13 Neoplasms

sary. A spray tip is placed just above the target site and sprayed either in an ever-widening circle or in a back-and-forth ‘paintbrush’ pattern until the entire lesion is covered. Freezing should be carried just outside the border of the lesion. Total thaw time (the time from stopping freezing until all white frosted areas on the surface disappear or all hard areas resolve on palpation) is approximately 20 to 30 seconds.

A crusted/vesicular stage will occur, followed by eschar. This usually resolves or falls off around 14 days. A smooth, pinkish residual remains, which fades in time. Occasionally, hyperkeratotic or other lesions may need superficial shave excisions. When this occurs, usually no suturing is required, but local anesthetic is usually necessary.

Lubritz RR: Cryosurgery of benign and premalignant cutaneous lesions. In: Zacarian SA, ed: Cryosurgical advances in dermatology and tumors of the head and neck. Springfield, IL, Charles C Thomas, 1977:55–73.

Lubritz RR: Cryosurgery of nonmalignancies. In: Zacarian SA, ed: Cryosurgery for skin cancer and cutaneous disorders. St Louis, CV Mosby, 1985:49–58.

Muriello JA, Napolitano J, McLean I: Actinic keratosis and dysplasia of the conjunctiva: clinicopathological study of 45 cases. Can J Ophthalmol 30:312–316, 1995.

Torre D, Lubritz RR, Kuflik E, eds: Practical cutaneous cryosurgery. East Norwalk, CT, Appleton & Lange, 1988:61–86.

Tseng SH, Chen YT, Huang FC, et al: Seborrheic keratosis of conjunctiva simulating a malignant melanoma: an immunocytochemical study with impression cytology. Ophthalmology 106:1516–1520, 1999.

COMPLICATIONS

Removal with curette or scissors generally requires routine measures for hemostasis, such as the use of Gelfoam dressing or the application of aluminum chloride (precautions should be taken around the eye for any chemical hemostasis). However, patients who receive anticoagulants must be observed and cautioned regarding prolonged bleeding.

COMMENTS

Care should be taken during cryosurgical procedures around the eye to avoid unnecessary harm to the global structures. When the technique described is used for raised seborrheic keratoses, the lesions should not be frozen too hard; if this happens, the operator must wait until the lesion is partially thawed before continuing. Clinical experience is necessary to judge the degree of freezing required for these techniques; too much freezing can result in scarring or pigmentary changes that are out of proportion to the tumor being treated. Patients should be informed of the possibility that pigmented lesions may not lose all their color after cryosurgical treatment. Occasionally, fissures occur within a lesion. Liquid nitrogen sprayed under too great a pressure into such an opening can lead to ‘ballooning’ of the eyelid. This is usually self-limited but can have an alarming appearance. The use of topical 5FU or imiquimod is also used for the selective treatment of multiple actinic keratoses. However, these treatments are usually not indicated for individual lesions and should not be used on the eyelids or above the inferior periorbital ridge.

ETIOLOGY/INCIDENCE

Basal cell carcinoma (Figure 122.1) accounts for 80–90% of eyelid malignancies and occurs more commonly in Caucasians. Prolong or significant unprotected exposure to UV radiation has proven to be tumorigenic. The tumor most commonly arises in the lower eyelids, followed by the medial canthus, the upper eyelids, and the lateral canthus. Basal cell carcinoma is slow growing, locally invasive, and rarely metastasizes. Prognosis is good with early detection and treatment with a cure rate of 95%.

DIAGNOSIS

Clinical signs and symptoms

Patients often present complaining of a painless, nonhealing ulcer. History may elicit a long history to sun exposure. Symptoms are: painless nodule with a shiny and waxy, indurated, firm and immobile, pearly, rolled border and with fine telangiectatic vessels on the surface (Figures 122.1 and 122.2).

Clinically, basal cell carcinoma can be grouped into three types: nodular, nodulo-ulcerative (rodent ulcer) and morpheaform or sclerosing.

Laboratory findings

Histology

Typical findings include nests of basaloid cells with a peripheral palisading pattern. Tumor cells have large, oval or elongated nuclei with scant cytoplasm, contraction artifact at the periphery of the tumor along with desmoplasia of the surrounding stroma.

REFERENCES

Kuflik EG: Cryosurgery updated. J Am Acad Dermatol 31:925–944, 1994.

Lubritz RR: Cryosurgery of benign lesions. Cutis 16:426–432, 1975.

Lubritz RR: Cryosurgery for benign and malignant skin lesions: Treatment with a new instrument. South Med J 69:1401–1405, 1976.

