Melanocytic and pseudomelanocytic nests coexist in interface dermatitis from head-neck sun-exposed skin: A report of three cases.

Discrete junctional cellular aggregates ("nests"), partially staining with melanocytic markers, are described in lichenoid tissue reaction, mainly from chronically sun-exposed skin. The concomitant epidermal flattening and papillary dermal fibrosis with melanophages, may raise the differential diagnosis to that of a regressing melanoma. We describe three cases of interface dermatitis of the head/neck area with clinicopathological features of melanotic discoid lupus erythematosus. These cases showed junctional aggregates, a few composed of inflammatory cells and colloid bodies ("pseudomelanocytic nests"), while others composed of S100- but MART-1+, MITF+, and SOX-10+ cells ("true melanocytic nests"); negativity of the melanocytic component for PRAME was a clue to benignity. True junctional melanocytic nesting may be induced by lichenoid dermatoses on chronically sun-damaged skin. The presence of colloid bodies and of the double negativity for S100 (within nests) and PRAME (both within nests and single melanocytes), together with clinicopathological correlation, avoids misdiagnosis.

A Clinicopathological Study of 29 Spitzoid Melanocytic Lesions With ALK Fusions, Including Novel Fusion Variants, Accompanied by Fluorescence In Situ Hybridization Analysis for Chromosomal Copy Number Changes, and Both TERT Promoter and Next-Generation Sequencing Mutation Analysis.

ALK-fused spitzoid neoplasms represent a distinctive group of melanocytic lesions. To date, few studies addressed genetic and chromosomal alterations in these lesions beyond the ALK rearrangements. Our objective was to study genetic alterations, including ALK gene fusions, telomerase reverse transcriptase promoter (TERT-p) mutations, chromosomal copy number changes, and mutations in other genes. We investigated 29 cases of Spitz lesions (11 Spitz nevi and 18 atypical Spitz tumors), all of which were ALK immunopositive. There were 16 female and 13 male patients, with age ranging from 1 to 43 years (mean, 18.4 years). The most common location was the lower extremity. Microscopically, all neoplasms were polypoid or dome shaped with a plexiform, predominantly dermally located proliferation of fusiform to spindled melanocytes with mild to moderate pleomorphism. The break-apart test for ALK was positive in 17 of 19 studied cases. ALK fusions were detected in 23 of 26 analyzable cases by Archer FusionPlex Solid Tumor Kit. In addition to the previously described rearrangements, 3 novel fusions, namely, KANK1-ALK, MYO5A-ALK, and EEF2-ALK, were found. Fluorescence in situ hybridization for copy number changes yielded one case with the loss of RREB1 among 21 studied cases. TERT-p hotspot mutation was found in 1 of 23 lesions. The mutation analysis of 271 cancer-related genes using Human Comprehensive Cancer Panel was performed in 4 cases and identified in each case mutations in several genes with unknown significance, except for a pathogenic variant in the BLM gene. Our study confirms that most ALK fusion spitzoid neoplasms can be classified as atypical Spitz tumors, which occurs in young patients with acral predilection and extends the spectrum of ALK fusions in spitzoid lesions, including 3 hitherto unreported fusions. TERT-p mutations and chromosomal copy number changes involving 6p25 (RRB1), 11q13 (CCND1), 6p23 (MYB), 9p21 (CDKN2A), and 8q24 (MYC) are rare in these lesions. The significance of mutation in other genes remains unknown.

Cytoprotective effects of ß-melanocortin in the rat gastrointestinal tract.

Recently discovered anti-inflammatory and immunomodulatory properties of melanocortin peptides led to the conclusion that they might serve as new anti-inflammatory therapeutics. The purpose of this work was to examine the effectiveness of ß-melanocortin (ß-MSH) in two experimental models: ethanol-induced gastric lesions and TNBS (2,4,6-trinitrobenzenesulfonic acid)-induced colitis in male Wistar rats. Three progressive doses of ß-MSH were used: 0.125, 0.250 and 0.500 mg/kg. Our results suggest that ß-MSH acts as a protective substance in the gastric lesions model, which can be seen as a statistically significant reduction of hemorrhagic lesions at all three doses, compared to the control group. The most efficient dose was 0.250 mg/kg. Statistically significant reduction in mucosal surface affected by necrosis and the reduction of overall degree of inflammation in the colitis model indicates an anti-inflammatory effect of ß-MSH at a dose of 0.250 mg/kg. The results justify further research on ß-MSH peptide and its derivates in the inflammatory gastrointestinal diseases, and point out the possibility of using ß-MSH in studies of digestive system pharmacology.

