14-3-3σ/Stratifin and p21 limit AKT-related malignant progression in skin carcinogenesis following MDM2-associated p53 loss.

To study mechanisms driving/inhibiting skin carcinogenesis, stage-specific expression of 14-3-3σ (Stratifin) was analyzed in skin carcinogenesis driven by activated rasHa/fos expression (HK1.ras/fos) and ablation of PTEN-mediated AKT regulation (K14.creP/Δ5PTENflx/flx). Consistent with 14-3-3σ roles in epidermal differentiation, HK1.ras hyperplasia and papillomas displayed elevated 14-3-3σ expression in supra-basal keratinocytes, paralleled by supra-basal p-MDM2166 activation and sporadic p-AKT473 expression. In bi-genic HK1.fos/Δ5PTENflx/flx hyperplasia, basal-layer 14-3-3σ expression appeared, and alongside p53/p21, was associated with keratinocyte differentiation and keratoacanthoma etiology. Tri-genic HK1.ras/fos-Δ5PTENflx/flx hyperplasia/papillomas initially displayed increased basal-layer 14-3-3σ, suggesting attempts to maintain supra-basal p-MDM2166 and protect basal-layer p53. However, HK1.ras/fos-Δ5PTENflx/flx papillomas exhibited increasing basal-layer p-MDM2166 activation that reduced p53, which coincided with malignant conversion. Despite p53 loss, 14-3-3σ expression persisted in well-differentiated squamous cell carcinomas (wdSCCs) and alongside elevated p21, limited malignant progression via inhibiting p-AKT1473 expression; until 14-3-3σ/p21 loss facilitated progression to aggressive SCC exhibiting uniform p-AKT1473. Analysis of TPA-promoted HK1.ras-Δ5PTENflx/flx mouse skin, demonstrated early loss of 14-3-3σ/p53/p21 in hyperplasia and papillomas, with increased p-MDM2166/p-AKT1473 that resulted in rapid malignant conversion and progression to poorly differentiated SCC. In 2D/3D cultures, membranous 14-3-3σ expression observed in normal HaCaT and SP1ras61 papilloma keratinocytes was unexpectedly detected in malignant T52ras61/v-fos SCC cells cultured in monolayers, but not invasive 3D-cells. Collectively, these data suggest 14-3-3σ/Stratifin exerts suppressive roles in papillomatogenesis via MDM2/p53-dependent mechanisms; while persistent p53-independent expression in early wdSCC may involve p21-mediated AKT1 inhibition to limit malignant progression.

Esthetic and medical tattooing: Part I: Tattooing techniques, implications, and adverse effects in healthy populations and special groups.

Tattooing, the introduction of exogenous pigments into the skin, has a rich history spanning thousands of years, with cultural, cosmetic, and medical significance. With the increasing prevalence of tattoos, understanding their potential complications and contraindications is of growing importance. The most common complications are hypersensitivity reactions, which may vary in morphology and timing. Infectious complications are often due to inadequate aseptic and hygienic practices during the tattooing process or healing period. Tattoo pigment can present diagnostic challenges, affecting cancer diagnosis and imaging. This CME article explores the history, cultural significance, epidemiology, chemistry, technique, contraindications, and complications of tattoos. Appreciating these factors can help individuals considering tattoos understand the safety and potential risks of their body art, and provide physicians with a thorough understanding of tattooing if consulted.

A pilot study of p53 immunohistochemistry in atypical squamous lesions, using a vulvar scoring system.

BACKGROUND: Histopathologic overlap between cutaneous squamous cell carcinoma (cSCC) and its indolent mimics likely leads to the overdiagnosis of cSCC. OBJECTIVE: To perform a pilot study of the p53 immunohistochemical scoring system developed on vulvar squamous lesions in cSCC. METHODS: The consistency and reliability of p53 immunostaining using a scoring system developed on vulvar cases, as compared with TP53 genomic sequencing, was studied in an initial cohort of 28 cutaneous cases. p53 labeling was further assessed in an additional 63 cases of atypical squamous lesions, including 20 atypical squamous lesions classified by the authors as benign, 22 cases diagnosed as cSCC without high-risk features, and 21 cases of high-risk cSCC (cSCC-HR). RESULTS: The concordance of p53 labeling and TP53 sequencing was 82.1%. Four positive patterns of p53 mutation were identified: basal, parabasal/diffuse, null, and cytoplasmic. p53 positivity in atypical, benign squamous lesions (10%) was significantly lower than that of low-risk cSCC (63.6%, p = 0.0004) or cSCC-HR (90.5%, p < 0.0001). p53 positivity in low-risk cSCC versus cSCC-HR was not statistically significant (p = 0.07). CONCLUSION: p53 Labeling may be a helpful biomarker to support the diagnosis of cSCC and distinguish cSCC from atypical but benign mimics.

