Mid Dermis Research Articles

Enhanced and Sustained Cutaneous Delivery of Vismodegib by Ablative Fractional Laser and Microemulsion Formulation

Oral administration of vismodegib for basal cell carcinoma treatment is limited by significant class-specific systemic side effects. We investigated the approach of combining ablative fractional laser-assisted drug delivery with an extended-release microemulsion formulation of vismodegib to provide efficient cutaneous delivery invivo. The developed formulation consisted of an oil-in-water microemulsion stabilized by Tween-80. Pig skin was exposed to ablative fractional laser followed by topical application of vismodegib microemulsion for 4 hours. At 4 hours, 2 days, 5 days, and 9 days, we evaluated vismodegib biodistribution in superficial, mid, and deep dermis and plasma (n= 189 measurements) and assessed local skin reactions. Sustained topical delivery of vismodegib was detected in all depths of ablative fractional laser-exposed skin over the course of the study, with peak concentrations found at 5 days and 9 days. The highest vismodegib concentrations reached 1,409.7 μmol/liter in superficial dermis and 62.3 μmol/liter in deep dermis, exceeding steady-state plasma concentrations previously reported for oral administration of vismodegib (5.5-56.0 μmol/liter). Ablative fractional laser increased vismodegib uptake up to 16.6-fold compared with intact skin. Only mild local skin responses to vismodegib were observed, and no vismodegib was detected in plasma. We report sustained topical delivery of vismodegib invivo at high concentrations with favorable skin tolerability, suggesting a future safer vismodegib treatment.

Trichoadénome : description anatomoclinique et dermatoscopique

Trichoadenoma is a very rare follicular tumour with a remarkable histopathological appearance. In this article we present a series of 12 cases of trichoadenoma, as well as the anatomoclinical and dermatoscopic findings in a typical case. We discuss these findings in the light of an extensive literature research. We collated 12 cases of trichoadenoma of indisputable diagnosis made at the dermatopathology laboratory of the Dermatological Clinic of the University Hospitals of Strasbourg over a 30-year period (1989-2018). The 12 cases comprised 7 women and 5 men, of average age 58.9 years, the majority having lesions on the cephalic extremity followed by the buttocks and thighs. Histopathological examination, which was similar in all 12 cases, showed multiple epidermal cysts containing an eosinophil lamellar keratin with a stratified wall without any visible hair, located in the superficial and mid dermis and appearing to be stacked on top of one another. In immunohistochemistry, broad spectrum keratin markers were still positive, the follicular marker Ber-EP4 weakly expressed and PHLDA1 was negative. For the case examined using polarized-light dermatoscopy, small rounded white-yellow areas were observed corresponding to cystic structures surrounded by irregular linear vessels. Trichoadenoma is a rare tumour seen in middle-aged adults of mean age 45 years, and has no sexual predominance. It is asymptomatic, slow-growing, variable in colour, measures less than one centimeter and is most often located on the face or buttocks. In terms of histology, the juxtaposition of multiple small cystic structures suggests a follicular origin. Differential diagnosis is made with trichoblastomas, which always intensely express PHLDA1 and/or Ber-EP4, desmoplastic trichoepithelioma, which consists of multiple much thinner spans in a highly fibrous stroma with clearly visible arborescent vessels over a white-yellow ivory background at dermatoscopy, microcystic carcinoma, which has a deeper extension, and plaque milium, in which the cysts are larger.

Recurrent pyogenic granuloma with satellitosis in a 5-year-old child

A 5-year-old male child presented with multiple asymptomatic red raised lesions over the left lateral side of his abdominal wall since 2 years. Cutaneous examination revealed multiple bright red, nontender, dome-shaped papules, and nodules arranged discretely. At few places, the lesions coalesced to form plaques with crusting on the surface. The lesions appeared to be arranged in a peculiar manner; with an increased concentration of the lesions in the vicinity of an atrophic central scarred area (of previous surgery) and few satellite discrete papules and nodules away from it. The differential diagnoses of pyogenic granuloma (PG), epithelioid hemangioendothelioma, and bacillary angiomatosis were considered. Histopathological examination from a nodule revealed angiomatous tissue composed of dilated thin-walled capillaries and groups of poorly canalized vascular tufts located in the upper and mid dermis suggestive of PG. A diagnosis of recurrent PG with satellitosis in a 5-year-old child was made. This case is described for the rarity of the condition in children and to emphasize the alarming presentation of a benign condition.

