Wain L. White

Atypical Spitz nevi/tumors : Lack of consensus for diagnosis, discrimination from melanoma, and prediction of outcome

The biological nature of Spitz nevi/tumors and their diagnostic distinction from, or relationship to, melanoma remain unresolved issues. In this report, a series of 30 melanocytic lesions removed from 28 patients, including atypical Spitz nevi/tumors and metastasizing Spitzoid tumors/melanomas, were evaluated by a panel of dermatopathologists to evaluate interobserver diagnostic concordance and to assess the prognostic power of histological criteria. For inclusion in the study, each lesion had to display some criteria for the Spitz nevus, and in addition one of the following was required: (1) definitive clinical outcome such as metastasis or death of disease, or (2) long-term follow-up if the patient remained disease free. Each lesion was reviewed independently and blinded as to the clinical data by 10 pathologists, who categorized them as (1) typical Spitz nevus/tumor, (2) atypical Spitz nevus/tumor, (3) melanoma, (4) tumor with unknown biological potential, or (5) other melanocytic lesion. There was limited discussion of criteria before the review. Evaluation of 17 Spitzoid lesions yielded no clear consensus as to diagnosis; in only one case did six or more pathologists agree on a single category, regardless of clinical outcome. Notably, however, some lesions that proved fatal were categorized by most observers as either Spitz nevi or atypical Spitz tumors. Conversely, seven or more pathologists scored 13 lesions as melanoma. These results illustrate (1) substantial diagnostic difficulties posed by many Spitz tumors, especially those with atypical features, even among experts, and (2) the lack of objective criteria for their distinction from melanoma and for gauging their malignant potential. Nevertheless, our observations do suggest that a biological relationship exists between the Spitz nevus/tumor and melanoma.

Mucocutaneous criteria for the diagnosis of Behçet's disease: An analysis of clinicopathologic data from multiple international centers

BACKGROUND Although four of five of the new international criteria for the diagnosis of Behçets disease relate to mucocutaneous lesions, disagreement exists as to the exact nature of cutaneous lesions (e.g., vessel-based vs follicular). OBJECTIVE Our purpose was to review clinical data, clinical photographs, and skin biopsy specimens from multiple medical centers throughout the world to monitor current practice in the implementation of mucocutaneous diagnostic criteria for Behçets disease. METHODS Ten medical centers responded to a request to collaborate by sending clinical data, photographs of cutaneous lesions, and biopsy specimens from 22 patients. RESULTS Of specimens from 22 patients, 14 revealed a histopathologic pattern of neutrophils containing perivascular and interstitial inflammation, whereas specimens from three patients revealed only mononuclear cells in a vessel-based pattern. Biopsy specimens from three patients revealed primarily folliculocentric inflammation and an additional two specimens were from erythema nodosum-like lesions. CONCLUSION Perivascular inflammation was the predominant histopathologic finding in specimens of cutaneous lesions in this clinical series. Folliculocentric lesions could not be predicted on the basis of review of clinical photographs. Histopathologic assessment of cutaneous lesions is crucial if the proposal is accepted that exclusion of folliculocentric lesions is important to ensure accurate implementation of diagnostic criteria in patients with suspected Behçets disease.

Utility of Rush Paraffin‐Embedded Tangential Sections in the Management of Cutaneous Neoplasms

Background. Mohs micrographic surgery (MMS) modified by the use of tangential, formalin‐fixed, paraffin‐embedded histologic specimens is advantageous in treating selected skin neoplasms. Objective. To review the use of our experience with a modification of MMS to treat lentigo maligna melanoma (LMM), lentigo maligna (LM) and other melanoma in situ (MIS) lesions, dermatofibrosarcoma protuberans (DFSP), atypical fibroxanthoma (AFX), and angiosarcoma. Methods. Our experience utilizing a modification of MMS in the treatment of 77 patients with LM or other MIS, 23 patients with LMM, 11 patients with DFSP, 1 patient with AFX, and 1 patient with angiosarcoma was reviewed. Length of follow‐up and rate of recurrence were examined. A literature review of this pertinent modification of the Mohs technique was performed. Results. One hundred fourteen patients underwent MMS for melanocytic (LM, MIS, LMM), spindle cell (DFSP, AFX), and vascular malignant neoplasms. One patient developed locally recurrent LM and one patient with LMM developed satellite metastasis. Regional lymph node metastasis occurred in one patient with LMM and in a patient with angiosarcoma. Conclusion. The use of Mohs micrographic surgery in conjunction with rush formalin‐fixed, paraffin‐embedded tangential histologic sections provides the accuracy and tissue conservation of the Mohs procedure while ensuring more confident interpretation of histology in cases of lentigo maligna, lentigo maligna melanoma, dermatofibrosarcoma protuberans, atypical fibroxanthoma, and angiosarcoma.

Low-dose weekly methotrexate for unusual neutrophilic vascular reactions: Cutaneous polyarteritis nodosa and Behçeťs disease

Low-dose weekly methotrexate therapy has been used to treat patients with psoriasis for more than 20 years. This regimen has also been used to treat rheumatoid arthritis, inflammatory bowel disease, primary sclerosing cholangitis, and corticosteroid-dependent asthma. We report two patients with Behçets disease with cutaneous neutrophilic vascular reactions and three with cutaneous polyarteritis nodosa who responded dramatically to low-dose weekly methotrexate therapy.

