Vacuolar Interface Dermatitis as a Histologic Reaction Pattern of Sjögren's Syndrome: A Case Report.

Sjögren's syndrome (SS) has been widely known for its dry mouth and dry eyes presentation. Extraglandular disease manifestations may be protean and pose a challenge for clinicians, especially when the typical known manifestations are absent. Skin involvement of SS is variable, and cutaneous signs and symptoms may be the initial presentation of this syndrome. Vacuolar interface dermatitis has been linked to dermatomyositis and systemic lupus erythematosus, but rarely to SS. Herein, we present the case of an 87-year-old man who presented for widespread itchy erythematous scaly plaques that were refractory to topical corticosteroids as well as discontinuation of possible offending medications. A biopsy demonstrated vacuolar interface dermatitis in the setting of strongly positive anti-SSA. Hydroxychloroquine treatment was effective in resolving the plaques.

Navigating patients with atopic dermatitis or chronic spontaneous urticaria during the COVID-19 pandemic.

A rapid spread of different strains of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to an unprecedented pandemic. Since the onset of the coronavirus disease 2019 (COVID-19) pandemic, the medical body has encountered major obstacles concerning disease management at different levels. Even though patients infected with this virus mainly present with respiratory symptoms, it has been associated with a plethora of well-documented cutaneous manifestations in the literature. However, little investigations have been conducted concerning COVID-19 and its impact on skin disorders mediated by type 2 inflammation leaving multiple dermatologists and other specialists perplexed by the lack of clinical guidelines or pathways. This review focuses on the effects of this pandemic in patients with skin disorders mediated by type 2 inflammation, specifically atopic dermatitis and chronic spontaneous urticaria. In addition, it will provide clinicians a guide on treatment and vaccination considerations for this stated set of patients.

Characterizing the presence of neutrophil extracellular traps in neutrophilic dermatoses.

Neutrophil extracellular traps (NETs) are implicated in the pathogenesis of multiple inflammatory dermatoses. However, characterization of NETs in neutrophilic dermatoses was performed on very limited number of patients; this limitation precluded definitive conclusions. In this case series of 57 patients, we compared the amounts of neutrophils producing NETs in cutaneous lesions of different entities of neutrophilic dermatoses (17 with pyoderma gangrenosum, 37 with Sweet's syndrome and three with subcorneal pustular dermatosis). NETs were identified by double immunofluorescence on formalin-fixed paraffin-embedded skin biopsies using antibodies against elastase and citrullinated histone 3. Percentages of neutrophils showing NETs were high across all three entities (62.9% in PG, 48.5% in SS and 37.8% in subcorneal pustular dermatosis). The differences in mean percentages were significant between entities, with PG showing significantly superior percentage of NETs compared with SS. In our series, 15.8% of neutrophilic dermatoses were associated with malignancies, 10.5% with autoimmune diseases and 73.7% were idiopathic. Percentages of NETs were not statistically different between aetiologies. These findings suggest that NETs are abundantly produced in the various entities and different aetiologies of neutrophilic dermatoses. In comparison with SS, the superior percentage of NETs in PG is clinically mirrored in its greater ulceronecrotic nature.

Investigating the presence of neutrophil extracellular traps in septal and lobular cutaneous panniculitides.

BACKGROUND: Panniculitides are a heterogeneous group of inflammatory dermatoses involving the subcutaneous fatty tissue. Histologically, they are classified into septal and lobular panniculitis, according to the predominant localization of the inflammatory infiltrate. Neutrophils are frequently found in panniculitis, mainly at the early stages. Here, we investigated whether neutrophils contribute to various types of cutaneous panniculitis by releasing neutrophil extracellular traps (NETs). MATERIALS AND METHODS: Formalin-fixed paraffin-embedded skin biopsies from 25 patients with panniculitis were included in the study. Our cohort was divided into n = 10 erythema nodosum (septal panniculitis) and n = 15 lobular panniculitis, including n = 7 lupus panniculitis, n = 1 pancreatic panniculitis, n = 1 Weber-Christian disease, n = 1 deep fungal infection, n = 2 lipodermatosclerosis, and three cases did not have an identified etiology. The presence of neutrophils and NETs was assessed by double immunofluorescence using antibodies against elastase, a neutrophilic marker, and citrullinated histone 3, a marker of NETs. RESULTS: The mean percentages (±SEM) of elastase-positive neutrophils showing NETs were 44% ± 3% in erythema nodosum and 43% ± 7% in lobular panniculitis. The difference was not statistically significant and reflects the implication of NETs not only in severe scarring lobular panniculitis but also in benign non-scarring self-remitting reactive inflammation such as erythema nodosum. In tissues, NETs were located in the interlobular septa in erythema nodosum and in the inflamed fat lobules in lobular panniculitis. CONCLUSIONS: NETs are massively present in septal and lobular subtypes of panniculitides, suggesting their involvement in tissue damage.

