Diagnosis of Malignant and Benign Lid Lesions Made Easy


  • 11.1

  • 11.2

  • 11.3

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Periocular skin lesions are commonly seen in practice. It is easy to get lost in this chapter, so read this introduction carefully. It gives you an overview of the information in the whole chapter. The main goal of the evaluation of a lid lesion is to rule out malignancy. The most common skin malignancy is basal cell carcinoma. Because basal cell carcinoma causes more than 90% of skin cancers, it is essential for you to confidently diagnose it. The easy way to diagnose basal cell carcinoma is to learn the characteristics of epithelial cell malignancy:

  • Ulceration

  • Lack of tenderness

  • Induration

  • Irregular borders and asymmetric shape

  • Telangiectasia

  • Pearly borders

  • Loss of lid margin architecture

We talk about these features in detail, so don’t memorize them now. If these features of malignancy are present, a biopsy should be performed to rule out malignancy. If none of these characteristics of malignancy are present, it is highly unlikely that the lesion is malignant. Once you have excluded malignancy, the important part of the evaluation is over. Spend time understanding these characteristics of malignancy rather than trying to learn the names of all the benign lesions that may occur. Get a picture in your mind of what these lesions look like. Don’t lose sight of the forest while trying to learn all the trees. Eventually, you will be able to name the majority of benign lesions, as well.

The skin has two layers, the epidermis and the dermis . Basal cell and squamous cell carcinomas arise from the epidermis. The dermis contains the skin appendages , or adnexa (the added-on features). The adnexa include hair follicles, oil (sebaceous) glands, and sweat glands. The most common adnexal malignancy is sebaceous cell carcinoma. This malignancy does not have a characteristic appearance. Sometimes a yellow pigmentation of sebaceous cell carcinoma may be noted. A chronic unilateral blepharoconjunctivitis or an eyelid margin lesion extending from the posterior lamella onto the skin should suggest a possible diagnosis of sebaceous cell carcinoma.

Pigment cells are found at the base of the epidermis. Pigment cell malignancy, or melanoma , is unusual in the periocular area, but may occur. We describe the characteristics of pigmented lesions that should make you suspect melanoma.

After you are familiar with the characteristics of epithelial cell malignancies—basal cell and squamous cell carcinomas—you are not likely to miss a cutaneous malignancy. Although any adnexal malignancy (almost always sebaceous cell carcinoma) is rare, you should keep the diagnosis in mind. All the other lesions are benign. Eventually, you can recognize the names of all the benign epithelial, adnexal, and melanocytic skin lesions (known as Aunt Minnies).

Let’s talk about the Aunt Minnies. How do you recognize your aunts and uncles at a family reunion? How do you tell your Aunt Minnie from your Aunt Blanche from your Aunt Muriel? They all look different and you have seen them many times before. We take this daily form of pattern recognition for granted. It is no different for lid lesions. After you see a lesion and learn its name, you will eventually be able to recognize it again. We discuss this concept further later in this chapter.

The last section of the chapter deals with biopsy techniques, including both incisional biopsy (removing a portion of a tumor) and excisional biopsy (removing an entire tumor). Three important techniques are the shave biopsy, punch biopsy, and cyst marsupialization. These techniques are discussed in detail.

Skin Anatomy

Layers of the Skin

The eyelid skin is the thinnest skin in the body. This skin contains two layers:

  • Epidermis

  • Dermis

The epidermis is the continually dividing superficial layer of the skin that covers the body. The dermis is the deep layer of the skin. Other than in the eyelid, there is a layer of subcutaneous fat deep to the dermis ( Figure 11.1 ). The eyelid skin is tightly bound to the underlying orbicularis muscle.

Figure 11.1

The skin and appendages. ( A ) The layers of the skin. ( B ) The adnexa of the skin.

Cells destined to become the surface of the skin start as undifferentiated basal cells along the junction of the epidermis and dermis. As these epidermal cells differentiate and move toward the skin surface, they lose their nuclei, flatten, and become keratinized. The most common skin malignancy, basal cell carcinoma, arises from these undifferentiated cells in the basal layer. Because these cells are not producing keratin, basal cell carcinomas do not have excessive keratin production, or hyperkeratosis, as part of their clinical picture. In contrast, squamous cell carcinoma arises from more superficial epidermal skin cells, known as squamous cells, which produce keratin. Consequently, squamous cell carcinoma is associated with hyperkeratosis.

Appendages of the Skin

The dermis contains the skin appendages or adnexa (see Figure 11.1 ). The adnexa are the specialized tissues added on to the skin, including:

  • Sebaceous glands

  • Sweat glands

  • Hair

Each adnexal tissue contains specialized cells that may create either solid or cystic cell proliferations. Common tumors arising from the adnexa include chalazia and various cysts. Chalazia arise from the specialized sebaceous glands of the tarsal plate, the meibomian glands. The most common cyst in the periocular area, the apocrine hidrocystoma, arises from the apocrine sweat glands along the lid margin. We talk about this later. For now, just remember that there can be solid and cystic tumors of each adnexal tissue.

The dermis also contains a number of other tissues, including vascular, fibrous, and neural elements. Each of these tissues may give rise to tumors that are rarely seen in the eyelids. You are not likely to see many of these lesions, so they are not covered in this text ( Box 11.1 ).

