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

VI. Benign keratosis consists of a benign proliferation of epidermal cells, usually acanthotic in form, which does not fit into any known classification.

Precancerous Tumors of the Surface Epithelium

I.Leukoplakia—this is a clinical term that describes a white plaque but gives no information about the underlying cause or prognosis; the term should not be used in histopathology.

II.Xeroderma pigmentosum—see section Congenital Abnormalities earlier in this chapter.

III. Radiation dermatosis

A.The chronic e ects include atrophy of epidermis, dermal appendages, and noncapillary blood vessels; dilatation or telangiectasis of capillaries; and frequently hyperpigmentation.

B.Squamous cell carcinoma (most common), basal cell carcinoma, or mesenchymal sarcomas such as fibrosarcoma may develop years after skin irradiations (e.g.,

after radiation for retinoblastoma).

IV. Actinic keratosis (senile keratosis; solar keratosis) occurs as multiple lesions on areas of skin exposed to sun (Fig. 6.30; see Fig. 6.24).

A

C

A.Fair-skinned people are prone to development of multiple neoplasms, including solar keratosis and basal and squamous cell carcinomas.

B.The lesions tend to be minimally elevated, slightly scaly, and flesh-colored to pink, but present as a papilloma or as a projecting cutaneous horn.

A cutaneous horn (cornu cutaneum) is a descriptive clinical term. The lesion has many causes. Actinic keratosis frequently presents clinically as a cutaneous horn, but so may verruca vulgaris, seborrheic keratosis, IFK, squamous cell carcinoma (uncommonly), and even sebaceous gland carcinoma (rarely). Approximately 77% are associated with benign lesions at the base, 15% are premalignant, and 8% are associated with malignant lesions. The most common histopathologic benign diagnosis is seborrheic keratosis; premalignant, actinic keratosis; and malignant, squamous cell carcinoma.

C.Histologically, actinic keratosis is characterized by focal to confluent parakeratosis overlying an epidermis of variable thickness.

1.Both cellular atypia and mitotic figures appear in the deeper epidermal layers, which may form buds extending into the superficial dermis.

B

Fig. 6.30 Actinic keratosis. A, The clinical appearance of a lesion involving the left upper lid. B, Histologic section shows a papillomatous lesion that is above the skin surface, appears red, and has marked hyperkeratosis and acanthosis. C, Although the squamous layer of the skin is increased in thickness (acanthosis) and the basal layer shows atypical cells, the normal polarity of the epidermis is preserved.

Actinic keratosis may become quite pigmented and then mimic, both clinically and histopathologically, a primary melanocytic tumor.

Squamous cell carcinoma infrequently and basal cell carcinoma rarely may arise from actinic keratosis.

phocytes and some plasma cells.

Actinic keratosis may resemble squamous cell carcinoma or Bowen’s disease. It differs from the former in not being invasive and from the latter in not showing total replacement (loss of polarity) of the epidermis by atypical cells.

ing the treatment of malignant eyelid tumors supports complete surgical removal using histologic controls for verifying tumorfree surgical margins.

I.Basal cell carcinoma (Figs 6.31 and 6.32; see Fig. 6.24)

A.Over 500 000 new cases of skin cancer occur each year in the United States; at least 75% are basal cell carci-

noma. Approximately 16% are located on the eyelids, most commonly on the lower eyelids.

B.Basal cell carcinoma is by far the most common malignant tumor of the eyelids, occurring most frequently on the lower eyelid, followed by the inner canthus, the upper eyelid, and then the lateral canthus. It occurs most commonly in fair-skinned people on skin areas exposed to ultraviolet radiation (i.e., sun-exposed areas).

C.The neoplasm has no sex predilection, is found most often in whites, mainly in the seventh decade of life, and tends to be only locally invasive, almost never metastasizing.

The overproduction of sonic hedgehog, the ligand for PTC (tumor suppressor gene PATCHED) mimics loss of ptc function and induces basal cell carcinomas in mice; it may play a role in human tumorigenesis.

D.The clinical appearance varies greatly, but most present as a painless, shiny, waxy, indurated, firm, pearly nodule with a rolled border and fine telangiectases.

1.Ulceration and pigmentation may occur.

2.Rarely, metastases may occur.

E.Histologically and clinically, the tumor has considerable variation, but it can be grouped into three types: nodular, superficial, and morpheaform.

