Keratoacanthoma Research Articles

A Case Report of a Keratoacanthoma of the Lip in a Pediatric Patient and Narrative Review.

Keratoacanthoma (KA) is a self-regressing cutaneous tumor sharing clinical and histopathological similarities with squamous cell carcinoma. It is relatively uncommon and presents diagnostic challenges, particularly in pediatric patients. This paper presents a case study of KA affecting the upper lip keratosis in a 6-year-old girl. Through a comprehensive analysis of the pathogenesis, differential diagnosis, and treatment approaches of KA in children based on existing literature, we aim to offer clinical insights and guidance for practice.

Keratoacanthoma versus Squamous-Cell Carcinoma: Histopathological Features and Molecular Markers.

Considerable controversy exists within the field of dermatopathology in differentiating keratoacanthoma (KA) from squamous-cell carcinoma (SCC). KAs are rapidly growing, benign squamous tumors that are typically well differentiated. This controversy stems from the diverging perspectives on the management, classification, and diagnosis of each entity. Many believe that KAs are benign neoplasms in which intervention may be unnecessary since they are self-limiting and resolve on their own. On the other hand, SCC needs to be treated, as it carries significant morbidity and mortality risks. Early diagnosis and treatment are vital to prevent serious consequences of SCC. Nevertheless, KAs may resemble SCC grossly and microscopically. Various ancillary tests, including immunohistochemical (IHC) staining, have been proposed to differentiate between these entities, though mixed patterns of expression can limit the diagnostic utility of these techniques. Research into this topic is ongoing, with newer genetic and molecular findings illuminating the previously difficult-to-understand aspects of KA and increasing our understanding of this entity. In this review, KA and SCC will be compared along the lines of histological features, genetic, immune, and molecular markers, differential diagnosis, and management to clarify the similarities, differences, and misconceptions about both entities.

Gene expression landscape of cutaneous squamous cell carcinoma progression.

Cutaneous squamous cell carcinomas (cSCCs) are the second most common human cancer and have been characterized by RNA sequencing (RNA-Seq); however, the transferability of findings from individual studies may be limited by small sample sizes and diverse analysis protocols. To define the transcriptome landscape at different stages in the progression of normal skin to cSCC via a meta-analysis of publicly available RNA-Seq samples. Whole-transcriptome data from 73 clinically normal skin samples, 46 actinic keratoses (AK) samples, 16 in situ SCC samples, 13 keratoacanthoma (KA) samples and 147 cSCC samples [including 30 samples from immunocompromised patients and 8 from individuals with recessive dystrophic epidermolysis bullosa (RDEB)] were uniformly processed to harmonize gene expression. Differential expression, fusion detection and cell-type deconvolution analyses were performed. Individual RNA-Seq studies of cSCC demonstrated study-specific clustering and varied widely in their differential gene expression detection. Following batch correction, we defined a consensus set of differentially expressed genes (DEGs), including those altered in the preinvasive stages of cSCC development, and used single-cell RNA-Seq data to demonstrate that DEGs are often - but not always - expressed by tumour-specific keratinocytes (TSKs). Analysis of the cellular composition of cSCC, KA and RDEB-cSCC identified an increase in differentiated keratinocytes in KA, while RDEB-cSCC contained the most TSKs. Compared with cSCC arising in immunocompetent individuals, cSCC samples from immunosuppressed patients demonstrated fewer memory B cells and CD8+ T cells. A comprehensive and unbiased search for fusion transcripts in cSCC and intermediate disease stages identified few candidates that recurred in >1% of all specimens, suggesting that most cSCC are not driven by oncogenic gene fusions. Finally, using Genotype-Tissue Expression (GTEx) data, we distilled a novel 300-gene signature of chronic sun exposure that affirms greater cumulative ultraviolet (UV) exposure in later stages of cSCC development. Our results define the gene expression landscape of cSCC progression, characterize cell subpopulation heterogeneity in cSCC subtypes that contribute to their distinct clinical phenotypes, demonstrate that gene fusions are not a common cause of cSCC and identify UV-responsive genes associated with cSCC development.

Identifying SCC Lesions Capable of Spontaneous Regression by Using Immunohistochemistry: A Systematic Review and Meta-Analysis.