Primary cutaneous actinomycosis: a diagnosis consideration in people living with HIV/AIDS

BackgroundOwing to similar clinical presentations, as of cutaneous disease of different etiologies, and extreme rarity in the global incidence; primary cutaneous actinomycosis often remains as diagnostic challenges.Case presentationHerein, we describe a case of primary cutaneous actinomycosis, erroneously treated as cutaneous tuberculosis, in a patient living with AIDS. On clinical examination, the characteristic lesion, resembling cutaneous tuberculosis, observed on the dorsum of a left leg. No other lesion elsewhere on the body was observed, however. Cytological examinations of the stabbed biopsy were negative for malignant cells; although hyper-keratosis and mild-acanthosis of epidermis, acute inflammatory infiltrates comprising plasma cell, macrophages and neutrophils were observed in the upper and mid dermis. The pus aspirated from lesion grew a molar tooth, adherent colonies in microaerophilic condition. Further, identifications and susceptibility pattern against recommended antibiotics were assessed as per the CLSI (Clinical and Laboratory Standard Institute) guidelines. Subsequently, the case was then, diagnosed as primary cutaneous actinomycosis. Radiographic imaging of abdomen and lungs were normal; no feature of disseminated actinomycosis seen. Penicillin G followed by Penicillin V, was prescribed for 12 months. The patient underwent progressive changes and no relapse noted on periodic follow-up.ConclusionThe case underscores cutaneous actinomycosis requires a diagnosis consideration, especially in People Living with HIV/AIDS (PLHA), where myriad of opportunistic cutaneous infections are common.

Angiolymphoid hyperplasia with eosinophilia

A 45-year-old male presented with multiple discrete and confluent erythematous plaques, distributed on the malar area and bridge of nose of 1-year duration those were blanching on diascopy. There was no history of photosensitivity. There were no skin lesions elsewhere. Blood examination was normal and antinuclear antibody profile was negative. Skin biopsy showed the upper dermis, mid dermis, and subcutaneous tissue packed with vascular spaces lined by epithelioid endothelial cells with eosinophilic infiltrate, diagnostic of angiolymphoid hyperplasia with eosinophilia. The patient was treated with Nd-Yag laser resection.

Histopathological study of post kala-azar dermal leishmaniasis and its importance for diagnosis in a peripheral tertiary institution

Histopathological study of post kala-azar dermal leishmaniasis and its importance for diagnosis in a peripheral tertiary institution - IJCED- Print ISSN No: - 2581-4710 Online ISSN No:- 2581-4729 Article DOI No:- 10.18231/2581-4729.2019.0003, IP Indian Journal of Clinical and Experimental Dermatology-IP Indian J Clin E

Hamartome folliculaire basaloïde : étude anatomoclinique

Basaloid follicular hamartoma (BFH) is a rare tumor first described in 1985. It bears clinical and histologic similarities with basal cell carcinoma (BCC), in particular the so-called infundibulocystic form. We performed a single-center clinicopathological study of a series of typical cases of this entity that is occasionally difficult to diagnose. All cases of BFH seen at the Dermatopathology Laboratory of Strasbourg University Hospital were included and analyzed by means of HE staining and Ber-EP4and PHLDA1immunolabelling. Diagnosis was made in the event of basaloid proliferation with anastomosing cords developed from a hair follicle. Clinical data were collected from clinical files. We identified 15cases in 13patients of mean age 44.8years (range: 4to 90) and the sex-ratio was 5/8. Lesions consisted of flesh-colored papules measuring 0.3to 1.2cm in diameter, without any preferential site. Three patients had multiple lesions consisting of several coalescent papules on a breast for one, sparse papules on the back for another, and hundreds of linear unilateral BFHs, associated with osseous abnormalities, characteristic of Happle-Tinschert syndrome, for the third. All tumors were limited to the superficial and mid dermis, with a vertical orientation and connection to the epidermis in 14of the 15patients. In some cases, the outermost cells were basophilic while the central cells were eosinophilic. Peripheral palisading and clefting were frequently observed. Keratin cysts or sebaceous ducts were consistently present, indicating follicular differentiation. Ber-EP4+ cells were restricted to the periphery of the cords and PHLDA1was weakly expressed. BFH is a rare entity that must be differentiated from BCC. It presents as solitary or multiple lesions, either grouped in plaques or with a generalized or linear unilateral distribution. Generalized BFH may be associated with autoimmune diseases and linear unilateral BFH with osseous, dental and cerebral abnormalities in Happle-Tinschert syndrome. It is important to distinguish BFH from BCC to avoid inappropriate aggressive treatment.

