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Skin tumors

Dr Hideghéty Katalin PhD

Clinic of Oncotherapy, Univ. Szeged

Epidermal tumors

In situ cc. : Morbus Bowen, M Queyrat

Basal cell carcinoma

Squamosus cell carcinoma

Bőrfüggelék malignómák:

Szőrtüszőből, faggyú és verejtékmirigyekből kiinduló karcinómák

Merkel cell carcinoma

Lymphomas: T cell cutan lymphoma, Mycosis fungoides

Melanoma malignum

Secundaer tumors: Cutaneous, subcutaneous metastases

Skin tumors

BIOPSY-

HISTOLOGY!

Aetiology• Genetic factors: Xeroderma pigmentosum, neurofibroma (may transform to

neurofibrosarcoma)

• Enviromental factors:

– Ultraviolet light (especially in those with fair skin.)

– Tar, arsenic, mineral oils.

• X-ray: diagnostic or therapeutic.

• Long standing scars, fistulas, sinuses.

• Viruses: Burkitt lymphoma ----------- EB

– HPV

– Kaposi sarcoma ( herpes simplex virus- 8)

• Drugs: long lasting use of immunosuppressant like azathioprime,

cyclophosphamide, cyclosporine or even steroids.

Premalignant skin diseases:

• Actinic or solar

keratosis- Actinic

cheilitis

• Bowen's disease

• Chronic scars: burn,

lupus vulgaris, DLE

• Dysplastic nevi and

large congenital nevus

Actinic keratoses

10% risk of malignant transformation

Hypertrophic AK’s

• Liquid nitrogen cryotherapy

• Topical therapies

– 5-FU (Efudex)

– Imiquimod (Aldara)

• Curettage for hypertrophic lesions

Treatment of AK’s

Intraepithelial cc.

• Bowen disease

• Erythroplasia Queyrat

• Breast and vulvar Paget disease

Erythroplasia Queyrat

Morbus Bowen treated with Photo-

Dynamic Therapy (PDT)

Brown, The Lancet Oncology, 2004

Paget disease

Rare intraepidermal adenocarcinoma

It can mimic inflammatory or infectious status

Paget disease of the breast associated frequently

with breast cancer (in 50% palpable cc.)

Biopsy-histology!

PAGET DISEASE

Dysplastic nevi

•Precursors for melanoma

•Markers for melanoma

Lentigo maligna melanoma

• Non-melanoma skin cancers (NMSC)

– Basal cell carcinoma

– Squamous cell carcinoma

– Keratoacanthoma

Risk factors for development of BCC and SCC

• Fair skin (Fitzpatrick’s types I-III)– Blue eyes

– Red hair

• Family history– Genetic syndromes

• Chronic sun exposure

• Old age

• Arsenic, tar

Basal cell carcinoma

BCC- clinical types

• Nodular

– Pigmented

– Infiltrative

• Superficial

• Morpheaform

Nodular BCC

• Chronic lesion

• Easy bleeding

• Pearly border

• Surface telangiectasias

• Head and neck, trunk,

and extremities

Pigmented BCC

• Similar to nodular but with

black discoloration

– Melanin deposits

• Pigmented races

• Face, trunk, and scalp

Superficial BCC

• Erythematous scaly plaque

• Slow growth

• Asymptomatic

• Trunk, extremities, face

Morpheaform BCC

• Resembles scar

• Asymptomatic and slow

growing

• Ill-defined margins

• Marked subclinical

extension

• BCC is the most frequent skin cancer (80%)

– BCC is 4x more frequent than SCC

• Metastases are rare (<1% of cases)

Local destruction of tissue

Treatment of BCC

• Curettage electrodessication (ED/C)

• Surgical excision• Traditional

• Mohs surgery

• Radiation therapy

• Topical therapy– imiquimod

Curable in

>95%

important

the longterm

cosmetic,

funcional

result

High risk areas

Swanson

Radiation therapy

Only in 8-10 %

convencional fractionation wherever possible

3D planning, use of modern treatment technique

Interdisciplinary decision

Dermato-oncology team

Radiation oncologist

Surgeon

Dermato-oncologist

Pathologist

Radiologist/expert

in nuclear medicine

Dermatologists

PATIENT

Basalioma treatment

Radiotherapy PDT treatment

Radiotherapy PDT treatment

Radiotherapy PDT treatment

Radiotherapy PDT treatment

Keratoacanthoma

• Low grade SCC

• Rapid growth over

weeks

• Trauma, sun exposure,

HPV 11 and 16

• May progress to

invasive SCC

Invasive SCC

• Erythematous nodule

• Indurated lesion

• Sun-exposed skin

– Men > women

• Slow growth

Invasive SCC

Treatment of SCC

The prognosis is generally good.

