Ординатура / Офтальмология / Английские материалы / Ocular Pathology_6th edition_Yanoff, Sassani_2009

A

C

ness replacement of the epithelium by atypical, often bizarre and pleomorphic epithelial cells.

b.Dyskeratotic epithelial cells may be seen.

Rarely, mucoepidermoid differentiation can be seen in the neoplasm.

c.The involved epithelial area is thickened and sharply demarcated from the contiguous, normal-appearing conjunctival epithelium.

The thickening usually ranges from approximately two to five times normal thickness, but may be greater in malignant transformation of papillomas.

d.Polarity of the epithelium is lost.

e.Mitotic figures are commonly found.

f.The basement membrane of the epithelium is intact, and no invasion of the subepithelial tissue occurs.

g.Conjunctival squamous cell carcinoma intensely expresses immunoreactivity for the tyrosine kinase EGF receptor. Studies involving the induction of apoptosis in serum-deprived cultured conjunctival epithelial cell have demon-

B

Fig. 7.21 Squamous cell carcinoma. A, The patient had a vascularized, elevated pearly lesion at the temporal limbus in the right eye. In addition, he had a pterygium nasally in the left eye. Excisional biopsy of the lesion in the right eye was diagnosed as carcinoma in situ. B, Histologic section of another case shows full-thickness atypia and loss of polarity. A diagnosis of carcinoma in situ would be made here. C, Other regions of this case show malignant epithelial cells in the substantia propria of the conjunctiva, forming keratin pearls in some areas representing invasive squamous cell carcinoma.

strated that EGF and retinoic acid play key roles in the maintenance of the ocular surface.

h.Conjunctival intraepithelial neoplasia and squa-

mous cell carcinoma are associated with preferential expression of p63 in the immature dysplastic epithelial cells. The staining for p63,

which is a homologue of the tumor suppressor gene p53, is not correlated with MIB-1 expression and, therefore, appears not to be linked to cell proliferation.

Never clinically, but occasionally histologically, CIN may resemble superficially the intraepithelial carcinoma of the skin described by Bowen (Bowen’s disease) or the intraepithelial carcinoma of the glans penis described by Queyrat (erythroplasia of Queyrat). Both entities are specific clinicopathologic entities and their terms should be restricted to their proper use, which never includes carcinoma in situ of the conjunctiva or any conjunctival neoplasm.

B.Squamous cell carcinoma with superficial invasion (see Fig. 7.21)

In addition to the epithelial changes of CIN, invasion by the malignant, pleomorphic, atypical squamous epithelial cells occurs through the epithelial basement membrane into the superficial subepithelial tissue.

Rarely, squamous cell carcinoma with superficial (micro)stromal invasion can arise primarily in the cornea (squamous cell carcinoma of the cornea) without extension to the corneoscleral limbus.

C.Squamous cell carcinoma with deep invasion (see Fig. 7.21)

In addition to the epithelial changes of CIN, there is invasion by the malignant squamous epithelial cells through the epithelial basement membrane deep into the subepithelial tissue or even into adjacent structures.

Spindle-cell carcinoma is a rare variant of squamous cell carcinoma, and may arise from the conjunctiva. Positive staining with cytokeratin and epithelial membrane antigen markers is helpful in differentiating the variant from other spindle-cell tumors such as amelanotic melanoma, malignant schwannoma, fibrosarcoma, leiomyosarcoma, and malignant fibrous histiocytoma. Malignant fibrous histiocytoma rarely arises in the conjunctiva.

D.Squamous cell carcinoma with metastasis

All the features of squamous cell carcinoma with deep invasion are involved, plus evidence of metastasis. Metastatic squamous cell carcinoma may be an atypical presentation of HIV infection.

III.Carcinoma derived from the basal cells of conjunctival epithelium

Basal cell carcinoma rarely arises from the conjunctiva or caruncle.

The lid differs from the conjunctiva in being a site of preference for basal cell carcinoma.

IV. Carcinoma derived from the mucus-secreting cells and squamous cells of conjunctival epithelium Mucoepidermoid carcinoma (Fig. 7.22) is a rare conjunctival tumor characteristically composed of mucus-secreting cells intermixed with epidermoid (squamous) cells.