Box 11.1

Eyelid Adnexa

Sebaceous glands

  • Meibomian glands of the tarsal plate

  • Zeis glands associated with the eyelash follicle

  • Tiny sebaceous glands associated with vellus hairs (thin hairs covering the skin)

  • Sebaceous glands associated with the eyebrow hairs

  • Sebaceous glands in the caruncle

Sweat glands

  • Eccrine glands (present over the entire surface of the eyelid)

  • Apocrine glands (the glands of Moll associated with eyelash follicles)


  • Eyelashes

  • Vellus hairs of the skin

  • Eyebrow hairs

Malignant Tumors of the Epidermis

Characteristics of Malignancy

This is the most important section of this chapter. Remember that the main goal of evaluating a lid lesion is to rule out malignancy. The most common skin malignancy is basal cell carcinoma, which arises from the epidermis. Basal cell carcinoma represents more than 90% of lid malignancies. If you can recognize basal cell carcinoma, you can recognize the majority of skin cancers affecting the eyelids. Review the characteristics of skin malignancy listed in Box 11.2 . If you remember these characteristics, you will have little difficulty in diagnosing cutaneous malignancies.

Box 11.2

Characteristics of Skin Malignancy

  • Ulceration: Malignant lesions tend to ulcerate; benign lesions don’t ulcerate.

  • Lack of tenderness: Malignant lesions are not painful or tender to touch.

  • Induration: Malignant lesions tend to be firm.

  • Irregularity: Malignant lesions have irregular borders and asymmetric shapes.

  • Loss of lid margin architecture: Malignancies tend to destroy normal anatomic features.

  • Telangiectasia: Focal telangiectasias on the periphery of a tumor suggest malignancy.

  • Pearly borders: Rolled translucent margins that are whitish in appearance are characteristic of basal cell carcinoma.


Ulceration is commonly seen in malignant tumors of the epidermis. Malignant cells grow rapidly, tending to outgrow their blood supply, causing areas of central ulceration. Despite areas of ulceration, often associated with bleeding, malignant lesions do not tend to be painful, nor are they tender to touch. Think of this in terms of the bowel tumors that you saw in medical school. Despite the tumor being very large and irregular, often with areas of necrosis, the patient had no pain from the tumor itself. Pain only developed when the tumor caused another problem such as a bowel obstruction or perforation. Tumor necrosis or ulceration of normal tissues results in the common symptom of blood in the stool.


All malignancies, including skin cancers, tend to be firm or indurated, so palpate each skin lesion (remember the firm bowel tumor). Benign lesions such as cysts and other epithelial lesions feel soft, similar to the surrounding skin. Again, in medical school we learned the importance of palpation in the breast, rectal, and prostate examinations.


Malignant tumors are composed of cell populations that grow at different rates. These varying growth patterns create lesions with irregular margins and asymmetric shapes. The margins of malignant lesions tend to be scalloped. Benign lesions tend to have smooth borders. Irregular borders make the shape of the lesion asymmetric so that it is not easy to imagine folding the lesion in half on itself. Look at any skin markings on your own body. Likely they are round and symmetric.

Pearly Borders and Telangiectasia

Pearly borders and telangiectasias are pathognomonic for basal cell carcinoma. Heaped-up edges often surround an area of central ulceration. With the slit beam focused on the edge of these lesions, there appears to be a translucency to the lesion (pearly borders). Likely, this appearance arises from the proliferating cells in the basal layer of the epidermis showing through the more superficial layers of the epidermis. Telangiectasias are the dilated and irregular vessels accompanying the pearly margins of the basal cell carcinoma. Review the photographs of typical basal cell carcinomas and make sure in your mind that you recognize all the features of epithelial cell malignancy ( Figure 11.2 ).

Figure 11.2

Typical examples of basal cell carcinoma. ( A ) Note the classic features—pearly margins and telangiectasias—in this small nodular basal cell carcinoma on the upper eyelid margin. ( B ) Pearly margins and an irregular shape are prominent in this basal cell carcinoma. Note the central ulceration and loss of the lid margin architecture. ( C ) This basal cell carcinoma is pearly white and has typical telangiectasias. Note the indurated thickening of the lid margin. The eyelashes are gone (madarosis), and the lid margin is altered. The tumor margins are not distinct in this example. ( D ) A more nodular basal cell carcinoma with distinct pearly margins, telangiectasias, and central ulceration. ( E ) Nodular basal cell carcinoma with crusting over central ulceration. ( F ) The most obvious feature of this basal cell carcinoma is ulceration. ( G ) Lower eyelid margin destruction. Punctum is ectropic. Note pearly margins and telangiectasia. ( H ) Upper eyelid margin destruction with obvious eyelash loss. Pearly margins and ulceration are present. ( I and J ) Morpheaform subtype of basal cell carcinoma. This type of basal cell carcinoma has less apparent clinical margins. These require a larger excision than you would expect! The telangiectasias in ( I ) and thickening of the skin strongly suggest a basal cell carcinoma and should prompt a biopsy. The sclerosing changes in ( J ) pulling the eyelids away from the eye suggest a biopsy. The defect after excision of these diffuse lesions may be large.