Imaging studies

Imaging studies are often not necessary. However, radiological imaging of the facial and orbital bones and soft tissue may be helpful for an invading or deep tumor in the medial canthus.

The application of ultrasonography is producing controversy due to the inaccuracy in delineating malignant from benign lesions with a success rate of approximately 20%.

FIGURE 122.1. The lesion is located in the lateral one-third of the lower lid of the left eye. Note the indurated, whitish, raised border with a central ulceration. The purple dot was the marking made prior to Mohs surgery. The patient ultimately underwent a left lower lid reconstruction.

include dermatitis, keratinization of the conjunctiva and chronic keratitis.

Chemotherapy (5-FU, cisplastin), although not curative, may be helpful in managing lesions located in the medial canthus, recurrent and invasive tumors, and large tumors where surgical resection may result in cosmetic deformity and functional defect.

Photodynamic therapy (PDT) with photosensitizers may be an effective treatment for superficial tumors. The success rate for PDT ranged from 50%–83%.

Systemic retinoid and alpha interferon have shown some efficacy but the long term toxicity of systemic retinoid agents generally excludes them as treatment of choices for most patients.

Surgical

Mohs micrographic surgery have gained wide acceptance among ophthalmologist. The 5-year recurrence rates for treated basal cell carcinoma after Mohs surgery was 1.0%, 7.5% after cryosurgery, 7.7% after desiccation and curettage, 8.7% after radiotherapy and 10.1% after surgical excision.

Electrodessication and curettage is a used method. Although quick to destroy tumor cells the surgeon cannot visually detect the depth of microscopic tumor invasion and surgical margin. Tumors lest than 5 mm in diameter have a 15% recurrence rate, while tumors with a diameter of 3 cm or greater have a 50% recurrence rate within 5 years when treated by electrodessication and curettage.

Cryosurgery may be considered for small, clinically welldefined primary tumors. It is reserve for patients who are debilitated with medical conditions that preclude other types of surgery. Cryosurgery is a viable alternative in tumors involving the inner canthus, thereby minimizing damage to the lacrimal system.

Carbon dioxide laser may be considered when a bleeding diathesis is present. This laser approach provides a bloodless field, minimal postoperative pain and good postoperative appearance without scar formation.

FIGURE 122.2. Basal cell carcinoma of lower lid.

Laser Doppler may be useful in delineating tumor margin. This instrument measures the rate of blood flow and it has been shown that cutaneous perfusion is significantly higher is affected area.

Cytology is another mean to diagnosed basal cell carcinoma. Although it is sufficiently accurate in diagnosis basal cell carcinoma, it is not sufficiently sensitive when planning surgical management.

Differential diagnosis

●Sebaceous gland carcinoma, eyelid.

●Squamous cell carcinoma, eyelid.

●Chronic chalazion.

TREATMENT

Medical

Radiation therapy is reserve for recurring tumors or tumors requiring difficult or extensive oculoplastic surgery. It eliminates skin grafting with good cosmetic results. Side effects

SUMMARY

Basal cell carcinoma is the most common eyelid tumor. Although surgical management is the treatment of choice, medical management may serve as an adjunct to surgery. Death from metastasis is highly unusual. Prevention for primary or recurrent should include the application of sunscreen, wearing long sleeve shirt and broad-brimmed hat, avoid sun exposure during midday and schedule regular follow-up after treatment. Although basal cell carcinoma is diagnosed in the sixth and seventh decade of life, basal cell carcinoma diagnosed in young adults should warrant a full workup to rule out other systemic disease.

REFERENCES

Cook BE, Jr, Bartley GB: Epidemiologic characteristics and clinical course of patients with malignant eyelid tumors in an incidence cohort in Olmstead County, Minnesota. Ophthalmology 106(4):746–750, 1999.

Eagle RC: Eyelid and lacrimal sac. In: Eye pathology-an atlas and basic text. Philadelphia: WB Saunders, 1999:223–224.

McLean IW: Tumors of the eyelid. Tumors of the eye and ocular adnexa. In: Atlas of tumor pathology. Washington, DC, Armed Forces Institute of Pathology, 1994:18–22.

123 CAPILLARY HEMANGIOMA 228.01

(Angioblastic Hemangioma, Benign

Hemangioendothelioma,

Hemangioblastoma, Strawberry

Hemangioma)

Matthew W. Wilson, MD, FACS

Memphis, Tennessee

Roderick N. Hargrove, MD

Memphis, Tennessee

Capillary hemangiomas are among the most common orbital tumors that occur in the pediatric population. They are not true neoplasms but rather hamartomatous proliferations of primitive vasoformative tissues. Capillary hemangiomas consist of anastomosing blood-filled endothelium-lined channels that typically have an infiltrative growth pattern with no true encapsulation. Recent studies suggest that infantile hemangiomas may have a placental origin.

