Cutaneous markers of internal malignancy

What are cutaneous markers of internal malignancy?

Skin changes may be the first sign of an internal problem including a visceral 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

Genetic diseases which carry an increased risk of internal malignancy and skin signs as part of the syndrome include:

• Basal cell naevus syndrome (Gorlin syndrome)
• Birt–Hogg–Dubé syndrome
• Cowden disease
• Gardner syndrome
• Lynch syndrome (Muir-Torre syndrome)
• Multiple endocrine neoplasm type 2B
• Neurofibromatosis
• Peutz-Jeghers 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 neoplastica
• Extramammary Paget disease
• Florid cutaneous papillomatosis
• Palmoplantar keratoderma
• Pityriasis rotunda
• Sign of Leser-Trelat
• Tripe palms

Erythematous

• Acute febrile neutrophilic dermatosis (Sweet syndrome)
• Dermatomyositis
• Eosinophilic dermatosis of haematologic malignancy
• Erythema gyratum repens
• Hypertrophic osteoarthropathy and digital clubbing
• Multicentric reticulohistiocytosis
• Necrolytic migratory erythema

Bullous

• Paraneoplastic pemphigus

Miscellaneous

• Carcinoid syndrome
• Granulomatous dermatitis
• Hypertrichosis lanuginosa acquisita
• Paraneoplastic pruritus (cancer itch)
• Trousseau syndrome

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

Paraneoplastic symptoms and signs 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.