Regina Fink-Puches

A variant of lymphomatoid papulosis simulating primary cutaneous aggressive epidermotropic CD8+ cytotoxic T-cell lymphoma. Description of 9 cases.

Lymphomatoid papulosis (LyP) is a recurrent, self-healing eruption belonging to the spectrum of cutaneous CD30+lymphoproliferative disorders. Three main histologic subtypes of LyP are recognized: type A (histiocytic), type B (mycosis fungoides—(MF)-like), and type C (anaplastic large cell lymphoma–like). We reviewed 26 biopsies from 9 patients (M:F=6:3, median age: 29; mean age 27,2; age range 10 to 38) who presented with clinical features typical of LyP but with histopathologic aspects that resembled primary cutaneous aggressive epidermotropic CD8+cytotoxic T-cell lymphoma. In all but 1 case atypical lymphoid cells showed expression of CD30, and in 8 of 9 cases a T-cell cytotoxic phenotype could be observed (βF1+, CD3+, CD4−, CD8+). Expression of at least 1 cytotoxic marker (TIA-1, granzyme B) was observed in all cases. Polymerase chain reaction analysis of the T-cell receptor genes revealed a monoclonal rearrangement in 2 of 5 cases tested. Follow-up data available for 8 patients (mean follow-up time: 84 mo, median: 32.5 mo; range: 1 to 303 mo) revealed that none of them developed systemic involvement or signs of other cutaneous lymphomas. This cytotoxic variant of LyP may be histopathologically indistinguishable from primary cutaneous aggressive epidermotropic CD8+ cytotoxic T-cell lymphoma, and may be the source of pitfalls in the diagnosis and classification. We propose the term LyP type D for this unusual variant of the disease. Accurate clinicopathologic correlation is required in this setting, with crucial implications regarding prognosis and management of patients.

Cutaneous manifestations of blastic plasmacytoid dendritic cell neoplasm-morphologic and phenotypic variability in a series of 33 patients.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a neoplasm derived from precursors of plasmacytoid dendritic cells. Cutaneous involvement represents often the first manifestation of the disease. We studied 45 skin biopsies from 33 patients (M:F=7.25:1; median age: 71 y; age range: 30 to 89) with BPDCN to delineate histopathologic and immunophenotypic features of this disease. Patients presented with generalized (n=18), localized (n=6), or solitary (n=9) macules, plaques, and/or tumors. Staging investigations at presentation were negative in 20 patients. Unusual histologic features included a perivascular/periadnexal pattern (6 biopsies from 4 patients) and the presence of pleomorphism of neoplastic cells with blastoid cells admixed with elongated, twisted, or hyperchromatic cells (observed in 24 specimens). Negativity of 1 among the 4 markers CD4, CD56, CD123, and TCL-1 was seen in 11 biopsies, and of 2 markers in 4 biopsies. Staining for CD68 revealed positivity of the majority of cells in 1 and of scattered cells in 24/37 stained cases. Terminal deoxynucleotidyl transferase was observed in 22/37 stained cases. Staining for Bcl-6, MUM-1 and FOX-P1 revealed positivity of a variable proportion of neoplastic cells in 16/30, 19/29, and 21/23 cases, respectively. Our study shows that cutaneous lesions of BPDCN display a greater variability of morphologic and phenotypic features than recognized earlier. Discrete perivascular infiltrates, pleomorphic morphology of neoplastic cells, and unusual phenotypic profiles may be the source of diagnostic pitfalls. These atypical variants should be recognized to make an early diagnosis and to manage properly patients with this aggressive hematological disorder.

Age-related prevalence of dermoscopy patterns in acquired melanocytic naevi.

Background  Based on the dermoscopic classification of acquired melanocytic naevi, six different dermoscopic types can be distinguished by morphology (globular, globular‐reticular, globular‐homogeneous, reticular, reticular‐homogeneous, homogeneous) and by pigment distribution (uniform, central hyperpigmentation, central hypopigmentation, peripheral hyperpigmentation, peripheral hypopigmentation, multifocal hyper/hypopigmentation). It has been suggested that most individuals harbour one predominant dermoscopic type among their naevi.

