Module 13B Pre-malignant/malignant non melanoma skin tumours and Lymphomas
Chapter 21 – Pre-malignant/malignant non melanoma skin tumours and Lymphomas
There is a podcast on this module that you can listen to either before you do the reading of the module or after, whichever you prefer! Podcast on non melanoma skin cancers. Just click on the little arrow next to the loudspeaker motif on the left side of the bar to start the podcast.
The video below describes the images used to illustrate this part of Module 11.
Habif does this section extremely well. He goes into it in sufficient detail to make it worthwhile for Australian readers. He first of all deals with basal cell skin cancer and notes that about one third of all BCCs occur in areas of the skin that receive little or no UV radiation. BCCs are uncommon on the back of the hands, unlike squamous cell skin cancers and notes that the more you wrinkle, the less likely you are to get BCCs. Sun exposure tends to be intermittent rather than cumulative in these patients. He goes into the histological characteristics of BCCs and I think it is important to know the five major histologic patterns to know which ones are relatively benign and which ones tend to go deeper and pose more of a problem. Note particularly the infiltrative or morpheaform lesions but they represent a relatively small proportion of the tumours that are seen. If a tumour has previously been treated it may well assume an infiltrative pattern.
He has some excellent pictures of nodular basal cell skin cancers occurring in different sites in the body and also of morpheaform BCCs and pigmented BCCs.
However the commonest variant that we are likely to see is the superficial basal cell skin cancer, particularly on the back and limbs. Usually these lesions look almost psoriasiform with some superficial scaling but if you blanch them and look at the edges, you will see the characteristic infiltrated pearly papular edge.
Morphoeic BCC on the nose best shown by blanching the surrounding skin outlining the white infiltrating scar like bcc. It is easy to miss this lesion.
Large superficial bcc on the back that has been slowly growing for 10 years
Regressed scarred superficial bcc on the back.
The nevoid basal carcinoma syndrome or the Gorlin-Goltz Syndrome is an autosomal dominant inherited disorder with a high penetrance that gives multiple BCCs occurring at a young age. It is usually associated with palmar pits and jaw cysts and also with multiple milia. There is usually some degree of hypertelorism (widely separated eyes) and a prominent forehead. These patients develop basal cell skin cancers as I say from an early age and continue to develope them right through their life.
Note the multiple bccs especially around the medial epicanthi
Basal cell nevus syndrome with multiple lesions on the neck.
Palmar pits in a case of basal cell nevus syndrome.
On page 816 Habif goes into the management of basal cell skin cancers and the risk of recurrence. Because they are relatively benign tumours and because many people get them as they get older, it is important to use a modality that is appropriate for the nature of the tumour and the age of the patient. He goes into this very well, particularly looking at the risk of recurrence with electrodessication and curettage.
He does a particularly good section on the recurrent basal cell carcinoma and it is important to know that these are often much more aggressive and require much wider excisions than you might think.
Other treatment modalities for BCCs include Imiquimod cream although this is mainly for superficial basal cell skin cancers and for small nodular BCCs. It is not appropriate for recurrent or infiltrative tumours. The same restrictions apply to the use of Photodynamic (PDT)Therapy in the treatment of BCCs.
Recurrent BCC on the forehead. This will require a wide excision.
In Australia virtually everyone develops solar keratoses. If a local solar keratosis is painful it usually means that it has developed into an invasive squamous cell skin cancer. Some histopathologists believe that solar keratoses are all squamous cell skin cancers but just in situ. He also does a good section there on actinic keratosis versus squamous cell carcinoma. Watch SCCs that occur on the lip and also those that may occur on the lower legs. They have a much higher risk of metastasis. Watch also the scalp in the elderly.
Various treatment modalities for actinic keratosis are looked at including Efudix cream and Imiquimod. Different areas of the body have to be treated for different times with Efudix cream. Note that the lower legs take a lot longer than say the face. Habif has some excellent pictures on the use of Efudix cream on solar keratoses in these areas including the lip but he also raises the issue of contact allergy to 5 FU. It should be suspected if there is intense redness and vesiculation occurring very early in treatment.
Recent Summary of Topicals for treatment of Solar keratoses.
Not only is 5-fluorouracil (5-FU) effective, “but it has become increasingly difficult to get some of the newer topical agents covered by health insurance plans, especially Medicare. This is the reality now,” Dr. Marcus said at the annual meeting of the American Academy of Dermatology.
