Extragenital cutaneous warts - clinical presentation, diagnosis and treatment.

Extragenital cutaneous warts are benign epidermal tumors caused by human papillomaviruses (HPVs) and a frequent reason for patients to consult a dermatologist. Depending on wart type and site involved, the clinical presentation is highly varied. Given that warts represent a self-limiting condition, a wait-and-see approach may be justified. However, treatment is always indicated if the lesions become painful or give rise to psychological discomfort. Factors to be considered in this context include subjective disease burden, patient age, site affected, as well as the number and duration of lesions. Destructive treatment methods involve chemical or physical removal of diseased tissue. Nondestructive methods consist of antimitotic and antiviral agents aimed at inhibiting viral proliferation in keratinocytes. Some of the various immunotherapies available not only have localized but also systemic effects and are thus able to induce remission of warts located at any distance from the injection site. Especially patients with warts at multiple sites benefit from this form of treatment. Intralesional immunotherapy using the mumps-measles-rubella (MMR) vaccine is a particularly promising option for the treatment of recalcitrant warts in adult patients. For children, on the other hand, HPV vaccination is a novel and promising approach, even though it has not been approved for the treatment of cutaneous warts. At present, there is no universally effective treatment available. Moreover, many frequently employed therapies are currently not supported by conclusive clinical trials.

Indoleamine 2,3-dioxygenase expression in early keratocyte neoplasia of the lower lip correlates to the degree of cell atypia.

Actinic cheilitis (AC) is an early keratocyte neoplasia with inflammation that occurs in the lip vermillion with the potential to develop into invasive squamous cell carcinoma (SCC). The expression of the intracellular enzyme indoleamine 2,3-dioxygenase (IDO) by antigen-presenting cells and/or tumor cells has been described to arrest T cell proliferation by degrading the essential amino acid tryptophan from the environment. The expression of IDO in AC may support cancer progression by inhibiting T cell-mediated rejection responses. The aim of this study was to identify the cellular nature and extent of IDO expression in early keratocye neoplasia of the lower lip (n=25), and to correlate IDO expression to the severity of epithelial atypia (KIN I°- KIN III°) and to the extent of actinic inflammation. The expression of IDO was analyzed together with expression markers for T-cells (CD3), myeloid DCs (S100, CD11c), macrophages (CD68, CD11c), and Langerhans cells (CD1a) by immunohistochemistry and immunofluorescence analysis. Analyses showed that IDO was expressed in myeloid S100(+) CD11c(+) DCs. The expression of IDO correlated significantly with the degree of epithelial atypia (P=0.0005) but not to the extent of inflammation (P=0.4283). Expression of IDO in early atypic skin epithelial conditions might be a predictor to promote carcinogenesis.

Cutaneous macroglobulinosis deposits in a patient with IgM paraproteinemia/incipient Waldenström macroglobulinemia.

A 43-year-old healthy patient developed disseminated flat skin-colored to red-brown papules over a few months. These papules were the result of cutaneous IgM deposits representing the first symptom of a hitherto undiagnosed IgM paraproteinemia. This extremely rare skin manifestation of IgM paraproteinemia e. g. possibly incipient Waldenström macroglobulinemia should be included in the histopathological differential of eosinophilic dermal deposits.

[Progressive nodular histiocytosis--rare variant of cutaneous non-Langerhans cell histiocytosis]. / Progressive noduläre Histiozytose--seltene Variante einer kutanen Non-Langerhanszell-Histiozytose.

Progressive nodular histiocytosis is an extremely rare skin disease is clinically characterized by the coincidence of two distinct lesions, namely, superficial xanthomatous papules up to 5 mm and deep nodules and tumors 1-3 cm. Histologically the nodules represent spindle cell xanthogranulomas. We report a 24-year-old women with these findings. The distinction from other non-Langerhans cell histiocytoses, in particular multiple juvenile xanthogranulomas, which may be more likely to show spontaneous remission, is somewhat unclear; patients with progressive nodular histiocytosis usually follow a serious and disfiguring clinical course.

Mycosis fungoides palmaris et plantaris--an unusual variant of cutaneous T-cell lymphoma.

Mycosis fungoides (MF) represents a low-risk, cutaneous, non-Hodgkin, T-cell lymphoma with a wide spectrum of clinicopathological manifestations and therefore may mimic a number of other dermatoses. Sometimes the clinical diversity makes the diagnosis of MF, and especially its atypical forms, challenging. We report on an 18-year old male patient, who had been previously diagnosed with palmoplantar eczema. Clinical, histopathological, immunohistochemical and molecular findings revealed an atypical case of MF.

