Educational and practice gaps in the management of volar melanocytic lesions.

BACKGROUND: The benign and malignant patterns of acral melanocytic naevi (AMN) and acral melanomas (AM) have been defined in a series of retrospective studies. A three-step algorithm was developed to determine when to biopsy acral melanocytic lesions. This algorithm has only been applied to a Japanese population. OBJECTIVES: Our study aimed to review the current management strategy of acral melanocytic lesions and to investigate the utility of the three-step algorithm in a predominately Caucasian cohort. METHODS: A retrospective search of the pathology and image databases at Mayo Clinic was performed between the years 2006 and 2016. Only cases located on a volar surface with dermoscopic images were included. Two dermatologists reviewed all dermoscopic images and assigned a global dermoscopic pattern. Clinical and follow-up data were gathered by chart review. All lesions with known diameter and pathological diagnosis were used for the three-step algorithm. RESULTS: Regular fibrillar and ridge patterns were more likely to be biopsied (P = 0.01). The majority of AMN (58.1%) and AM (60%) biopsied were due to physician-deemed concerning dermoscopic patterns. 39.2% of these cases were parallel furrow, lattice-like or regular fibrillar. When patients were asked to follow-up within a 3- to 6-month period, only 16.7% of the patients returned within that interval. The three-step algorithm would have correctly identified four of five AM for biopsy, missing a 6 mm, multicomponent, invasive melanoma. CONCLUSION: We found one major educational gap in the recognition of low-risk lesions with high rates of biopsy of the fibrillary pattern. Recognizing low-risk dermoscopic patterns could reduce the rate of biopsy of AMN by 23.3%. We identified two major practice gaps, poor patient compliance with follow-up and the potential insensitivity of the three-step algorithm to small multicomponent acral melanocytic lesions.

Chronic interstitial granulomatous dermatitis in coccidioidomycosis.

Coccidioides species are soil-dwelling fungi endemic to the Southwest U.S.A., especially Arizona and California and Northern Mexico. The cutaneous findings of coccidioidomycosis have a wide range of pathology, which includes organism-specific and reactive processes. Interstitial granulomatous dermatitis (IGD), a granuloma annulare-like reaction, has been described, in a limited form, in association with acute pulmonary coccidioidomycosis. We present a case of chronic, widespread IGD spanning over 9 years in association with an active coccidioidomycosis infection. Similar clinical and histopathological features have been described in association with drug reactions, connective tissue diseases, systemic vasculitis, lymphomas, other infectious diseases and inflammatory bowel disease. Our patient's dramatic presentation and chronic course expands upon the clinical spectrum of IGD occurring in association with pulmonary coccidioidomycosis. While IGD in association with coccidioidomycosis is rare, both dermatologists and general practitioners see IGD reactions, and our case highlights the importance of identifying the underlying driver.

Cutaneous legionellosis: case report and review of the medical literature.

Discrete nodules developed on the leg of a 27-year-old immunosuppressed woman after an allogeneic stem cell transplant. Biopsy and culture grew Legionella pneumophila serogroup 8. On day 7 of azithromycin treatment, respiratory distress and abnormal liver transaminases developed, and the patient died on day 14. Review of the medical literature identified 19 reports of Legionella species-associated skin or soft tissue infections (total of 20 patients, 13 with confirmed infection). Manifestations of the 13 confirmed cases included erythematous macular rash (n = 7), erythema after thoracentesis (n = 1), abscess formation (n = 4), respiratory symptoms (n = 6), and abnormal chest radiographs (n = 8). Six required surgical exploration and débridement, and 7 were immunocompromised. Rash and respiratory infection improved with antibiotics in 10, but 3 died. Immunosuppression may predispose transplant recipients to Legionella infections. Diagnostic biopsies may facilitate appropriate treatment.

Activating BRAF mutations in eruptive melanocytic naevi.

