Chapter 11

1. Name the four cell layers of the epidermis?
2. What are the embryological origins of keratinocytes and melanocytes?
3. Are the appendages derived from the epidermis or the dermis?
4. What gives spindle cells their ‘prickles’?
5. Are cells of the stratum corneum (horny cell layer) nucleated?
6. What is the significance of the bulge region?
7. Where are mast cells found in the skin?

1. The four layers of the epidermis are the basal cell layer, spindle cell layer, granular cell layer, and stratum corneum
2. The embryological origins of keratinocytes and melanocytes are ectoderm and neural crest respectively
3. The appendages — that is the pilosebaceous units (hair follicles and sebaceous glands) and eccrine sweat glands —are epidermal structures that have grown down into the dermis. They are made up of specialised keratinocytes. If the epidermis between the appendages is damaged they can repopulate the epidermis.
4. Desmosomes attach epidermal cells together. If the cell shrinks (as in tissue processing for histology) the desmosomes appear as prickles
5. No: the last nucleated layer of the epidermis is the granular layer. Cells of the horny layer (stratum corneum) are dead and contain no nuclei.
6. The significance of the bulge region is that it is the area close to where the sebaceous gland adjoins the hair follicle, and which is thought to be the site of the stem cell pool of keratinocytes and melanocytes.
7. Mast cells are found in the in the dermis

Pigmentation Questions

1. What is a mutagen? How does it differ from a carcinogen?
2. What is the upper limit of UVR in nanometres
3. Is heat loss achieved by eccrine or apocrine sweating in man?
4. What are the two main classes of melanin called?
5. Why may melanin appear blue?
6. Name two disease states that highlight the photoprotective properties of melanin
7. Why do you not sunburn on your palms?
8. What is the dominant melanin class in red hair?

Answers to pigmentation questions

1. A mutagen, like UVR, damages the structure of DNA such that if the DNA is not repaired an inheritable change occurs—a mutation. A carcinogen is anything that promotes cancer development or growth and is not be a mutation (e.g. hormones in breast and prostate cancer)
2. 400nm. (anything between 400 and ~ 800 is visible light).
3. There are three types of glands in skin; eccrine and apocrine sweat glands, and sebaceous glands. Sebaceous glands produce sebum, and increased sebum production is a cause of acne. Eccrine sweat glands produce ‘sweat’—the fluid we all recognise—and it is these eccrine glands that play such a key role in human heat loss. Humans have about 3 million eccrine sweat glands. Apocrine sweat glands are poorly understood glands in man, largely confined to the axillae and the genital regions, and do not play any meaningful role in heat loss in man.
4. Eumelanin, which is brown or black, and pheomelanin, which is red or yellow.
5. Scattering of light is wavelength dependent, so blue light may be ‘bounced back’ to the viewer relatively more.
6. Vitiligo and albinism.
7. The palms and soles have a very thick epidermis particularly the stratum corneum — this blocks nearly all the incident UVR photons.
8. Pheomelanin.

1. In sunshine which waveband predominates, UVA, UVB or UVC?
2. In sunshine which waveband contributes most to sunburn, UVA or UVB?
3. Are patients with xeroderma pigmentosum abnormally sensitive to X-irradiation?
4. Is UVR less than 320 nm blocked by the atmosphere?
5. What does the term action spectrum mean?

1. UVA is the dominant waveband in sunshine comprising over 90% of incident radiation. There is no UVC as the ozone layer blocks it.
2. UVB in natural sunshine is the main cause of sunburn, not UVA
3. Read the section again! XP patients are principally sensitive to UVR.
4. False. UVR below 290nm, not 320nm, is blocked by the atmosphere
5. The propensity of radiation at a given wavelength to cause some action.

1. Name two ways in which skin protects itself against future UVR damage
2. Name some of the mediators of UVR induced erythema
3. Skin hyperproliferates following UVR exposure. True or false?
4. Is immediate pigment darkening protective?
5. When does erythema from sunburn peak?
6. Does blue or red light scatter more?
7. What determines how well you tan?

