Matthew C. Sniegowski

Ocular Adnexal Diffuse Large B-cell Lymphoma: A Multicenter International Study

IMPORTANCE The clinical features of diffuse large B-cell lymphoma (DLBCL) subtype of ocular adnexal lymphoma have not previously been evaluated in a large cohort to our knowledge. OBJECTIVE To investigate the clinical features of ocular adnexal DLBCL (OA-DLBCL). DESIGN, SETTING, AND PARTICIPANTS This retrospective international cooperative study involved 6 eye cancer centers. During 30 years, 106 patients with OA-DLBCL were identified, and 6 were excluded from the study. The median follow-up period was 52 months. MAIN OUTCOMES AND MEASURES Overall survival, disease-specific survival (DSS), and progression-free survival were the primary end points. RESULTS One hundred patients with OA-DLBCL were included in the study (median age, 70 years), of whom 54 (54.0%) were female. The following 3 groups of patients with lymphoma could be identified: primary OA-DLBCL (57.0%), OA-DLBCL and concurrent systemic lymphoma (29.0%), and ocular adnexal lymphoma relapse of previous systemic lymphoma (14.0%). Of 57 patients with primary OA-DLBCL, 53 (93.0%) had Ann Arbor stage IE disease, and 4 (7.0%) had Ann Arbor stage IIE disease. According to the TNM staging system, 43 of 57 (75.4%) had T2 tumors. Among all patients, the most frequent treatments were external beam radiation therapy with or without surgery (31.0%) and rituximab-cyclophosphamide, hydroxydaunorubicin, vincristine sulfate, prednisone (CHOP) or rituximab-CHOP-like chemotherapy with or without external beam radiation therapy (21.0%). The 5-year overall survival among the entire cohort was 36.0% (median, 3.5 years; 95% CI, 2.5-4.5 years). Relapse occurred in 43.9% (25 of 57) of patients with primary OA-DLBCL. Increasing T category of the TNM staging system was predictive of DSS (P = .04) in primary OA-DLBCL, whereas the Ann Arbor staging system was not. However, when taking all 100 patients into account, Ann Arbor stage was able to predict DSS (P = .01). Women had a longer median DSS than men (9.8 years; 95% CI, 1.9-17.7 years vs 3.3 years; 95% CI, 1.6-5.0; P = .03). CONCLUSIONS AND RELEVANCE Most patients with primary OA-DLBCL were seen with Ann Arbor stage IE and TNM T2 disease. The 5-year overall survival was between 2.5 and 4.5 years, which is the 95% CI around the median of 3.5 years in this cohort. Increasing T category appears to be associated with decreased DSS among patients with primary OA-DLBCL. When taking all patients into account, sex and Ann Arbor stage also seem to be DSS predictors.

Ocular adnexal lymphoma: validation of American Joint Committee on Cancer seventh edition staging guidelines

Background/aims To validate the prognostic significance of the American Joint Committee on Cancer (AJCC) seventh edition staging criteria for ocular adnexal lymphoma (OAL) of all histologic subtypes. Methods Retrospective review of clinical records for all consecutive patients with OAL treated from November 1998 to December 2012. Results 130 patients were evaluated, 82 with primary and 34 with secondary OAL. Fourteen patients were excluded due to incomplete records. 71 women (61.2%) and 45 men (38.8%) had a median age of 61.5 years. Patients were followed for a median of 32.5 months. Treatment varied, in part, related to lymphoma histologic subtype. Overall, there were 17 recurrences (8 local and 9 distant) in patients with primary OAL. For primary OAL, the 5-year disease-free survival (DFS) and overall survival (OS) rates were 55.9% and 85.8%, respectively. For primary OAL, while there was a trend towards decreased 5-year DFS for more aggressive subtypes, this was not statistically significant. More advanced Ann Arbor stage was associated with decreased 5-year DFS; however, this trend was not statistically significant. However, increased AJCC seventh edition T category was associated with decreased 5-year DFS (T1=67.8%, T2=59.2%, T3=28.6%, T4=33.3%; p=0.025). Conclusion AJCC seventh edition T category was predictive of DFS in patients with OAL.