1.Nodular (garden-variety) type occurs most commonly (96%):

a.Small, moderate-sized, or large groups or nests of cells resembling basal cells show peripheral palisading.

1). Cells in the nests contain large, oval, or elongated nuclei and little cytoplasm, may be pleomorphic and atypical but tend to be fairly uniform, and may contain mitotic

figures.

2). The abnormal cells show continuity with the basal layer of surface epithelium.

b.The neoplasm may show surface ulceration, large areas of necrosis resulting in a cystic structure, areas of glandular formation, and squamous or sebaceous di erentiation (nodular basal cell carcinoma variants include keratotic, adenoidal, and pigmented).

Basal cell carcinomas with areas of squamous differentiation, even if quite large, behave clinically as a basal cell carcinoma, not as a squamous cell carcinoma. Thus, classifying them separately and calling them basal–squamous (basalosquamous) cell carcinomas serves no clinically useful purpose. Similarly, in lesions with mature sebaceous differentiation, there is no useful reason to call them sebaceous epitheliomas. Some basal cell carcinomas may be heavily pigmented from melanin deposition and clinically simulate malignant melanomas.

c.The surrounding and intervening invaded dermis

undergoes a characteristic pseudosarcomatous (resembling a sarcoma) change called desmoplasia (i.e., the fibroblasts become large, numerous, and often bizarre, and the mesenchymal tissue becomes mucinous, loose, and “juicy” in appearance).

The stromal desmoplastic reaction is typical of the basal cell neoplasm and helps differentiate the tumor from the similarly appearing adenoid cystic carcinoma

(see Fig. 14.37), which frequently has an amorphous, relatively acellular surrounding stroma.

d.Ductal and glandular di erentiation may occur in basal cell carcinoma. Such tumors are more

common on the eyelid, face, and scalp, and display the presence of ducts of varying size and glandular structures occasionally suggesting apocrine secretion.

e.There is a significantly increased prevalence and density of demodicosis in patents with eyelid basal cell carcinoma compared to control individuals, and may act as a triggering factor for carcinogenesis in individuals predisposed by trauma, irritation, or chronic inflammation.

f.Eyelid location is a predictive factor for extensive subclinical spread of basal cell carcinoma.

2.Superficial basal cell carcinoma shows irregular buds of basaloid cells arising from a unicentric focus or multicentric foci of the epidermal undersurface.

The superficial location makes this type the easiest to cure.

3.Morpheaform (fibrosing) type

a.Rather than growing in nests of cells with peripheral palisading, the neoplastic basaloid cells grow in thin, elongated strands or cords, often only one cell layer thick, closely resembling metastatic scirrhous carcinoma of the breast (“Indian file” pattern).

b.The stroma, rather than being juicy and loose

(desmoplastic), shows considerable proliferation of connective tissue into a dense fibrous stroma, reminiscent of scleroderma or morphea.

The tumor strands tend to shrink in processing, leaving surrounding retraction spaces.

c.In the morpheaform variant, it is di cult clinically to determine the limits of the lesion. The tumor tends to be much more aggressive, to invade much deeper into underlying tissue, and to recur more often than the nodular or superficial type.

4.Linear basal cell carcinoma has been proposed as a distinct clinical entity found along relaxing skin tension lines of the lower eyelid and cheek, characterized by increased subclinical extension and an aggressive tumor behavior.

The basal cell nevus syndrome (Gorlin’s syndrome), inherited in an autosomal-dominant fashion, consists of multiple basal cell carcinomas of the skin associated with defects in other tissues such as odontogenic cysts of the jaw, bifid rib, abnormalities of the vertebrae, and keratinizing pits on the palms and soles. Histologically, the skin tumors are indistinguishable from the noninherited form of basal cell carcinoma. The defective gene is in the tumor suppressor gene PATCHED, a gene on chromosome 9q.

II.Squamous cell skin carcinoma (Fig. 6.33; see Fig. 6.24)

A.Squamous cell carcinoma rarely involves the eyelid and is seen at least 40 times less frequently than eyelid basal cell carcinoma.

1.The most frequent sites of periocular involvement are the lower eyelid (49%), medial canthus (36%), and the upper eyelid (23%).

The opposite situation exists in the conjunctiva (see

p.245–247 in Chapter 7), where squamous cell carcinoma is the most common epithelial malignancy and basal cell carcinoma is the rarest.

