64 ORBIT, EYELIDS, AND OCULAR ADNEXA

SQUAMOUS CELL CARCINOMA (SCC) 8% of eyelid CA (BCC is 40x more common); most common site is upper lid. Presents as a red, scaly, fastgrowing lesion, pain from perineural invasion, dyskeratosis, waxy or glassy appearance, and inflammation at the base. Can arise from AK; also associated with HPV. Other risk factors include sun exposure, fair skin, red hair, family or personal history of skin CA, inherited DNA repair defect, and albinism.

Pathology: pink-colored tumor cells that have violated and are above the basement membrane (mnemonic: Pink and above); can have metastatic spread. Look for actinic keratosis at margin (good prognosis, metastasis in <0.5%).

Xeroderma pigmentosa: autosomal recessive defect of DNA repair with increased risk of SCC and BCC.

Treat with excision, 5-FU, cisplatin, or radiation therapy.

Neoplastic, Eyelid and Orbital: Pigmented Lesions

CUTANEOUS MALIGNANT MELANOMA Rare on eyelid (<1% of eyelid CA); slowly growing pigmented lesion (may be amelanotic) that is highly malignant. One third of cases arise de novo, one third from preexisting nevus or oculodermal melanocytosis (ODM), and one third from conjunctival primary acquired melanocytosis (PAM). Frequently metastasizes, with high mortality. Treat with wide excision with permanent sections and possible sentinel node exploration. Biopsy all new pigmented lesions in patients >40 years old.

Superficial spreading: 80% of cutaneous melanoma.

Nodular: most common of eyelid melanomas but least common overall (only 10% of melanomas); vertical spread >1.5 mm; worse prognosis (unlike BCC, where nodular form is better prognosis than morpheaform).

Giant congenital nevus: >10 mm horizontal size; 10% risk of malignant melanoma (MM).

Lentigo maligna (Hutchinson’s freckle): pale brown macule with irregular borders usually in elderly patients; see best with Wood’s light. Ten percent become lentigo maligna melanoma.

EPHELIS, FRECKLE Common, benign pigmented macule. Pathology shows no increased number of melanocytes, but increased melanosomes from resident dendritic melanocytes (inoculated into neighboring keratinocytes for storage).

LENTIGO SIMPLEX Small brown macules on skin and mucous membranes. Peutz-Jeghers syndrome has multiple lesions associated with gastrointestinal polyps.

NEVI Flat to raised pigmented lesion that represent a collection of melanocytes. If cystic on pathology, then is a benign nevus (cysts form as

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the epidermal melanocytes attempt to return to their neural crest origin, dragging epithelial cells into the dermis, which then create cysts). Nevi often show pigment exhaustion with time.

Junctional: nests of nevus cells in epidermis; well-defined, darkly pigmented macules. Lowest malignant potential.

Compound: cell clumps in the lower epithelium and dermis; less dark and slightly elevated. Some malignant potential from the intradermal portion. Most congenital nevi are compound type.

Dysplastic nevus: compound nevus with architectural disorder and atypia, present in 5% of all Caucasians. Multiple lesions present in familial dysplastic nevus syndrome (B-K mole syndrome). Can transform into MM.

Intradermal: blue cells (specialized melanocytes, not the common dendritic melanocyte) with less nesting; confined to dermis with clear band separating it from the epidermis, and clear intranuclear spaces. Lesions are pale-tan color, more elevated (may be mistaken for squamous papilloma or wart), and may contain hair. Highest malignant potential.

Blue nevus: embryonic melanocytes that never completed their journey to the epidermis and remain trapped within the dermis; blue from the Tyndall effect because they are deeper and not superficial.

Ocular melanosis (if dermal, called Ota’s nevus): dendritic melanocytes trapped in dermis; unilateral. More common in Asians. Risk for melanoma.

PRIMARY ACQUIRED MELANOSIS (PAM) Conjunctiva melanoma in situ, occuring primarily in adults; unilateral; waxes and wanes. Excise with wide margins with random conjunctival biopsy; look for junctional pathology indicating nevus versus atypia. Risk for MM. See Chapter 3.

PRIMARY ORBITAL MELANOMA Usually from meninges; slightly increased risk of choroidal melanoma. Risk factors: Caucasian, ocular melanocytosis.

Neoplastic, Orbital: Lacrimal Gland Tumors

GENERAL Comprise 13% of orbital neoplasms. In a comprehensive practice, approximately 25% of lacrimal gland lesions are epithelial tumors (mostly pleomorphic adenoma, followed by adenocystic carcinoma, and pleomorphic adenocarcinoma). The other 75% of nonepithelial lacrimal gland lesions are mostly lymphoid hyperplasia, dacryoadenitis, lymphoma, and rarely plasmacytomas. In a referral practice, about 50% of lacrimal lesions are inflammatory or lymphoid, and 50% are epithelial neoplasms. Approximately 50% of these epithelial tumors are pleomorphic adenomas, and 50% are malignant tumors. Of these malignant tumors, about 50% are adenocystic carcinoma, and 50% of these are basaloid subtype.