Effects of alpha-melanocortin enantiomers on acetaminophen-induced hepatotoxicity in CBA mice.

Proteins and peptides in mammals are based exclusively on L-amino acids. Recent investigations show that D-amino acids exhibit physiological effects in vivo, despite of their very small quantities. We have investigated the hepatoprotective effects of the Land D-enantiomers of alpha-melanocortin peptide (alpha-MSH). The results showed that peptide-enantiomerism is related to the protective effects of melanocortin peptides in vivo. L-alpha-MSH exhibited potent hepatoprotective effect in the experimental model of acetaminophen induced hepatotoxicity in male CBA mice, while its D-mirror image was inefficient. Furthermore, the antibody to the L-peptide did not recognize the D-structure. The results indicate that the opposite peptide configuration may be used to modulate its function and metabolism in vivo and in vitro.

The incidence of basal cell carcinoma in Croatia: an epidemiological study.

The aim of the study was to investigate the basal cell carcinoma (BCC) incidence in Croatia in the 2003-2005 period. Data were collected from University Department of Dermatology and Venereology, Zagreb University Hospital Center and National Cancer Registry. The age-specific incidence rate and age-standardized incidence rate were calculated per 100,000 inhabitants according to the latest population census in Croatia from 2001. In the study period, there were 7,244 BCC cases (3,519 men and 3,725 women) in Croatia. The crude incidence rate for the Croatian population of 100,000 was 54.9 for men and 53.9 for women. The age-standardized incidence rate (adjusted for the world standard population) was 33.6 for men and 24.5 for women. The head and neck were almost exclusive localizations of BCC. The highest BCC incidence was recorded in Zadar County. The incidence of BCC was high in both littoral and inland counties of Croatia. Study results will serve as reference figures on studying the trend of BCC incidence in Croatia and Europe in the forthcoming years.

Localized Perforating Granuloma Annulare.

Perforating granuloma annulare (PGA) is a rare type of granulomatous skin disease. The etiology and pathogenesis of PGA are still unknown. Diagnosis and treatment of PGA is complex and challenging. We present the case of a 31-year-old male patient with a localized form of PGA successfully treated with topical steroids.

Gingival Papillomatosis as the Oral Sign of Cowden Syndrome: A Case Report.

Cowden syndrome (CS) is a rare autosomal dominant, hereditary, multiorgan disease with higher risk for malignancies (breast, thyroid, endometrium). Mucocutaneous lesions occur in 90% of cases and are characterized by facial trichilemmomas, oral mucosal papillomas, and benign acral keratoses. We present the case of a 39-year-old female patient with the chief complaint of "white spots" on the upper and lower attached gingiva accompanied with skin changes on the face, hands, and soles. The patient's family medical history revealed that her mother had an endometrial polyp and the sister had thyroid cancer. In the patient's medical personal history she reported follicular thyroid adenoma, thyroid abnormalities (i.e. lymphocytic thyroiditis), fibrocystic changes and juvenile breast papillomatosis, lipoma, multiple fibromas, and genitourinary tumors. Based on extensive family and personal medical history, physical examination and histopathological findings, diagnostic criteria were fulfilled for the diagnosis of Cowden syndrome.

Cutaneous Pseudolymphoma: A Case Report.

