3.3.15 Paraneoplastic Disorders

EL10

Cutaneous markers of internal malignancy.

No clear data in general, however, prevalence of association of skin signs with the individual neoplasm exist.

Cutaneous markers for underlying malignancies (not including metastases). Parallel course for tumour or blood diseases and skin findings, with improvement when neoplastic proliferation is removed or treated and worsening with recurrence or progression. 

• 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
• Factors related to neoplastic disorders are: immune reaction and production of  tumor-associated antibodies from tumor or lymphoma cells or T cells or certain cytokines, enzymes, embryonic or fetal or other growth factors / proteins, hormones or hormone precursors incl. altered pathways of several metabolisms.

Very different and depending on the underlying disease producing several clinical patterns involving all skin structures incl. adnexes, musculoskeletal system and nerves.

The localization may be localized or generalized, mostly symmetrical because of circulating factors.

• Obligate paraneoplastic disorders /syndromes (almost 100% tumour-associated): Necrolytic migratory erythema (glucagonoma syndrome), acrokeratosis paraneoplastica of Bazex, acanthosis nigricans maligna, paraneoplastic pemphigus, erythema gyratum repens, hypertrichosis lanuginosa acquisita.
• Obligate paraneoplastic genodermatoses/syndromes:  Birt–Hogg–Dubé syndrome, Cowden disease, Gardner syndrome, basal cell naevus syndrome, Peutz-Jeghers syndrome, Torre-Muir syndrome.
• Facultative paraneoplastic disorders (less reliable markers, but still deserve investigation): Ichthyosis acquisita, thrombophlebitis migrans, dermatomyositis in adults, bullous pemphigoid, Sweet’s syndrome, paraneoplastic pruritus, endocrine flushing ( carcinoid). 

The laboratory work up is depending of the suspected tumor which includes skin biopsy, immunofluorescence, immunoblotting and tumor markers. Blood marker of hematological diseases.

Depends on skin signs, often similar microscopic picture as the disease the paraneoplastic one is mimicking. Some are specific: dermatomyositis or in correlation with the clinic such as genodermatoses related neoplasias.

Depending on type of paraneoplastic disorder. Removal of tumor can lead to complete resolution of symptoms.

Depending on underlying neoplasm.

Often to be made by clinical picture and case history and laboratory and imaging techniques/ procedures.

The clinical picture resembles the picture of a skin disorder, therefore, a great variety has to be excluded.

No prevention possible despite early detection by regular tumor prevention programs. Family members of some syndromes with genetical background need to be regularly checked.

Therapy depends on underlying tumor / hematological disease.

Because of orphan status of paraneoplastic skin disorders always dermatologic examination necessary and interdisciplinary work up.