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Figure 50-5.  Melanocytoma of the optic nerve.

15.What is the main route of distant spread of uveal melanoma?

Melanoma spreads to extraocular locations primarily by hematogenous metastasis to liver. Metastatic uveal melanoma to skin, lung, and other organs is less common but often occurs. Because there are no lymphatic channels in the eye, lymphogenous metastasis does not occur.

16.What is a melanocytoma?

A melanocytoma is a variant of benign nevus that has distinct clinical and histopathologic features. Clinically, it is usually detected on and next to the optic disc as a deeply pigmented lesion that may have a feathery border because of involvement of the nerve fiber layer of the retina (Fig. 50-5). It also can occur as a deeply pigmented lesion in the ciliary body or choroid. Histopathologically, it is composed of round-to-oval cells that have densely packed cytoplasmic melanosomes, small uniform nuclei, and few prominent nucleoli. Like other uveal nevi, it rarely gives rise to uveal melanoma.

17.What is the most acceptable method of treating a choroidal melanoma that occupies more than half of the globe and has produced severe visual loss?

Enucleation, because there is little hope for useful vision and the patient’s quality of life would be better, and extensive ocular follow-up would not be so necessary.

18.What is the most often used alternative to enucleation for a medium-sized melanoma located posterior to the equator?

Brachytherapy with a radioactive plaque is most common, and irradiation and proton beam irradiation is the second most common.

19.What is the most common treatment for a melanoma that occupies two clock hours of the ciliary body?

The most common treatment is resection of the tumor by iridocyclectomy or application of radioactive plaque, depending on several clinical circumstances.

20.What is the most acceptable method of management for an asymptomatic pigmented lesion that measures 3 mm in diameter and 1 mm in thickness and has fine drusen on its surface?

It is managed with baseline fundus photographs and examination every 6 to 12 months. Most such lesions are benign nevi that remain stationary.

Bibliography

Shields JA, Shields CL: Diagnostic approaches to posterior uveal melanoma. In Shields JA, Shields CL, editors: Intraocular tumors: a text and atlas, Philadelphia, 1992a, W.B. Saunders, pp 155–169.

Shields JA, Shields CL: Differential diagnosis of posterior uveal melanoma. In Shields JA, Shields CL, editors: Intraocular tumors: a text and atlas, Philadelphia, 1992b, W.B. Saunders, pp 137–153.

Shields JA, Shields CL: Introduction to melanocytic tumors of the uvea. In Shields JA, Shields CL, editors: Intraocular tumors: a text and atlas, Philadelphia, 1992c, W.B. Saunders, pp 45–49.

Shields JA, Shields CL: Management of posterior uveal melanoma. In Shields JA, Shields CL, editors: Intraocular tumors: a text and atlas, Philadelphia, 1992d, W.B. Saunders, pp 171–205.

Shields JA, Shields CL: Melanocytoma. In Shields JA, Shields CL, editors: Intraocular tumors: a text and atlas, Philadelphia, 1992e, W.B. Saunders, pp 101–115.

Shields JA, Shields CL: Posterior uveal melanoma. Clinical and pathologic features. In Shields JA, Shields CL, editors: Intraocular tumors: a text and atlas, Philadelphia, 1992f, W.B. Saunders, pp 117–136.

1.What is the most common malignant intraocular neoplasm?

Uveal metastasis, usually from a distant primary carcinoma, is thought to be the most common malignant intraocular neoplasm. An estimated 66,000 patients develop uveal metastases each year. However, most are terminally ill patients, few of whom are evaluated ophthalmologically or pathologically. In contrast, only 1800 cases of uveal melanoma and 300 cases of retinoblastoma occur yearly in the United States.

Many textbooks state that uveal malignant melanoma is the most common primary intraocular tumor, but this statement actually applies only to the United States and Europe, because uveal melanoma has a propensity for fair-skinned, blue-eyed persons. Throughout Africa, Asia, and South America, where melanoma is relatively rare, retinoblastoma is the most common primary intraocular tumor. Kivelä has estimated that approximately 1000 more retinoblastomas than uveal melanomas occur yearly in the world.1,2

2.What is the characteristic shape of choroidal malignant melanoma?

