Carcinoma of the skin (overview) C44.L

Cutaneous carcinomas are malignant epithelial tumors of the skin with destructive growth and potential metastasis. They originate from epithelial keratinocytes and are responsible for non-melanocytic skin cancers. Carcinomas of the skin are characterized by a wide range of clinical symptoms and varying prognoses (see classification).

Carcinoma of the skin (classification)

Squamous cell carcinoma of the skin (SCC)

• In situ squamous cell carcinoma of the skin
  • In situ carcinoma of the actinic keratosis type
  • In situ carcinoma of Bowen's disease type
• Invasive squamous cell carcinoma of the skin
  • Squamous cell carcinoma of the skin - classic type -
  • Follicular squamous cell carcinoma (originating in the upper infundibular region of the hair follicle)
  • Acantholytic SSC
  • Mucinsecreting SSC
  • Desmoplastic SSC
  • Small cell SSC
  • Clear cell SSC
  • Lymphoepithelioma-like carcinoma of the skin.
  • Keratoacanthoma
  • Verrucous carcinoma:
    • Carcinoma cuniculatum
    • Cutaneous verrucous carcinoma (papillomatosis cutis carcinomatosa)
    • Oral verrucous car cinoma (florid oral papillomatosis)
    • Condylomata gigantea (Buschke-Löwenstein tumor).

Basal cell carcinoma of the skin

• Nodular basal cell carcinoma (>50% of cases)
• Superficial basal cell carcinoma (15% of cases)
• Sclerodermiform basal cell carcinoma (about 25% of cases)
• Pigmented basal cell carcinoma
• Ulcerated basal cell carcinoma
• Destructive basal cell carcinoma (ulcus terebrans) (<1% of cases)
• Premalignant fibroepithelioma (Pinkus tumor)

Adnexal carcinoma:

• Eccrine adnexal carcinoma:
  • Porocarcinoma and hidradenocarcinoma, eccrine
  • spiradenocarcinoma and cylindrocarcinoma
  • Other eccrine carcinomas (eccrine carcinoma, adenoid cystic carcinoma, mucinous carcinoma, polymorphous sweat gland carcinoma).
• Apocrine adnexal carcinoma:
  • Agressive digital papillary adenoma.
  • Apocrine sweat gland carcinoma
  • Paget 's disease
  • Extramammary Paget's disease
  • Malignant mixed tumor
  • Microcystic adnexal carcinoma
  • Cribriform apocrine carcinoma of the skin
• Follicular adnexal carcinoma:
  • Pilomatrix carcinoma
  • Tricholemmal carcinoma.

Neuroendocrine differentiated carcinoma:

• Merkel cell carcinoma.

In common medical usage, carcinomas of the skin/mucosa are also named according to their location. Common names are:

• Lip carcinoma
• Carcinoma of the tongue
• Penile carcinoma
• Vulvar carcinoma

The development of malignancies, which begins with the transformation of the cell into a tumour cell, is now understood as a multiphase phenomenon that can last for years or even decades. It is a gradual disturbance of biological equilibrium processes, at the beginning of which the transformation (by chemical, physical, viral etc. influences) of gene sequences (proto-oncogenes) into oncogenes takes place (initiation). In epidermal malignancies, the p53 gene is the best known tumour suppressor gene. 60-75% of squamous cell carcinomas show alterations of the p53 gene. Mutations in the p53 gene are typical UV damage. They cause that UV damage is no longer repaired to a sufficient extent. Oncogenes of the ras family (mutations in the ras gene lead to growth impulses) and bcl-2 (apoptosis inhibitors) are also involved.

The transformation area generally remains without growth tendency at first; only with further exposure to carcinogens or unspecific damage (co- and syncarcinogenesis) does the tissue transform towards preneoplasia (see below precancerosis, AIN, KIN, CIN, PIN), which may persist for a long time as a precursor of the malignant tumour (latency phase) or even regress. Finally, preneoplasia turns into primary neoplasia, the malignant tumour, which sooner or later manifests itself clinically.