1. Increase in pigmentation (tanning) and thickening of the epidermis are two mechanisms of photoadaptation
2. Prostaglandin E2 and nitric oxide are two mediators of erythema in response to UVR
3. A trick (or a bad) question. Immediately after UVR exposure, cell proliferation stops or slows down. Following a period of repair there is then a burst of hyperproliferation.
4. We do not understand what immediate pigment darkening is for. It is not thought to protect against UVR. It is a bit of a mystery.
5. Unless the burn is exceedingly severe (in which case it may be delayed) at 8-24 hours
6. Blue light scatters more than red light. In general the darker your natural skin colour (i.e. the more constitutive pigmentation you have) the more you are able to increase your pigment. For any one individual the greater the degree of erythema after UVR the greater the increase in pigmentation (tanning). Most of these processes are under strong genetic control.

1. What is meant by the statement that UVR is a tumour promoter?
2. Are tumour suppressor genes dominant or recessive?
3. What is meant by immunosurveillance?
4. Name two types of genetic change important in skin cancer
5. Is HPV relevant to skin cancer?

1. We have already discussed that UVR can cause mutations. However UVR can also increase the growth of clones of cells that already harbour mutations. This distinct activity is called tumour promotion.
2. At the cellular level tumour suppressors are recessive. You have to knock out both alleles to inactivate their function. Of course if one allele is mutated at birth, then there is only one more allele to inactivate. At the level of the person however such defects will appear to be inherited in an autosomal dominant pattern.
3. Immunosurveillance. This refers to the apparent ability of the immune system to mount a response against aberrant clones of cells.
4. Types of genetic change in skin cancer, include point mutations, chromosomal loss, and smaller areas of deletion together with duplication of chromosomal material
5. The exact role of HPV in skin cancer is still up for grabs. There is a causal role for cervical cancer and anal cancer and perhaps some other genital cancers, but for common skin cancers the role is at yet undefined.

1. Which is more common, BCC, SCC or AK?
2. Name two precursor lesions of SCC
3. What is the name for a BCC precursor?
4. Give five risk factors for NMSC
5. Are KA capable of metastasis?
6. In what way are IECs said to be like psoriasis?
7. Name an inherited syndrome that shows an increased incidence of BCC
8. Are BCC derived from the basal cell layer?
9. What is it about pale skin that increases the risk of skin cancer?

1. AKs are much more common than BCC or SCC. BCC are perhaps five times more common than SCC
2. Intraepithelial carcinoma (IEC) or AK
3. Trick question! We do know of any precursor for a BCC
4. Could include: body site, ambient UVR exposure, DNA repair mechanisms, pigmentation, inherited syndromes (e.g. xeroderma pigmentosa, or Gorlin’s syndrome), immunosuppression, X-irradiation or PUVA treatments.
5. KAs cannot metastasise — they are benign lesions, not cance
6. IEC especially on the lower leg often present as red scaly plaques which on many occasions can be confused with psoriasis.
7. Gorlin’s syndrome, also known as Nevoid Basal Cell Carcinoma Syndrome.
8. The cells of a BCC resemble basal cells but we are not certain of their cellular origin. Some believe them to be derived from hair follicle keratinocytes.
9. Pale skin has relatively too little melanin. Since melanin blocks harmful photons of UVR then the skin is less protected.

1. What does C+C stand for?
2. Why is C+C not an appropriate treatment for most SCCs?
3. Name two chemotherapeutic treatments for AKs
4. Is Mohs’ surgery useful for AKs?
5. The pathology report shows that an SCC has been incompletely excised. What do you advise?
6. What particular problems do morphoeic BCCs cause therapeutically?
7. Is cryotherapy suitable for superficial BCCs?

1. C+C stands for curettage and cautery. The lesion is scraped horizontally with the curette and then haemostasis achieved with the cautery.
2. SCC are cancers that are capable of metastasis, and it is therefore important to ensure the primary tumour has indeed been removed entirely — only excision achieves this.
3. Topical non-steroidal agents such diclofenac, imiquimod, topical fluorouracil, or photodynamic therapy.
4. Mohs’ surgery is not indicated for AKs. AKs can be far more easily treated using cryotherapy, C+C or topical therapeutic agents.
5. You must go back and re-excise the cancer if at all possible.
6. Morphoeic BCC have poorly defined edges and are often much larger than they appear to the naked eye. On the face Mohs surgery is often indicated for such tumours.
7. Superficial BCC are so named because their growth pattern is almost confined to the epidermis or upper dermis. They may well be quite large (say 6cm by 6cm). Cryotherapy is a useful treatment in this situation (as long as the tumour is not indurated or thicker).