Dr. Marcus, a dermatologist in Wyckoff, N.J., noted that 5-FU blocks methylation of deoxyuridylic acid to thymidylic acid in DNA, altering only fast-dividing cancerous cells. The agent is available in 1%, 2%, and 5% solutions, and in 1% and 5% creams. “We don’t really use the solutions much anymore; they’re very irritating,” Dr. Marcus said. “The 1% cream is less irritating, but 5% cream is really the gold standard.” Her approach is to have patients apply the 5% 5-FU cream to the affected area twice a day for 3 weeks. Another option is a 0.5% 5-FU cream with a microsphere delivery system “that traps the active ingredients in the skin surface to increase efficacy and decrease irritancy,” she said. “Some people use this for maintenance or cycle therapy prior to cryosurgery.”
As for side effects, 5-FU elicits erythema, scaliness, and crusting (which can be avoided with the milder preparations); but these conditions are self-limited, Dr. Marcus noted. Some dermatologists use topical steroids or hyaluronic acid gels “to make the erythema go away faster,” she added. “There are studies that say if you use these topical steroids, it curtails efficacy and you might lose some efficacy. That might be true. However, you have to make it user-friendly for the patient. Use your clinical judgment.”
Other topical preparations for actinic keratoses on the market include:
•Diclofenac sodium 3% in 2.5% hyaluronic acid gel. This colorless agent is designed to be applied twice a day for 2-3 months. “That can pose a compliance issue for some patients,” Dr. Marcus said. “The mechanism is unknown, but it probably functions as an NSAID that may involve prostaglandin levels in UV exposed skin and upregulation of COX-2, which may promote proliferation. Cyclooxygenase is the rate-limiting enzyme step in prostaglandin synthesis.”
Dr. Marcus said that that diclofenac sodium 3% in 2.5% hyaluronic acid gel may be best suited for patients with mild lesions and for pre- or post cryosurgery.
•Imiquimod. A 5% formulation of imiquimod “is becoming the new gold standard of topical therapies, but it can be irritating,” Dr. Marcus said. A 3.75% formulation is available that is designed to be used for 2 weeks, followed by a 2-week break, and then the patient repeats the cycle, Dr. Marcus said, adding that she uses the 3.75% formulation most often for her patients with actinic keratoses.
Dr. Marcus described imiquimod as an immune response modifier that induces mRNA encoding cytokines like alpha-interferon, TNF, and interleukin-12 for a cytotoxic T-lymphocyte response.
“There’s a direct proapoptotic effect in changing cancerous cells as a result of bypassing transduction paths activating caspase-3 downstream of membrane-bound death receptor activation,” she said. “You can get a severe reaction, but there shouldn’t be a lot of pain. You get excellent cosmetic results upon healing.”
Dermatologists often tweak the frequency of application, she added, and results from some studies suggest that outcomes with imiquimod are similar to those obtained with 5-FU, while others hint that imiquimod may provide longer-lasting results. “Field-directed therapy is the advantage since it brings out subclinical lesions, but you need a lot of hand holding to encourage patients with this phenomenon,” Dr. Marcus said.
DSAP Disseminated Superficial Actinic Porokeratoses are seen on sun exposed areas of the skin in people who have inherited the Autosomal dominant gene. You can get a linear version if there has been a post zygotic DNA mosaicism following Blachko's lines. These cells have a defect in a cholesterol gene and they respond to a topical statin (cholesterol inhibitor) . They also respond to prolonged Efudix or the recent 4% variant Tolak cream.
Photodynamic therapy is useful for field therapy, and it is done in one office visit, so compliance is not an issue, Dr. Marcus said. Photodynamic therapy also is covered by Medicare. “It may illicit some burning and require hand holding, but is effective,” she said. “The key is combination therapy.”
The video below is on Actinic Keratoses management by Ted Rosen.
Probably some sccs or hypertrophic solar keratoses in this lot!
Efudex used on the face for extensive solar keratoses
These are porokeratoses, an autosomal dominant inherited form of solar damage with a small risk of forming SCCs.
Squamous cell skin cancer is potentially a metastatic tumour and hence has to be approached much more aggressively than basal cell skin cancer. The vast majority of lesions should be excised if at all possible. Squamous cell skin cancer is very common in individuals who have ingested arsenic in the past or in people who are immunosuppressed and have had previous high levels of sun exposure. Most arise from pre existing solar keratoses but not all.
On page 797 he goes into the differentiation of keratoacanthoma from squamous cell skin cancer and also deals with the mode of spread of squamous cell skin cancer.
Extensive SCC behind the ear in a male. Bad site at the best of times for an SCC.
Rapidly growing scc on the lip
Ulcerated scc on the leg. These lesions have a 30% risk of metastasising to groin lymph glands!
Bowen’s Disease is SCC in situ just involving the epidermis. It can remain in this stage for many years spreading slowly peripherally without breaking the basement membrane. Many of these lesions are viral induced. Provided they do not occur in hair bearing areas they can be treated by topical methods, including liquid nitrogen and Imiquimod cream but if they do involve a hair follicle, they tend to go down the follicle and may not respond to these more superficial types of therapy.