Pseudolymphoma is a benign, reversible, inflammatory, reactive, and polyclonal lymphocyte proliferation, which regresses spontaneously or heals after elimination of the causal factor. A female patient, aged 33, presented with a painful, erythematosus, radiant tumor formation on the skin in the temporal region. The patient had enlarged lymph nodes on the right side of the neck before the appearance of that tumor formation. The dermatoscopic finding was nonspecific. After the tumor biopsy was performed, the diagnosis of reactive lymphatic proliferation - pseudolymphoma or cutaneous lymphoma of B-cell immunophenotype - was established histologically. After we completely excised the skin change, the immunohistochemical finding indicated fluoride skin lymphocyte hyperplasia of B- and T-lymphocytes. The results of other findings were normal (serologic test for Borrelia burgdoferi, ultrasound of the cervical and supraclavicular lymph nodes, as well as ultrasound of the abdomen and axillary and inguinal regions). However, the etiology of the disease remains unknown. This case report confirms that the correlation between clinical presentation, dermatoscopic examination, histologic and immunohistochemical analysis, and the therapy response is crucial for diagnosis of pseudolymphoma and patient outcome.

Oral and Vulvar Lichen Sclerosus.

Lichen sclerosus (LS) is a chronic, inflammatory, mucocutaneous disorder of genital and extragenital skin (1). Simultaneous involvement of the oral mucosa is extremely rare, but it may be the only affected area (2). A 55-year-old woman was referred to the Department of Oral Medicine, School of Dental Medicine University of Zagreb due to whitish lesions on the right ventrolateral part of the tongue and buccal mucosa with desquamative gingivitis (Figure 1, a-c). The lesions were asymptomatic but indurated on palpation. Histology was conclusive for oral lichen sclerosus (OLS). The lesions on gingiva were successfully treated with betamethasone ointment, three times a day for two weeks. One year earlier, she had been referred to the Department of Dermatology and Venereology with progressive pruritus and dyspareunia, white patches, obliteration of the labia minora, and stenosis of the introitus (Figure 2). Histology was conclusive for vulvar LS (Figure 3, a and b). She was successfully treated for 5 months with clobetasol propionate 0.05% ointment. The patient was taking levothyroxine to treat hypothyroidism associated with Hashimoto's thyroiditis and was otherwise healthy. Oral LS is clinically characterized by the appearance of white macules, papules, or plaques mostly appearing on labial mucosa but also on buccal, palate mucosa and on the lower lip (2,3). On the genitals, it typically manifests as atrophic white plaques, which may be accompanied by purpura or fissuring (1). While vulvar LS is often associated with pruritus, dyspareunia, and dysuria, OLS is often asymptomatic, although pain, soreness, pruritus, and tightness when opening the mouth can be present (1,2). Oral manifestations of LS, as well as association of anogenital and oral LS, are rarely reported in the literature (4-6). Tomo et al. searched the Medline database for papers reporting oral LS cases with histological diagnosis confirmation from 1957 to 2016 and found only 34 cases of oral LS with histopathologic confirmation of the diagnosis (4). Kakko et al. reported 39 histologically proven cases of OLS (2). Attilli et al. (5) reviewed the clinical and histologic features of 72 cases of LS with oral/genital involvement. They reported that LS was diagnosed with exclusive genital lesions in 45, exclusive lip involvement in 20, and orogenital involvement in only 7 cases (5). Some believe that many cases of clinically diagnosed lichen planus may actually be LS and that isolated oral mucosal LS may not be as rare as is generally thought (2). While vulvar LS can occur at any age with increasing incidence with age, the median age of patients with OLS was 34 years and most of the patients were female (1,2,5). Due to the small number of patients in the literature, treatment recommendations for OLS are not available. In case of symptomatic oral lesions, topical or intralesional corticosteroids are considered to be the first-line treatment (2). First-line treatment for anogenital LS is a potent to very potent topical corticosteroid ointment, and second-line therapies include topical calcineurin inhibitors 1% pimecrolimus and 0.1% and 0.03% tacrolimus (1). For treatment-resistant genital LS, oral retinoids, methotrexate, and possibly local steroid injections for single lesions are mainly applicable for women (1). There is limited evidence for systemic treatments for both conditions. If it is not treated, genital LS is associated with a greater degree of scarring and an elevated risk of progression to squamous cell cancer; however, malignant transformation of OLS has not been reported (1-6). Due to the very rare presentation in the oral cavity, it is important to notice these lesions during a dental exam.