ETIOLOGY/INCIDENCE

There is a 3 : 2 female-to-male incidence ratio. These tumors follow a characteristic clinical course with a period of rapid hypertrophy for 3 to 12 months followed by a period of stabilization and then involution. The major degree of involution takes place by age 5 years, although lesser degrees of tumor regression may be noted until the end of the first decade. Involution is complete with no significant cosmetic sequelae in the majority of cases. In some larger lesions, however, especially those with a combined subcutaneous and superficial component, it is not uncommon to observe residual cosmetic defects. Ocular complications, such as amblyopia, have been noted in 50% to 75% of patients with orbital and adnexal hemangiomas. Rare dermatologic and systemic complications may occur.

COURSE/PROGNOSIS

Capillary hemangiomas usually present within the first 6 months of life, with one third of the lesions evident at birth. Rapid hypertrophy ensues for 3 to 12 months, followed by stabilization and then involution over the next 5 to 10 years. Clinically, these are benign tumors. Complications relate to amblyopia and cosmesis.

DIAGNOSIS

Clinical signs and symptoms

Clinical diagnosis is most often based on presentation. There are three clinical presentations of the disease:

1.Most commonly, a bluish-purple subcutaneous mass with normal overlying skin is noted in the anterior orbit.

Laboratory findings

●B-scan ultrasound reveals an irregular mass that blends into the surrounding orbital structures. A-scan demonstrates low internal reflectivity in areas of proliferating endothelial cells, some moderate reflectivity in regions of ectatic vascular channels and high reflectivity near fibrous septa that divide the tumor.

●Computed tomography reveals a well defined or infiltrating lesion that is isodense to the extra-ocular muscles and optic nerve. There may be enlargement of the orbit without evidence of bony erosion. Contrast material may help to delineate the tumor borders and major feeder vessels.

●Magnetic resonance imaging (MRI) reveals a hyperintense tumor on T2-weighted images against a hypointense background of orbital fat. The contrast on T1-weighted images is not as significant, but it is enhanced by the administration of gadolinium-DTPA and the implementation of fat-suppression protocols. Dynamic contrast MRI shows early focal enhancement, which helps differentiate hemangiomas from other orbital masses that diffusely enhance.

●Angiography is rarely diagnostic and is seldom used except before surgical manipulation.

●Biopsy is most often reserved for the infant with a rapidly expanding proptosis and an absence of superficial abnormalities or discoloration. Hemostasis control via compression, cauterization, or hemostatic agents is usually sufficient. Histopathologic findings are summarized as follows:

●Masses of endothelial cells with increased mitotic figures have occasional vascular spaces characterized by small, irregular lumens;

●Reticulin stain may delineate the vasculature nature of the tumor in questionable cases;

●Weibel–Palade bodies occur within tumor cells in well differentiated hemangiomas.

Differential diagnosis

●Rhabdomyosarcoma.

●Lymphangioma.

●Choloroma.

●Neuroblastoma.

●Other neoplasms (Ewing’s sarcoma, medulloblastoma and Wilms’ tumor).

●Orbital cysts (dermoid).

●Cellulitis.

TREATMENT

Unless there are specific ocular, dermatologic, or systemic indications for rapid resolution, treatment should be withheld because all therapeutic modalities have significant real or theoretic risks. Ocular indications for treatment include occlusion of the visual axis, compression of the optic nerve or corneal exposure secondary to severe proptosis. When treatment is indicated, the use of intralesional steroids has assumed a prominent role.

Usually, no ocular medications are administered after surgery.

Other cryoprobes that involve the use of other cryogens are satisfactory; however, the contact time is doubled or tripled. This is a very superficial dysplasia and requires only a very superficial freeze.

Squamous cell carcinoma

Squamous cell carcinoma is treated in the same manner, but more aggressive cryotherapy (triple freeze-thaw) with wider margins around the tumor and deeper sclerectomy and keratectomy are necessary. Deep invasion of the sclera and cornea requires full eye wall resection. Lamellar transplants are seldom used because they cover the signs of an early recurrence. Small intraocular extension can be treated with iridocycletomy, whereas more extensive intraocular extensions may require enucleation.

