PARANEOPLASTIC SKIN SYNDROMES Juraj Hegyi 2/21/22 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 • Scleromyxoedema • Livedo reticularis • Chronic urticaria • Erythema anulare centrifugum • • • Hypertrichosis lanuginosa acquisita 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