International board certification in dermatopathology: paving the way for the future.
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Biomedical subjects
Publications and source records attributed to Helmut Kerl.
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A new group of subcutaneous, natural killer (NK), NK/T-cell, and other cytotoxic T-cell lymphomas of the skin has been recently described, and some have been included as distinct clinicopathologic entities in the classification of hematologic malignancies recently proposed by the World Health Organization. In the European Organization for Research and Treatment of Cancer classification for cutaneous lymphomas, they would be classified either as CD30- large T-cell lymphoma, small/medium pleomorphic T-cell lymphoma, or subcutaneous T-cell lymphoma. Precise clinicopathologic and prognostic features of all of them have not yet been well characterized. We studied retrospectively 81 biopsies from 50 patients with subcutaneous, blastic natural killer (NK), NK/T-cell, or other non-mycosis fungoides cytotoxic T-cell lymphomas of the skin. Clinical, morphologic, phenotypical, and genetic features and data on Epstein-Barr virus association allowed us to classify our cases according to the following 7 categories: a) subcutaneous "panniculitis-like" T-cell lymphoma (SPTCL): 10 cases (estimated 5-year survival: 80%); b) blastic NK-cell lymphoma: 12 cases (estimated 5-year survival: 0%); c) nasal-type extranodal NK/T-cell lymphoma: 5 patients (estimated 5-year survival: 0%); d) epidermotropic CD8+ T-cell lymphoma: 5 cases (estimated 5-year survival: 0%); e) cutaneous gamma/delta T-cell lymphoma: 8 cases (estimated 5-year survival: 0%); f) cutaneous alpha/beta pleomorphic T-cell lymphoma: 8 cases (estimated 5-year survival: 0%); and g) cutaneous medium/large pleomorphic T-cell lymphoma, not otherwise specified: 2 cases. Our study shows that these cutaneous lymphomas can be classified according to precise diagnostic categories. With the exception of SPTCL, analysis of follow-up data from our patients showed that these groups of lymphomas are characterized by an aggressive course, regardless of the diagnostic category.
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Using human skin explants, we investigated the effects of two different sunscreen preparations containing a chemical UVB filter alone [sun protection factor (SPF) 5.2] or UVA+UVB filter [SPF 6.2] on sunburn cell formation, dendritic cell (DC) migration, CD86- and CD1a-positive cell number, and tumor necrosis factor alpha (TNFalpha) and interleukin (IL)-1, IL-10, and IL-12 production in the skin after irradiation with different doses of solar-simulated UV radiation. Sunscreen- or placebo-treated skin explants were irradiated with solar-simulated UV radiation at 0.5, 1, and 2 minimal erythematous dose equivalents (MEDE) (as determined in an in vivo human study) multiplied by the SPF of the placebo or sunscreens. After irradiation, skin explants were floated on RMPI medium for 48 h. Cells that had emigrated and the skin explants were histologically analyzed, and the soluble mediators were measured in the supernatants by ELISA. Exposure to UV radiation led to concentration-dependent increases in sunburn cell formation and TNFalpha production but a concentration-dependent decrease in DC migration and CD86- and CD1a-positive cell number in the epidermis. Both chemical sunscreens protected against those alterations. The immunoprotective capacity of the sunscreens correlated with their SPF but was independent of the sunscreens' UVA protection capacity, suggesting that UVA is not a major factor for immunosuppression under the conditions used in the model. UV irradiation did not significantly affect the vitality of emigrated DC; the expression of HLA, CD80, and lag on emigrated cells; the number of CD1a-positive cells in the dermis; or the production of IL-1, IL-10, and IL-12. We conclude that our model may be useful in determining the immunoprotective capacity of sunscreens.
