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BACKGROUND: Vitiligo is a skin disease characterized by a complex etiopathogenesis. Keratinocyte apoptosis may play a role in vitiligo pathogenesis. Aquaporin-3 (AQP-3) is an aqua-glyceroporin that controls keratinocyte proliferation and differentiation. AIM: To assess the immunohistochemical expression of AQP-3 in lesional and perilesional skin of vitiligo patients compared to healthy control skin. METHODS: A total of 20 patients with generalized non-segmental vitiligo and 20 age- and sex-matched healthy controls were included. Lesional and perilesional skin of vitiligo patients, as well as normal skin of control subjects, were biopsied. The immunohistochemical expression of AQP3 in the epidermis was examined. RESULTS: Compared to control skin, both lesional and perilesional skin showed a significant reduction in the intensity of membranous staining of AQP-3 (p < 0.001, p = 0.002, respectively). Moreover, the membrano-cytoplasmic pattern of AQP-3 staining was significantly detected in 80% of lesions and 85% of perilesional biopsies, while it was absent in control skin (p < 0.001). Additionally, nuclear AQP-3 expression was significantly detected in 35% of lesions and 55% of perilesional biopsies, while it was not detected in control skin (p = 0.012, p < 0.001, respectively). No statistically significant difference was detected between lesional and perilesional skin. CONCLUSIONS: To our knowledge, this is the first immunohistochemical research to show a significant abnormal nuclear expression of AQP-3 in lesional and perilesional skin of vitiligo patients. This abnormality may reflect impaired functions of AQP-3, leading to keratinocyte apoptosis with subsequent melanocyte death and development of vitiligo.

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OBJECTIVES: To evaluate the efficacy and tolerability of needling/microneedling as an adjunct to NB-UVB phototherapy in the treatment of stable refractory patches of acral vitiligo, based upon clinical and immunohistochemical assessment of melanocyte count and distribution in response to needling/microneedling. MATERIALS AND METHODS: Twenty patients with stable acral vitiligo (≥2 patches) were enrolled. One of the two index patches was randomized to receive needling or microneedling in conjunction with NB-UVB. Patients received phototherapy sessions 3 times weekly, while needling was carried out on biweekly basis for 6 months. Assessment was done clinically using point counting method, VESTA, and global patients' satisfaction, and immunohistochemically by quantitative assessment of melanocyte count by Melan-A. RESULTS: No statistically significant difference was observed between NB-UVB monotherapy and either of the combined therapy regimens as regards the mean percentage change in vitiligo surface area (p = .451), mean change in absolute melanocyte count from baseline (p = .589), and mean VESTA (p = .916). Patches subjected to adjuvant microneedling/needling were afflicted by koebnerization in 50% and 20% of cases, respectively. CONCLUSION: Neither microneedling nor needling appear to confer an added therapeutic value to NB-UVB phototherapy in the treatment of stable acral vitiligo. Moreover, both carry the risk of koebnerization.

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BACKGROUND AND OBJECTIVES: In the last decades, attention to the role of lymphangiogenesis in psoriasis has been paid. Our study was conducted to evaluate podoplanin-stained lymphatic vessels and the level of lymphangiogenesis in papular psoriatic lesions and psoriatic plaques and ascertain if podoplanin provides any additional prognostic information. MATERIALS AND METHODS: Number of lymphatic vessels and total lymphatic vessel area were morphometrically analyzed in podoplanin-stained sections, using anti-D2-40, together with the immunohistochemical study of epidermal Ki-67 in psoriasis vulgaris (n = 20) (papules = 7 and plaques = 13) and control skin specimens (n = 20). RESULTS: The number of lymphatic vessels and total lymphatic vessel area were higher in psoriasis cases compared with normal skin (p = 0.01, p = 0.01 respectively). In psoriatic plaques, the number of lymphatic vessels, total lymphatic vessel area, and epidermal Ki-67 immunoreactivity were higher than in papular lesions (p = 0.002, p = 0.008, and p = 0.01, respectively). CONCLUSIONS: Psoriasis vulgaris is found to be a lymphangiogenesis-dependent disease, and the lymphatic vascular network is in remodeling and expanding process. Podoplanin may be implicated in the pathogenesis of psoriasis and could be used as a prognostic biomarker for disease severity and progression.

