72–74 Extensive involvement of squamous cell carcinoma. 72: Invasion of the orbit with squamous cell carcinoma which is also present as three lesions on the forehead.This patient died of his disease within the year. 73:This 40-year-old male had had a ‘basal cell carcinoma’ removed by Mohs surgery. He complained about an enlarging mass in the area of tumor removal but was told by his ophthalmologist that this was just scar tissue and not to worry. Note the fullness in the area of the lower lid as it joins the medial canthus.This was very thickened, firm tissue. It was obviously some sort of tumor. 74:The tumor, which was actually a squamous cell carcinoma, was removed with frozen section evaluation of the margins.There was

invasion of the medial 72 orbit. An exenteration

was required. Within the year there were metastases to the lymph nodes.The patient was lost to follow-up.

73

74

Adenocanthoma 25

KERATOACANTHOMA

In the first edition of this textbook, keratoacanthoma was described as ‘a benign lesion which clinically resembles a squamous cell carcinoma’. In the recent past it has been reclassified as squamous cell carcinoma – keratoacanthoma type33. It is characterized by rapid growth, but after 6–8 weeks it usually reaches a maximum size of 1–2 cm (0.4–0.8 in). Clinically, the lesions are raised, dome-shaped tumors with distinct borders and a central keratin core. The tumors usually occur in Caucasians in the fifth, sixth, or seventh decade. However, in a study done in Hawaii, the incidence in ethnic Japanese was 22 per 100,000. This compared to 104 cases per 100,000 in the white population (59–61).33

Complete excision is the treatment of choice. If the tumor is removed before it becomes too large, less tissue destruction occurs, and the reconstruction is usually simpler and yields better cosmetic and functional results. Recurrences of keratoacanthomas occasionally occur, and, in some cases, these tumors have a somewhat aggressive behavior. Other modalities of treatment, such as radiation therapy and cryotherapy, have also been used successfully to treat keratoacanthoma.34

ADENOCANTHOMA

An unusual variance of squamous cell carcinoma is the adenoid squamous cell carcinoma (adenocanthoma). This tumor often occurs in actinically damaged skin and is characterized by the formation of gland-like structures. The tumor usually occurs in middle-aged and elderly persons with fair complexions. Clinically, adenoid squamous cell carcinoma has no distinct features and may resemble keratoacanthoma, basal cell carcinoma, or squamous cell carcinoma.36

A case study of a patient with AIDS and squamous cell carcinoma suggested to the authors that human papilloma virus might play a role in the cause of squamous cell carcinoma.37

TREATMENT

As with basal cell carcinoma, the cure rate for squamous cell carcinoma is best with surgical excision using microscopic control. In one retrospective study, no recurrences were found if frozen section control was used during the initial tumor removal.38 However, treatment by radiation therapy showed a control rate of 95%.25 In a study using cryotherapy, one recurrence was found among patients followed for five years, but the authors felt that this sample was not sufficiently large to give statistically meaningful results.20

COMMENT

Since eyelid squamous cell carcinoma behaves much like basal cell carcinoma, the best control rate is obtained with surgery using microscopic evaluation of the margins. If surgery is not indicated for various reasons, radiation therapy would be the next treatment of choice.

26 Malignant Tumors

SEBACEOUS GLAND CARCINOMA

Sebaceous gland carcinoma may arise from the glands of Zeis, the sebaceous glands associated with the hair follicles on the skin of the eyelid, the meibomian glands, the sebaceous glands located in the caruncle, or the sebaceous glands of the eyebrow. The incidence as reported by western authors is approximately 1% of malignant eyelid tumors.35, 39 However, in a report from Korea, the incidence is different. Sebaceous cell carcinoma was reported as 42.2%, basal cell carcinoma as 36.8%, and squamous cell carcinoma as 10.5%.7 In a retrospective study of 88 sebaceous carcinomas, two arose in the eyebrow, eight arose in the caruncle, and 78 arose in the eyelid. The majority of eyelid tumors were present on the upper lid, but a significant number were also present in the lower lid.34

The average age of the appearance of sebaceous cell carcinoma is 61 years, but the tumor can occur as early as the second decade. There seems to be no sex or race predilection.34, 40

Sebaceous cell carcinoma usually presents as an enlarging mass, and there is often a history of previous incision and drainage of a chalazion. When a chalazion does not heal with repeated surgical treatments, a biopsy is usually taken, and the diagnosis of meibomian cell carcinoma can then be made. Whether these are examples of a sebaceous cell carcinoma arising in a previous chalazion,41 or whether the proper diagnosis was consistently missed since the chalazion material was not sent for pathological evaluation, is a moot point.