Keratoacanthoma (KA) and squamous cell carcinoma (SCC) are two cutaneous conditions with morphological resemblance, which can complicate the diagnosis in some cases. Using immunohistochemistry staining of biomarkers could be beneficial in resolving this obstacle. We investigated a variety of biomarkers assessed in different studies in order to find the most important and helpful biomarkers for differentiation between SCC and lesions capable of spontaneous regression. MEDLINE via PubMed and Google Scholar database were used to identify relevant literature up to 15 June 2022. The aim of our analyses was to determine the capability of biomarkers to distinguish between SCC and lesions capable of spontaneous regression using calculated individual and pooled odds ratios (OR) and 95% confidence intervals (CI) and I2 tests. Six potential biomarkers were CD10 with pooled OR= 0.006 (95% CI: 0.001-0.057) and I2=0%; COX-2 with pooled OR=0.089 (95% CI: 0.029-0.269) and I2=17.1%; elastic fibers with pooled OR= 6.69 (95% CI: 2.928-15.281) and I2=0%; IMP-3 with pooled OR=0.145 (95% CI: 0.021-1.001) and I2=44.5%; P53 with pooled OR=0.371 (95% CI: 0.188-0.733) and I2=55.9%; AT1R with OR=0.026 (95% CI: 0.006-0.107). We suggest the utilization of the following IHC biomarkers for discrimination between lesions with spontaneous regression such as KA and SCC: CD10, COX-2, and elastic fibers.

Intralesional Methotrexate Injection for the Treatment of Epithelial Crateriform Tumor.

Intralesional methotrexate injection (IL-MTX) is an appropriate strategy for treating epithelial crateriform tumors (ECTs) when surgical excision can result in functional or cosmetic defects; however, not all ECTs are responsive to this treatment. This study aimed to evaluate the effectiveness of IL-MTX for ECTs and to determine the differences in clinical response according to the pathological features. The medical records of patients treated with IL-MTX for their ECTs were retrospectively reviewed. Effectiveness was evaluated in terms of size reduction and flattening. Twenty-five cases of ECTs with biopsy were included in this study. Eight cases of keratoacanthoma (KA) and 15 cases of squamous cell carcinoma (SCC) were identified, but 2 cases could not be clearly distinguished. Seventeen patients (68%) showed a response after injection, and response rate in KA and SCC were 75% (6/8) and 60% (9/15), respectively. Nine patients showed complete resolution with IL-MTX. Patients received 3 injections, and regression was observed in 7.56 weeks after the first injection. According to histopathological results, patients with KA and SCC received 2 and 3.33 injections, respectively, and complete resolution was observed after 7 and 7.67 weeks, respectively. IL-MTX is safe and effective, and could be considered as a useful non-surgical treatment option for ECTs. Both KA and crateriform SCC showed good response; However, KA showed a better response.

Combined treatment of a giant palpebral keratoacanthoma

Aims/Purpose: To highlight the relevance of a therapeutic approach adapted to the clinical characteristics of the eyelid lesion found at the time of surgery to ensure an optimal functional and aesthetic result.Methods: Clinical case assessed, intervened and followed up at our centre.Results: A 76‐year‐old woman consulted for a nodular umbilicated lesion of recent appearance on the outer third of the upper eyelid of the left eye (UELE) measuring 0.5 cm in greatest diameter and 0.5 cm in elevation. The patient was placed on the waiting list for surgical excision and subsequent pathological examination (PE) of the lesion to confirm the initial clinical suspicion of keratoacanthoma (KA). One month later, the patient went to the operating room for surgery. During this time the lesion increased its initial size by more than 4 times, had a large necrotic centre, active borders and generated an evident left mechanical ptosis. As an alternative to the complete excisional surgery initially proposed, we offered the injection of neoadjuvant intralesional chemotherapy (CT) with the aim of reducing the size of the lesion to obtain a better functional and aesthetic result. The patient accepted this therapeutic alternative. KA was treated with weekly intralesional injections of 1 mL of methotrexate (MTX) 12.5 mg/mL. In our case, 3 injections were necessary to achieve a 78% reduction in the diameter of the lesion to allow reconstruction of the UELE with grafting of the contralateral upper eyelid. One week after the third injection of MTX, reconstruction of the UELE was performed after excisional surgery with wide margins for PE. One week later, the PE result ruled out malignancy and the graft had a pink appearance with complete vascular permeability, so the sutures were removed. Two weeks after reconstruction, the functional and aesthetic results were satisfactory.Conclusions: Therefore, in our experience, we recommend the above combined treatment for giant palpebral KA and stress the relevance of a therapeutic approach adapted to the clinical characteristics of the palpebral lesion at the time of surgery to ensure an optimal functional and aesthetic outcome.