Primary clinical response and long-term follow-up of solar keratoses treated with topically applied 5-aminolevulinic acid and irradiation by different wave bands of light

Photodynamic therapy with 5-aminolevulinic acid (ALA-PDT) is based on photosensitization by endogenous synthesis of protoporphyrin IX and its transient accumulation especially in malignant epithelially derived tissues. Recent studies have indicated that ALA-PDT is effective for the treatment of solar keratoses (SK), but there has been a lack of long-term clinical follow-up. The goal of the present study was to investigate the immediate and long-term effect of ALA-PDT on SK. Twenty-eight patients with a total of 251 SK were enrolled in the study. Standard treatment involved the topical application of 20% ALA, under occlusive and light-shielding dressing for 4 hours before exposure to UVA and/or different wave bands or wave band combinations of polychromatic visible light (full-spectrum visible light, and/or different wave bands of filtered visible light > 515, > 530, > 570, or > 610 nm) in one or two treatment sessions. The primary complete response rate of SK to ALA-PDT was 64% after one treatment, but 85% when the responses to a second treatment were included. Taken all treatments together, the complete response rate for lesions on face, scalp and neck was 93% for full-spectrum visible light, 96% for the combination of full-spectrum visible light and filtered light, 91% for different wave bands of filtered visible light, and 100% for the combination of long wave UVA and full-spectrum visible light, respectively. The complete response rate for lesions on forearms and hands was 51% for full-spectrum visible light and 33% for the combination of full-spectrum visible light and filtered light. The greater response rate for SK on the face, scalp, and neck was associated with a higher surface fluorescence and immediate response rate after ALA photosensitization at these sites (chi 2; p = 0.0001). However, due to the treatment protocol the mean light dose applied to lesions on the face, scalp and neck (50 J cm-2) was substantially higher than that for lesions on forearms and hands (35 J cm-2). In the long term follow-up of SK on face scalp and neck, the projected disease-free rate at 36 months after therapy was 71% for lesions treated with full-spectrum visible light versus 23% for lesions treated with different wave bands of filtered light (Log rank-Mantel Cox; p = 0.0001). These results indicate that treatment with full-spectrum visible light at higher light doses may be the most effective and promising form of light exposure in ALA-PDT of SK.

Time Required for a Complete Skin Examination With and Without Dermoscopy: A Prospective, Randomized Multicenter Study

OBJECTIVE To determine the time required to perform a complete skin examination (CSE) as a means of opportunistic screening for skin cancer both without and with dermoscopy. DESIGN Randomized, prospective multicenter study. SETTING Eight referral pigmented lesion clinics. Patients From June 2006 to January 2007, 1359 patients with at least 1 melanocytic or nonmelanocytic skin lesion were randomly selected to receive a CSE without dermoscopy or CSE with dermoscopy. For each patient, the total number of lesions and the duration of the CSE were recorded. A total of 1328 patients were eligible for analysis (31 were excluded because of missing data). MAIN OUTCOME MEASURES The median time (measured in seconds) needed for CSE with and without dermoscopy and according to total cutaneous lesion count. RESULTS The median time needed for CSE without dermoscopy was 70 seconds and with dermoscopy was 142 seconds, a significant difference of 72 seconds (P < .001). The use of dermoscopy increased the duration of CSE, and this increase was in direct proportion to the patients total lesion count. In contrast, the time required to perform a CSE without dermoscopy remained the same irrespective of whether the patients had few or many lesions. CONCLUSIONS A CSE aided by dermoscopy takes significantly longer than a CSE without dermoscopy. However, a thorough CSE, with or without dermoscopy, requires less than 3 minutes, which is a reasonable amount of added time to potentially prevent the morbidity and mortality associated with skin cancer.