Multiple Keratoacanthoma-like Syndromes: Case Report and Literature Review.

Keratoacanthoma (KA) is a fast-growing skin tumor subtype that can be observed as a solitary lesion or rarely as multiple lesions in the context of rare genetic syndromes. Syndromes with multiple keratoacanthoma-like lesions have been documented as multiple self-healing squamous epithelioma (Ferguson-Smith syndrome), eruptive keratoacanthoma of Grzybowski, multiple familial keratoacanthoma of Witten and Zak Muir-Torre syndrome, and incontinentia pigmenti. The treatment approach of those entities is challenging due to the numerous lesions, the lesions' undefined nature, and the co-existence of other malignant skin tumors. Herein, we report a case of a 40-year-old woman who developed multiple treatment-resistant Ferguson-Smith-like keratoacanthomas with a co-existing large and ulcerated invasive squamous cell carcinoma and microcystic adnexal carcinoma on the scalp. Multiple keratoacanthomas on her extremities were successfully treated with oral acitretin (0.5 mg/kg/day) in combination with topical Fluorouracil (5-FU) 5%, while excision and plastic surgery restoration were performed to treat the ulcerated cancer lesion on her scalp. Due to the interesting nature of this rare syndrome, we performed a literature review including case reports and case series on multiple-KA-like lesions syndromes and focusing on diagnosis and therapy approaches. We also conducted a comparison of patient reports, which included assessing the clinical appearance of the lesions and evaluating the success and progress or the failure of various treatment approaches that were implemented.

[Translated article] Dermoscopy of Squamous Cell Carcinoma: From Actinic Keratosis to Invasive Forms.

When the dermoscopy of squamous cell carcinoma and its precursors we differentiate among keratin-related, vascular, and pigment-related criteria. Non-pigmented actinic keratoses are characterized by the "strawberry pattern". Pigmented actinic keratosis shows a significant dermatoscopic overlap with lentigo maligna, but the presence of pigmented scales, erythema, and prominent follicles favors its diagnosis. Bowen's disease is characterized by clustered glomerular vessels, white-yellowish scales, and brown or grey dots arranged in lines in its pigmented variant. Finally, dermoscopy allows us to detect invasive squamous cell carcinoma in its early stages and differentiate it from its precursors. Furthermore, its presentation may vary depending on the degree of differentiation, with keratin-associated criteria predominating in well-differentiated tumors, while an atypical vascular pattern will predominate in poorly differentiated tumors.

Dermoscopy of Squamous Cell Carcinoma: From Actinic Keratosis to Invasive Forms. / Dermatoscopia del carcinoma epidermoide: de la queratosis actínica a las formas invasivas.

When performing the dermoscopy of squamous cell carcinoma and its precursors we differentiate among keratin-related, vascular, and pigment-related criteria. Non-pigmented actinic keratoses are characterized by the "strawberry pattern". Pigmented actinic keratosis shows a significant dermatoscopic overlap with lentigo maligna, but the presence of pigmented scales, erythema, and prominent follicles favors its diagnosis. Bowen's disease is characterized by clustered glomerular vessels, white-yellowish scales, and brown or grey dots arranged in lines in its pigmented variant. Finally, dermoscopy allows us to detect invasive squamous cell carcinoma in its early stages and differentiate it from its precursors. Furthermore, its presentation may vary depending on the degree of differentiation, with keratin-associated criteria predominating in well-differentiated tumors, while the atypical vascular pattern will predominate in poorly differentiated tumors.

Clinical factors associated with skin neoplasms in individuals with Lynch syndrome in a longitudinal observational cohort.

