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including autoantibodies&#44; were normal&#44; and the Mantoux test and interferon gamma release assay were negative&#46; Doppler ultrasound showed no signs of thrombosis or thrombophlebitis&#46; Histologic examination of 1 of the lesions showed a preserved&#44; unaltered epidermis but extensive dermal and subcutaneous necrosis with a predominantly lymphocytic inflammatory infiltrate in the septa and lobules of the subcutaneous tissue&#46; Atypical lymphocytes were not observed&#46; Additional findings included signs of vasculitis and scant numbers of histiocytes and lymphocytes forming granulomas &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; Cultures were negative&#46; Based on the above findings&#44; a diagnosis of nodular vasculitis was established&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">Chest radiography and a total body computed tomography scan revealed a solid nodule at the base of the right lung&#46; Fine-needle aspiration showed findings compatible with BRAF wild-type metastatic melanoma&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Having ruled out all other possible causes&#44; the patient was diagnosed with paraneoplastic nodular vasculitis associated with metastatic melanoma&#46; The lesions did not respond to treatment with nonsteroidal anti-inflammatory drugs&#44; oral corticosteroids&#44; or local wound care with hydrocolloid dressings&#46; According to the indications of the oncology department&#44; the patient was administered pembrolizumab 200<span class="elsevierStyleHsp" style=""></span>mg every 3 weeks&#46; After 2 cycles&#44; the lung metastases reduced in size&#44; the subcutaneous nodules disappeared&#44; and all the ulcers showed a reduction in diameter and depth&#46; Unfortunately&#44; the patient fell 4 months after starting treatment and sustained a head injury that required prolonged hospitalization and discontinuation of chemotherapy&#46; His condition progressively deteriorated and he died 2 months later&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Paraneoplastic dermatoses are skin manifestations that are detected before&#44; concurrently with&#44; or after the diagnosis of malignancy&#46; In 1976&#44; Curth proposed 6 criteria for identifying a paraneoplastic dermatosis &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#44; but most authors now agree that the first 2 criteria are sufficient to determine a link&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">Nodular vasculitis is a mostly lobular form of panniculitis with associated vasculitis&#46; It is diagnosed at an average age of 56 years<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> and presents as painful&#44; erythematous&#44; frequently ulcerated&#44; subcutaneous nodules on the posterior aspect of the legs&#46; It has been described in association with tuberculosis&#44;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> autoimmune diseases&#44; inflammatory bowel disease&#44; hematologic diseases&#44; and other infections&#46; Certain medications have also been implicated&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">We detected just 2 cases of nodular vasculitis associated with malignancy in our review of the literature&#46; They involved a 63-year-old woman with lung adenocarcinoma<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a> and a 71-year-old woman with metastatic adenocarcinoma of the colon diagnosed 2 years after the initial diagnosis of nodular vasculitis&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Other paraneoplastic syndromes that should be considered in patients with lesions of this type and associated malignancy are other forms of vasculitis and panniculitis and superficial migratory thrombophlebitis&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">The most common form of paraneoplastic vasculitis is vasculitis&#44; which is mostly seen in association with hematologic malignancies&#44;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">6</span></a> but also lung&#44; prostate&#44; breast&#44; colon&#44; and kidney cancer&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a> It usually manifests as palpable&#44; sometimes ulcerated&#44; purpuric lesions on the lower limbs&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">The classic form of paraneoplastic panniculitis is pancreatic panniculitis&#44;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> which is a lobular panniculitis associated with fat necrosis in patients with pancreatic cancer&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a> It manifests as ulcerated&#44; erythematous nodules on the upper and lower limbs and is accompanied by fever&#44; weight loss&#44; and elevated amylase and lipase levels&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Superficial migratory thrombophlebitis is characterized by recurrent episodes of segmental thrombosis in the superficial veins&#46; It usually manifest as painful lower limb nodules&#44; with histology showing vascular occlusion of a medium or large vein in the subcutaneous tissue&#46; It can occur in association with an occult malignancy &#40;Trousseau syndrome&#41;&#44; in particular mucinous adenocarcinoma&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">Paraneoplastic nodular vasculitis is treated by addressing the underlying malignancy and prescribing anti-inflammatories&#44; rest&#44; and elevation and compression of the affected limb&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">We have reported&#44; to our knowledge&#44; the first case of paraneoplastic nodular vasculitis associated