Paraneoplastic pemphigus associated with follicular dendritic cell sarcoma and Castleman disease

SIR, Paraneoplastic pemphigus (PNP) is an autoimmune blistering and erosive mucocutaneous disease associated with neoplasia, most commonly of lymphoreticular origin, first described by Anhalt et al. An alternative term, paraneoplastic autoimmune multiorgan syndrome, has since been proposed to define a condition in which patients, in addition to severe, often fatal pulmonary involvement and deposition of autoantibodies in different organs, may display lesions that resemble pemphigoid, erythema multiforme, graft-versus-host-disease and lichen planus as well as classic pemphigus. We report a patient with a lichen planus-like mucocutaneous variant of PNP associated with follicular dendritic cell (FDC) sarcoma and Castleman disease (CD), emphasizing in particular the rarity of PNP in association with such a type of sarcoma. A 53-year-old woman had painful persistent oral erosions accompanied by dry cough, dysphagia and weight loss since December 2002. She had been given topical and systemic corticosteroids at another hospital, with no improvement. In June 2003, when the patient was referred to our institute, she presented with extensive erosions of the oral mucosa (Fig. 1a), tongue and conjunctiva and a 3-week history of lichenoid papules symmetrically distributed on the trunk (Fig. 1b) and extremities. Laboratory examinations revealed mild anaemia (haemoglobin 10Æ7 g dL; normal 12–16) and positive antinuclear antibodies with speckled pattern at a titre of 1 : 160. Histology from a papular area showed a lichenoid interface dermatitis with numerous necrotic keratinocytes (Fig. 2a). Direct immunofluorescence disclosed intercellular deposits of IgG throughout the epidermis, whereas indirect immunofluorescence demonstrated IgG autoantibodies directed to the intercellular substance of stratified epithelium, namely monkey oesophagus, and also of rat bladder transitional cell epithelium. An immunoprecipitation analysis, carried out as reported, identified a complex of three antigens: proteins of 210 and 190 kDa that could represent desmoplakin II ⁄envoplakin and periplakin, respectively, and the as yet uncharacterized 170-kDa antigen (Fig. 2b). A specific enzyme-linked immunosorbent assay, using recombinant desmoglein (Dsg) 1 and Dsg3 proteins, did not detect antibodies to either Dsg1 or Dsg3. A diagnosis of PNP was made and a search for an underlying neoplasm revealed, on abdominal computed tomographic scans, a 9 · 5 · 8 cm soft tissue mass in the right retroperitoneal area. The mass was excised and pathological examination showed histological features of FDC sarcoma in association with residual foci of CD of the hyaline-vascular type. On immunohistochemistry, the tumour cells of the sarcoma had a CD21+, CD35+, nerve growth factor receptor-positive, actinpositive phenotype. Within 3 weeks after resection of the tumour the mucocutaneous manifestations continued to deteriorate and therapy was initiated with intravenous methylprednisolone 80 mg daily and azathioprine 100 mg daily for 15 days, but this was ineffective. Pulsed intravenous methylprednisolone 250 mg daily for 5 days, and subsequently, a cycle of high-dose intravenous immunoglobulins 0Æ6 g kg daily for five consecutive days resulted in moderate clinical improvement. However, she developed ingravescent dyspnoea: respiratory function tests disclosed restrictive pulmonary changes, whereas positron emission tomography of the chest showed features suggestive of secondary lung involvement by sarcoma. She died of respiratory failure in April 2004. In our patient, the association of PNP with FDC sarcoma, a rare malignant neoplasm of follicular dendritic cells, is unique. Notably, the FDC sarcoma arose from CD, as seen in only one previously reported case. Although there is no firm evidence a