Ординатура / Офтальмология / Английские материалы / Basic Sciences in Ophthalmology_Velayutham_2009

Fig. 14.14: Squamous cell carcinoma shows eosinophili nests of malignant squamous epithelial cells and foci of keratinization

HPEhowever large the tumor, it does not extend deeply into the dermis or ulcerate the epithelium.

2)Ulcerative type: There is erosion of eyelids with absence of eyelashes. Advanced lesions have enlarging ulcers with prominent rolled out pearly white borders with distinct margins. HPE shows loss of epithelium centrally and invasion into dermis. Nodulo ulcerative type starts as nodular and as nodules increase in size central ulceration occurs.

3)Sclerosing or morpheaform type: It is a pale indurated plaque and resembles morphea (circumscribed form of scleroderma). It has indistinct margins and does not ulcerate till late. It shows widespread superficial multicentric involvement. HPE shows discrete islands of tumor cells encased in dense connective tissue network beneath an intact epithelium. Invasion into deeper structures of eyelid.

4)Multicentric type: It has diffuse irregular nodular surface with telangiectatic vessels. HPE shows diffuse multicentric involvement of epidermis extending into the superficial dermis. Subepidermal nests of tumor cells that are distinct from most of the tumor are also seen.

Histopathology of Basal Cell Carcinoma

Under light microscope it appears 'blue' and 'below' the surface. Neoplastic basaloid cells are arranged in large masses or fields, smaller nests or cords. Periphery of tumor lobules show characteristic peripheral palisading of nuclei (picket fence appearance). Empty spaces or clefts may be seen between tumor lobules and surrounding stroma due to shrinkage of mucin rich stroma during processing. Fibrous stroma separating tumor lobules are more fibrotic and denser than normal dermis- (desmoplasia) due to stimulation of fibrosis by tumor (Fig. 14.15).

Fig. 14.15: Basal cell carcinoma. Shows nests, cords and lobules of neoplastic basaloid cells with peripheral palisading of nuclei

Histologic Variants

Tumor shows differentiation towards various epidermal appendages—

1)Adenoid cystic variantmucin production is evident.

2)Keratotic basal cell carcinoma—keratinised horn cystspilar differentiation.

3)Sebaceous differentiation.

4)Pigmented basal cell carcinoma—cells contain melanin pigment.

5)Pseudo-cystic basal cell carcinomaNecrobiosis in centre of a large mass of tumor cells.

6)Morpheaform basal cell carcinomaSlender cords or tendrils of tumor cells embedded in densely fibrotic stroma.

7)Solid type.

8)Meta typical or basosquamous variant—more aggressive and shows infiltrative pattern.

Lesions in advanced cases shows extensive areas of ulceration called 'rodent ulcer'. It produces disfiguring facial destruction. Basal cell carcinoma rarely metastasizes. Metastatic tumors are of metatypical or basosquamous type. Deeply infiltrative, ulcerative lesions invade orbital bones and meninges causing secondary meningitis, which may be fatal.

In 0.7% of cases, multiple basal cell carcinomas occur on face and body of young patients. Nevoid basal cell carcinoma syndromebasal cell nevus or Gorlin Goltz syndrome.

Other lesions in Gorlin Goltz syndromeOdontogenic keratocysts of jaw.

Bifid ribs.

Neurologic abnormalities. Endocrine disorders.

Basal cell carcinoma in such patients may contain spicules of bone.

button or mushroom configuration (diagnostic of uveal melanoma). Ruptured ends of Bruch's membrane exert a compressive effect on the waist of the tumor causing vascular congestion in the apex.

4)Diffuse flat choroidal malignant melanoma—occasionally malignant melanoma thickens the choroid without forming an elevated mass. It is less well differentiated, extends extraocularly invades optic nerve and has poorer prognosis.

Color and pigmentation

Commonly lesions are unpigmented or amelanotic. Most are light brown to grey and less commonly jet-black in color. Degree of pigmentation varies within different sites of same tumor and both heavily pigmented cells and relatively amelanotic cells may be seen.

