Sehu - Ophthalmic Pathology-2005

30 C H A P T E R 2

Eyelid - Tumours

Basal cell carcinoma - Sclerosing type

small ulcer

atrophic epidermis

hyperplastic epidermis

solid basal cell carcinoma

small islands of tumour cells within dense fibrous tissue

Figure 2.39

Eyelid - Tumours

Basal cell carcinoma - Sclerosing type

small

palisading

islands of tumour cells

basal cells

sweat duct

mast cells

fibroblasts

lymphocytes

Figure 2.41

keratin

lid margin

eyelashes

Figure 2.43

anterior surface

Eyelid - Tumours

Squamous cell carcinoma

Figure 2.44

levator

Sommering's cataract

destruction of eyelid by massive tumour

normal

Eyelid - Tumour lower lid Squamous cell carcinoma - Exenteration

Figure 2.46

Eyelid - Tumour Squamous cell carcinoma

normal skin

ulcerated surface

secondary lymphocytic infiltrate

degenerate artery (intimal fibroplasia)

massive tumour in upper Iid

Eyelid - Tumour

Squamous cell carcinoma - Exenteration

Figure 2.45

hyperkeratosis + parakeratosis = SOLAR KERATOSIS

Figure 2.47

Figure 2.44 The specimen in Figure 2.43 has been cut vertically to remove a central block (see “Macroscopic examination or specimen ‘grossing’ ” in Chapter 1), which is positioned to show the cut surface. This reveals the deep invasion of a squamous cell carcinoma into the substance of the lid. In practice, clearance blocks would be taken from the lateral and medial borders.

Figure 2.45 Macroscopic appearance of an exenteration specimen for squamous cell carcinoma with extensive invasion of the upper lid. Prior to the exenteration, the patient had cataract surgery which was only partially successful, leaving behind a Sommering’s cataract.

Figure 2.46 Low power microscopic appearance of an exenteration specimen for squamous cell carcinoma with extensive invasion of the upper lid. (Same case as that shown in Figure 2.45.)

Figure 2.47 Squamous carcinomas often arise in sectors of solar/actinic keratosis. The surface still maintains integrity and there is little secondary inflammation. The malignant cells are inducing a fibroblastic reaction.

Figure 2.48 Ulceration is a common occurrence in squamous carcinomas and this leads to extensive lymphocytic infiltration and fibrosis. The inflammatory process also damages the walls of underlying blood vessels.

necrosis of cancer cells predisposes to ulceration

squamous differentiation

surrounding fibrosis

Figure 2.49

Eyelid - Tumour

Squamous cell carcinoma

mitoses

Figure 2.51

Figure 2.49 Even at moderate magnification, it is possible to see that within the islands of malignant cells there is differentiation to form squamous cells. The surface cells of the tumour disintegrate and provide a substrate for bacterial infection with secondary leucocytic inflammatory infiltration. The underlying dermal tissue responds to the inflammatory process in the form of lymphocytic infiltration.

Figure 2.50 In three dimensions, the finger-like extensions of a squamous cell carcinoma are cut in different planes so that some islands contain basal cells.

Clinical presentation

•Yellow nodule that may or may not be ulcerated.

•Plaque-like lesion.

•Chronic blepharoconjunctivitis especially with loss of lashes (Figure 2.53).

•Recurrent eyelid inflammation similar to a chalazion.

•Metastasis to lymph nodes and viscera if correct diagnosis is delayed. It is more common in the elderly, females, and in the upper lid.

Pathogenesis

Unknown.

Possible modes of treatment

Wide surgical excision or exenteration is preferred. Adjunctive radiotherapy for advanced cases (but the tumour has a tendency to be radioresistant).

Macroscopic

If a sebaceous carcinoma is suspected, the pathologist should be informed and fresh (unfixed) tissue should be submitted immediately for frozen section for fat stains (normal tissue processing removes fat).

Specimens submitted may present as:

•a lid wedge excision including a pale yellow nodular tumour (Figure 2.54)

•fragments resembling the granular material seen in a chalazion

•an exenteration (Figure 2.55).

Microscopic

Nodular tumours Revision of the normal histology provides a better understanding of the variable appearance of sebaceous gland carcinoma (Figure 2.56). The basic element of a sebaceous gland is the lobule which is outlined by a single cuboidal basal layer. These cells mature in an orderly fashion into large cells with lipid-laden foamy cytoplasm and a small nucleus. In the neck of the follicle, the cells fragment to release lipid into the ducts (holocrine secretion).

In a well differentiated sebaceous gland carcinoma, the morphology is lobular and the centre of the lobule contains foamy cells. The basal cells may fail to differentiate into foamy cells and the lobules are filled with small basophilic cells (Figure 2.57).