Remarkably, there are differences to basal cell carcinoma in the behaviour of the tumour cell assemblies when stained with the antibody BerEp4, which detects the "epithelial cell adesion molecule" EpCAM. Since this antibody is not expressed in squamous cell carcinomas, it represents an important differentiation possibility between the two tumour entities.

Predisposing factors in the development of malignant epithelial tumours:

• Physical carcinogenesis: UV rays, ionizing rays, infrared rays
• Chemical carcinogenesis: methylcholantrenes, benzpyrene, azo dyes; by means of corrosive agents Food, exhaust fumes and cigarette smoke can spread carcinogenic substances.
• Viral carcinogenesis: Oncogenic viruses (human papilloma viruses: HPV 5, 16, 18) can cause malignant tumours. Viral genes are transferred into the genome of host cells, causing a transformation of the infected cells.
• Immunological carcinogenesis: Mutation of one or more cells to malignancy is assumed. The properties changed by mutations are transferred to the daughter cells. This process is suppressed when the immune system is functioning normally. A tumor disease only develops when individual tumor cells temporarily elude the immune system's grip and can grow into a larger tumor cell complex through cell division.
• Chronic inflammation: Tumour formation due to the chronic inflammatory stimulus, e.g. lichen planus, lichen sclerosus et atrophicus, lupus vulgaris, porokeratosis, chronic ulcers, fistulas.
• Genodermatoses: Xeroderma pigmentosum, epidermodysplasia verruciformis, albinism
• Individual factors: light skin, ray scars.

• Degree x (Gx): no determination possible
• Grade 1 (G1): < 25%
• Grade 2 (G2): 25-50%
• Grade 3 (G3): 50-75%
• Grade 4 (G4): > 75%.

• tumour thickness >2mm
• Penetration depth from Clark level 4
• Degree of de-differentiation from grade 3
• Perineural invasion

See under the respective entities.

In the case of invasively growing carcinomas of the skin, a surgical procedure will generally be regarded as the first choice therapy.

In principle, "the bigger the better" applies. This basic principle bears the danger of overtherapy. In this respect, the safety distance of the first excision is individually selected, adapted to the localisation, tumour size and type, growth behaviour - continuous or discontinuous - as well as the age of the patient. This "individualized" procedure requires a high level of competence in histological workup. The complete visualization of the excision margins by means of a three-dimensional examination technique (3D-histology) is superior to any other histological procedure in terms of sensitivity. A surgical procedure secured in this way can reduce the local recurrence rate to below 2%. If necessary and sensible, it allows to work with small safety margins during primary excision and still avoid local recurrences. In the case of an R1 resection, topographical preparation of the excidate and assignment of a tumour excision allows a precise and gentle follow-up operation until the tumour is free.

Each tumor entity and its subtypes has its specific local infiltration patterns. Often they are asymmetrical, not distributed over the entire circumference and thus clinically difficult to assess. This must be taken into account especially in the case of desmoplastic squamous cell carcinoma (high local recurrence rate) or even in the case of very large tumour nodes.

1. Boehringer A et al (2015) Analysis of incomplete excisions of basal-cell carcinomas after breadloafmicroscopy
   compared with 3D-microscopy: a prospective randomized and blindedstudy
   . J Cutan Pathol doi: 10.1111/cup.12535Breuninger
   H (2011) Project Sentinel Node in squamous cell carcinoma. Abstract CD 46th DDG meeting AKS23/04
2. Breuninger H (2015) Safety distances for malignant skin tumours. derm 21: 203-212
3. Farasat S et al (2011) A new American Joint Committee on cancer staging system for cutaneous squamous cell carcinoma: Creation and rationale for inclusion of tumor (T) characteristics. J Am Acad Dermatol in press
4. Mieczko A et al (2011) BerEP4-negative basal cell carcinoma of the palm: Case report and literature review. JDDG 9:140-143