management of non melanoma skin cacer

management of

care and after care M.D. Njoo, M.D. Phd

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Management Of Non-Melanoma Skin Cancer Care and After Care M.D. Njoo, M.D. Phd

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Foreword The incidence of non-melanoma skin cancer (NMSC) has been increasing globally over the past 20 years. Ultraviolet radiation is the greatest risk factor for the development of NMSCs. There is indeed a predisposition for these cancers to occur on sun-exposed areas and caucasians are the most affected population group. Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are two most common types of NSMC. BCC is the most common skin cancer type in many countries.

Although the mortality rate is relatively low, NMSCs may inflict significant morbidity to the patient since they mostly occur on cosmetic essential areas and tend to occur as a chronic, recurrent disease.

This booklet discusses the management of NMSC. It covers topics varying from epidemiology, clinical manifestations to treatment and after treatment strategies. Finally, preventive measures are presented. The management of NMSC does not stop with the eradication of the primary lesion(s). The management of NMSC goes way beyond that !

Oldenzaal, 2014 M.D.Njoo, M.D. PhD, dermatologist

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Epidemiology p7

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Risk Factors p13

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Clinical Presentation p19

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Management of NMSC p43

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After Care Strategies p67

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Follow Up, Surveillance and Education p77

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Conclusion p81

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Case studies p83

Literature References p91

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Clinical Presentation

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a Basal Cell Carcinoma (BCC) b Squamous Cell Carcinoma (SCC)

Clinical Presentation — Basal Cell Carcinoma

3—a

Basal Cell Carcinoma (BCC) BCC is the most common form of NMSCs and it accounts for about 75% to 80% of all cases. 37—38 BCC is rarely seen at childhood, except in syndromal cases, such as the Gorlin-Goltz syndrome. Two third of the cases are seen after the age of 50. However, the incidence in younger patients is increasing, due to increased sun exposure.

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Clinical Presentation — Basal Cell Carcinoma

Pathophysiology BCC originates from the basal keratinocytes of the epidermis and adnexal structures (hair follicle, eccrien sweat ducts).

UVR can damage DNA and its repair system and also can alter the hosts immune system. BCC grows by direct extension and appears to require the surrounding stroma to facilitate its growth. This could be the reason why the malignant cells do not have the potency to metastasize though blood vessels or lymphatic system. BCC is therefore also termed as basalioma, to characterize its relatively benign growth pattern.

The course of BCC is unpredictable. Usually BCC remain small for years with little tendency to grow, particularly in older people. On the other hand it may grow rapidly or proceed by successive spurts of extension of tumour and partial regression. If left untreated, it may spread locally to the bone or other tissues beneath the skin.

BCC is also reported to occur on sites of previous trauma, such as scars, thermal burns, injury and after ionizing radiation treatments.

Location BCC usually develops on chronically sun-exposed areas of the skin, especially the head and neck. The predilections areas on the face show an H-configuration (fig—01). Strikingly, this distribution does not correspond well with areas of maximal UVR exposure. Also relatively sun-protected areas can be affected, such as the inner canthus and the retroauricular region. In about 30% of the cases, BCC even occur on areas with little or no sun exposure at all, such as the abdomen and the back. In contrary to SCC, these tumours are not common on the back of the hands and the forearms.

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Clinical Presentation — Basal Cell Carcinoma

fig—01

Distribution of BCC on the face corresponding to H zone

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Clinical Presentation — Basal Cell Carcinoma

Clinical types BCC present many clinical signs. In some cases BCC may resemble benign skin disorders (eczema) or tumours (benign nevus) and therefore not easily and rapidly recognized by the patient as malignant. Clinical forms don’t always correspond well with their respective histologic pictures, since several mixed histologic types exist. Therefore a pre-treatment skin biopsy is always recommended to confirm the histologic diagnosis. In table—04 histologic types are listed together with their rates of occurrence. 39

table—04

type

rate of occurence

NODULAR

21%

SUPERFICIAL

17%

MICRONODULAR

15%

INFILTRATIVE

7%

MORPHEAFORM

1%

MIXED PATTERN (two or more types of the above)

38,5%

NODULAR TYPE BCC

Nodular BCC is the most common clinical type of BCC and presents as a reddish- brown or pearly, translucent papule with telangiectasia. The lesion may have rolled borders and a central depression (fig—02). Nodular BCC may bleed spontaneously or develop into ulcer sometimes referred to as a rodent ulcer (fig—03). Ulcers may partially heal and the surface may form crusts, scales and scars and then bleed again. This cycle may repeat over years and masses of enormous sizes may be attained. Nodular BCC is usually located on the face and neck, however other locations are possible. One should always exclude the presence of a BCC when a leg ulcer does not heal after a period of conventional therapy (fig—04).