SuPAR, a potential inflammatory mediator in psoriasis pathogenesis.

Psoriasis is an inflammatory skin disorder that is strongly associated with the metabolic syndrome. The sole reliance on clinical examination to guide prognostication and treatment is insufficient at best; accurate diagnostic and prognostic psoriatic molecular biomarkers are needed. Soluble urokinase plasminogen activator receptor (suPAR) has been implicated in inflammation. The aim of this study is to determine whether suPAR plays a role in the pathogenesis of psoriasis and whether an association exists between suPAR levels, disease severity, and other variables like insulin, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). This study also compares the pattern of uPAR staining in healthy vs psoriatic skin: 39 psoriatic and 30 control subjects were included. Two biopsies (affected and unaffected skin) and one biopsy were taken from psoriasis patients and healthy controls, respectively, with uPAR staining of all skin biopsies. Blood samples from all subjects were obtained to determine suPAR, ESR, CRP, and fasting insulin levels. uPAR staining was prominent in unaffected skin from psoriasis patients and healthy individuals vs weak/absent uPAR staining in psoriatic skin. CRP, ESR and suPAR levels were not significantly elevated in the mild psoriasis group compared to healthy controls. The loss of epidermal uPAR is suggestive of its tentative role in the pathogenesis of psoriasis. Patients with mild-moderate psoriasis possibly lack the powerful association attributed to metabolic syndrome in psoriatic patients. Further studies on larger cohorts are needed to ascertain the validity of the mentioned conclusions.

Update on the use of dapsone in dermatology.

Dapsone (4,4'-diaminodiphenylsulfone) is the only remaining sulfone used in anthropoid therapeutics and is commercially available as an oral formulation, an inhaled preparation, and a 5% or 7.5% cream. Dapsone has antimicrobial effects stemming from its sulfonamide-like ability to inhibit the synthesis of dihydrofolic acid. It also has anti-inflammatory properties such as inhibiting the production of reactive oxygen species, reducing the effect of eosinophil peroxidase on mast cells and down-regulating neutrophil-mediated inflammatory responses. This allows for its use in the treatment of a wide variety of inflammatory and infectious skin conditions. Currently in dermatology, the US Food and Drug Administration (FDA)-approved indications for dapsone are leprosy, dermatitis herpetiformis, and acne vulgaris. However, it proved itself as an adjunctive therapeutic agent to many other skin disorders. In this review, we discuss existing evidence on the mechanisms of action of dapsone, its FDA-approved indications, off-label uses, and side effects.

Neutrophil Extracellular Traps are Present in Immune-complex-mediated Cutaneous Small Vessel Vasculitis and Correlate with the Production of Reactive Oxygen Species and the Severity of Vessel Damage.

Formation of neutrophil extracellular traps has been implicated in autoimmunity. However, the presence and clinical relevance of neutrophil extracellular traps in immune-complex-mediated cutaneous small and medium vessel vasculitides has not been investigated. This study retrospectively analysed 72 patients with histology-proven hypersensitivity vasculitis (n = 21), IgA vasculitis (n = 22), urticarial vasculitis (n = 22), erythema elevatum diutinum (n = 3) and polyarteritis nodosa (n = 4). Neutrophil extracellular traps were detected in hypersensitivity vasculitis, IgA vasculitis, urticarial vasculitis and erythema elevatum diutinum, but not in polyarteritis nodosa lesions. Neutrophil extracellular traps were found around inflamed vessels, and their formation was highest early after the onset of vasculitis and decreased progressively thereafter. Neutrophil extracellular traps were strongly correlated with the histological severity of vasculitis and the production of reactive oxygen species. Both hypersensitivity vasculitis and IgA vasculitis showed significantly more neutrophil extracellular traps than did urticarial vasculitis, independent of the histological severity and duration of vasculitis. These results provide evidence on the implication of neutrophil extracellular traps in the early phases of immune-complex-mediated small vessel vasculitis.