Approximately 60% of choroidal malignant melanomas have a mushroom or collar-button configuration (Fig. 51-1). Melanomas initially have a dome or almond shape when they arise in the choroid. The mushroom or collar-button configuration develops after the tumor ruptures or erodes through the Bruch’s membrane and invades the subretinal space, where it forms a round or ovoid nodule.

3.Is a mushroom configuration pathognomonic for choroidal melanoma?

A mushroom or collar-button configuration almost always signifies that a choroidal tumor is a malignant melanoma. Few things in medicine are pathognomonic, however. Exceedingly rare mushroomshaped choroidal metastases, hemangiomas, and schwannomas have been reported.3-5

4.What important prognostic features of uveal melanoma can be assessed during routine histopathologic examination?

Tumor size and cell type are two of the most important prognostic factors that can be assessed during routine histopathologic evaluation of uveal melanoma. Larger tumors and tumors that contain epithelioid cells have a poorer prognosis. Tumor size generally is expressed in millimeters as the largest basal tumor diameter. Other prognostic features include mitotic activity (expressed as the number of mitoses in 40 high-power fields), the presence of extrascleral extension, extracellular matrix patterns called vascular loops and networks, lymphocytic infiltration, and involvement of the ciliary body.6-8

Figure 51-1.  Mushroom-shaped choroidal melanoma.

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5.What factors does the American Joint Commission on Cancer (AJCC) Cancer Staging Manual use to stage uveal melanoma?

Tumor size, ciliary body involvement, and extraocular extension are important factors used to prognostically stratify uveal melanomas in the AJCC’s TNM classification (T is the size of the tumor, N denotes lymph node involvement, M is for metastasis). The staging manual includes a chart that uses both the tumor’s largest basal diameter and its largest thickness to assign tumors to size categories. Tumors greater that 18 mm in diameter are in size category 4. Tumors that involve the ciliary body and/or show extraocular extension have a poorer prognosis.9

6.What is the Callender classification?

In 1931, Major George Russell Callender reported that there was an association between survival and histologic characteristics of uveal melanomas called cell type. Callender showed that uveal melanomas may contain two types of spindle cells (spindle A and spindle B cells) and less-differentiated epithelioid cells. Dr. Ian McLean modified Callender’s classification in 1978. Spindle A and spindle B melanomas were lumped together as spindle melanomas in the modified classification, and necrotic and fascicular variants were deleted.10,11

7.What is the most common cell type?

Most medium or large melanomas that are enucleated and examined histopathologically are mixed-cell tumors that contain a mixture of spindle and epithelioid cells. Eighty-nine percent of the melanomas that were enucleated in the Collaborative Ocular Melanoma Study (COMS) were mixed-cell tumors.

8.How are melanoma cell types distinguished histopathologically?

Melanoma cells are readily differentiated by the characteristics of their nuclei. Spindle A cells have long, tapering cigar-like nuclei, an absent or indistinct nucleolus, and a characteristic longitudinal stripe caused by a fold in the nuclear membrane. Spindle B nuclei are oval and plumper and have less finely dispersed chromatin and a distinct nucleolus (Fig. 51-2). Epithelioid cell nuclei are typically round and vesicular and have a prominent reddish-purple nucleolus (Fig. 51-3). The chromatin is coarse and often clumps along the inside of the nuclear membrane (peripheral margination of chromatin). Spindle melanoma cells grow as a syncytium, making it difficult to discern the cytoplasmic margins of the bipolar fusiform cells. Epithelioid cells are poorly cohesive and their cytoplasmic margins are readily discernible.12

Figure 51-2.  Spindle B melanoma cells.

Figure 51-3.  Epithelioid melanoma cells.

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9.Which cell type has the worst prognosis?