In less well differentiated tumours, the basal cells predominate and the cytoplasm contains small circular spaces which represent the lipid globules which were removed during paraffin processing (Figure 2.58). The lipid is preserved in frozen sections and stains positively with appropriate stains (Figure 2.59).

In completely dedifferentiated tumours, lipid spaces are rare and are seen only in thin sections at high magnification (Figure 2.60). In such advanced cases, the tumour infiltrates the eyelids extensively (Figure 2.61).

Diffuse intraepithelial spread Intraepithelial spread can be extensive (Figure 2.62) and requires high magnification for identification of the limits (Figures 2.63, 2.64). The malignant cells within the normal epithelial cells possess foamy cytoplasm and show nuclear atypia. Fat stains (Figure 2.64) and immunohistochemistry can be helpful in determining the boundaries of spread.

Immunohistochemistry

The central foamy cells are identified with human milk fat globule-1 (HMFG1 – Figure 2.64) and epithelial membrane antigen (EMA). The smaller peripheral basal cells stain with cytokeratin markers (PKK1 MNF116).

Malignant – rare

The following are extremely rare in clinical practice but must be considered in the differential diagnosis in the scenario of rapidly growing tumours.

Metastasis

Suspicion of metastasis should be aroused in the presentation of a rapidly growing tumour of the eyelid. The location of the primary tumours is similar to those described for intraocular metastasis.

Cutaneous melanoma

Malignant melanoma arising from the epidermis of the eyelid is extremely rare and is easily recognised by heavy pigmentation of a rapidly spreading flat area (lentigo maligna) or a nodular tumour. The histological appearances are similar to those described for intraocular melanoma.

Kaposi’s sarcoma

Previously extremely rare, the incidence of this tumour has increased along with the increased incidence of the acquired immune deficiency syndrome (AIDS). Rapidly growing erythematous swelling of the eyelid in an immunocompromised patient should lead to a suspicion of this tumour. The histological feature is the presence of malignant spindle cells surrounding vessels with thin walls.

Merkel cell tumour

A smooth elongated ovoid mass projecting from the surface of the upper lid is the characteristic appearance of this tumour. The cells forming the tumour are of neuroendocrine type and are arranged in nests.

Lymphoma

The histological appearances of malignant lymphoid tumours of the eyelid are similar in appearance to conjunctival lymphomas.

Eyelid - Tumour

Sebaceous gland carcinoma

Figure 2.53

ulcerated tumour nodule

extensive tumour infiltration

of both upper and lower

lids

Eyelid - Tumour

Sebaceous gland carcinoma

Figure 2.55

ulcerated surface

Figure 2.57

Figure 2.53 Slit lamp photograph of a patient presenting with severe unilateral blepharoconjunctivitis. Biopsies of the upper and lower lids were performed and these revealed diffuse intraepithelial spread of a sebaceous gland carcinoma involving both skin and conjunctiva. Note the loss of lashes.

Figure 2.54 Two levels of a wedge excision of an eyelid containing a solid sebaceous gland carcinoma. In the centre of the specimen, the tumour fills the tarsal plate.

Figure 2.55 An exenteration specimen in which there was extensive unilateral tumour infiltration in both lids. The diagnosis was delayed until a lymph node metastasis was identified. The patient ultimately died of lung metastases. See Figure 2.61.

Eyelid - Tumour

Sebaceous gland carcinoma skin surface

normal tarsal plate

conjunctival surface

Figure 2.54

duct wall formed by squamous epithelium

disintegrating cells secrete lipid into duct (holocrine

secretion) lipid laden sebaceous

cells

cuboidal basal cells

Eyelid - Tumour

Normal Meibomian gland

Figure 2.56

foamy cytoplasm

mitotic figure

Eyelid - Tumour

Sebaceous gland carcinoma

Figure 2.58

Figure 2.56 To appreciate the morphology of sebaceous gland carcinoma,

it is important to revise the normal tissue histology of Meibomian gland lobules and ducts.

Figure 2.57 A well differentiated sebaceous gland carcinoma recapitulates the normal gland by the formation of foamy cells within the centres of the tumour lobules. As the tumour dedifferentiates, cells retain the features of basal cells and form nests and cords within the tumour lobules.

Figure 2.58 In a poorly differentiated sebaceous gland carcinoma, the diagnostic feature is the presence of small clear fat spaces.

mitosis

binucleate cells

multiple fat spaces

extent of spread

Eyelid - Tumour

Sebaceous gland carcinoma - Intraepithelial spread

Figure 2.62

Figure 2.59 Lipid within the cytoplasm in a sebaceous gland carcinoma is best demonstrated by the Oil red O stain in fresh frozen sections.

