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Surgical intervention is seen as the gold standard in the treatment of Squamous cell carcinoma. Yet, in cases of recurrence, repeated surgical procedures may unwittingly foment the rise of reactive keratoacanthomas at the surgical margins or edge of a newly placed skin graft.

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.

Background Sorafenib is an oral multikinase inhibitor that targets Raf serine/threonine receptor tyrosine kinases and inhibits tumor cell growth and angiogenesis. Cutaneous toxicities of sorafenib are common, including cutaneous eruptions (such as truncal erythema and seborrheic-dermatitis-like changes) and hand–foot syndrome. Keratoacanthomas and squamous cell carcinomas have been reported previously; however, we report a case of multiple eruptive keratoacanthomas in the form of Grzybowski syndrome after initiation of sorafenib. Case presentation We report a 63-year-old Caucasian male who developed multiple cutaneous eruptive keratoacanthomas after starting sorafenib 400 mg twice daily. He had a known history of hepatitis-C-related cirrhosis and hepatocellular carcinoma, and previously had actinic keratosis and skin squamous cell carcinoma excision. Approximately two and a half months after starting sorafenib, the patient initially developed two lesions, one on each forearm, and after excision, these lesions demonstrated histological features of squamous cell carcinoma. One month later, the patient presented with approximately 48 new skin lesions of varying size on the back, bilateral upper limbs, and face requiring excisional biopsy of a large number of these lesions. Histopathology showed eruptive invasive keratoacanthomas (Grzybowski syndrome). Sorafenib was temporarily stopped and subsequently restarted at a lower dose. Acitretin 25 mg daily was commenced after few weeks, and no further keratoacanthomas developed during his treatment. Conclusions We report a unique case of sorafenib-associated Grzybowski syndrome. Temporary interruption and dose reduction of sorafenib and use of acitretin appeared to prevent further development of keratoacanthomas.

The use of an automatic histopathological image identification system is essential for expediting diagnoses and lowering mistake rates. Although it is of enormous clinical importance, computerized breast cancer multiclassification using histological pictures has rarely been investigated. A deep learning-based classification strategy is suggested to solve the challenge of automated categorization of breast cancer pathology pictures. The attention model that acts on the feature channel is the channel refinement model. The learned channel weight may be used to reduce superfluous features when implementing the feature channel. To increase classification accuracy, calibration is necessary. To increase the accuracy of channel recalibration findings, a multiscale channel recalibration model is provided, and the msSE-ResNet convolutional neural network is built. The multiscale properties flow through the network’s highest pooling layer. The channel weights obtained at different scales are delivered into line fusion and used as input to the next channel recalibration model, which may improve the results of channel recalibration. The experimental findings reveal that the spatial recalibration model fares poorly on the job of classifying breast cancer pathology pictures when applied to the semantic segmentation of brain MRI images. The public BreakHis dataset is used to conduct the experiment. The network performs benign/malignant breast pathology picture classification collected at various magnifications with a classification accuracy of 88.87 percent, according to experimental data. The diseased images are also more resilient. Experiments on pathological pictures at various magnifications show that msSE-ResNet34 is capable of performing well when used to classify pathological images at various magnifications.

Programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors have demonstrated their efficacy in the treatment of various malignancies. Despite their benefits, their immunomodulatory activities can cause unpredictable cutaneous adverse events (CAE). This study aimed to identify characteristics of CAE in patients treated with PD-1/PD-L1 inhibitors through the medical records, photographs, and pathology reports. Fifty CAE occurred in 47 (2.75%) of 1711 patients treated with PD-1/PD-L1 inhibitors. Pruritic, psoriasiform, urticarial, and acneiform eruptions were the four most common types. Melanoma patients showed CAE more frequently than other malignancies. Acneiform eruption occurred more often at ages under 60 years. Urticarial eruption appeared earlier, while keratoacanthoma appeared later after immunotherapy. The overall survival times were not significantly different between the two groups with and without CAE by Kaplan-Meier analysis (p = 0.055). Studies on CAE may provide more information to understand these drugs and to help manage the patients.