Management of lentigo maligna and lentigo maligna melanoma with paraffin-embedded tangential sections: Utility of immunoperoxidase staining and supplemental vertical sections

BACKGROUND The use of frozen sections in the management of lentigo maligna and lentigo maligna melanoma has been the focus of some controversy. OBJECTIVE Our purpose was to utilize paraffin-embedded tangential sections in the management of two cases of lentigo maligna and three cases of lentigo maligna melanoma. METHODS A modification of Mohs micrographic surgery using rush paraffin-embedded sections with adjunctive immunoperoxidase staining (HMB-45) and supplemental vertical sections was employed. RESULTS This method resulted in enhanced histologic evaluation of section margins and did not compromise the diagnosis of the primary invasive melanoma or Breslow measurements. CONCLUSION Mohs micrographic surgery modified by the use of rush paraffin-embedded sections allows adjunctive immunoperoxidase staining and supplemental vertical sections that may be helpful in the management of lentigo maligna and lentigo maligna melanoma.

Cutaneous changes of dermatomyositis in patients with normal muscle enzymes: Dermatomyositis sine myositis?

BACKGROUND Dermatomyositis sine myositis may have various connotations. Controversy exists as to nomenclature, degree of evaluation required, therapy, and course (e.g., does true dermatomyositis of the skin only exist?). OBJECTIVE The purpose of this study was to assess prospectively patients with the clinicopathologic features of dermatomyositis and normal muscle enzyme serum levels to determine their course in terms of the onset of muscle disease. METHODS Thirteen patients were studied by complete history and clinical examination, laboratory studies, electromyography, and skin and muscle biopsy. They were observed for 1 to 6 years. RESULTS Patients were classifiable into three groups: (1) cutaneous changes only, (2) cutaneous changes only at baseline with subsequent development of myositis, and (3) cutaneous changes with normal muscle enzyme serum levels at baseline but with myositis demonstrated by electromyography and/or muscle biopsy specimens. CONCLUSION Significantly different prognostic and therapeutic implications are present in patients with dermatomyositis with normal muscle enzyme serum levels depending on the results of electromyography, muscle biopsy, and clinical observation.

Livedo vasculitis: vasculitis or thrombotic vasculopathy?

Elevated fibrinopeptide A levels, suggestive of a thrombogenic state, were observed in six patients with livedo vasculitis. Serological studies demonstrated normal complement levels, and circulating immune complexes were not identified by standard assays. Morphological studies showed no evidence of immune complex deposition or a neutrophilic vascular reaction. These results support classification of this disorder as a thrombogenic vasculopathy rather than as a small vessel vasculitis. Further investigations into the thrombotic abnormalities underlying this entity are warranted.

Adult pityriasis rubra pilaris: A 10-year case series

BACKGROUND Pityriasis rubra pilaris (PRP) often has a devastating impact on the lives of patients. Descriptions of its histopathologic features are not uniform. Finding a successful therapy can be challenging. OBJECTIVE Our purpose was to examine the histopathologic features and response of patients to our standard therapy of an oral retinoid and concomitant or later addition of low-dose weekly methotrexate. METHODS A retrospective chart review was done on 24 patients with PRP seen from March 1986 to March 1996. Biopsy specimens from 19 patients were reexamined. Telephone follow-up was conducted to determine maintenance of remission. RESULTS All patients had the adult acquired form of PRP. Biopsy specimens from nine patients were characterized by prototypical findings of PRP, while the others included both typical and other features. Twenty-two patients were treated with either isotretinoin, 40 mg twice daily, or etretinate, 25 to 75 mg/day. Six patients with more disabling involvement had low-dose weekly methotrexate ranging from 5 to 30 mg started concurrently. Five patients had weekly methotrexate added at a later time. Seventeen patients showed 25% to 75% response after 16 weeks of therapy. All patients whose skin cleared maintained their remission. CONCLUSION Initial oral retinoid plus concurrent or later low-dose weekly methotrexate resulted in 25% to 75% improvement of PRP in 17 of 24 patients after 16 weeks of therapy. Some of the atypical features seen in biopsy specimens emphasize the importance of clinical and histopathologic correlation in establishing the diagnosis.

Low-dose methotrexate treatment in elderly patients with bullous pemphigoid

BACKGROUND Various treatments have been used for elderly patients with bullous pemphigoid. The most common is moderate-dose to high-dose prednisone, either alone or in combination with other oral or topical agents. OBJECTIVE The aim of this study was to evaluate the efficacy of low-dose methotrexate as a steroid-sparing agent in patients with bullous pemphigoid. METHODS. A retrospective chart review of 34 patients with bullous pemphigoid seen from 1989 through the first half of 1993 was conducted. The diagnosis of bullous pemphigoid was confirmed by direct or indirect immunofluorescence microscopy, or salt-split skin sections. Eight of 34 elderly (> 60 years old) patients with therapy-resistant bullous pemphigoid received low-dose weekly methotrexate (average, 5 to 10 mg) in combination with oral prednisone. RESULTS Patients who received combination therapy required significantly lower (p < or = 0.02) doses of prednisone to control their disease at 1 month compared with baseline doses. CONCLUSION In this elderly patient population the side effect profile of the methotrexate was acceptable and well tolerated. We therefore recommend methotrexate and low-dose corticosteroid as first-line combination therapy for selected elderly patients with bullous pemphigoid.

The histopathology of pathergy: a chronologic study of skin hyperreactivity in Behçet's disease

Background many patients with Behçets disease (BD) demonstrate hyperreactivity (pathergy), and the induced skin lesions may serve as a model for the disease.