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Clinical Presentation — Basal Cell Carcinoma

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fig—02

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Typical nodular BCC with pink reddish pearly surface and teleangiectasia

fig—03

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fig—04

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Always suspect a BCC in a nonhealing leg ulcer. This was a infiltrative type BCC.

fig—05

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fig—06

Rodent ulcer. Histologic examination showed a nodular type BCC with ulceration

A pigmented BCC on the left groin, resembling a malignant melanoma

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A cystic type BCC on the lower eye lid of a 52 year old woman

fig—07

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A morpheaform BCC on the upper lip; Note the indistinct borders

Clinical Presentation — Basal Cell Carcinoma

08a

fig—08a

08b

A typical solitary superficial BCC on the upper chest

fig—08b

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fig—09

10a

Superficial BCC mistaken for eczema and treated with corticosteroids for months without any result

fig—10a

10b

fig—10b

A 58 year old male patient exhibiting multiple superficial BCCs on the back

Basosquamous BCC on the lower leg. Histologically proven after excision biopsy

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Mixed type BCC. Histology showed nodular type mixed with superficial type

Clinical Presentation — Basal Cell Carcinoma

11a

fig—11a

11b

Examples of recurrent BCCs arising in an old scar

fig—11b

Examples of recurrent BCCs arising in an old scar

PIGMENTED TYPE BCC

Some BCCs may contain melanin resulting in a brown, black, or blue coloration throughout the whole lesion. The lesion may resemble a malignant melanoma or seborrhoic keratosis.

However, closer inspection or dermatoscopic examination can reveal the typical pearly, white translucent borders and the absence of a pigment network. Only a skin biopsy can confirm the diagnosis and the histologic pattern is usually of the nodular type (fig—05).

CYSTIC TYPE BCC

This rare subtype presents as a smooth, round cystic mass or nodule. Cystic BCC are usually smaller lesions and behaves like a nodular BCC. A common location is the under eye lid, so this lesion may be mistaken for a chalazion. A biopsy therefore is mandatory. (fig—06)

MORPHEAFORM TYPE BCC

Morpheaform BCC, also known as sclerosing BCC, appears as a waxy, firm, flat-to-slightly elevated, either pale white, yellowish or skin-colored plaque that resembles localized scleroderma, hence the term morpheaform (fig—07). Lesions 26

Clinical Presentation — Basal Cell Carcinoma

may become depressed and firm, and may then look like a scar.

Difficulty for the treatment lies in the indistinct margins, the lesion seems to gradually spread into normal adjacent skin.

The only therapeutic option is wide excision, preferably using Moh’s micrographic surgery.

SUPERFICIAL TYPE

Superficial BCC (sBCC) is the least aggressive type of BCC. It usually occurs on the trunk or limbs and there may be one of more lesions at a time (fig—08a & 08b). The tumor grows slowly and peripherally, sometimes for several centimeters. The lesion is circumscribed, round to oval, red scaling plaque which can resemble a plaque of eczema, psoriasis, extramammary Paget’s disease or Bowen’s disease (fig—09). Close inspection can however, reveal the thin raised pearly whitish borders.

The typical features can also be revealed by eliminating the redness in the lesion using lateral finger pressure.

MIXED HISTOLOGIC TYPES

These are the most common type (38,5% of the cases).

Mixed histologic types can be suspected clinically but can only be confirmed by histologic examination of a skin biopsy (fig—10a). Possible mixes are nodular- with morpheaform type or nodular -with superficial type. Rarely, a basosquamous type can be seen histologically; this is a mixed type NMSC revealing histologic features of both BCC and SCC in one lesion (fig—10b).

RECURRENT BCC

Any BCC can recur, but mostly after inadequate treatment.

