Cutaneous signs of malignancy (paraneoplastic dermatoses)

Overview

Paraneoplastic dermatoses are skin conditions arising as a remote effect of malignancy - not from direct invasion - via ectopic hormone/growth factor secretion, autoimmune cross-reactivity, or hypercoagulability. They may precede cancer diagnosis, making recognition potentially lifesaving.

Presentation

•Acanthosis nigricans - velvety brown-black thickening in axillae, neck, groin; mucosal variant and 'tripe palms' highly specific for malignancy

•Malignant form: older adult, non-obese, non-diabetic, rapid onset, mucosal involvement - vs benign form associated with insulin resistance and obesity

•Dermatomyositis - heliotrope rash (blue-purple periorbital discolouration + oedema), Gottron papules (violaceous flat-topped papules over knuckles), shawl/V-sign photosensitive rash, mechanic's hands, periungual erythema + proximal muscle weakness

•Necrolytic migratory erythema - cyclical erosive rash (macules → blisters → erosions → crusted hyperpigmented lesions) in perineum, perianal, lower abdomen; associated weight loss, diabetes, anaemia, glossitis

•Paraneoplastic pemphigus - almost always painful oral erosions + conjunctival/genital involvement + polymorphic skin blisters; more mucosal and more refractory than classic pemphigus vulgaris

•Sweet syndrome - sudden tender red-violet mammillated plaques on face/neck/upper limbs + fever + raised CRP/ESR + peripheral neutrophilia

•Trousseau syndrome - recurrent thrombophlebitis at unusual/migrating sites (chest wall, arms); warfarin-resistant (mucin activates factor X directly)

•Erythema gyratum repens - 'wood-grain' concentric gyrate bands with trailing scale moving several cm/day; essentially pathognomonic for malignancy

Investigations

🥇 First-line

•FBC, LFTs, calcium, LDH, CRP/ESR; CK (markedly raised in dermatomyositis); CT chest/abdomen/pelvis (broad malignancy screen); skin biopsy (confirms dermatosis)

🥈 Second-line

•anti-TIF1-gamma (anti-p155/140) in dermatomyositis - positive = red flag for underlying cancer; fasting glucagon (>500 pmol/L in glucagonoma); upper GI endoscopy (acanthosis nigricans/Leser-Trélat); DIF of perilesional skin (paraneoplastic pemphigus - IgG + complement in intercellular spaces and BMZ); serum protein electrophoresis/bone marrow biopsy if haematological malignancy suspected

•Gold standard (dermatomyositis): MRI muscle + muscle biopsy + EMG

🚨

Anti-TIF1-gamma (anti-p155/140) positivity in dermatomyositis substantially raises the probability of cancer-associated dermatomyositis - trigger a thorough malignancy screen.

Management

•Overarching principle: treat the underlying malignancy first - remission often resolves the dermatosis

•Dermatomyositis: prednisolone 1 mg/kg/day, tapered by CK and clinical response; refractory: add azathioprine or methotrexate (or mycophenolate mofetil)

•Paraneoplastic pemphigus: prednisolone +/- rituximab or ciclosporin; mucosal care; response poor unless tumour treated

•Necrolytic migratory erythema: surgical resection of glucagonoma if operable; octreotide (somatostatin analogue) if inoperable; nutritional supplementation (zinc, amino acids)

•Sweet syndrome: prednisolone - produces rapid dramatic improvement; treat underlying haematological malignancy

•Trousseau syndrome: LMWH preferred over warfarin (mucin-mediated coagulation is warfarin-resistant)

Complications

•Paraneoplastic pemphigus - bronchiolitis obliterans (severe, often fatal; highest mortality of all paraneoplastic dermatoses)

•Dermatomyositis - interstitial lung disease (major mortality cause), aspiration pneumonia, cardiac arrhythmias/cardiomyopathy

•Glucagonoma/NME - ~50-80% are malignant with metastases at presentation

•Trousseau syndrome - PE, arterial thrombosis, stroke from non-bacterial thrombotic endocarditis

⚠️

Paraneoplastic pemphigus carries the worst prognosis of all paraneoplastic dermatoses - bronchiolitis obliterans may progress even after tumour treatment.

Key associations

Classic paraneoplastic dermatoses and their malignancy associations

Dermatosis	Associated malignancy	Key distinguishing feature
Acanthosis nigricans	Gastric adenocarcinoma (most common)	Velvety, hyperpigmented flexural plaques; mucosal involvement = highly specific for malignancy
Leser-Trélat sign	GI adenocarcinoma, lymphoma	Sudden eruption/rapid increase in seborrhoeic keratoses; often co-occurs with acanthosis nigricans
Dermatomyositis	Ovarian, lung, GI, breast cancers	Heliotrope rash, Gottron papules, proximal muscle weakness
Necrolytic migratory erythema	Glucagonoma (pancreatic alpha-cell tumour)	Cyclical erosive rash in perineum/lower abdomen; raised glucagon
Paraneoplastic pemphigus	NHL, CLL, Castleman disease, thymoma	Refractory painful oral erosions + polymorphic skin blisters
Sweet syndrome	AML (most common haematological)	Tender red-violet oedematous plaques + fever + neutrophilia
Trousseau syndrome	Mucin-secreting adenocarcinoma (pancreatic, gastric, lung)	Migratory superficial thrombophlebitis in unusual sites
Acquired ichthyosis	Hodgkin lymphoma (classic)	Adult-onset dry scaling skin; no personal/family history of ichthyosis
Erythema gyratum repens	Lung cancer (most common)	'Wood-grain' gyrate bands moving several cm/day - essentially pathognomonic