COMPLICATIONS

Although deep cryotherapy may result in iritis, posterior synechiae and corneal scarring, the complications of superficial cryosurgery are minimal, even when the cornea is treated. To avoid adherence of the cryoprobe, it is of utmost importance to have the probe completely frozen before ocular application. If the probe is applied warm and then frozen, it will cause a tight ocular adherence that is not easily removed. The use of the thawing option with some cryoprobes markedly decreases the cytotoxic effects of cryotherapy.

Waring GO III, Roth AM, Ekins MB: Clinical and pathologic description of 17 cases of corneal intraepithelial neoplasia. Am J Ophthalmol 97:547–559, 1984.

125 CRANIOPHARYNGIOMA 237.0

Mandeep S. Tamber, MD

Toronto, Ontario

Abhaya V. Kulkarni, MD, PhD, FRCSC

Toronto, Ontario

ETIOLOGY/INCIDENCE

Craniopharyngiomas are benign neuroepithelial tumors of the parasellar region that are believed to develop from squamous cell remnants of Rathke’s pouch. Although histologically benign, their involvement of neural structures in the suprasellar region, vis-à-vis local invasion of the optic apparatus, hypothalamus and pituitary, greatly complicates their management.

Craniopharyngioma is the most common non-glial intracranial tumor of childhood, constituting 2.5–4% of pediatric brain tumors overall and fully 46% of childhood tumors of the sellar and parasellar region. That being said, craniopharyngioma remains a rare diagnosis, with an incidence of approximately 1.3 per million person-years.

COMMENTS

An obvious advantage of cryosurgery over other methods of treating CIN is that ‘root tips’ that are missed with surgery alone, especially at the limbus, can be treated. This procedure results in a higher cure rate and is more cost effective than most other procedures. The use of surgical excision combined with cryotherapy has almost tripled previous cure rates of the use of surgery alone.

Despite the low virulence rate of CIN, it can be difficult to cure. CIN recurrence is dependent more on how the treatment is performed than on the clinical appearance, presence of early invasion, degree of dysplasia, or cell type. However, not all incompletely excised lesions recur. Recurrence most often develops in the first 2 years after surgery but has been reported as late as 10 years. The highest recurrence rates occur with lesions that involve more than two thirds of the limbus and with repeat operations.

REFERENCES

Erie JC, Campbell RJ, Liesegant TJ: Conjunctival and corneal intraepithelial and invasive neoplasia. Ophthalmology 93:176–183, 1986.

Fraunfelder FT, Wingfield D: Management of intraepithelial conjunctival tumors and squamous cell carcinomas. Am J Ophthalmol 95:359–363, 1983.

Frucht-Pery J, Rozenman Y: Mitomycin C therapy for corneal intraepithelial neoplasia. Am J Ophthalmol 117:164–168, 1994.

Tabin G, Levin S, Snibson G, et al: Late recurrences and the necessity for long-term follow-up in corneal and conjunctival intraepithelial neoplasia. Ophthalmology 104:485–492, 1997.

Tsubota K, Kajiwara K, Ugjin S, Hasegawa T: Conjunctival brush cytology. Acta Cytol 34:233–235, 1990.

COURSE/PROGNOSIS

Despite recent advances in treatment modalities, craniopharyngioma remains a challenging entity. Most studies quote a 90% 10-year survival. There is a 1–2% risk of perioperative mortality. Permanent endocrine replacements are required for 85–90% of patients, mostly for the correction of ADH, cortisol and thyroxine deficiencies. A significant proportion of patients suffer major non-endocrine morbidity, including visual deficits (13–38%), seizures (12–18%), stroke (2–4%) and hypothalamic dysfunction (obesity, hypersomnolence, neurobehavioral effects).

DIAGNOSIS

Clinical signs and symptoms

Clinical manifestations depend largely upon the origin, direction and degree of tumor extension and the consequent involvement of surrounding neurovascular structures. Localized sellar tumors compress the pituitary gland, producing endocrine deficiency states (diabetes insipidus, short stature). Prechiasmatic tumors emerge from the sella and grow forward along the optic nerves, resulting in often severe visual compromise (reduced acuity, hemianopsias, optic atrophy). Retrochiasmatic tumors protrude behind the chiasm, shifting it anteriorly and distorting the third ventricle and hypothalamus. Accordingly, retrochiasmatic tumors are known to produce hydrocephalus (headache, papilledema) and hypothalamic dysfunction (endocrine and neuropsychological disturbances).