The presence or absence of epithelioid cells in a uveal melanoma has an important effect on prognosis. If no epithelioid cells are present, the expected survival at 15 years is 72%. If epithelioid cells are present (mixed, epithelioid, or necrotic cell type), the survival at 15 years drops to 37%. A tumor composed entirely of spindle A cells is now considered to be a benign nevus incapable of metastasis. Tumors composed entirely of epithelioid cells have the worst prognosis. Overall, approximately 50% of patients with uveal melanoma will die from their tumors.8

10.What special new tests are powerful prognostic indicators for patients with uveal melanoma?

Special new tests that are powerful prognostic predictors for patients with uveal melanoma include:

1.Assessment for nonrandom chromosomal anomalies in the tumor cells;

2.Gene expression profiling.

Nonrandom chromosomal abnormalities including loss of chromosome 3 and gains in chromosome 8 are associated with metastatic death. Monosomy 3 is a significant predictor of poor prognosis in uveal melanoma. In one study, 57% of patients with monosomy 3 had developed metastases at 3 years, compared to none of the patients with disomy 3. Chromosomal 3 abnormalities can be identified using a variety of techniques including fluorescence in situ hybridization and DNA amplification and microsatellite assay.

Gene expression profiling (GEP) of uveal melanomas by microarray analysis has disclosed two classes of tumors that differ markedly in their potential for metastasis. Class I melanomas are lowgrade tumors with less than 5% risk for metastasis. In contrast, patients with class II melanomas have a greater than 90% risk for metastasis. The GEP of class II melanomas resembles primitive neural/ ectodermal stem cells. They typically have other high-risk features including epithelioid cells, vascular mimicry patterns, and monosomy 3. GEP is available as a proprietary commercial test.13-15

KEY POINTS: PROGNOSTIC FACTORS IN UVEAL MELANOMA

Size

Ciliary body involvement Cell type

Extraocular extension Mitotic activity Lymphocytic infiltration Vascular mimicry patterns

Nonrandom chromosomal abnormalities (monosomy 3—poor prognosis) Gene expression profile (class 2—poor prognosis)

11.What is the most common site of metastatic uveal melanoma?

The liver is the most common site. Liver metastases occur in 93% of patients who develop metastatic uveal melanoma. Other sites include the lungs (24%) and bone (16%).16

12.What was the Collaborative Ocular Melanoma Study?

The COMS was a large prospective, randomized, multicentered study funded by the National Eye Institute that investigated the treatment of choroidal malignant melanoma. The arm of the study that focused on medium-sized tumors compared survival after enucleation and radioactive iodine 125 (125I) plaque brachytherapy. The large tumor study compared survival after standard enucleation and enucleation preceded by external beam radiotherapy.17

13.What were the results of the COMS?

The medium-sized tumor arm of the COMS showed that survival was similar after both enucleation and plaque brachytherapy. The large tumor arm showed that “sterilization” of large melanomas with preenucleation external-beam radiotherapy did not improve survival.18,19

14.How are most uveal melanomas treated?

Today, most posterior uveal melanomas are treated with radioactive plaques. Plaque-treatment failures and eyes with larger tumors and/or tumor-related complications, such as secondary glaucoma or

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20.What primary tumors are responsible for most uveal metastases?

Most uveal metastases come from breast carcinoma in women and lung carcinoma in men. Breast carcinoma is responsible for more than half of all ocular metastases. Nearly one-fifth are caused by lung cancer. Most women with uveal metastases from breast tumors have a history of breast carcinoma. In contrast, uveal metastasis may herald the presence of an occult lung cancer.25

21.How is immunohistochemistry (IHC) used to assess uveal metastases?

Primary uveal melanomas usually can be distinguished from uveal metastases using routine light microscopy. When a metastasis is found in a patient with no prior history of cancer, IHC often can suggest the identity of the primary tumor. For example, breast and lung cancers frequently stain positively (i.e., are immunoreactive) for cytokeratin 7 (CK7) and are negative for CK20. In contrast, most gastrointestinal cancers are CK20 positive. Immunoreactivity for specific markers that are expressed only by certain cancers is particularly helpful. Examples include the BRST2 marker in breast carcinoma, the TTF1 marker in lung cancer, and PSA and PSAP in prostate cancers.