These tumors may also present as eyelid inflammation, and the initial diagnosis is often overlooked as the patient is treated for meibomianitis or a blepharoconjunctivitis. On rare occasions, this tumor may present as a lacrimal gland tumor,42 or it may clinically appear to be a basal cell carcinoma (75–82).43

The sebaceous cell carcinoma can be aggressive with orbital extension or systemic metastasis. In a series of sebaceous cell carcinomas collected at the Armed Forces

75

Institute of Pathology, orbital invasion occurred in 17% of 88 patients, and lymph node metastasis developed in 8% of 74 patients with follow-up information. Ten patients (13.5%) died with probable or proved metastasis.34

Metastasis of sebaceous cell carcinoma is usually along the path of lymphatic drainage. The most frequently involved nodes are the preauricular and the submaxillary, but the entire cervical chain may contain metastatic tumor.44 Spread to other organs, including lungs, brain, liver, pericardium, and bone may occur.34

Rao et al.40 performed a clinical pathological study on 95 cases of sebaceous cell carcinoma. Included in this study were correlations between various variables and mortality rates. No mortalities occurred in tumors which presented in the lower lid. However, there was a 27% mortality with tumors of the upper lid and a 14% mortality with tumors of the caruncle.

The degree of sebaceous differentiation was determined and tumors were classified as well differentiated, moderately differentiated, and poorly differentiated. Well differentiated tumors had a mortality of 7%, the moderately differentiated tumors had a mortality of 29%, and the poorly differentiated tumors showed a 60% mortality. The tumors were also divided into degrees of infiltration. Those tumors with high infiltration had a 40% mortality rate compared to a 10% mortality rate in tumors with minimal infiltration.

Two types of intraepithelial carcinomatous changes were observed. One resembled the intraepithelial spread of Paget’s carcinoma of the breast into the nipple and into the surrounding areola and skin (Paget’s disease of the breast); the other was more diffuse and resembled a primary in situ carcinoma such as Bowen’s disease of the skin. There was a 41% mortality in those tumors exhibiting an intraepithelial change, and only an 11% mortality where this change was not observed.

The invasion pattern was also correlated with mortality. There was a 100% mortality in those patients in which the tumor invaded the vascular system. In those patients with lymphatic invasion there was an 83% mortality, and in patients with orbital invasion there was a 70% mortality. If

76

75 Sebaceous cell carcinoma.The medial aspect of the right lower lid is somewhat enlarged.The patient presented with a biopsy diagnosis of basal cell carcinoma.The entire tumor was removed, and the pathological diagnosis was sebaceous cell carcinoma.

76 Sebaceous cell carcinoma presenting as a slowly enlarging mass in the medial aspect of the left lower lid.This had been clinically diagnosed as a chalazion and was treated medically for about six months.

77 Small sebaceous cell carcinoma in the center of the left lower lid.

Note that this lesion is not too different in appearance from the lesions in 39 and 67.

78 Sebaceous cell carcinoma presenting as a papillomatous lesion of the left caruncle in a 90-year-old male.

79 Sebaceous cell carcinoma of the left upper lid in an 82-year-old female.

80 Sebaceous cell carcinoma in an 85-year-old female who had an incision and drainage for a chalazion in the left upper lid on two occasions in the year prior to this photo.The third chalazion treatment included a biopsy which showed the tumor to be a sebaceous cell carcinoma.

81 Sebaceous cell carcinoma presenting as conjunctivitis. A 70-year-old male with redness of the bulbar and tarsal conjunctiva. He had conjunctival contraction of the lower lid. A mucous membrane graft was planned to increase his lower fornix. A routine biopsy at surgery showed a sebaceous cell carcinoma.

82 Sebaceous cell carcinoma. Elderly woman with a two-year history of an eyelid growth.The tumor was on the lid and the eye beneath was normal.

28 Malignant Tumors

none of these three types of invasion was present, there was a 16% mortality.

Etiological factors associated with sebaceous cell carcinoma are essentially unknown. However, two patients are reported in which tumors occurred after radiation therapy for retinoblastoma.34

Pathological diagnosis of sebaceous cell carcinoma can sometimes be confusing. It is important that the pathologist be made aware that sebaceous cell carcinoma is being considered as a diagnosis. The oil-red-O stain for fat is helpful in making the diagnosis. In one report, the conclusion was that a panel of commonly available antibodies may help distinguish among periorbital sebaceous, basal, and squamous cell carcinomas. These antibodies included anti-EMA, BRST-1, and Cam5.2.45 Others also found that antibody staining could distinguish sebaceous cell carcinoma from other eyelid neoplasms.46 The author has personally seen two cases of sebaceous cell carcinoma referred with a pathological diagnosis of squamous cell carcinoma. A third case, which actually had pagetoid spread of carcinoma along the tarsal conjunctival surface, had a histological diagnosis of chronic inflammation.