All the characteristics of malignancy are not always seen in each tumor. When one or more characteristics of malignancy exist, consider a biopsy. Look at the photos in Figure 11.2 and see how many of the features of malignancy are likely present in each example. Study these pictures carefully so you won’t miss a basal cell carcinoma. Hone your diagnostic skills and identify the subtype. Keep in mind that morpheaform lesions are not always so obvious. If you see an area of “inflammation” that does not improve with time or treatment, consider a biopsy. (You see an example in the dermatitis section in this chapter). Until you get experience, you might want to refer the patients with morpheaform lesions (see Figure 11.2I and J ). Excision is surprisingly large.

Loss of Eyelid Margin Architecture

A skin malignancy may destroy the normal architecture of the lid margin. Often the tumor outgrows its blood supply, leading to ulceration and subsequent destruction of surrounding tissue. This characteristic destruction of tissues does not occur with benign lesions. Suspect malignancy when an area of lash loss or lid margin destruction is present. Remember, the goal is to diagnose malignancy. When your diagnostic skills become more sophisticated, you may be able to tell the type of skin cancer based on the location and how the lesion affects the lid margin. Study the skin carefully during the slit lamp examination. Use the slit lamp as the equivalent of the gynecologist’s colposcope used to diagnose potential malignancies of the cervix. Remember that squamous cell carcinoma tends to be the most superficial of skin cancers. These tumors may present with only scaling of the superficial epidermis in the early phases. Basal cell carcinoma begins a little deeper with rolled edges at the periphery pulling normal skin into the lesion. You do not see keratinization on the examination. Because basal cell and squamous cell carcinomas are epithelial lesions, they affect the anterior lamella initially. Sebaceous cell carcinoma affects the posterior lamella first in most patients. Look at the area of distortion or destruction of the lid margin for these clues to the type of malignancy. Don’t lose sight of the goal, which is learning to differentiate malignant from benign lesions first.

Basal Cell Carcinoma

Basal cell carcinoma, like squamous cell carcinoma, is related to ultraviolet or actinic damage. Consequently, basal cell carcinoma is most common in fair-skinned patients whose skin tends to burn rather than tan in the sun. The lower lid and medial canthus are the most commonly affected locations, probably related to getting more sun exposure than the upper lid. The hallmarks of basal cell carcinoma are pearly borders with telangiectasia. Central ulceration is common. The lesions are not painful and not tender to touch. The border and contour of the lesion are generally irregular. Destruction of normal lid architecture occurs when the lesion involves the lid margin. Lashes are often lost. Hyperkeratosis is not a common finding associated with basal cell carcinoma, because these tumors arise from cells in the basal layer of the epidermis.

Basal cell carcinoma and squamous cell carcinoma may be recognized by the company that they keep. Other signs of actinic damage to the skin, especially in a patient with light skin and blue eyes, should heighten your suspicion of a skin malignancy. Look for signs of sun damage on your patient’s face to help you diagnose basal cell carcinoma ( Figure 11.3 ). Don’t forget to look at the entire face. A patient presenting with ectropion, ptosis, or any other eyelid problem may have a basal cell carcinoma elsewhere on the face ( Figure 11.4 )!

Figure 11.3

( A ) Basal cell carcinoma with diffuse margins. Note light irises and weathered skin on cheek. ( B ) Large defect after excision.

Figure 11.4

Don’t forget to examine the entire face for suspicious lesions. This nasal basal cell was diagnosed in a patient who came in for an unrelated eyelid ectropion.

A rare genetic disorder, basal cell nevus syndrome, predisposes patients to multiple basal cell carcinomas. This autosomal dominant syndrome is also known as Gorlin syndrome. Multiple organ systems are involved aside from the skin, including the nervous, endocrine, and skeletal systems. Patients have palmar and plantar pits (tiny depressions), intracranial calcification, ovarian fibromas, jaw cysts, rib and vertebral abnormalities, and a typical facies with frontal bossing and a prominent jaw.

The genetic defect has been located on chromosome 9q involving a mutation on the PTCH ( PATCHED ) gene. Patients should be identified as early as possible and have frequent skin examinations. The lesions typically occur on the face, chest, and back. Basal cell carcinoma may occur in areas not exposed to the sun, including at the base of the skin pits on the palms and soles of the feet.

In about 10% of cases, no skin lesions develop. At the other extreme, literally thousands of basal cell carcinomas may occur. In these cases, the basal cell carcinomas can grow to be almost continuous on the facial skin. Lesions are removed as early as possible. Over time, only the worst lesions are excised because complete eradication is impossible.

This disorder is rare, but you should consider it in any young patient (adolescent or young adult) with basal cell carcinoma or in patients with multiple lesions and a strong family history.

Vismodegib is a relatively new treatment for advanced basal cell carcinoma. More than 90% of basal cell carcinomas have a mutation that causes activation of the hedgehog pathway, which is crucial for embryonic development but normally has limited activity in adult tissues. Vismodegib is an oral medication that specifically blocks the hedgehog pathway, inhibiting the growth of these cancers. The effect of treatment dissipates if the medication is stopped, however. There are many side effects of the treatment that can limit its use; however, it can be an alternative to exenteration or other radical excisions ( Figure 11.5 ). Vismodegib has no effect on squamous cell carcinoma, melanoma, or sebaceous cell carcinoma.

Figure 11.5

Advanced basal cell carcinoma treated with vismodegib. ( A ) Indurated ulcerated lesion with total ptosis. ( B ) After a few months of treatment the lesion is much smaller. Other skin lesions have cleared up. ( C ) After 9 months of treatment the surface ulceration has healed. The eyelid is scarred closed. The many other lesions on his face have cleared up. Hair loss and some malaise have resulted as side effects of the ongoing treatment.