Fractional laser-assisted topical delivery of bleomycin quantified by LC-MS and visualized by MALDI mass spectrometry imaging

Bleomycin exhibits antiproliferative effects desirable for use in dermato-oncology but topical use is limited by its 1415 Da molar mass. Ablative fractional laser (AFL)-assisted drug delivery has been shown to enhance drug uptake in skin. The aim of this study was with AFL to deliver bleomycin into skin, quantify uptake, and visualize biodistribution with mass spectrometry. In a Franz diffusion cell study, pig skin samples (n = 66) were treated with AFL (λ = 10,600 nm), 5% density, and 0, 5, 20, or 80 mJ/microbeam (mb) pulse energies before exposure to bleomycin for 0.5, 4, or 24 h. Bleomycin was quantified in biopsy cryosections at depths of 100, 500, and 1500 µm using high-performance liquid chromatography-mass spectrometry (LC-MS), and drug biodistribution was visualized for 80 mJ/mb samples by matrix assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI). The pulse energies 5, 20, and 80 mJ/mb resulted in microscopic ablation zones (MAZs) reaching superficial, mid, and deep dermis respectively. Bleomycin was successfully delivered into the skin and deeper MAZs and longer exposure time resulted in higher skin concentrations. After 24 h, AFL exposure resulted in significant amounts of bleomycin throughout all skin layers (≥510 µg/cm3, p ≤ .002). In comparison, concentrations in intact skin exposed to bleomycin remained below limit of quantification. MALDI-MSI supported the quantitative LC-MS results by visualizing bleomycin biodistribution and revealing high uptake around MAZs with delivery into surrounding skin tissue. In conclusion, topical drug delivery of the large and hydrophilic molecule bleomycin is feasible, promising, and should be explored in an in vivo setting.

Ulcerative Lupus Vulgaris Primarily Involving the Ear Lobule.