Lymphocytoma cutis (LC) is considered as the stereotypical example of the cutaneous B-cell pseudolymphomas. It can be induced by various antigenic stimuli including arthropod bites, vaccination, and drugs among others. In endemic regions, Borrelia burgdorferi is the principal causative agent for LC. We studied retrospectively 108 biopsies from 106 patients (male : female, 48 : 58; mean age, 44.6; median, 51.5; range, 3-81) with B. burgdorferi-associated LC retrieved from the files of the Department of Dermatology of the University of Graz (Austria). Only cases with a B. burgdorferi etiology (typical locations, positivity of serologic and/or polymerase chain reaction (PCR) tests, clinical history) were included in the study. Lesions were located on the nipple (63 cases), earlobe (18 cases), genital region (9 cases), and trunk or extremities (16 cases). PCR analysis of B. burgdorferi DNA was positive in 54 of 80 cases tested (67.5%). In 47 cases, we could retrieve data on serologic examination for B. burgdorferi antibodies performed at the time of diagnosis of LC. Positivity was found in 45 patients (IgG+/IgM+, 5 cases; IgG+/IgM-, 37 cases; IgG-/IgM+, 3 cases; IgG-/IgM-, 2 cases). Histology revealed dense lymphoid infiltrates with prominent germinal centers (GCs) in all cases. Atypical morphologic and/or immunophenotypic features of the GCs were commonly observed. In 5 cases, due to confluence of large follicles, the histopathologic pattern simulated that of a large B-cell lymphoma. PCR analysis of the IgH gene rearrangement performed in 33 cases showed a polyclonal pattern in 31 cases and a monoclonal band in 2. In summary, B. burgdorferi-associated LC can present with misleading histopathologic, immunophenotypic, and molecular features, and integration of all data is necessary for a correct diagnosis.
BACKGROUND: Inflammatory pseudotumor (IPT) also known as inflammatory myofibroblastic tumor (IMT) or plasma cell granuloma (PCG) has been rarely reported in the skin. METHODS: We describe five patients with cutaneous IPT and present clinicopathologic features along with detailed immunohistochemical analysis including anaplastic lymphoma kinase (ALK)-1. RESULTS: The patients age ranged from 15 to 89 years with a median of 56 years. All patients presented with solitary, firm, papules and nodules. There was no evidence of constitutional symptoms, local recurrence, or lymph node involvement. Histopathological examination revealed two distinct patterns; one type (n = 3) displayed dense, lymphoplasmacytoid infiltrates containing lymphoplasmacytoid cells and plasma cells with occasional germinal centers and hyalinized collagen bundles but was devoid of a myofibroblastic component. It showed features of tumors previously described as cutaneous PCG. Although an infectious etiology, including Borrelia burgdorferi-specific DNA, could not be demonstrated, we observed many features that overlapped with those of fibrous nodules of acrodermatitis chronica atrophicans. The other pattern (n = 2) revealed spindled myofibroblasts focally arranged in a fascicular pattern, an admixed lymphoplasmacytoid infiltrate set in a background of thickened collagen bundles, findings akin to the conventional type of IMT. The cases with a myofibroblastic component (n = 2) did not show any evidence of ALK-1 reactivity. CONCLUSIONS: We believe that the term cutaneous IPT subsumes lesions of diverse etiology. Tumors with detectable myofibroblasts represent true cases of IMT. Cutaneous PCG is a discrete disorder biologically distinct from conventional IMT representing a reaction pattern that is also found in disorders, such as spirochete-induced fibroid nodules and localized chronic fibrosing vasculitis.
The correct classification of locoregional metastases of malignant melanoma to skin is central to the planning of treatment. Local recurrence means persistence of neoplastic cells at the local site by virtue of incomplete excision of the primary melanoma. Standard treatment is excisional surgery. In contrast, locoregional metastases of malignant melanoma (satellites, in-transit metastases) are metastases around a primary melanoma or between a primary melanoma and regional lymph nodes. They represent intralymphatic or hematogenous spread of neoplastic cells. We present a variety of available treatment options and discuss especially topical imiquimod as a novel approach for the palliative treatment of locoregional cutaneous melanoma metastases in selected patients.
Intravascular large B-cell lymphoma is a malignant neoplasm characterized by the proliferation of large B cells (rarely of T lymphocytes) confined within the blood vessels. Although the disease can be limited to the skin, involvement of other organs is common. We report a case of intravascular large B-cell lymphoma colonizing the vessels of preexisting cutaneous cherry hemangiomas.