Loss of ferrochelatase is protective against colon cancer cells: ferrochelatase a possible regulator of the long noncoding RNA H19.

BACKGROUND: Ferrochelatase (FECH) is the last enzyme of the heme biosynthesis pathway. Deficiency in FECH was associated with many diseases, including protoporphyria. Correlation studies showed that variations of FECH expression was detected in human carcinomas and more specifically in colon cancer. Nevertheless, the potential role of FECH in colon cancer carcinogenesis in vitro was not depicted yet. METHODS: A small interfering RNA (siRNA) was used to knockdown FECH in human Caco-2 colon cancer cells. The effect of FECH down-regulation on the cellular proliferation, the migration and the expression of target genes was assessed in cancer cells and compared to human normal fibroblasts. RESULTS: Following FECH down-regulation, our results demonstrated that the proliferation of Caco-2 cells was not affected. Furthermore, the migration of cancer and normal cells was affected, only when an additional stress factor (H2O2) was applied to the medium. The expression of twist, snail, hypoxia induced factor (HIF-1α) and vascular endothelial growth factor (VEGF) was reduced in Caco-2 cells. Conversely, VEGF and HIF-1α expression were upregulated by up to 2 folds in control fibroblasts. Interestingly, the pro-carcinogenic long noncoding RNA (LncRNA) H19 was 70% down-regulated in Caco-2 cells upon FECH down regulation whereas no effect was observed in normal fibroblasts. CONCLUSIONS: In conclusion, we showed that loss of FECH is protective against colon cancer tumorigenesis in vitro and this effect could possibly be mediated through inhibition of H19.

Investigating the presence of neutrophil extracellular traps in cutaneous lesions of different subtypes of lupus erythematosus.

Neutrophil extracellular traps (NETs) are implicated in the pathogenesis of systemic lupus erythematosus (SLE). However, little is known about the implication of NETs in cutaneous lupus. In this case series of 30 patients, we compared the amounts of neutrophils producing NETs in cutaneous lesions of different subtypes of lupus (5 with discoid lupus or DLE, 5 with subacute cutaneous lupus or SCLE, 11 with acute cutaneous SLE, 7 with lupus panniculitis and 2 with chilblains). Immunofluorescence was performed on formalin-fixed paraffin-embedded skin biopsies using antibodies against neutrophilic granules (elastase, myeloperoxidase, PR-3 proteins and citrullinated histone 3). Dihydroethidium staining was performed to detect reactive oxygen species (ROS), known inducers of NETs. NETs were detected in the different subtypes of cutaneous lupus as well as in cutaneous lesions of SLE. The amounts of neutrophils producing NETs were significantly higher in lupus panniculitis (49%), acute cutaneous SLE (41%) and DLE (32%), in comparison with SCLE (5%) and chilblains (0%). This suggests that NETs might be associated with more tissue damage and scarring. ROS were observed in the different cutaneous subtypes of lupus independent of NETs.

Neutrophils contribute to vasculitis by increased release of neutrophil extracellular traps in Behçet's disease.

BACKGROUND AND OBJECTIVES: Behçet's disease (BD) is a multi-system inflammatory disorder that can cause vasculitis. Here we questioned whether Neutrophils in BD cause vasculitis via releasing Neutrophil Extracellular Traps (NETs), a process called NETosis. METHODS: Circulating neutrophils were isolated from a cohort of Middle Eastern BD patients with an active disease and healthy volunteers. The percentage of NETs release was monitored in neutrophils stimulated or not with BD serum, and treated or not with Colchicine, Dexamethasone, Cl-amidine or N-Acetyl Cysteine (NAC). The mRNA expression levels of PAD4 (a key enzyme in NETosis) was also assessed. The effect of NETs on the proliferation and cell death of endothelial cells was investigated using an in vitro co-culture model. The presence of NETs in skin tissues of BD patients was examined using immunolabeling of NETs associated proteins. RESULTS: Circulating Neutrophils from BD patients were more prone to release NETs in vitro and expressed higher levels of PAD4 compared to healthy volunteers. Spontaneous NETs formation in BD neutrophils was inhibited by Colchicine and Dexamethasone, two drugs used to treat BD. NETs formation was also inhibited by Cl-amidine, a specific PAD4 inhibitor, and by NAC, a ROS inhibitor. Interestingly, serum from BD patients stimulated circulating neutrophils from healthy volunteers to release more NETs and increased their mRNA PAD4 expression. Moreover, endothelial cells cultured in the presence of NETs from BD patients showed a decrease in proliferation and an increase in apoptosis and cell death. Finally, NETosis was predominantly identified around affected blood vessels in biopsies of vasculitis from BD patients. CONCLUSION: Our results provide evidence on the implication of NETosis in the pathophysiology of BD especially in inducing vasculitis.