It may recur superficially in scar tissue and also deep in the dermis or even in the subcutaneous fat. The clinical picture can differ from the initial lesion. Erosions, crusts, papules, cysts and scaly noduli appearing in and around old scars are always suspicious (fig—11 a & 11b). Sometimes the recurring lesion is so subtle that the diagnosis can easily be missed. A skin 27

Clinical Presentation — Basal Cell Carcinoma

biopsy at least is recommended. Tumors of morpheaform and basoquamous types have the greatest rates to recur. BCCs on the nose, perinasal area and ear also bear a high recurrence rate. Furthermore the larger the tumor (greater than 2 cm in diameter) the greater the chance for recurring. Recurrent BCCs often require more aggressive treatment with wide excisions or Mohs’ micrographic surgery.

NEVOID BASAL CELL CARCINOMA SYNDROME (GORLIN-GOLTZ SYNDROME)

This is a rare autosomal dominant inherited syndrome with high penetrance and variable expressivity. The gene is located on chromosome 9q22,3-q31. Persons with this syndrome exhibit multiple BCCs at birth or in early childhood. There is a great variation in the number of BCCs. The median number is eight. Although many patients have no BCC or only a few, cases with more than 1000 BCCs are reported in the literature. Destructive tumors are rarely seen before puberty. More aggressive BCC types occur after puberty, so all patients should be on regular check-up schedule. Other characteristics of this syndrome include skeletal abnormalities (especially facial and vertebral) and disorders of the central nervous system. 40

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Clinical Presentation — Basal Cell Carcinoma

prognosis Since BCC, in general, does not metastasize the TNM classification is not applicable. The most important prognostic variables are histologic type, localization and size of the tumor (table—05). table—05

Prognostic factors of BCC 47

prognostic factor

low risk

high risk

histologic type

nodular

micronodular, morpheaform

localization

trunk

h-zone

size

< 2 cm

> 2 cm

primary tumor

recurrent tumor

recurrency

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Management Of NMSC — Pharmacologic Methods

Multidisciplinary management of NMSC As earlier stated, worldwide incidence rates of NMSCs are increasing. As a result, the flow of skin cancer patients to the hospitals and skin clinics are increasing as well. Studies have shown that dermatologst spend about 50% of their time in the treatment of premalignacies and NMSCs. 16 These factors all contribute to the tendency that there will soon not be enough dermatologists available to treat all patients with NMSCs. To anticipate on the emerging patient population dermatologists are forced to train their assisting and nursing personnel to efficiently manage skin cancer. Specialized dermatological nurses, nurse practitioners and physician assistants are shown to improve medical, psychosocial and lifestyle outcomes for other chronical skin diseases, such as leg ulcers, atopic eczema and psoriasis. These disciplines may all participate in treatment strategies, secondary prevention and counselling. For example they can perform skin biopsies, photodynamic therapy, topical therapies (5-fluorouracil and imiquimod), cryotherapy and simple excisions. This multidisplinary approach enhances the capacity of the dermatological department to treat skin cancers. 73,74 Nowadays, many nurses already fullfill additional tasks such as taking history and completing questionnaires regarding risk factors and general health issues. Therefore it seems logical to train the existing supporting personnel for these extra tasks. The dermatologist should always remain responsible for the the final clinical diagnosis and therapeutic work-out.

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After Care Strategies

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After Care Strategies

5â&#x20AC;&#x201D;a

Several after care treatments can further optimize wound healing and treatment outcomes of NMSCs. These treatments can be easily carried out at home and are of minor inconveniences to the patient.

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After Care Strategies

28a

fig—28a

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fig—26b

Front view of a forehead with multiple actinic keratoses just after treatment with imiquimod 3 times weekly for 4 weeks.

After 1 week twice daily application of a Aloe Vera complex containing a moisturizing creamgel and occlusive ingredients (Alhydran ®)

Adjunctive local therapies Local therapies with 5-Fluorouracil, cryotherapy of imiquimod may cause temporary inflammatory reactions such as redness, swelling erosions or crusting. These therapies can be supported by post-treatment applications of disinfecting, anti-inflammatory and/or moisturizing agents. By doing this, wound healing can be speeded up and secondary bacterial infections prevented. Moisturizing agents have the ability to preserve or increase the moisture content of the skin. Many of these agents also contain substance that have disinfecting and wound healing properties. Emollients can both soften the skin and moisturize due to their occlusive properties.