with metastatic melanoma&#46; Although the association between nodular vasculitis and malignancy is rare&#44; an active search for cancer as a possible trigger should always be conducted in the absence of other plausible causes&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Funding</span><p id="par0070" class="elsevierStylePara elsevierViewall">No funding was received for this study&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Conflicts of Interest</span><p id="par0075" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">A&#44; Deep ulcers with an erythematous border and a fibrinous base that persisted despite treatment with nonsteroidal anti-inflammatory drugs&#44; oral corticosteroids&#44; and local dressings&#46; B&#44; Reduction in the diameter and depth of ulcers after 2 cycles of pembrolizumab&#46; C&#44; Linear&#44; erythematous&#44; subcutaneous nodules in the lower limbs&#46; D&#44; Complete resolution of nodules with mild postinflammatory hyperpigmentation after 2 cycles of pembrolizumab&#46;</p>"
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          "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Histologic image &#40;hematoxylin&#8211;eosin&#44; original magnification &#215;20&#41; showing extensive involvement of the dermis and the septa and lobules of the subcutaneous fatty tissue &#40;A&#41;&#44; extensive necrosis in these locations &#40;B&#41;&#44; signs of vasculitis &#40;C&#41;&#44; and scant associated granulomas &#40;D&#41;&#46;</p>"
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Criteria&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&#46; Concurrent onset&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">The dermatosis and malignancy appear concurrently&#46;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">2&#46; Parallel course&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">If the malignancy is successfully treated or recurs&#44; the dermatosis will follow a similar course&#46;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">3&#46; Uniformity&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">A specific malignancy is usually associated with a specific dermatosis&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">4&#46; Statistical significance&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">There is a statistically significant association between the malignancy and the dermatosis based on case-control studies&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">5&#46; Genetic basis&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">A genetic association exists between the dermatosis and the malignancy&#46;&nbsp;\t\t\t\t\t\t\n
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Case and Research Letter
Atypical Nodular Vasculitis—A Diagnostic Clue in Metastatic Melanoma
Vasculitis nodular de presentación atípica: la clave para el diagnóstico en un caso de melanoma metastásico
D. Nieto Rodrígueza,
Autor para correspondencia
dnr348@gmail.com

Corresponding author.
, A. Mayor Ibargurena, L. Quintana Castanedoa, M.J. Beato Merinob, P. Herranz Pintoa
a Servicio de Dermatología, Spain
b Servicio de Anatomía Patológica del Hospital Universitario La Paz, Spain
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including autoantibodies&#44; were normal&#44; and the Mantoux test and interferon gamma release assay were negative&#46; Doppler ultrasound showed no signs of thrombosis or thrombophlebitis&#46; Histologic examination of 1 of the lesions showed a preserved&#44; unaltered epidermis but extensive dermal and subcutaneous necrosis with a predominantly lymphocytic inflammatory infiltrate in the septa and lobules of the subcutaneous tissue&#46; Atypical lymphocytes were not observed&#46; Additional findings included signs of vasculitis and scant numbers of histiocytes and lymphocytes forming granulomas &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; Cultures were negative&#46; Based on the above findings&#44; a diagnosis of nodular vasculitis was established&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">Chest radiography and a total body computed tomography scan revealed a solid nodule at the base of the right lung&#46; Fine-needle aspiration showed findings compatible with BRAF wild-type metastatic melanoma&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Having ruled out all other possible causes&#44; the patient was diagnosed with paraneoplastic nodular vasculitis associated with metastatic melanoma&#46; The lesions did not respond to treatment with nonsteroidal anti-inflammatory drugs&#44; oral corticosteroids&#44; or local wound care with hydrocolloid dressings&#46; According to the indications of the oncology department&#44; the patient was administered pembrolizumab 200<span class="elsevierStyleHsp" style=""></span>mg every 3 weeks&#46; After 2 cycles&#44; the lung metastases reduced in size&#44; the subcutaneous nodules disappeared&#44; and all the ulcers showed a reduction in diameter and depth&#46; Unfortunately&#44; the patient fell 4 months after starting treatment and sustained a head injury that required prolonged hospitalization and discontinuation of chemotherapy&#46; His condition progressively deteriorated and he died 2 months later&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Paraneoplastic dermatoses are skin manifestations that are detected before&#44; concurrently with&#44; or after the diagnosis of malignancy&#46; In 1976&#44; Curth proposed 6 criteria for identifying a paraneoplastic dermatosis &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#44; but most authors now agree that the first 2 criteria are sufficient