Squamous Cell Carcinoma

Squamous cell carcinoma may resemble basal cell carcinoma clinically. Although differentiating between these two lesions may not always be clinically possible, there should be little doubt about the presence of an epithelial malignancy based on the characteristics outlined above. Squamous cell carcinoma is much less common than basal cell carcinoma, representing less than 5% of lid tumors. If you have to guess the diagnosis, you should guess basal cell carcinoma because it is so much more common.

Squamous cell carcinoma can appear as a nodule or an indurated plaque with some hyperkeratosis ( Figure 11.6 ). Often the scaly skin falls off, strongly suggesting a squamous cell cancer or its precursor, actinic keratosis (discussed later in this chapter). Ulceration is sometimes present. Generally, the pearly margins and telangiectasias of basal cell carcinoma are not seen.

Figure 11.6

Squamous cell carcinoma. A malignancy is obvious in this indurated mass. The hyperkeratosis should suggest a squamous cell carcinoma, which was confirmed on biopsy.

Squamous cell carcinoma is usually more aggressive than basal cell carcinoma. The margins of squamous cell carcinoma may be diffuse, resulting in a large area of subclinical tumor involvement ( Figure 11.7 ). Neurotrophic spread (along nerves) occurs in squamous cell carcinoma but is uncommon in basal cell carcinoma ( Figure 11.8 ). Squamous cell carcinoma in the periocular area with the presence of cranial nerve palsy suggests neurotrophic spread into the cavernous sinus ( Figure 11.9 ).

Figure 11.7

Squamous cell carcinoma. You should be thinking malignancy because of the tissue destruction, bleeding, and induration. Hyperkeratosis suggests squamous cell carcinoma. Notice how far the thickened skin extends laterally beyond the more obvious lesion.

Figure 11.8

Recurrent squamous cell carcinoma. Note the large size, diffuse margins, and hyperkeratinization. This lesion was considered unresectable because of the size and degree of neurotrophic spread. The patient underwent a course of radiation therapy.

Figure 11.9

Intracranial neurotrophic spread of squamous cell carcinoma. ( A ) Elderly man with a complete ptosis of left upper eyelid. He has had several squamous cell cancers removed from his forehead. ( B ) He has a complete third nerve palsy, meaning both the upper and lower divisions of cranial nerve III are likely infiltrated with tumor. ( C ) Coronal CT scan showing a large orbital mass, presumably within the supraorbital nerve. ( D ) Coronal CT scan showing an enlarged cavernous sinus. The tumor is unresectable. ( E ) Intraoperative incisional biopsy of mass through a vertical eyelid split anterior orbitotomy. You can see the cut ends of the eyelid margins. The mass is the dark area inferior to the rim. The diagnosis of squamous cell carcinoma was confirmed. The patient was treated with proton beam radiation with no progression over 2 years.

Like basal cell carcinoma, squamous cell carcinoma arises in sun-damaged skin. The features of cutaneous actinic damage, such as deep wrinkles, skin thinning, generalized telangiectasias, and mottled pigmentation, may be seen (see Figure 11.24 later in the chapter). Scaling keratotic lesions and actinic keratoses, the precursors of squamous cell carcinoma, are often present.


Keratoacanthoma is considered to be a low-grade squamous cell carcinoma. This tumor has a characteristic appearance different than that of most squamous cell carcinomas. A large lesion with a central crater filled with a keratin plug is typical. The lesion often appears in a few weeks and may spontaneously resolve. This lesion is discussed in the section Sun-Damaged Skin and Related Conditions. An illustration of this is shown in Figure 11.26 .

Malignant tumors of the dermis are very rare and are not considered here. The dermis contains the adnexa of the periocular skin. Sebaceous cell carcinoma is the most common adnexal malignancy and is discussed next.

Malignant Tumors of the Adnexa: Sebaceous Cell Carcinoma

Sebaceous Glands in the Periocular Area

Basal cell and squamous cell carcinomas comprise greater than 90% of the malignancies of the eyelids. Sebaceous cell carcinoma is rare, representing between 1% and 5% of eyelid cancers in the Western world. Sebaceous cell carcinoma arises within the sebaceous glands of the skin and therefore is referred to as an adnexal malignancy. As a reminder, the sebaceous glands in the periocular area are the following:

  • Meibomian glands located within the tarsal plates

  • Glands of Zeis associated with the eyelash follicles

  • Sebaceous glands of the periocular skin

  • Sebaceous glands in the caruncle

  • Sebaceous glands associated with eyebrow follicles

The presence of specialized sebaceous glands in the periocular area, such as the meibomian glands and glands of Zeis, makes the occurrence of sebaceous cell carcinoma in the periocular area more common than anywhere else in the body.

Clinical Characteristics

Sebaceous cell carcinoma has no characteristic appearance; consequently, it is known as a masquerader. You won’t see many sebaceous cell cancers. I have included some representative case photos here. Be especially suspicious if you see a unilateral blepharoconjunctivitis or a chronic or recurrent “chalazion.” In my experience, the classic recurrent chalazion is an unusual presentation. An erythematous or thickened eyelid with conjunctivitis is more common ( Figure 11.10A ). The blepharoconjunctivitis may present as a chronic condition (see Figure 11.10B ). In some patients, many medical or surgical treatments will have been tried without relief, because the diagnosis of sebaceous cell carcinoma will not have been considered.

