Chapters – Page 5 – Kugler Publications

Pathological Evaluation of Orbital and Periorbital Tumors

Space-occupying mass lesions in the orbit and peri-orbit are rather uncommon but can be a diagnostic challenge for ophthalmologists and orbital surgeons. In some patients, the combination of clinical presentation and imaging is sufficient to reach a diagnosis; however, many others require morphologic evaluation. The histo-pathologic specification can only be definite by biopsy. The etymologic origin of “biopsy” stems from the Greek words “bios,” meaning “life,” and “opsis,” meaning “sight or view,” together crudely meaning, “to view life.” Plainly, the examination of “live tissue.” Tissue acquisition can be performed via excisional, incisional, core, fine-needle aspiration (FNAB), aspiration-cutter, intraoperative biopsy with frozen-section (FS), or Mohs methods. Occasionally, sentinel node biopsy is utilized for staging purposes of certain orbital tumors.1-3
Most anterior and well-delineated orbital masses can be sampled with any approach: incisional, core, or FNAB. The terms “incisional” and “excisional” are sometimes used interchangeably, but in actuality, “incisional” biopsy refers to cutting into a lesion to sample a portion of tissue solely for the purpose of obtaining a tissue sample, while “excisional” biopsy, implies removal of the tumor and some surrounding normal tissue.1 Naturally, the excised tissue provides more material for histopathologic examination. While incisional biopsy can also obtain a sufficient quantity of tissue for lesions in the anterior orbit, incising tissue acquisition in the posterior orbit can be complex, increasing the risk of complications. In addition, posterior orbital surgery typically requires general anesthesia to facilitate a higher diagnostic yield. Lastly, aspiration is the least invasive technique, and expectedly, offers the least amount of material.4

Enucleation and Exenteration

Eye removal is done for managing cancers, infections, inflammatory disorders, and intractable eye pain. It involves the removal of the eye by evisceration, enucleation, or orbital exenteration (Fig. 15-1). Evisceration involves removing the intraocular contents while preserving the outer scleral ocular coat and its orbital attachments. Enucleation consists of removing the entire eyeball; thus, the muscles and optic nerve must be detached. Orbital exenteration consists of removing all the orbit’s contents to bone (including periosteum).
Evisceration is rarely used in ocular oncology due to risks related to seeding the orbit with the tumor, recur-rence, and metastatic spread.1 In ophthalmic oncology, enucleation is most commonly used for advanced uveal melanoma and RB, whereas orbital exenteration is most commonly required for managing

Systemic Treatment of Uveal Melanoma: Insights and Emerging Strategies

Uveal melanoma (UM) is a relatively rare cancer, but is the most common primary intraocular malignancy (see Chapter 25) and comprises 5% of all melanoma diagnoses in the United States.1,2 UM arises from melanocytes within the capillary-rich uveal tract, with the most frequent locations being the choroid (90%), ciliary body (6%), and iris (4%).3 Although UM occurs with an incidence of ~2,000 cases per year, it is an aggressive cancer.4,5 Screening with periodic, abdominal radiographic imaging, 25%–30% of patients are diagnosed with metastatic UM within 5 years (see Chapter 27). Exiting the eye by hematogenous spread, commonly reported metastatic sites include the liver (89%), lung (29%), and bone (17%).6 The latency between the treatment of the primary tumor and the emergence of metastases ranges from months to decades, underscoring the likelihood of early dissemination from the primary site and variable metastatic growth rates.7 Unfortunately, there is no standardized consensus and known effective treatment for advanced UM in the adjuvant or metastatic settings. The prognosis is poor once metastasis develops, with a median overall survival of 10.2 months.8 Long-term sur-vival is unusual except in rare patients with isolated liver metastases amenable to surgical resection. When available and clinically appropriate, treatment within a clinical trial is recommended.
Although UM differs from cutaneous melanoma both clinically and biologically, treatment options for advanced stages have largely been adopted with much lower resultant response rates.9 Similarly, in that UM metastases are less responsive than cutaneous melanoma to both chemotherapy and immune checkpoint inhibitors, several treatment modalities have been evaluated, including systemic chemotherapy, immunotherapy, and molecularly targeted agents for the MAPK pathway. As the most common initial site of metastasis is the liver, palliative management includes liver-directed therapies such as bland embolization, chemoembolization, radioembolization, immunoembolization, and hepatic arterial infusion of chemotherapy. In this chapter, we review the molecular pathogenesis of UM, its prognosis, and advances in the management of metastatic UM (Mind map 14-1).

Local Chemotherapy for Intraocular Tumors

Techniques for delivering chemotherapeutic agents for intraocular tumors have evolved. In addition to the traditional intravenous chemotherapy, more localized intra-arterial, periocular, and intravitreal chemotherapy (IVC) techniques place chemotherapeutic agents into the eye. Ocular chemotherapy achieves maximum local drug concentrations, improves efficacy, and minimizes adverse effects.
RB and vitreoretinal lymphoma are 2 intraocular tumors where periocular and intraocular chemotherapy are widely used. This chapter focuses on the medications and techniques of ocular chemotherapy.

Topical Chemotherapy for Ocular Tumors

Eye cancer management has shifted towards less invasive treatment modalities to achieve maximum tumor control as well as globe and vision salvage. For example, topical chemotherapy and immunotherapy agents are now commonly used as primary or adjuvant treatments for many eye tumors. This chapter discusses the pharmacology, doses, indications, mechanisms of action, and side effects of ophthalmic topical chemotherapy.