HPEtwo major types are seen-

1)Spindle cells are syncytium bipolar fusiform cells with long tapering processes and grow as parallel fascicles. They form a syncytium. The cytoplasmic margins of individual cells are indistinct. There are two subcategories

SpindleAand spindle B cells. SpindleA cells have bland, slender, cigar shaped nuclei with finely dispersed chromatin and indistinct nucleoli. Longitudinal fold in nuclear membrane is seen as a chromatin stripe or line in many cells. Spindle B cells are less differentiated than spindle A cells. Nuclei are plumper, oval and have distinct nucleolus and coarser chromatin pattern.

2)Epithelloid cells—they are the least differentiated of uveal melanoma cells. Tumors rich in epithelioid cells have poorer prognosis. Cells have abundant cytoplasm, are polyhedral with distinct cytoplasmic margin and poorly cohesive. Nuclei are larger, round or oval and vesicular. Typically, they have large reddish purple nucleoli. Nuclear chromatin is coarse and clumps along the inner side of nuclear membrane (peripheral margination of chromatin).

Variants of Epithelioid Cells

Small uniform epithelioid cells, highly anaplastic tumor giant cells and occasionally spindle shaped epitheloid cells can be seen.

Based on cell cytology, uveal melanomas are of 5 types—Callender classification—based on prognosis from best to worse-

1)Tumor composed entirely of nevus cells or benign spindle A cellsspindle cell nevus.

2)Spindle melanomas—composed of malignant spindle A cells, spindle B cells or mixture of spindle A and B cells.

3)Fascicular melanoma—predominantly spindle B cells arranged in the form of fascicles or interlacing bundles.

4)Melanoma of mixed cell type—mixture of spindle and epitheloid cells. Most large tumors treated by enucleation are mixed cell melanoma (Fig. 14.16).

5)Epithelioid melanoma—shows only epithelioid cells. It is rare and has the poorest prognosis.

6)Totally necrotic melanomas—behave like mixed cell type.

Prognosis depends on tumor size and cell type. Mortality is greater if tumor contains epithelioid cells. Large melanomas have poorer prognosis than small and medium size tumors. Small melanomas are likely to be spindle cell tumors with better prognosis. Vascular loops and network of loops indicate poorer prognosis.

Spread—it rarely invades optic nerve and extends out of the eye through emissarial canals of vessels and nerves in the sclera via lumina of vortex vein. Haematogenous spread to liver occurs.

Ciliary Body Melanoma

It is less common than choroidal tumors. Has more spherical shape. It is large when first detected as they are hidden behind iris.

Iris:

Most melanocytic lesions of iris are benign nevi or low-grade spindle cell tumors. Features suggesting that pigmented iris tumor is a melanoma are - large size, documented growth, increased IOP, hyphema and tumor vascularity.

Differential Diagnosis of Malignant Melanoma of Choroid-

1)Carcinoma of breast (adenocarcinoma).

2)Bronchogenic carcinoma (tumor shows squamous cell differentiation or oat cell carcinoma appearance).

Fig. 14.16: Choroidal melanoma showing spindle and epithelioid melanoma cells

RETINOBLASTOMA

Histogenesis

It is derived from cells of sensory retina. Cellular differentiation is neural or mixed neuroglial. Suffix "blastoma" emphasizes the presence of primitive immature embryonic appearing blastemal cells that form the tumor. It is frequently bilateral. It often shows multicentric growth within the same eye. Multiple primary tumors in single eye differ from multiple deposits of tumor along the retinal surface because of seeding of the tumor.

Gross appearance is white, encephaloid or brain like. Lighter flecks of calcification may be seen—gritty to cut.

It may be

1)Exophytic.

2)Endophytic.

3)Mixed.

4)Diffuse infiltrating growth pattern.

Endophytic variety arises from inner layers of retina. Retina remains attached and seeding of vitreous and anterior chamber occurs. Differential diagnosisresembles uveitis and ocular toxocariasis.

Exophytic variety causes outward growth of tumor toward subretinal space. Differential diagnosis—Coat’s disease with exudative retinal detachment.