The type of treatment depends on the site, size of the lesion and the

age , general health and cosmetic appearance of the patient.

• Excision of the lesion is the treatment of choice in patients under 60.

– Curettage and cautery

– Cryotherapy for small lesions.

• Radiotherapy when surgery is contraindicated in elderly or diseased

patient or when the surgery is very difficult e.g. near the eye.

Large > 15 mm tumors/at the high risk areas

>20 mm at other areas

Locally advanced, deep infiltrating, unfavourable

localised from cosmetic or functional aspect

recurrent tumors

age > 55 years

Indication of RT

Cutaneous lymphomas

T cell lymphoma

- patch

- plaque

- tumor stage

B cell lymphoma – secundaer manifestations

Cutaneous T-cell Lymphoma(Mycosis fungoides)

• 1. premycotic patch stage

poikiloderma

• Plaque stage

Tumor stage

Malignant Melanoma (MM)

Risk factors- MM

• Fair skin, red hair, and blue eyes

• Intermittent sun exposure

– Sunburns

– Tanning beds

• Freckles and melanocytic nevi

• Family history of melanoma

Clinical types- MM

Superficial spreading melanomaLentigo maligna melanoma

Acral lentiginous melanoma Nodular melanoma

ABCD of Melanoma

• Asymmetry

• Border irregularity

• Color variegation

• Diameter >6mm

Prognostic features- MM

• Good prognosis

– Breslow < 1mm

• Intermediate prognosis

– Breslow 1-4mm

• Bad prognosis

– Breslow >4mm

Treatment of MM

• Surgical excision

– In situ = 5 mm margin

– Invasive= 1-3 cm depending on Breslow’s depth

Sentinel lymph node biopsy- MM

• Recommended for MM with Breslow 1-4mm

– Lymphadenectomy for positive nodes

• Powerful prognostic feature for disseminated disease

Adjuvant Radiation Therapy

in N+ dissected lymphnode region in the case

of capsule invasion or >3+lgl

3DCRT

Dose: 50 + 10 Gy

Adjuvant Chemotherapy

– response 25%, durable control 1%

– no survival advantage demonstrated

– single agent dacarbazine (DTIC)

– multiple combinations carmustine, cisplatin,

DTIC, tamoxifen

Adjuvant Immunotherapy

Interferon

>4mm or N+

high dose IFN-alpha-2b, improved disease-free

and overall survival approx. 1 year

26% dropout rate toxicity

Lentigo maligna 5 yr cure 80% (disfiguring, debilitating

location)

Residual, recurrent, unresectable

In transit metastasis

Palliation: circumscribed manifestation

- lymphnode mets

- bone mets

- brain mets

Radiotherapy of Melanoma

Melanoma malignum

FDG-PET positive tumor outside the norm. CT volume N=6

MM

• Incidence and deaths on rise

• Survival rates increasing due to detection and thorough

treatment

• Depth and nodal status most important prognostic

indicators

• SLD useful

• Adjuvant systemic and RT defined

• Novel agents for metastatic disease

Ipilimumab is a monoclonal anti-

body that targets cytotoxic T lym-

phocyte associated antigen 4

(CTLA-4).

This marker is associated with

promoting a regulatory response by

the immune system, slowing it

down.

By knocking it out, ipilimumab

may shift the body’s immune

response from inaction into action.

Mutated in 60-70% of melanoma

90% of mutations are V600E

Davies et al. Nature 2002; 417:949-54 & Wan PT et al. Cell. 2004 19;116(6):855-67

B-RAF, An Oncogene in 7% of

Human Cancers

Response Rates & B-RAF

Mutation Status

combination chemotherapy

response rate

Wild type B-RAF 33%

Mutant B-RAF 11%

Chang et al. J Transl Med. 2004 Dec 21;2(1):46.

NRASB-RAF

MEK

ERK

MAP kinase pathway

inhibitors in melanoma

PD0325901

ARRY-142886

BAY 43-9006/sorafenib

CHR-265 PLX4032

SB-590885

Cutanious soft tissue sarcomas

Dermatofibrosarcoma protuberans

Sarcoma Kaposi

Malignus fibrosus histiocytoma, fibrosarcoma, haemangiopericytoma,

angiosarcoma, liposarcoma, neurofibroma

Sarcoma Kaposi

Radiosensitive disease

Dose: (12-15x2 Gy)