwent SLNB at The University of Texas MD Anderson Cancer Center between December 2000 and July 2008 are the subject of this report. Sentinel lymph node biopsy was performed as previously described by our group, and patients were prospectively followed up.
Findings on preoperative lymphoscintigraphy, SLNB, histopathologic examination of the primary tumor and sentinel lymph nodes (SNL), and nodal recurrence after SLNB.
Tumor sites were as follows: bulbar conjunctiva only, 14 patients; palpebral conjunctiva only, 8 patients; both bulbar and palpebral conjunctiva, 4 patients; and eyelid skin only, 4 patients. At least 1 SLN was identified in all patients. The median number of SLNs removed was 2 (range, 1-5). The most common basin sampled was the intraparotid (16 patients), followed by submandibular (level I) (11 patients), preauricular (9 patients), and superior cervical (level II) (6 patients). Five patients had SLN metastasis. Among the 25 patients with negative SLNB findings, there were 2 false-negative events. There were no false-negative events among patients treated during the last 4.5 years of the study. The mean Breslow thickness was 2.57 mm (range, 0.62-12 mm) among patients with negative SLNB and 4.86 mm (range, 2.0-7.2 mm) among patients with positive SLNB findings (P = 0.055). Ulceration was present in 11 patients (39%): 4 (80%) of 5 patients with positive SLNB and 7 (28%) of 25 with negative SLNB, including both patients with false-negative results. The median time from SLNB to last contact was 2 years (range, 10 months to 6 years).
Sentinel lymph node biopsy is effective for identifying nodal micrometastasis in patients with ocular adnexal melanoma and provides important prognostic information. The false-negative event rate in our series improved in the last 4 years, most likely because of a better technique and better patient selection for SLNB. We recommend consideration of SLNB for patients with intermediate-thickness ocular adnexal melanoma and those with ulceration.