Examples of natural moisturizers are lactic acid, glycerin and urea. Emollients usually contain petrolatum, fatty acids and oils of different plants (such as Aloe Vera), fatty alcohols, wax esters, silicone oils, dimethicone and many others. (fig—28a & 28b) Most used topical disinfecting agents are fusidin acid or mupirocin. 49

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After Care Strategies

A recent study from Gent University compared the occlusive and hydrating properties of three fluid silicone gels and a hydrating gel-cream (Alhydran ®) on the forearms of 40 healthy volunteers. They concluded that this well balanced hydrating gel-cream can provide the same occlusive and hydrating properties as silicone gel (fig—29). The authors even suggest that this cream can eventually replace silicones in scar prevention and treatment. 75

Water loss of the skin

fig—29

Quantity of water that passes the body through the outer layer of the skin (Transepidermal water loss)

18 16 14 12 8 6 1h

2h

3h

4h

5h Measurements

Damaged skin treated with Alhydran Healthy skin

Protection from UV rays It is generally advised to protect fresh and maturating scars against UV rays. It is known that exposure to UV rays can induce hyperpigmentation and aggravate clinical experience. Moreover, fresh scars can easily get sunburn reactions after exposure to UV rays. Strikingly, only a few studies have investigated the effect of UV radiation on maturating scars and wound healing. Nevertheless broad spectrum sunscreens should be used at regular time intervals until the end of the maturation phase (1 to 2 years).

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Clinical Presentation — Basal Cell Carcinoma

Abnormal scar prevention and scar remodeling It is generally known that normal scar formation may take as long as 2 years until an acceptable scar has developed. During scar formation unwanted symptoms such as pain, stinging, itch, redness and oedema may occur. These complaints may all resolve spontaneously. In some cases however 3 forms of abnormal scars may develop (fig—30a, 30b &30c): HYPERTROPHIC SCAR

Abnormal proliferation of the scar, which do not extend beyond the edges of the original excision.

KELOIDS

Excessive proliferation of the scar with a size that extend far beyond the original edges of the excision.

ATROPHIC SCARS

Sunken scar formations below the skin level. Also broadened scars can be atrophic. These scars are caused by excessive tension on the scars and reduced elasticity of scar tissue.

Examples of broadened atrophic are scars on the back and over joints.

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After Care Strategies

30a

fig—30a

Hypertrophic scar

30b

fig—30b

Keloidal scar

30c

fig—30c

Broadened atrophic scar on the back

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After Care Strategies

The following treatments are available to treat surgical scars which occur after excisional surgery.

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5â&#x20AC;&#x201D;b

After Care Strategies

Microporous tapes Immediately after sutures are placed, adhesive microporous products such as tapes or steristrips should be used over the excision wounds. It is known that these tapes can reduce water vapor transmission, control homeostasis and shorten the period to scar maturation. Also after sutures are removed these tapes may again be placed over the fresh scar for 1 or 2 weeks longer. After this period, silicones can be used to further promote normal scar formation.

Silicones Silicones are synthetic cross-linked polymers of dimethylsiloxane. For the treatment of hypertrophic scars and after the keloid has been excised, silicones are available in gel, creams or sheets. New generation scar gels are non greasy, non sticky and are enriched with vitamin E. Different studies have shown the beneficial effects of silicones in scar management. The use of silicones may reduce symptoms of itching, swelling and redness. Studies have shown that after application of silicones, scars are significantly improved in color, pliability, height, itching- and pain complaints. The mechanisms of action of silicones are not fully understood. However, most investigators seem to agree that silicones work by hydrating and occluding the scars and therefore reducing TEWL (transepidermal water loss), normalizing hydration state of keratinocytes and finally downregulating excessive collagen production.â&#x20AC;&#x2030;76 According to the 2002 International Clinical Recommendations on Scar Management, silicone should be the first line of treatment in the initial management of all scars and particularly in the prevention of keloids and hypertrophic scars.â&#x20AC;&#x2030;77 Gels are best suitable for locations on the face and neck, whilst sheets are more suitable for scars located on the trunk.