Most tumors have mixed endo-exophytic growth pattern and 1.4% of Retinoblastomas diffusely thickens the retina without forming distinct massdiffusely infiltrating type seen in older children (6 years) .

HPERetinoblastoma arises from and destroys the retina. Under low power tumor appears blue, pink and purple. Blue areas represent viable parts of tumor and are composed of poorly differentiated neuroblastic cells with basophilic nuclei and scanty cytoplasm. Retinoblastoma cells are seen as sleeves or cuffs of viable cells measuring 90-100 microns in radius, generally around blood vessels. Retinoblastoma cells readily outgrow their blood supply and undergo necrosis.

Pink areas represent necrotic tumor cells which lose their basophilic nuclear DNA and appear pink or eosinophilic.

Purple areas are necrotic parts of tumor which show dystrophic calcification, and appear reddish purple on H & E, stained sections.

Many mitotic figures are seen and intensely basophilic DNA released from necrotic tumor cells may deposit in vessel walls, iris stroma, trabecular meshwork, walls of Schlemm's canal, lens capsule and retinal internal limiting membrane. Tumor cells collect on inner surface of Bruch's membrane forming focal detachment of RPE. Extensive seeding from involved vitreous and inner and outer surfaces of retina make it difficult to diagnose multifocal retinoblastoma (Fig. 14.17A and B).

A

B

Fig. 14.17A and B: Retinoblastoma - showing 1. dystrophic calcification 2. flexner wintersteiner rosettes 3. necrotic tumor cells (A), Cross section of optic nerve showing extensive infiltration by retinoblastoma cells

Retinoblastoma shows varying degrees of differentiation-

1)Homer—Wright rosettes—indicates neuroblastic differentiation. There is no central lumen and constituent cells encompass central tangle of nerve filaments. They are non-specific and also seen in neuroblastoma and medulloblastoma.

2)Flexner Wintersteiner rosettesare characteristic of retinoblastoma and represent early retinal differentiation. They have central lumen, which corresponds to subretinal space and are also seen in malignant medulloepithelioma (Diktyoma) and pineal tumors.

3)Fleurettes—represent photoreceptor differentiation and cells have prominent eosinophilic cellular processes. They may show small bouquet of tumor

cells aligned along a segment of neoplastic external limiting membrane. Tumors composed entirely of Fleurettes are called retinocytomas or retinomas and thought to be benign tumors. The cells are bland, have low nuclear/ cytoplasmic ratio, finely dispersed chromatin, fem mitosis and absent necrosis.

Calcification is seen in viable parts of the tumor and thought to be due to retinoblastoma that has undergone spontaneous regression. They have fish flesh appearance and contain abundant calcification likened to cottage cheese appearance. Annulus of RPE depigmentation typically surrounds the tumor.

Occasionally retinoblastoma undergoes spontaneous regression, resulting in degenerated phthisical eye with foci of calcified tumor cells in a matrix of glial scar tissue and extensive intraocular necrosis.

Optic nerve invasion is a characteristic feature of retinoblastoma and prognosis depends on depth of optic nerve invasion. Mortality rates are—

1)No optic nerve invasion- 8%.

2)Tumor invaded upto lamina cribrosa15%.

3)Tumor with retrolaminar invasion44%.

4)With extension beyond surgical margin64%.

So, a long segment of optic nerve should be removed with enucleated eye and sent for HPE.

Extraocular extension of tumor

1)Reach brain by infiltration of optic nerve, through orbital bones or foramina from areas of orbital involvement.

2)By CSF to subarachnoid space of brain and spinal cord.

3)Blood borne metastasis to lungs, bones and brain.

4)To pre-auricular and cervical lymph nodes if tumor reaches lymphatics in

conjunctiva.

Metastasis occurs within 2 years of treatment. Histologic parameters of aggressive clinical behavior-

1)Lack of differentiation (absence of rosette formation).

2)Vitreous seeding.

3)Invasion into choroid.

4)Invasion into optic nerve.