BACKGROUND: Little is known about patient-specific risk factors for skin neoplasia in individuals with Lynch syndrome (LS). OBJECTIVE: Identify clinical factors associated with development of skin neoplasms in LS. METHODS: Clinical data were systematically collected on a cohort of LS carriers (confirmed pathogenic germline variants in MLH1, MSH2, MSH6, PMS2, or EPCAM) age ≥18 undergoing clinical genetics care at Dana-Farber Cancer Institute from January 2000 to March 2020. Multivariable logistic regression was performed to evaluate clinical factors associated with skin neoplasia. RESULTS: Of 607 LS carriers, 9.2% had LS-associated skin neoplasia and 15.0% had non-LS-associated skin neoplasia; 58.2% (353/607) had documentation of prior dermatologic evaluation; 29.7% (38/128) with skin neoplasms lacked a history of visceral LS-associated malignancy. LS-associated skin neoplasms were significantly associated with male sex, age, race, MLH1 pathogenic germline variants, MSH2/EPCAM pathogenic germline variants, and personal history of non-LS skin neoplasms. Non-LS-associated skin neoplasms was significantly associated with age, number of first- and second-degree relatives with non-LS-associated skin neoplasms, and personal history of LS-associated skin neoplasms. LIMITATIONS: Single-institution observational study; demographic homogeneity. CONCLUSIONS: Skin neoplasms are common in individuals with LS. We identified clinical factors associated with LS- and non-LS-associated skin neoplasms. Regular dermatologic surveillance should be considered for all LS carriers.

Intralesional 5-fluorouracil as a management for cutaneous squamous cell carcinomas: A rural Australian retrospective case series.

While the gold standard treatment for cutaneous squamous cell carcinomas (cSCCs) is surgical removal, there is a risk of infection, cosmetic and functional deficits. Intralesional 5-fluorouracil (5-FU) has been shown to be a potential non-surgical treatment modality for cSCCs in the literature. The aim was to investigate the safety and feasibility of using intralesional 5-FU to treat cSCCs. A literature review was conducted and a retrospective case series analysed patients who commenced intralesional 5-FU treatment for at least one cSCC between 1 January 2018 and 1 January 2019 at a private clinic in Orange, Australia. Inclusion criteria include: at least one cSCC was treated; only intralesional 5-FU was used; and treatment was ceased due to complete or inadequate remission, or adverse effects. There were 15 patients (7 female, 8 male, 60-99 years) and 20 out 21 cSCC lesions (82.6%) cleared while one lesion (4.3%) recurred. Six lesions (26.1%) ulcerated, four lesions became infected (17.4%) and one patient had an allergic reaction. The average number of treatments required for clearance was four (range 1-35), and the average 5-FU dose used was 75 mg (range 50-150 mg). Across 25 studies, 656 out of 708 lesions cleared (92.66%). Adverse effects were self-limiting and mostly well-tolerated. Intralesional 5-FU is an affordable and non-invasive non-surgical treatment modality that appears feasible to use for cSCCs and has a relatively low treatment-associated morbidity. Future clinical trials can help develop a protocol to guide clinicians in its use.

[Keratoacanthoma of the penis: A case report and literature review].

OBJECTIVE: To explore the clinical characteristics and treatment options of keratoacanthoma (KA) of the penis. METHODS: We report the diagnosis and treatment of a case of penile keratoacanthoma in our hospital and review the literature. RESULTS: The patient was admitted due to the discovery of a "new lesion on the glans for 4 months," diagnosed with a penile tumor, underwent tumor resection surgery, with histopathological examination revealing squamous epithelial hyperplasia, thickening, and excessive keratinization. The postoperative pathological diagnosis was penile keratoacanthoma. There was no recurrence or metastasis during follow-up. CONCLUSION: KA is a relatively rare benign tumor with potential malignant transformation, and close follow-up is necessary postoperatively.

Multiple eruptive squamoproliferative lesions during anti-PD1 immunotherapy for metastatic melanoma: Pathogenesis, immunohistochemical analysis and treatment.

Treatment with anti-PD1 inhibitors may enhance the risk for developing low grade squamoproliferative skin tumors. Immunohistochemical (IHC) analysis of the immune tumor microenvironment (TME) allows exploration of the pathogenesis and relationship with the PD1/PDL1 axis. Patients with eruptive keratoacanthoma (KA)-like lesions were recruited from the Melanoma Institute Australia, a tertiary referral specialist melanoma treatment center from January 2015 to August 2017. Clinicopathologic evaluation and IHC features of tumor cells (PDL1 expression) and peritumoral microenvironment (PD1, FOXP3, PDL1, CD4:CD8 expressing cells) in 12 eruptive KA-like lesions, were compared with solitary KAs in age and sex matched non-anti-PD1 treated controls. Four patients with repeated episodes of eruptive KA-like and lichenoid lesions developing 2-7 months after commencing pembrolizumab for AJCC stage IV melanoma, were recruited. Eruptive KA-like squamoproliferative lesions occurred in sun exposed sites and in areas of resolving, concomitant or delayed lichenoid reactions. Histologically, the lesions were well-differentiated squamoproliferative lesions resembling infundibulocystic squamous cell carcinoma or KA. IHC of cases and controls revealed low PDL1 expression of both squamous tumor cells and the TME immune cells. The numbers of immunosuppressive FOXP3 positive Tregs and PD1-expressing T-cells were higher in the cases than the controls but the CD4:CD8 ratio (2:1) was similar. The patients best responded to acitretin and were managed surgically if they demonstrated neoplastic features. Accelerated squamoproliferative growth in actinically damaged keratinocytes associated with lichenoid eruptions may be unmasked in patients treated with anti-PD1 immunotherapy potentially contributed to by a local cutaneous immunosuppressed TME.