Prolonged Treatment of Eosinophilic Erythema Annulare with Chloroquine.

Dear Editor,Eosinophilic annular erythema (EAE) is a rare figurate dermatitis of unknown etiology with prominent tissue eosinophilia. A 59-year-old male patient presented with a one-month history of itchy, polycyclic, annular, and partially serpiginous lesions involving the back, the gluteal region, and the extremities (Figure 1, a, b). There was no medical history of drug intake. High potency local steroids and antihistamines were prescribed, but without adequate therapeutic results. Extensive laboratory work-up including serological infectious disease testing was performed and was within normal ranges. Histopathological examination of a biopsy taken from a lesion on the gluteus showed perivascular lymphocytic infiltrate around superficial and deep vascular plexus with admixture of eosinophils that was found interstitially (Figure 2, a,b) and within the lobules of subcutaneous fat. The overlying epidermis was unremarkable. There were no signs of flame figures and granulomatous inflammation. Based on the clinical and histopathological findings, a diagnosis of EAE was established. The patient was given 40 mg of prednisone orally which resulted in partial improvement, but the lesions relapsed soon after the dose was tapered down to 20 mg. Chloroquine was started at a dose of 4 mg/kg daily for 10 days, then 250 mg daily for next the 10 weeks, resulting in complete clearance of all the lesions, which was sustained for over 2 years of follow-up. It is still matter of debate whether EAE is a clinical subtype of Wells syndrome (WS) presenting with an annular or figurate pattern or is a distinct entity. In recently published paper, El-Khalawany et al. argued that EAE is a peculiar clinical variant of WS, because flames figures, blood and tissue eosinophilia, and granulomatous infiltrate can be observed in well-developed and long-standing lesions (1). The etiology of EAE is still unknown, although it has been suggested that it occurs as a result of a hypersensitivity reaction to an unidentified allergen (2). EAE has been associated with Helicobacter pylori, Borrelia burgdorferi, and hepatitis C virus infection, diabetes mellitus, chronic kidney disease, thymoma, autoimmune pancreatitis, autoimmune hypothyroidism, and internal malignances (clear cell renal carcinoma, metastatic prostate adenocarcinoma) (3,4). Clinically, EAE is characterized by asymptomatic or mildly pruritic urticarial papules and plaques in annular configuration, mainly on the trunk and proximal extremities (5). Histologically, as in our patient, EAE is characterized by the appearance of a superficial and deep perivascular inflammatory infiltrate composed of lymphocytes and abundant eosinophils and absence of epidermal change (5). There is no standard treatment for EAE. Systemic steroids and antimalarials are the usual first-line options (5). Other treatment options include dapsone, indomethacin, cyclosporine, and UVB therapy (1,3,5). Response to antimalarials is usually observed within the first 2-4 weeks (2). However, as in our case, it may take several weeks for patients to respond to antimalarial treatment, and complete regression may even take longer (3). We believe that EAE should be treated with antimalarials over a longer time period in order to avoid frequent relapses.

Poikilodermatous Mycosis Fungoides - Rare Entity, Different Treatment Modalities.

Poikilodermatous mycosis fungoides (PMF) is a rare clinical variant of early-stage MF with peculiar histological features. Poikiloderma occurs in many different clinical conditions, which makes a diagnostic procedure more complicated. PMF belongs to a group of MF variants with low risk of disease progression. We report a case of a 64-year-old woman, who presented with mottled skin aspect of erythema, poikilodermatous patches (hypopigmentation, hyperpigmentation, atrophy, and telangiectasia) on more than 80% of the body. Based on clinical, histopathological, and immunohistochemical findings, we established the diagnosis of PMF. Staging procedure determined stage IIA. As skin-directed therapy was the treatment of choice, the patient was successfully treated with psoralen-UVA (PUVA), nbUVB plus retinoid (Re-nbUVB), and PUVA plus retinoid (Re-PUVA), however, with rapid recurrence.