April 2003

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Diagnosis: Paraneoplastic pemphigus

Laboratory, Radiologic, and Histopathologic Data:
Indirect immunofluorescence of the patient's serum on monkey esophagus and rat bladder was performed. This test was positive in a 1:1,280 dilution for monkey esophagus. Serum glucagon level was slightly elevated. The abdominal mass detected on physical examination was imaged with Computed Tomography scan revealing an 8 cm x 3 cm irregular soft-tissue mass in the mid-abdomen adjacent to the aorta. Positron emission tomography did not reveal increased uptake of FDP in this same region. Tissue sample of the abdominal mass was obtained via laparotomy. This showed hyalinized collagen with occasional clusters of small, round lymphocytes with scant cytoplasm, slightly irregular nuclei, condensed chromatin, and indistinct nucleoli (Figs 4 & 5). Immunohistochemical stains revealed a low-grade non-Hodgkin's lymphoma: CD10+, CD20+ (Fig 6), BCL-6+ indicative of B-cell follicular differentiation.

Hospital Course:
The patient was initially started on high-dose intravenous corticosteroids and had a slow, but definite, improvement of her lesions. Once the diagnosis of B-cell lymphoma was made, the patient was started on CHOP chemotherapy and rituxan. The patient's skin lesions improved and the patient was discharged to a short-term nursing facility. She continued to improve and her corticosteroids were tapered. Unfortunately, three months after the diagnosis was made, the patient became septic from a bacterial superinfection of her resolving lesions and expired.

Discussion:

Paraneoplastic pemphigus is an autoimmune, acantholytic mucocutaneous disease first described in 1990 by Anhalt et al. The original criteria include: (1) painful mucosal erosions and a polymorphous skin eruption in the context of an occult or comfirmed neoplasm; (2) histopathologic features of intraepidermal acantholysis, keratinocyte necrosis, and vacuolar-interface dermatitis; (3) direct immunofluorescence findings of intercellular epidermal IgG and C3 deposition +/- granular linear complement deposition along the basement membrane zone; (4) serum autoantibodies that bind stratified squamous epithelia as well as simple, columnar, and transitional epithelia by indirect immunofluorescence; and (5) a complex of four proteins (250, 230, 210, and 190 kd) immunoprecipitated from keratinocytes (an additional 170 kd antigen has been identified).

There are approximately 150 reported cases, with an average age range of 45-70 years and no gender predominance. Clinical manifestations include mucosal involvement in all (oral and conjunctival erosions) with erythema, flaccid to tense blisters, erosions, and crusting on the trunk, proximal extremities, and palmoplantar surfaces. The histologic features include intraepidermal acantholysis, suprabasilar clefting, keratinocyte necrosis, basal vacuolization, and interface dermatitis. Direct immunofluorescence of perilesional skin shows IgG +/- C3 deposition on epidermal intercellular spaces and the basement membrane zone. Indirect immunofluorescence using serum samples demonstrate antibody deposition with monkey esophagus (sensitivity 86%) and rat bladder (specificity 83-99%).

Paraneoplastic pemphigus has been associated with benign and malignant neoplasms including (in decreasing order of frequency): non-Hodgkin's lymphoma, CLL, Castleman's tumor, thymoma, poorly differentiated sarcoma, WaldenstrÖm's macroglobulinemia, inflammatory fibrosarcoma, bronchogenic SCC, round-cell liposarcoma, Hodgkin's disease, and T-cell lymphoma. Disease course does not parallel that of the underlying malignancy. Prognosis is generally poor. Death is usually secondary to sepsis, gastrointestinal bleeding, respiratory failure, or multiple organ failure.

References:

1. Anhalt GJ, Kim SC, Stanley JR, Korman NJ, Jabs DA, et al. Paraneoplastic pemphigus. N Engl J Med 323:1729-35, 1990.
2. Fitzpatrick's Dermatology in General Medicine, 5th ed. (Freedberg IM, Eisen AZ, Wolff K, Austen KF, Goldsmith LA, Katz SI eds.). New York: McGraw-Hill, 1999. pp 654-63.
3. Joly P, Richard C, Gilbert D, Courville P, Chosidow O, et al. Sensitivity and specificity of clinical, histologic, and immunologic features in the diagnosis of paraneoplastic pemphigus. J Am Acad Dermatol 43:619-26, 2000.
4. Kimyai-Asadi A and Jih MH. Paraneoplastic pemphigus. Int J Dermatol 40:367-72, 2001.
5. Robinson ND, Hashimoto T, Amagai M, and Chan LS. The new pemphigus variants. J Am Acad Dermatol 40:649-71, 1999.