Sir, Lupus vulgaris (LV) is the most common clinical variant of cutaneous tuberculosis. It was first described by Erasmus Wilson in 1865.[1] Clinically, the early lesions of LV are characterized by soft reddish brown plaques with an ‘apple jelly nodule’ appearance on diascopy and in the later stages present with healing and scarring in one area and active disease in another.[2] The different forms of LV include plaque, ulcerative or mutilating, vegetating, tumor-like, and papular and nodular forms.[3] We report an unusual case of ulcerative type of LV of the ear lobe. A 24-year-old girl presented to our department with ulceration of the left earlobe for 6 months. It started as a papule which slowly increased in size and broke down to form an ulcer. She did not give any history of trauma or ear piercing prior to the onset of the lesion. There was also no history of tuberculosis in the past or a family history of the same. There was no history suggestive of immunosuppression. The cutaneous examination showed a well-defined ulcer of size 1 × 2 cm on the tip of the left earlobe [Figure 1]. The margins were undermined and the floor was covered with slough [Figure 2]. The surrounding skin was erythematous with mild scaling. The general and systemic examination was normal. A Mantoux test showed an induration of size 11 × 12 mm after 48 hours. Chest X ray was normal. PCR (Polymerase Chain Reaction) and BACTEC (Becton Dickinson Diagnostic Instrument Systems) tests were not done due to financial constraints.Figure 1: An ulcer over the left ear lobeFigure 2: The ulcer base shows slough with surrounding erythemaThe histopathological examination of the skin biopsy showed ulceration of the epidermis and confluent epithelioid granulomas in the mid and deep dermis. The epithelioid granulomas showed minimal central caseous necrosis and peripheral palisades of histiocytes and lymphocytes [Figures 3 and 4]. However, Ziehl–Neelsen stain was negative for acid-fast bacilli. The features were consistent with granulomatous skin lesion. Other routine blood investigations were unremarkable. A final diagnosis of ulcerative LV was made due to the presence of caseating granulomas on histopathology and positive Mantoux test. The patient was treated with Cat 1 anti-tubercular treatment (ATT) under the Revised National Tuberculosis Control Programme which resulted in complete healing of the ulcer [Figure 5].Figure 3: Epithelioid granuloma with minimal central caseous necrosis (H and E, 40×)Figure 4: Epidermis is focally ulcerated with dermis showing confluent epithelioid granulomas (H and E, 4×)Figure 5: The ulcer healed with scar formation after 6 months of anti-tubercular therapyThe ulcerative type of LV is uncommon and it is characterized by scarring and deformity. The mode of infection is thought to be endogenous or exogenous inoculation following minor trauma.[1] In India, the common sites of involvement are buttocks, thighs, and legs, whereas in the European population, the head and neck are most commonly involved.[4] In a study done in India, ulcerative type of LV was the least common (14.2%).[5] Case reports of LV affecting the face indicate that the cheeks and nose are the most frequently affected sites.[6] Although the pinna may be involved by contiguity from a cheek lesion, primary involvement of the ear lobe is extremely rare.[78910] The above case reported here is unusual because of the exclusive involvement of the ear lobe and the occurrence in an immunocompetent girl without any past or family history of tuberculosis. Long-standing ulcerative LV in addition to scarring and deformity can lead to squamous cell carcinoma. Clinical dermatologists need to be aware of the myriad clinical presentations of this condition and make a correct diagnosis, and promptly treat as it can be disfiguring and destructive. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

Conundrums of hypothyroidism

<p class="abstract">A 46 year old female came with complaints of dryness of skin and severe hair loss since 2-3 years. There was history of intermittent low grade fever, swelling all over body since 1 year; patient also complained of tingling numbness over bilateral legs and forearms along with difficulty in swallowing food. On further probing, history of difficulty in lifting arms above the head, constipation, generalised fatigue and drowsiness could be elicited. Patient also noticed raised skin coloured asymptomatic lesions over buttocks. On examination loss of eyebrows and alopecia in frontal and parietal scalp was seen. There was prominent follicular ostia and atrophy on scalp and body. Depressed keratotic papules with a generalized doughy feel of skin was appreciated all over body. A differential diagnosis of connective tissue disorder, widespread alopecia areata, folliculotropic mycosis fungoides, hypothyroidism and atopic dermatitis was made. Laboratory investigations revealed a low T3, T4 with a significantly raised TSH suggestive of a primary hypothyroidism. On histopathology mucin deposition in papillary and mid dermis was seen along with non-scarring pattern of alopecia. A diagnosis of hypothyroidism was made and patient was started on Tab. levothyroxin 75 micrograms once daily for 4 months along with hematinics, multivitamins and calcium supplements. Regular and frequent application of emollients was advised to the patient.</p>

Lysyl oxidase-like-2 mutations and reduced mRNA and protein expression in mid-dermal elastolysis.