Experience and challenges for biologic use in the treatment of moderate-to-severe psoriasis in Africa and the Middle East region.

The incidence of psoriasis in Africa and the Middle East (AfME) is high as in other regions and represents a significant problem for both dermatologists and patients. Psoriasis co-morbidities such as obesity, cardiovascular disease and psoriatic arthritis (PsA) are also particularly common in these regions and may be under-recognized and under-treated. Despite this, regional guidelines to aid physicians on the appropriate use of biologic agents in their clinical practice are limited. A group of expert dermatologists from across the AfME region were surveyed to help establish best practice across the region, alongside supporting data from the literature. Although biologics have significantly improved patient outcomes since their introduction, the results of this survey identified several unmet needs, including the lack of consensus regarding their use in clinical practice. Discrepancy also exists among AfME physicians concerning the clinical relevance of immunogenicity to biologics, despite increasing data across inflammatory diseases. Significant treatment and management of challenges for psoriasis patients remain, and a move towards individualized, tailored care may help to address these issues. The development of specific local guidelines for the treatment of both psoriasis and PsA could also be a step towards understanding the distinct patient profiles in these regions.

High prevalence of metabolic syndrome in patients with psoriasis in Lebanon: a prospective study.

BACKGROUND: Psoriasis is a chronic inflammatory disease that affects not only the skin but also other organs as well. Genetic factors play an important role in individual predisposition. Lately, a positive association has been confirmed between psoriasis and metabolic syndrome (MBS), in western as well as in Middle Eastern countries. AIM: Assess the prevalence of MBS in Lebanese patients with psoriasis and the differential effect according to types and disease severity. METHODS: This was a case-control study including 150 psoriasis patients and 150 age- and gender-matched controls admitted to the dermatology clinics at the American University of Beirut-Medical Center, a tertiary care center in Beirut. Psoriasis severity was assessed by the Psoriasis Area Severity Index (PASI). Blood samples were collected from fasting subjects and tested for glucose, HDL cholesterol, triglycerides, and C-reactive protein (CRP). Multivariate binary logistic regression models were built to assess the relationship between MBS and psoriasis, after adjustment for smoking as a possible confounding variable. RESULTS: Patients with psoriasis were two times more likely to have MBS as compared to controls (35.3% vs 18.0%, P < 0.001) with an odds ratio (OR) of 2.4. All components of MBS were more prevalent in psoriasis patients than in controls. PASI score was greater in patients with MBS than those without MBS (10.5 ± 11.5 vs. 7.0 ± 8.1, P = 0.05). MBS prevalence tended to be higher in the inverse type than in others (52.2% versus 32.3%; P = 0.06) and in patients with nail pitting versus those without (45.3% vs. 28.2%; P = 0.03). CONCLUSIONS: This was the first study to assess the prevalence of MBS in Lebanese subjects with psoriasis and, to our knowledge, the first study that showed a higher likelihood of MBS in patients with inverse psoriasis and with nail pitting.

Identification of several mutations in ATP2C1 in Lebanese families: insight into the pathogenesis of Hailey-Hailey disease.