Lasers in Ophthalmic Oncology

Gerhard Meyer-Schwickerath, MD, was intrigued by the chorioretinal lesions, similar to diathermy scars, found in patients who had stared at a solar eclipse. In 1946, this observation prompted his first experiments with a car-bon-arc lamp from an old episcope. However, it wasn’t until 1949 that Meyer-Schwickerath used carbon arc photocoagulation as an alternative to enucleation for posterior choroidal melanomas.1,2 Then, in 1952, Vogel reported their results using xenon arc photocoagulation for 61 intraocular tumors.3-5
This chapter concentrates on newer ophthalmic lasers used in ophthalmic oncology. For example, Foulds used lower-energy, long-exposure combinations of argon green and then krypton red.6 Then, a wide-spot infrared laser (TTT) was introduced by Oosterhuis, popularized by Shields, and then largely abandoned.7 Most recently, PDT involves systemic intravenous administration of a photosensitizing dye (hematoporphyrin), which is then activated by a nonthermal laser.8
Thus, ophthalmic lasers and their applications have evolved into an accepted therapeutic option for select benign and malignant intraocular tumors.1-8 This chapter describes the attributes, applications, tissue interactions, current practice indications, and complications of ophthalmic laser photocoagulation for intraocular tumors.

Towards Holistic Ophthalmic Oncology Care

Despite the advances in the clinical management of ocular and periocular tumors that have significantly improved life expectancy and visual prognosis, many barriers to care delivery remain.1-3 Structural separations between the ocular oncologist, oculoplastics specialist, pathologist, radiation oncologist, medical oncologist, and other stakeholders may contribute to inconsistent referral practices, poor communication, inappropriate or delayed referrals, duplication of efforts, and interruptions in the continuity of care. These disruptions may lead to a fragmented and stressful experience for both patient and caregiver. Improved integration between caregivers, services, and institutions at all stages of the clinical encounter can provide a holistic experience that improves patient outcomes and quality of life while advancing knowledge in ophthalmic oncology (Mind map 10-1).

International Outreach: Improving Global Retinoblastoma Outcomes

RB is the most common primary intraocular malignancy of childhood, and > 8,000 children are diagnosed each year worldwide.1,2 In high-resource settings with infrastructure and support, the survival of children with RB can be nearly 100%.3,4 In contrast, in low- and middle-resource countries, eye cancer specialists and support are lacking, leading to survival rates approximating 10%.3-5 In that more than 80% of the children diagnosed with pediatric cancer live in low- and middle-resource countries, many more children are dying of RB than surviving.6-11 Given this disparity, it is important to identify what can be done to save the lives of RB children in low- and middle-resource countries.
That said, the World Health Organization (WHO) has identified RB as one of the most curable pediatric index cancers, stating a goal of at least 60% survival by 2030.12 This will require cooperation between ophthalmic and pediatric oncology. Governments and nongovernmental organizations will need to work towards allocating highly specific resources, education/training, and infrastructure. Thus, RB can serve as a model for other pediatric cancers by implementing effective education, training, and capacity-building initiatives that are scalable and adaptable. Many strategies are already known to be effective: multidisciplinary care teams, well-defined referral networks, resource-adapted treatment guidelines, as well as early programs to promote early detection and awareness.

A Review of Intraocular and Orbital Tumor Registry Studies

“Do you speak ocular tumor?” Dr. Finger asked this question in his thought-provoking editorial for the journal Ophthalmology nearly 20 years ago.1 Since then, there have been numerous advances in diagnostic and thera-peutic modalities for eye cancers. However, this question is just as relevant as it was 2 decades ago. The extent of tumor at presentation, defined by cancer staging, is an essential factor that determines disease prognosis, guides treatment planning, helps plan and evaluate clinical trials, and aids in the exchange and comparison of information across treatment centers.1,2 At a multicenter or global level, a uniform cancer classification is critical for clearly conveying clinical experience to others without ambiguity. A standardized cancer staging system enhances communication amongst specialists involved in tumor care: eye cancer specialists, pediatric oncologists, radiologists, radiation therapists, ophthalmic pathologists, geneticists, and researchers. With this in mind, Dr. Finger led the pursuit to develop the most scientifically sound language to address eye cancers: the AJCC eye cancer staging system (Mind map 8-1).
The AJCC, in conjunction with its international counterpart, the Union for International Cancer Control (UICC), joined forces to develop a consensus staging system for cancers of the eye, lids, and orbit. Dr. Finger was selected to chair the 7th edition AJCC effort for ophthalmic oncology in 2003. His philosophy to approach this task was “what is made by the community will be used by the community” (see Chapter 1). Upon review of their research and clinical reputation, Dr. Finger rallied to bring the leading specialists in each tumor type to the discussion table and laid the foundations of the AJCC-OOTF.
The process involved the formation of expert clinical and pathology peer review. An initial group re-examined the literature for each type of eye cancer and synthesized an evidence-based medical consensus on paper. Another group of similar experts critically reviewed the staging proposal. Both teams reviewed the final draft. This process was conducted through monthly phone meetings and periodic in-person discussions over 4 years. The community’s efforts resulted in the 7th edition AJCC eye cancer staging system in 2009.3 As the AJCC staging system is periodically updated with newly available medical evidence, the 8th edition of AJCC staging was drafted with the participation of 58 specialists from 13 countries.4
Since its publication, this staging system has become universally accepted by tumor registries worldwide, prominent ophthalmology journals, and their associated societies. The widespread utilization of ophthalmic AJCC staging can be revealed by searching PubMed for the terms “AJCC” and “eye”. One of the major advantages of the AJCC TNM staging system is that it can be modified in response to newly acquired clinical and pathologic data, improved understanding of cancer biology, and other factors affecting prognosis. The evidence-based modifications are made meticulously, and the revision cycle usually spans 5–7 years. The intent is to provide ample time for implementing changes in clinical management and cancer registry operations.
Herein, we discuss the impact of AJCC staging by outlining how it has improved the abilities of eye cancer specialists and thus saved the lives of patients.