Ординатура / Офтальмология / Английские материалы / Clinical Ophthalmology A Systematic Approach 7th Edition_Kanski, Bowling_2011

kanski 7th

Malignant and premalignant epibulbar tumours

Primary acquired melanosis

Primary acquired melanosis (PAM) is a unilateral condition that typically affects white individuals with a fair complexion.

1Histology shows one of the following:

aPAM without melanocytic cellular atypia is a benign intraepithelial proliferation of epithelial melanocytes with no risk of malignant transformation (Fig. 12.8A).

bPAM with melanocytic cellular atypia shows an increase in the number of intraepithelial melanocytes that exhibit pleomorphism. PAM with atypia, if severe, can be regarded as melanoma in situ that has a 50% chance of manifesting infiltration malignancy within 5 years.

2 Presentation is usually after the age of 45 years.

3Signs cannot distinguish between the two histological types.

•Irregular, unifocal or multifocal areas of flat, golden brown-dark chocolate epithelial pigmentation which typically involve the limbus and interpalpebral region (Fig. 12.8B).

•Because any part of the conjunctiva may be affected, it is important to evert the eyelids (Fig. 12.8C).

•PAM may expand, shrink or remain stable for long periods of time. It may also lighten or darken focally.

•Malignant transformation to melanoma should be suspected by the sudden appearance of one or more nodules in otherwise flat lesions (see Fig. 12.9D).

4Investigations involve biopsy with immunohistochemistry because the clinical features of PAM with and without atypia are the same.

5Treatment of small lesions involves excision. Large widespread lesions should undergo incision biopsy from various sites. Lesions showing PAM with atypia are treated with cryotherapy or topical mitomycin C.

6Differential diagnosis includes conjunctival naevus, epithelial (racial) melanosis, congenital ocular melanocytosis and Addison disease.

619 / 1137

kanski 7th

Fig. 12.8 Primary acquired melanosis (PAM). (A) Histology shows an intraepithelial proliferation of conjunctival epithelial melanocytes; (B) large area of PAM; (C) small area of PAMassociated with lentigo maligna of the lid margin

(Courtesy of J Harry and G Misson, from Clinical Ophthalmic Pathology, Butterworth-Heinemann 2001 – fig. A; B Jay – fig. B; D Selva – fig. C)

Fig. 12.9 Conjunctival melanoma. (A) Histology shows melanoma cells within the epitheliumand subepithelial stroma; (B) pigmented melanoma; (C) amelanotic melanoma; (D) multifocal melanoma arising fromPAM

(Courtesy of J Harry – fig. A)

Melanoma

Conjunctival melanoma accounts for about 2% of all ocular malignancies.

Diagnosis

1Histology shows sheets of melanoma cells within the subepithelial stroma (Fig. 12.9A).

2Classification

3Presentation is in the 6th decade except in patients with the rare dysplastic naevus syndrome who develop multiple melanomas earlier.

4Signs

•Melanoma arising de novo or from a pre-existing naevus appears as a black or grey vascularized nodule that may be fixed to the episclera.

•A common site is the limbus (Fig. 12.9B) although the tumour may arise anywhere in the conjunctiva.

•Amelanotic tumours are pink and have a characteristic smooth ‘fish-flesh’ appearance (Fig. 12.9C) that may give rise to diagnostic problems.

•Multifocal lesions arise from PAM with atypia are characterized by areas of thickening and nodularity (Fig. 12.9D).

5Differential diagnosis includes a large naevus, ciliary body melanoma with extraocular extension, melanocytoma (see Fig. 12.8D) and pigmented conjunctival carcinoma in a dark-skinned individual.

Treatment

620 / 1137

kanski 7th

•Circumscribed lesions are treated by excision with a wide margin and cryotherapy. If histology reveals tumour extension to the deep surface of the specimen, adjunctive radiotherapy can be administered.

•Diffuse melanoma associated with PAM is treated by excision of localized nodules and cryotherapy or mitomycin C to the diffuse component.

•Orbital recurrences (Fig. 12.8A) are treated by local resection and radiotherapy. Exenteration (Fig. 12.8B) does not improve the survival rate and is therefore reserved for patients with extensive and aggressive disease that cannot be controlled by other methods.

Prognosis

The overall mortality is 12% at 5 years and 25% at 10 years. The main sites for metastases are regional lymph nodes, lung, brain and liver. Poor prognostic indicators include:

•Multifocal tumours.

•Extralimbal tumours involving the caruncle, fornix or palpebral conjunctiva.

•Tumour thickness of 2 mm or more.

•Recurrence.

•Lymphatic or orbital spread.

Ocular surface squamous neoplasia

Definition

Ocular surface squamous neoplasia (OSSN) describes a spectrum of benign, pre-malignant and malignant unilateral slowly-progressive epithelial lesions of the conjunctiva and cornea. Risk factors include ultraviolet light exposure, human papilloma virus (type 16) infection, AIDS, xeroderma pigmentosum and stem cell therapy.

