What are cutaneous markers of internal malignancy?

Skin changes can often be the first sign of a deeper problem including an internal malignancy. Signs of skin disease may precede, occur with, or follow the detection of associated cancer. These skin diseases can be a feature of undiagnosed cancer and may be the prompt for a thorough examination in patients. Or in a patient whose cancer is in remission, these skin diseases may be the initial sign of cancer recurring.

Cutaneous markers can be classified into 2 major types:

• Genetically determined syndromes with a cutaneous component (genodermatoses) that predispose at-risk individuals to develop cancer
• Paraneoplastic syndromes which occur as a result of circulating factor(s) or presumed factors produced by the underlying cancer

Genodermatoses

Skin diseases that come under the group of genodermatoses include:

• Birt–Hogg–Dubé syndrome
• Cowden disease
• Gardner syndrome
• Gorlin syndrome (basal cell naevus syndrome)
• Multiple endocrine neoplasm type 2B
• Neurofibromatosis
• Peutz-Jeghers syndrome
• Torre-Muir syndrome
• Progeria (premature ageing syndromes)

Paraneoplastic syndromes

Cutaneous paraneoplastic syndromes can be categorised according to the type of lesion they produce.

Papulosquamous

• Acanthosis nigricans
• Acquired ichthyosis
• Acrokeratosis paraneoplastica
• Extramammary Paget disease
• Florid cutaneous papillomatosis
• Palmoplantar keratoderma
• Pityriasis rotunda
• Sign of Leser-Trelat
• Tripe palms

Erythematous

• Dermatomyositis
• Erythema gyratum repens
• Hypertrophic osteoarthropathy and digital clubbing
• Multicentric reticulohistiocytosis
• Necrolytic migratory erythema
• Sweet disease
• Eosinophilic dermatosis of haematologic malignancy

Bullous

• Paraneoplastic pemphigus

Miscellaneous

• Generalised granuloma annulare (rarely)
• Granulomatous dermatitis
• Carcinoid syndrome
• Hypertrichosis lanuginosa acquisita
• Trousseau syndrome
• Paraneoplastic pruritus (cancer itch)

As well as cutaneous signs and symptoms, paraneoplastic syndromes may affect endocrine, neuromuscular, musculoskeletal, cardiovascular, haematological, gastrointestinal or renal function.

Paraneoplastic symptoms may be caused by:

• Immune reaction: antibodies, T cells or cytokines
• Hormones or hormone precursors
• Enzymes
• Embryonic or fetal proteins
• Altered metabolic pathways
• Unknown factors