Malignant lesions

Basal cell carcinoma

Basal cell carcinoma (BCC, rodent ulcer) is the commonest form of skin cancer and typically affects individuals between the ages of 40 and 79 years; more than 50 per cent are male and more than 85 pet cent of these lesions occur in the head and neck region. These tumours are thought to originate from pluripotential epithelial cells of the epidermis and hair follicles. BCCs grow slowly, but become locally invasive and penetrate deeper tissues — hence the term rodent ulcer (Fig 13.35 and Fig 13.36). Metastasis is rare. The patient gives a history of a ‘spot’ that fails to heal. Typically these tumours have a nodular appearance with a pearly rolled edge (which is apparent on stretching the skin) and telangiectatic vessels. Histologically, 26 different varieties of BCC have been described. However, clinically the following are recognised, in order of frequency:

• nodular: 50—54 per cent;

• superficial: 9—11 per cent;

• cystic: 4—8 per cent;

• pigmented: 6 per cent;

• morpheic: 2 per cent.

 Several treatments are possible, as follows.

 • Surgical excision — the treatment of choice with cure rates between 85 and 95 per cent.

•       Electrodessication and curettage commonly used for small superficial lesions (2—5 mm in diameter) gives cure rates between 85 and 100 per cent.

•       Radiotherapy. BCC is very radiosensitive and has an overall response of 92 per cent in selected patients. This is reserved for elderly patients who are not suitable for surgery or for specialised anatomical sites.

• Mob’s micrographic surgery (chemosurgery) involving serial horizontal excision and mapping of the tumour. Usually reserved for recurrent lesions, tumours in difficult areas or those with indistinct borders (morpeaform).

  Following complete excision it is unnecessary routinely to followup these patients unless they have a familial disposition for BCC formation (Gorlin’s syndrome).

  Squamous cell carcinoma

  Squamous cell carcinoma (SCC) is a malignant tumour that arises in an area that has had some premalignant change. These turnouts appear more inflammatory, feel more indurated and ulcerate sooner compared with BCC. The malphigian or squamous cell layer of the skin is implicated in the development of this cancer. There is a strong correlation with damage to the skin by the sun (Fig. 13.37a and b), and can be experimentally produced by ultraviolet light. Occa­sionally it arises as a complication of long-standing chronic granolas, such as syphilis, lupus vulgaris and leprosy, chronic ulcers, osteomyelitis, Hydradenitis suppurativa, long-standing venous ulcers or old burn scars. Histologically, these tumours are characterised by invasive nests of cells showing variable central keratinisation and horn cell formation. There is no peripheral palisading as occurs in BCC. The cells vary from large, well-differentiated cells to completely anaplastic cells. Lesions of the ear and lip metastasise much earlier even when they are relatively well differentiated. Regional nodes may become enlarged, either as a result of infection of the ulcer or from metastases. Treatment should primarily involve complete eradication of the tumour by the following methods.

 •  Surgical excision is the most appropriate treatment for SCC of the skin, with the surgical margin being dependent on the tumour diameter and on the site of the lesion.

•   Radiotherapy should be used for massive unresectable tumours in critical anatomical sites. Postoperatively it may be used for persisting tumour or where clearance is doubtful.

  Verrucous carcinoma

Verrucous carcinoma are well-differentiated SCC which invade locally but rarely metastasise. These commonly occur on the palm and soles; here they are known as carcinoma ciniculatum

Keratoacanthoma

Keratoacanthoma (molluscum sebaceum) (Fig. 13.38) arises as a rapid proliferation of squamous epidermal cells. The nodule grows rapidly for 6—8 weeks at which time it usually begins to resolve spontaneously. Keratoacanthoma must be distinguished from 8CC. Usually rapid evolution to relatively large size, irregular crater shape and keratotic plug, and the undamaged surrounding skin make a distinction possible. Spontaneous healing further confirms the diagnosis. Histologically, it is difficult to differentiate between a keratoacanthoma and SCC. There is also a possibility of a highly anaplastic SCC behaving like a keratoacanthoma. Excision biopsy is mandatory if the diagnosis is in doubt as curetted specimens yield poor sections.