Laboratory findings

Cranial computed tomography (CT) and magnetic resonance (MR) imaging are the current imaging standards. The presence of suprasellar calcification, best demonstrated by CT, is important information for the surgeon, for it signals potentially difficult surgical extirpation. Sellar enlargement may also be visualized.

MR imaging is essential for preoperative planning, for it provides exquisite detail regarding the precise configuration of the solid ± cystic components of the tumor, as well as its relationship to surrounding neurovascular structures (Figure 125.1).

Comprehensive neuro-ophthalmological and endocrine evaluations also form part of the preoperative assessment of the child with craniopharyngioma.

therapy, either in the form of conventional fractionated external beam radiation, or stereotactic radiosurgery. In terms of local tumor control, data appears to suggest that both treatment alternatives are equivalent. With respect to treatment complications, radiotherapy results in delayed endocrine and visual defects similar to those observed following surgery, but the severity of these complications, particularly with respect to hypothalamic dysfunction, appears to be reduced. It must be remembered, however, that radiotherapy has its own inherent risks (cognitive dysfunction, second malignancy).

A third treatment alternative, reserved for cystic tumors, is cyst drainage followed by intracystic instillation of bleomycin or phosphorus-32.

At time of writing, chemotherapy for craniopharyngioma remains investigational.

TREATMENT

Craniopharyngioma is a complex clinicopathological condition that requires a multidisciplinary approach to treatment. The surgeon must bear in mind the goals of treatment as well as the sequelae of therapy. Treatment should be individualized so as to achieve the best possible retention of quality of life.

The optimal management strategy for these lesions remains controversial. At some centers, the treatment philosophy includes an initial attempt at gross total resection, based on the premise that total resection offers the best opportunity for tumor free survival. However, this aggressive surgical position is associated with significant upfront risks to endocrine, hypothalamic, and visual function.

In an effort to avoid surgical injury to these critical structures, others have adopted a less aggressive surgical position, advocating safe partial resection followed by adjuvant radio-

FIGURE 125.1. A sagittal T1-weighted MRI with gadolinium showing a typical large craniopharyngioma. The tumor is inhomogeneously enhancing and involves the sellar and suprasellar regions, with expansion into the third ventricle.

REFERENCES

Chiou SM, Lunsford LD, Niranjan A, et al: Stereotactic radiosurgery of residual or recurrent craniopharyngioma, after surgery, with or without radiation therapy. Neuro-oncol 3:159–166, 2001.

Duff JD, Meyer FB, Ilstrup DM, et al: Long-term outcomes for surgically resected craniopharyngiomas. Neurosurgery 46:291–305, 2000.

Hasegawa T, Kondziolka D, Hadjipanayis CG, et al: Management of cystic craniopharyngiomas with phosphorus-32 intracavitary irradiation. Neurosurgery 54:813–820, 2004.

van Effenterre R, Boch A-L: Craniopharyngioma in adults and children: a study of 122 surgical cases. J. Neurosurg. 97:3–11, 2002.

126 DERMOID 224.9

(Dermoid Cyst, Epidermoid Cyst,

Epibulbar Dermoid, Limbal Dermoid,

Lipodermoid, Dermolipoma)

Richard M. Robb, MD

Boston, Massachusetts

ETIOLOGY/INCIDENCE

Dermoids are choristomas that occur on or around the eye in two forms. One form is a cystic lesion with an inward-facing epidermal lining that surrounds a cavity filled with keratin, cholesterol clefts, oily sebum, and hairs. The wall of a true dermoid cyst contains dermal appendages, such as hair follicles and sweat glands. Epidermoid cyst walls lack these appendages. The other form of dermoid is a solid lesion at the corneal limbus or under the lateral bulbar conjunctiva.

DIAGNOSIS

Clinical signs and symptoms

Cystic dermoids most often occur at the superior orbital margin. If they are anterior to the orbital septum, they are usually recognized early in childhood. They have a soft rubbery consistency and are not attached to the overlying skin but may be bound to underlying periosteum. There often is a shallow crater in the orbital bone just under the lesion. Occasionally, the cysts have a dumbbell shape, with one end extending around the orbital margin and through the septum. Dermoid cysts that are

Henderson JW: Orbital tumors. 3rd edn. New York, Raven, 1993:53–61.

McNab AA, Wright JE, Caswell AG: Clinical features and surgical management of dermolipomas. Aust N Z J Ophthalmol 18:159–162, 1990.

Nevares RL, Mulliken JB, Robb RM: Ocular dermoids. Plast Reconstr Surg 82:959–964, 1988.

