Gamma‐delta T‐cell lymphoma arising in a long‐standing cutaneous plaque

The precise classification and characterization of primary cutaneous gamma‐delta T‐cell lymphoma (PCGD‐TCL) has been hindered by clinical and morphologic features that overlap with other lymphomas, especially subcutaneous panniculitis‐like T cell lymphoma (SPTCL). The recent World Health Organization/European Organization for Research and Treatment of Cancer (WHO/EORTC) classification distinguishes the more aggressive PCGD‐TCL from the usually indolent SPTCL, however. We report a 30‐year‐old woman with an indurated violaceous plaque on the left cheek that had been present for several years. Biopsies showed a dense lymphocytic infiltrate involving the subcutis and dermis that consisted mostly of small and medium‐sized lymphocytes, some with irregular nuclear contours and dense chromatin. These cells were positive for TIA‐1, TCR‐gamma and CD8, but negative for beta‐F1 and granzyme‐B. Staging with positron emission tomography–computed tomography (PET/CT), CBC and bone marrow with flow cytometry identified lymphadenopathy as well as blood and marrow involvement by an abnormal TCRgd‐positive T‐cell proliferation (Ann Arbor Stage IV). The patient's history of a long‐standing lesion in this case is unusual, in that gamma‐delta T‐cell lymphomas are typically rapidly progressive neoplasms. As such, it raises the possibility of ‘transformation’ of a long‐standing inflammatory process into an overt lymphoma.     

Narrowband ultraviolet B phototherapy in the treatment of cutaneous graft‐versus‐host disease in oncohaematological paediatric patients

Background Graft‐versus‐host disease (GVHD) represents an important complication following allogeneic bone marrow transplantation. In recent years, narrowband ultraviolet B (NB‐UVB, 311–313 nm) has been found to be a beneficial adjuvant treatment in patients refractory to first‐line immunosuppressive drugs. Objectives The aim of this study is to analyse retrospectively the clinical outcome of 10 GVHD paediatric patients treated with NB‐UVB therapy. Patients and methods Ten paediatric patients (six girls and four boys: median age 12·5 years, range 4–20) with cutaneous GVHD were enrolled in the study: five patients with chronic GVHD and five patients with an overlap syndrome GVHD. All patients had already been shown to be resistant to first‐choice immunosuppressive protocols, and were treated with NB‐UVB phototherapy until a clinical remission of skin lesions occurred. Results A complete response (absence of lesions) was achieved in 80% of the cases (eight patients) after a median number of 29 treatments, corresponding to a median of 7·5 weeks (52 days) of treatment (range 3–13 weeks), with an average cumulative dose of 28·71 J cm^?2 (range 1·02–70·38 J cm^?2). Only two patients reported a partial remission (< 18% of body surface area involved). During the follow‐up period, a complete remission after 1 year was observed in 75% of patients and after 2 years in 71% of the evaluable patients. Conclusions This study provides evidence that NB‐UVB phototherapy represents a valid second‐line treatment in paediatric patients affected by GVHD and refractory to immunosuppressive first‐line treatment.     

Distinct age‐matched serum biomarker profiles in patients with cutaneous T‐cell lymphoma

Immunological functions decline with age. Because MS/SzS predominately affects the elderly, it is important to distinguish age‐related from cancer‐specific changes. Also, MF and SzS are malignancies of CD4⁺ T‐lymphocytes, further compromising an immune state of the patients. The objectives of this study were to distinguish disease‐specific immunological deterioration by performing comparative age ‐ matched Luminex multiplex assessment of 34 serum biomarkers between patients with MF/SzS, HIV‐infected individuals and normal controls. Controlling for age, expression level appears to significantly differ between patients with MF/SzS and controls for the following biomarkers: G‐CSF, IL‐5, MIP‐1β, TNF‐α, VEGF, EOTAXIN, IL‐8, IL‐12, IL‐2R, IP10, MCP‐1, MIG, TNFR1 and TNFR2 (P < 0.05), while others showed normal age‐related changes. Interestingly, cluster analysis placed MF/SzS profiles closer to HIV. This further underscores an immunologically compromised state of patients with MF/SzS and suggests its potential self‐perpetuating role in disease progression.     

