Ординатура / Офтальмология / Английские материалы / Basic Sciences in Ophthalmology_Velayutham_2009
.pdf
Ocular Pathology |
213 |
Dermoid Cysts (Fig. 14.7)
It is due to trapping of surface ectoderm within the apposing sutures of the orbital bones. This heterotopic cyst is lined by epidermis and skin appendages. There is a cyst cavity filled with skin cells, keratin, sweat and sebaceous secretions and hairs. Ruptured cyst elicits an intense granulomatous foreign body tissue reaction.
Sudoriferous Cysts (Hidrocystoma)
They are benign cystic dilatations of sweat gland origin. They contain clear fluid and are transilluminant. With hemorrhage there is discoloration of the cyst. There are two types:
1)Apocrine hidrocystomaIt arises from sweat glands of Moll near the lid margin. It appears as single or multiple elevated translucent nodules. HPE shows a complex arborizing lumen lined by monolayer or bilayer of cuboidal epithelium, showing decapitation or apical snouting.
2)Eccrine hidrocystoma—it represents tissue retention cyst of sweat gland duct. It appears as solitary dilated cyst lumen with regular, smooth lining epithelium. Increased fluid pressure within may flatten the lining epithelium.
Squamous Papilloma (Skin Tag, Fibroepithelial Polyp)
Sessile or pedunculated proliferation of benign epidermis and is the most common benign eyelid lesion. It may be single or multiple and present on periorbital skin and lid margins. HPEshows elongated tongues of vascularised loose connective tissue. They are covered by acanthotic squamous epithelium.
Fig. 14.7: Dermoid cyst: Cyst lined by epidermis and shows sebaceous lobules in the wall
214 |
Basic Sciences in Ophthalmology |
Seborrheic Keratosis
It is seen in elderly patients as sharply demarcated superficial lesions that sit anterior to the plane of surrounding epidermislike a button on the skin surface. It shows a greasy or scaly, "stuck on" appearance. It is often sessile and pigmented.
HPE shows upward papillomatous proliferation of basaloid cells resembling normal epidermal basal cells situated above the plane of surrounding skin. Under low power appears blue in color. Thick surface layer of keratin is present. Within the acanthotic epithelium circular spaces filled with keratin called "horn cysts" or pseudohorn cysts are found. They represent invagination of surface keratin - hyperkeratotic variant. In the adenoid variant, dermis shows interweaving bands of benign basal cells. Other histologic type is acanthotic type. Most tumors show combination of all three histologic types (Fig. 14.8).
Inverted Follicular Keratosis (basosquamous Cell Acanthoma)
It is considered to be an irritated form of seborrheic keratosis. It shows pseudocarcinomatous hyperplasia and has inverted cup shaped configuration and surface invaginations.
HPE shows marked hyperkeratosis. Proliferating basaloid cells are situated adjacent to concentric whorls of squamous epithelium (squamous eddies). Intercellular spaces between squamous cells are widened due to intracellular and intercellular edema, referred to as acantholysis.
Fig. 14.8: Seborrheic keratosis: Shows squamous papilloma with hyperkeratosis, basilar acanthosis and intraepithelial horn cysts
Ocular Pathology |
215 |
Keratoacanthoma
It is a crater shaped squamous cell lesion and arises rapidly in elderly patients. It then undergoes spontaneous resolution. It was classified in the past as pseudocarcinomatous hyperplasia. It is now considered as 'deficient squamous cell carcinoma' that tends to involutes spontaneously. Rare cases invade deeply like squamous cell carcinoma. It is important to correlate the clinical history with tissue histopathology. It can arise along any hairy skin surface including periorbital skin. There is an increased incidence in AIDS patients.
Clinically a firm dome shaped nodule surrounds keratin filled excavation. There is rapid growth, which usually peaks by 8 weeks, then slowly involutes over a period of upto 12 months. Many patients will not tolerate the wait and justifiably seek its removal. It should be completely excised, because histopathologically it is similar to squamous cell carcinoma.
HPE shows central crater filled with densely packed keratin, enclosed by markedly acanthotic squamous epithelium, that typically extends like a lip or buttress over the side of the crater. The abnormal epidermal cells have pale, glassy cytoplasm. The presence of intraepidermal neutrophilic abscesses are helpful in distinguishing Keratoacanthoma from squamous cell carcinoma. Underlying dermis also shows intense band of inflammation. The base of a well-developed lesion appears regular and well demarcated. Margins are relatively smooth and pushing rather than infiltrative. Striking invasive acanthosis with abundant mitosis, focal atypia and dyskeratosis may predominate towards the periphery of the lesion. An incisional biopsy from this area will mislead to malignant interpretation.