Melanoma

Cutaneous melanoma is a malignant neoplasm arising from epidermal melanocytes. The earliest description is in the writings of Hippocrates in the fifth century BC. John Hunter described a ‘cancerous fungous excrescence’ in 1787, which has subsequently been diagnosed as a melanoma. It has been considered a rare tumour with unpredictable behaviour. It varies from spontaneous regression to rapid progression and death. However, the disease is no longer rare. The rate of increase in the incidence of melanoma is greater than for any other cancer in Caucasians with the exception of bronchogenic carcinoma. Its incidence has doubled every 10 years in countries close to the equator and every 10—15 years in more temperate zones. Incidence has quadrupled in Australasia and doubled in Norway, Britain, America and Canada in the last 30 years. This increase in incidence is not observed in other skin cancers. The incidence is 40 per 100 000 in Queens land, Australia, but only 4 per 100 000 in Scotland. It accounts for almost all the deaths from skin cancer.

It is likely that between a third and a half of all melanomas develop in a benign naevus of many years’ standing. Mela­noma does not exhibit any overall sex predilection. The commonest site for females is the lower leg and in males the front or back of the trunk. In the Bantu, the sole of the foot is the most frequent site; they can also occur on the palms and other depigmented areas, but do not arise in the black skin of the remainder of the body for a reason that is not understood. Rarely, melanoma arises in the eye, in the meninges or at the mucocutaneous junction zones, e.g. anus and mouth. There is now strong evidence that the increase in exposure to sunlight is mainly responsible for the rapid increase in this skin cancer. It is well known that solar irradiation, which is now much more dangerous as a result of the decreasing ozone layer, is associated with all skin cancers. Ethnic origin, climate, socioeconomic status and lifestyle are all risk factors interacting with sun exposure. The other evidence with reference to sun exposure is that patients with pathological conditions, such as albinism and xeroderma pigmentosa, are susceptible to forming melanomas. A proportion will arise in a Hutchinson’s freckle (see below). Clark et al. in 1975 produced a concept of a ‘radial growth phase’ to describe the atypical proliferation of intraepidermal melanocytes which precedes the development of dermal invasion (vertical growth phase) in all except nodular melanoma.

Four parameters of histological grading are used, as follows.

 1. The most important parameter is the depth of invasion as measured by the thickness (Fig. 13.39). The thickness is measured by an optical micrometer from the top of the granular layer of the epidermis to the deepest melanoma cells in the dermis (Breslow, 1975). There is good evi­dence that tumour thickness is a better measure of prog­nosis than level of invasion, and also more reproducible by different observers. Lesions less than 0.76 mm in thickness have a very favourable prognosis.

2. Ulceration, and

3. a high mitotic rate carry a poor prognosis.

4.Regression, if present, for some thin melanomas may have an appreciable risk of metastases, presumably because the lesion at some point in the past had been of a sufficient thickness to have metastasised.

Clinical features

Clinically, five types are recognised:

• lentigo maligna;

•  superficial spreading;

• nodular;

• acral-lentiginous;

• amelanotic.

Superficial spreading melanomas are the most common (64 per cent). They occur on any part of the body and are usually greater than 0.5 mm in diameter. A variegated coloured pattern and an irregular edge are characteristic. The lesion is usually palpable.

Nodular melanoma. This is the most malignant, occurring in about 12—25 per cent of cases and found in the younger age groups. It may occur on any part of the body, and is always palpable and usually convex in shape. The colour is commonly uniform and is usually blue, grey or black. It sharply delineates from the surrounding tissue, and has a smooth surface and an irregular outline. Ulceration may occur earlier, leading to weeping or bleeding.

Lentigo maligna melanoma (Hutchinson’s melanotic freckle) is the least common (7—15 per cent) and least malig­nant. It occurs most frequently on the face in people aged over 60 years. It may occur on any part of the body habitual­ly exposed to the sun. It begins as an irregularly pigmented, flat, brown macule which grows very slowly over a period of 1—15 years, advancing and regressing in various areas. There is a great variation in colour from brown to tanned black within the tumour itself. Malignant change is recognised by thickening and the development of discrete tumour nodules. They may ultimately grow to 5 cm and a very irregular outline is also characteristic (Fig. 13.40a and b).

Acral-lentiginous melanoma. These occur on the palms and soles and also include subungual melanomas (Fig. 13.41). They are the most common type of melanoma found in Japan. They carry a poor prognosis similar to nodular melanoma.

Amelanotic. In this form, the lesion may be pink but usu­ally close inspection will reveal some pigmentation at the base (Fig. 13.42). Amelanotic melanoma seem to carry an even worse prognosis than nodular pigmented melanoma. They may often present with regional lymph node metastases.

