PARANEOPLASTIC SKIN SYNDROMES Juraj Hegyi 1/14/22 Paraneoplastic Syndromes (PNS) ● Paraneoplastic syndromes are a heterogeneous group of rare diseases, which are caused by a change in the response of the immune system to the present neoplasm ● Are defined as non-metastatic systemic manifestations, irregularly accompanying cancers ● They are conditioned by the presence of the tumor, but they manifest in the tissue in which the tumor is not present Paraneoplastic Syndromes (PNS) ● Endocrinological, neurological, cutaneous, GI, hematological, non-specific ● First described PNS 1890 M.Auché ● Skin PNS Helene Ollendorf Curth Pathophysiology ● ● Formation of antibodies directed against tumors cells, they cause a cross-reaction against healthy tissue Formation and release of physiologically active substances by the tumor itself (hormones, hormonal precursors, enzymes, cytokines) ● Production of embryonic proteins (CEA, AFP, CA19-9.…) ● Idiopathic Epidemiology ● Men 10-15% ● Women 2-20% ● Distribution the same in both sexes regardless of age ● PNS death statistics are not available Paraneoplastic Syndromes (PNS) ● There is a time coincidence between the onset of the syndrome and cancer At the same time • In progress • Precedes the manifestation There is a parallel relationship between the syndrome and the tumor (regression during successful therapy, flare-up on exacerbation) • ● Paraneoplastic skin syndromes ● Obligatory ● Facultative • Acanthosis nigricans maligna • Dermatomyositis • Leser-Trélat sign • Pemphigus paraneoplasticus • Ichtyosis acquisita • Sweet syndrom • Hypertrichosis lanuginosa acquisita • Scleromyxoedema • Livedo reticularis • Chronic urticaria • Erythema anulare centrifugum • • Acrokeratosis paraneoplastica Bazex Erythema necrolyticum migrans Erythema necrolyticum migrans ● Glucagon secreting tumor of the pancreas ● Often preceded by the tumor ● Peripherally spreading erythema, maculopapules and blisters, painful eroded lesions ● Annular and circinary weeping lessions ● Glossitis, stomatitis, DM, anemia, weight loss ● intertriginous areas, face, torso and limbs Erythema necrolyticum migrans Erythema necrolyticum migrans Erythema necrolyticum migrans ● Frequent candida or bacterial superinfections ● Differentily sometimes mistaken for candidiasis or intertriginous dermatitis ● Therapy depends on the treatment of underlying disease, otherwise symptomatic Erythema gyratum repens ● Rapidly spreading, migrating erythema ● Marked to almost debilitating pruritus ● Propagation centrifugally on upper torso and limbs ● Appears a few months before tumor ● Bizarre, tree-like shapes with “Wood graine” ● Tumors of the lung, esophagus, stomach, breast, uterus, prostate ● Disappears several weeks after tumor removal Erythema gyratum repens Erythema gyratum repens ● Dg. made by clinical image ● non-specific histology, acanthosis, hyperkeratosis, focal parakeratosis, islet spongiosis, perivascular mixed round cell infiltrate ● Neither general nor topical CS have a major effect ● Retinoids also have no significant effect ● Symptomatic alleviation of pruritus, treatment of the underlying disease Hypertrichosis lanuginosa acquisita ● Rapid formation of fine lanuginous, unpigmented hair ● Glossitis with red tongue ● Tumors of the colon and rectum, stomach, bladder, lungs and breast ● Noticeably more common in women ● diff. other causes of acquired hypertrichosis should be ruled out (porphyria, AIDS) Hypertrichosis lanuginosa acquisita Acrokeratosis paraneoplastica Bazex ● Rare dermatosis, typical for men ● Up to 65% precedes the tumor by up to a year! ● Psoriasiform lesions, erythemosquamous ● Hyperkeratotic deposits on the fingers, toes, auricles, tip of nose, elbows and knees ● Gradual development of lesions ● Dystrophic nail changes ● Squamous cell carcinomas of the pharynx, esophagus, larynx, lung, urogenital tract, lymphoma Acrokeratosis paraneoplastica Bazex Acrokeratosis paraneoplastica Bazex Acrokeratosis paraneoplastica Bazex ● Treatment of the underlying disease ● Topical keratolytics, retinoids in combination with CS ● CS in general, retinoids in general, PUVA ● Prognosis depends on the underlying disease ● Think of dg., look for malignancy! Acanthosis nigricans maligna ● Symmetrically thickened velvety skin of yellow-brown to grayblack color with hyperkeratotic papules ● Intertriginous region, neck, extensor surfaces of the limbs, nipples, sometimes on the mucous membranes of the lips and mouth ● Gastrointestinal adenocarcinomas (70-90%), more rarely lung, uterine, ovarian, prostate, lymphoma and sarcoma ● Distinguish the benign form, which arises in childhood most often in the axilla or in adulthood in obese patients with hyperhidrosis and/or diabetes ● Marked pruritus Acanthosis nigricans maligna Acanthosis nigricans palmaris ● ● ● Occurs in 75% concomitantly with acanthosis nigricans Diffusely thickened rough skin, yellowish color Palms with a typically furrowed surface and small hyperkeratotic skin colored papules Acanthosis nigricans palmaris Leser - Trélat sign/syndrome ● Characterized by the eruptive emergence of numerous rapidly growing seborrheic warts on the torso, limbs, and later in the face ● Annoying with severe pruritus ● About 20% is associated with acanthosis nigricans ● Leser-Trélate syndrome occurs in tumors of the stomach and colon, breast, lung, ovary, uterus, kidney, liver and pancreas ● Also associated with HIV Leser - Trélat sign/syndrome Pemphigus paraneoplasticus ● Severe erosive stomatitis, pharyngitis and conjunctival involvement ● Skin blisters, lichenoid manifestations resembling GVHD ● Multiforme manifestations and palm involvement ● Lung involvement is typical (bronchiolitis obliterans, alveolitis) ● Non-Hodgkin lymphoma, thymomas, sarcomas, Castleman's tumor Pemphigus paraneoplasticus Erythema annulare centrifugum ● Reddish slow-growing deposits with raised edges and a sunken center with collarlike peeling ● Resembles hives ● Has been described in lymphomas, breast, lung and gastrointestinal cancers ● Also infections, infestations, autoimmune diseases Erythema annulare centrifugum ● Diff. dg. Erythema gyratum repens, erythema necrolyticum migrans, tinea, hives ● Treat underlying diseases, antihistamines, antiphlogistics Take home message ● Cutaneous paraneoplastic syndromes represent a heterogeneous group of skin diseases, the recognition of which may enable the early detection of an as yet unmanifested malignancy ● Approximately 70% of neoplasias in patients with manifest paraneoplastic syndrome can be detected by a simple clinical examination and basic screening ● Unfortunately, most skin paraneoplastic syndromes are associated with unresponsive cancers and the prognosis is often poor ● Think about cancer as a possible diagnosis Good Luck on the Exam