to determine a link&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">Nodular vasculitis is a mostly lobular form of panniculitis with associated vasculitis&#46; It is diagnosed at an average age of 56 years<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">2</span></a> and presents as painful&#44; erythematous&#44; frequently ulcerated&#44; subcutaneous nodules on the posterior aspect of the legs&#46; It has been described in association with tuberculosis&#44;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a> autoimmune diseases&#44; inflammatory bowel disease&#44; hematologic diseases&#44; and other infections&#46; Certain medications have also been implicated&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">We detected just 2 cases of nodular vasculitis associated with malignancy in our review of the literature&#46; They involved a 63-year-old woman with lung adenocarcinoma<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">4</span></a> and a 71-year-old woman with metastatic adenocarcinoma of the colon diagnosed 2 years after the initial diagnosis of nodular vasculitis&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">5</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Other paraneoplastic syndromes that should be considered in patients with lesions of this type and associated malignancy are other forms of vasculitis and panniculitis and superficial migratory thrombophlebitis&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">The most common form of paraneoplastic vasculitis is vasculitis&#44; which is mostly seen in association with hematologic malignancies&#44;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">6</span></a> but also lung&#44; prostate&#44; breast&#44; colon&#44; and kidney cancer&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">7</span></a> It usually manifests as palpable&#44; sometimes ulcerated&#44; purpuric lesions on the lower limbs&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">The classic form of paraneoplastic panniculitis is pancreatic panniculitis&#44;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">8</span></a> which is a lobular panniculitis associated with fat necrosis in patients with pancreatic cancer&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">9</span></a> It manifests as ulcerated&#44; erythematous nodules on the upper and lower limbs and is accompanied by fever&#44; weight loss&#44; and elevated amylase and lipase levels&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Superficial migratory thrombophlebitis is characterized by recurrent episodes of segmental thrombosis in the superficial veins&#46; It usually manifest as painful lower limb nodules&#44; with histology showing vascular occlusion of a medium or large vein in the subcutaneous tissue&#46; It can occur in association with an occult malignancy &#40;Trousseau syndrome&#41;&#44; in particular mucinous adenocarcinoma&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">10</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">Paraneoplastic nodular vasculitis is treated by addressing the underlying malignancy and prescribing anti-inflammatories&#44; rest&#44; and elevation and compression of the affected limb&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">3</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">We have reported&#44; to our knowledge&#44; the first case of paraneoplastic nodular vasculitis associated with metastatic melanoma&#46; Although the association between nodular vasculitis and malignancy is rare&#44; an active search for cancer as a possible trigger should always be conducted in the absence of other plausible causes&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Funding</span><p id="par0070" class="elsevierStylePara elsevierViewall">No funding was received for this study&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Conflicts of Interest</span><p id="par0075" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
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        "fuente" => "<span class="elsevierStyleItalic">Source</span>&#58; Adapted from Thiers et al&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a>"
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Criteria&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Definition&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46; Concurrent onset&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">The dermatosis and malignancy appear concurrently&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46; Parallel course&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">If the malignancy is successfully treated or recurs&#44; the dermatosis will follow a similar course&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&#46; Uniformity&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">A specific malignancy is usually associated with a specific dermatosis&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#46; Statistical significance&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">There is a statistically significant association between the malignancy and the dermatosis based on case-control studies&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&#46; Genetic basis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">A genetic association exists between the dermatosis and the malignancy&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Curth&#39;s postulates for paraneoplastic dermatoses&#46; These criteria are used to determine a consistent relationship between an internal malignancy and a dermatosis&#46;</p>"
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