Diagnostic application of cyclin D1 fluorescent in situ hybridization for histologically undetermined early lesions of acral melanoma in situ: A case series.

Histologically undetermined early acral melanoma in situ (HUAMIS) is rare but a diagnostic challenge, being clinically and dermoscopically MIS (late onset, a large size (>7 mm), parallel ridges pattern) but microscopically without recognizable cytological atypia. Cyclin D1 (CCND1) gene amplification is a genetic aberration occurring in the early radial growth phase of AMs and could thus help determine malignancy for this disease. We determine the value of CCND1 amplification by FISH as a diagnostic marker for HUAMIS. CCND1 amplification was examined in paraffin-embedded skin biopsies and excisions using a dual-probes fluorescence in situ hybridization (FISH) (11q13 and CEP11). One FISH-negative case 6 was additionally examined by Mypath Melanoma (qRT-PCR). Seventeen cases (12 dysplastic nevi, 3 AMIS, and 2 invasive AM) were served as negative controls for FISH. All six patients (4 females and 2 males) were Hispanic. Pigment lesions were on the left plantar foot (4), right third finger palm (1), and right thumb subungual (1). All cases showed similar clinical and dermoscopical characteristics, including late onset (50 to 74 years old), long duration (from 2 to 15 years), large-sized pigments (from 16 to 40 mm), and a parallel ridge pattern. Junctional melanocytes with no or minimal atypia from five cases showed CCND1 amplifications. Four of 5 cases were received 1st or/and 2nd wide excisions, which demonstrated foci of histologically overt MIS. One FISH-negative case 6 demonstrated "likely malignancy" scores (>2) by Mypath Melanoma (qRT-PCR). None of negative controls showed the amplification. We propose here a simple CCND1 FISH is a practical diagnostic test to determine the malignancy of the very early progression phase of AM preceding histopathologically defined MIS. Cases presented here could be an indolent subtype of AMIS characterized by carrying a long latent radial growth phase without vertical growth, mimicking lentigo maligna.

The (pro)renin receptor and body fluid homeostasis.

The renin-angiotensin system (RAS) has long been established as one of the major mechanisms of hypertension through the increased levels of angiotensin (ANG) II and its resulting effect on the sympathetic nerve activity, arterial vasoconstriction, water reabsorption, and retention, etc. In the central nervous system, RAS activation affects body fluid homeostasis through increases in sympathetic nerve activity, water intake, food intake, and arginine vasopressin secretion. Previous studies, however, have shown that ANG II can be made in the brain, and it could possibly be through a new component called the (pro)renin receptor. This review intends to summarize the central and peripheral effects of the PRR on body fluid homeostasis.

Seborrheic keratosis: reflectance confocal microscopy features and correlation with dermoscopy.

BACKGROUND: Differentiation between seborrheic keratosis (SK) and skin cancers may be difficult. Reflectance confocal microscopy (RCM) enables noninvasive assessment of skin neoplasms at cellular-level resolution. OBJECTIVE: We sought to describe RCM features of SK and to correlate these RCM findings with dermoscopic structures. METHODS: Clinical, dermoscopic, and RCM images of 45 consecutive SK were obtained at a private and university dermatology clinic. Fourteen SK were biopsied because of equivocal clinical or dermoscopic features. RESULTS: With RCM, all SK displayed a regular honeycomb pattern of the epidermis and densely packed, round to polymorphous, well-circumscribed dermal papillae at the dermoepidermal junction, features suggestive of a benign neoplasm. RCM features indicating the diagnosis of SK were also observed, including epidermal projections (43/45 SK; 96%) and keratin-filled invaginations (36/45 SK; 80%) at the lesion surface; corneal pseudocysts at epidermal layers (19/45 SK; 42%); and melanophages (21/45 SK; 47%) and dilated round and linear blood vessels (21/45 SK; 47%) in the papillary dermis. Of biopsied SK, 93% (13/14) displayed at least 3 characteristic RCM findings in the absence of RCM features suggestive of malignancy. LIMITATIONS: This was a limited study sample and retrospective study design. CONCLUSIONS: SK display a distinct set of RCM criteria despite their variable clinical and dermoscopic appearances.

Brain-targeted (pro)renin receptor knockdown attenuates angiotensin II-dependent hypertension.

The (pro)renin receptor is a newly discovered member of the brain renin-angiotensin system. To investigate the role of brain (pro)renin receptor in hypertension, adeno-associated virus-mediated (pro)renin receptor short hairpin RNA was used to knockdown (pro)renin receptor expression in the brain of nontransgenic normotensive and human renin-angiotensinogen double-transgenic hypertensive mice. Blood pressure was monitored using implanted telemetric probes in conscious animals. Real-time PCR and immunostaining were performed to determine (pro)renin receptor, angiotensin II type 1 receptor, and vasopressin mRNA levels. Plasma vasopressin levels were determined by ELISA. Double-transgenic mice exhibited higher blood pressure, elevated cardiac and vascular sympathetic tone, and impaired spontaneous baroreflex sensitivity. Intracerebroventricular delivery of (pro)renin receptor short-hairpin RNA significantly reduced blood pressure, cardiac and vasomotor sympathetic tone, and improved baroreflex sensitivity compared with the control virus treatment in double-transgenic mice. (Pro)renin receptor knockdown significantly reduced angiotensin II type 1 receptor and vasopressin levels in double-transgenic mice. These data indicate that (pro)renin receptor knockdown in the brain attenuates angiotensin II-dependent hypertension and is associated with a decrease in sympathetic tone and an improvement of the baroreflex sensitivity. In addition, brain-targeted (pro)renin receptor knockdown is associated with downregulation of angiotensin II type 1 receptor and vasopressin levels. We conclude that central (pro)renin receptor contributes to the pathogenesis of hypertension in human renin-angiotensinogen transgenic mice.

Reflectance confocal microscopy in the daily practice.

Reflectance confocal microscopy (RCM) allows noninvasive imaging of the epidermis and superficial dermis. Like dermoscopy, RCM acquires images in the horizontal plane (en face), allowing assessment of tissue pathology underlying dermoscopic structures of interest at a cellular-level resolution. Thus, clinicians using dermoscopy may find RCM to be particularly useful. Our aim was to show the value of RCM for diagnosis and management decisions related to pigmented and nonpigmented skin neoplasms seen in daily practice. Six cases of clinically and dermoscopically equivocal skin lesions, for which RCM facilitated making the correct diagnosis, are presented. Final diagnoses were made based on histopathologic analysis. Three flat pigmented skin lesions with dermoscopic signs of regression showed distinct RCM features that allowed their correct classification as pigmented basal cell carcinoma, pigmented actinic keratosis, and melanoma on sun-damaged skin. A flat nonpigmented skin lesion on the face, which did not show distinct clinical or dermoscopic features, was correctly diagnosed as basal cell carcinoma based on RCM findings. In addition, the response of a pigmented actinic keratosis and a melanoma in situ on sun-damaged skin to noninvasive topical treatment was monitored using RCM. RCM is a promising and practical imaging tool for the diagnosis and follow-up of pigmented and nonpigmented skin lesions.