Mucoepidermoid carcinoma can also arise from the caruncle. A third type of cell, called intermediate or basal cell, may also be found.

A.Some tumors show a predominance of epidermoid cells, whereas others have mainly mucus-secreting cells.

B.The tumors appear to be aggressive locally and tend to recur rapidly after excision; a wide local excision is therefore recommended.

C.Histologically, lobules of tumor cells show a variable admixture of epidermoid and mucus-secreting cells.

Histochemical stains for mucin are most helpful in confirming the diagnosis.

Pigmented Lesions of the Conjunctiva

See section Melanotic Tumors of Conjunctiva in Chapter 17.

Laugier–Hunziker syndrome is a rare acquired hyperpigmentation of the oral mucosa and lips, which is often associated with longitudinal melanonychia (black pigmentation of the nails). It may also be associated with conjunctival and penile pigmentation. Histopathologic examination demonstrates basal epithelial melanosis, moderate acanthosis, and superficial pigmentary incontinence. Electron microscopic examination reveals increased number of normal-appearing melanosomes inside basal keratinocytes and dermal melanophages.

Stromal Neoplasms

I.Angiomatous—see discussions of hamartomas and vascular mesenchymal tumors on pp 543–548 in Chapter 14.

II.Pseudotumors, lymphoid hyperplasia, lymphomas, and leukemias (Fig. 7.23)—see discussions of tumors of the reticuloendothelial system, lymphatic system, and myeloid system on p. 568 in Chapter 14.

A.Extranodal marginal-zone B-cell lymphoma of mucosaassociated lymphoid tissue (MALT) constitutes about

88% of all lymphoma involving the ocular adnexa. It tends to appear in patients with a history of autoimmune disease or chronic inflammatory disorders. It has been reported in a child. Rarely, it may arise in Tenon’s

capsule. These lesions respond well to conventional treatment; however, there is a high rate of recurrence.

At least three different site-specific chromosomal translocations involving the nuclear factor-kappaB have been implicated in the development and progression of MALT lymphoma. The most common such translocation is t(11;18) (q21;q21), resulting in the fusion of the cIAP2 region on chromosome 11q21 with the MALT1 gene on chromosome 18q21, and is said to be involved in more than one-third of cases. In gastric MALT lymphoma, t(11;18) (q21;q21) is significantly associated with infection by CagA-positive strains of Helicobacter pylori, and eradication of the organism is standard therapy for all H. pylori- positive gastric MALT lymphomas. Oxidative damage may play a role in the development of this translocation. Translocation t(14;18) (q32;q21) is also commonly found in this disorder, and the specific translocation varies considerably with the primary location of the disease. MALT lymphoma has also been found in a patient with adult inclusion conjunctivitis.

1.CD43-positive ocular lymphomas are associated with a higher rate of subsequent distant recurrence and rate of lymphoma-related death.

2.Uncommonly, conjunctival B-cell lymphoma may present as an ulcerating tarsal conjunctival mass.

The spontaneous regression of a large B-cell lymphoma involving the conjunctiva and orbit has been reported. Mantle cell lymphoma has presented as a marked follicular conjunctivitis in both eyes with a nodal mass in the right upper eyelid, and nuchal lymphadenopathy. The diagnosis was made on conjunctival biopsy.

B.Although rarely found in the conjunctiva, T-cell lymphoma must be considered in the di erential diagnosis of gelatinous lesions of the conjunciva. It is characterized by positive staining with CD-45 RO (T-cell

marker) and negativity with CD-20 (B-cell marker). Additionally, positivity for T-cell receptor gene rearrangement with clonality confirms the diagnosis.

C.Lethal midline granuloma associated with natural killer

(NK)/T-cell lymphoma and Epstein–Barr virus infection has presented involving the conjunctiva. This lethal midline granuloma, which is a very rare, angiocentric

NK/T-cell lymphoma associated with Epstein–Barr virus infection, demonstrated features of a highly

malignant, CD3 and BCL2-positive T-cell lymphoma with features of an NK/T-cell origin (CD56+, T-cell intraceullar antigen (TIA+), T-cell receptor rearrangement: germline). All lymphoma cells were said to be positive for Epstein-Barr virus RNA. At presentation the patient was otherwise a healthy, immunocompetent,

Caucasian.