IHC also is used as a prognostic marker and a guide to therapy. For example, breast carcinomas that express estrogen receptors can be treated with tamoxifen and aromatase inhibitors, whereas tumors that express HER/2neu can be treated with trastuzumab (Herceptin).26

22.What types of hemangiomas occur in the choroid?

Choroidal hemangiomas are classified as capillary, cavernous, or mixed. They are composed of thinwalled vessels and have little stroma (Fig. 51-4). Sporadic hemangiomas tend to be discrete, localized, elevated reddish-orange tumors. The choroidal hemangiomas that occur in patients with SturgeWeber syndrome are typically diffuse with indistinct tapering margins. These obscure the underlying choroidal architecture and impart a “tomato ketchup” appearance to the fundus.27

23.If choroidal hemangiomas are benign, why are they treated?

Choroidal hemangiomas are treated to save vision or the eye itself. Although they are benign from a systemic standpoint, choroidal hemangiomas cause retinal detachment and secondary glaucoma via iris neovascularization and/or a papillary block mechanism. The latter can lead to loss of the globe. Hemangiomas usually are treated with photodynamic therapy or laser photocoagulation.28,29

24.How does retinoblastoma typically present in the United States and Europe?

In the United States and Europe, retinoblastoma typically presents with leukocoria (a white pupillary reflex). Smaller tumors that involve the macula initially may present with strabismus. All children with strabismus should have a careful fundus examination to exclude retinoblastoma or other significant macular pathology. In developing countries, children often present in an advanced stage of the disease with a large orbital tumor secondary to extraocular extension.30

25.How old are patients when diagnosed with retinoblastoma?

The mean age at diagnosis is 18 months. Patients who have the familial form of the disease (i.e., who have germ-line mutations) are diagnosed earlier (mean age 12 months), probably because only a solitary “hit” or gene inactivation is required. Sporadic somatic cases occur in slightly older patients; they are diagnosed at a mean age of 24 months.30

Figure 51-4.  Choroidal hemangioma.

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26.What does retinoblastoma look like grossly?

Grossly, retinoblastoma has a distinctly encephaloid or brainlike appearance. This is not surprising because the tumor arises from the retina, which is a peripheral colony of brain cells. Foci of dystrophic calcification occur in many retinoblastomas. These foci of calcification are evident grossly as lighter flecks.

27.What is an exophytic retinoblastoma?

Retinoblastoma shows several growth patterns. Exophytic retinoblastoma arises from the outer retina and grows in the subretinal space, causing retinal detachment (Fig. 51-5). Endophytic retinoblastoma arises from the inner layers of the retina, which remains attached (Fig. 51-6). Endophytic tumors invade the vitreous and may seed the anterior chamber, forming a pseudohypopyon of tumor cells. Most large retinoblastomas exhibit a combined endophytic/exophytic growth pattern. The diffuse infiltrative growth pattern is relatively rare and occurs in older children. The retina in such cases is diffusely thickened without a distinct tumefaction.30

28.Why does retinoblastoma appear blue, pink, and purple under low-magnification light microscopy?

The blue, pink, and purple areas evident on low-magnification light microscopy of retinoblastoma represent zones of viable, necrotic, and calcified tumor, respectively. Areas of viable tumor are basophilic. Retinoblastoma is composed of poorly differentiated neuroblastic cells that have intensely basophilic nuclei and scanty cytoplasm. Retinoblastoma cells tend to outgrow their blood supply rapidly and undergo spontaneous necrosis. The necrotic parts of the tumor are eosinophilic because the dead cells lose their basophilic nuclear DNA. Dystrophic calcification often occurs in necrotic parts of the tumor. The calcium has a purple hue in sections stained with hematoxylin and eosin.31

29.What do rosettes signify in retinoblastoma?

Rosettes are histologic markers for tumor differentiation in retinoblastoma. Homer Wright rosettes reflect low-grade neuroblastic differentiation. They are nonspecific and occur in other tumors such as

Figure 51-5.  Exophytic retinoblastoma with total retinal detachment.

