Classification of cysts with follicular germinative differentiation.

BACKGROUND: Cysts are very common in the routine of dermatopathology but follicular germinative (trichoblastic) differentiation in cysts is seen rarely. The presence of follicular germinative differentiation in a cyst alerts to consider the possibility of a basal cell carcinoma (BCC) arising in a cyst. METHODS: Five cystic lesions with zones of follicular germinative differentiation were collected. Hematoxylin and eosin sections were reassessed for architecture, types of follicular differentiation and stromal characteristics; immunohistochemical studies with Ber-EP4 were analyzed. Articles about follicular germinative differentiation in cystic lesions were reviewed. RESULTS: Cystic lesions with follicular germinative differentiation have been described in the literature under various names including trichoblastic infundibular cyst, cystic trichoblastoma, cystic panfolliculoma (CPF), dermoid cyst with basaloid proliferations, folliculosebaceous cystic hamartoma and BCC occurring in infundibular cysts. The lesions presented by us could be classified as three cystic trichoblastomas, one CPF and one cystic hamartoma with follicular germinative differentiation. CONCLUSIONS: Histopathologically, cystic trichoblastomas can be separated from CPFs. Some lesions defy classification and may be regarded as cystic follicular hamartomas. The presence of follicular papillae and bulb-like structures, advanced follicular differentiation like that of inner and outer root sheath exclude the differential diagnosis of BCC arising in a cyst.

High incidence of heparin-induced allergic delayed-type hypersensitivity reactions in pregnancy.

BACKGROUND: Among the most frequent adverse effects of subcutaneous heparin treatment, heparin-induced skin lesions occur with an incidence of 10.3% in nonpregnant female patients. Clinical observations suggest an even higher risk during pregnancy. OBJECTIVES: We sought to determine the incidence and causes of heparin-induced skin reactions during pregnancy in a prospective cohort study. METHODS: Pregnant women with subcutaneous heparin treatment were prospectively examined for skin reactions. If a skin lesion was observed, further diagnostics were performed (skin biopsy, subcutaneous provocation, clinical/laboratory assessment for thrombosis, bleeding, and heparin-induced thrombocytopenia [HIT]). Safety parameters were also analyzed (cross-allergies, frequency of thromboembolic and bleeding complications, HIT, and pregnancy outcome). RESULTS: Among 111 pregnant patients, 22 (19.8%) had heparin-induced skin reactions (95% CI, 13% to 29%). All lesions were caused by allergic delayed-type hypersensitivity (DTH) reactions and not by HIT or other rare conditions. The median time of onset was 50.5 days (range, 5-184 days). The cross-reactivity rate was 33.3%. While nadroparin treatment exhibited a higher DTH risk than dalteparin (hazard ratio [HR], 26.7; 95% CI, 3.4-211.0; P = .00187), enoxaparin treatment was not significantly different from dalteparin treatment (HR, 5.6; 95% CI, 0.3-96.1; P = .238). Three thromboembolic events and 1 major bleeding event occurred. CONCLUSIONS: Among patients receiving long-term heparin anticoagulation during pregnancy, heparin-induced skin lesions are frequent (incidence, 19.8%) and are all caused by allergic DTH reactions. Nadroparin has the highest frequency of skin lesions (approximately 65% at 100 days), which is significantly higher than that of dalteparin (HR, 26.7). Therefore nadroparin use should be avoided in pregnancy when possible.

Incidence and causes of heparin-induced skin lesions.

BACKGROUND: Little is known about the incidence and causes of heparin-induced skin lesions. The 2 most commonly reported causes of heparin-induced skin lesions are immune-mediated heparin-induced thrombocytopenia and delayed-type hypersensitivity reactions. METHODS: We prospectively examined consecutive patients who received subcutaneous heparin (most often enoxaparin or nadroparin) for the presence of heparin-induced skin lesions. If such lesions were identified, we performed a skin biopsy, platelet count measurements, and antiplatelet-factor 4 antibody and allergy testing. RESULTS: We enrolled 320 patients. In total, 24 patients (7.5%, 95% confidence interval [CI] 4.7%-10.6%) had heparin-induced skin lesions. Delayed-type hypersensitivity reactions were identified as the cause in all 24 patients. One patient with histopathologic evidence of delayed-type hypersensitivity tested positive for antiplatelet-factor 4 antibodies. We identified the following risk factors for heparin-induced skin lesions: a body mass index greater than 25 (odds ratio [OR] 4.6, 95% CI 1.7-15.3), duration of heparin therapy longer than 9 days (OR 5.9, 95% CI 1.9-26.3) and female sex (OR 3.0, 95% CI 1.1-8.8). INTERPRETATION: Heparin-induced skin lesions are relatively common, have identifiable risk factors and are commonly caused by a delayed-type hypersensitivity reaction (type IV allergic response).