BACKGROUND: Hailey-Hailey disease (HHD) is an inherited blistering dermatosis characterized by recurrent erosions and erythematous plaques that generally manifest in intertriginous areas. Genetically, HHD is an autosomal dominant disease, resulting from heterozygous mutations in ATP2C1, which encodes a Ca2+/Mn2+ATPase. In this study, we aimed at identifying and analyzing mutations in five patients from unrelated families diagnosed with HHD and study the underlying molecular pathogenesis. OBJECTIVES: To genetically study Lebanese families with HHD, and the underlying molecular pathogenesis of the disease. METHODS: We performed DNA sequencing for the coding sequence and exon-intron boundaries of ATP2C1. Heat shock experiments were done on several cell types. This was followed by real-time and western blotting for ATP2C1, caspase 3, and PARP proteins to examine any possible role of apoptosis in HHD. This was followed by TUNEL staining to confirm the western blotting results. We then performed heat shock experiments on neonatal rat primary cardiomyocytes. RESULTS: Four mutations were detected, three of which were novel and one recurrent mutation in two families. In order for HHD to manifest, it requires both the genetic alteration and the environmental stress, therefore we performed heat shock experiments on fibroblasts (HH and normal) and HaCaT cells, mimicking the environmental factor seen in HHD. It was found that stress stimuli, represented here as temperature stress, leads to an increase in the mRNA and protein levels of ATP2C1 in heat-shocked cells as compared to non-heat shocked ones. However, the increase in ATP2C1 and heat shock protein hsp90 is significantly lower in HH fibroblasts in comparison to normal fibroblasts and HaCaT cells. We did not find a role for apoptosis in the pathogenesis of HHD. A similar approach (heat shock experiments) done on rat cardiomyocytes, led to a significant variation in ATP2C1 transcript and protein levels. CONCLUSION: This is the first genetic report of HHD from Lebanon in which we identified three novel mutations in ATP2C1 and shed light on the molecular mechanisms and pathogenesis of HHD by linking stress signals like heat shock to the observed phenotypes. This link was also found in cultured cardiomyocytes suggesting thus a yet uncharacterized cardiac phenotype in HHD patients masked by its in-expressivity in normal health conditions.

Guidelines for the Topical Treatment of Psoriasis Vulgaris in the Levant and Iraq Area.

Psoriasis vulgaris is a common chronic, inflammatory, multisystem disorder that affects approximately 1.5% to 3.4% of the population in the Middle East. The disease has an impact on the quality of life in a significant number of affected patients. The majority of patients (approximately 70%) have mild to moderate psoriasis that is manageable with topical agents, which generally show a high efficacy to safety ratio. Topical agents can be used alone when treating patients with limited disease or may be used as adjunctive therapy for patients with more extensive psoriasis undergoing systemic treatment. Treatment should also be customized to meet individual patients' needs. To optimize the topical treatment of psoriasis in the Levant and Iraq area, dermatology experts from Iraq, Jordan, Lebanon, Palestine, and Syria met and initiated a project to develop guidelines and recommendations for the topical management of psoriasis. The guidelines are based on literature evidence and experts' opinions. We present recommendations for the use of topical corticosteroids, vitamin D analogues, calcineurin inhibitors, tazarotene, salicylic acid, anthralin, and coal tar, as well as combination therapy, based on their efficacy and safety profiles.

Cutaneous sarcoidosis: clinicopathologic study of 76 patients from Lebanon.

BACKGROUND: Sarcoidosis is a multi-system granulomatous disease of unknown etiology. The skin is involved in 25% of cases. Studies on cutaneous sarcoidosis from our region are lacking. OBJECTIVES: This study was conducted to describe clinical and histopathologic findings in all patients diagnosed with cutaneous sarcoidosis at the American University of Beirut Medical Center between 1992 and 2010 and to compare findings with those published in the literature. METHODS: Clinical charts of patients with cutaneous sarcoidosis were retrospectively reviewed. Extracutaneous lesions were classified by organ involvement. Treatment was documented. Pathology specimens were reviewed. RESULTS: Cutaneous sarcoidosis was diagnosed in 76 Lebanese patients, 79% of whom were women. Mean age at diagnosis was 48 years. A total of 29% of patients had systemic disease that was commonly associated with lupus pernio lesions and subcutaneous sarcoidosis. The most common cutaneous lesions were sarcoidal plaques. The histopathologic features in our series did not differ from those described in the literature, except for the documented presence of a grenz zone. Interestingly, 23% of biopsy specimens contained perineural granulomas, raising the possibility of tuberculoid or borderline tuberculoid leprosy. Foreign bodies were detected in 10% of cases (all had systemic involvement), supporting the opinion that sarcoidosis and granulomatous foreign body reaction are not mutually exclusive. CONCLUSIONS: The clinical and histopathologic features of cutaneous sarcoidosis patients in the present series are generally comparable with those published in the literature, with minor differences. Clinically, the most commonly seen lesion was plaque. Microscopically, cutaneous sarcoidosis may exhibit a grenz zone and may show perineural inflammation and foreign bodies.