Figure 51-6.  Endophytic retinoblastoma.

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neuroblastoma. Flexner-Wintersteiner rosettes represent early retinal differentiation. They are highly characteristic for retinoblastoma, but they are not pathognomonic, as they are also found in some medulloepitheliomas.30-33

30.How are Homer Wright and Flexner-Wintersteiner rosettes distinguished histopathologically?

The nuclei of Homer Wright rosettes encircle a central tangle of neural filaments (Fig. 51-7). No lumen is present. Flexner-Wintersteiner rosettes have a central lumen that corresponds to the subretinal space (Fig. 51-8). The cells that enclose the lumen are joined by a girdle of apical intercellular connections analogous to the retinal external limiting membrane. Cilia, the precursors of photoreceptors, project into the lumen of the rosette.32

31.What are fleurettes?

Fleurettes are aggregates of neoplastic photoreceptors (Fig. 51-9). Photoreceptor differentiation is the highest degree of differentiation found in retinoblastoma. Fleurettes are composed of groups of bulbous eosinophilic cellular processes that correspond to photoreceptor inner segments. They are often aligned along a segment of neoplastic external limiting membrane in a bouquet-like arrangement.30,34

32.What is a retinoma or retinocytoma?

A retinoma or retinocytoma is a highly differentiated retinal tumor that typically contains photoreceptor differentiation. Each of the two names for this tumor has its proponents. Retinoma/retinocytoma is considered to be a benign manifestation of the retinoblastoma gene. Compared to retinoblastoma, the tumor cell nuclei are quite bland and mitoses and apoptotic cells are absent. However, both copies of the Rb1 gene are lost or mutated in these lesions as well as in retinoblastoma. This observation indicates that additional mutations other than the mutation in Rb1 are necessary for the development of retinoblastoma. Retinoma/retinocytoma is thought to be a precursor lesion for retinoblastoma, and rare cases of malignant transformation have been documented. Clinically, retinoma/retinocytoma is characterized by a translucent fish-flesh appearance; abundant calcification, which occurs within viable

Figure 51-7.  Homer Wright rosettes, retinoblastoma.

Figure 51-8.  Flexner-Wintersteiner rosettes, retinoblastoma.

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parts of the tumor; and an annulus of retinal pigment epithelium (RPE) depigmentation. The tumor may resemble retinoblastomas that have regressed after radioor chemotherapy. At one time, retinomas/ retinocytomas were thought to be retinoblastomas that had undergone spontaneous regression.35,36

33.What are the most important prognostic features of retinoblastoma?

Important prognostic features of retinoblastoma that can be assessed histopathologically include the presence and degree of optic nerve invasion, extrascleral extension, uveal invasion, and anterior segment involvement. Unlike uveal melanoma, the size of the tumor does not appear to be important. Mortality rises as the depth of tumor invasion into the optic nerve increases. Retrolaminar optic nerve invasion is equivalent to extraocular extension. Although anterior segment involvement is thought to confer poorer prognosis, its significance is uncertain because it tends to be found in eyes with other high-risk features.37,38

34.What histopathologic risk factors found in enucleated eyes with retinoblastoma are indications for adjuvant chemotherapy?

Certain histopathologic features are indications for adjuvant chemotherapy in most centers. These include:

1.tumor invasion of the optic nerve behind the lamina cribrosa (retrolaminar optic nerve invasion) or to the surgical margin;

2.massive invasion of the choroid;

3.any amount of concurrent prelaminar optic nerve and nonmassive choroidal invasion.

Massive choroidal invasion has been defined as greater than 3 mm in diameter or involving the full thickness of the choroid.39,40

35.How does retinoblastoma kill?

Many children who die from retinoblastoma have some degree of intracranial involvement. This is caused by direct extension of tumor cells along the optic nerve, subarachnoid space, or orbital

foramina. Distant hematogenous metastases to bone and viscera can develop after the tumor invades the richly vascularized uvea. Anterior extrascleral extension provides access to conjunctival lymphatics and may be associated with regional lymph node metastases.41

36.The retinoblastoma gene is located on what chromosome?