Multidisciplinary management of lacrimal sac/nasolacrimal duct carcinomas

Purpose: To determine the rates of globe-sparing treatment and useful final visual function in patients with primary lacrimal sac/nasolacrimal duct carcinomas treated with multidisciplinary therapy. Methods: The medical records of 14 patients with primary lacrimal sac/nasolacrimal duct carcinoma treated at 1 institution were retrospectively reviewed. Results: The patients were 9 men and 5 women; the median age at diagnosis was 58.5 years (range, 45–73 years). Seven patients presented with epiphora, 7 with a palpable mass in the inferomedial orbit, and 2 with dacryocystitis. In 3 patients, the diagnosis of cancer was not considered until during or after dacryocystorhinostomy. Seven patients had squamous cell carcinoma, 2 transitional cell carcinoma, 2 adenoid cystic carcinoma, and 1 each adenocarcinoma, poorly differentiated carcinoma, and inverted papilloma with carcinoma in situ transformation. Nine patients underwent surgical resection of the lacrimal sac and nasolacrimal duct and resection of the medial upper and lower eyelids, including canaliculi, partial ethmoidectomy, and medial maxillectomy. One patient underwent lacrimal sac biopsy only as another primary malignancy was discovered during the work-up for systemic disease. Four patients underwent orbital exenteration because of extensive involvement of the orbital soft tissue. Radiotherapy was recommended for 13 patients; in 1 patient, radiotherapy was not recommended because the patient had an inverted papilloma with carcinoma in situ transformation that was completely excised. The median radiation dose was 60 Gy. Eight patients received chemotherapy either concurrent with radiation therapy (5 patients), as neoadjuvant treatment (1 patient), or for progressive or metastatic disease (3 patients). The median follow-up time was 27 months (range, 6–96 months). In 10 patients, the globe was spared. In 9 of these 10 patients, visual acuity was the same as at baseline or better than 20/40 at last follow up. Conclusions: With multidisciplinary therapy, the eye can be spared and reasonable visual function can be preserved in most patients with primary lacrimal sac/nasolacrimal duct carcinomas.

Ophthalmic complications of targeted cancer therapy and recently recognized ophthalmic complications of traditional chemotherapy

As our understanding of cancer pathophysiology has increased, so have the number of targeted therapeutic agents available. By targeting specific molecules involved in tumorigenesis, targeted therapeutic agents offer the potential for significant efficacy against tumor cells while minimizing the adverse effects. We highlight the recently recognized ophthalmic complications of targeted cancer therapy, as well as recently recognized complications of traditional chemotherapeutic agents.

Mutational landscape of lacrimal gland carcinomas and implications for treatment

Lacrimal gland carcinomas are rare. Identification of molecular abnormalities underlying lacrimal gland carcinogenesis is critical to the development of new targeted therapies for lacrimal gland carcinomas. The purpose of our study was to look for mutations that can be targeted as new treatments for lacrimal gland carcinomas.

Correlation of American Joint Committee on Cancer T category for eyelid carcinoma with outcomes in patients with periocular Merkel cell carcinoma.

Purpose: Merkel cell carcinoma is a rare but potentially deadly cancer of the eyelid. To date, no studies have reported on clinical parameters at initial presentation of the eyelid tumor that may correlate with disease-free survival (DFS). The purpose of this study was to determine whether the American Joint Committee on Cancer (AJCC) T category for eyelid carcinoma correlates with metastasis and DFS in patients with Merkel cell carcinoma of the periocular region. Methods: This is a retrospective cohort study from a tertiary referral cancer center. All consecutive patients treated for eyelid or periocular Merkel cell carcinoma between November 1, 1998, and November 1, 2012, were reviewed. The main outcome measures included AJCC T category for eyelid carcinoma and Merkel cell carcinoma at presentation, nodal metastasis at presentation, metastasis during follow up, and DFS. Results: The study included 18 patients, 7 men and 11 women, with median age of 68.5 years. The AJCC T categories for both eyelid carcinoma and Merkel cell carcinoma were significantly correlated with DFS. Using the T categories for eyelid carcinoma, when TX and T2a were grouped into a single category and T2b and T3a into another category, the estimated DFS rate at 3 years was 100% for patients with TX or T2a lesions and 57% for patients with T2b or T3a lesions (p = 0.0298). Four patients (22%) had lymph node metastasis at presentation. Presence of lymph node metastasis at presentation was the strongest single predictor of shorter DFS and an increased risk of metastasis during follow up (p = 0.0222). Conclusions: The AJCC eyelid carcinoma T at presentation correlates with DFS in patients with Merkel cell carcinoma of the periocular region. The DFS rate at 3 years was significantly worse for patients with T2b or more extensive tumors by eyelid carcinoma T category. Presence of lymph node metastasis at presentation was predictive of shorter DFS and an increased risk of metastasis during follow up.