Figure 2.60 In a thin plastic section stained with toluidine blue, the tiny lipid spaces in a sebaceous gland carcinoma can be identified at high magnification. Within the lobules the cells show marked variation in size and shape in this poorly differentiated tumour.

Figure 2.61 Blocks from the specimen shown in Figure 2.55 were taken from the upper and lower lid and recombined to show the extent of infiltration by a sebaceous gland carcinoma in both lids.

Figure 2.62 In a case similar to that shown in Figure 2.53, the intraepithelial spread of a sebaceous gland carcinoma covers the tarsal and bulbar conjunctiva and the adjacent lid margin. A small nodular tumour represents the original focus. The circled area over the limbus indicates the histology shown in Figure 2.63.

Figure 2.63 Histology from the limbus marked with a circle in Figure 2.62. The malignant cells possess foamy cytoplasm which permits the distinction from normal cells that have lost their orderly arrangement due to tumour cell infiltration. The underlying stroma contains lymphocytes and plasma cells.

Soft tissue tumours

Benign

Hamartomas and choristomas

A hamartoma is a benign tumour arising from tissue elements normally present at that site. The most common tissue sources are blood vessels and nerves.

Hamartomas differ from choristomas, which are benign tumours arising from tissues that are not normally present at that site.

Vascular

Capillary/cavernous haemangioma Benign tumours composed of either capillaries or larger vessels occur in early childhood. Their clinical appearances are quite distinct and biopsy is rarely indicated. They have a tendency to regress although surgical intervention may be required if there is visual obscuration. See Chapter 5 in haemangiomas of the orbit for a histological description.

Lymphangioma This tumour is formed by dilated lymphatics which contain pink staining lymph. Inspissation leads to compression of the thin-walled lymphatic channels which rupture and induce bleeding and inflammation. This explains the slow enlargement of these hamartomas.

Neural: neurofibroma

Neural tumours are described in Chapter 5.

Malignant

Malignant soft tissue tumours of the eyelid are rare (for example rhabdomyosarcoma) and are identical to those described in Chapter 5.

Lacrimal drainage system

Infections

Dacryocystitis

Inflammation of the lacrimal sac may be acute or chronic. The patient presents with a painful swelling in the medial canthus. Depending on the patency of the canaliculi, the swelling may be reducible with purulent discharge through the puncti. The aetiology is most commonly secondary to a nasolacrimal duct obstruction with stasis of drainage. In extreme forms, this condition may progress to an orbital cellulitis. Treatment is initially medical with antibiotics to contain the infection, although recurrent or chronic cases may require surgery (dacryocystorhinostomy) during which part of the wall of the lacrimal sac should be sent for histological examination. Numerous Gram positive and Gram negative bacterial pathogens have been isolated from extruded material, with the most common being

Staphylococcus aureus.

Macroscopic examination of a part of or the whole of an inflamed lacrimal sac reveals a thickened wall and purulent or mucoid material in the lumen (Figure 2.65). On histological examination thickening of the wall is due to lymphocytic infiltration with follicle formation in the submucosa. Purulent exudate in the lumen is responsible for necrosis of the epithelium (Figure 2.66), which also undergoes squamous metaplasia due to chronic irritation (Figure 2.67).

Mucocoele

If chronic inflammation is controlled, a lacrimal sac enlarges due to mucous secretion by the goblet cells in the epithelium.

Dacryolith

Hard stone-like structures may form within the lumen of an inflamed lacrimal sac or canaliculus – so called “dacryolith”. These structures are usually formed by inspissated mucous and clumps of bacteria (Figure 2.68, left), but occasionally a foreign body such as a lash may be identified (Figure 2.68, right).

Canaliculitis

Inflammation of the canalicular system is less common than dacryocystitis. Epiphora with surrounding mucopurulent conjunctivitis are the usual clinical features. The canalicular area is inflamed and the associated punctum may be pouting or shut.

Actinomyces israelii is the most commonly identified pathogen. Firm gritty concretions are often evident which present as small yellow “sulphur granules” (Figure 2.69). Histology reveals clumps of fine branching fungal filaments within inflammatory tissue and mucous (Figures 2.69, 2.70).

Numerous other pathogens have been described, including bacterial (for example Proprionibacterium proprionicum), fungal (for example Candida sp., Aspergillus sp.), and viral (HSV/HZV). Canaliculitis may also result from spread of infection from a pre-existing dacryocystitis.