Mid-dermal elastolysis (MDE) is a rare skin condition, characterized by selective loss of elastic fibres in the mid dermis. The pathogenesis of MDE is still unclear. To investigate expression of lysyl oxidase-like 2 (LOXL2) in a reasonable sample of patients with MDE and to search for mutations in LOXL2. We investigated archived lesional tissue of 13 patients with MDE and skin tissue samples of 10 sex- and age-matched healthy controls (HCs). Gene and protein expression of LOXL2 was investigated using real-time reverse-transcription PCR and immunohistochemistry. Mutation analysis was performed using the Sanger method. We observed decreased LOXL2 mRNA expression in lesional skin of patients with MDE (0.48±0.16) compared with healthy skin of the same patients (1.5±0.51) and normal skin of HCs (1.9±0.13). Compared with healthy patient skin (epidermis 2.38±1.6, dermis 1.2±1), LOXL2 protein expression in lesional patient skin (epidermis 1.1±0.7, dermis 0.3±0.45) was significantly decreased (P<0.04 and P=0.02, respectively). Mutation analysis of the entire LOXL2 gene could be performed for five patients, all of whom were found to have at least one mutation in the LOXL2 gene. Three of these had a mutation in the promoter region (c.967 G>C, c.1022 C>T, and c.1025 G>A, respectively), and one of them also had a mutation in the splice region of intron 11/exon 12 (IVS11-1 G>A). Of the remaining two patients, one had a mutation in exon 3 (T1391), and the other had a mutation in exon 11 (C663Y). Our present data suggest that decreased elastin renewal due to LOXL2 mutations and consecutive reduced LOXL2 expression contribute to the pathogenesis of MDE.

Cutaneous mucinosis of infancy: report of a rare case and review of the literature.

Cutaneous mucinosis of infancy (CMI) is a rare dermatologic condition, first reported in 1980 and currently classified within the complex group of papular mucinoses. We report a case of CMI and review the prior 13 cases in the literature. The patient was a 5-year-old girl who presented with asymptomatic dermal papules and plaques on her leg and back with no overlying color change. These lesions were first noticed during infancy and had become slightly more evident over time. The patient had a history of birthmarks and eczema. Her family history included eczema, allergies, photosensitivity, and Graves disease. Pre-biopsy clinical differential diagnosis included connective tissue nevus, granuloma annulare, myofibroma, lipofibroma, and lymphangioma. Biopsies revealed significant increase in interstitial mucin within the reticular and mid dermis, without significant sclerosis or fibroblastic proliferation. The relatively quiescent pattern of interstitial mucinosis with slight fibrocyte hyperplasia presenting as dermal papules-plaques on the trunk and extremities was most consistent with a diagnosis of CMI. We report another case of CMI in an otherwise healthy patient. Our patient is unique as she is the first CMI patient with a family history of Graves disease, although our patient appeared euthyroid. We will also review the literature on this rare entity.

Sweet's syndrome in a patient with chronic lymphocytic leukaemia

Bullous Sweet's syndrome is a rare variant of the inflammatory neutrophilic dermatosis characterised by painful bullous skin lesions, fever, leukocytosis and a neutrophilic infiltrate of the dermis. The condition may...

Granulome annulaire élastolytique à cellules géantes : étude anatomoclinique

Annular elastolytic giant cell granuloma (AEGCG), a rare entity first described in 1979, is very similar to O'Brien actinic granuloma (AG), first described in 1975. Since then, many cases have been published under one or other of the two names. We performed a single-centre histopathology study to identify the distinguishing features and determine whether there was any objective difference between AEGCG and AG. Cases classed as AEGCG or AG at the dermatopathology laboratory in Strasbourg were included and analysed using haematoxylin-eosin, orcein and Alcian blue staining. The diagnosis was made in the event of granuloma rich in multi-nucleated giant cells and reduction or disappearance of elastic tissue. Clinical data were collected from the analysis requests and clinical files. We identified 73cases: 12classed as AEGCG and 61classed as AG. Mean age was 60.5years with a sex ratio of 0.55. The duration of the disease ranged from 8days to 17years. A single lesion was seen in 52% of cases with multiple lesions in the remaining cases. Lesions measured between 0.3 and 10cm and exhibited a predilection for photo-exposed areas, chiefly on the head, neck and upper limbs. In most cases, an annular erythematous edge was seen together with a light centre, and slow centrifugal spread. The diagnosis was made by a clinician in only 5.5% of cases. These granulomas were chiefly in the superficial and mid dermis and only rarely deep, and contained numerous giant cells with a constant contingent of lymphocytes, but plasma cells were also seen in half of the cases. Orcein staining revealed marked decrease or total disappearance of elastic tissue within the granulomatous area together with elastophagocytosis in practically all images. More rarely, there was evidence of necrobiosis, palisading granuloma, vascular involvement or orcein-stained asteroid bodies. There were no notable clinical or histological differences between the cases initially classed as AEGCG or AG. AEGCG is a separate entity from annular granuloma that must be assimilated with O'Brien actinic granuloma. The central role of elastic fibres seems clear, but that of ultraviolet radiation remains more controversial. The term annular elastolytic giant cell granuloma seems more appropriate since it is more descriptive and carries no physiopathological implications. There appears to be a significant association with sarcoidosis and with diabetes in a minority of cases, thus warranting screening for these diseases.