A paradoxical finding for this benign lesion is perineural invasion. A helpful feature in diagnosis is that kratoacanthomas sit atop the undisturbed dermal sweat glands. An excision biopsy with adequate tumor free margins is ideal.
Pseudocarcinomatous Hyperplasia
It is a benign proliferation of epidermis stimulating an epithelial neoplasm. It is seen at the edge of burns or ulcers, near basal cell carcinoma, malignant melanoma and around chronic inflammation.
HPEthere is irregular invasion of the dermis by squamous cells. It may show mitotic figures. There is no dyskeratosis or atypia. Neutrophils are seen admixed with squamous cells.
Melanocytic Lesions of Eyelid
Junctional nevus Proliferation of benign nevus cells within the epidermis appearing as nests. They are darkly pigmented macules. Nevus cells are seen in the epidermal-dermal junction. Intradermal macrophages with ingested melanin seen (melanophages).
Compound nevus: It is lighter in colour and slightly elevated. Most congenital
216 |
Basic Sciences in Ophthalmology |
nevi are compound nevi. Maturing nests of nevus cells descend into the dermis, so nevus cells appear within both the epidermis and the dermis. As the dermal migration continues, nevus cells lose their nesting tendency. Deep in the dermis, they appear as sheets of bland small blue cells resembling mature lymphocytes. Individual cells become compact with reduction of cytoplasm and melanin synthesis.
Intradermal nevus: It is pale tan in colour and more elevated. Nevus cells are totally confined to the dermis. A thin band of collagen is often seen between the intra dermal nevus and the uninvolved epidermis. Maturing nevus cells shrink, are less cohesive, exhaust their pigment and may resemble lymphocytes. Clinically it may present as a nodule or a sessile papule with hairs.
Blue nevus (Dermal melanocytoma): It is composed of slender, wavy, dendritic melanocytes. It rarely exceeds 1 cm in diameter. These cells produce abundant melanin pigment and extracellular pigment is ingested by dermal melanophages. Increased number of neighboring fibroblasts leads to focal dermal fibrosis.
Nevus of Ota (Oculodermal melanocytosis): It is a blue brown cutaneous discoloration seen along distribution of ophthalmic and maxillary division of trigeminal nerve, including eyelid skin, periorbital skin and ipsilateral conjunctiva and sclera, and is always unilateral. HPE shows increased number of melanocytes in the dermis.
Invasive malignant melanoma arising in eyelid skin is rare and is less than 1% of all primary eyelid malignancies.
Adnexal Lesions of Eyelid
Sebaceous adenoma
It is a well circumscribed benign lesion composed of multiple irregular glandular lobules with a biphasic cell population of mature sebaceous epithelium and lesser extent of basaloid appearing germinative cells (primitive adnexal epithelium) .
Sebaceous carcinoma (Meibomian gland carcinoma)
It can present as chalazion within the tarsal plate and is more common in women and Asians, so recurrent chalazia should be submitted for HPE. It rarely presents as chronic unilateral keratoconjunctivitis due to intraepithelial spread of tumor, which replaces conjunctival epithelium in a pagetoid fashion. 2/3 rd of cases arise in upper eyelid (because of greater mass of Meibomian gland tissue in upper eyelid). It is rare before 40 years. Incidence is same as squamous cell carcinoma of eyelid.
Gross: It is yellow in colour with nodular appearance resembling chalazion. It is well circumscribed, sometimes encapsulated or may be ulcerated or fungating infiltrative growth. It may completely replace the meibomian gland in the tarsus.
HPE-Tumor is seen as lobules and in sheets. Lobules resemble normal
Ocular Pathology |
217 |
sebaceous glands, in size and shape. There is no peripheral palisading. Nuclei of cells are larger, pleomorphic, hyperchromatic and more atypical. Mitotic figures are common and atypical. Cytoplasm of tumor cells has foamy vacuolated appearance. Large lobules show necrosis centrallycomedo carcinoma pattern. Tumor invades and replaces eyelid skin and conjunctival epithelium in pagetoid fashion (Fig. 14.9).
Spread is by direct extension to regional lymph nodes and to distant sites.
Benign Sweat Gland Tumors
Syringoma
It arises from eccrine sweat ducts and appears as multiple small soft papules involving lower eyelid. HPEDermis shows dilated sweat ducts, embedded in dense fibrous stroma. Ductal elements are round, oval or teardrop shaped and lined by attenuated bilayer of cuboidal epithelium. Lumen may contain amorphous material.
Pleomorphic Adenoma
It presents as a small firm, immobile dermal nodule and may also be seen in eyelid skin. HPECords and nests of basaloid epithelium seen within a mucoid stroma. Tubular lumina are cystically dilated and surrounded by epithelial bilayer—inner cuboidal and outer-spindled myoepithelial layer. Myoepithelial layer produces stromal elements like cartilage, hyaline and dense fibrosis.