Non-invasive evaluation of dermal elastosis by in vivo multiphoton tomography with autofluorescence lifetime measurements

The non-invasive differentiation of dermal elastic fibres from solar elastosis in vivo is of great interest in dermatologic research, especially for efficacy testing of anti-ageing products. To date, no studies on multiphoton excited fluorescence lifetime characteristics of human elastic fibres and solar elastosis are reported. The goal of the present work was the identification of differential criteria for elastic fibres and solar elastosis by the analysis of fluorescence decay curves acquired by time-correlated single photon counting in vivo multiphoton tomography. For this purpose, fluorescence lifetime measurements (FLIM) were performed with 47 volunteers of different age groups at sun-protected and sun-exposed localizations. Bi-exponential curve fitting was applied to the FLIM data, and characteristic differences between age groups and localizations were found in both relevant fit parameters describing the decay slope. The FLIM analyses have shown that dermal autofluorescence has different lifetimes depending on age and in part on localization.     

Somatostatin receptor scintigraphy in primary cutaneous T‐ and B‐cell lymphomas

Background Monitoring and repeated staging is of substantial importance in many patients with primary cutaneous T‐cell lymphomas (CTCL). For primary cutaneous B‐cell lymphomas (CBCL), extensive initial staging is the mainstay for correct diagnosis. Aim To evaluate the value of somatostatin receptor scintigraphy using the radiolabeled somatostatin analog ¹¹¹In‐pentetreotide in comparison to conventional imaging methods for the staging of patients with primary CTCL and primary CBCL. Methods Twenty‐two patients (15 patients with histologically verified CTCL and 7 patients with histologically verified CBCL) were included. Stage of disease was established by physical examination, laboratory screening, skin inspection, palpation of superficial lymph nodes, sonography and computed tomography (CT) in patients with advanced clinical stage. Focally elevated tracer uptake of ¹¹¹In‐pentetreotide was compared to common imaging modalities, physical aspect and digital photographs of the respective skin lesions. Results Of the 15 patients with CTCL, only 4 (27%) showed positive scintigraphic results, but not in all sites of lymphomatous involvement. None of the five patients with mycosis fungoides in stage I, nor any of the four patients with Sézary syndrome, had a positive ¹¹¹In‐ pentetreotide scan. Of the seven patients with CBCL three positive scintigraphic results (43%) could be obtained: in two patients with a follicular center lymphoma and one patient with a diffuse large B‐cell lymphoma – leg type, but again not in all apparent sites of lymphoma. Conclusions Based on our results, we do not recommend the use of somatostatin receptor scintigraphy for routine staging of patients with CTCL and CBCL. As our series includes only 22 patients, and the number of patients with rarer variants of CTCL was rather small, it might be too premature to abandon SST‐R in the staging of patients with cutaneous lymphomas.     

Update on the anti‐programmed cell death‐1 receptor antibodies in advanced cutaneous squamous‐cell carcinoma

Regarding the rising incidence and the not negligible mortality, the treatment of cutaneous squamous‐cell carcinoma (cSCC) has a high clinical relevance. Immune checkpoint inhibitors (ICI), especially anti‐programmed cell death‐1 receptor (anti‐PD‐1) antibodies such as pembrolizumab and cemiplimab have shown promising results in Phase 2 studies for patients with locally advanced and/or metastatic cSCC. We are presenting a review of the latest results in the treatment of cSCC with ICI. Patients with locally advanced or metastatic cSCC have been treated with cemiplimab 3 mg/kg every 2 weeks. For locally advanced cSCC, an objective response was observed in 44% of patients, 13% patients with a complete response, and 31% with a partial response. For metastatic patients, the overall response rate was 49.2%. The approved dose for cemiplimab in the United States and Europe is 350 mg every 3 weeks. These ICI seem to achieve higher response rates compared with epidermal growth factor receptor (EGFR) inhibitors, with a durable response superior to both chemotherapy and EGFR inhibitors. The side effect profile of anti‐PD‐1 antibodies appears to be favorable compared to chemotherapy. In this way, PD‐1 inhibitors are expected to become the new gold‐standard treatment for patients with locally advanced and metastatic cSCC.     