Acral Persistent Papular Mucinosis with Partial Response to Tacrolimus Ointment.

Dear Editor: Acral persistent papular mucinosis (APPM) is a rare subtype of localized lichen myxedematosus (LM)1 with unknown etiology. To our knowledge only six cases tried treatment1,2,3, and two cases showed family history1. A 53-year-old woman presented with asymptomatic 1~3 mm flesh-colored papules symmetrically located on both dorsum of hands and wrists, and on anterior chest. It first appeared 7~8 years ago and did not disappear. She was previously healthy and no abnormalities were found in annual check-up. Her two brothers had same lesions on their dorsum of hands. Biopsy was done on the hand lesion and discrete mucin depositions in upper dermis with spared grenz zone confirmed the diagnosis of APPM (Fig. 1). Fig. 1 (A) Epidermis is normal. Deposition of bluish material is seen at upper to mid dermis, fairly discrete (H&E, ×20). (B) Small grenz zone was spared. Fibroblasts were present among the deposition but not seem to be proliferated. Inflammatory ... Tacrolimus ointment 0.1% was applied once a day for 15 weeks but responded partially (Fig. 2). Fig. 2 (A) Left dorsum of hand and anterior chest before treatment. (B) Left dorsum of hand and anterior chest after 15 weeks of tacrolimus ointment 0.1% application. In our patient, anterior chest was also involved and differential diagnosis with discrete papular lichen myxedematosus (DPLM–other subtype of LM) was needed. In DPLM, papules may occur anywhere on the body, usually asymmetrically. Histologically, DPLM shows more diffuse deposition of mucin than APPM, which interspersed among large collagen bundles in the reticular dermis4. Our patient showed characteristic symmetric distribution of papules on the extensor side of distal upper extremities, and characteristic histologic features such as focal accumulation of mucin in upper dermis and spared grenz zone. These features fit well into the diagnostic criteria of APPM4, so we concluded the diagnosis was APPM. Since we didn't do biopsy on the chest lesion, we couldn't completely rule out the possibility of the chest lesion being DPLM accompanied with APPM of hands. But since there are no reported cases of two other types occurring at once, it is reasonable to think chest lesion was also APPM. There was a report of successful treatment of two DPLM cases with tacrolimus ointment5, but our case was the first reported case to apply tacrolimus in APPM. In contrast to DPLM, our patient showed only partial response despite fifteen weeks of long term application. This might imply that the pathogenesis of two diseases is different. It is known that tacrolimus inhibits tumor necrosis factor (TNF)-α secretion in human keratinocytes and transforming growth factor (TGF)-β-nduced collagen synthesis. TNF-α and TGF-β stimulate glycosaminoglycan synthesis from skin fibroblast, and Rongioletti et al.5 suggested that inhibiting these cytokines might be the mechanism of the tacrolimus on DPLM. The difference of the contributing proportion of these cytokines in DPLM and APPM might be the reason for different response to tacrolimus. Although the etiology of APPM is yet unknown, our patient showed familial occurrence and it raises the possibility of the genetic role in APPM pathogenesis along with previous reports of familial occurrences1. Our case gives some notable points on the pathophysiology of APPM, and we hope that this case may add to the growing body of literature of APPM.