Figure 11.10

Sebaceous cell carcinoma. ( A ) The most common presentation is a subtle thickening of the lid margin. These lesions often have a yellowish hue. This is seen in thin lines along the eyelid margin, giving a tigroid appearance to the thickened tissue. ( B ) Advanced sebaceous cell carcinoma presenting as an advanced unilateral chronic blepharoconjunctivitis. Remember blepharitis is a bilateral disorder. Any unilateral blepharitis should have a biopsy.

Biopsy should be performed for chronic unilateral blepharoconjunctivitis or recurrent chalazia. In some cases, the conjunctival spread predominates, so don’t forget to evert the eyelid. In other patients, sebaceous cell carcinoma may present as a subtler thickening of the lid and lid margin (see Figure 11.10 ). You should consider the diagnosis if you see a lid margin lesion that appears to arise from or extend over the margin onto the tarsal conjunctiva (see Figure 11.10 ). The presence of any yellowish material within a malignant-appearing lesion should suggest the diagnosis of sebaceous cell carcinoma.

Again, in my experience, the notion that a sebaceous cell carcinoma can resemble a chalazion is unlikely. Figure 11.11C and D has photos of the only case of sebaceous cell carcinoma that I have seen that might be mistaken for a chalazion, and it was easily distinguished from an inflammatory lesion on clinical examination. Nevertheless, to be safe, you should send a specimen of any atypical or recurrent chalazion for pathologic examination. Obvious pagetoid spread is not common in my experience ( Figure 11.12 ). I do map biopsies on every patient to rule out conjunctival spread. You need to palpate the neck and preauricular areas for any palpable nodes. The use of the sentinel node biopsy technique for the evaluation of sebaceous cell carcinoma is controversial.

Figure 11.11

Sebaceous cell carcinoma. ( A ) Ulcerated lesion at eyelid margin. You should be thinking basal cell carcinoma, but the yellowish hue and extension onto the back of the tarsus suggest a sebaceous cell carcinoma, proven on the incisional biopsy. Conjunctival biopsies were performed showing no pagetoid spread beyond clinical tumor. Pentagonal wedge is the starting point for excision of the sebaceous cell carcinoma, guided by permanent-section analysis. ( B ) More advanced ulceration. Again, your first thought is malignancy. This case needs a biopsy. Always be thinking basal cell carcinoma, but this lesion has some yellowish color and seems to involve the posterior lamella more than usual. ( C ) An eyelid mass. At first glance, this could be a chalazion, but the lesion is indurated and irregular. There is no recent history of eyelid swelling or tenderness. ( D ) Eversion of the eyelid in ( C ); a mass originates from the tarsus. There should be no confusion about the fact that this is not a chalazion. This patient needs a biopsy, either a punch biopsy of the posterior lamella or a wedge resection. At some point, map biopsies of the conjunctiva and definitive treatment are necessary.

Figure 11.12

Advanced sebaceous cell carcinoma with eyelid thickening and obvious pagetoid spread. This patient requires an orbital exenteration.

Biopsy Technique

Full-thickness lid biopsy has been recommended for the diagnosis of sebaceous cell carcinoma. When there is diffuse thickening of the lid with no obvious mass, it is a good idea to do a full-thickness lid biopsy. A full-thickness specimen gives the pathologist an opportunity to see the architecture of both affected and normal lid tissues, including the conjunctival epithelium. If a large mass is present, a generous incisional biopsy of the mass itself is usually diagnostic and a full-thickness biopsy is not necessary. Small biopsies of the conjunctiva alone may be difficult to interpret. Oil red-O stain on fresh tissue was recommended for the diagnosis of sebaceous cell carcinoma in the past. Although oil red-O does stain the sebaceous material within the tumor, the histologic and cytologic features of the tumor (including the typical foamy cytoplasm seen in the dysplastic sebaceous cells) are diagnostic in most cases without this staining. The histopathologic differentiation between more poorly differentiated sebaceous cell and squamous cell carcinomas can be difficult. Immunohistochemistry can be helpful in this regard.

Remember that sebaceous cell carcinomas are rare tumors. If you suspect a sebaceous cell carcinoma, be sure to let the pathologist know. General and dermatologic pathologists see few, if any, of them. When there is any question about the diagnosis of a sebaceous cell carcinoma, consultation with an ophthalmic pathologist is appropriate. He or she is likely to have the most experience and should be able to provide the most accurate diagnosis.

The presence of a sebaceous gland should raise the possibility of Muir–Torre syndrome. Although it is a rare syndrome, the diagnosis of an eyelid sebaceous neoplasm may be its first manifestation. Muir-Torre syndrome is an autosomal dominant disease associated with multiple keratoacanthomas and visceral malignancies, especially genitourinary and gastrointestinal ones. Tumors of the breast and lung are associated, but less commonly seen. The genetic markers of the syndrome include a mutational inactivation of mismatch repair genes MSH2 and MLH1 , MSH6 and PMS2 . Immunohistochemistry of the eyelid tumor showing staining for these markers can point to a diagnosis of the syndrome. Several cases of Muir–Torre syndrome of the eyelids have been reported with both benign and malignant sebaceous carcinomas, although I have not personally seen this in 40 cases of sebaceous cell carcinoma.

