Cutaneous presentation of tumours

A Lang Oct 2013

Background• Skin changes can be the first sign of

an internal neoplasm.• They may become more apparent

following detection of a malignant tumour.

• Skin diseases may indicate recurrence of cancer in previously remitting patients.

• Genetic syndromes with a cutaneous component are named genodermatoses. These predispose individuals to cancer development.

• Paraneoplastic syndromes may occur as a result of circulating factors produced by the underlying malignancy.

1) Genodermatoses• Cowden’s disease

A rare autosomal dominant condition.Characteristic papules on body (hamartomas).1

Diverse phenotypes with an increase risk of breast, endometrial, thyroid, kidney and colorectal cancers.

• Gardner syndrome

-Benign lipomas, frontal & maxillary osteomas.(often get exophthalmos)

-Related to familial adenomatous polyposis(FAP). Colon polyps become malignant and extracolonic tumours of thyroid, craniofacial skeleton & cysts of the epidermis.

Picture from case study. 2

• Muir-Torre syndrome

MTS is a rare autosomal dominant disorder characterised by sebaceous cyst tumours.

Common internal malignancies associated with the syndrome include GI, GU & breast cancers.

78 year old male with a lobulated mass in left upper eyelid & lateral canthus.3

Neurofibromatosis4

• NF type 1 (von Recklinghausen disease)

-Neurofibromatosis is a genetic disorder inherited in an autosomal dominant fashion.-It presents with a phenotype of benign tumours of the nervous system all over the body. These soft tissue tumours can grow to incredible sizes and be debilitating. They may cause damage to nerves & underlying structures due to compressive effects.-Every year in the UK, 300 babies are born with the condition.

• NF type 2 (schwannoma)A less common variant of the disorder presents with acoustic neuromas of CN8 and leads to hearing loss in both ears.

Characteristic café au lait spots of NF 1.

Elderly gentleman with severe NF type 1

Gorlin’s syndrome• Also known as naevoid basal cell carcinoma.• An inherited mutation which has a phenotupe of skin

tags and cysts, cysts on the jaw, limb abnomalities, medulloblastoma & benign tumours of the ovaries.

• Also, calcified falx cerebri on MRI.• Treatment can involve cryotherapy for skin lesions.5

MEN syndromes• Multiple endocrine neoplasia (MEN) syndromes

are inherited conditions in which several endocrine glands develop benign or malignant tumours or hyperplasia. Either type 1 or type 2.6

• MEN type 2B disease (development of medullary carcinoma of the thyroid and phaeochromocytoma. (>BP))

• MEN type 2B disease is characterised by early development of mucosal neuromas.

• These appear as shiny bumps around the lips, tongue and in the mouth, bumps on the eyelids, cornea and conjunctiva.

• GI tract growths cause diarrhoea, constipation and in rare occasions, megacolon.

• Individuals often have a Marfanoid appearance.

2) Paraneoplastic syndromes

• Sweet’s syndrome -Also known as acute febrile neutrophilic dermatosis & presents with pyrexia and the appearance of tender red lumps (erythematous plaques) on the skin.

-In 50% of cases, the aetiology cannot be determined, however, examples of causes include URTIs, IBD, RA and pregnancy.

-In rare cases it may be associated with internal malignancy (acute myelogenous leukaemia (20% of cases)) or an underlying blood disorder.7

• Acanthosis palmaris (Tripe palms)

• Thickened, leathery palms with the appearance of tripe associated with internal tumours in 90% of cases. (usually ca of stomach or lung)

• The skin disease is very rare, but usually precedes the cancer diagnosis

• Often seen in conjunction with acanthosis nigricans. (hyperpigmentation)

Acanthosis nigricans in axilla

• Bazex syndrome• ‘Acrokeratosis neoplastica’ has features similar to

psoriasis and is often associated with SCC of the GI tract.5

• >M:F ratioPainful paronychia (swollen cuticles)

• Dermatomyositis• A rare, acquired disease of muscles which

presents with skin rash. It is part of the inflammatory myopathies group of diseases. It can be a sign of many internal malignancies, but particularly ovarian8, lung, pancreatic, stomach & colorectal cancers & non-Hodgkin lymphoma.

