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We will consider specific clinical and histological features of the following tumors in this
|Squamous cell carcinoma|
|Microcystic adnexal carcinoma|
Selected references are given after each entity. An overall reference is: Schoelch SB, Barrett TL,
and Greenway HG: Recognition and Management of High-Risk Cutaneous Tumors. Dermatologic Clinics 1999;
17: 93 - 111.
Squamous Cell Carcinoma
Squamous cell carcinoma is the second most common form of skin cancer in Caucasians (Johnson).
Cutaneous SCCs are responsible for 2000 - 5000 deaths annually in the U.S. (Salasche). Most cutaneous
SCCs are at low risk for recurrence or metastasis, however a subset occurs which may be very aggressive.
The 5 year survival rate for metastatic SCC is only 25%. A primary goal therefore is to identify the
patient at risk for metastasis.
|Size greater than 2 cm|
Depth of invasion 4mm or greater
Ear or lip
Chronic ulcer, sinus tract, radiation, and scar
Aggressive histologic subtype:
Size and depth of invasion
Size and depth of invasion are the two most important prognostic factors. For all primary SCCs of the
skin, the long term (> 5 year) metastatic rate is 5.2%. Lesions larger than 2 cm have double the
local recurrence rate and three times the metastatic rate of lesions less than 2 cm (Johnson). Tumors
greater than 4mm in depth have a higher metastatic and recurrence rate than those less than 4 mm. In one
study, lesions with a depth of less than 4mm have a recurrence rate of 5.3% and a metastatic rate of 6.7%
while tumors with a depth of greater than or equal to 4mm have a recurrence rate of 17.2% and a
metastatic rate of 45.7% (Rowe). Additional studies may show depth to have similar significance in SCC
as it does in melanoma.
The ear and the lip are two sites consistently reported to have a higher risk of metastasis. Johnson
sites a metastatic incidence of 11% for the ear and 13.7% for the lip. According to Salasche, the upper
lip, the commissure and the pinna of the ear are especially dangerous locations. There are also reports
that the dorsum of the hand is a high risk site, however, data on this appears conflicting.
Tumors which enlarge visibly between diagnosis and treatment are especially dangerous. Rapidly
growing lesions on the ear and eyelid have three times the metastatic rate of slower growing SCCs.
Immunosuppressed patients are at risk to develop more SCCs and, once developed, their SCCs are more
aggressive. The usual SCC to BCC ratio changes from 1:4 to 1.2:1. According to Salasche, transplant
patients usually develop tumors 5 - 10 years after transplantation and the lesions tend to be multiple,
occurring in crops. The metastatic rate is 12.9% with a high percentage resulting in the death of the
There is often a latency of 20 - 30 years from development of the primary condition and the
occurrence of an SCC. However, according to Johnson, SCCs which arise in chronic ulcers or sinus tracts
have a metastatic rate of 18 - 31% while those arising in sites of radiation dermatitis have a 20 - 26%
metastatic rate. SCC arising in a scar is also reported to behave aggressively.
Poorly differentiated histology is seen in only 19.1% of all cutaneous SCC but accounts for 51% of all
metastasizing cutaneous SCCs (Johnson). These tumors have more than double the local recurrence rate and
almost three times the metastatic rate of well and moderately differentiated SCCs.
The most common SCC that we encounter in the skin is a SCC arising in an actinic keratosis. This
tumor is usually small and well differentiated and has a good prognosis. SCC's with acantholytic
(pseudoglandular) or cystic features are more aggressive than a typical SCC arising in an actinic
Recurrent tumors have a 25 - 45% metastatic rate depending on the site (Johnson). The overall
metastatic rate for recurrent SCC is 25%. When the recurrent site is the lip, the metastatic rate is
31.5% and when the recurrent site is the ear, the metastatic rate is 45%.
Evidence of perineural invasion on histologic examination has a severe prognosis. The incidence of
perineural invasion by SCCs is about 4%. Recurrent tumors are more likely to demonstrate perineural
invasion. Lesions with perineural invasion have a local recurrence rate of 47.2% and a metastatic rate
of 47.3% overall. In one study of 187 SCCs of the lower lip, 60% of the lesions with perineural
invasion metastasized. As with BCCs with perineural invasion, clearance of SCCs demonstrating perineural
invasion may require much larger surgical defects than expected from the clinical appearance of the
The peripheral branches of the trigeminal and facial nerves are particularly susceptible to invasion
by neurotropic SCC and lesions occurring in these areas should carry a high index of suspicion. Direct
intracranial extension may occur via these nerves. If perineural invasion is undetected during initial
treatment it may be several years before symptoms occur. Symptoms of perineural invasion include pain,
burning, anesthesia or paresthesia, and rarely facial paralysis.