Unusual Growth Characteristics

Sebaceous cell carcinoma has two unusual growth characteristics that make removal difficult. The first is pagetoid spread. Intraepithelial sebaceous cell carcinoma may spread superficially over large areas of the conjunctiva. Secondly, sebaceous cell carcinoma appears to arise from multifocal noncontiguous tumor origins. These characteristics make excision of sebaceous cell carcinoma more complicated than that of the more common cutaneous malignancies. Basal cell and squamous cell carcinomas arise from a single origin and tend to spread radially. Clinical margins can be approximated and then confirmed with frozen sections. With sebaceous cell carcinoma, the true pathologic margins are often not clinically visible, even with slit lamp examination, because of the pagetoid spread. Noncontiguous tumor origins make intraoperative margin confirmation of tumor removal unreliable, because the surgical margin may be free of tumor, but another focus of tumor may be just beyond the first margin.

Most sebaceous cell carcinomas originate in the meibomian glands or Zeis glands. Beyond the two unusual growth characteristics described above, remember that sebaceous cell carcinoma can arise in the caruncle, eyelid skin, or lash follicles (from pilosebaceous glands), making the diagnosis even easier to miss.

Tumor Excision

For these reasons, the excision of sebaceous cell carcinoma is somewhat specialized. Preoperatively, map biopsies of the conjunctiva are done to determine the probable peripheral extent of any pagetoid spread. From the results of these permanent section biopsies, a surgical excision is planned. I take several biopsies from the skin surrounding the known lesion to use as scout biopsies for the excision to be performed later. I also take a few biopsies well away from the tumor to check to see if I might be missing an area of pagetoid disease. As you can imagine, this is not a foolproof technique.

At the time of excision, generous margins are taken to include the involved areas of the tarsus, lid margin, skin, and conjunctiva. There is some controversy about the usefulness of frozen sections in sebaceous cell carcinoma; pagetoid spread may be difficult to identify using this technique because of poor resolution and tissue artefacts of freezing. Permanent sections can be evaluated overnight to determine if margins are clear of tumor. This is somewhat tedious. These procedures must be started early in the week to permit further resection if necessary prior to reconstruction. There is controversy about the effectiveness of Mohs excision for sebaceous cell carcinoma because frozen-section analysis is involved in the standard Mohs surgery. A “slow Mohs” excision can be performed where the Mohs surgeon uses permanent-section analysis rather than the frozen-section technique. This is generally how my cases are currently handled.

The defect is then reconstructed using the usual techniques of repair. Because sebaceous cell carcinoma often involves the upper lid, reconstruction is often complicated. In cases where areas of pagetoid spread remain after the majority of tumor has been removed, treatment with mitomycin C can be used. These cases are at risk for severe exposure problems as a result of the often large conjunctival excision and the toxicity of the mitomycin C.

Sebaceous cell carcinoma is an uncommon tumor. It is difficult to diagnose because of its many manifestations. It is difficult to excise because of pagetoid spread and noncontiguous tumor origins. Unlike with basal cell carcinoma and squamous cell carcinoma, there is a possibility of regional lymph node metastasis ( Figure 11.13 ). In most patients, no regional disease is present at the time of diagnosis. Fortunately, local resection is usually curative. If all four lids are involved or orbital fat is invaded, orbital exenteration is required (see Figure 16.21, Figure 16.22, Figure 16.23 ). Death caused by sebaceous cell carcinoma is possible, but rare.

Figure 11.13

An unusually aggressive sebaceous cell carcinoma. ( A ) A large mass of tumor is seen in the superior fornix originating from the upper lid tarsus. ( B ) Regional and in-transit lymphatic metastases were present. Despite orbital exenteration, neck dissection, and radiation therapy, the patient died a few months after diagnosis.

Owing to the difficulties involving adequate resection and the complexity of repair, the occasional eyelid surgeon should refer these patients for more specialized care.

Benign lesions arising in the sebaceous glands include chalazia, sebaceous hyperplasia, and sebaceous adenoma. These lesions are discussed later in the chapter.


  • At this point in this chapter, you should be able to diagnose the majority of the malignant lid lesions encountered in practice.

  • The diagnosis of most cutaneous malignancies is based on recognition of the clinical characteristics of malignancy that help you identify basal cell carcinoma and squamous cell carcinoma.

  • Important! What are the clinical characteristics of skin malignancy?

  • What growth characteristics make sebaceous cell carcinoma difficult to resect?

  • Chronic unilateral conjunctivitis or a presumed chalazion resistant to treatment should alert you to the possible diagnosis of sebaceous cell carcinoma.

Pigmented Lesions: Ruling Out Melanoma

General Concepts

Although eyelid melanomas are rare, we are all concerned about the possibility of a pigmented lesion being a melanoma. This section helps you to differentiate benign from malignant pigmented lesions of the skin. Let’s start with these basic concepts ( Box 11.3 ).

  • The majority of pigmented lesions are not melanoma.

  • Any type of skin lesion may be pigmented depending on the patient’s skin coloring.

  • Not all pigmented lesions are nevi ( Figure 11.14A ).