Diagnosis

1Histology shows the following spectrum:

aConjunctival epithelial dysplasia with dysplastic cells in the basal layers of the epithelium.

b Carcinoma in-situ with dysplastic cells involving the full thickness of the epithelium (Fig. 12.10A).

cSquamous cell carcinoma is rare and is characterized by invasion of the underlying stroma (Fig. 12.10B).

2Presentation is usually in late adult life with ocular irritation or a mass.

3Signs are variable and clinical differentiation between the three histological types is unreliable. Most tend to occur within the interpalpebral fissure mostly at the limbus, although they may involve any part of the conjunctiva or cornea. The following appearances may be seen.

aGelatinous mass with superficial vessels (Fig. 12.10C).

bWhite leukoplakic plaque that covers the lesion (Fig. 12.10D).

c Papillomatous lesion with corkscrew-like surface blood vessels (Fig. 12.10E).

dSquamous cell carcinoma is a fleshy, pink papillomatous mass with feeder vessels or occasionally it may exhibit diffuse growth and masquerade as ‘chronic conjunctivitis’. Corneal involvement may occur (Fig. 12.10F) but intraocular extension is uncommon and metastatic disease extremely rare.

4Special investigations include ultrasonic biomicroscopy (UBM) to estimate the depth of invasion, exfoliative cytology and impression cytology.

621 / 1137

kanski 7th

Fig. 12.10 Ocular surface squamous neoplasia. (A) Histology of carcinoma in situ shows dysplastic changes throughout the thickened epithelium; (B) histology of squamous cell carcinoma shows downward proliferation of irregular, dysplastic, squamous epitheliumwith infiltration of subepithelial tissue; (C) gelatinous lesion with surface vessels; (D) leukoplakic lesion; (E) papillomatous lesion; (F) very extensive carcinoma with corneal involvement

(Courtesy of J Harry – figs A and B; R Bates – fig. E; B Damato – fig. F)

Treatment

Excision with 2–3 mm margins and assessment of surgical clearance with frozen sections is the traditional method. Measures aimed at reducing recurrences include adjunctive cryotherapy, brachytherapy or topical chemotherapy with mitomycin C, 5-fluorouracil and interferonalpha 2b.

Lymphoproliferative lesions

Most conjunctival lymphoproliferative lesions are reactive lymphoid hyperplasia, a proliferation of B and T cells with germinal follicle formation (Fig. 12.11A). Conjunctival lymphoma may arise in three clinical settings. (a) de novo, (b) extension from orbital lymphoma and (c) occasionally associated with systemic involvement. Sometimes reactive lymphoid hyperplasia undergoes transformation to lymphoma. Most conjunctival lymphomas are B cell lymphomas and arise from MALT (mucosa-associated lymphoid tissue).

1 Presentation is usually in late adult life with irritation or painless swelling which may be bilateral.

2Signs

•Slowly-growing, mobile, salmon-pink or flesh-coloured infiltrate on the epibulbar surface (Fig. 12.11B) or in the fornices (Fig. 12.11C).

•Rarely, a diffuse lesion (Fig. 12.11D) may mimic chronic conjunctivitis.

3Treatment is most frequently with radiotherapy. Other options include chemotherapy, excision, cryotherapy and local injection of interferon alpha-2b.

622 / 1137

kanski 7th

Fig. 12.11 Conjunctival lymphoproliferative lesions. (A) Histology of reactive lymphoid hyperplasia shows a germinal lymphoid follicle consisting of immature lymphoid cells at the centre and mature cells at the periphery; (B) epibulbar lymphoma; (C) forniceal lymphoma; (D) diffuse lymphoma

(Courtesy of J Harry and G Misson, from Clinical Ophthalmic Pathology, Butterworth-Heinemann 2001 – fig. A.)

Kaposi sarcoma

Kaposi sarcoma is a slow-growing tumour which occurs in patients with AIDS.

1 Histology shows proliferation of spindle-shaped cells, vascular channels and inflammatory cells (Fig. 12.12A).

2Presentation is in adult life with irritation or painless discoloration.

3 Signs. A flat bright-red lesion (Fig. 12.12B) that may mimic a subconjunctival haemorrhage.

4Treatment is required for cosmetic reasons, bleeding or infection. Options include focal radiotherapy and excision with or without adjunctive cryotherapy.

623 / 1137

kanski 7th

Fig. 12.12 Conjunctival Kaposi sarcoma. (A) Histology shows proliferation of vascular endothelial cells, occasional mitotic figures, vascular channels and chronic inflammatory cells; (B) clinical appearance

(Courtesy of J Harry – fig. A)

Copyright © 2011 Elsevier Inc.All rights reserved. Read our Terms and Conditions of Use and our PrivacyPolicy.