Coagulation and ablation patterns of high-intensity focused ultrasound on a tissue-mimicking phantom and cadaveric skin

High-intensity focused ultrasound (HIFU) can be applied noninvasively to create focused zones of tissue coagulation on various skin layers. We performed a comparative study of HIFU, evaluating patterns of focused tissue coagulation and ablation upon application thereof. A tissue-mimicking (TM) phantom was prepared with bovine serum albumin and polyacrylamide hydrogel to evaluate the geometric patterns of HIFU-induced thermal injury zones (TIZs) for five different HIFU devices. Additionally, for each device, we investigated histologic patterns of HIFU-induced coagulation and ablation in serial sections of cadaveric skin of the face and neck. All HIFU devices generated remarkable TIZs in the TM phantom, with different geometric values of coagulation for each device. Most of the TIZs seemed to be separated into two or more tiny parts. In cadaveric skin, characteristic patterns of HIFU-induced ablation and coagulation were noted along the mid to lower dermis at the focal penetration depth of 3 mm and along subcutaneous fat to the superficial musculoaponeurotic system or the platysma muscle of the neck at 4.5 mm. Additionally, remarkable pre-focal areas of tissue coagulation were observed in the upper and mid dermis at the focal penetration depth of 3 mm and mid to lower dermis at 4.5 mm. For five HIFU devices, we outlined various patterns of HIFU-induced TIZ formation along pre-focal, focal, and post-focal areas of TM phantom and cadaveric skin of the face and neck.

Interstitial Granulomatous Dermatitis: A Clinicopathological Study.

Interstitial granulomatous dermatitis (IGD) is an uncommon granulomatous dermatitis occurring in the setting of highly reactive immune states, with a polymorphic clinical presentation. Because there is overlap with other entities [namely palisading neutrophilic granulomatous dermatitis (PNGD)], controversy exists regarding its classification. To understand if there are features allowing clear-cut distinction between IGD and PNGD. Retrospective analysis of 10 cases previously diagnosed as IGD or PNGD, from 2000 to 2013, with review of the histopathologic findings and clinical correlation. Six females and 4 males presented mostly with erythematous papules/nodules (n = 7) but also with erythematous annular plaques (n = 3). In 2 patients, the lesions coexisted. They were mostly distributed symmetrically on the limbs. Associated disease was observed in 6 patients. Regarding histopathology, an inflammatory infiltrate occupying the superficial and mid dermis was present in 40% of cases, with an interstitial component in all biopsies and a palisaded arrangement in 60%. Neutrophils and mononuclear cells were present in all cases in varying proportions. Necrobiosis was found in 70%, and leukocytoclasia was observed in 80% of biopsies. Coexistence of the interstitial and palisaded inflammatory patterns occurred in 90% of cases, with no correlation between tissue neutrophilia and the predominant pattern of the infiltrate. There was also no clear-cut correlation between the infiltrate pattern and semiologic aspect of the lesions. Therefore, the features described in our study suggest that IGD and PNGD belong to the same clinicopathological spectrum.

Pseudo-kaposi sarcoma (acroangiodermatitis): occurring after bullous erysipelas

Pseudo-Kaposi sarcoma is a benign reactive vascular proliferative disorder, which can be seen at any age. It occurs when the chronic venous pressure changes result in vascular proliferation in the upper and mid dermis. This disease is divided into two subtypes: the most frequent subtype is the Mali type and seen in early ages. The Mali type is seen in chronic venous insufficiency and in those patients with arteriovenous shunts. The rare subtype is the Stewart-Bluefarb type. This disease must be distinguished from Kaposi sarcoma because of their clinical resemblance. Herein, we present a patient with pseudo-Kaposi sarcoma, which developed after bullous erysipelas.

Gemcitabine in Blastic Plasmacytoid Dendritic Cell Neoplasm (CD4+CD56+ hematodermic neoplasm)