OBJECTIVE: To assess the role of foot dermatomycosis (tinea pedis and onychomycosis) and other candidate risk factors in the development of acute bacterial cellulitis of the leg. METHODS: A case-control study, including 243 patients (cases) with acute bacterial cellulitis of the leg and 467 controls, 2 per case, individually matched for gender, age (+/-5 years), hospital and admission date (+/-2 months). RESULTS: Overall, mycology-proven foot dermatomycosis was a significant risk factor for acute bacterial cellulitis (odds ratio, OR: 2.4; p < 0.001), as were tinea pedis interdigitalis (OR: 3.2; p < 0.001), tinea pedis plantaris (OR: 1.7; p = 0.005) and onychomycosis (OR: 2.2; p < 0.001) individually. Other risk factors included: disruption of the cutaneous barrier, history of bacterial cellulitis, chronic venous insufficiency and leg oedema. CONCLUSIONS: Tinea pedis and onychomycosis were found to be significant risk factors for acute bacterial cellulitis of the leg that are readily amenable to treatment with effective pharmacological therapy.
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PCBCL are a heterogeneous group of B-cell lymphomas that originate in the skin, with the absence of extracutaneous disease at diagnosis. Overall, these cutaneous lymphomas have an excellent prognosis. Recurrences are common but dissemination is rare. The EORTC classification allows a more uniform diagnosis and treatment of patients with PCBCL. Careful clinical and pathologic correlation is critical in confirming a diagnosis of PCBCL, before deciding on therapy. Several therapeutic options that are aimed at cure, are available. In most instances, chemotherapy should not be the first line of treatment.
Squamous cell carcinomas in psoralen-plus-ultraviolet A (PUVA) treated patients frequently exhibit p53 tumor suppressor genes and Ha-ras protooncogenes that are mutated at dipyrimidine sites and carry the ultraviolet fingerprint (i.e., C-to-T or CC-to-TT transitions). To further broaden the knowledge of genetic mutations in PUVA-associated skin cancer, we used DNA sequencing analysis to study the mutational spectrum of the INK4a-ARF locus in 26 squamous cell carcinomas from 11 long-term PUVA-treated psoriasis patients and classified the mutations by origin (ultraviolet, ultraviolet and/or PUVA, or other). Nineteen INK4a-ARF missense/nonsense mutations were found in exons 1alpha, 1beta, and 2 in 11 of 26 squamous cell carcinomas (42%) from seven of 11 patients (64%). Eleven mutations (58%) were of the ultraviolet type; three (16%) were of the ultraviolet and/or PUVA type (i.e., C-to-T transitions at dipyrimidine sites opposite a 5'TpG sequence, a potential psoralen binding site); and five (26%) were of other type. Interestingly, 10 of 11 patients (91%) showed intron polymorphism C500G at the 3' untranslated region of exon 3. These data indicate that (i) INK4a-ARF mutations frequently occur in PUVA-associated squamous cell carcinomas; (ii) ultraviolet B radiation is the major cause of these mutations; and (iii) PUVA itself may play no direct role in development of most INK4a-ARF mutations.
We conducted a randomized trial designed to calculate human in vivo immune protection factors of two sunscreen preparations in a model of ultraviolet-induced local suppression of the induction of contact hypersensitivity to 2,4-dinitrochlorobenzene. Seventy-five male subjects were exposed in a multistage study to multiples of their individual minimal erythema dose of solar-simulated ultraviolet radiation with or without protection by an ultraviolet B sunscreen (sun protection factor 5.2) or a broad-spectrum ultraviolet A + B sunscreen (sun protection factor 6.2). After 24 h subjects were sensitized with 50 microL of 0.0625% 2,4-dinitrochlorobenzene on a nonirradiated or ultraviolet-irradiated field on the buttock that was unprotected or protected by sunscreen. Three weeks after sensitization the subjects were challenged with varying concentrations of 2,4-dinitrochlorobenzene on their upper inner arm, and the contact hypersensitivity response was determined at 48 and 72 h based on a semiquantitative clinical score, contact hypersensitivity lesion diameters, and dermal skin edema measurement by 20 MHz ultrasound. The 50% immunosuppressive dose ranged from 0.63 to 0.79 minimal erythema dose, depending on the endpoint parameter. Both sunscreens offered significant immunoprotection (p = 0.014-0.002) and their immune protection factor ranged from 4.5 to 5.8 (ultraviolet B sunscreen) and from 7.7 to 11 (ultraviolet A + B sunscreen). The immune protection factor of the ultraviolet B sunscreen was similar to the sun protection factor (5.2), whereas the sunscreen with broad-spectrum ultraviolet A + B protection exhibited better immunoprotective capacity than predicted from the sun protection factor.