A range of clinical signs:

-Red and blueish patches on sun-exposed skin.-Heliotrope eyelids (purple)-Purple spots on bony prominences such as MCP & IP joints. (known as Gottron’s papules)-Scaly scalp with much dandruff.-Less commonly there is poikiloderma (atrophic, thin, pale skin)

Heliotrope eyelid

• 2o Hypertrophic osteoarthropathy

-A clinical sign of internal malignancy (peripheral non-small cell ca of lung) or chronic disease.

-The underlying disease usually precedes the cutaneous sign, however, there have been cases of the clubbing preceding identification of internal malignancy.

• Necrolytic migratory erythema

-Rash affecting any site, but particularly the groin, lower legs, genitalia and anal regions. It is a ring-shaped reddened area which blisters and crusts over eventually resulting in necrosis of the skin.

-Due to excessive levels of glucagon circulating in the blood which could be a result of the glucagonoma tumour of the pancreas, but also to other causes of excessive glucagon.

• Generalised granuloma annulare

-A rare presentation of underlying lymphoma, HIV infection or solid tumours.

-Presents as a dessiminated papules arranges in rings.

• Erythema annulare centrifugum-Red, annular skin eruptions are a rare sign of malignancy.

Erythema due to an underlying gastric carcinoma.

• Trousseau’s syndrome (sign of malignancy)

-A clinical sign of gliomas and adenocarcinomas of the pancreas and lung associated with hypercoaguability.

-Crops of tender nodules are seen in affected veins and migratory blood clots are seen in deep and superficial veins of the extremities.9

For reference1 Eng C. Will the real Cowden syndrome please stand up: revised diagnostic criteria. J Med Genet. 2000;37:828-830.

2 Vaswani B A, Shah M, Shah P M, Parikh B J, Anand A S, Sharma G L. Giant mesenteric fibromatosis in Gardner's syndrome. Indian J Cancer. 2011;48:140-2.

3 Rishi K, Font RL. Sebaceous gland tumors of the eyelids and conjunctiva in the Muir-Torre syndrome: a clinicopathologic study of five cases and literature review. Ophthal Plast Reconstr Surg. 2004 Jan;20(1):31-6.

4 Harvard Medical School Centre for Neurofibromatosis and Allied Disorders. CNfAD: What is NF? [online]. Available from: http://www.cnfad.org/nf.html/ [Accessed 20 October 2013].

5 New Zealand Dermatological Society Incorporated. DermNet NZ: Cutaneous markers of internal malignancy. [online]. Available from: http://www.dermnetnz.org/systemic/malignancy.html/ [Accessed 20 October 2013].

6 Stanford Medicine Cancer Institute. Medullary Thyroid Cancer (MTC). [online]. Available from: http://cancer.stanford.edu/information/geneticsAndCancer/types/mtc.html/ [Accessed 20 October 2013].

7 British Association of Dermatologists. Patient Information Leaflet: Sweet’s Syndrome (Acute Febrile Neutrophilic Dermatosis). [online]. Available from: http://www.bad.org.uk/Portals/_Bad/Patient%20Information%20Leaflets%20(PILs)/Sweets%20Syndrome%20May%202012%20-%20lay%20reviewed%20May%202012.pdf/ [Accessed 20 October 2013].

8 Hill CL, Zhang Y, Sigurgeirsson B, Pukkala E, Mellemkjaer L, Airio A, Evans SR, Felson DT. Frequency of specific cancer types in dermatomyositis and polymyositis: a population-based study. Lancet. 2001;Jan 13;357(9250):96-100.

9 Varki A. Trousseau's syndrome: multiple definitions and multiple mechanisms. Blood. 2007;Sep 15;110(6):1723-9.