    Figure 11.14

    Pigmentation of skin lesions. ( A ) A pigmented nonpigment cell tumor: a seborrheic keratosis. ( B ) A nonpigmented pigment cell tumor: a compound nevus.

  • In fact, not all nevi are pigmented (we cover this later) (see Figure 11.14B ).

Box 11.3

Pigmented Skin Lesions: Concepts to Remember

  • Most pigmented lesions are not melanomas.

  • Any skin lesion may be pigmented.

  • Not all pigmented lesions are nevi.

  • Not all nevi are pigmented.

Characteristics of Benign Pigment Cell Tumors

Benign lesions grow in a controlled manner with the cell population under normal biologic controls. Features of benign pigmented lesions include:

  • Uniform color

  • Regular smooth borders

  • Symmetric shape

Small variations in color from light brown to brown are normal. In general, benign lesions appear to have smooth edges and a symmetric shape ( Figure 11.15 ).

Figure 11.15

A benign nevus. Note the uniform color, smooth border, and symmetric shape.

Characteristics of Malignant Pigment Cell Tumors: Melanoma

Because many of the pigmented lesions seen on the face are not of pigment cell origin, the characteristics of epidermal malignancy emphasized earlier should be applied to any pigmented lesion. These serve as a starting point for diagnosing malignancy.

Several clinical features that should make you suspicious that a pigmented lesion is a melanoma are listed in Box 11.4 .

Box 11.4

Characteristics of Pigment Cell Malignancy: Melanoma

  • Recent onset of pigmented lesion

  • Change in existing pigmented lesion

  • Irregular margins

  • Asymmetric shape

  • Color change or presence of multiple colors

  • Large size greater than 6 mm in diameter

The recent onset of a pigmented lesion or a change in the color, shape, or size of any existing lesion suggests an uncontrolled pattern of growth. This may signal the start of melanoma. Pigmented lesions that have irregular margins also suggest uncontrolled growth. An asymmetric shape, such that the lesion cannot be folded on itself, suggests a diagnosis of melanoma ( Figure 11.16A ). Many melanomas have several colors within the lesion, ranging from a light white or tan to very dark black (see Figure 11.16B ). In between are shades of red and blue; hence, the term red, white, and blue sign as an indication of melanoma. Large pigmented lesions (>6 mm in diameter or the size of a traditional wooden pencil eraser) may be associated with melanoma. Strongly consider a biopsy for any pigmented tumor larger than 1 cm in diameter (see Figures 11.16 and 11.17 ). It is best to perform a punch biopsy for a suspected melanoma. This technique allows more accurate evaluation of the depth of the tumor (Breslow level).

Figure 11.16

Cutaneous melanoma. ( A and B ) Cutaneous melanoma showing irregular margins and asymmetric shape. The lesion on the right varies in thickness. ( C ) Pigmented lesion in the lower eyelid in a blue-eyed patient. ( D ) Darkly pigmented lesion, also melanoma. All of these lesions are lentigo maligna melanoma, arising from a benign area of pigmentation.

Figure 11.17

( A ) Most melanomas on the head and neck arise from lentigo maligna over time. This is a superficial melanoma, melanoma maligna melanoma in situ. You can see two biopsy sites. In many cases, the positive biopsy sites are in what appears as unpigmented tissue, resulting in a larger-than-expected defect after excision. ( B ) An ignored, large lentigo maligna melanoma. Notice the ulceration and variation in color, size, and thickness.

You rarely see a melanoma of the eyelid. You see many pigmented benign lesions. The challenge is to sort out all the normal lesions from the rare abnormal lesion. Learn to recognize what is normal and what doesn’t quite look right. This approach gives you the confidence that you are not missing one of these rare tumors. Pay close attention to the discussion above about pigmented lesions in general and the life cycle of nevi in particular. Next, if you have a clear idea about the warning signs of a melanoma (reread the last paragraph and review the photos of melanoma here), you won’t miss the rare atypical or malignant pigmented lesion. Look again at the melanoma images here. They are all arising from lentigo maligna, the most common type you see. It is easy to recognize the advanced cases. Study the first two images to recognize the irregular borders as well as the variation in pigmentation and thickness. Lentigo lesions transform over time from normal pigment—to atypia (lentigo maligna)—to lentigo melanoma maligna melanoma (in situ to deep). I have included photos of all these stages. Commonly one tumor shows all the transitions. Can you see over time how these lesions might progress to be like the advanced cases?

If you feel compelled to learn more about melanoma, read on. There are four forms of cutaneous melanoma:

  • Superficial spreading melanoma

  • Nodular melanoma

  • Lentigo maligna melanoma

  • Acral melanoma (palms and soles)

As I said, the most common type seen on the head and neck is the lentigo maligna form. This form appears in elderly patients and develops slowly over time. First a mottled pigmentation forms (lentigo). Over time, usually thought to be accelerated by sun exposure, some of the melanocytes become atypical (lentigo maligna). Clinically, portions of the lesion darken, and the pigmentation extends in area. The malignant degeneration proceeds slowly over time to become frank melanoma with areas of differing pigmentation, coloring, and pattern (lentigo maligna melanoma). Usually, the entire lesion is not frankly malignant; rather, different regions of the lesion have varied degrees of atypia and frank malignancy ( Figure 11.18 ). In some cases, the eyelid skin pigmentation extends onto the conjunctiva. The conjunctival version of lentigo when seen in isolation is known as primary acquired melanosis. The conjunctival lesion may undergo malignant degeneration as well (a progressive degeneration known as melanosis with atypia turning into melanoma; the histopathologic progression is described as primary acquired melanosis, primary acquired melanosis with atypia, and finally conjunctival melanoma).