Other benign sweat gland tumors are—syringocystadenoma papilliferum, eccrine spiradenoma and clear cell hidradenoma.
Pilar Tumors
Fig. 14.9: Meibomian gland carcinoma—Lobules of malignant epithelial cells involving full thickness of eyelid.
218 |
Basic Sciences in Ophthalmology |
They are tumors of hair forming elements.
Trichoepithelioma (Brooke's tumor) , trichilemmoma, trichofolliculoma, pilomatricoma (Benign calcifying epithelioma of Malherbe).
Fibrous tumors—fibrous histiocytoma, juvenile fibromatosis, angiofibroma.
Neural Tumors:
Neurofibroma
It may be isolated, diffuse or plexiform. Isolated neurofibroma is a haphazard accumulation of bland, elongated spindled cells with oval, wavy nuclei. Mast cells may be seen. Plexiform neurofibroma shows sharply demarcated nests of proliferating endodermal fibroblasts and Schwann cells in a myxoid background.
Vascular Tumors
Capillary hemangioma: It is seen in children as non-capsulated proliferation of capillaries and pericytes. Larger collecting vessels are also present (Fig. 14.10).
Cavernous hemangioma: It is seen in adults and composed of large dilated, endothelium lined vascular spaces filled with blood and separated by delicate septa that contain smooth muscle (Fig. 14.11).
Lymphangioma
It has endothelium lined vascular spaces without pericytes. Vascular endothelium is attenuated and incompletely lines the spaces. Significant stromal lymphoid aggregates or lymphoid follicles with germinal centers are seen. Blood or serous fluid may be seen within the irregular vascular spaces (Fig. 14.12).
Kaposi sarcoma in periocular region is indicative of full blown AIDS.
Fig. 14.10: Capillary hemangioma-non encapsulated proliferation of capillaries and larger collecting vessels
Ocular Pathology |
219 |
Fig. 14.11: Cavernous hemangioma—pseudocapsulated vascular lesion with large blood filled spaces separated by delicate fibrous septa
Fig. 14.12: Lymphangioma—lymphoid aggregates she with in fibrous sepfa that divide irregular thin walled endothelial lined fluid shones
Lymphoid Tumors
Benign reactive lymphoid hyperplasia shows polymorphous proliferation of mature lymphocytes, plasma cells and histiocytes.
Atypical lymphoid hyperplasia shows monotonous proliferation of lymphocytes with cytological irregularities.
Non-Hodgin’s + lymphoma shows monotonous proliferation of neoplastic lymphocytes.
220 |
Basic Sciences in Ophthalmology |
Multiple myelomaIn disseminated multiple myeloma eyelid and periorbital involvement is seen. Epidermis is spared and dermis shows sheets of atypical plasma cells with abundant Russell bodies.
Miscellaneous lesionsMetastatic cancer.
- Merkel cell tumor (Neuroendocrine carcinoma of skin) .
Pyogenic Granuloma (Fig. 14.13)
It shows exuberant proliferation of granulation tissue following accidental or surgical trauma. It is an exaggerated tissue healing response. It is a rapidly growing smooth, red purple lobulated mass. HPEIt is composed of radiating capillaries and fibroblasts with a mixed inflammatory infiltrate of lymphocytes and polymorphs.
Premalignant Condition of Eyelid
Actinic Keratosis - Senile keratosis
Actinic keratosis or solar keratosis is a premalignant squamous cell lesion. It develops on sun exposed skin of fair skinned middle-aged individuals.
Clinically it appears as scaly, keratotic, flat-topped or erythematous nodules. It sometimes shows a nodular, horny or warty configuration and measures only few mm.
HPEepidermis is thickened and is replaced by atypical squamous cells. Parakeratosis is usually present and granular layer is absent. Irregular buds of atypical keratocytes extend into papillary dermis at the base of some lesions. Disease spares the opening of pilosebaceous units. Underlying dermis shows solar elastosis (elastotic degeneration similar to pterygium and pinguecula) and moderate lymphoplasmacytic infiltrates.
Fig. 14.13: Pyogenic granuloma—exuberant granulation tissue composed of fibroblasts, capillaries and a mixed inflammatory infiltrate
Ocular Pathology |
221 |
Patients often have other cutaneous premalignant and malignant lesions, including squamous cell, basal cell and adnexal carcinomas and malignant melanoma. If untreated 12 to 13% develop squamous cell carcinoma. Prognosis of squamous cell carcinoma arising in actinic keratosis is excellent because metastases very rarely occur (0.5%).