Differentiating cutaneous diseases that mimic each other clinically and histopathologically can at times be a challenging task for the dermatopathologist. At the same time, differentiation of entities with overlapping features may be crucial for patient management. Although not seen in normal skin, plasmacytoid dendritic cells usually infiltrate the skin in several infectious, inflammatory/autoimmune and neoplastic entities. Plasmacytoid dendritic cells can be identified in tissue using specific markers such as CD123 and/or blood-derived dendritic cell antigen-2. Plasmacytoid dendritic cells are the most potent producers of type I interferons and their activity may therefore be assessed indirectly in tissue using human myxovirus resistance protein A, a surrogate marker for type I interferon production. In recent years, accumulating evidence has established the utility of evaluating for specific plasmacytoid dendritic cell-related parameters (plasmacytoid dendritic cell content, distribution and clustering and/ or human myxovirus resistance protein A expression) as a diagnostic tool in differentiating cutaneous diseases with overlapping features such as the alopecias, lupus and its mimics, and neoplastic entities. In this review, we provide an update on the current evidence on this topic and on the contexts where this can be a useful adjunct to reach the histopathological diagnosis.

Background Surgical excision is the paradigm treatment option for non-melanoma skin cancer (NMSC), however intralesional fluorouracil (IL 5-FU) is an efficacious alternative and superior to other chemotherapy agents in NMSC. Yet, little summative data exists on the topic. Objective To assess the efficacy of IL 5-FU in the treatment of NMSC. Methods and materials A systematic review was performed using PubMed, Embase and Web of Science databases. 19 studies were included. ANOVA test was used to compare the duration of lesion prior to therapy and resolution time following IL 5-FU treatment. A two-way proportion test was performed to compare the clearance rate between squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and keratoacanthoma (KA). Results There was no significant difference between the clearance rate of SCC and BCC after IL 5-FU therapy (87 % vs 91.4%, respectively; P=0.2); however, the clearance rate of both SCC and BCC was significantly greater than that of KA (74.5%; Pl0.007); 95% CI [2.56%n19.1%]. Lesion duration and resolution time did not significantly differ across SCC, BCC, and KA (Pg0.3). Conclusion While majority of data is derived from individual cases, IL 5-FU achieved higher clearance rate in SCC and BCC groups than in KA group. J Drugs Dermatol. 2021;20(2):192-198. doi:10.36849/JDD.2021.5518.

The distinction between Keratoacanthoma (KA) and Cutaneous Squamous Cell Carcinoma (cSCC) is critical yet usually challenging to discriminate clinically and histopathologically. One approach to differentiate KA from cSCC is through assessing the immunohistochemical staining patterns of the three indicators, β-catenin, C-Myc, and CyclinD1, which are critical molecules that play important roles in the Wnt/β-catenin signaling pathway. Ki-67, as a proliferation biomarker for human tumor cells, was also assessed as an additional potential marker for differentiating KA from cSCC. In this report, these four indicators were analyzed in 42 KA and 30 cSCC cases with the use of the computer automated image analysis system. Computer automated image analysis is a time-based and cost-effective method of determining IHC staining in KA and cSCC samples. We found that C-Myc staining was predominantly localized in the nuclei of basal cells within KA patients, whereas cSCC staining was predominantly localized in the nuclei of diffuse cells. This C-Myc staining pattern has a sensitivity of 78.6% and a specificity of 66.7% for identifying KA. Moreover, positive rates of distinct expression patterns of C-Myc and Ki-67 may also serve as a means to clinically distinguish KA from cSCC. Taken together, our results suggest that these markers, in particular C-Myc, may be useful in differentiating KA from cSCC.

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.

Keratinocyte skin cancers are the most frequent malignancy, accounting for approximately 30% of all cancers. Although beta genus HPV are the main etiologic agents for squamous cell carcinoma development in patients with epidermodysplasia verruciformis and organ transplant recipients, their role in non-melanoma skin cancer (NMSC) progression in the general population remains controversial. The aim of our review is to summarize current scientific data and to systematically analyse evidence regarding the role of HPV in keratinocyte skin cancers. A total of 2284 patients were included, of which 724 with actinic keratoses, 290 with Bowen's disease, 949 with cutaneous squamous cell carcinomas and 321 with keratoacanthomas. In the case of actinic keratoses, the majority were positive for beta (n = 372, 58.49%) and gamma HPV (n = 256, 40.25%) and only a few (n = 6, 0.94%) were positive for alpha subtypes. Similarly, most of the cutaneous squamous cell carcinomas were positive for beta (n = 248, 55.98%) and gamma HPV (n = 172, 33.82%) and 23 cases (2.42%) were positive for alpha subtypes. Bowen's disease lesions were mostly positive for beta (n = 43, 55.84%) and alpha HPV (n = 30, 38.96%), in contrast to the gamma genus (n = 4, 5.19%). Keratoacanthomas showed a high distribution among beta genus (n = 79, 50.31%) and an equal proportion between alpha (n = 39, 24.84%) and gamma (n = 39, 24.84%) genera. Studies published so far identifying HPV in keratinocyte skin cancers reflect the difference in detection methods rather than a type-specific tendency towards either actinic keratoses, Bowen's disease, squamous cell carcinoma or keratoacanthoma. On the other hand, recent evidence regarding the role of HPV vaccination in patients with non-melanoma skin cancer brings into perspective the idea of a beta-HPV vaccine or a combined alpha and beta-HPV vaccine that could be used as an adjuvant treatment measure in patients with recalcitrant non-melanoma skin cancer.