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Classic erythema nodosum leprosum (ENL) is characterized clinically by abrupt eruption of tender erythematous nodules, papules and plaques. Variable atypical patterns have been described, for example pustular, bullous, ulcerative, necrotic and Sweet's syndrome-like ENL. We aim to review previously reported cases of atypical ENL addressing the diagnostic and therapeutic aspects of these uncommon presentations. A search of medical literature for all cases of atypical ENL was conducted in the PubMed database till 2020. Data of patients with atypical ENL were collected and analyzed to describe the epidemiological, clinico-histological and therapeutic features. The major five clinically described presentations of atypical ENL include vesiculo-bullous lesions (46 % of patients), ulcero-necrotic lesions (41 %), erythema multiforme-like lesions (28 %), Sweet's syndrome-like lesions (11 %) and pustules (9 %). The skin lesions were accompanied by fever and constitutional symptoms in all patients. Oral steroids and thalidomide were the main lines of therapy in most of the reported patients. Dermatologists and pathologists should keep in mind the clinical variability of ENL to avoid misdiagnosis and delayed management. Early recognition can help control disease progression and save the patients from further complications.

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Background: Vitiligo is a skin disease with complex, multifactorial pathogenesis. Abnormalities in surrounding keratinocytes may cause melanocyte death due to deprivation of growth factors. Narrow band ultraviolet B (NB-UVB) is an effective therapeutic option especially in patients with generalized disease.Objective: The aim of this study was to identify histopathological changes in lesional and perilesional skin of vitiligo patients and the effect of NB-UVB therapy on them.Methods: Twenty patients were enrolled in this study. They received NB-UVB twice weekly on non-consecutive days for a total of 40 sessions. Skin biopsies from lesional and perilesional skin were obtained from each patient before and after therapy.Results: After therapy, 10% of patients showed excellent clinical response, 10% showed good response, 40% showed moderate response, 35% showed poor response and 5% showed progressive disease. Before therapy, 50% of patients showed a basal lymphocytic infiltrate with a perivascular lymphocytic infiltrate in both lesional and perilesional skin. 40% of them showed additional hydropic degeneration of lower epidermis with apoptotic keratinocytes in 20% of them. After therapy, these inflammatory changes were significantly reduced (p=0.04).Conclusion: NB-UVB is an effective method of treatment of vitiligo. This may be due to its immunosuppressive effects. Also, keratinocyte apoptosis may have a role in pathogenesis of vitiligo