Tumours

Carcinomas of the lacrimal sac are extremely rare, and in some reported series papillomas were not identified. A pre-existing chronic dacryocystitis may complicate the diagnosis. Carcinomas present clinically with a hard mass in the medial canthus with epiphora in the late stage. The tears may be blood stained. Advanced cases may involve the nasopharynx.

The tumours can be papillary (Figure 2.71) or solid. Squamous cell carcinomas can occur and the histology is identical to that described in the eyelid. Transitional carcinomas have an epithelial component consisting of columnar cells which resemble the normal epithelium of the sac (Figures 2.72, 2.73).

Lymphomas of the lacrimal sac have also been described.

Eyelid - Tumour

Sebaceous gland carcinoma - Intraepithelial spread

tumour cells

normal cells

Figure 2.64

Lacrimal drainage system - Chronic dacryocystitis

mucous

PMNLs

ulcer

lymphocytes and plasma cells

in submucosa thickened fibrous wall

Figure 2.66

Lacrimal drainage system - Chronic dacryocystitis / Dacryolith

eyelash

Figure 2.68

Lacrimal drainage system - Chronic dacryocystitis

mucopurulent material in lumen

thickened wall of lacrimal sac

Figure 2.65

PMNLs

columnar stratified epithelium with goblet cells

diffuse lymphocytic infiltrate

mantle zone

lymphoid follicle

germinal centre

Lacrimal drainage system - Dacryocystitis

Figure 2.67

Figure 2.64 An immunohistochemical marker for the cytokeratins (MNF116) present in the epidermis and adnexal structures stains malignant sebaceous gland cells infiltrating the conjunctival epithelium. In another case, tissue from the conjunctiva in intraepithelial spread was frozen and stained for lipid (inset). This technique clearly identifies the lipid within tumour cells (Oil red O stain).

Figure 2.65 A patient with chronic dacryocystitis complained of a persistent large swelling of the medial canthus and epiphora. A dacryocystorhinostomy was performed in which intraoperatively an enlarged thickened sac was removed. When the specimen was divided, the lumen contained mucous and purulent material and the sac wall was thickened.

Figure 2.66 Low power illustration of chronic dacryocystitis reveals pus and mucous in the lumen and a dense chronic inflammatory infiltrate in the submucosa. Focal ulceration is a common feature. PMNLs polymorphonuclear leucocytes.

Figure 2.67 In some specimens, the chronic lymphocytic reaction in the submucosa may develop lymphoid follicles with germinal centres and mantle zones. This example demonstrates metaplasia from the columnar ciliated epithelium (transitional) to squamous epithelium due to chronic irritation.

Figure 2.68 A female patient complained of epiphora but did not refrain from using mascara, hence the brown appearance of the dacryolith which was removed during dacryocystorhinostomy (left). As can be seen, a perfect cast of the lacrimal sac and part of the nasolacrimal duct was obtained! The dacryoliths extracted from the canaliculi (right) are much smaller (compare scales). In this example, a lash behaved as a nidus for inspissation of mucus.

Chronic canaliculitis /

Figure 2.69

Lacrimal drainage system - Lacrimal sac

Transitional cell carcinoma

nodular external surface

nodular projctions on cut surface

fibrovascular core

Figure 2.71

Lacrimal drainage system - Lacrimal sac

Transitional cell carcinoma

blood vessel

mitotic figures

columnar tumour cells

Lacrimal drainage system -

Chronic canaliculitis /

Actinomyces

Gram stain

Gram stain

Figure 2.70

Lacrimal drainage system - Lacrimal sac

Transitional cell carcinoma

cilia

Transitional papillary carcinoma

neoplastic columnar epithelial cells

fibrovascular core

Figure 2.72

Figure 2.69 Sulphur granules (inset) extruded from the canaliculus in a case of actinomyces infection have a granular surface. Even at low power, it is possible in an H&E stain and a Gram stain to identify clumps of actinomyces within inspissated mucous (see Figure 2.70).

Figure 2.70 Actinomyces appear as fine branching Gram positive filaments (upper). The morphology of the filaments is improved by a red counterstain (lower).

Figure 2.71 The papillary pattern of growth in a lacrimal sac tumour characterises a transitional cell carcinoma. The cut surface has a nodular appearance and each papillary projection has a central fibrovascular core.

Figure 2.72 In this papillary transitional cell carcinoma (lower), the tumour cells are elongated and have some resemblance to the overlapping nuclei seen in the columnar ciliated epithelium of the normal lacrimal sac (upper).

Figure 2.73 The cells in a poorly differentiated transitional cell carcinoma are elongated and, in this regard, resemble normal columnar epithelium, although there is marked variation in nuclear chromatin. In such tumours, the mitotic rate is high.