skin cancer |prevention and treatment

 Introduction and Epidemiology

These are arguably the most common cancers in sub-Sahara Africa.

There are various types of skin cancer which include Kaposi’s sarcoma, squamous cell carcinoma (SCC), malignant melanoma and basal cell carcinoma (BCC).

Dermatofibrosarcoma protuberans, Merkel  cell carcinoma, keratoacanthoma, spindle cell tumors, sebaceous carcinomas, microcystic adnexal carcinoma, others.

In our set up the first three are the most common.

Epidemiology .

Chronic skin infections (including HPV) and chronic skin ulcers are key causes of skin  cancer.

Ionizing radiation, environmental carcinogens, artificial UV radiation, sun exposure,  aging, and light skin color predispose one to developing various types of skin cancer. 

Other risk factors include albinism and other genetic syndromes such as congenital  melanocytic nevi syndrome, characterized by the presence of nevi (birthmarks or moles), xeroderma pigmentosa.

Non-melanoma (basal and squamous cell carcinoma) skin cancers (NMSC) are the most  common types of skin cancer in our environment, but melanomas are also not uncommon.

Minimizing exposure to sources of ultraviolet radiation (the sun and sunbeds), following sun protection measures include wearing sun protective clothing (long-sleeved shirts, long trousers, and broad-brimmed hats).

This is especially true for persons with albinism.

A good rule of thumb for decreasing ultraviolet light exposure is to avoid the sun between the hours of 9 a.m. and 3 p.m. 

 Diagnosis

Symptoms include changes in skin colour, non-healing ulcers and changes in existing moles (melanoma). 

Melanoma .
Most melanomas are brown to black looking lesions. A few melanomas are pink, red or  fleshy in color and may be difficult to recognize.

Warning signs of malignant melanoma  include changes in the size, shape, color or elevation of a mole. Other signs are the  appearance of a new mole during adulthood or pain, itching, ulceration or bleeding. An  often-used mnemonic is “ABCDE”, where A= asymmetrical, B= “borders” (irregular), C= “color” (variegated), D= “diameter” (larger than 6 mm—the size of a pencil eraser) and E= “evolving.”Squamous cell carcinoma may occur in chronic ulcers. They may present us scaling, thickened patch on sun-exposed skin. Some are firm or hard nodules which may be dome shaped like keratoacanthomas. Ulceration and bleeding may occur.

Basal cell carcinoma usually presents as a raised, smooth, pearly bump on the sun-exposed  skin of the head, neck or shoulders. Crusting and bleeding in the center of the tumor  frequently develops. It is often mistaken for a sore that does not heal. This form of skin cancer carries the best prognosis and with proper treatment can be completely eliminated, often without scarring.

Special emphasis on malignant melanoma.

Physical examination with special attention to other suspicious pigmented lesions, tumor satellites, in-transit metastases, regional lymph node and systemic metastases is mandatory. A skin biopsy performed under local anesthesia is often required to assist in making or confirming the diagnosis. Elliptical excisional biopsies may remove the tumor, followed by histological analysis and Breslow scoring. 

 Staging and risk assessment

Investigations.

Lactate dehydrogenase (LDH) tests are often used to screen for metastases.

Others are chest X-rays, and in some cases CT and MRI, scans.

Sentinel lymph node biopsies may be performed in patients to assess spread to the lymph nodes.

A diagnosis of melanoma is supported by the presence of the S-100 protein marker and HMB-45 monoclonal antibody  (Human Melanoma Black). 

Confirmation of the clinical diagnosis is done with a skin biopsy.