Pfeiffer RL, Nichol RJ: Dermoid and epidermoid tumors of the orbit. Arch Ophthalmol 40:639–664, 1948.

Robb RM: Astigmatic refractive errors associated with limbal dermoids. J Pediatr Ophthalmol Strabismus 33:241–243, 1996.

Sullivan GL: Caveat chirugicus. Trans Am Ophthalmol Soc 70:328–336, 1972.

Zaidman GW, Johnson B, Brown SI: Corneal transplantation in an infant with corneal dermoid. Am J Ophthalmol 93:78–83, 1982.

127 EWING’S SARCOMA 170

Terry D. Wood, MD

Portland, Oregon

Julie Falardeau, MD, FRCSC

Portland, Oregon

●Prognosis improves if the site is distal (e.g. hands, feet), the tumor is small, and most importantly, if the tumor has not metastasized at the time of diagnosis.

●There is good pathologic response to chemotherapy.

DIAGNOSIS

Laboratory findings

●Current histologic testing requires more fresh tissue than previously required.

●The biopsy site should be in the area to be included in the radiation field.

●Biopsy should be done only by those with prior experience with this type of tumor because the long-term prognosis depends on where and how the biopsy is performed and how adjacent tissues are managed.

Differential diagnosis

●Primary lymphoma of bone.

●Embryonal rhabdomyosarcoma.

●Metastatic neuroblastoma.

●Small cell osteogenic sarcoma.

Ewing’s sarcoma belongs to a family of malignancies known as small, blue, round cell tumors of childhood. Sarcomas are generally thought of as deriving from mesoderm, but the embryological origin of Ewing’s sarcoma is neuroectoderm. The underlying genetic defect is a chromosomal translocation. In greater than 95% of cases, the translocation is t(11;22)(q24;q12); the Ewing sarcoma gene (EWS) on chromosome 22, whose function is unknown, fuses with the FLI-1 proto-oncogene on chromosome 11. The result is a chimeric protein with increased transcriptional activity and the ability to induce neoplastic transformation in fibroblasts.

Ewing’s sarcoma can occur at any age, although it usually appears during the first or second decade of life with a peak incidence during the second decade. The male to female ration is 1.4 : 1. This tumor most often originates in bone, but it may also arise from soft tissue. The most common areas of origin are the femur, pelvis, tibia, humerus, fibula, scapula and ribs. The most common site of metastasis is to the lung. Only 2% to 3% of Ewing’s sarcomas arise from the head and neck. Papilledema has been reported as a rare sign of intracranial involvement. Orbital involvement includes proptosis and swelling of orbital tissue, with or without decreased vision and is usually secondary to metastatic disease.

The cause is unknown; there is an increased incidence in patients with retinoblastoma and in areas of prior irradiation. The annual incidence is 0.6 to 0.8 in 1 million population.

COURSE/PROGNOSIS

●The most common presenting complaint is intermittent pain.

●A fever is present in 20% of cases.

●The prognosis has markedly improved during the past 25 years, with survival rates increasing from 10% to 70%.

The treatment of Ewing’s sarcoma requires a multidisciplinary approach and the patient is best referred to a tertiary center with experience with this tumor. The management team usually includes a pediatric oncologist, a radiation therapist, an orthopedic oncologist and an orbital surgeon.

Systemic

●Multiagent chemotherapy agents include vincristine, cyclophosphamide, actinomycin D and doxorubicin. For resistant cases, ifosfamide has been advocated.

●Newer agents include granulocyte colony-stimulating factor and recombinant human cytokine glycoprotein.

Local

●Wide en bloc resection is performed.

●Most patients have postoperative radiation therapy with chemotherapy.

COMPLICATIONS

Radiation

●The usual local complications can occur.

●Pathologic fractures can occur.

●There is a long-term risk of secondary local malignancy (40× increase at 60-Gy dose).

●The risks of radiation have increased as the survival rates of patients have increased.

Chemotherapy

●As with all antimetabolite agents, multiple complications can occur.

●Alkylating chemotherapeutic agents have been associated with late secondary malignancies.

REFERENCES

Dalley RW: Fibrous histiocytoma and fibrous tissue tumors of the orbit. Radiol Clinics N Amer 37:1:185–194, 1999.

Jakobiec FA, Tannenbaum M: The ultrastructure of orbital fibrosarcoma. Amer J Ophthalmol 77:6:899–917, 1974.

Weiner JM, Hidayat AA: Juvenile fibrosarcoma of the orbit and eyelid. Arch Ophthalmol 101:253–259, 1983.