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.

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.

Keratoacanthoma (KA) is an epithelial tumor of the skin, classically considered as having a malignant transformation risk of 15%; however, many authors and the new World Health Organization (WHO) Classification of skin tumors consider KA as an incipient variant of the cutaneous squamous cell carcinoma (SCC). The aims of the study were to assess the clinical, histopathological (HP) and immunohistochemical (IHC) aspects of the KA and the role of these factors in malignancy occurrence. The studied group comprises 194 patients diagnosed with KA or malignant KA, hospitalized in the Clinic of Dermatology, Emergency County Hospital, Craiova, Romania, between 2006 and 2019. There were 83 males and 111 females, aged 34 to 90 years, 57.21% of the patients being from the rural environment. The histopathology diagnosed 51 KAs and 143 malignant KAs (SCCs). Clinical diagnosis had a limited value in detecting the absence or presence of malignancy in the KA lesion, due to a low accuracy (36.08% and 29.89%, respectively) and specificity (23.07% and 27.02%, respectively); therefore, the HP exam of the surgical excision specimen has a paramount importance in establishing the diagnosis. IHC analysis revealed that the immunostainings for apoptosis-associated proteins and keratinocyte proliferative activity [p53, B-cell lymphoma-2 (Bcl-2), Ki-67 and proliferating cell nuclear antigen (PCNA)] provide some arguments to differentiate between KA and SCC in the studied cases. The correlation of clinical, HP and IHC data lead to an accurate diagnosis of KA; moreover, the clinical, HP and IHC data sustain the idea that KA is a particular form of well-differentiated SCC, which require an active therapeutic attitude.

Pseudocarcinomatous hyperplasia (PCH) is a benign reactive epithelial proliferation that may be associated to lymphomas of the skin or external mucous membranes. We present a case of single lesion mycosis fungoides (Woringer-Kollop's reticulosis pagetoid) associated with PCH that was initially misdiagnosed as squamous cell carcinoma (SCC) and review all PubMed-indexed previously reported cases on lymphomas of the skin or external mucous membranes associated to PCH, SCC, and keratoacanthomas. Including our own case, we collected data of 114 cases of cutaneous or mucosal lymphoproliferative disorders associated to PCH, 3 cases associated to SCC, and other 3 cases associated to keratoacanthomas. All cases were tabulated to the following parameters whenever data was available: sex, age, previous medical conditions, number of lesions (single × multiple), site of involvement (mucosa, skin or both), clinical impression, initial equivocal histopathologic diagnosis, final diagnosis, keratinocytic atypia (presence × absence), lymphocytic atypia (presence × absence), CD30-status, and treatment.

Keratinocyte cancers are the most common malignancy among people with European ancestry, and are very common on sun-exposed areas of the head and neck. Incidence is directly correlated with latitude and annual ultraviolet radiation incidence, although there are a number of other environmental, occupational and genetic risk factors, and keratinocyte cancers become more common at middle age. Basal cell carcinomas (BCC) are the most common, comprising 80% of keratinocyte cancers, but have a very low rate of metastases and low mortality. Squamous cell carcinomas (SCC) make up 20% of keratinocyte cancers, and have relatively infrequent metastases, at 5-16%. While there are no precursor lesions for BCC, SCC represents the final stage in a spectrum of cellular atypia and dysplasia, from actinic keratoses to in situ SCC to invasive SCC. Dermoscopy is a well-established diagnostic tool for keratinocyte cancers, and reflectance confocal microscopy is emerging as another useful diagnostic tool, particularly on functionally and cosmetically sensitive sites like the face.