Intralesional Treatments for Invasive Cutaneous Squamous Cell Carcinoma.

Cutaneous squamous cell carcinoma (cSCC) is the second most frequent cancer in humans and has the potential to progress locally, metastasize, and cause death in a subset of patients. cSCC is especially common in the elderly, and it will probably represent a major health concern in the near future. Surgery is the standard treatment for cSCC, but intralesional therapies can sometimes be considered for certain patients and under certain circumstances. The choice of intralesional treatment depends on the patient's characteristics and the clinician's previous experience and expertise. Here we are reviewing intralesional treatments for cSCC and keratoacanthoma (KA). We have started with some classic drugs, such as methotrexate and 5-fluorouracil, bleomycin, interferon, and cryosurgery, but also comment on electrochemotherapy. Finally, we have focused on novel therapies, some of which are under development, and future perspectives, including intralesional immunotherapy and oncolytic viruses.

Two Cases of Unusual Clinical Features of Keratoacanthoma

The Iraqi and the Yemeni dental literature lack documentation of keratoacanthoma (KA). It uncommonly appears at the mucocutanous junction and very rarely reported to arise in the mucous membrane. Nevertheless, it has such a chance; therefore, it is necessary to bring the attention of dental practitioners to this lesion. It is a benign epithelial tumor that frequently affects the face of old people. It usually, appears as an exophytic nodule with a central keratin plug that grows rapidly but with several poses. Clinically and microscopically KA is similar to squamous cell carcinoma (SCC) and can be occasionally misdiagnosed therefore it is important to be biopsied and carefully interpreted. This report presents two clinically unusual cases of KA.

Multiple keratoacanthoma Involving Lower Lip: Case Report and literature review

Keratoacanthoma (KA) is a benign epithelial proliferative lesion which frequently occurs on the sun exposed areas of the skin. KA originates within the pilosebaceous apparatus of the skin, may be solitary or multiple and character by spontaneous resolution. Keratoacanthoma is believed to have a good prognosis despite its clinical and histological resemblance to well differentiated squamous cell carcinoma (SCC). The aim of this paper is to briefly review and discuss the literature about multiple keratoacanthoma involving the lower lip in a 67-year-old male.

Simultaneous dual-wavelength digital holographic microscopy as a tool for the analysis of keratoacanthoma skin samples

A keratoacanthoma (KA) skin tumor is usually caused by sun exposure and may be an alert sign prior to the development of a more aggressive tumor or skin cancer. Studying the shape of the KA cells and their 3D rendering visualization are important parameters to prevent its evolution to higher stages of tumor cells or skin cancer. KA cells shape can be obtained through digital holographic microscopy; for that purpose, a setup with two illumination wavelengths (532 and 638 nm) is implemented to render a synthetic wavelength of 3.2 μm that avoids wrapping the optical phase of the processed holograms and increases measurement range. To recover the optical phase, two off-axis digital holograms are simultaneously recorded at each wavelength. From the processed hologram height variations, the shape and length of KA cells, as well as the stratum corneum epidermal layer, are obtained as phase images. The results achieved aid to discriminate healthy from malignant cells.