B.From the 1960s to the 1980s, the incidence of squamous cell skin carcinoma increased 2.6 times in men and 3.1 times in women, attributed to presumed voluntary exposure to sunlight (ultraviolet radiation).

C.Intraepidermal squamous cell carcinoma (squamous cell carcinoma in situ)

1.When epidermal atypia becomes full-thickness, intraepidermal squamous cell carcinoma (carcinoma in situ) is present. It may arise de novo or from precancerous keratoses (e.g., actinic keratosis).

2.Clinically, the area is indurated and plaquelike.

3.Histologically, the lesion resembles the precancerous keratoses except for more advanced changes.

a.Carcinoma in situ is characterized by replacement of the epidermis by an atypical proliferation of keratinocytes showing loss of polarity, nuclear hyperchromatism and pleomorphism, cellular atypia, and mitotic figures. Better differentiation may be accompanied by the presence of “squamous pearls or dyskeratotic pearls” formed by clusters of abnormal gradually keratinizing atypical squamous cells.These structures must be di erentiated from “horn cysts” that are common in benign squamous lesions and consist of keratin-filled cysts that do not display the gradual keratinization commonly found in dyskeratotic pearls, or with the “squamous eddy” typical of IFK.

b.The overlying stratum corneum is parakeratotic.

D.Invasive squamous cell carcinoma

1.Carcinoma in situ may remain fairly stationary or enlarge slowly and invade the dermis (i.e., invasive squamous cell carcinoma).

2.Histologically, if the intraepidermal squamous cell carcinoma penetrates through the epidermal basement membrane and invades the dermis, the lesion is classified as invasive squamous cell carcinoma.

The supporting dermal stroma then undergoes a proliferative, desmoplastic, pseudosarcomatous reaction.

Human papillomavirus (HPV) type 16 viral DNA has been found in a recurrent squamous cell carcinoma of the lid.

3.Squamous cell skin carcinomas less than 2 mm thick (approximately 50% of total) almost never metastasize (“no-risk carcinomas”); of those

A

C

between 2 and 6 mm thick (moderate di erentiation and invasion not extending beyond the subcutis), approximately 4.5% metastasize (“low-risk carcinomas”); and of those over 6 mm thick, especially with infiltration of the musculature, perichondrium, or periosteum, approximately 15% metastasize (“high-risk carcinomas”).

a.The rate of regional lymph node metastasis in patients with eyelid or periocular squamous cell carcinoma may be as high as 24%. Sentinel lymph node biopsy may be helpful in the evaluation of conjunctival and eyelid malignancies. Preoperative lymphoscintigraphy facilitates identifying sentinel lymph nodes.

b.Overexpression of cluster of di erentiation 44 variant 6 is correlated with the progress and metastasis of ocular squamous cell carcinoma and is associated with proliferating cell nuclear antigen labeling index.

c.Perineural invasion is an adverse prognostic finding. Cutaneous squamous cell carcinoma may show perineural spread of the neoplasm through the orbit. They may also metastasize to regional lymph nodes in about 24% of patients.

4.Squamous cell carcinoma needs to be di erentiated from pseudocarcinomatous (pseudoepithelioma-

B

Fig. 6.33 Squamous cell carcinoma. A, The patient had an ulcerated lesion of the lateral aspect of the eyelids that increased in size over many months. B, Histologic section of the excisional biopsy shows epithelial cells with an overall pink color that infiltrate the dermis deeply. The overlying region is ulcerated. C, Increased magnification shows the invasive squamous neoplastic cells making keratin (pearls) in an abnormal location (dyskeratosis). Numerous mitotic figures are present. Note the pseudosarcomatous (dysplastic) change in the surrounding stroma.

tous) hyperplasia, which shows minimal or absent individual cell keratinization and nuclear atypia (see Fig. 6.28).

E.Bowen’s disease (intraepidermal squamous cell carcinoma, Bowen type)

1.Bowen’s disease is a clinicopathologic entity that consists of an indolent, solitary (or multiple), erythematous, sharply demarcated, scaly patch. It grows slowly in a superficial, centrifugal manner, forming irregular, serpiginous borders.

The lesions may remain relatively stationary for up to 30 years.