Chromosome 13, found in the segment of the long, or “q,” arm that is designated the 1 to 4 band (13q1–4).42

37.How is the retinoblastoma gene classified?

The retinoblastoma (Rb1) gene is the paradigmatic example of a recessive oncogene. The Rb1 gene is called a recessive oncogene because both copies of the gene must be lost or inactivated before a tumor can develop. Normal individuals have two functional copies of the Rb1 gene, although only one is needed for normal functioning. The gene’s protein product, called Rb1 protein, is found in the nucleus, where it interacts with other transcription factors to control the cell cycle. Absence of Rb1 protein allows continual cell division and lack of terminal differentiation.42

38.If the Rb1 gene is recessive, why do cases of familial retinoblastoma appear to be inherited in an autosomal-dominant fashion?

Patients with hereditary retinoblastoma are heterozygous for the Rb1 gene. The genotype of carriers includes a single functional wild-type gene. The second copy of the Rb1 gene has been lost or

Figure 51-9.  Fleurettes in retinoblastoma.

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inactivated or produces a defective gene product. A retinoblastoma will develop when a retinal cell loses its single functional copy of the Rb1 gene. A mating between a normal individual (Rb1+/+) and a heterozygous carrier (Rb1+/−) gives rise to 50% normal offspring and 50% heterozygous carriers—a 50/50 ratio that perfectly mimics autosomal dominant transmission.

39.What does bilateral retinoblastoma signify clinically?

The presence of bilateral retinoblastoma indicates that the affected patient has a germ-line mutation in the Rb1 gene and is capable of transmitting the tumor to offspring.

40.Can a child with a unilateral retinoblastoma have a germ-line mutation?

Yes. Unfortunately, the presence of a unilateral tumor does not exclude a germ-line mutation and transmissible disease. Only approximately 60% of patients with familial retinoblastoma actually develop bilateral tumors.

41.Are most retinoblastomas familial?

No, most retinoblastomas occur sporadically in infants who have no family history of the disease. Nearly ¾ of sporadic retinoblastomas are caused by somatic mutations in retinal cells, which cannot be passed on to offspring. Such somatic sporadic tumors are invariably unilateral and unifocal. The remaining fourth of sporadic retinoblastomas are caused by germ-line mutations in the Rb1 gene (i.e., they are new familial cases). These are often bilateral and can be passed on to offspring in what appears to be autosomal dominant transmission. Only 5 to 10% of retinoblastomas occur in patients with a family history of the tumor.

42.Why are sporadic retinoblastomas caused by somatic mutations in the Rb1 gene always unilateral and unifocal?

A sporadic somatic retinoblastoma is caused by the inactivation of both Rb1 genes in a single retinal cell. The spontaneous mutation rate of the Rb1 gene is very low. Hence, the chance of this occurring in more than a single retinal cell is infinitesimally small. Therefore, sporadic somatic retinoblastomas always are unilateral and unifocal. In contrast, it is highly probable that one or more gene inactivations will occur in both retinas of a heterozygous carrier, because the mutation rate is substantially smaller than the number of mitoses involved in the development of the retina, and genes usually are lost during cellular division. That is why familial cases typically are bilateral and may be multifocal.

43.Are patients with hereditary retinoblastomas at risk for other nonocular tumors?

Yes. Between 20% and 50% of patients who have germ-line mutations in the retinoblastoma gene will develop a second malignant neoplasm within 20 years. One of the most interesting and characteristic secondary tumors is pineoblastoma, a retinoblastoma-like tumor of the pineal gland. The association of pineoblastoma and hereditary retinoblastoma has been termed trilateral retinoblastoma. There

also is a 500-fold increase in the incidence of osteogenic sarcoma in retinoblastoma gene carriers. Patients also are at risk to develop radiation-induced orbital sarcomas (e.g., osteogenic sarcomas) after external-beam radiotherapy for retinoblastoma, which is why oncologists currently try to avoid this therapy.