Aberrant p16, p53 and Ki-67 immunohistochemistry staining patterns can distinguish solitary keratoacanthoma from cutaneous squamous cell carcinoma

Keratoacanthoma (KA) is widely considered a benign, usually self-resolving, neoplasm distinct from cutaneous squamous cell carcinoma (cSCC), while some consider KA to be indistinguishable from cSCC. Published studies indicate utility for p16, p53, Ki-67 immunostaining and elastic van Gieson (EVG) in the assessment of KA and cSCC. We compared clinical features and staining patterns for p16, p53, Ki-67 and EVG in fully excised KA, cSCC with KA-like features (cSCC-KAL) and other cSCC (cSCC-OTHER). Significant differences between KA, cSCC-KAL and cSCC-OTHER were found for head and neck location (20%, 86%, 84%), and duration <5 months (95%, 63%, 36%). KA shows both a mosaic pattern for p16 (>25-90% of neoplasm area) and peripheral graded pattern for p53 (up to 50% moderate and strong nuclear staining) in 92% compared with 0% of cSCC-KAL and 0% of cSCC-OTHER. In contrast, a highly aberrant pattern (usually null) for one or both p16 and p53, was present in 0% of KA, 83.8% of cSCC-KAL and 90.9% of cSCC-OTHER. Abnormal distribution of Ki-67 beyond the peripheral 1-3 cells was uncommon in KA (4.2%) and common in cSCC-KAL (67.6%) and cSCC-OTHER (88.4%). Moderate to striking entrapment of elastic and collagen fibres was present in the majority of KA (84%), cSCC-KAL (81%) and cSCC-OTHER (65%). KA are clinically distinct neoplasms typically of short duration occurring preferentially outside the head and neck and generally lacking aberrations of p16, p53 and Ki-67, compared with cSCC that have high rates of aberrant or highly aberrant p16, p53 and Ki-67, but EVG lacked specificity.

Distinguishing Keratoacanthoma from Well-Differentiated Cutaneous Squamous Cell Carcinoma Using Single-Cell Spatial Pathology

Keratoacanthoma (KA) is a common keratinocyte neoplasm that is regularly classified as a type of cutaneous squamous cell carcinoma (cSCC) despite demonstrating benign behavior. Differentiating KA from well-differentiated cSCC is difficult in many cases due to the substantial overlap of clinical and histological features. Currently, no reliable discriminating markers have been defined, and consequently, KAs are often treated similarly to cSCC, creating unnecessary surgical morbidity and healthcare costs. In this study, we used RNA sequencing to identify key differences in transcriptomes between KA and cSCC, which suggested divergent keratinocyte populations between each tumor. Imaging mass cytometry was then used to identify single-cell tissue characteristics, including cellular phenotype, frequency, topography, functional status, and interactions between KA and well-differentiated cSCC. We found that cSCC had significantly increased proportions of Ki67+ keratinocytes among tumor keratinocytes, which were dispersed significantly throughout non-basal keratinocyte communities. In cSCC, regulatory T-cells were more prevalent and held greater suppressive capacity. Furthermore, cSCC regulatory T-cells, tumor-associated macrophages, and fibroblasts had significant associations with Ki67+ keratinocytes as opposed to avoidances with KA, indicating a more immunosuppressive environment. Our data suggest that multicellular spatial features can serve as a foundation to enhance the histological discrimination of ambiguous KA and cSCC lesions.

Mechanism underlying follicular hyperproliferation and oncogenesis in hidradenitis suppurativa

Hidradenitis suppurativa (HS) is a skin disorder that causes chronic painful inflammation and hyperproliferation, often with the comorbidity of invasive keratoacanthoma (KA). Our research, employing high-resolution immunofluorescence and data science approaches together with confirmatory molecular analysis, has identified that the 5'-cap-dependent protein translation regulatory complex eIF4F is a key factor in the development of HS and is responsible for regulating follicular hyperproliferation. Specifically, eIF4F translational targets, Cyclin D1 and c-MYC, orchestrate the development of HS-associated KA. Although eIF4F and p-eIF4E are contiguous throughout HS lesions, Cyclin D1 and c-MYC have unique spatial localization and functions. The keratin-filled crater of KA is formed by nuclear c-MYC-induced differentiation of epithelial cells, whereas the co-localization of c-MYC and Cyclin D1 provides oncogenic transformation by activating RAS, PI3K, and ERK pathways. In sum, we have revealed a novel mechanism underlying HS pathogenesis of follicular hyperproliferation and the development of HS-associated invasive KA.