Small-incision, sutureless repair of subconjunctival fat prolapse.

Purpose: To present a new, small-incision, sutureless surgical technique for the repair of subconjunctival fat proplase. Methods: This is a retrospective interventional case series. Four eyes of 3 patients who presented with prolapsed subconjunctival fat were surgically repaired using a small-incision, sutureless technique with fibrin glue. No prolapsed subconjunctival fat was excised. Results: The surgical treatment of prolapsed subconjunctival fat using a small-incision, sutureless technique with fibrin glue was successful in all 4 eyes. There have been no cases of recurrence of the prolapsed subconjunctival fat with a mean follow up of 31 months. Conclusions: Small-incision, sutureless repositioning of subconjunctival fat using fibrin glue is an effective new surgical technique for the management of prolapsed subconjunctival fat.

Orbital and Ocular Adnexal Lymphoma

Lymphomas result from neoplastic transformation of cells that reside predominantly within lymphoid tissues. Ocular adnexal lymphoma (OAL) refers to lymphoma that involves the conjunctiva, lacrimal gland, eyelid, or orbit. Most OALs are low-grade B-cell non-Hodgkin lymphoma, and approximately half of OALs are of the mucosa-associated lymphoid tissue (MALT) type [1–3]. Orbital lymphoma is the most common primary orbital malignancy in adults and accounts for approximately 11 % of all orbital masses and 34 % of orbital malignancies [2]. The majority of OALs are non-Hodgkin B-cell lymphoma and are seen primarily in adults in the sixth to eighth decade of life. OAL accounts for 8 % of all extranodal lymphomas and only 1–2 % of all non-Hodgkin lymphomas [2–7]. While OAL is often viewed as a localized disease process, studies have demonstrated that up to 36 % of patients with primary OAL have systemic involvement at the time of diagnosis, depending on the elements of their staging work-up [8–10]. This chapter discusses the classification, staging, treatment options, and outcomes for OAL.

Merkel cell carcinoma of the eyelid and periocular region.

Merkel cell carcinoma (MCC) in the eyelid and periocular region can be treated surgically, in most cases, with preservation of the eye and reasonable visual function. Adjuvant radiation therapy, sentinel lymph node biopsy, and chemotherapy should be considered for MCC of the eyelid and periocular region, especially for larger tumors that are T2b or more advanced and lesions that present with regional nodal or distant metastasis.

Re: "American joint committee on cancer (AJCC) clinical classification predicts conjunctival melanoma outcomes"

1. Shields CL, Kaliki S, Al-Dahmash SA, et al. American Joint Committee on Cancer (AJCC) clinical classification predicts conjunctival melanoma outcomes. Ophthal Plast Reconstr Surg 2012;28:313–23. 2. Edge SB, Byrd DR, Compton CC, et al. American Joint Committee on Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010:50–1. 3. Paridaens AD, Minassian DC, McCartney AC, et al. Prognostic factors in primary malignant melanoma of the conjunctiva: a clinicopathological study of 256 cases. Br J Ophthalmol 1994;78: 252–9. 4. Savar A, Ross MI, Prieto VG, et al. Sentinel lymph node biopsy for ocular adnexal melanoma: experience in 30 patients. Ophthalmology 2009;116:2217–23. 5. Savar A, Esmaeli B, Ho H, et al. Conjunctival melanoma: localregional control rates, and impact of high-risk histopathologic features. J Cutan Pathol 2011;38:18–24. 6. Shields CL, Markowitz JS, Belinsky I, et al. Conjunctival melanoma: outcomes based on tumor origin in 382 consecutive cases. Ophthalmology 2011;118:389–95.e1–2. 7. Nasser QJ, Esmaeli B. Letter to the editor regarding: Shields CL, Markowitz JS, Belinsky I, et al. Conjunctival melanoma: outcomes based on tumor origin in 382 consecutive cases. Ophthalmology 2011;118:389–95. 8. Shields CL, Shields JA. In reply to: Nassar QJ, Esmaeli B. Conjunctival melanoma: outcomes based on tumor origin in 382 consecutive cases. Ophthalmology 2011;118:389–95.