2.Bowen’s disease is associated with other skin tumors, both malignant and premalignant, in up to 50% of patients, and with an internal cancer in up to 80% of patients.

Arsenic concentration in Bowen’s disease lesions is high and may even cause them. Recently, the relationship of Bowen’s disease to internal cancer has been questioned; the final word has yet to be written.

3.Rarely, Bowen’s disease may invade the underlying dermis, and then it behaves like an invasive squamous cell carcinoma.

4.Histologically, the lesion is characterized by a loss of polarity of the epidermis so that the normal epidermal cells are replaced by atypical, sometimes vacuolated or multinucleated, haphazardly arranged cells not infrequently showing dyskeratosis and mitotic figures that are often bizarre.

The basal cell layer is intact, and the underlying dermis is not invaded.

Histologically, the clinicopathologic entity of Bowen’s disease and intraepidermal squamous cell carcinoma unrelated to Bowen’s disease (see earlier) cannot be distinguished. Bowen’s disease is not a histopathologic diagnosis but rather a clinicopathologic one.

F.Adenoacanthoma, a rare tumor, may represent a pseudoglandular (tubular and alveolar formations in the tumor) form of squamous cell carcinoma, or it may be an independent neoplasm.

T ehprognosis is somewhat more favorable than for the usual squamous cell carcinoma.

Clear cell acanthoma (Degos’ acanthoma) is a benign, solitary, well-circumscribed, noninvasive neoplasm. Histologically, there is a proliferation of glycogen-rich, clear, large epidermal cells.

Tumors of the Epidermal Appendages (Adnexal

Skin Structures)

Benign adnexal tumors include apocrine or eccrine hydrocystoma

(80%), pilomatrixoma (5%), syringoma (5%), trichilemmoma

(5%), syringocystadenoma papilliferum (2%), trichoepithelioma

1%, and trichofolliculoma (1%).

I.Tumors of, or resembling, sebaceous glands

A.Congenital sebaceous gland hyperplasia (organoid nevus syndrome, nevus sebaceus of Jadassohn, congenital sebaceous gland hamartoma)

1.Congenital sebaceous gland hyperplasia consists of a single, hairless patch, usually on the face or scalp, that usually reaches its full size at puberty.

2.The tumor seems to be a developmental error, resulting in a localized hyperplasia of sebaceous glands frequently associated with numerous imperfectly developed hair follicles and occasionally apocrine glands.

T ehtumor can be considered hamartomatous.

Epibulbar choristoma and conjunctival choristomas, choroidal colobomas, macro optic discs, and focal yellow discoloration in the fundus may occur in the nevus sebaceus of Jadassohn. Linear nevus sebaceus syndrome consists of nevus sebaceus of Jadassohn, seizures, and mental retardation.

3.Histologically, a group or groups of mature sebaceous gland lobules, with or without hair follicles, and frequently with underlying apocrine glands, are

present just under the epidermis, along with overlying papillomatosis.

Basal cell carcinoma may develop in up to 20% of the lesions, and more rarely other tumors may develop (e.g., syringocystadenoma papilliferum and sebaceous carcinoma). Moreover, syringocystadenoma papilliferum may mimic basal cell carcinoma clinically.

B.Acquired sebaceous gland hyperplasia (senile sebaceous gland hyperplasia, senile sebaceous nevi, adenomatoid sebaceous gland hyperplasia)

1.Acquired sebaceous gland hyperplasia consists of one or more small, elevated, soft, yellowish, slightly umbilicated nodules occurring on the face (especially the forehead) in the elderly.

2.Histologically, a greatly enlarged sebaceous gland is composed of numerous lobules grouped around a central large sebaceous duct.

Sebaceous gland hyperplasia may follow chronic dermatitis, especially acne rosacea and rhinophyma.

C.Adenoma sebaceum of Pringle (angiofibromas of face;

Fig. 6.34)

1.The small, reddish, smooth papules seen on the

nasolabial folds, on the cheeks, and on the chin in people with tuberous sclerosis (see p. 34 in Chapter

2)have been called adenoma sebaceum (Pringle) but are truly angiofibromas.

A

B

Fig. 6.34 Adenoma sebaceum of Pringle in tuberous sclerosis.

A, Clinical appearance. B, Dermal capillary dilatation and fibrosis are typical components of the lesion (i.e., angiofibroma).