Solitary Keratoacanthoma at the Recipient Site of a Full-Thickness Skin Graft: A Case Report and Review of the Literature.

A 57-year-old man presented with a pigmented papule, 0.4 cm in diameter, on the left lower eyelid. Skin biopsy revealed a basal cell carcinoma, which was excised through a wide excision followed by a full-thickness skin graft (FTSG). Two weeks after the surgery, an erythematous nodule developed in the lower margin of the graft recipient site. The nodule size increased rapidly over 2 weeks, becoming dome-shaped with a central hyperkeratotic plug. A diagnosis of keratoacanthoma (KA) was made, and surgical excision was performed. Histological findings revealed a large, well-differentiated squamous tumor with a central keratin-filled crater and buttress. The human papilloma virus (HPV) genotyping results were negative. Risk factors for KA include trauma, old age, exposure to ultraviolet (UV) radiation, immunosuppression, and HPV infection. KA has most often been reported to develop at the donor site. Although the pathogenesis of KA is unclear, trauma is believed to act as a second insult to a preceding oncogenic insult, such as exposure to UV radiation, resulting in a koebnerization. Herein, we report a case of solitary KA at a FTSG recipient site. This report presents information that may provide guidance during dermatologic surgeries.

The diagnostic value of imaging techniques for keratoacanthoma: A review

Keratoacanthoma (KA) is a fast-growing skin tumor with solitary KA being the most common type. KAs rarely metastasize and subside spontaneously. Although histopathology is the gold standard for the diagnosis of KA, its histopathological features are sometimes difficult to distinguish from those of other skin tumors. Imaging studies have certain advantages in the preoperative diagnosis of KA; they not only show the exact shape of the lesion but can also accurately determine the extent of the lesion. Combined with histopathological examination, these findings help establish a diagnosis. By summarizing the imaging features of KA, this article aimed to improve radiologists' understanding of the disease and help in the clinical and differential diagnosis of KA.

Diagnostic Approach to Keratoacanthoma : Differentiating with Squamous Cell Carcinoma

Keratoacanthoma (KA) is a cutaneous neoplasms from the pilosebaseous unit, characterized as a rapidly growing tumor and usually show spontaneous regression. A major difficulty in dealing with these neoplasms is to differentiating them from squamous cell carcinoma, clinically and histologically. However, the change for regression has led keratoacanthoma as benign tumors with different pathophysiological mechanism from cutaneous squamous cell carcinoma (cSCC). The similarities between keratoacanthoma and cSCC, especially the well-differentiated variant cSCC, has led to the general recommendation for surgical excision of keratoacanthoma to make sure that a potentially malignant cSCC is not left untreated. Differentiating KA with cSCC would change management strategies to the less invasive treatment modalities, prevent surgical morbidity, and reduce healthcare costs. Methods : We searched for relevant journal articles in PubMed with a systematic search using PICO, with the keyword “Keratoacanthoma“ or “Squamous cell carcinoma“ and “Diagnostic“ or “History, physical examination, histology“. We got 825 publications and we filtered by the last five years and we generated 12 publications from 2017-2022 after we checked from the title and abstract for relevancy. Conclusion : The review revealed that keratoacanthoma can be distinguished from squamous cell carcinoma from the biological differences of spontaneous regression, very rapid growth and the absence of malignant features. It can also be distinguished by the histological and immunohistochemistry examination such as the presence of epithelial lips, neutrophilic microabscesses within the atypical epithelium, firm boundaries between tumor and stroma, ulceration, many mitotic cells and pleomorphic or anaplastic. The study also show that CD1a and Hsp60 can help distinguish between KA and SCC.

To treat or not to treat: PD-L1 inhibitor-induced keratoacanthoma and squamous cell carcinoma.