Light and electron microscopy of eruptive collagenoma.

Connective tissue nevi may be multiple or solitary, sporadic or familial. Eruptive collagenoma is a variant of the acquired collagenomas characterized by multiple sclerotic papules with an acute onset. A 13-year-old girl reported that in the past year, small asymptomatic lesions began to appear in her skin, 30 lesions were seen in the trunk, 5 in the cervical region and 1 in the face. Light microscopy with hematoxylin and eosin staining showed sparse collagen fibers, with Weigert staining diminished elastic tissue was observed. Scanning electron microscopy of the dermis showed individualized collagen fibers forming waved compact masses and not bundles. Transmission electron microscopy also showed sparse and loose collagen fibers with different diameters in cross sections.

Discrimination of facial appearance stimuli in body dysmorphic disorder.

Cognitive-behavioral models of body dysmorphic disorder (BDD) propose that information-processing biases--in particular, selective attention to a defect in one's appearance as well as improved aesthetical perception--might contribute to the development or maintenance of the disorder. In the present study, the authors tested the hypothesis that patients with BDD discriminate facial appearance stimuli more accurately than controls. Sixty female patients from a dermatological clinic participated in the study: 21 patients with BDD, 19 patients with disfiguring dermatological conditions, and 20 patients with nondisfiguring dermatological disorders. Participants rated dissimilarities between pictures of neutral faces that had been manipulated with regard to aesthetic characteristics. Manipulation ratings of participants with BDD were significantly more accurate than those of both control groups. Implications of these results for cognitive theories of BDD are discussed.

Elastic tissue damage in cephalic acquired cutis laxa.

Cutis laxa is a rare condition characterized by diminished elastic tissue. We report the histological changes from a 22-year-old male patient, who presented since 4 years hanging and inelastic facial skin, giving him an older appearance. The palpebral, preauricular and submandibular skin obtained after a facelift were examined. Conventional light microscopy with hematoxylin-eosin staining showed perivascular lymphocytic infiltrates and crossed-over collagen fibers. With Weigert staining, a lessening of elastic fibers with fragmentation, shortening and clumping was seen. The oxytalanic fibers in the papillary dermis were also affected, ranging from absence or reduction to flattening with clumping of the fibers, giving an irregular contour to the basal membrane zone. These findings were more intense in the palpebral skin. Transmission electronic microscopy showed reduction of the elastic fibers, a granular degeneration of the elastic tissue was found and collagen fibers were normal. Similar to light microscopy, at the ultrastructural level, the basal membrane has an irregular contour.

Cutaneous leishmaniasis: clinical report of two cases and review of the recent literature.

With 1-1.5 million cases reported every year cutaneous leishmaniasis represents an increasing health problem. The course of cutaneous leishmaniasis varies from a single self-healing ulcer to a persistent ulcer or progressive mucosal disease with nasopharyngeal destruction. An enormous array of topical and systemic treatment modalities has been endorsed. The response to treatment depends on the species of parasite as well as the host's immunological and genetic status. Species-specific treatment guidelines based on evidence from controlled studies are highly desirable. We present two cases of cutaneous leishmaniasis, one in a child and one during pregnancy, reviewing various diagnostic and therapeutic measures with special attention to problems in young and pregnant patients.

Absence of classical MAP kinase pathway signalling in Merkel cell carcinoma.

Merkel cell carcinoma (MCC) is a highly metastatic skin tumor. To assess the relevance of the Ras/Raf/MEK/MAP kinase pathway, we analyzed for activating B-Raf mutations and we elucidated the presence of the Raf Kinase Inhibitor Protein (RKIP) and extracellular signal-regulated kinase (ERK) as well as the phosphorylation status of ERK. All MCC samples were negative for the B-Raf(V600E) mutation. Remarkably, RKIP, which was shown to interfere with the activation of MEK by Raf, was highly expressed in primary as well as in metastatic MCC. Immunohistochemical analysis of the phosphorylation status of ERK revealed in 42 out of 44 samples a complete lack of activated ERK in the tumor cells although ERK is expressed; in the two positive cases phosphorylated ERK was restricted to a minor fraction of the tumor cells. Western blot analysis of three MCC-derived cell lines revealed in one case the pattern present in situ (i.e. high RKIP expression and complete absence of phosphorylated ERK). In summary, our data demonstrate the inactivity of the classical MAP kinase signal transduction pathway in MCC, which seems to be because of lack of activation as well as active deactivation. These findings should be accounted for in future therapeutic approaches for this tumor.