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After Care Strategies

31a

fig—31a

Before use of a gel silicon sheet

31b

fig—31b

After use of a gel silicon sheet

Intralesional corticosteroids The intralesional injection of corticosteroids is the most commonly used therapeutic modality in the treatment of longstanding hypertrophic scars and keloid. Corticosteroids inhibit inflammation and collagen production in scars. For many physicians triamcinolonacetonide (10–40 mg/ml) is the most commonly used corticosteroid, although no defined protocols exist specifying the most adequate concentration of this drug. Common side effects are atrophy, hypopigmentation 75

After Care Strategies

and teleangiectasias. Furthermore, it is important not to inject too deeply into subcutaneous tissues to avoid fat atrophy. Corticosteroids may be combined with other therapies such as silicone sheets or cryotherapy with liquid nitrogen. Recurrent rates of monotherapy with 40 mg/ml are reported to be between 7%–50%, so combination therapies are probably the best option. 38 Intralesional corticosteroids are most suitable for locations on the trunk and extremities. Caution is needed for use of this treatment for scars on the face.

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Case Studies Case.1 Case.2 Case.3 Case.4 Case.5

Treatment of actinic keratoses after topical imquimod 5% cream Treatment of actinic keratoses after cryotherapy Treatment of Atopic eczema Treatment of Hyperkeratotic hand eczema Treatment of inflamed hypertrophic scar

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Case.2 ALHYDRAN

Treatment of actinic keratoses after cryotherapy Case report Age patient

72 years old

Gender

Male

Diagnosis

Actinic keratoses after cryotherapy

Treatment

Alhydran cream twice daily for 14 days

Study design

Patient had 2 lesions of actinic keratoses on the scalp region.

Both lesions were treated with 2 cycli of liquid nitrogen spray.

Patient applied Alhydran twice daily open application for 14 days as after treatment.

Clinical result The treated skin areas closed after 14 days leaving no scar formation or hypopigmentation.

Experience of physician

Experience of patient

- Alhydran can be used easily without local side effects - Alhydran can be used as an alternative for fusidinic acid cream - Alhydran does not cause bacterial resistance in contrast to fusidinic acid - Alhydran cream proved to have fast wound healing effects

- Easy in use - No skin irritation or other side effects - Fast clinical results, only within days

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Case.5 BAP SCAR CARE T

Treatment of inflammed hypertrophic scar Case report Age patient

42 years old

Gender

Female

Diagnosis

Inflammed hypertrophic scar on right upper arm after excision of primary melanoma

Treatment

BAPSCARCARE T silicone sheet used daily for 1 month

Study design

Patient had complaints of an itchy and inflammed hypertrophic scar on the upper arm, which had existed for 3 months. The scar was the result of an excision 4 months ago of primary melanoma.

Patient applied BAPSCARCARE T for 1 months. Dressing was changed every 3 to 5 days.

Clinical result Signs of inflammation (itching, swelling and redness) had dissapeared.

Experience of physician

Experience of patient

- BAPSCARCARE T is convenient in use causing no local side effects - BAPSCARCARE T provided fast antiinflammatory effects - Unwanted symptoms completely cleared after 1 month of use

- Easy in use and effective within days - No skin irritation or other side effects - Can be used under clothing without any inconvenience

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Dr. M.D. Njoo achieved his medical degree at the Rijksuniversiteit in Groningen in 1995. Subsequently, he worked 8 months as a senior house officer at the Department of Dermatology, University Hospital Dijkzigt, Rotterdam. Betweeen november 1995 and october 1999 he worked as a senior house officer at the Netherlands Institute for Pigmentary Disorders, in Amsterdam where he has developed a great affinity towards the treatment of pigmentary skin problems. In 2000 he achieved his PhD degree on the theses Treatment of vitiligo at the University of Amsterdam. In 2004 he finished his training as a dermatologist. Since 1 april 2004 Dr. Njoo is working as a dermatologist at the Department of Dermatology of the Ziekenhuisgroep Twente, location Hengelo (Ov.), the Netherlands. Dr. Njoo has published more than 50 scientific papers in both national and international journals. Furthermore he is medical editor of the popular website www.huidarts.com and chief editor of the medical journal Kompakt Dermatology. His favourite topics in dermatology are oncology, flebology, psoriasis, pigment disorders and photo- and lasertherapy.

Dr. Njoo is also an expert in minimal invasive procedures of aesthetic dermatology (www.davidnjoo.nl). The main goal in his profession is to achieve optimal patient satisfaction using innovative dermatological treatments and patient care technologies.