Paraneoplastic pemphigus (PNP), first described in 1990, is an autoimmune mucocutaneous blistering disease which is associated with an underlying malignancy and is characterized by polymorphic clinical signs. Pathogenesis is due to an aberrant autoimmune response against the proteins of the plakin family such as plectin, envoplakin, periplakin, desmoplakin I and II, and bullous pemphigoid antigen I (BP230), although several cases of PNP with antibodies to desmoglein (Dsg) 1 and 3 have been described. A 77-year-old man was admitted to our Oral Medicine Unit because of recalcitrant severe oral bullous ⁄erosive mucositis with crusting lesions of the lips, accompanied by marked conjunctivitis of both eyes, with cutaneous bullous lesions of the abdomen and bilaterally of the hip and inguinal area. Nikolsky’s sign, performed on the oral mucosa and skin, was positive. Oral biopsy revealed suprabasal epithelial detachment with an eosinophilic and neutrophilic infiltrate. Direct immunofluorescence showed positive fluorescence in the intercellular cement substance (ICS) of IgG and complement 3c, while IgA and IgM were negative. Indirect immunofluorescence, using normal human skin as substrate, showed an intercellular signal confined to the ICS with a titre of 1 : 360. Enzyme-linked immunosorbent assay gave a value of 54 U mL)1 for Dsg1 (normal 0–14) and a value of 162 U mL)1 for Dsg3 (normal 0–14), confirming a diagnosis of pemphigus vulgaris. PNP was suspected due to the severe and polymorphic mucocutaneous involvement, in particular of the conjunctiva and labial mucosa, which resembled erythema multiforme-like lesions. Routine haematological tests, serum tumour markers [b2-microglobulin, prostate-specific antigen (PSA), alpha-fetoprotein, carcinoembryonic antigen, Ca 19-9, Ca 72-4, Ca 125, acid phosphatase, Bence-Jones proteinuria], chest X-ray, echocardiogram, colonoscopy and oesophagogastroduodenoscopy were negative except for microhaematuria and an elevated level of PSA (49Æ1 ng mL)1; normal 0–4). A total body computed tomography (CT) scan revealed enlargement of the prostate, while bone scintigraphy revealed multiple foci of increased uptake (L2–L3, D8–D10). An ultrasound-guided needle biopsy of the prostate revealed a diffuse infiltration of adenocarcinoma. The prostate cancer grading (Gleason scale) was 8 (4 + 4). Immunoblotting analysis revealed the presence of antibodies to 250-, 210-, 190-, 160- and 130-kDa proteins (Fig. 2). So, in line with the criteria previously proposed,2 a diagnosis of PNP was confirmed. Our patient was diagnosed with a diffuse infiltration of prostate adenocarcinoma and bone metastasis. Over time, he developed mucocutaneous manifestations of PNP with a high positive titre of anti-Dsg1 and Dsg3. To our knowledge, despite the wide variety of haematological (Hodgkin and non- Hodgkin lymphoma, Castleman disease, thymoma)4 and nonhaematological malignancies (pancreas, colon, breast)2 related to PNP, it appears that this is the first case of PNP with metastatic prostate cancer. The only previous patient with PNP and prostate cancer also had chronic lymphoid leukaemia,10 so in that case the role of prostate cancer appears to be unlikely, although it might have contributed, as the most common malignancies related to PNP are nonhaematological. Another paraneoplastic case with prostate cancer has been described, but this was paraneoplastic bullous pemphigoid, associated with breast cancer.

Metastatic prostate cancer presenting as paraneoplastic pemphigus: a favourable clinical response to combined androgen blockade and conventional immunosuppressive therapy

MIGNOGNA, MICHELE DAVIDE;FORTUNA, GIULIO;LEUCI, STEFANIA;RUOPPO, ELVIRA
2009

Abstract

Paraneoplastic pemphigus (PNP), first described in 1990, is an autoimmune mucocutaneous blistering disease which is associated with an underlying malignancy and is characterized by polymorphic clinical signs. Pathogenesis is due to an aberrant autoimmune response against the proteins of the plakin family such as plectin, envoplakin, periplakin, desmoplakin I and II, and bullous pemphigoid antigen I (BP230), although several cases of PNP with antibodies to desmoglein (Dsg) 1 and 3 have been described. A 77-year-old man was admitted to our Oral Medicine Unit because of recalcitrant severe oral bullous ⁄erosive mucositis with crusting lesions of the lips, accompanied by marked conjunctivitis of both eyes, with cutaneous bullous lesions of the abdomen and bilaterally of the hip and inguinal area. Nikolsky’s sign, performed on the oral mucosa and skin, was positive. Oral biopsy revealed suprabasal epithelial detachment with an eosinophilic and neutrophilic infiltrate. Direct immunofluorescence showed positive fluorescence in the intercellular cement substance (ICS) of IgG and complement 3c, while IgA and IgM were negative. Indirect immunofluorescence, using normal human skin as substrate, showed an intercellular signal confined to the ICS with a titre of 1 : 360. Enzyme-linked immunosorbent assay gave a value of 54 U mL)1 for Dsg1 (normal 0–14) and a value of 162 U mL)1 for Dsg3 (normal 0–14), confirming a diagnosis of pemphigus vulgaris. PNP was suspected due to the severe and polymorphic mucocutaneous involvement, in particular of the conjunctiva and labial mucosa, which resembled erythema multiforme-like lesions. Routine haematological tests, serum tumour markers [b2-microglobulin, prostate-specific antigen (PSA), alpha-fetoprotein, carcinoembryonic antigen, Ca 19-9, Ca 72-4, Ca 125, acid phosphatase, Bence-Jones proteinuria], chest X-ray, echocardiogram, colonoscopy and oesophagogastroduodenoscopy were negative except for microhaematuria and an elevated level of PSA (49Æ1 ng mL)1; normal 0–4). A total body computed tomography (CT) scan revealed enlargement of the prostate, while bone scintigraphy revealed multiple foci of increased uptake (L2–L3, D8–D10). An ultrasound-guided needle biopsy of the prostate revealed a diffuse infiltration of adenocarcinoma. The prostate cancer grading (Gleason scale) was 8 (4 + 4). Immunoblotting analysis revealed the presence of antibodies to 250-, 210-, 190-, 160- and 130-kDa proteins (Fig. 2). So, in line with the criteria previously proposed,2 a diagnosis of PNP was confirmed. Our patient was diagnosed with a diffuse infiltration of prostate adenocarcinoma and bone metastasis. Over time, he developed mucocutaneous manifestations of PNP with a high positive titre of anti-Dsg1 and Dsg3. To our knowledge, despite the wide variety of haematological (Hodgkin and non- Hodgkin lymphoma, Castleman disease, thymoma)4 and nonhaematological malignancies (pancreas, colon, breast)2 related to PNP, it appears that this is the first case of PNP with metastatic prostate cancer. The only previous patient with PNP and prostate cancer also had chronic lymphoid leukaemia,10 so in that case the role of prostate cancer appears to be unlikely, although it might have contributed, as the most common malignancies related to PNP are nonhaematological. Another paraneoplastic case with prostate cancer has been described, but this was paraneoplastic bullous pemphigoid, associated with breast cancer.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11588/375793
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