Development and validation of a HPLC-UV based method for the extraction and quantification of methotrexate in the skin.

An innovative and sensitive HPLC-UV method for the extraction and quantification of methotrexate (MTX) in skin layers was developed and validated. Owing to the physico-chemical characteristics of the drug and the nature of the tissue, it was necessary to use folic acid (FA) as an internal standard for MTX quantification in the dermis. MTX (and FA) analysis was performed on a Phenomenex Jupiter C18 column, using a 50 mm sodium acetate buffer (pH 3.6) and methanol mixture (87:13, v/v) as mobile phase, pumped at 1 ml/min. The absorbance was monitored at 290 nm. The method was selective, linear in the range 0.11-8.49 µg/ml for extraction solvent and 0.05-8.94 µg/ml for pH 7.4 phosphate-buffered saline, precise and accurate, with lower limits of quantitation of 0.11 µg/ml (extraction solvent) and 0.05 µg/ml (pH 7.4 phosphate-buffered saline). The method developed is suitable for the quantification of MTX in skin layers at the end of in vitro permeation experiments; the overall mass balance was 96.5 ± 1.4%, in line with the requirements of the Organisation for Economic Co-operation and Development guideline for the testing of the chemicals (Skin absorption: in vitro method).

Keratoacanthoma, committed stem cells and neoplastic aberrant infundibulogenesis integral to formulating a conceptual model for an infundibulocystic pathway to squamous cell carcinoma.

Keratoacanthomas (KAs) are distinctive tumors that are defined by their clinical and histopathological features. Their relationship and distinction from squamous cell carcinoma (SCC), however, remain controversial. All cytogenic and immunohistochemical markers that have been applied in this quest have failed. A close relationship of KAs to hair follicles has been recognized. The descriptive term infundibulocystic or infundibular SCC was introduced to define a more broad-based pathway encompassing KAs. The follicular infundibulum roles in respect to neoplasia and wound healing are important elements in understanding the pathogenesis of KAs. Mouse models for KA have provided insights into the relationship of KA to follicles and SCCs. These advances and together with the diverse clinical and histopathological aspects of KA have contributed to the formulation of a conceptual pathway. The central element is that ultraviolet (UV)-mutated or activated committed infundibular stem cells are driven by the combination of a mutated oncogenic RAS pathway linked with the Wnt/beta-catenin pathway responsible for stem cell maintenance, hair follicle development, wound healing and driving KA proliferation and terminal keratinization. The existence and activation of this mutated pathway may form the basis of the paradoxical emergence of KAs and SCCs in patients receiving BRAF and PD-1 inhibitor therapy.

Intralesional methotrexate in dermatology: Diverse indications and practical considerations.

Intralesional methotrexate (IL-MTX) is a long-established treatment, which is arguably underutilized by dermatologists. We describe the underlying evidence base and practical considerations for its broad range of cutaneous indications, including in cutaneous oncology (keratoacanthomas, squamous cell carcinomas, lymphomas), inflammatory dermatology (nail psoriasis, plaque psoriasis, pyoderma gangrenosum, cutaneous Crohn's disease, amyloidosis), cutaneous infections (viral warts) and for treatment of filler complications. In certain circumstances, IL-MTX can be more efficacious and less invasive than other treatments, with fewer adverse effects. Dermatologists should consider using IL-MTX for a range of recalcitrant cutaneous conditions, particularly for those patients not amenable to surgery or systemic therapy.

Dermatoscopic findings and dermatopathological correlates in clinical variants of actinic keratosis, Bowen's disease, keratoacanthoma, and squamous cell carcinoma.

