Manuel Valdebran

Nuclear and cytoplasmic features in the diagnosis of banal nevi, Spitz nevi, and melanoma

BACKGROUND Many authors have described cytologic features in a variety of melanocytic lesions but, to our knowledge, a statistical analysis of sensitivity, specificity, and overall accuracy of these features alone or in combination has not been performed. OBJECTIVE We sought to determine the diagnostic value of nuclear and cytoplasmic characteristics in the diagnosis of melanocytic lesions via multivariate statistical analysis. METHODS This is a retrospective observational study conducted on 300 melanocytic lesions. We evaluated a series of distinctive features; subsequently a multivariate model was used to determine sensitivity and specificity. RESULTS Major features that favor a diagnosis of melanoma include: pleomorphism with enlarged nuclei, mitotic figures, notching/corrugation of the nuclear envelope, and peppered moth nucleus. Features with intermediate value include: solid hyperchromasia, vesicular nucleus with single round nucleolus, and nuclear/cytoplasmic ratio greater than 4:1. LIMITATIONS Limitations of this study include its retrospective nature, and the reliance on the original diagnostic classification of each neoplasm. CONCLUSION Our data suggest that some nuclear alterations have greater value in the diagnosis of benign and malignant melanocytic lesions.

Localized pretibial bullous pemphigoid arising in a patient on pembrolizumab for metastatic melanoma

Author(s): Amber, Kyle T; Valdebran, Manuel; Lu, Yuxin; De Feraudy, Sebastien; Linden, Kenneth G

The Role of Eosinophils in Bullous Pemphigoid: A Developing Model of Eosinophil Pathogenicity in Mucocutaneous Disease.

Bullous pemphigoid (BP) is an autoimmune blistering disease which carries a significant mortality and morbidity. While historically BP has been characterized as an IgG driven disease mediated by anti-BP180 and BP230 IgG autoantibodies, developments in recent years have further elucidated the role of eosinophils and IgE autoantibodies. In fact, eosinophil infiltration and eosinophilic spongiosis are prominent features in BP. Several observations support a pathogenic role of eosinophils in BP: IL-5, eotaxin, and eosinophil-colony stimulating factor are present in blister fluid; eosinophils line the dermo-epidermal junction (DEJ) in the presence of BP serum, metalloprotease-9 is released by eosinophils at the site of blisters; eosinophil degranulation proteins are found on the affected basement membrane zone as well as in serum corresponding with clinical disease; eosinophil extracellular DNA traps directed against the basement membrane zone are present, IL-5 activated eosinophils cause separation of the DEJ in the presence of BP serum; and eosinophils are the necessary cell required to drive anti-BP180 IgE mediated skin blistering. Still, it is likely that eosinophils contribute to the pathogenesis of BP in numerous other ways that have yet to be explored based on the known biology of eosinophils. We herein will review the role of eosinophils in BP and provide a framework for understanding eosinophil pathogenic mechanisms in mucocutaneous disease.

Nevus Sebaceous of Jadassohn With Eight Secondary Tumors of Follicular, Sebaceous, and Sweat Gland Differentiation.

To the Editor:Nevus sebaceous of Jadassohn (NSJ), also known as organoid nevus or pilosyringosebaceous nevus is an infrequent hamartoma, evolving from a disorder in epithelial, sebaceous, pilar, and apocrine structures. It is often recognized shortly after birth. NSJ is typically located on the scal

Polarized Microscopy in Lesions With Altered Dermal Collagen.

Abstract:Alterations in dermal collagen are noted in dermatofibroma, dermatofibrosarcoma protuberans, morphea, lichen sclerosus et atrophicus, hypertrophic scars, and keloids. The authors sought to determine whether variations in birefringence of collagen by polarized microscopy could be of help in diagnosing such conditions. Representative hematoxylin and eosin sections of 400 cases, including dermatofibroma, dermatofibrosarcoma protuberans, hypertrophic scars, keloid, morphea, and lichen sclerosus, were examined under polarized microscopy. Distinct patterns of birefringence of collagen for each disease were noted under polarized microscopy. This study highlights the use of polarized microscopy as adjunctive tool in differentiating different diseases with collagen alteration.