If you find this useful please saythanks in your way: dramroo

624 / 1137

kanski 7th

Overview

In general, uveal melanomas are three times more common in patients with blue/grey than brown irides. They are extremely rare in blacks and there is no sexual predominance. Conditions associated with or predisposing to uveal melanomas are: (a) fair skin, (b) light iris colour,

(c) numerous cutaneous naevi, (d) congenital ocular melanocytosis, (e) oculodermal melanocytosis (naevus of Ota), (f) uveal melanocytoma,

(g) dysplastic cutaneous naevi, (h) familial cutaneous melanoma and (i) NF1. About 8% of uveal melanomas arise in the iris. The prognosis is very good and only about 5% of patients develop metastases within 10 years of treatment.

Diagnosis

1Histology in the majority shows spindle cells (see below) that are of low-grade malignancy (Fig. 12.14A). A minority contain an epithelioid cell component and can be more aggressive.

2Presentation is in the 5th–6th decades, a decade earlier than ciliary body and choroidal melanoma, usually with enlargement of a pre-existing iris lesion.

3Signs

•A pigmented (Fig. 12.14B) or non-pigmented nodule (Fig. 12.14C) at least 3 mm in diameter and 1 mm thick, usually located in the inferior half of the iris and often associated with surface blood vessels.

•Pupillary distortion, ectropion uveae and occasionally localized cataract may be seen, although these can also occur with naevi.

•The tumour usually grows very slowly along the iris surface and may invade the angle (Fig. 12.14D) and anterior ciliary body.

•Complications include hyphaema, cataract and glaucoma.

4Rare variants

aDiffusely growing intrastromal melanoma may give rise to ipsilateral hyperchromic heterochromia (Fig. 12.14E).

b'Tapioca melanoma’ is characterized by multiple surface nodules (Fig. 12.14F).

Fig. 12.14 Iris melanoma. (A) Histology shows infiltration of the entire thickness of the stroma; (B) highly pigmented tumour; (C) amelanotic tumour; (D) invasion of the angle; (E) extensive diffusely growing tumour; (F) ‘tapioca’ melanoma

(Courtesy of J Harry and G Misson, from Clinical Ophthalmic Pathology, Butterworth-Heinemann 2001 – fig. A; C Barry – fig. B; R Curtis fig. D; B Damato – fig. F)

Treatment

1Observation of suspicious lesions involves documentation by slit-lamp examination, gonioscopy and photography. Follow-up should

626 / 1137

kanski 7th

be life-long because growth may occur after several years of apparent inactivity.

2Iridectomy for small tumours (with iris reconstruction to reduce postoperative photophobia), and iridocyclectomy for tumours invading the angle.

3 Radiotherapy with a radioactive plaque (brachytherapy) or external irradiation with a proton beam.

4Enucleation may be required for diffusely growing tumours, if radiotherapy is not possible.

Metastatic tumours

Metastasis to the iris is rare and is characterized by a fast-growing white, pink or yellow mass (Fig. 12.15A) which may be associated with anterior uveitis and occasionally hyphaema. Small multiple deposits may also be seen (Fig. 12.15B).

Fig. 12.15 Iris metastasis. (A) Metastasis frombreast; (B) multiple small deposits

(Courtesy of P Saine – fig. A; B Damato – fig. B)

Miscellaneous tumours

1Juvenile xanthogranuloma is a rare idiopathic granulomatous disease of early childhood that involves the skin, muscle, stomach, salivary glands and other organs. Iris involvement is characterized by a localized or diffuse yellow lesion (Fig. 12.16A) that may be associated with spontaneous hyphaema, or less commonly anterior uveitis and glaucoma. Treatment is with topical steroids.

2Leiomyoma is an extremely rare benign tumour which arises from smooth muscle. The appearance is similar to that of an amelanotic melanoma, except that it does not have a predilection for the inferior half of the iris (Fig. 12.16B). Often the diagnosis can be established only histologically.

3Melanocytoma is a deeply-pigmented nodular mass with a mossy, granular surface and no intrinsic vessels, most frequently occupying the peripheral iris (Fig. 12.16C). It may undergo spontaneous necrosis resulting in seeding of the iris stroma and chamber angle. Dispersion of melanophages may result in elevation of intraocular pressure.

627 / 1137

kanski 7th

Fig. 12.16 (A) Juvenile iris xanthogranuloma; (B) leiomyoma; (C) melanocytoma

(Courtesy of BJ Zitelli and HW Davis, from Atlas of Pediatric Physical Diagnosis, Mosby 2002 – fig. A; B Damato – fig. B)

Copyright © 2011 Elsevier Inc.All rights reserved. Read our Terms and Conditions of Use and our PrivacyPolicy.

If you find this useful please saythanks in your way: dramroo

628 / 1137