MAGE-A3 is a frequent tumor antigen of metastasized melanoma.

MAGE-3 or MAGE-A3 is one of the best-characterized tumor antigens. Due to its tumor-restricted expression pattern and its recognition by both cytotoxic and helper T cells it constitutes a promising tumor antigen for anticancer immunotherapy, notably of malignant melanoma. Surprisingly, however, only very limited information is available on the frequency and consistency of its expression in metastatic melanoma lesions. We have now investigated the presence of MAGE-A3 mRNA in 316 tumor samples from 147 melanoma patients by RT-PCR. MAGE-A3 mRNA was detectable in 62% of metastases, and expression did not depend on the site of the metastases (skin, lymph node, and internal organs), age, sex, or duration of disease. Southern blot hybridization of the PCR product enhanced sensitivity of detection, and 26% more samples (13/50 samples tested) scored positive, indicating an even higher MAGE-A3 mRNA frequency than determined by simple ethidium bromide gel analysis. In 62 patients, we were able to investigate MAGE-A3 expression in several metastases from the same patient, and unexpectedly, both MAGE-A3-positive and MAGE-A3-negative metastases were found in 32% of these patients (20 of 62). Immunohistochemistry (using mAb 57B) demonstrated that the expression pattern was usually also heterogeneous with positively and negatively stained tumor cells within one metastasis. However, most (90%) of the metastases (47/52) gave a partially positive signal. Taken together, MAGE-A3 is a common and frequent tumor antigen in metastasized melanoma, but its expression is often heterogeneous.

Circulation and homing of melanoma-reactive T cells to both cutaneous and visceral metastases after vaccination with monocyte-derived dendritic cells.

Anticancer immune therapies aim at the induction of tumor-specific T cells, which ultimately should kill tumor cells. The effector cells should, therefore, not only exert cytotoxic activity but also home to and infiltrate the tumor site. Hence, monitoring of immune modulating therapies should not be restricted to the circulating pool of peripheral blood mononuclear cells (PBMC) but also include tumor-infiltrating lymphocytes (TIL), as well as the correlation of these findings to the clinical course. We report here on the longitudinal immunologic workup of a melanoma patient who developed remarkably potent ex vivo detectable antimelanoma cytotoxic T-cell (CTL) responses after vaccinations with autologous peptide-pulsed dendritic cells. Such potent CTL responses to multiple tumor antigens have, to the best of our knowledge, not been described previously in melanoma patients, neither spontaneously nor after any therapy. This patient first experienced a transient response to therapy but finally succumbed to disease progression and died. Progression was associated with the decline of the numbers of tumor-reactive T cells in circulation and at skin metastases in addition to the loss of MHC class I antigens. The immunologic analysis revealed that fully functional tumor-specific T cells were present in the peripheral blood of this patient during the phase of a relatively stable disease, and in situ tetramer staining demonstrated that these cells were also accumulated at cutaneous and visceral tumor sites. Furthermore, comparative clonotype mapping of PBMC and TIL depicted an overlapping TCR repertoire usage among these 2 compartments. Since strong CTL responses as observed in this patient are the goal of cancer vaccination but are so far only rarely observed, the thorough analysis of patients exhibiting either exceptional clinical and/or immunologic responses appears critical to understanding how vaccine therapies work and can be further improved.

[Pseudosarcomatous variant of a genital fibroepithelial stromal polyp in a pregnancy]. / Pseudosarkomatöse Variante eines genitalen fibroepithelialen stromalen Polypen bei einer Schwangeren.

Fibroepithelial stromal polyps are benign neoplasms of the lower genital tract occurring mostly in young to middle-aged women in their reproductive years. Clinically they appear as tender, skin-colored, sack-like tumors and usually have a bland microscopic appearance. Sometimes, especially during pregnancy or with hormone therapy, a worrisome hypercellular and pseudosarcomatous pattern can be seen in the dermis. Awareness of this neoplasm with a possibly high degree of atypia is of crucial importance in order to avoid unnecessary radical surgery.

[Cholesterol emboli during coumarin therapy]. / Cholesterin-Embolie unter Cumarin-Therapie.

A 71-year-old patient suddenly developed a painful, bizarre livid erythema on the right foot. Based upon the clinical and histological presentation, cholesterol emboli were diagnosed. These cholesterol emboli were induced by therapy with phenprocoumon (a coumarin derivative), which had been initiated 5 months previously. Arterial emboli may rarely occur during anticoagulation and have to be included in the differential diagnosis.