Figure 11.18

Lentigo maligna and lentigo maligna melanoma. Malignant transformation of lentigo maligna to lentigo maligna melanoma. The dark raised areas have turned into malignancy. Note that the skin pigmentation has extended onto the conjunctiva, which should be biopsied as well.

Melanomas are treated by surgical excision with larger free margins than epithelial tumors. In years past, noneyelid cutaneous melanomas were treated with wide excision with margins ranging from 3 to 5 cm. Now, narrower margins are taken depending on the thickness of the melanoma (Breslow level). These margins range from 0.5 to 1 cm (melanoma in situ) to 2 cm (melanomas > 2 mm). Margins greater than 2 cm have not been associated with increased survival times in thicker tumors.

Because the eyelid skin is so thin, the prognostic factors and guidelines for the margin of resection related to the Breslow level do not apply precisely to eyelid cutaneous melanomas. Three options exist for excision. You may choose to excise the lesion with a reasonable margin and send it to your pathologist for permanent sections, re-excise if necessary, and resubmit and then reconstruct when the margins are clear. Secondly, you may send the patient to a Mohs surgeon who may choose to do a slow Mohs excision with permanent sections (as discussed for sebaceous cell carcinoma). Lastly, the Mohs surgeon may perform the excision utilizing immunohistochemical markers for melanoma antigens to facilitate reading the frozen sections. The immunohistochemical stain MART-1 effectively labels the melanocytes. If the stained tissue shows signs of melanoma, such as nests of atypical melanocytes, further resection is done. If no staining is seen, the resection is considered complete. Several studies (not involving eyelid melanomas) show comparable cure rates of cutaneous melanoma with Mohs resection compared with wide resection.

Don’t be surprised if the area of excision of a lentigo maligna or lentigo maligna melanoma is much greater than you anticipate. The areas of atypical cells usually extend well beyond the clinical margins. Like sebaceous cell carcinoma, these tumors should be referred to a specialist until you have sufficient experience to repair an unexpectedly large defect.

Benign Tumors of the Eyelid

Aunt Minnies: Pattern Recognition of Benign Skin Lesions

The majority of tumors in the periocular area are benign. Given the large number of tissues within the skin, you can imagine that there are a huge number of possible benign cell proliferations. Here is where you need to step back and get the big picture again. There are many benign proliferations arising from the epithelial tissues. Add to those the lesions arising from the tissues of the adnexal structures: the hair follicles and associated erector pili muscles, the various sebaceous glands in the periocular tissue including the meibomian, Zeis, and pilosebaceous glands, and the apocrine and eccrine sweat glands. Finally, add all the other tissues within the dermis: fibrous, vascular, and neural tissues. Each of these tissues can give rise to a benign periocular tumor. Fortunately, a relatively small number of tumors occur commonly. With time, you recognize them by their characteristic appearance.

You have already been introduced to the term Aunt Minnie . A medical school professor of mine called pulmonary lesions that were diagnosed by sight or pattern recognition on chest x-ray Aunt Minnies. Take a look at the Aunt Minnie in Figure 11.19 . This Aunt Minnie is a rare skin tumor known as a cylindroma; several tumors collectively form a turban tumor. Once you have seen a patient with cylindromas, you always recognize these lesions. You may not remember that these benign tumors are thought to arise from sweat glands and that the multiple form of cylindroma occurs as a familial disease, but you recognize that the tumor is benign (none of the characteristics of malignancy that we discussed are present). The diagnosis of cylindroma and the name turban tumor are easy to remember once you have seen this lesion.

Figure 11.19

Aunt Minnie pattern recognition of cylindroma, a type of sweat gland tumor, also known as a turban tumor.

(From Krachmer JH, Mannis MJ, Holland EJ, eds. Cornea and external disease: clinical diagnosis and management . St Louis: Mosby, 1997.)

The majority of benign lid lesions are like this. After you have seen one and learned to recognize it, you recognize others that look just like it. That is not to say that an understanding of the cell origin or the histopathology of the lesion is not important. But the most important point to understand is that the lesion is benign. Remember the big picture. This lesion has none of the clinical characteristics of malignancy that we have discussed. When you evaluate a patient with a lid lesion, first focus on whether the lesion is benign or malignant. After you have seen the common lesions several times, you learn the names.


  • When evaluating a lid lesion, determine if the clinical features suggest malignancy. If so, plan a biopsy. If none of the characteristics of malignancy are present, the lesion is probably benign.

  • What are the characteristics of malignant epidermal skin lesions?

  • What are the characteristics of the malignant pigment cell tumor, a melanoma?

  • For many lesions, you have sight or pattern recognition and know its Aunt Minnie name. For other lesions, you have to be content with just knowing that they are not malignant.

  • We discuss the Aunt Minnies of benign lid lesions that arise from the epithelium, adnexa, and pigment cells. Other more unusual lesions arising from vascular, fibrous, and neural elements are not discussed.

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Mar 21, 2021 | Posted by in OPHTHALMOLOGY | Comments Off on Diagnosis of Malignant and Benign Lid Lesions Made Easy

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