Clinical utility of intralesional methotrexate to distinguish crateriform keratinocytic tumors before surgeryDear Editors,Keratoacanthoma (KA) and cutaneous squamous cell carci-noma (CSCC) may adopt an identical crateriform morpho-logy. Nowadays, the debate about whether KA is a distinct entity, or a low-grade variant of cutaneous squamous cell carcinoma (CSCC) still persists. Since CSCC is a more ag-gressive neoplasm, misdiagnosing crateriform lesions may have a negative impact on the patient's prognosis. Evaluating a partial biopsy is extremely challenging to confidently dis-tinguish KA from CSCC [1]. No distinctive gene expression profiles have been identified and no pathognomonic criteria to unequivocally differentiate between KA and CSCC exist [2]. Consequently, the surgical approach remains the gold standard in the management of crateriform tumors, especi-ally those arising on the face.

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.

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Patients who present with multiple keratoacanthomas (KAs) associated with prurigo nodularis often pose a treatment challenge. These lesions often require aggressive treatment, such as Mohs micrographic surgery, surgical excision, electrodesiccation and curettage, intralesional steroid injection, and long-term acitretin. 5-Fluorouracil (5-FU) cream 5% has been shown to be effective; however, topical options are limited when 5-FU fails. We have found success using a high-potency topical steroid under occlusion, resulting in resolution of KAs and prurigo nodules.

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.

INTRODUCTION The nose is the most common area where malignant skin tumors occur. Repair with a flap after tumor excision provides esthetically and functionally acceptable results. In this study, we aimed to present the use of an omega (Ω) advancement flap, which can be applied in all anatomic regions of the nose, in 2 cm or smaller defects. METHODS Between 2015 and 2017, 18 patients underwent repair with omega (Ω) advancement flap in the nose after tumor removal. The pathology of 17 patients was basal cell carcinoma, and keratoacanthoma in 1 patient. The average defect diameter was 1.6 × 1.56 cm. The defects were in the nasal tip, nasal wing, lateral nasal wall, and supratip region. After tumors were excised from the safe margin, and were repaired using an omega advancement flap in the same session. RESULTS No flap necrosis, dehiscence, or infection was observed in the early postoperative period. Three patients developed hematoma under the flap, which was drained. No tumor recurrence was observed during the postoperative follow-up period. The results were satisfactory in all patients. CONCLUSION The omega advancement flap is a safe procedure that can be easily applied in the same session for the repair of small-to-medium-sized nasal defects.

Keratoacanthoma (KA) is a cutaneous tumor arising on sun-exposed skin and characterized by self-limiting growth and involution. We reported a case of a 92-year-old man presented a 4.5x3.5 cm nodular lesion with a central keratin-filled crater on his left cheek. We performed surgical excision and histopathological examination revealed a keratoacanthoma with perineural invasion. A close follow-up was carried out. (www.actabiomedica.it).

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.

Scalp lesions can be classified as congenital, traumatic, inflammatory, or neoplastic in origin. Although patients presenting with scalp masses are frequently seen in daily practice, differentiation of scalp lesions is often challenging for radiologists who are not familiar with the imaging of cutaneous lesions. The majority of scalp lesions are fortunately benign, with cystic lesions accounting for over 50% of all benign scalp lesions. Such lesions include trichilemmal cysts (pilar cysts), sebaceoma, epidermoid cysts, dermoid cysts, and teratoid cysts. Radiologists may also occasionally encounter benign neoplasms of the scalp, including melanocytic nevi, keratoacanthoma, pilomatricoma, neurofibroma, and lipoma. Malignant scalp tumors are uncommon; however, they carry a potential risk of delayed detection, resulting in poorer outcomes. Most scalp lesions show nonspecific imaging findings, although some possess characteristic features on CT and MRI. Radiologists must be familiar with the appearances of common scalp lesions to reach an accurate diagnosis. Hence, the aim of this article is to describe the clinical and imaging features of scalp lesions.