44.Can retinoblastoma develop without mutations in the Rb1 gene?

Unusual retinoblastoma-like tumors that have no mutations in the Rb1 gene have been reported. These are characterized by high levels of amplification of the MYCN oncogene. These aggressive tumors comprise less than 3% of retinoblastomas and typically occur as unilateral tumors in young infants less than 6 months of age. They resemble neuroblastomas histopathologically and lack rosettes, which typically are numerous in retinoblastomas removed from very young infants. The cells also have prominent nucleoli. About one-fifth of unilateral retinoblastomas that occur in infants less that 6 months of age are Rb1+/+ MYCNA tumors.43

KEY POINTS: RETINOBLASTOMA

1. Tumor suppressor gene is on chromosome 13 (13q1–4) 2. Most cases are sporadic (75% somatic, 25% germ line) 3. Bilaterality indicates transmissible germ-line mutation

4. Heritable cases pass disease to 50% of offspring (autosomal dominant pattern) 5. Heritable cases are at risk for second tumors

CHAPTER 51  OCULAR TUMORS  407

Figure 51-10.  Coats disease.

45.Name the three diseases that are most often confused with retinoblastoma clinically.44-47

•Persistent fetal vasculature (also called persistent hyperplastic primary vitreous)

•Coats disease

•Ocular toxocariasis

46.How does Coats disease differ clinically from retinoblastoma?

Coats disease is characterized by an exudative retinal detachment caused by leaky congenital vascular anomalies in the retina (Fig. 51-10). The subretinal fluid is rich in lipid-laden macrophages and cholesterol crystals, which appear as empty clefts in microscopic sections. Histopathologically, the retina contains abnormal telangiectatic vessels, and its outer layers are massively thickened by hard exudates. A bullous retinal detachment may abut the lens, displacing it anteriorly and causing pupillary block glaucoma. Coats disease usually occurs unilaterally in boys between ages 4 and 10. It usually is confused clinically with exophytic retinoblastoma. Affected patients typically show xanthocoria rather than leukocoria.48,49

47.What are the characteristic features of persistent fetal vasculature (persistent hyperplastic primary vitreous?

Persistent fetal vasculature, previously called persistent hyperplastic primary vitreous, is a congenital disorder that is present at birth. It is almost always unilateral and classically is found in a microphthalmic eye. Leukocoria is caused by a plaque of fibrovascular tissue that adheres to the posterior surface of the lens. The ciliary processes typically are disclosed by dilating the pupil because their tips are attached to the edge of the retrolental plaque and are drawn centrally. Congenital retroblastomas have been reported but are exceedingly rare. On average, retinoblastomas are diagnosed at age 18 months.45,46,50

48.What is the second most common primary intraocular tumor of childhood?

Embryonal medulloepithelioma is the second most common primary intraocular tumor of childhood. Medulloepitheliomas probably are derived from anlagen of the embryonic medullary epithelium, which lines the forebrain and optic vesicle. Most of these rare tumors become symptomatic around age 4 years and are diagnosed at 5 years of age.33,51,52

49.Where are most medulloepitheliomas located?

Most medulloepitheliomas are ciliary body tumors that arise from the neuroepithelial layers on its inner surface. Rare medulloepitheliomas of the optic nerve have been reported, however.53,54

50.What is a teratoid medulloepithelioma?

In addition to bands, cords, and rosettes of neoplastic neuroepithelium and pools of hyaluronic acid, teratoid medulloepitheliomas contain foci of heteroplastic tissue including hyaline cartilage, rhabdomyoblasts, striated muscle, and/or brain. (Fig. 51-11) More than a third of medulloepitheliomas are teratoid. Nonteratoid medulloepitheliomas lack heteroplastic elements. Both benign and malignant variants of teratoid and nonteratoid tumors occur.

51.Is medulloepithelioma associated with other tumors?

Rarely, embryonal medulloepithelioma occurs in patients who have the pleuropulmonary blastoma syndrome. Pleuropulmonary blastomas are rare embryonal tumors of the lung that occur in infants.