TNM Staging for Malignant Melanoma

Stage 0:  Melanoma in situ (Clark Level I)
T1a:  Less than 1.0 mm primary tumor thickness, without ulceration, and 
 mitosis < 1/mm2
T1b:  Less than 1.0 mm primary tumor thickness, with ulceration or mitoses ≥ 
 1/mm2
T1b: Less than 1.0 mm primary tumor thickness, with ulceration or mitoses ≥ 
 1/mm2
T2a:  1.01–2.0 mm primary tumor thickness, without ulceration
T2b: 1.01–2.0 mm primary tumor thickness, with ulceration
T3a:  2.01–4.0 mm primary tumor thickness, without ulceration
T3b: 2.01–4.0 mm primary tumor thickness, with ulceration
T4a: Greater than 4.0 mm primary tumor thickness, without ulceration.
T4b:  Greater than 4.0 mm primary tumor thickness, with ulceration
Nodal Status N
N1 Single positive lymph node
N2 Two to three positive lymph nodes or regional skin/in-transit metastasis
N3 Four positive lymph nodes or one lymph node and regional skin/in-
 transit metastases
Distant Metastasis M
M1a: Distant skin metastasis, normal LDH
M1b: Lung metastasis, normal LDH
M1c: Other distant metastasis or any distant metastasis with elevated LDH

Classification.

Melanoma is divided into the following types: Lentigo maligna melanoma,superficial spreading melanoma, acral lentiginous melanoma, mucosal melanoma, nodular melanoma, desmoplastic melanoma, amelanotic melanoma, others.

Management

Treatment is dependent on type of cancer, location of the cancer, age of the patient, and whether the cancer is primary or a recurrence.

Options include surgery, radiation therapy (external beam radiotherapy or brachytherapy), topical chemotherapy (imiquimod or  5-fluorouracil) and cryotherapy (freezing the cancer off) .

In the case of disease that has  metastasized, further surgical procedures or chemotherapy may be required.

 Surgery

Wide excision of primary tumors with safety margins is recommended.

Sentinel lymph node biopsy has been developed to reduce the complications of lymph node surgery.

If a lymph node is positive, a radical lymph node dissection will often be performed. 

Chemotherapy and immunotherapy.

Various chemotherapy agents are used, including dacarbazine (also termed DTIC), immunotherapy (with interleukin-2 (IL-2) or interferon (IFN)), as well as local perfusion.  Other drugs used are temozolamide, cisplatin, and cyclophosphamide.

The overall success in metastatic melanoma is quite limited.

Radiation therapy,

It is often used after surgical resection for patients with locally or regionally advanced  melanoma or for patients with unresectable distant metastases.

 Patient information and follow-up

Melanoma patients should be instructed on avoidance of sunburns, extended unprotected  solar or artificial UV exposure and on lifelong regular self-examinations of the skin and  peripheral lymph nodes.

Patients have follow-up visits every 3months during the first 3 years and every 6–12 months thereafter. Serum S-100 may be useful follow-up.

Routine  imaging techniques are not recommended.

Pharmacological management

Dacarbazine, temozolamide, cisplatin, cyclophosphamide, interferon-alpha. In resource limited settings, a combination of cisplatin and dacarbazine can be used. Where  resources are available, interferon alpha- 2B and dacarbazine can be used.

Prognosis

Early disease is curable with surgery and adjuvant therapy.

Metastatic disease carries a poor  prognosis. 

 References

  1. Gilchrest BA, Eller MS, Geller AC, et al. The pathogenesis of melanoma induced by ultraviolet radiation. N Engl J Med 1999;340:1341-1348
     
  2. Meves A, Repacholi MH, Refhuess EA, et al. Promoting safe and effective sun protective strategies. J Am Acad Dermatol 2003;49: 1203-1204.
     
  3. Kasper, Dennis L; Braunwald, Eugene; Fauci, Anthony; et al. (2005). Harrison’s Principles of Internal  Medicine, 16th ed. New York: McGraw-Hill. ISBN 0-07-139140-7 [Amazon-US | Amazon-UK].
     
  4. Marks R (January 1995). “An overview of skin cancers. Incidence and causation”. Cancer 75 (2 Suppl): 607–12. doi:10.1002/1097- 0142(19950115)75:2+<607::AID-CNCR2820751402>3.0.CO;2-8. PMID 7804986.
     
  5. Malignant Melanoma: eMedicine Dermatology”. http://emedicine.medscape.com/article/1100753- overview.
     

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Dr Mathu

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