In the study by Rao et al.(1978), sebaceous cell carcinoma was mistakenly diagnosed by contributing pathologists in 39 of the 95 cases studied. The three most common incorrect diagnoses were squamous carcinoma, adenocarcinoma, and basal cell carcinoma.40

TREATMENT

The best treatment for eyelid margin tumors is complete surgical excision with 5–6 mm (0.2 in) or more of normal tissue on all sides. Frozen section evaluation of the margins should also be employed in combination with wide surgical excision when treating sebaceous cell carcinoma, since it is often difficult to delineate the tumor margins by macroscopic inspection. In a series of 11 patients, there was only one recurrence using this technique.47 If pagetoid spread occurs on the bulbar conjunctiva, then exenteration is the treatment of choice. If there is some pagetoid spread on the tarsal conjunctiva, wide excision may be used, but careful follow-up is necessary. Reconstruction can then be done at the time of tumor removal (306–309).

Some authors recommend exenteration for eyelid lesions measuring 2 cm (0.8 in) or more that have been present for at least six months.48

Once the diagnosis of sebaceous cell carcinoma is made, a metastatic work-up should be performed. If there appears to be any tumor along the lymphatic drainage system, a neck dissection is then indicated.

Radiation therapy is considered significantly less effective than complete surgical excision. Patients treated with radiation therapy have a four-year mortality of 78% compared with a four-year mortality of 33% in patients with simple tumor excision. In those patients treated with wide excision, the mortality was 7%.40 Other reports have also cautioned against radiation therapy because of the recurrence following this type of treatment.49 However, a report of two patients followed for 39 and 46 months showed no recurrences after radiation therapy. The authors concluded that >55 Gy of radiation dose when given appropriately is a curative treatment for eyelid sebaceous cell carcinoma. They suggested it as an alternative for patients not desiring surgery.50

LYMPHOMA

Lymphomatous infiltrates which affect the eye and ocular adnexa usually appear in the orbit or the subconjunctival area. However, occasionally these infiltrates affect the eyelid tissues. The degree of malignancy varies from lymphoid hyperplasia to malignant lymphoma. The diagnosis of various stages of malignancy is based on histological evaluation of the tissues, and in some cases, the immunological classification of the B cells or T cells which are present in a lymphocytic infiltrate.

The subconjunctival lymphocytic infiltrate has the appearance of a salmon-colored, fleshy mass, hence, the description ‘salmon patch’ (83). When the tumor is in the eyelid and not subconjunctival, it may be smooth, firm, and beige in color.

Polymorphic B-cell lymphoma of the eyelid, usually occurring in immunologically deficient patients, presents as a thickened, necrotic palpebral conjunctiva with ulceration involving the external surface of the lid and complete loss of lashes.51 Lymphoma of the eyelid can also present as unilateral ptosis or thickening in the upper or lower lid.(84–88). Patients might be sent for cosmetic eyelid surgery to remove the ‘bags’ in the lids. These patients actually have lymphomatous infiltrates. A unilateral eyelid fullness may be excess orbital fat on one side but the diagnosis of lymphoma should be entertained.

In a patient with chronic lymphocytic leukemia, a lacrimal sac swelling with epiphora was actually lymphoma of the lacrimal sac (84).

Lymphomatous infiltrates which present in the ocular adnexa may be associated with lymphoma in other parts of the body. Therefore, once the diagnosis of eyelid lymphoma is made, the patient should have proper staging for other evidence of lymphomatous infiltration.

TREATMENT

If no other areas of infiltration are found, the appropriate treatment is radiation therapy. Oncologists may choose to treat with chemotherapy or a combination of radiation and chemotherapy.

COMMENT

It should be emphasized that what is pathologically diagnosed as benign lymphoid hyperplasia may convert to malignant lymphoma at a later date. For this reason, lymphoid hyperplasia should be very carefully evaluated and, perhaps, treated with radiation therapy.

83 Malignant lymphoma presenting as a ‘salmon patch’ under the bulbar conjunctiva of the left eye.

84 Malignant lymphoma.The patient presented with a swelling in the area of the left lacrimal sac. Surgical exploration revealed malignant lymphoma in the lacrimal sac.