BACKGROUND: Adverse reactions after cosmetic lip augmentation with synthetic implant materials include inflammation, infection, and extrusion of and foreign body reaction to the implant. Clinically, all of them are characterized by pain, erythema, swelling, and formation of papules and/or pustules. OBJECTIVE: To describe an unusual herpes simplex virus infection in a 48-year-old female patient after cosmetic lip augmentation with expanded polytetrafluoroethylene threads clinically resembling a foreign body reaction. METHODS: Case report and literature review. RESULTS: A histopathologic examination showed no signs of a foreign body reaction. Instead, herpes simplex virus-specific DNA was demonstrated by polymerase chain reaction from lesional tissue. CONCLUSION: Cosmetic lip augmentation with expanded polytetrafluoroethylene threads may be complicated by a delayed local herpes simplex virus infection clinically mimicking a foreign body reaction to the implant.
BACKGROUND: There is a need for better standardization of the dermoscopic terminology in assessing pigmented skin lesions. OBJECTIVE: The virtual Consensus Net Meeting on Dermoscopy was organized to investigate reproducibility and validity of the various features and diagnostic algorithms. METHODS: Dermoscopic images of 108 lesions were evaluated via the Internet by 40 experienced dermoscopists using a 2-step diagnostic procedure. The first-step algorithm distinguished melanocytic versus nonmelanocytic lesions. The second step in the diagnostic procedure used 4 algorithms (pattern analysis, ABCD rule, Menzies method, and 7-point checklist) to distinguish melanoma versus benign melanocytic lesions. kappa Values, log odds ratios, sensitivity, specificity, and positive likelihood ratios were estimated for all diagnostic algorithms and dermoscopic features. RESULTS: Interobserver agreement was fair to good for all diagnostic methods, but it was poor for the majority of dermoscopic criteria. Intraobserver agreement was good to excellent for all algorithms and features considered. Pattern analysis allowed the best diagnostic performance (positive likelihood ratio: 5.1), whereas alternative algorithms revealed comparable sensitivity but less specificity. Interobserver agreement on management decisions made by dermoscopy was fairly good (mean kappa value: 0.53). CONCLUSION: The virtual Consensus Net Meeting on Dermoscopy represents a valid tool for better standardization of the dermoscopic terminology and, moreover, opens up a new territory for diagnosing and managing pigmented skin lesions.
We report an unusual case of congenital melanocytic nevus presenting in a 19-year-old African woman as widespread papules and variably sized nodules and tumors affecting the entire body, including the palms, soles, and oral mucous membrane. Histopathologic examination of 3 representative skin lesions showed mainly dermal aggregations of round to oval, focally pigmented, monomorphous melanocytes, arranged in nodular and plexiform patterns. Scattered areas with spindle-shaped dendritic melanocytes surrounded by fibrosis were also noted in the center of the lesions. The clinical and histopathologic findings were similar to those in 2 other previously reported cases, except that in 1 of the earlier cases the skin nodules were composed of spindle-shaped cells, suggesting a type of blue nevus. The findings in our case indicate a broader spectrum of morphologic features in this condition, with dermal aggregations of melanocytes showing congenital features, representing a common histopathologic denominator. Based on this observation, we suggest the term "widespread congenital dermal nevus with large nodules" to be the most appropriate for this rare, but distinctive, type of congenital nevus.