Cutaneous involvement in lymphoblastic lymphoma

Lymphoblastic leukemia/lymphoma (LBL) is a malignant neoplasm of precursor lymphocytes of B‐ or T‐cell phenotype. Involvement of the skin is relatively uncommon. We examined retrospectively the clinicopathologic, immunophenotypic, and molecular genetic features of six patients with cutaneous involvement of LBL (B‐LBL=5; T‐LBL=1). Patients presented clinically with solitary, large tumors located on the head (3 cases) or the back (1 case), or with generalized tumors (2 cases). Ulceration was uncommon. In two patients the onset of skin lesions was concomitant to the diagnosis of lymphoblastic leukemia. Histopathologic examination showed in all cases a dense, diffuse, monomorphous infiltrate located in the entire dermis and subcutaneous fat. A typical “starry sky” pattern was observed in the majority of the lesions. In some areas neoplastic cells were aligned in a “mosaic‐like” fashion. Cytomorphologically, medium sized lymphoid cells with round or convoluted nuclei, inconspicuous nucleoli and scant cytoplasm predominated. There were no significant differences in the histopathologic features of skin lesions in T‐ and B‐LBL. In B‐LBL, CD79a was more useful than CD20 in determining the phenotypc of neoplastic cells (4/5 cases positive for CD79a as compared to 2/5 cases positive For CD20). TdT, CD10 and CD43 were positive in 4 cases, CD34 in 2. The case of T‐LBL revealed positivity for CD 1a, CD3, CD43 and TdT, and negativity for CD34 and for B‐cell markers. All neoplasms were positive for CD99 and bcl‐2, and showed a high proliferation rate. Molecular genetic analysis of JH and T‐cell receptor (TCR) genes performed using a polymerase chain reaction technique revealed a monoclonal rearrangement of JH genes in all five B‐LBLs. One of these cases showed also a concomitant TCR‐γ gene rearrangement. A monoclonal rearrangement of the TCR‐γ gene was detected in the case of T‐LBL. Our study shows that skin lesions of LBL present characteristic clinicopathologic and molecular features allowing the differentiation from other cutaneous lymphomas, even in cases without clinical history of previous precursor lymphoblastic leukemia/lymphoma.

Cutaneous spindle-cell B-cell lymphoma: a morphologic variant of cutaneous large B-cell lymphoma.

The morphologic spectrum of large B-cell lymphoma is broad. Several unusual variants have been described such as lymphoma with myxoid stroma, sclerosing B-cell lymphoma, signet ring–cell lymphoma, and multilobated B-cell lymphoma among others. We report on five cases of cutaneous large B-cell lymphoma in which the neoplastic cells were spindle-shaped. In two cases, the clinical features fulfilled those of a primary cutaneous lymphoma; in the three other cases, the lymphoma most likely arose primarily in the skin, but incomplete clinical workups precluded definite categorization. The patients ranged in age from 30 to 89 years and presented with solitary lesions on the trunk or head. Histopathologic examination revealed nodular or dense diffuse infiltrates involving the entire dermis as well as the subcutaneous fat in some cases. Thickened collagen bundles between the spindled cells were present in one case. Cytomorphologic analysis showed the presence of round or oval medium-sized and large-sized lymphocytes with features of centrocytes and centroblasts in some foci, with others dominated by cells with spindle-shaped, elongated, twisted nuclei with dispersed chromatin and scant cytoplasm. Immunohistologic analysis revealed that both round or oval and spindled cells were positive for CD20 in all cases; in all cases tested, these cells were also positive for MIB-1 and were negative for CD3, CD5, CD43, CD45RO, CD21, CD30, CD68, S-100, HMB-45, actin, smooth-muscle actin, and cytokeratin. Bcl-2 was expressed in one of three cases tested. Analysis of the rearrangement of the JH gene by polymerase chain reaction performed in one case showed a monoclonal pattern. Spindle-cell large B-cell lymphoma represents a distinctive rare subtype of the cutaneous large B-cell lymphoma and can arise primarily in the skin in some cases. Recognition of this variant is necessary to avoid misdiagnosis of other cutaneous malignant spindle-cell tumors.

Reflectance confocal microscopy of facial lentigo maligna and lentigo maligna melanoma: a preliminary study.

Background  Facial lentigo maligna (LM) and lentigo maligna melanoma (LMM) may be difficult to diagnose clinically and dermoscopically. Reflectance confocal microscopy (RCM) enables the in vivo assessment of equivocal skin lesions at a cellular level.

The additive value of second opinion teleconsulting in the management of patients with challenging inflammatory, neoplastic skin diseases : a best practice model in dermatology?

Background  Telemedicine is the practice of healthcare using interactive processes of communication to facilitate healthcare delivery, including diagnosis, consultation and treatment, as well as education and transfer of medical data. The aim of teledermatology, just as telemedicine, is to promote best practice procedures and to improve the consistency and competence of health care.

Febrile ulceronecrotic pityriasis lichenoides et varioliformis acuta

An unusually severe form of pityriasis lichenoides et varioliformis acuta (PLEVA) with a fatal outcome in an 82-year-old woman is reported. After a period of a mild eruption, extensive polymorphous, papular and ulcerohemorrhagic skin lesions developed, associated with intermittent high temperature and constitutional symptoms. Skin biopsies showed the typical histopathological changes of PLEVA. Early recognition of this severe variant of PLEVA is important, since the fulminating course can lead to death.