2.Histologically, the sebaceous glands are usually atrophic.

Dilated capillaries and fibrosis are seen in the smaller lesions, whereas capillary dilatation is minimal or absent in the larger lesions, where markedly sclerotic collagen is arranged in thick concentric layers around atrophic hair follicles.

D.Sebaceous adenoma

1.Although rare, it has a predilection for the eyebrow and eyelid and appears as a single, firm, yellowish nodule.

The presence of a solitary sebaceous gland lesion (mainly adenoma) may be associated with a visceral malignancy, primarily of the gastrointestinal tract (Muir–Torre syndrome). Both clear-cut benign sebaceous and transitional squamosebaceous neoplasms should be considered as possible manifestations of the syndrome. Multiple sebaceous adenomas and extraocular sebaceous carcinoma have been reported in a patient with multiple sclerosis.

2.Histologically, the irregularly shaped lobules are composed of three types of cells.

a.Generative or undi erentiated cells

These are identical in appearance to the cells present at the periphery of normal sebaceous glands. Their presence allows the diagnosis to be made.

b.Mature sebaceous cells

c.Transitional cells between the preceding two types

E.Sebaceous gland carcinoma (Fig. 6.35; see Fig. 6.4B)

1.Sebaceous gland carcinoma is more common in middle-aged women, has a predilection for the eyelids, and arises mainly from the meibomian glands but also from the glands of Zeis.

a.It is the most common eyelid malignancy after basal cell carcinoma

b.In descending order of frequency, it a ects the upper lid (two to three times more often than the lower), the lower lid, the caruncle, then the brow.

2.Clinically, a sebaceous gland carcinoma is often

mistaken for a chalazion. The lesion, however, may mimic many conditions, and is called the great masquerader.

Any recurrent chalazion should be considered for histologic study, and any chronic, recalcitrant, atypical blepharitis or atypical unilateral papillary conjunctivitis should be considered for biopsy.

3.The mortality rate is approximately 22%.

Treatment by Mohs micrographic surgery may significantly reduce the mortality.

4.Histologically, irregular lobular masses of cells resemble sebaceous adenoma but tend to be more bizarre and to show distinct invasiveness.

Mutational inactivation of p53 may be involved in the progression of sebaceous carcinoma.

a.Focally, cells show abundant cytoplasm signifying sebaceous di erentiation.

b.Fat stains of frozen sections of fixed tissue show that many of the cells are lipid-positive.

c.The malignant epithelial cells may invade the

epidermis, producing an overlying change resembling Paget’s disease called pagetoid change.

Intraepithelial sebaceous carcinoma (pagetoid change) can spread to the conjunctiva and cornea. Resultant diffuse loss of lashes may simulate a blepharitis. Rarely, intraepithelial sebaceous carcinoma may be the only evidence of the lesion with no underlying invasion present. The intraepithelial invasion may involve the lids and conjunctiva together, or only the conjunctiva and cornea.

II.Tumors of or resembling hair follicles

A.Trichoepithelioma (epithelioma adenoides cysticum, benign cystic epithelioma)

Trichoepithelioma is probably a special variety of trichoblastoma, characterized by its almost universal facial location, its dermal rather than subcutaneous location, its mainly cribriform pattern, and its compartmentalized clefts between fibroepithelial units. Trichoblastoma, a benign tumor of hair germ cells (follicular germinative cells), includes the entities panfolliculoma, trichoblastoma with advanced follicular differentiation, immature trichoepithelioma, and trichoepithelioma.

1.The tumor may occur as a single nodule (Fig. 6.36), as a few isolated nodules, or as multiple symmetric nodules with onset at puberty. It occurs predominantly on the face and is inherited as an autosomaldominant trait (Brooke’s tumor).

2.The nodule is small and rosy yellow or glistening

flesh-colored, and tends to grow to several millimeters or even to 1 cm.

3.Histologically, multiple squamous cell cysts (i.e., horn cysts, consisting of a keratinized center surrounded by basaloid cells) are the characteristic finding and represent immature hair structures.

a.Basaloid cells, indistinguishable from the cells that constitute basal cell carcinoma, are present around the horn cysts and in the surrounding tissue as a lacework or as solid islands.

b.Occasionally the cysts have openings to the skin surface and resemble abortive hair follicles.

c.The cysts may rupture, inducing granulomatous inflammation, or they may become calcified.