When to suspect tinea; a histopathologic study of 103 cases of PAS‐positive tinea

The histopathologic features of tinea vary widely and its diagnosis could be easily missed if the index of suspicion is not high. We aimed in this study to detect histopathologic features that could be a clue for diagnosis

Feature characterization of scarring and non-scarring types of alopecia by multiphoton microscopy (Conference Presentation)

Treatment and management of alopecia are highly determined by an accurate diagnosis, which can be challenging due to the lack of methods to properly visualize hair follicles. Current standard diagnosis is based on dermoscopy for non-scarring alopecia and scalp biopsy for scarring types of alopecia. Dermoscopy can be inconclusive, while biopsy is a painful procedure. In this study, we used a clinical tomograph based on multiphoton microscopy (MPM) to non-invasively image the scalp of 5 healthy subjects and of 12 patients affected by non-scarring alopecia (androgenetic and areata) and scarring alopecia (frontal fibrosing). MPM is capable of non-invasive in vivo imaging of follicular structures in human scalp including hair shafts, hair follicles and sebaceous glands via two-photon excited fluorescence (TPEF) from keratin and NADH/FAD and of the papillary dermis surrounding the hair follicles through second harmonic generation (SHG) from collagen and TPEF from elastin fibers. In normal and non-scarring alopecia patients, MPM often identified presence of sebaceous glands associated with hair follicles, while MPM images of scarring alopecia were characterized by miniaturization of hair follicles as well as by presence of macrophages and lymphocytes surrounding hair follicles. A quantitative analysis involving measurement of hair follicle diameter sizes showed they were significantly smaller in scarring comparing to non-scarring alopecia patients and to normal scalp subjects (p < 0.043). This study shows, in a limited number of patients, that MPM imaging can non-invasively identify morphological features that distinguish scarring from non-scarring alopecia.

Blood flow quantification of biopsied skin lesions using a laser speckle imaging dermatoscope (Conference Presentation)

Dermatoscopes are commonly utilized by medical professionals for the qualitative visual inspection of skin lesions. While automated image processing techniques and varied illumination strategies can aid in structural analysis of lesions, robust quantification of functional information is largely unknown. To address this knowledge gap, we have developed a compact, handheld dermatoscope that enables real-time blood flow measurements of skin using coherent illumination and laser speckle imaging (LSI). A second color camera attached to the dermatoscope helps with the simultaneous real-time observation of the skin lesions and allows the user to acquire and save color images via a custom Graphical User Interface. In-vitro characterization utilizing a blood flow phantom demonstrated that the dermatoscope is capable of quantifying changes in blood flow across a physiologically relevant range even when used in a handheld manner with ambient lighting. We also demonstrated that the dermatoscope can quantify blood flow in skin lesions in human subjects and that significant differences in blood flow are present among lesion types. There was significantly increased blood flow relative to the surrounding skin in cherry angiomas compared to solar lentigos (p<0.05), which was expected based on the vascular and pigment compositions of the two lesion types. Furthermore, we have compared blood flow maps collected from potentially cancerous lesions prior to histological analysis to determine whether blood flow measurements can help in the diagnosis of benign and malignant skin lesions. Information provided by the LSI dermatoscope may help with earlier and more accurate diagnoses of pigmented skin lesions.

Feature characterization of scarring and non-scarring types of alopecia by multiphoton microscopy: ALOPECIA AND MULTIPHOTON MICROSCOPY

Non‐invasive visualization of hair follicles is important for proper diagnosis and management of alopecia; however, histological assessment remains the gold standard. Laser imaging technologies have made possible noninvasive in vivo evaluation of skin and hair follicle. The aim of this study was to evaluate the ability of multiphoton microscopy (MPM) to non‐invasively identify morphological features that can distinguish scarring from non‐scarring alopecia.

Nuclear and cytoplasmic features in the diagnosis of Clark's nevi

Interpretation of Clarks nevi has generated debate over the years; although criteria have been proposed for grading morphological features of melanocytes, there is still confusion and variability in the assessment of these lesions.