1. Are MM more common than SCC
2. Are melanocytic nevi precursors of MM
3. What does ‘acral ‘ refer to
4. What type of MM shows a similar age incidence pattern with AK or SCC
5. What are the problems with the ABCD(E) system of MM diagnosis
6. What does the ugly duckling sign mean?
7. Should all new onset pigmented lesions be seen by a doctor?
8. Does HPV cause melanoma?
9. Is intermittent UVR exposure relevant to relevant to BCC as well as MM?
10. Is cryotherapy a suitable treatment for small superficial spreading melanomas?
11. Define Breslow thickness

1. BCC are more common than SCC, and SCC more common than MM
2. It is estimated that up to 50% of MM arise in preexisting melanocytic nevi
3. Body site: the palms and soles. These melanomas are not related to UVR (but those on the dorsal sun exposed aspects of the hands and feet are)
4. Lentigo maligna melanoma. This type of melanoma is most common on continuously sun exposed sites such as the face and back of hands, and is related to cumulative sun UVR.
5. The ABCD system relies on knowing that the index lesion is either a MM or a melanocytic nevus. In practice many doctors or lay persons cannot do this and mistakenly apply the rule to other lesions such as seborrhoeic keratoses.
6. This terminology aims to highlight that a melanocytic nevus that looks unlike a person’s other melanocytic nevi should be viewed with additional suspicion.
7. No, it is normal for a person to acquire many pigmented lesions during their life particularly in late childhood and early adult life. A new onset of what appears to be a melanocytic nevus in late middle age or old age should attract more suspicion.
8. No, HPV does not cause melanoma. The debate is whether HPV may play a role in some cases of NMSC especially in patients who are immunosuppressed.
9. Epidemiological data suggest that BCC risk is highest in groups that receive intermittent exposure rather than the highest cumulative exposure like for SCC.
10. No! Such a belief is likely to ensure one gets a visit from the General Medical Council and the lawyers. Never use cryotherapy for either a known melanoma or any primary melanocytic lesion.
11. The Breslow thickness is the distance in mm from the granular layer to the bottom of the abnormal proliferation of melanocytes.

1. What is the differences between a Spitz nevus and a blue nevus?
2. Are seborrhoeic keratoses rich in sebaceous glands?
3. What happens if you pinch a dermatofibroma?
4. What site is particularly common for pyogenic granulomas?
5. How could you tell the difference between a venous lake and a melanotic macule of the lip?
6. Do clinical atypical nevi show dysplasia?
7. Name two risk factors of freckles
8. At what age are melanocytic nevi most prevalent?

1. A Spitz nevus describes a particular histopathological appearance of a benign melanocytic nevi that is easily confused with a melanoma. They are more common in childhood and often appear quite red. A blue nevus is type of melanocytic nevus in which the melanocyte or nevus cells are deep in the dermis and therefore appear blue.
2. Seborrhoeic keratosis often appear greasy but this appearance has nothing to do with sebaceous glands or sebum.
3. If you pinch the skin over a dermatofibroma, you see that the dermatofibroma is tethered to the epidermis and a dimple occurs over the lesion.
4. Pyogenic granuloma are relatively common on the fingers.
5. Pressure applied to venous lakes should empty the blood and allow them to be distinguished from melanotic macules.
6. Atypical nevi. The terminology and definitions in this area are a mess. Clinically ‘atypical nevi’ are often completely normal histologically, and vice versa. These terms are better avoided.
7. Freckles are the result of the interaction between sun exposure and sensitive skin — so think, red hair, pale skin, excess sun exposure etc.
8. Melanocytic nevi are probably most common in the third and fourth decades — or at least most apparent during this period as they often lose their pigment in later life.

1. Name three risk factors for KS?
2. What cell type is affected in KS?
3. Name two common sites affected by Paget’s disease of the skin.
4. Name a cutaneous sarcoma.

1. Risk factors for KS include: HIV infection; immunosuppression following organ
   transplantation; other forms of immunosuppression; certain types of
   Mediterranean ancestry and old age; living in SubSaharan Africa.
2. KS is a tumour of the lymphatic endothelium
3. Nipple, and perianal or genital areas
4. Dermatofibrosarcoma Protuberans