Background Eruptive squamous atypia (ESA), which is an idiopathic, sometimes koebnerizing, proliferation of atypical but well-differentiated keratinocytes (also termed eruptive keratoacanthoma), is often misdiagnosed as cancer and managed by excisional surgery, provoking further koebnerization. A clear definition of this phenomenon and treatment outcome data are lacking. Objective To define ESA and evaluate efficacy of intralesional (IL) 5-fluorouracil (5-FU) treatment. Methods A retrospective cohort study examined patients with ESA that arose spontaneously or within a recent surgical scar and was treated with IL 5-FU at a tertiary academic center between January 2008 and December 2016. Complete clearance, partial clearance, and number of surgical excisions performed were tabulated. Results Of 30 patients with 136 ESA lesions, 20 (67%) had resolution of ESA with IL 5-FU monotherapy. In all, 10 patients (33%) required additional therapy (topical 5-FU, steroids, cryotherapy, or acitretin). No IL 5-FU–treated ESA lesions required surgical excision. The number of excisional procedures decreased significantly (P = .006), with 27 patients (90%) needing fewer excisions 12 months after versus 12 months before initiation of IL 5-FU therapy. Dyspigmentation was the only adverse event. Limitations Limitations include retrospective analysis and use of data from a single institution. Conclusion With close clinical monitoring, IL 5-FU can be used to successfully treat ESA.

We appreciate the interest of the authors in our review of keratoacanthoma (KA).1 They raise several points that were discussed in our manuscript. First, they suggest that the histopathological differentiation from KA and well-differentiated squamous cell carcinoma (SCC) is not as problematic as reviewed; however, they qualify that an "adequate specimen is required" and "partial biopsies are not reliable." This is a key point we discussed, as a portion of biopsies may be too small to identify important architectural features or may be unrepresentative of the tumor, which limits the ability of the pathologist to distinguish between KA and SCC2-4 , and typically leads to an overcall of SCC to avoid a missed malignancy. Indeed, most experienced dermatopathologists can accurately discriminate between KA and SCC when an ample biopsy representative of the tumor is obtained. Second, they question the practicality of using the stereotypical triphasic evolution pattern of KA to aid in diagnosis and state that "patient history is likely to be unreliable."

Multiple self-healing squamous epithelioma (MSSE, Ferguson-Smith disease) and Loeys-Dietz syndrome (LDS) are allelic conditions associated with pathogenic variants in the transforming growth factor beta receptor 1 gene (TGFBR1). We describe a patient with a novel missense variant in this gene: c.664G > A, p.[Gly222Arg], who clinically presents with both syndromes. The patient also has a history of gastric antral vascular ectasia, which has not been reported previously in LDS.

BACKGROUND Sebaceous neoplasms (SN) may appear sporadically in the general population but may also be part of the Muir-Torre variant of Lynch syndrome (MT-LS). There are few studies in southern Europe on the incidence of MT-LS in the population of patients with SN. AIM To retrospectively review patients with SN and to analyse their clinical features and the incidence of MT-LS. METHODS Patients with SN diagnosed between 1995 and 2015 were enrolled in the study. The diagnosis of MT-LS was made according to established clinical criteria and, whenever possible, was confirmed by germline mutation analysis. RESULTS In 60 patients (32 men, 28 women, mean age 69.22 years), 96 SN were diagnosed: 65 adenomas (67.7%), 16 sebaceomas (16.7%) and 15 carcinomas (15.6%). Of the 60 patients, 50 (83.3%) had a single SN and 10 (16.7%) had multiple lesions. Patients diagnosed with MT-LS (12 patients, 20%) were younger (63.25 years vs. 70.71 years), and had a higher incidence of extrafacial SN (4/12 patients, 33.3%), and were significantly (P

Keratoacanthoma (KA) is a common skin tumour that remains controversial regarding classification, epidemiology, diagnosis, prognosis and management. Classically, a KA manifests as a rapidly growing, well-differentiated, squamoid lesion with a predilection for sun-exposed sites in elderly people and a tendency to spontaneously regress. Historically, KAs have been considered a variant of cutaneous squamous cell carcinoma (cSCC) and are often reported as KA-type cSCC. However, the penchant for regression has led many to categorize KAs as biologically benign tumours with distinct pathophysiological mechanisms from malignant cSCC. The clinical and histopathological similarities between KA and cSCC, particularly the well-differentiated variant of cSCC, have made definitive differentiation difficult or impossible in many cases. The ambiguity between entities has led to the general recommendation for surgical excision of KAs to ensure a potentially malignant cSCC is not left untreated. This current standard creates unnecessary surgical morbidity and financial strain for patients, especially the at-risk elderly population. There have been no reports of death from a definitive KA to date, while cSCC has an approximate mortality rate of 1·5%. Reliably distinguishing cSCC from KA would shift management strategies for KAs towards less-invasive treatment modalities, prevent unnecessary surgical morbidity, and likely reduce associated healthcare costs. Herein, we review the pathophysiology and clinical characteristics of KA, and conclude on the balance of current evidence that KA is a benign lesion and distinct from cSCC.