Acitretin combined with NB‐UVB in the treatment of cutaneous CD30‐positive anaplastic large cell lymphoma

Cutaneous CD30⁺ lymphoproliferative disorders represent a spectrum of skin lymphatic reticular proliferative diseases, including lymphomatoid papulosis (LYP), primary cutaneous anaplastic large cell lymphoma (PC‐ALCL), and borderline lesions between them. Although they all express CD30 as a phenotypic marker and share overlapping immunophenotypic features, they differ in clinical manifestations, pathological features, treatment, and prognosis. LYP is a kind of benign disease characterized by recurrent papules and nodules, and may spontaneously regress. PC‐ALCL presents with solitary tumor or local grouped nodules characterized by large T‐cells and may completely or partially resolve in fewer than half of cases. We reported a case of patient with clinical manifestation and pathologic features consistent with LYP in its early stages, which later turned into PC‐ALCL. This patient was treated with acitretin combined with NB‐UVB and had an obvious response.     

Depth‐resolved measurement of the dermal matrix composition by multiphoton laser tomography

Background: In the last years, multiphoton laser tomography (MLT) has emerged as a promising tool for non‐invasive diagnostics in dermatology and other medical specialties. The present work is dedicated to the question to what degree the measurement depth and the thickness of the epidermis influence the evaluation of dermal matrix composition and if recommendations for future measurement procedures can be given. Methods: In a study group of 30 healthy volunteers aged 21–82 years multiphoton depth‐resolved measurements of autofluorescence and second harmonics have been performed in order to evaluate the dermal matrix composition. Results: Characteristic intensity curves depending on the penetration depth were derived and differences between age groups were found. Conclusion: With the present work we provide evidence for the accuracy of the measurement of dermal matrix composition by MLT and give detailed advice for the measurement procedure. Furthermore, we propose the use of depth‐dependent emission intensity curves for monitoring of anti‐aging treatment.     

Generalized fixed drug eruption mimicking CD8+ cutaneous T‐cell lymphoma in HIV

We present a case of a widespread fixed drug eruption histologically mimicking CD8 positive cutaneous T‐cell lymphoma (CTCL). CTCL has several potential histological and clinical mimics, and accurate diagnosis relies on a combination of clinicopathological correlation and molecular studies. We add generalized fixed drug eruption to the list of possible CTCL mimics.     

T‐cell receptor gene rearrangement analysis of sequential biopsies in cutaneous T‐cell lymphomas with the Biomed‐2 PCR reveals transient T‐cell clones in addition to the tumor clone

Detection of a dominant T‐cell clone by T‐cell receptor (TCR) gene rearrangement analysis is often essential for the diagnosis of cutaneous T‐cell lymphomas (CTCL). The occurrence of T‐cell clones in addition to the diagnostic T‐cell clone during the course of CTCL has been reported, but the data of these studies have been contradictory. We retrospectively evaluated the data of 114 lesional skin biopsies from 26 patients with Mycosis fungoides and two patients with primary cutaneous anaplastic large cell lymphoma, which were analysed with the standardized Biomed‐2 PCR for the TCRγ and TCRβ locus. A dominant T‐cell clone was repetitively detected in 93% (26/28) of patients. Additional T‐cell clones appeared temporarily in 39% (11/28) of patients. Correlation with the clinical data did not show an association of the presence of additional T‐cell clones with age, number of treatments, progression of disease or survival. Our findings demonstrate that a persistent T‐cell clone, most likely the disease causing tumor clone, is detectable in almost all CTCL patients. In addition, transiently appearing T‐cell clones frequently occur during the course of disease. The biological relevance of these additional clones has still to be determined. However, it is important to take the possibility of additional T‐cell clones into account for diagnostic analyses.     

Therapeutic removal of amyloid deposits in cutaneous amyloidosis by localised intra‐lesional injections of anti‐amyloid antibodies

Please cite this paper as: Therapeutic removal of amyloid deposits in cutaneous amyloidosis by localised intra‐lesional injections of anti‐amyloid antibodies. Experimental Dermatology 2010; 19 : 904–911. Abstract: In the skin, amyloidosis can be found with or without systemic disease. Primary cutaneous amyloidosis defines those amyloidoses restricted to the skin without involvement of other systems. Here, we used conformation‐specific antibodies to characterise both fibrillar and oligomeric amyloid aggregates in the skin from patients with cutaneous amyloidosis. Localised cutaneous amyloidosis with different morphology was reproduced in mice by intra‐dermal (i.d.) and subdermal administration of amyloid‐enhancing factor. Moreover, we demonstrated that conformational antibodies were effective in clearing amyloid deposits caused by localised intra‐lesional injections without the necessity of an immune response. Given the accessibility and amyloid localization in this disease, direct i.d. injections of conformational antibodies could be a convenient and direct method for treatment.