Non-melanoma skin cancer (NMSC), predominantly squamous cell carcinoma (SCC) and basal cell carcinoma, is increasing worldwide. Dermatoscopy, which is one of the non-invasive diagnostic techniques, is important for early diagnosis of NMSC. In this study we aimed to determine dermatoscopic features of keratinocyte derived tumors including actinic keratosis (AK), Bowen's disease (BD), keratoacanthoma (KA), and SCC and correlate the dermatoscopic findings with pathology. A total of 242 lesions from 169 patients were included in the study and dermatoscopic and dermatopathological findings of the lesions were retrospectively studied. Revised pattern analysis was used for the dermatoscopic evaluation. Among 242 lesions, 145 were clinically flat (86 AK, 30 BD, and 29 SCC). Presence of vessels, ulceration, fiber sign, keratin mass, and blood spots decreased the probability of a lesion being AK. When the differential diagnosis was considered between KA and SCC vs AK and BD; vessel presence, ulceration, fiber sign, blood spots, white structureless, keratin, and centred vessels favored the diagnosis of KA and SCC. Our results may contribute to the determination of the lesions to be biopsied in patients with multiple AK on chronically sun damaged skin. In non-pigmented lesions when a final diagnosis cannot be established, knowledge of dermatopathologic and dermatoscopic correlation may significantly assist interpretation of dermatoscopic patterns and clues.

Debulking followed by intralesional 5-fluorouracil for the treatment of cutaneous squamous cell carcinoma and keratoacanthoma: A retrospective analysis.

Debulking followed by intralesional 5-fluorouracil (deb-IL5FU) is a nonsurgical modality which has been used to treat skin cancer anecdotally for many years. There are few in depth studies examining this technique and success rate of intralesional 5-fluorouracil (IL5FU) for the treatment of cutaneous squamous cell carcinoma (cSCC). To evaluate the response rate of deb-IL5FU for the treatment of cSCC and to determine which patient factors were associated with tumor clearance or treatment failure. A retrospective chart analysis of patients with the diagnosis of cSCC or keratoacanthoma (KA) and subsequent deb-IL5FU treatment. Sixty-one patients with a total of 315 tumors (cSCC and KA), were treated using deb-IL5FU. The overall tumor clearance rate was 89%. This was highest for well-differentiated SCC, SCC, KA-type SCC, and KA. Tumors on the trunk and extremities showed high clearance rates while tumors on the scalp/face/neck/ears showed lower clearance rates. Immunocompetent patients cleared more tumors compared to immunocompromised patients. Limitations included the retrospective nature of this analysis as well as a small sample size. Treatment of cSCC and KA with deb-IL5FU demonstrated high tumor clearance rates. Lower rates of clearance were seen in males, immunosuppressed patients, tumors located on the scalp and face/neck/ears.

Evaluation of relationship between antihypertensive drug usage and dermatoscopic features in patients with keratinizing skin cancer.

Keratinizing skin cancers including actinic keratoses (AK), in situ squamous cell carcinoma/Bowen's disease/intraepidermal carcinoma (IEC), invasive cutaneous squamous cell carcinoma (cSCC) and keratoacanthoma share similar dermatoscopic features and also reveal different patterns that assist in their diagnosis. Recently epidemiological studies reveal the association between antihypertensive drugs and skin cancer risk, especially cSCC. This study aims to determine the dermatoscopic features of keratinizing skin cancer in patients using antihypertensive drug and compare with non-users. A total of 46 patients with 64 keratinizing skin cancer lesions were included in the study. The demographic, clinical characteristic of patients, the number, duration, localization and dermatoscopic features from each lesion were collected. First, we evaluated the dermatoscopic features according to the histopathologic diagnosis. Then, all patients were divided into two groups as users of antihypertensive drugs and non-users. The dermatoscopic features were compared in terms of antihypertensive drug usage and histopathologic diagnosis in antihypertensive drug users and non-users, separately. The users of anti-hypertensive drugs were 22 (47,8%) and non-users 24 (52,2%). Of the total 64 lesions including 47 AK, 5 IEC, 10 cSCC, and 2 keratoacanthoma were evaluated. White structureless area was found statistically significant in cSCC lesions of patients using antihypertensive drugs (P = .004). This finding in cSCC may be a clue for antihypertensive drug usage and these drugs may be a predisposan factor for dermal fibrosis. Regardless of histopathology, dermatoscopic features show no statistically difference between antihypertensive drug users and non-users (P > .05). Clearer results can be obtained by conducting more detailed and long-term studies.