Keratoacanthoma (KA) and squamous cell carcinoma (SCC) are rare side effects of programmed cell death ligand-1 (PD-L1) inhibitors that can disrupt therapy. There is no consensus on optimal treatment. We investigated the management strategy and factors influencing pathophysiology. An institutional cancer registry and literature search were used for this retrospective study. Only PD-L1-induced KA and SCC cases were included. Pathology specimens were stained with immune markers and management strategies were analyzed.Four cases were identified at our institution. Immunohistochemistry of atypical keratinocytes revealed PD-1/PD-L1 positivity, high p53, and low bcl-2 for all cases with differential expression of CD44 and beta-catenin for KA versus SCC. Nivolumab was continued or temporarily held with complete resolution. In addition, a literature search identified 30 additional cases of KA/SCC after PDL-1 inhibitor use. The most common treatment was excision/destruction followed by topical and/or intralesional corticosteroids. Therapy was definitely withheld in 22% of KA patients and in 9% of SCC cases. The expression of PD-L1 by atypical keratinocytes helps to explain the effects of nivolumab on the development of cutaneous neoplasms. The expression of immune markers provides mechanistic insights into pathophysiology. Management may be achieved with conservative therapy and without treatment interruption.

Low detection rate of human papillomavirus in patients with cutaneous squamous cell carcinoma and keratoacanthoma

The role of human papillomavirus (HPV) in keratoacanthoma (KA) remains unclear. To identify possible differences in HPV DNA, detected by next-generation sequencing (NGS), between KAs and cutaneous squamous cell carcinomas (cSCCs), which may suggest different pathogenesis. We extracted DNA from formalin-fixed and paraffin-embedded (FFPE) tissue blocks from samples of 151 patients (105 with cSCCs and 46 with KAs). HPV DNA was detected using the NGS-based Ezplex®kit. HPV detection rates and other clinical characteristics were compared. HPV was detected in 6.7% (7/105) of cSCC and 10.9% (5/46) of KA samples. Eight alpha-HPV genotypes (16, 57, 81, 31, 33, 45, 53, and 58) were detected, with HPV 16 being the most common. Only one type (57) is commonly classified as cutaneous type, and the rest are all mucosal types. HPV detection rate did not significantly differ between the KA and cSCC groups. HPV detection was relatively low in KA and cSCC samples. HPV might be related to the pathogenesis of only selected KA and cSCC cases.

33407 Accuracy of clinical-dermatoscopic versus dermatopathologic diagnosis of melanoma and nonmelanoma skin cancer

Results from a retrospective, quantitative, cross-sectional study to assess the agreement and accuracy of the clinical dermatoscopic diagnosis of melanoma and nonmelanoma SC in comparison with dermatopathologic examinations. In total, 3205 patients were evaluated, with a 67-year mean age. Of these patients, 1603 (50.1%) had a clinical-dermatoscopic hypothesis of AC, with 859 (53.4%) being female and 744 (46.6%) being male patients. Of the suspected cases, 1300 had a clinical-dermatoscopic diagnosis of BCC; 230, SCC; 34, MM; and 39, keratoacanthoma (KA), with a dermatopathologic confirmation of 90.85%; 67.39%; 93.5%; and 85.64%, respectively. The clinical dermatoscopic versus dermatopathologic agrement for all the SC was statistically significant, according to Kappa coefficient and chi-square test. For KA, our accuracy was 85.64%, and these data are the first publication that correlate the clinical dermatoscopic suspect of KA with dermatopathologic confirmation. Our findings show our BCC clinical accuracy (90.85%) is in accordance with the literature. However, for SCC and MM, we had an accuracy greater than what had been published until then, respectively, 67.39 and 93.5%. In conclusion, an exact diagnosis of SCC depends on clinical, dermatoscopic, and histopathologic criteria. Likewise, MM, in which clinical diagnosis’ assertiveness is only 76%, SCC’s clinical diagnosis may be considered a fragile issue because KA is often confused with SCC. In these cases, dermatoscopy has the ability to speed up the therapeutic management of SC which needs more immediate management, even more so when the dermatopathologic diagnosis, the gold-standard tool for diagnosing SC, may be delayed or not available.

35328 Morbidities associated with solitary keratoacanthomas

Background: Keratoacanthomas (KA) are classically described as benign tumors that undergo a period of rapid growth followed spontaneously regress several months later. Despite the propensity to naturally regress, most clinicians do not postpone treatment to wait for this to occur. This is likely due to the inability to predict maximal size and potential development of pain and extensive, local destruction and scarring. Some studies have also identified extensive perineural invasion as a complication of KAs.