Erythroplasia of Queyrat is SCC in situ occurring on the glans penis and spreading. Again this can be treated by superficial methods or by Moh’s surgery.
Leukoplakia is basically just white skin on the lip. When there is abnormal epithelization on the lip the tissue absorbs water and it looks white. Not all leukoplakia is pre malignant hence it is important to take a shave biopsy and look at this histologically before advising further therapy. If it is pre malignant, it can be dealt with by a CO2 laser. Many cases occur in smokers and they can resolve if smoking is given up.
Area of SCC in situ on the lower leg.
Area of leukoplakia that had developed a full blown invasive SCC. Because of the extent he was treated with radiotherapy.
SCC in situ on the penis sometimes known as Erythroplasia of Queyrat. This is often due to an oncogenic papilloma virus
Verrucous carcinoma is a rare tumour that often occurs on the palms of the hands and the soles of the feet and is mistaken for a chronic wart but it slowly progresses and in fact is just an SCC in situ. It may in fact have come from an oncogenic papilloma virus. This is dealt with in page 836 and on this page Habif also goes into the question of arsenical keratosis and arsenic related skin disease but virtually all the lesions with arsenic are SCCs but the characteristic lesions are often hyperkeratotic lesions on the palms of the hands.
This is a verrucous carcinoma of the foot- Viral induced
Remember to look in the mouth when examining patients. An scc of the tongue may be missed!
Cutaneous t-cell and B cell lymphomas are also dealt with in this section. These lymphomatous conditions are not common but they are worth knowing something about. T cell lymphoma or mycosis fungoides is dealt with on page 837. Habif goes into the issue of lymphocytes that initially show a tendency to invade the epidermis producing a chronic dermatitic pattern. These well defined skin lesions subsequently change, associated with the lymphocytes becoming less well differentiated and subsequently moving out from the skin into the local draining lymph nodes and gaining access to the systemic circulation. The local lesions initially are flat patches that subsequently become more infiltrated with atypical cells and become thicker and itchier. Habif goes into the topic of premycosis fungoides and the poikilodermatous parapsoriasis type lesions. It is worth reading through the various stages of this tumour looking at the pictures that he provides. This particular tumour is often best treated with ultraviolet light early in the course of the disease.
Sezary’s syndrome is a leukemic form of mycosis fungoides and the patient presents with erythroderma. It is a much more difficult condition to treat. At presentation it looks like a severe generalised atopic dermatitis so consider Sezary's if you have someone older presenting like this with no past history of "eczema"
The B cell lymphomas are not covered by Habif But you might look at Dermnet B Cell Lymphomas Essentially they present as purple or red nodules on the head or neck mainly and you need a punch biopsy to diagnose them. The pathologist will use a series of immunoperoxidase stains to identify the types of lymphocytes involved because the prognosis differs depending on the type. The prognosis of the commonest B cell lymphomas Follicular and marginal types is excellent. 90% 10 year survival.
T cell lymphoma at the plaque stage. Large discoloured indurated area on the forearm.
Sezary syndrome, a generalised sytemic T cell lymphoma presenting as a red man with abnormal Sezary cells circulating in the bloodstream.
B cell lymphoma in the scalp. Angiosarcomas can also start in this site also and present like an unusual bruise in the scalp.
Paget’s Disease of the breast and extramammary Paget’s are rarer tumours. Extramammary Paget’s is often associated with underlying rectal or urethral tumours and occurs in these areas. Paget’s Disease of the breast is an extension on to the breast areola of a ductal carcinoma. There are good pictures of these conditions on page 850 and 851.
Habif ends this chapter looking at the issue of cutaneous metastases and gives good tables indicating the origins of these lesions. Lung, melanoma, colon and kidney are high on the list of skin metastases in males. Breast and ovary, along with melanoma and colon are commonest in females. There are some characteristic presentations including what is called carcinoma encuirase where a breast carcinoma extends out into the skin causing peau d'orange due to lymphatic obstruction.
Extramammary Pagets disease involving the vulva. This was a vulval adenocarcinoma.
Mammary Pagets a ductal carcinoma spreading out onto the areola and breast. Beware making a diagnosis of unilateral nipple eczema!
Extramammary Pagets in a male. This one had no associated malignancy.
Merkel Cell carcinoma is a rare skin cancer seen in elderly severely sun damaged patients or in younger immunosuppressed transplant patients who are also badly sun damaged. It is rapidly growing, painless and difficult to diagnose dermatoscopically beforehand. It rapidly spreads both by lymphatics and blood stream. There is a 30% mortality at 1 year after diagnosis! Wide 2 cms clinical excision margins followed by radiotherapy to the tumour site and draining lymph nodes.
Merkel Cell Carcinoma
Merkel Cell Carcinoma
Merkel Cell Carcinoma Dermatoscopy
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