Keratoacanthoma centrifugum marginatum (KCM) is an uncommon variant of keratoacanthoma. Keratoacanthoma centrifugum marginatums are most commonly seen on sun-exposed surfaces and present with progressive peripheral expansion and raised, hyperkeratotic borders. Central clearing with atrophy and lack of spontaneous clearance are other key clinical characteristics. The majority of cases are benign with a low risk of metastasis. The size of such growths is variable with reported cases ranging from 5.0cm×5.0cm to as large as 20.0cm×14.0cm. Treatment options include surgical excision, oral retinoids, and intralesional chemotherapeutics such as methotrexate or bleomycin. We herein present a case of KCM manifesting as an exophytic, crateriform plaque in a 61-year-old man.

Keratoacanthoma (KA) is a common cutaneous neoplasm which often resembles typical squamous cell carcinoma (SCC) in both its clinical and historical presentation. Several studies have attempted to identify methods for distinguishing between KA and SCC, however, none of these have proven to play any obvious roles in these tumors. Given this we went on to evaluate mitochondrial microsatellite instability (mtMSI) in KA and SCC in an effort to understand these tumors better. DNA was isolated from paired normal and tumoral tissues donated by 57 KA patients and 43 SCC patients. MtMSI was then analyzed using eight microsatellite markers and was observed in 2 (3.5%) of the 57 KA patients and 8 (18.6%) of the 43 SCC patients, respectively. MtMSI was also shown to affect different locations depending on tumor type. In KA patients, mtMSI was detected at mitochondrial D514 D-loop and presented with (CA) n repeats, in contrast, all of the SCC patient experienced mtMSI at the D310 with (C)n repeats of the D-loop region. These differences in location were found to be significant, which may support the hypothesis that KA and SCC have different pathogenetic pathways. Our results also suggest that mtMSI may be a candidate for developing novel differential diagnostic methods for KA and SCC.

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.

Keratoacanthoma centrifugum marginatum (KCM) of the skin is a rare variant of cutaneous keratoacantoma. KCM was first reported in 1962 andpresents with progressive peripheral expansion , no spontaneous clearing and a bank-shaped outer wall with concurrent central healing. Treatment options include topical and systemic therapies.Surgical intervention is the preferred therapy for solitary KCM. We report on surgery and photodynamic therapy delivered sequentially to treat a giant facial Keratoacanthoma centrifugum marginatum patient. It was safe and effective .

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 asist 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 patient 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=0.004). 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>0.05). Clearer results can be obtained by conducting more detailed and long-term studies. This article is protected by copyright. All rights reserved.

Purpose To characterize the clinical and histopathologic features of actinic granuloma of the conjunctiva. Design Retrospective observational case series Methods Institutional pathology records between 2014 and 2020 were searched for all cases of conjunctival actinic granuloma. Information collected included age, sex, ocular and medical history, clinical findings, laboratory workup, treatment, follow-up, pathologic diagnosis, and histopathologic inflammation pattern. Results Eight eyes of 8 patients, 5 men and 3 women, with a median age of 43 years (mean 49, range 24-83) were identified. Clinical diagnosis was pterygium (n = 4, 50%), inflamed pterygium (n = 1, 13%), pterygium vs conjunctival squamous cell carcinoma (n = 1, 13%), episcleritis vs inflamed pinguecula (n = 1, 13%), and scleritis vs keratoacanthoma (n = 1, 13%). Of 5 lesions with follow-up information, none recurred following excision with a median follow-up of 9 weeks (mean 19 weeks, range 1-61 weeks). Allergy/atopy was documented in 4 of 7 (57%) patients with available medical information. There were no other systemic associations. Histopathologically, actinic granuloma was associated with pterygium (n = 6, 75%) and pinguecula (n = 2, 25%). All lesions were composed predominantly of histiocytes and a variable number of foreign body–type giant cells associated with a focus of severe actinic elastosis. The inflammatory pattern was giant cell (n = 4, 50%), sarcoidal (n = 2, 25%), histiocytic (n = 1, 13%), and combined histiocytic and sarcoidal (n = 1, 13%). Conclusion Conjunctival actinic granuloma has diverse clinical and histopathologic manifestations, which need to be distinguished from other autoimmune, neoplastic, and infectious etiologies. This lesion frequently occurs in pre-existing pterygium and pinguecula and may be associated with allergy and atopy.