Prurigo pigmentosa: a clinicopathologic study of 4 cases from the middle East.

Prurigo pigmentosa (PP) is a rare inflammatory dermatosis originally reported in Japan. Since then, most reports have originated from Asia, and to a lesser extent from Europe. Although the pathogenesis remains unclear, it is now established that PP is linked to ketoacidotic states. Four patients diagnosed with PP were identified from the dermatopathology database at the American University of Beirut Medical Center between January 2009 and December 2013. Clinicopathologic findings in the 4 patients were similar to those previously reported in the literature. The patients were all female with a mean age of 23.5 years. They all presented with itchy erythematous reticulated papulovesicles/plaques leaving variable reticulated brownish patches. Two patients had, in addition, annular lesions arranged en cocarde and pustules, respectively. In 3 patients, the rash was associated with fasting or dieting. The rash had a predilection to the trunk and proximal part of the upper extremities. One patient had intergluteal area involvement. Two biopsy specimens revealed psoriasiform hyperplasia and neutrophilic exocytosis mimicking psoriasis or an impetiginized spongiotic dermatitis. One biopsy specimen exhibited a mild superficial perivascular lymphocytic infiltrate with ballooning and reticular degeneration, a picture mimicking a viral exanthema. Another biopsy specimen exhibited a picture similar to chronic spongiotic dermatitis. Although mostly described in Japan, PP has been described much less frequently in the Middle East region likely due to mis/underdiagnosis. Therefore, increased awareness is necessary especially because fasting is a common religious practice among Arab countries. Further investigations are necessary to better understand the etiopathogenesis of this rare entity.

Pityriasis rubra pilaris: clinicopathological study of 32 cases from Lebanon.

BACKGROUND: Pityriasis rubra pilaris (PRP) is an uncommon papulosquamous disorder of unknown etiology. Studies on this condition from our region are lacking. METHODS: To describe the clinical and histopathological findings as well as response to treatment of all patients diagnosed with PRP at the American University of Beirut Medical Center between 1995 and 2010 and compare our findings with those published in the literature. RESULTS: Pityriasis rubra pilaris was diagnosed in 32 patients (16 males, 16 females). Age of onset ranged between 2.5 and 70 years. The majority of patients (n=15) were classified as type I (47%) followed by type III (n=9, 28%) and type IV (n=6, 19%). Based on treatment responses, retinoids appear to be very effective in our population as all patients treated with isotretinoin or acitretin had excellent response. In addition to checkerboard alternating orthokeratosis/parakeratosis, which was observed in 31 cases, interesting features, including the presence of follicular plugging in all 21 cases in which follicles were available for examination, eosinophils in 12 cases, and focal acantholysis in three cases were observed. CONCLUSIONS: Features of patients with PRP in our study are generally comparable to those published in the literature, with minor differences. Microscopically follicular plugging, in addition to checkerboard alternating orthokeratosis/parakeratosis, may serve as clues to PRP diagnosis. The presence of eosinophils and focal acantholysis, observed in a few cases, should not exclude PRP diagnosis.

Fibroblast-activation protein: valuable marker of cutaneous epithelial malignancy.

Fibroblast-activation protein (FAP) is a key protein that is characteristically expressed by carcinoma-associated fibroblasts (CAFs). It has been shown to be expressed in CAFs of 90 % of internal epithelial cancers as well as cutaneous epithelial malignancies. We have recently shown that this marker is useful in differentiating between morpheaform/infiltrative BCC from desmoplastic trichoepithelioma (TE). Given this, we sought to assess FAP expression in both benign and malignant cutaneous epithelial entities. Immunohistochemical FAP staining was performed on BCC (n = 26), SCC (n = 26), porocarcinoma (n = 10), metastatic adenocarcinoma (n = 12), keratoacanthoma (KA) (n = 16), TE (n = 14), pseudoepitheliomatous hyperplasia (n = 15), poroma (n = 15), syringoma (n = 10), and chondroid syringoma (n = 6). Control group consisted of scars (n = 10). FAP expression was observed in all scars and all malignant entities, but not in any of the benign cases. Interestingly, ten KA cases exhibited positivity, whereas six were negative. In summary, FAP is a reliable marker of cutaneous epithelial malignancy.