Patient and Tumour Characteristics of Keratoacanthoma in a Large, Community-based Cohort Study from Queensland, Australia.

Keratoacanthomas are common keratinocyte skin tumours. However, there is little community-based data published on the clinical features of keratoacanthoma. The aim of this study was to describe the patient and tumour characteristics of keratoacanthomas, as well as their treatment patterns. Data were obtained from the QSkin Sun and Health study, a prospective cohort of 40,438 randomly sampled and consented participants aged 40-69 years in Queensland, Australia. In 2010, a baseline survey collected data, including demography, phenotype, ultraviolet radiation exposure, medical history and lifestyle. Histopathological reports of keratoacanthomas arising until 30 June 2014 were reviewed. In total, 584 participants developed 738 keratoacanthomas; 18% of participants developed multiple tumours. Common patient characteristics were male sex (58%), age ≥60 years (76%), fair skin (80%), and previous history of actinic keratoses/keratinocyte cancers (89%). Keratoacanthomas were commonly located on the legs/feet (48%), and rarely on the the head/neck (7%). Excision was the most frequently used surgical method (71%) Evidence of histopathological regression was reported in 67% of keratoacanthomas, suggesting a potential for spontan-eous resolution in a significant proportion of keratoacanthomas.

The first report of diagnosing of keratoacanthoma in Chinese Han patients using dermoscopy and reflectance confocal microscopy.

BACKGROUND: Keratoacanthoma (KA) is a special kind of tumor, which is regarded as a variant of squamous cell carcinoma (SCC) in some academic disciplines. But differentiating KA from SCC remains a diagnostic challenge. The noninvasive techniques dermoscopy and reflectance confocal microscopy (RCM) can provide new insights for diagnosis. OBJECTIVE: To observe the characteristics of KA under dermoscopy and reflectance confocal microscopy (RCM), in order to gain experience and reference for clinicians to facilitate earlier diagnosis. METHODS: We collected two cases of KA, which were confirmed by clinical and histopathological examination. The two cases were examined by dermoscopy and RCM, respectively. Then, we collected the microscopic characteristics of KA lesions. RESULTS: The dermoscopy features of KA are concentric circles of central crater, keratin mass, keratin scale, and polymorphic vascular pattern. The RCM features are described as refractile crust, atypical honeycomb pattern, dark center cells, large round nucleated cells, dendritic cells, and linear or round vessels traversing dermal papillae in the dermis. CONCLUSION: KA has some specific dermoscopy and RCM features, which can provide a basis for doctors to diagnose and intervene earlier.

Differentiating keratoacanthoma from squamous cell carcinoma-In quest of the holy grail.

To distinguish keratoacanthomas from squamous cell carcinomas remains a diagnostic challenge in dermatopathology. Several immunohistochemical and cytogenetic markers have been evaluated; however, so far there has been no unequivocal evidence supporting practical application of any of these markers. Recent studies have evaluated the composition of tumor-associated immune infiltrate, in particular the number and distribution of CD123-positive plasmacytoid dendritic cells in making this distinction; but these cells also do not appear to be a consistent biomarker in distinguishing keratoacanthoma from squamous cell carcinoma.

Plasmacytoid dendritic cells in keratoacanthoma and squamous cell carcinoma: A blinded study of CD123 as a diagnostic marker.

BACKGROUND: Histopathologic distinction between keratoacanthoma (KA) and squamous cell carcinoma (SCC) is challenging. We surmised that a discriminatory immunostain would be clinically meaningful. Previous investigators have found CD123-positive plasmacytoid dendritic cells (PDCs) are more prominent in KA than SCC. We sought to determine if CD123 immunostaining might have value as a diagnostic test for distinguishing KA from SCC. METHODS: We used blinded, semi-automated image analysis to compare CD123 expression in 66 KAs and 63 SCCs in a tissue microarray. RESULTS: PDCs were present in both KA and SCC. Mean PDC frequency was higher in KA than SCC (14.2 vs 11.2 mean cells/0.0945 square mm) but the difference was not statistically significant (P = 0.1240). There was no significant difference in mean PDC cluster frequency, mean intratumoral PDC frequency, or the percentage of PDCs as proportion of the total mononuclear inflammatory cell infiltrate between KA and SCC. CONCLUSION: CD123 immunostaining is not a clinically useful test for distinguishing KA from SCC.