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66ORBIT, EYELIDS, AND OCULAR ADNEXA

Ask about duration of symptoms; check VA, proptosis, palpation, and image. On CT, epithelial tumors are likely to be round, with bone indentation or erosion if malignant with irregular margins. Lymphoid or inflammatory lesions are usually oblong, ‘‘pancake’’ like.

Adenocarcinoma: rare but is the second most common malignant lacrimal tumor; not ductal; spread via lymphatics to lung. Usually fatal within 6 months.

ADENOCYSTIC CARCINOMA (ACC), CYLINDROMA Although a rare tumor, it is the most common malignant tumor of the lacrimal gland; increased incidence in males, with poor prognosis. Painful from perineural invasion (lacrimal nerve from CN V2) and bony destruction with rapid proptosis; symptoms duration <6 months. CT shows irregular bony erosion.

Pathology patterns: cribriform (‘‘purple Swiss cheese’’ appearance), basaloid (solid pattern; 50% of ACC, worse prognosis), comedocarcinoma (central necrosis), or tubular (ductal formation).

Incisional biopsy through lid; when confirmed by permanent pathology sections (never based on frozen sections alone), classically offer radical exenteration (2% cure), with or without chemotherapy. However, nonradical excision, then high-dose radiation therapy (e.g., proton beam) without chemotherapy or exenteration, is just as good. Overall 10-year mortality is 80% (1-year mortality without treatment is 100%).

INFLAMMATORY LESIONS May be from pseudotumor (hypocellular pathology), sarcoid (usually asymmetric but bilateral), and others. Typically short history; no bony involvement, oblong gland appearance on imaging, and involving orbital and palpebral lobes of lacrimal gland.

MALIGNANT PLEOMORPHIC ADENOMA, MALIGNANT MIXED CELL TUMOR Malignant transformation of pleomorphic adenoma with proliferating ductal epithelium in a tubular formation. Wide excision with radiation therapy recommended. More lethal than ACC; tendency for lung metastases, not intracranial spread.

PLEOMORPHIC ADENOMA, BENIGN MIXED CELL TUMOR Most common epithelial lacrimal tumor. Painless, slow growing, usually >9 months history of gland enlargement; superotemporal mass, ptosis, proptosis. Usually found in middle-aged females, with bony remodeling, not destruction.

Typically is a well-differentiated, well-circumscribed homogeneous mass with ductal proliferation and myoepithelium cells on pathology. Does not arise from acini; the ducts have cuboidal bilayer with inner mucinous cells and outer cells that differentiate into epithelium.

Excise entirely (excisional biopsy) because tumor may have areas of malignant transformation. Recurrence if capsule intact 3% (31% if

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capsule violated); increased malignant potential in recurrent tumors (10% risk of recurrence per decade).

PRIMARY LACRIMAL GLAND LYMPHOMA Enlarged gland with hypercellular pathology and rubbery consistency (no collagen), molding or putty-like on CT, shortor long-standing history of lacrimal gland swelling. See below.

Neoplastic, Orbital: Lymphoproliferative Lesions

GENERAL Comprise 18% of orbital neoplasms and are the most common intraorbital malignancies in adults (most patients are 60–90 years old). Tumors mold to structures in orbit. Lymphoproliferative lesions are a spectrum of disease, including B cell lymphoma (67%), lymphoid hyperplasia (16%), myeloma or Waldenstro¨m’s macroglobulinemia (9%), and histiocytosis (7%).

World Health Organization (WHO) classification of lymphomas: B cell neoplasms (primary interest of ophthalmologists), T cell neoplasms, and Hodgkin’s lymphoma.

Biopsy and send for flow cytometry: if T cells are predominant, then likely orbital inflammation; if mixture of T and B cells, then likely benign lymphoid hyperplasia; if majority are B cells, then diagnosis is likely lymphoma.

BENIGN LYMPHOID HYPERPLASIA Polyclonal (50% B cells, 50% T cells), may make follicles; overall 25% have systemic disease. Treat with steroids or may use chemotherapy if atypical cells are seen on pathology.

Benign reactive: 6% 5-year mortality, 15 to 25% systemic risk.

Atypical reactive: 19% 5-year mortality, 40% systemic risk

HISTIOCYTOSIS Also known as histiocytosis X or Langerhans’ cell tumors (Langerhans’ cells contain Bierbeck granules; do not confuse with Langhans’ multinucleated giant cells of foreign body granuloma). Spectrum of the following diseases (increasing severity alphabetically):

Eosinophilic granuloma: most common and benign histiocytosis affecting the orbit; slow growing orbital mass, usually superotemporal location. Presents by end of first decade with pain, proptosis, and lid swelling. No visceral involvement (usually skull bones involved and not systemic).

Patient looks good, but CT looks bad (lytic bony lesions). Pathology shows monoclonal histiocytic proliferation with many eosinophils.

Excisional biopsy is often curative. Use local curettage for isolated lesion or radiation therapy 400–600 cGy for multiple or inaccessible lesions. Chemotherapy (chlorambucil) is recommended for systemic involvement (more likely with Letterer-Siwe disease).

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