With perineural invasion, the local recurrence rate for standard excision followed by radiation is
almost 50%. For perineural SCC treated with radiation therapy alone, one series reported an 80%
recurrence rate. Mohs surgery followed by radiation appears to be the treatment of choice. Using Mohs
followed by radiation therapy, a recurrence rate of 6% can be inferred from three studies involving a
total of 32 patients. However, the cases in these series were followed for less than 3 years.
Additional studies involving larger numbers of patients and longer follow-up periods are presently being
SCCs of low risk can be treated effectively by a number of modalities. Mohs surgery remains the
treatment of choice for high risk SCCs with a recurrence rate of 3% compared to 13 % for non-Mohs
modalities (Johnson). 75% of local recurrences and more than 80% of metastases occur within the first 2
years, therefore close followup of these patients is important.
Adjuvant radiation therapy in high risk SCC without evidence of nodal spread has not been well
defined. Radiation plus elective lymph node dissection is believed to be 95% effective in resolving
occult disease in the neck, however, there have been no randomized trials that show improved survival
Salasche, in his review of high risk cutaneous SCCs of the head and neck without evidence of nodal
spread, reported that elective treatment of the neck either by radiation alone or modified radical neck
dissection or both should be considered in patients with SCC with poorly differentiated histology,
perineural invasion, high risk location or immunocompromised status. A multidisciplinary approach is
clearly indicated in these individuals. SCC which has spread beyond the regional lymph nodes has a
particularly grim prognosis (Johnson).
- Barrett T, Greenway H, Massullo V, Carlson C: Treatment of Basal Cell Carcinoma and Squamous Carcinoma with Perineural Invasion. Advances in Dermatology, Vol 8, 1993, Mosby Yearbook Inc, St. Louis, MO.pp 277-305.
- Berg D, Otley CC: Skin Cancer in Organ Transplant Recipients: Epidemiology, Patholgenesis and Management. JAAD 2002; 47: 1 - 17.
- Cherpelis BS, Marcusen C, Lang PG: Prognostic Factors of Metastasis in Squamous Cell Carcinoma of the Skin. Derm Surg 2002; 28: 268 - 273.
- Johnson TM, et al.: Squamous cell carcinoma of the skin (excluding the lip and oral mucosa). JAAD 1992, 26: 467 - 484.
- Rowe DE, Carroll RJ, Day CL: Prognostic factors for local recurrence, metastasis and survival rates in SCC of the skin, ear and lip. JAAD 1992, 26: 976 - 990.
- Salasche S, Cheney M, Varuares M: Recognition and management of the high - risk cutaneous squamous cell carcinoma. Curr Probl Dermatol 1993, 5: 141 - 192.
Sebaceous carcinoma is an aggressive tumor derived from the adnexal epithelium of sebaceous glands.
The tumor occurs most commonly in older adults and is slightly more common in women. The Meibomian
glands of the upper eyelid are the most commonly affected site. The tumor may be difficult to diagnose
and is often misdiagnosed as a chalazion or chronic conjunctivitis. The tumor may occur in extraocular
sites where it has a more favorable prognosis than ocular sites. Mortality rates for ocular sites are 20
- 30 %(Dzubow), however the following features are associated with an even more unfavorable prognosis.
|Size greater than 1 cm|
Involvement of both upper and lower eyelids
Infiltrative growth pattern
Tumors larger than 1 cm are reported to have a greater mortality than smaller lesions. Tumors present
for greater than 6 months have a mortality of 38 % compared to 14 %.
Origin from the Meibomian glands and glands of Zeis have the worst prognosis for gland of origin with
a mortality rate of 58%. If both upper and lower lids are involved, the mortality rate is 83%. This is
contrasted to a mortality rate of 28% for upper lid location only (Rao). Extraocular location has a
significantly better prognosis. Bailet (see Nelson) reported a review of 92 patients with extraocular SC
and found a recurrence rate of 29% and metastases in 21%.
Several features are associated with a more aggressive tumor. Rao found that tumors with poor
sebaceous differentiation are associated with a high mortality (60%). He also reported that
angiolymphatic invasion was associated with very aggressive behavior. A highly infiltrative growth
pattern was associated with a history of multiple recurrences, orbital invasion, regional nodal
metastasis and death. Pagetoid spread to the conjunctiva was seen in 59% of the fatal cases. EMA is a
very useful immunoperoxidase stain to highlight sebaceous differentiation in poorly differentiated
Evaluation of the patent with sebaceous carcinoma includes a complete skin exam, palpation of nodes
and an ophthalmology referral. Patients must be evaluated for the Muir-Torre syndrome and family history
reviewed for sebaceous neoplasms, keratoacanthomas, colorectal or genital malignancy.