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HINTERGRUND UND ZIELE: Die genaue Pathogenese der Psoriasis ist immer noch ungeklärt. Da SLURP1 wichtig ist für die normale Differenzierung von Keratinozyten, könnte es bei Psoriasis eine Rolle spielen. In dieser Studie untersuchten wir die immunhistochemische Färbung von SLURP1 bei Patienten mit Psoriasis vulgaris und deren möglichen Zusammenhang mit der Pathogenese der Erkrankung. PATIENTEN UND METHODEN: Es wurden Hautproben von 20 Patienten mit Psoriasis vulgaris, von 20 Patienten mit psoriasiformer Dermatitis sowie 20 normale Hautproben untersucht. Der Schweregrad der Psoriasis wurde anhand einer Kombination von PASI- und DLQI-Scores gemessen. Bei allen Psoriasis-Patienten wurden Biopsate aus läsionalen und aus nichtläsionalen Hautpartien entnommen. Bei psoriasiformer Dermatitis und Kontrollen wurde jeweils nur ein Hautbiopsat entnommen. Alle Schnitte wurden, entsprechend des Hersteller-Protokolls, einer SLURP1-Immunfärbung unterzogen. ERGEBNISSE: Hinsichtlich der SLURP1-Immunfärbung wurden zwischen läsionalen und nichtläsionalen Biopsaten von Psoriasis-Patienten sowie zwischen läsionalen Biopsaten von Psoriasis-Patienten und Patienten mit psoriasiformer Dermatitis signifikante Unterschiede festgestellt. Die Unterschiede zwischen nichtläsionalen Biopsaten von Psoriasis-Patienten und normalen Hautproben waren jedoch nicht signifikant. Darüber hinaus war der Grad der SLURP1-Immunanfärbung proportional zum Schweregrad der Psoriasis. SCHLUSSFOLGERUNGEN: Bei Psoriasis vulgaris ist die SLURP1-Immunfärbung in läsionaler Haut signifikant erhöht, nicht jedoch bei psoriasiformer Dermatitis. Dies spricht für eine Rolle von SLURP1 bei der Pathogenese der Psoriasis. SLURP1 lässt sich möglicherweise als biologischer Marker für den Schweregrad der Psoriasis einsetzen, wobei diese Hypothese noch weiterer Untersuchungen bedarf.

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BACKGROUND AND OBJECTIVES: The exact pathogenesis of psoriasis is still unclear. SLURP1 is vital for the normal differentiation of keratinocytes, and could therefore be involved in psoriasis. In this study we investigated the immunohistochemical staining reaction of SLURP1 in psoriasis vulgaris patients and its possible relation to disease pathogenesis. PATIENTS AND METHODS: 20 patients with psoriasis vulgaris, 20 patients with psoriasiform dermatitis and 20 normal skin samples were studied. Psoriasis severity was measured with a combination of PASI and DLQI scores. Lesional and non-lesional sites were biopsied for each psoriasis patient. A single biopsy sample was taken for cases with psoriasiform dermatitis and for controls. All sections were immunostained for SLURP1 according to the manufacturer's protocol. RESULTS: Significant differences were noted in SLURP1 immunostaining between lesional and non-lesional biopsies of psoriasis patients and between lesional biopsies of psoriasis patients and lesional sites of psoriasiform dermatitis. However, the differences between non-lesional biopsies of psoriasis patients and normal controls were not significant. Furthermore, the grading of SLURP1 immunostaining paralleled the degree of psoriasis severity. CONCLUSIONS: SLURP1 immunostaining is significantly increased in lesional skin of psoriasis vulgaris and not in psoriasiform dermatitis, which demonstrates the role of SLURP1 in the pathogenesis of psoriasis. SLURP1 could be used as a biological marker for psoriasis severity, and this hypothesis warrants further investigation.

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Background: Endometrial carcinomas are common gynecologic malignancies worldwide. In Egypt they represent 2.6 %. We evaluated the role of morphometry and MMP-9 immunohistochemical expression to differentiate atypical endometrial hyperplasia from low grade endometrial adenocarcinoma. Methods: 60 cases of endometrial lesions that included 25 cases of complex endometrial hyperplasia with atypia, 25 cases of low grade endometrioid adenocarcinoma, in addition to 10 cases of proliferative endometrium as a control group. Morphometric measurements and D-score were evaluated. MMP9 was performed using streptavidin ­biotin immunoperoxidase system. Results: D score was more than 1 in 100% of cases of proliferative endometrium. In atypical hyperplasia 28 % of cases had a D-score more than 1, 44% less than 0 and 28% of cases had a D score between 0 and 1 with uncertain prognosis. All carcinoma cases had D-score less than 0. MMP9 was positive in all cases of the study but differ in its degree of expression; proliferative endometrium with low expression. Atypical hyperplasia divided as 52% low expression and 48% high expression. Most of the Endometrial adenocarcinoma cases (92%) showed high expression. There was significant difference in expression of MMP9 in atypical endometrial hyperplasia and endometrial adenocarcinoma (p> 0.001). Conclusion: The relation between MMP9 expression and D-score value in cases of atypical endometrial hyperplasia was highly significant P>0.001Thus, incorporating both MMP9 immunoexpression and D-score value would increase the accuracy of diagnosis of atypical endometrial hyperplasia and low grade endometrial adenocarcinoma.