E

The horn cyst shows complete and abrupt keratinization, thereby distinguishing it from the horn pearl of squamous cell carcinoma, which shows incomplete and gradual keratinization.

B.Trichofolliculoma

1.Trichofolliculoma is found in adults and consists of a small, solitary lesion frequently with a central pore.

Trichoadenoma, a rare benign cutaneous tumor, resembles trichofolliculoma, but the cells appear less mature; conversely, the cells appear more mature than the cells in trichoepithelioma.

2.Histologically, a large dermal cystic space lined by squamous epithelium and containing keratin and hair shaft fragments is surrounded by smaller, welldi erentiated, secondary hair follicles.

C

C.Trichilemmoma (Fig. 6.37)

1.It tends to be a solitary, asymptomatic lesion located on the face and mainly found in middle-aged people. The lesion has no sex predilection.

2.Characteristically, trichilemmoma often shows a central pore that contains a tuft of wool-like hair.

Patients who have multiple (not solitary) facial trichilemmomas may have Cowden’s disease (multiple hamartoma syndrome), an autosomal-dominant disease characterized by multiple trichilemmomas, acral keratoses, occasional Merkel cell carcinoma, oral papillomas, goiter, hypothy-

roidism, ovarian cysts, uterine leiomyomas, oral and gastrointestinal polyps, and breast disease.

3.Histologically, a central cystic space represents an enlarged hair follicle.

a.A lobular acanthosis of glycogen-rich cells is oriented about hair follicles.

b.The edge of the lesion usually shows a palisade of columnar cells that resemble the outer root sheath of a hair follicle and rest on a well-formed basement membrane.

4.Desmoplastic trichilemmoma may simulate a verruca, follicular keratosis, or a basal cell carcinoma. It is characterized by the presence of central desmoplasia, outer root sheath di erentiation of the tumor cells, and CD34 positivity. These features help di erentiate it from basal cell carcinoma.

D.Trichilemmal carcinoma

1.Trichilemmal carcinoma is a rare tumor that arises from the hair sheath, mainly on the face or ears of the elderly. Actinic damage, long-term low-dose irradiation, and transformation from benign trichilemmoma have been postulated as possible pathogenetic mechanisms.

2.Histologically, it is composed of follicular-oriented, lobular sheets of atypical, clear, glycogen-contain- ing cells resembling the outer root sheath of a hair follicle.

3.Malignant proliferating trichilemmal tumor of the eyelid has ben reported. It was characterized by proliferation of outer hair sheath epithelium with multiple central areas of trichilemmal keratinization.

E.Calcifying epithelioma of Malherbe (pilomatricoma; see earlier section Benign Cystic Lesions)

F.Adnexal carcinoma—the term adnexal carcinoma should be restricted to those tumors that are histologically

identical to basal cell carcinoma but in which the site of origin (e.g., epidermis, hair follicle, sweat gland, sebaceous gland) cannot be determined.

III.Tumors of or resembling sweat glands: Apocrine sweat glands are represented in the eyelids by Moll’s glands; eccrine sweat glands are present in the lids both at the lid margin and in the dermis over the surface of the eyelid.

A. Syringoma (Fig. 6.38)

1.Syringoma is a common, benign, adenomatous tumor of the eccrine sweat structure occurring mainly in young women and consisting of small, soft papules, usually only 1 or 2 mm in size, found predominantly on the lower eyelids. It probably arises from intraepidermal eccrine ducts.

Rarely, malignant syringoma (well-differentiated eccrine carcinoma) may occur on the eyelid.

2.Histologically, dermal epithelial strands of small basophilic cells are characteristic, as are cystic ducts lined by a double layer of flattened epithelial cells and containing a colloidal material. The ducts often have comma-like tails that give them the appearance of tadpoles.

A

cs

cs

cs

cs

C

e

t

t

t

B

Fig. 6.38 Syringoma. A, Clinical appearance of lesions just below and nasal to seborrheic keratosis of left lower lid (same patient as in Fig. 6.26). B, Histologic section shows that the dermis contains proliferated eccrine sweat gland structures that form epithelial strands and cystic spaces (e, surface epithelium; t, tumor “ducts” and epithelial strands). C, Increased magnification demonstrates epithelial strands and cystic spaces lined by a double-layered epithelium (cs).