D.Benign lymphoid hyperplasia of the conjunctiva is particularly uncommon in children, but has been reported.

Polymerase chain reaction for Epstein–Barr virus was negative, and immunohistochemistry and flow cytometry were consistent with the diagnosis.

E.T-cell prolymphocytic leukemia, a rare and very aggressive hematological neoplasm, has presented with bilateral perilimbal conjunctival infiltrates, in which the diagnosis was confirmed on histopathologic examination. Conjunctival involvement has accompanied uveal (including anterior uveitis), palpebral, and orbital invasion by adult T-cell leukemia.

III.Juvenile xanthogranulomas—see p. 343 in Chapter 9.

IV. Neural tumors—see discussion of neural mesenchymal tumors on p. 558 in Chapter 14.

V.Fibrous tumors—see discussion of fibrous–histiocytic mesenchymal tumors on p. 551 in Chapter 14.

VI. Leiomyosarcoma and rhabdomyosarcoma—see discussion of muscle mesenchymal tumors on p. 554 in Chapter 14.

A.Rarely, rhabdomyosarcoma may present as a conjunctival lesion without orbital extension.

VII. Metastatic

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CORNEA

NORMAL ANATOMY

I.Introduction

A.In vivo confocal microscopy (CFM) is a valuable tool for the study of corneal diseases. CFM findings complement and corroborate histopathological analyses.

B.Multiple types of corneal disorders are discussed in this chapter. To appreciate the corneal disease state better, the normal anatomy must be understood.

One indication of the visual significance of each entity is the frequency for which corneal transplantation is required for each disorder. In one large study of 1540 corneal transplants, corneal edema was the most common cause (24.8%), followed by keratitis (24.5%) and corneal dystrophies (24.4%).

C.The cornea (Fig. 8.1) is a modified mucous membrane (it can also be considered, in part, as modified skin).

It is not surprising, therefore, that the cornea is affected in association with cutaneous disorders. For example, low corneal sensitivity, abnormal tear quality, decreased cellular cohesion, squamous metaplasia of the conjunctiva, and goblet cell loss have been described in the Hallopeau–Siemens subtype of dystrophic epidermolysis bullosa. Specific corneal abnormalities in this disorder may include recurrent corneal erosion, and superficial punctate corneal erosions.

1.The cornea is covered anteriorly by a nonkeratinizing squamous epithelium of approximately five layers, representing modified epidermis of skin.

Intermixed within the corneal epithelium are Langerhans’ cells (bone marrow-derived, CD Ia-expressing, dendriticappearing cells) and occasional dendritic melanocytes. Langerhans’ cell histiocytosis has presented as a limbal nodule in an adult.

a.The deepest layer of epithelial cells, the basal layer, is the germinative layer and is attached to its neighboring basal cells and overlying wing cells by desmosomes.

b.The basal cell layer is also attached by hemidesmosomes to its own secretory product, a somewhat irregular, thin basement membrane.

Three major types of molecules are found in the basement membrane: type IV collagen, heparan sulfate proteoglycans, and noncollagenous proteins (e.g., laminin, nidogen, and osteonectin). The basement membrane represents an important physiologic barrier between the epithelium and the stroma.

c.The flattened, nucleated, superficial epithelial cells desquamate into the overlying trilaminar (mucoprotein, water, lipid) tear film. The mucoprotein layer serves to adhere the tear film to the epithelial microvilli.

Corneal stem cells reside in the transitional epithelium between cornea and conjunctiva (i.e., the limbus).

Corneal limbal cells express K3 keratin marker for corneal-type differentiation, in contrast to conjunctival cells. In healing large corneal abrasions that reach the limbus, the stem cells regenerate new corneal epithelium by a process called conjunctival transdifferentiation. First, the healing epithelium shows conjunctiva-like