BACKGROUND: Eruptive melanocytic naevi (EMN) are melanocytic proliferations developing rapidly on previously unaffected skin in association with various clinical scenarios, most commonly systemic immunosuppression. However, the exact mechanism leading to development of EMN is not understood. In particular, it is not known whether EMN harbour the BRAF mutations which occur frequently in melanoma and most common naevi. OBJECTIVES: To evaluate whether activating BRAF mutations may play a role in genesis of EMN. METHODS: Genomic DNA was isolated from 20 EMN from a patient treated with 6-mercaptopurine (6-MP). Primary BRAF genotyping was performed by allelespecific polymerase chain reaction, followed by validation using direct sequencing. RESULTS: The BRAF V600E mutation was identified in 85% of EMN examined. CONCLUSIONS: Our results implicate mutational activation of the BRAF­MAPK pathway as a factor in development of EMN in the setting of 6-MP treatment. The mechanism leading to development of EMN in this, and potentially other patients, may relate to synergistic mutagenic effects of thioguanines and ultraviolet (UV) A. Together with the documented importance of BRAF mutations in melanoma development and maintenance, these findings highlight the importance of UVA protection, especially in patients treated with thiopurines such as 6-MP.

Primary cutaneous large cell lymphomas. Morphologic, immunophenotypic, and clinical features of 20 cases.

The morphologic, immunophenotypic, and clinical characteristics of 20 cases of primary cutaneous large cell lymphoma were analyzed. Immunoperoxidase stains in paraffin sections indicated B-cell phenotype in 14 cases and T-cell phenotype in six cases. By the Kiel classification, the B-cell lymphomas were classified into the following categories: follicular centroblastic (three patients), centroblastic/centrocytic with a predominance of large centrocytes (two patients), centroblastic (seven patients), and immunoblastic (two patients). The T-cell lymphomas (six cases) were all categorized as pleomorphic medium and large cell type. Three of these had an angiocentric growth pattern. The lymphocyte activation marker CD30 was expressed in three of the 20 cases. Among these 20 patients, the clinical course was remarkably variable. The only clinical or pathologic feature with prognostic significance was multicentricity of the skin lesions. All five patients with multifocal or disseminated skin lesions died within 13 months of their initial presentation; the median survival was 7 months. Most of the patients with localized skin lesions had an indolent clinical course with a median survival of 107 months. These results suggest that multicentricity of the skin lesions and necrosis are closely linked and are important prognostic features in cutaneous large cell lymphoma.

The clinical behavior of desmoplastic melanoma.

BACKGROUND: Desmoplastic melanoma (DM) is a rare variant of malignant melanoma. A better understanding of the clinical course of DM will impact on its treatment. METHODS: We reviewed the medical records of 59 patients with DM seen at the Mayo Clinics Scottsdale and Rochester since 1985. RESULTS: Thirty-seven (63%) patients were male with a mean age of 62.8 years. The mean DM thickness was 6.5 mm. A total of 23 patients (39%) experienced local recurrence (LR). LR correlated with positive, unknown, or <1 cm margins. Fifty percent of patients who locally recurred subsequently developed metastatic disease. No patients were found to have positive nodal disease during ELND (16) or SLN biopsy (12). Only 1 patient (2%) developed delayed regional node metastases. Sixteen patients developed metastatic disease. The most common site was the lungs (81%). CONCLUSIONS: LR is a significant problem and correlates with an increased risk of systemic metastatic disease. With the rare occurrence of lymphatic spread, we recommend patients undergo SLN biopsy only. DM appears to preferentially metastasize to the lungs and should be targeted when evaluating the patient for metastatic disease.

Acrodermatitis chronica atrophicans in the United States: clinical and histopathologic features of six cases.

Acrodermatitis chronica atrophicans is a chronic cutaneous disease caused by the Lyme disease spirochete Borrelia burgdorferi. Acrodermatitis chronica atrophicans is endemic in some regions of Europe but is only rarely seen in the United States. This report describes the clinical and histopathologic findings in six cases of acrodermatitis chronica atrophicans seen at the Mayo Clinic between 1912 and 1961. Histologic differences between early and late phases of the disease were observed, and multisystemic symptoms consistent with chronic Lyme disease were documented in a subset of the patients. All five patients from whom biographical data were available were European immigrants. Our data suggest that some of the first patients with Lyme disease in the United States came to the Mayo Clinic earlier in this century.

Interstitial granulomatous dermatitis associated with pulmonary coccidioidomycosis.