Important histologic feature in diagnosis is presence of actinic keratotic changes at the lateral epidermal margins of the invasive squamous cell carcinoma. Solar keratosis with squamous cell carcinoma is a separate nonaggressive entity distinct from squamous cell carcinoma arising de novo, which is capable of metastasis.
Histological types are:
-Hypertrophic
-Atrophic
-Bowenoid
-Solitary lichen planus like keratosis
Bowen's Disease of Eyelid
It is seen in fair skinned individuals at average age of 55 years. It is more common in men.
Clinically it appears as erythematous, pigmented, crusty, scaly, fissured keratotic plaques. Plaques are round, sharply demarcated, occasionally show heaped up margins. 2/3 rd of patients have single lesion and average size of lesion is 1.3 cm. 5% of cases show clinical and microscopic evidence of invasive carcinoma. 42% develop other cutaneous and mucocutaneous premalignant and malignant lesions—Actinic keratosis, basal cell carcinoma, squamous cell carcinoma and adenoid cystic (mucinous) carcinoma. 25% have primary internal or extra-cutaneous cancers. Early adequate excision of cutaneous lesions does not prevent subsequent development of systemic premalignant and malignant lesions. In order of frequency systemic lesions are respiratory system, gastrointestinal, genitourinary, reticuloendothelial, oral cavity, breast, endocrine, soft tissues and mucous membrane of conjunctiva and lip.
Lesions develop 6-7 years after Bowen's disease is noted or may co-exist at anytime. 75% of patients with Bowen's disease on follow up show evidence of primary systemic cancer. Strong evidence suggests inorganic arsenic (strong chemical carcinogen) as a cause of Bowen's disease. In addition, hereditary predisposition, exposure to petroleum by-products, trauma and cutaneous injury from ionizing radiation have been suggested.
HPE shows hyperkeratosis, plaque like acanthosis and hypogranulosis. Epidermis shows loss of normal polarity and architectureatypical epithelial proliferation with hyper chromatic nuclei, multinucleated cells and vacuolated cells. Abnormal keratinocytic maturation is evidenced by abnormal mitotic figures and malignant dyskeratotic cells. The above changes occur at all levels
222 |
Basic Sciences in Ophthalmology |
of the epidermis. It is confined by an intact dermo-epidermal basement membrane and the lesion represents intraepidermal squamous cell carcinoma (carcinoma in situ). The changes resemble that of actinic (solar) keratosis.
Difference- In Bowens serial sections shows involvement of the ducts of hair follicles and sebaceous glands. Lesions involve outer sheaths of hair follicles and eventually replace the sebaceous gland and cells. Sometimes, extensive skip areas of uninvolved epidermis are present. Presence of atypical vacuolated cells may be confused with sebaceous gland carcinoma.
Malignant Lesions of Epidermis of Eyelid
Squamous Cell Carcinoma
It is relatively rare compared to basal cell carcinoma. It affects elderly, fair skinned individuals and is common in lower lid margin. In upper eyelid and outer canthus, squamous cell carcinoma is more common than basal cell carcinoma. It may arise de novo or from intra epithelial carcinoma or actinic keratosis. It may also follow radiotherapy and in patients with xeroderma pigmentosum.
Clinically, It is an elevated, indurated plaque or nodule that tends to ulcerate and shows irregular borders. Well-differentiated tumors have grayish white granular appearance due to masses of keratin. Advanced cases metastasize to pre auricular and submandibular lymph nodes.
HPE—well differentiated tumors show polygonal cells with abundant eosinophilic cytoplasm. Dyskeratotic cells with formation of keratin pearls are seen. Nuclei are prominent, pleomorphic and hyperchromatic (Fig. 14.14). Spindle cell variant is rare. Cells are pleomorphic and hyperchromatic and spindle shaped, resembling fibroblasts. Cells extend into sub epithelial tissues from deeper layers of surface epithelium.
Basal Cell Carcinoma
It is the most common malignant tumor affecting periocular skin. It comprises 90% of all malignant eyelid tumors. It affects fair skinned adults and can occur in younger persons. It arises in sun-exposed skin and is thought to be caused by actinic damage. Basal cells normally contain 3 types of cells-
1)Basal cells.
2)Melanocyte cellsdevelop into nevi and malignant melanoma.
3)Primary epithelial germ cells—seen in the deepest layer of epidermis are
derived from surface ectoderm and develop into basal cell carcinoma. Basal cell carcinoma is 15-40 times more common than squamous cell carcinoma on eyelids. The site of occurrence in order of frequency is lower eyelid, inner canthus, upper eyelid and outer canthus.
Variants
1)Nodular type: It is a well circumscribed tumor with pseudo capsule and a firm elevated pearly white nodule with superficial telangiectatic vessels.