Once thought to be a natural killer cell lymphoma, blastic plasmacytoid dendritic cell neoplasm, also termed CD4+CD56+ hematodermic neoplasm, is a rare clinical entity which derives from plasmacytoid dendritic cells. Cutaneous predominant (with better prognosis) and non-cutaneous subtypes (often accompanied by mediastinal involvement and a poorer prognosis) have been described. Many patients are treated with CHOP-like regimens, but the prognosis remains poor. Patients presenting with only skin lesions (median survival 21 months) had a better prognosis than patients presenting with both cutaneous and extra-cutaneous disease.We describe an 86 yo female with a distant history of breast cancer. She noted rapid development of mildly itchy round pink cutaneous nodlues on the arms, buttock, and legs. She was treated with topical steroids without improvement. The CBC, calcium, and LDH were normal. ECOG 0. There was no adenopathy or organomegaly.Skin biopsy demonstrated a dense lymphoid infiltrate involving the upper and mid dermis, as well as adnexal structures, without epidermotropism. The infiltrate was composed predominantly of large to intermediate sized lymphoid cells having moderate amounts of cytoplasm and oval to cleaved nuclei having open chromatin and one or more small nucleoli. Mitotic figures were present. The neoplastic cells expressed CD4, CD56. Ki-67 was expressed by many of the cells. The cells were negative for CD1a, CD3, CD5, CD7, CD8, PAX-5, CD20, CD79a, CD10, CD23, CD30, CD163, bcl-2, bcl-6, myeloperoxidase, kappa/lambda light chains, p63, Tdt, tryptase, chromogranin, MART-1, mammoglobin, CAM 5.2, and AE1/3. The morphology and immunophenotype was consistent with a CD4+/CD56+ hematodermic neoplasm.The patient preferred no additional staging studies or therapy. Based on the available data, cutaneous-only disease was suggested. The disease was observed without intervention for a few weeks, but progressed on her skin. She then requested a gentle therapy that might provide palliative improvement and prevent progression.Gemcitabine (2′,2′-difluorodeoxycytidine) is a well tolerated pyrimidine antimetabolite that impairs DNA synthesis and promotes induction of apoptosis. In patients with relapsed or refractory aggressive non-Hodgkin lymphoma, gemcitabine led to a 20% response rate with median survival of 6 months.Therapy with Gemcitabine was administered at 1000 mg/M2 on days 1, 8, 15 every 28 days. There was rapid and marked improvement of the skin nodules. Treatment was very well tolerated with minimal bilateral leg edema. A 4 week chemotherapy holiday was associated with regrowth. Photographs document the disease progression before therapy and response of disease with ongoing therapy.Gemcitabine may provide palliative benefit in some patients with blastic plasmacytoid dendritic cell neoplasm.TablePre Therapy May 15 2014Day 1 Chemotherapy May 23 2014Day 22 Chemotherapy June 6 2014 [Display omitted] [Display omitted] [Display omitted] DisclosuresOff Label Use: Gemcitabine in blastic plasmacytoid dendritic cell neoplasm (CD4+CD56+ hematodermic neoplasm).

Lucio Leprosy with Lucio’s phenomenon, digital gangrene and anticardiolipin antibodies

Lucio's phenomenon (LPh) is considered a necrotizing panvasculitis and a variant of leprosy Type 2 reaction, clinically characterised by necrotic-haemorrhagic lesions on the extremities and trunk. LPh is observed in diffuse lepromatous leprosy (DLL or Lucio-Latapí leprosy). This is a distinct form of lepromatous leprosy (LL) reported mainly in Mexico. Anti-phospholipid antibody syndrome (APS) has been rarely described in LPh. We report a case of Lucio-Latapí leprosy with LPh observed in a patient from the province of El Oro in Ecuador, who presented clinical manifestations of long standing DLL (non-nodular infiltration of the skin, collapse of the nasal pyramid, madarosis, atrophy of the earlobes), of LPh (necrotic-haemorrhagic macules with irregular shapes) and of APS (necrosis of the right big and second toe). Histopathology showed perineural and periadnexal foamy macrophages with numerous bacilli (diagnostic of LL) in the subcutis, a mild lobular panniculitis with a large subcutaneous vessel infiltrated by macrophages in the wall (typical of LPh) and vessels of the superficial and mid dermis occluded by thrombi but without signs of vasculitis (typical of occlusive vasculopathy as in APS). Our observations suggest that some cases of LPh may be associated with APS. Anti-cardiolipin antibodies (aCL) and lupus anticoagulant (LA) should be tested in patients with LPh because this may have therapeutic implications.