Frank C. Powell

Pyoderma gangrenosum: clinicopathologic correlation and proposed diagnostic criteria

Pyoderma gangrenosum is a rare but significant cause of ulcerations. It is a diagnosis of exclusion. Herein, we suggest diagnostic criteria and some historical perspectives on the diagnosis of pyoderma gangrenosum.

Sister Mary Joseph's nodule: A clinical and histologic study

The clinical and histologic findings in eighty-five cases of tumors metastatic to the umbilicus were studied. Clinically, the lesions were seen as firm, indurated nodules, sometimes with fissuring or ulceration. In twelve cases, the initial presentation of the internal primary malignancy was an umbilical nodule. Histologic material from the metastatic umbilical tumor was studied in all cases but was diagnostic of the primary carcinoma in only twenty-one. In seventeen cases, the primary site was never reliably determined, while stomach, large bowel, ovary, and pancreas were the most frequent primary sites in the other cases. Most patients died within months after the appearance of the umbilical tumors, thus emphasizing the ominous significance of this sign of metastatic, usually intra-abdominal, malignant disease.

Histopathologic and immunopathologic study of pyoderma gangrenosum

Sixty‐three patients with pyoderma gangrenosum were seen and studied at the Mayo Clinic from 1971 to 1980. Biopsies from the erythcmatous border or necrotic edge of the pyoderma gangrenosum lesions usually demonstrated a characteristic pathogenic morphologic evolution. The early lesions revealed mild to moderate perivascular lymphocytic infiltrate associated with endothelial swelling. The fully developed lesions demonstrated necrosis in addition to a dense lymphocytic infiltration surrounding as well as involving the blood vessels. Extravasation of erythro‐cytes and thrombosis sometimes were seen. Ulceration, infarction, and abscess formation were found in the later stages of evolution. Direct immunofluorescence results were positive in the blood vessels of 36 of 65 (55%) specimens. IgM, C3, and fibrin were found in the papillary and retieular dermal vessels. IgG and IgA were only occasionally present. Pyoderma gangrenosum appears to be a reactive process that is manifested as a vasculilis. Biopsy material from the advancing active erylhc‐matous border has early characteristic derniatopathologic findings of lymphocytic vasculitis. Cutaneous vascular immune deposits suggest an immune pathogenesis of either an immune complex disease or lymphocytotoxic reaction.

Scleredema: A review of thirty-three cases

A review of thirty-three cases of scleredema, with particular reference to clinical and histologic findings, revealed that the disease was often of insidious onset and the course was usually prolonged. A preceding respiratory tract infection was uncommon and usually did not indicate a short course. The patients were divided into two groups according to the presence or absence of diabetes. Diabetes, when present, was typically the late-onset, insulin-dependent type and difficult to control. In many of these patients, the onset of scleredema was so subtle that it went unnoticed by the patient until pointed out by an examining physician.

Primary biliary cirrhosis and lichen planus

Lichen planus and primary biliary cirrhosis were seen in twenty-four patients. In seventeen patients, the cutaneous eruption followed the administration of D-penicillamine. In seven patients, lichen planus developed unrelated to therapy. Three of the latter group of patients were treated with D-penicillamine and had subsequent relapse or exacerbation of their preexisting lichen planus. The presence of lichen planus in patients with primary biliary cirrhosis and the propensity to develop this type of eruption while on D-penicillamine therapy are consistent with a graft-versus-host pathogenesis of primary biliary cirrhosis. Preexisting lichen planus should be regarded as a relative contraindication to the use of D-penicillamine in patients with primary biliary cirrhosis.

An association between HLA DR1 and lichen planus

Serological typing for HLA Class II antigens in 72 patients with lichen planus (LP) revealed a highly significant association with HLA DR1 and MT1 (DQw1). DR1 was present in 80% of patients with generalized LP, 54% with localized LP, 56% of patients with drug‐induced LP and in 31% of patients with mucosal LP, compared with 25% of normal controls. MT1 (DQw1) was found in 83% of the LP group and 62% of the normal controls. These findings strongly suggest a genetic predisposition or susceptibility to the development of generalized LP and perhaps also to drug‐induced LP.

The Anticentromere Antibody: Disease Specificity and Clinical Significance

Serum samples from 539 subjects were screened for the presence of the anticentromere antibody on a human laryngeal carcinoma (HEp-2) cell line (Antibodies, Inc.). The antibody was present in 61 patients (11%), most of whom had features of limited scleroderma or the CREST syndrome (calcinosis cutis, Raynauds phenomenon, esophageal dysfunction, sclerodactyly, and telangiectasia), either independently or in association with primary biliary cirrhosis. The antibody was rarely found in patients with rapidly advancing or diffuse scleroderma. The anticentromere antibody is therefore a useful prognostic indicator in patients with early scleroderma, as it may help to predict what pattern of scleroderma will evolve. Screening for this antibody should be conducted in all patients with Raynauds phenomenon, primary biliary cirrhosis, and scleroderma. Other previous studies have indicated a similar disease specificity and prognostic importance of this antibody.

Direct immunofluorescence in pyoderma gangrenosum

Direct immunofluorescence was done in fifty‐one cases of pyoderma gangrenosum. Biopsy specimens were taken from the peripheral erythematous zone of the lesion. In thirty‐one cases (61%), there was positive immunofluorescence, with perivascular deposition of immune reactants being the most frequent pattern (twenty‐seven cases). These findings support a vasculitic pathogenesis of pyoderma gangrenosum.

Genital Paget's disease and urinary tract malignancy

Eight cases of Pagets disease of genital mucosa with malignancy of the lower urinary tract are described. In five it was apparent that there was concurrence of two separate malignancies. In one patient with long-standing Pagets disease of the genital mucosa, carcinoma of the urethra and bladder developed subsequently in continuity with the genital lesion; the two lesions were indistinguishable histologically, suggesting extension of the Pagets disease into urothelium. In two patients with bladder malignancy, there was histologic evidence of outward pagetoid extension of this process along urothelium and onto the genital mucosa. The significance of genital Pagets disease is discussed in the light of these findings, and the possible origins of Paget cells within the epidermis are reviewed.

Discoid lupus erythematosus and monoclonal gammopathy

Of twelve patients with discoid lupus erythematosus and dysgammaglobulinaemia, eight had a monoclonal gammopathy with a benign course to date, two had smouldering myeloma, and two developed overt multiple myeloma. Six patients had generalized discoid lupus erythematosus, and six had skin lesions localized to the head and neck. Further screening of patients with discoid lupus erythematosus by serum protein electrophoresis is indicated to determine the significance of these findings.