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BACKGROUND: The distinction of trichoepithelioma from basal cell carcinoma in small superficial biopsies is important but often challenging. This has inspired many scientists to test the validity of immunohistochemical markers in the differential diagnosis. OBJECTIVES: To develop an immunohistochemical protocol that helps in differentiation between both trichoepithelioma (TE) and basal cell carcinoma (BCC) with higher sensitivity and specificity. METHODS: Using standard immunohistochemical techniques, we examined 10 TEs and 19 BCCs for the expression of CK19, Ki-67, androgen receptors (AR), CD10, and PHLDA1. RESULTS: Immunoreactivity of AR, Ki-67, and CD10 in tumor cells was significantly higher in BCC than TE with a diagnostic accuracy in BCC of 75.5%, 75.8%, and 79.3% respectively, whereas immunoreactivity of PHLDA1 in tumor cells and stromal CD10 was significantly higher in TE than BCC with a diagnostic accuracy in TE of 100% and 82.8%, respectively. In contrast, immunoreactivity for CK19 showed no statistically significant differences between both tumors. CONCLUSION: The analysis of CD10, Ki-67, and PHLDA1 can be used as a helpful immunohistochemical panel in the distinction between TE and BCC especially in small and superficial biopsies.

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Febrile ulceronecrotic Mucha-Habermann disease (FUMHD) is a rare severe variant of pityriasis lichenoides et varioliformis acuta characterized clinically by aggressive ulceronecrotic skin lesions associated with high fever and histologically by features typical of pityriasis lichenoides et varioliformis acuta. Despite the continuous addition of new case reports, no definite diagnostic criteria have been established, and an optimum treatment is still waiting. Herein, we review the different aspects of this rare entity, including pathogenesis, clinical and histopathological features, differential diagnosis, course, prognosis, and outcome. Different diagnostic and therapeutic challenges associated with FUMHD are also evaluated and discussed. We propose two sets of diagnostic criteria to define the disease more precisely and to avoid missing cases. The first comprises constant clinical and histopathological features that are always present in every case, the combination of which is necessary for diagnosis. The second set includes variable features that may be present in some cases and to which any emerging finding could be added. Although different therapeutic options have been used, there is no optimum therapy for FUMHD, and the disease still represents a therapeutic challenge.

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BACKGROUND: Melasma is a common pigmentary disorder that remains resistant to available therapies. OBJECTIVES: The aim of the present study was to evaluate the efficacy of erbium:YAG lasers in the treatment of refractory melasma and investigate the histopathological and ultrastructural changes between melasma skin and adjacent control skin before and after surgery. METHODS: Fifteen Egyptian female patients with melasma unresponsive to previous therapy of bleaching creams and chemical peels were included in this study. Full-face skin resurfacing using an erbium:YAG laser was performed. Clinical parameters included physician and patient assessment, and melasma area and severity index score were done. Adverse effects after laser resurfacing were recorded. Biopsies of lesions and adjacent healthy skin were stained using hematoxylin-eosin, immunohistochemically marked for Melan-A, and evaluated by electron microscopy. RESULTS: The amount of melanin, staining intensity, and number of epidermal melanocytes are increased in melasma lesions as compared to normal skin. Electron microscopic analysis revealed an increased number of mature melanosomes in keratinocytes and melanocytes, with more marked cytoplasmic organelles in melasma skin than in biopsy specimens from normal skin, suggesting increased cell activity. After surgery, the number of melanocytes and concentration of melanin decreased in melasma skin, and the mean melasma area and severity index score decreased dramatically. CONCLUSIONS: Erbium:YAG laser resurfacing effectively improves melasma; however, the almost universal appearance of transient postinflammatory hyperpigmentation necessitates prompt and persistent intervention.