129 HODGKIN’S DISEASE 201.9

Warren L. Felton, III, MD

Richmond, Virginia

topenia and low serum albumin. If untreated, patients with Hodgkin’s disease may die within two to three years of presentation. With treatment, Hodgkin’s disease may be cured in more than 80% of patients.

DIAGNOSIS

Clinical signs and symptoms

Patients with Hodgkin’s disease most often present with painless regional lymphadenopathy. The affected lymph nodes are located above the diaphragm in 80% of patients, including the neck, supraclavicular region, axilla, and anterior mediastinum. About one-third of patients present with systemic symptoms of fever, night sweats, or weight loss. Pruritis is also common. Pain at involved sites, including bone pain, induced by alcohol consumption is an uncommon but classic symptom. Extranodal involvement is uncommon.

ETIOLOGY/INCIDENCE

Hodgkin’s disease is a malignant lymphoma. Two entities are recognized. Classical Hodgkin’s lymphoma comprises the majority (95%), while nodular lymphocyte-predominant Hodgkin’s lymphoma (LPHL) is rare. Classical Hodgkin’s lymphoma is distinguished from non-Hodgkin’s lymphoma by the presence of Reed–Sternberg (RS) cells, predominantly B cell in origin (less than 2% derive from T cells). In LPHL, variants of RS cells termed lymphocytic and histiocytic (L&H) cells, are identified. In both forms, however, neoplastic cells make up only a small minority of the total cell population, which is primarily composed of reactive inflammatory cells.

The cause of Hodgkin’s disease is not known. Infectious and genetic factors are thought to play roles. The involvement of the Epstein–Barr virus (EBV) is well established, but a causative role is not proved. Familial clustering and concordance in firstdegree relatives, especially monozygotic twins, support a genetic predisposition to the disease in some patients.

Hodgkin’s disease is uncommon. The incidence is 2.4 per 100,000 per year and appears to be stable. In North America and Europe combined, 20,000 patients are diagnosed annually, of which 7800 are found in the United States. In Western developed countries, there is a bimodal incidence from ages 15 to 30 years and after age 50 years. In some developing countries, the disease is more common in childhood.

The male-to-female ratio is approximately 3 : 2. Immunosuppressed patients, including those with acquired immunodeficiency syndromes, are at a higher risk.

COURSE/PROGNOSIS

In most patients the disease begins in one lymphoid site and then extends to contiguous lymphoid tissue. Extranodal involvement may occur through direct invasion or hematogenous spread. Prognosis is determined by the stage of the disease, the presence of systemic symptoms, and whether there is bulky involvement of the mediastinum. Patients with early-stage Hodgkin’s disease are often asymptomatic and have a better prognosis, whereas those with systemic symptoms more typically have advanced-stage disease and a poorer prognosis, as do those with a bulky mediastinal mass. Other features indicating an adverse prognosis include male gender, age 45 years or older, elevated sedimentation rate, anemia, leukocytosis, lymphocy-

Ocular

Ocular manifestations of Hodgkin’s disease are rare and usually occur as a late complication or as a consequence of treatment; more rarely, ocular involvement is the initial presentation of the disease. Chorioretinitis, vitritis, and anterior uveitis are reported more often than other ocular findings.

●Anterior chamber: uveitis.

●Choroid: infiltration

●Conjunctiva: infiltration.

●Cornea: keratitis.

●Cortical visual loss: infiltration, tumor mass.

●Extraocular muscle: infiltration, Grave’s disease.

●Horner’s syndrome: cervical lymphadenopathy, infiltration.

●Iris: posterior synechiae.

●Lacrimal gland: infiltration.

●Lens: cataract.

●Lid: infiltration, ptosis.

●Ocular motor nerves: infiltration, tumor mass, increased intracranial pressure.

●Optic chiasm: infiltration.

●Optic nerve: infiltration, papilledema, paraneoplastic optic neuropathy, tumor mass.

●Orbit: infiltration, tumor mass, exophthalmos.

●Pupil: afferent papillary defect, parasympathetic dilatation, Horner’s syndrome.

●Retina: exudates, hemorrhages, ischemia, perivascular sheathing, vasculitis, Roth’s spots, central retinal artery occlusion, central retinal vein occlusion, serous macular detachment.

●Sclera: scleritis, episcleritis.

●Vitreous: infiltration.

●Other: visual field defects, visual hallucinations, gaze palsies, internuclear ophthalmoplegia, nystagmus, cavernous sinus syndrome, paraneoplastic cerebellar degeration, paraneoplastic myasthenia gravis syndrome, opsoclonusmyoclonus paraneoplastic syndrome, Sjögren’s syndrome, Vogt–Koyanagi–Harada syndrome, opportunistic infections.