Treatment is primarily surgical (Nelson). Current recommendations call for 0.5 - 0.6 cm margins for
primary tumors. Sebaceous carcinoma has a tendency for local recurrence due to the difficulties in
obtaining clear margins. Mohs surgery has been difficult to utilize due to the multicentricity of some
tumors, pagetoid spread and the difficulty in identifying malignant
sebaceous cells on frozen section. Yount reported six cases where he utilized Mohs surgery with
permanent sections. At an average follow-up of 56.8 months (range 34 - 84 months), one patient had
recurrence with metastatic disease. Radiation therapy has been considered as adjunctive or palliative
therapy but is generally not recommended as a primary treatment.
The significance of the pagetoid spread and the best method of treatment remains controversial (Yount,
Whitaker). Most authors recommend complete excision of all atypical cells. This may require
exenteration of the eye . Lisman reported 6 patients with extensive residual pagetoid spread after
primary excision treated with cryotherapy. The patients remained free of disease on follow-up biopsy at
6 - 50 months.
Metastatic disease occurs in 14 - 25 % of cases. Most metastases occur in regional lymph nodes,
followed by liver, lung, brain and bone. Regional lymph node metastases are treated with radical neck
dissection. Treatment of metastatic disease includes surgery, radiation, chemotherapy or a combination
of these modalities. Metastatic disease has a 50 - 67 % mortality (Nelson).
- Dzubow LM: Sebaceous carcinoma of the eyelid. Treatment with Mohs surgery. JDSO 1985, 11: 40 - 44.
- Lisman RD, Jakobie FA, Small P: Sebaceous carcinoma of the eyelids: the role of adjuvant cryotherapy in the management of conjunctival Pagetoid spread. Ophthalmology 1989, 96: 1021 - 1026.
- Nelson BR, et al.: Sebaceous carcinoma. JAAD 1995, 33: 1 - 15.
- Rao NA, et al.: Sebaceous carcinoma of the ocular adnexa: A clinicopathologic study of 104 cases with 5 year follow-up data. Human Path 1982, 13: 113 - 122.
- Whitaker DC: Sebaceous carcinoma of the eyelid, in: Surgical Dermatology and Advances in Current Practice. Mosby, 1993: 201 - 210.
- Yount AB, Bylund D, Pratt SG, Greenway HT: Mohs micrographic excision of sebaceous carcinoma of the eyelids. JDSO 1994, 20: 523 - 529.
Microcystic Adnexal Carcinoma
Microcystic adnexal carcinoma (MAC) is a locally aggressive tumor arising, most commonly, on the
central face of middle - aged patients. Clinically, the lesion presents as a pale yellow papule or
plaque in the nasolabial region, particularly the upper and lower lip. These lesions are not impressive
clinically and are ignored for years. The epidermis is usually normal. The lesions are highly
neurotropic and the patients may complain of a "full" sensation in the involved area or paresthesia or
pain. Originally believed to have features of both pilar and eccrine differentiation, the tumors are now
believed by most to be of eccrine origin.
|A lesion in the naso-labial area diagnosed as a desmoplastic trichoepithelioma or solitary syringoma The base of the lesion must be observed |
Look for perineural invasion
Histologically, the tumors are composed of strands of basaloid cells in a desmoplastic stroma. The
tumor is characterized by areas with gland - like structures, ductal differentiation as well as small
horn cysts. The cells are not pleomorphic and mitoses are uncommon. The tumors greatly resemble syringoma and desmoplastic
trichoepithelioma. Perineural invasion is a characteristic feature and is very useful in making a
correct diagnosis. Correct diagnosis requires a biopsy deep enough to see the base of the lesion.
MAC infiltrates widely through tissue. The tumor can penetrate into muscle, perichondrium and
periosteum. While recurrence rates after standard excision approach 47%, metastases have never been
Treatment is surgical. The literature is not clear about what constitutes adequate margins. Margins
have ranged from a few millimeters to 3 - 5 cm. In one study, 40 patents treated with wide local
excision had a recurrence rate of 59 % (Sebastien). Mohs would appear to be the treatment of choice,
since this technique allows for visualization of all margins and perineural spread can be followed.
However, studies using Mohs with long term follow-up of patients are not yet available.
- Burns MK, Cheen SP, Goldberg LH: Microcystic adnexal carcinoma: Ten cases treated by Mohs micrographic surgery. JDSO 1994, 20: 429 - 434.
- Sebastien TS, et al.: Microcystic adnexal carcinoma. JAAD 1993, 29: 840 - 845.