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BACKGROUND: Generalized eruptive keratoacanthoma (GEKA) is an extremely rare variant of keratoacanthoma that poses significant diagnostic and therapeutic challenges. PATIENTS: The study included three patients presenting with highly pruritic, generalized eruption of numerous small skin and flesh-colored follicular papules. They were mainly distributed on the face, neck, and trunk. Few larger nodules were also present. Mask-like facies, mucosal involvement, and ectropion were evident in two patients. Family history was irrelevant, and general examination was unremarkable. RESULTS: Histopathological examination revealed typical features of keratoacanthoma, particularly in the larger lesions. Routine laboratory tests were normal, and ultrasonography and computed tomography revealed no evidence of malignancy. Based on the clinicopathological correlation, the diagnosis of our cases was GEKA of Grzybowski. Acitretin 1 mg/kg per day and methotrexate 15 mg/week for three months were associated with mild or no response. Cyclophosphamide pulse therapy 1 g/month for six months was associated with complete clearance of the lesions in the first two patients, while the third was lost to follow-up after failure of acitretin therapy. CONCLUSION: Because of the extreme rarity of reported cases, the common absence of classic large lesions of keratoacanthoma, the atypical histological presentations in some cases, and absence of a uniformly effective therapeutic approach, we believe that GEKA still represents a diagnostic and therapeutic challenge. Cyclophosphamide pulse therapy is a promising alternative to oral retinoids.

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BACKGROUND: We have observed that hair thinning and/or loss occur at times as a presenting symptom or sign in patients with pityriasis versicolor (PV). OBJECTIVE: Our objective was to verify and explore this clinical observation and depict its underlying pathology. METHODS: A total of 39 patients with PV were examined during a period of 11 months and skin biopsy specimens were taken from lesional and nonlesional skin. Hematoxylin-eosin- and periodic acid-Schiff-stained sections were examined and described. Results were statistically analyzed. RESULTS: Hair loss and/or thinning within PV lesions was shown in 61.5% of patients (P value < .0005), appearing most commonly on forearms, abdomen, and neck as well as the beard area (only in male participants). Histopathologically, in addition to the classically described features of PV, basal hydropic degeneration, follicular degeneration, miniaturization, atrophy, plugging, and/or hair shaft absence occurred in 46% of lesional versus 20.5% of nonlesional biopsy specimens (P value < .05); these changes appeared to be directly or indirectly related to the presence of Malassezia organisms in hair follicles and/or stratum corneum. LIMITATIONS: Some patients with PV lesions on the face did not approve facial biopsy. CONCLUSION: This study provides clinical and histopathological evidence that PV lesions may be associated with hair thinning and/or loss.

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There is a growing evidence that cytokines are important in the depigmentation process of vitiligo, however, the exact mechanism is not fully understood. The aim of this work was to study the possible role of the tumor necrosis factor-α (TNF-α) cytokine in the depigmentation process of the disease. Twenty patients with generalized vitiligo were exposed to narrow-band ultraviolet B (NB-UVB) therapy thrice weekly for a total of 60 sessions. Immunohistochemical examination was done, to assess the TNF-α expression in lesional and perilesional skin as compared to normal control skin, before and after therapy. At baseline, positive lesional TNF-α expression was detected in 60 % of patients which was significantly higher as compared to perilesional skin (20 %) and negative expression in healthy control skin. Post-treatment, a statistically significant increase in TNF-α expression was detected in both lesional (90 %) and perilesional skin (70 %) as compared to baseline (P < 0.05). The significant increase of TNF-α in vitiligo lesions compared with perilesional and healthy skin suggests a possible involvement of this cytokine in the depigmentation of vitiligo. The increase in TNF-α expression after NB-UVB phototherapy suggests another role in repigmentation.

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