Laboratory findings

The diagnosis of Hodgkin’s disease rests on the biopsy of lymph glands or other involved tissue. Immunophenotype studies aid in distinguishing Hodgkin’s lymphomas from other pathologies (e.g. CD 15 and CD 30 in classical Hodgkin’s disease). Based on the number of Reed–Sternberg cells and the inflammatory

Less important to treatment than establishing the histopathologic subtype is the careful staging of the disease. Staging is based on the number of sites involved, whether one or both sides of the diaphragm is affected, tumor bulk (X), extranodal involvement (E sites), and the presence (B) or absence (A) of systemic symptoms. Stages I and II and stages III and IV are termed early-stage and advanced-stage Hodgkin’s disease, respectively. Staging is accomplished by history; physical examination; serum hematologic and chemistry studies; radiographic imaging, including thoracic, abdominal and pelvic computed tomography scans; and, in selected patients, positron emission tomography, gallium scan, magnetic resonance imaging, laparotomy, bone marrow biopsy and other procedures.

●Hematologic findings include elevated sedimentation rate, anemia, lymphopenia, eosinophelia, leukocytosis, monocytosis and thrombocytopenia.

●Other labarotory abnormalities may include liver functions, lactic dehydrogenase, alkaline phosphatase, albumin and calcium.

●Biopsy of orbital structures, optic nerve, optic chiasm, cavernous sinus, meninges, brain parenchyma, or other related tissue may be necessary to establish the diagnosis when an ocular manifestation is the presenting sign and lymphadenopathy is not evident on physical examination.

Differential diagnosis

The differential diagnosis of Hodgkin’s disease is that of lymphadenopathy, typically regional and less commonly generalized. When the presentation is extranodal, including ocular manifestations, the differential diagnosis is in part dependent on the site of involvement. In addition to non-Hodgkin’s lymphoma, conditions that should be considered include the following:

●Mediastinal neoplasms, germ cell tumors, thymoma, infections, primarily tuberculosis and inflammations, especially sarcoidosis.

●Primary cancers of the head, neck, lung, breast, thyroid and rectum.

●Generalized lymphadenopathies, including viral, fungal, bacterial and mycobacterial infections; human immunodeficiency virus-associated lymphadenopathy; and autoimmune disorders.

●For certain ocular or ophthalmologically related manifestations, the following conditions should be considered:

●Uveal tract infectious, inflammatory and neoplastic conditions;

Chemotherapy is increasingly used for all stages of the disease. Patients with early stage disease may be treated with combined chemotherapy followed by low-dose radiation to involved sites. Combined chemotherapy is the standard for patients with advanced-stage Hodgkin’s disease. The ABVD regimen is most commonly used in the United States. Stanford V and BEACOPP are other chemotherapeutic combinations.

●ABVD: doxorubicin (Adriamycin), bleomycin, vinblastine, dacarbazine.

●Stanford V: doxobubicin, vinblastine, mechlorethamine, vincristine, bleomycin, etoposide, prednisone.

●BEACOPP: bleomycin, etoposide, doxorubicin (Adriamycin), cyclophosphamide, vincristine (Oncovin), procarbazine, prednisone.

Both intravenous and oral corticosteroids are used in a variety of settings, including those with ocular impact, to reduce inflammation.

Local

For patients with early-stage disease and favorable prognosis, local radiation to involved sites and to adjacent sites, without chemotherapy, is a traditional option. However, low dose radiation restricted to involved regions, combined with chemotherapy, is more commonly employed. The role of radiation therapy in advanced-stage Hodgkin’s lymphoma is controversial and is most often directed at bulky sites of the disease. Radiation alone is not an option for patients with advanced stage disease. Radiotherapy, without or with chemotherapy, is used for the LPHL variant.

Local radiation therapy is directed to affected extranodal sites with ocular impact, including the orbit, optic nerve, optic chiasm, cavernous sinus and brain.

Surgical

The application of surgery is limited in Hodgkin’s disease. Surgical biopsy of lymph nodes or other involved sites is essential to establish the diagnosis and is sometimes indicated to determine the response to treatment. Surgical decompression of the orbit, optic nerve, optic chiasm, or cavernous sinus may be required when visual function is compromised by the mass effect of an advancing tumor.

Other

Salvage treatment for patients with relapsed Hodgkin’s disease includes chemotherapy for those initially receiving radiation