BACKGROUND: Coccidioides immitis is a soil-dwelling fungus found in arid regions of the Western Hemisphere. Interstitial granulomatous dermatitis is a histopathologic pattern that may be a reactive manifestation of diverse systemic diseases. OBJECTIVE: Our purpose was to describe clinical and histopathologic findings in 5 patients who presented with interstitial granulomatous dermatitis associated with pulmonary coccidioidomycosis. METHODS: Medical records and skin biopsy slides from 5 patients were retrospectively reviewed. RESULTS: In each patient, edematous papules, nodules, and plaques developed abruptly during the onset of an acute febrile illness. Coccidioidomycosis was confirmed by serology. Skin biopsy specimens revealed interstitial granulomatous dermatitis with neutrophils, leukocytoclasis, and eosinophils. Fungal stains (5/5 cases) and fungal cultures (2/2 cases) revealed no organisms within the skin biopsy specimens. CONCLUSION: Interstitial granulomatous dermatitis may be a presenting feature of pulmonary coccidioidomycosis and may possibly represent a reactive manifestation of the infection.

Collagenous fibroma (desmoplastic fibroblastoma).

Collagenous fibroma (desmoplastic fibroblastoma) is a recently described tumor that may arise in the subcutaneous tissue or skeletal muscle. We report a case of collagenous fibroma, occurring on the forehead of a 67-year-old man. An awareness of this entity is necessary to avoid confusion with other soft tissue neoplasms, especially extraabdominal fibromatosis.

Mohs micrographic excision of melanoma using immunostains.

BACKGROUND: Mohs excision of melanoma remains controversial, in part because of concerns regarding evaluation of frozen section margins. Several immunohistochemical stains are available for melanoma that can be used on frozen sections. OBJECTIVE: To review our experience with Mohs micrographic excision of melanoma using immunostains. METHODS: Sixty-eight patients were treated, including 46 with melanoma in situ and 22 with invasive melanoma, 62 of which were on the head or neck. HMB-45, MEL-5, Melan-A (A-103), and S-100 stains were employed. RESULTS: Sixty-seven of 68 tumors were excised to clear margins, requiring an average of 2.0 layers. Immunostains greatly enhanced detection of melanoma on frozen sections. The average margin required for clearance of in situ melanoma was 8.3 mm and of invasive melanoma was 11.1 mm. Only 23 of 46 (50%) in situ melanomas were clear with < or =6 mm margins; 15 mm margins were required to clear 96% of the tumors. Eleven of 22 (50%) invasive melanomas were clear with < or =6 mm margins; 26 mm margins were required to clear 95% of the tumors. Melan-A (A-103) was the most consistently crisp and easily interpreted immunostain. CONCLUSIONS: Mohs excision of melanoma using immunostains can be useful, especially for tumors on the head and neck. For routine excision, margins wider than those currently recommended may be required to ensure tumor clearance. We recommend that (1) biopsies be stained preoperatively for Melan-A and/or HMB-45, (2) a debulking layer be obtained for permanent sections prior to Mohs layers, and positive and negative control specimens from the tumor and distant skin should be employed for comparison of staining patterns. Large-scale prospective studies of in situ and invasive melanoma on the head and neck are necessary.

Clinical and histologic spectrum of human T-cell lymphotropic virus type I-associated lymphoma involving the skin.

BACKGROUND: Adult T-cell leukemia/lymphoma (ATL) is associated with infection with human T-cell lymphotropic virus type I (HTLV-I). OBJECTIVE: The objective was to describe the clinical, histopathologic, and immunologic features in three patients with ATL involving the skin. METHODS: Clinical histories and skin biopsy specimens were reviewed. Immunophenotypic studies were performed on peripheral blood lymphocytes (three patients) and on skin biopsy specimens (one patient). RESULTS: Serologic testing in each patient was positive for HTLV-I. Specific cutaneous lesions of ATL were diverse. Histologic features included markedly epidermotropic lymphoid infiltrates and dermal aggregates of lymphocytes and macrophages resembling granulomas. One patient died 3 months after diagnosis; the other two are alive with residual lymphoma. CONCLUSION: A spectrum of clinical, histologic, and immunophenotypic features are seen in ATL involving skin. Those cases with a chronic course may resemble mycosis fungoides clinically and histologically. Serologic testing for HTLV-I is recommended in all patients with cutaneous lymphoma from endemic areas and in those with other risk factors for HTLV-I infection.