Clinical recognition

Malignant melanoma is almost unknown before puberty. The development of a malignancy in a mole should be suspected if any of the following changes occur:

Major signs                   Minor signs

Change in size                   Inflammation
Change in shape               Crusting or bleeding
Change in colour              Sensory change, e.g. itch
                                       Diameter 5 mm or more

Suspicious lesions should be removed completely with a 2 mm margin; use of incision or punch biopsies is deprecated since accurate histological staging is impossible, and the treatment is dependent on the histology.

Spread

Malignant melanoma may spread by local extension, by the lymphatics or by the bloodstream. Tumour cells may reach the regional lymph nodes by embolism but spread by lymphatic permeation is also seen, producing local satellite (Fig. 13.43a) and/or in-transit’ deposits between the primary growth and the regional nodes (Fig. 13.43b) resulting in secondary lymphoedema. Blood-borne metastases are seen in the lungs, liver, brain, skin and rarely in the bones. They may also involve unusual sites, e.g. the small intestine, heart and breasts. Secondary deposits are typically black, but sometimes contain little or no melanin, even when the primary tumour is heavily pigmented. Extensive visceral involvement may cause melanuria.

Staging

Using the American Joint Committee on Cancer/Interna­tional Union Against Cancer (AJCC/UICC) staging system is recommended (Table 13.1).

Treatment

This is primarily surgical.

• There should be complete surgical excision.

• Minimum margin of 1.0 cm and a maximum of 2.0 cm should be made. This represents the clinical margins at surgery and not histopathological margins.

 • Wide excision was advocated first by Handley in 1907 based on his pathological studies of the frequency of centrifugal dermal lymphatic permeation into the surrounding skin. Surgeons recommended a 5-cm margin of excision around primary malignant melanomas; this is no longer advocated.

• Do not excise beyond the deep fascia.

• Margins may have to be altered for cosmetic or functional reasons, e.g. periorbital region.

Survival from primary melanoma management falls with increasing tumour thickness (Table 13.2).

Treatment of lymph nodes

Lymph node biopsy. Fine-needle aspiration cytology (FNAC) is preferable to excision biopsy. Open biopsy may increase risk of tumour spillage, but if needed the incision should be placed so that it can be excised in continuity with the lymph node field.

Elective node dissection. This is not recommended for the large majority of patients. A report of satellitosis or lymphatic invasion should warrant consideration of node dissection. Clinically involved nodes require therapeutic node dissection.

Therapeutic dissection for clinically positive nodes requires radical clearance by those with expertise in the sur­gery of this condition. Limited dissection or ‘node picking’ is not acceptable. Adequate clearance gives a good prognosis with a 10-year survival of 50 per cent when one node is involved. However, with more nodes involved or extranodal spread the survival rates decrease and radiotherapy may be considered. Groin dissections may be complicated by the development of lymphoedema.

Lymphatic mapping and sentinel node biopsy is a tech­nique initially described by Cabannas in 1974 for penile carcinoma and popularised by Morton in 1994 for mela­noma. This may provide an approach to identify those patients who may be appropriate for elective lymph node dissection by detecting the presence of micrometastases in the sentinel node. This technique identifies the first echelon nodes (‘sentinel node’) using lymphoscintography following an intradermal injection of radioactive colloid around the primary site. The position of these nodes is marked on the skin and identified intraoperatively by injecting patent blue dye around the site of the primary and using a hand-held gamma probe to help to identify the position of these nodes. This accurately indicates the presence or absence of micrometastases in a nodal field.

Loco-regional recurrent melanoma

Loco-regional recurrent melanoma involving skin and soft tissues when isolated should be treated surgically. Patients with multiple local or in-transit recurrences should be considered for specialist treatment with isolation perfusion with high-dose cytotoxic agents (Fig. 13.44). Carbon dioxide laser ablation may be used for multiple small cutaneous lesions; or surgical resection for isolated pulmonary, cerebral, intestinal and intraperitoneal recurrences. In some patients it is advisable not to resect subsequent cutaneous metastases as they can be used as an indicator of response to systemic therapies or monitoring that of new local treatments.

Melanoma in childhood

Melanoma in childhood is rare; however, the clinical behaviour is similar to that in adults. The differential diagnosis is of the pigmented Spitz naevus (juvenile melanoma) which has previously been confused as a melanoma. This is a variant of the compound naevus in childhood. In cases of malignant melanoma in childhood the treatment is exactly the same as that for melanoma in adults.