Corrigendum: Differential Immunoexpression of Inhibitory Immune Checkpoint Molecules and Clinicopathological Correlates in Keratoacanthoma, Primary Cutaneous Squamous Cell Carcinoma and Metastases.

This Corrigendum relates to the following article: https://doi.org/10.2340/actadv.v104.13381.

Generalized Eruptive Keratoacanthoma (GEKA) after Pfizer mRNABNT162b2 (Comirnaty®) COVID-19 Vaccination Successfully Treated with Cemiplimab.

In December 2020, a major vaccination program against COVID-19 commenced in Europe with vaccines such as Pfizer's mRNABNT162b2 (Comirnaty®). Subsequent reports of immediate and delayed skin reactions emerged. This study presents a case of a 64-year-old male who developed multiple keratoacanthomas approximately two weeks after receiving a second booster dose of the Pfizer vaccine. The patient, who had significant medical history of hypertension and diabetes, presented with erythematous, crateriform lesions on his limbs. A physical examination and histopathological analysis confirmed the diagnosis of Generalized Eruptive Keratoacanthoma (GEKA). Treatment involved cemiplimab I.v. 350 mg administered every three weeks. Within two months, the patient showed significant improvement, with the disappearance of all lesions. Dermoscopy and histopathological exams supported the GEKA diagnosis, which is a rare variant of multiple keratoacanthomas. This case suggests a potential immune-mediated mechanism triggered by the COVID-19 vaccine, leading to the rapid development of keratoacanthomas. Treatment with cemiplimab showed promise, highlighting the potential of immune checkpoint inhibitors in managing multiple keratoacanthomas. Further research is needed to explore the efficacy and safety of such treatments.

Intralesional methotrexate versus 5-flurouracil in the treatment of keratoacanthoma.

BACKGROUND: Keratoacanthoma (KA) is a benign neoplasm that affects mainly photodamaged skin. It is locally destructive and may rarely spread. Surgery is not always suitable and usually disfiguring. Thus, non-operative modalities represent good alternatives. OBJECTIVE: To assess and compare the efficacy of intralesional methotrexate (MTX) and 5-flurouracil (5-FU) in the treatment of KA. PATIENTS AND METHODS: Randomized controlled trial included 20 patients with biopsy proven KA divided into 2 equal groups; group (A) received intralesional MTX, 25 mg/ml and group (B) received intralesional 5-FU, 50 mg/ml every 2 weeks till complete clearance or for a maximum 5 sessions. RESULTS: In the MTX group, complete clearance was observed in 7 patients (70%) compared to 8 patients (80%) in the 5- FU group with no statistically significant difference. However, the median number of injections needed to achieve complete response in the MTX group was 3 sessions versus only 2 sessions in the 5-FU group. LIMITATIONS: the small sample size due to the relatively low incidence of KAs in our population. CONCLUSION: Intralesional therapy is a good alternative to surgery in selected cases of KA. Both drugs showed comparable efficacy, but 5-FU may give faster results, hence increasing patient satisfaction and compliance.

Keratoacanthoma and Cutaneous Squamous Cell Carcinoma With PD-1 and PD-L1 Inhibitor Use.

This cross-sectional study assesses risk of dermatological immune-related adverse events associated with immunotherapy for cancer.

Spontaneous resolution of eruptive papules following ablative laser resurfacing-Case report and review of laser-associated eruptive keratoacanthomas.

BACKGROUND: Keratoacanthomas (KAs) following laser treatment are a rare, but well-described entity. AIM: Herein, we describe a case of eruptive keratoacanthoma (KA) following laser resurfacing treatment and aim to better characterize laser-associated KAs. METHODS: A literature search was performed on PubMed reviewing laser-associated KAs including various characteristics: epidemiology, history of skin cancer, location, and number, type of laser, as well as the management and outcome. RESULTS: Fractional ablative was the most common type of laser triggering KAs, and most cases presented within the first month following treatment. The majority of cases of laser-induced KA had a prior history of a malignant or premalignant skin neoplasm. Laser-induced KAs were treated using modalities similar to KAs arising in other contexts. CONCLUSION: Clinicians need to be knowledgeable and prepared to understand, and manage complications following laser treatments, as rare as they may be, including KAs.

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.

A rapidly growing nodule on the face during pregnancy.

It is well known that adnexal skin tumors can simulate other cutaneous neoplasia and that various types of benign and malignant skin tumors can develop or modify during pregnancy. Here, we report a case of trichoblastoma mimicking a keratoacanthoma arising in a nevus sebaceous during pregnancy. Given its unique clinical and dermoscopic features, this case highlights the pivotal role of clinicopathological correlation in the diagnosis of adnexal tumors with an atypical clinical presentation.

Intralesional methotrexate as non-surgical therapy for giant keratoacanthoma on the nose.

Keratoacanthoma is an epithelial tumour derived from hair follicles. Clinical and histopathological features of keratoacanthoma can resemble that of squamous cell carcinoma. Different treatment alternatives have been described over the years including intralesional methotrexate injection. We present an interesting case of treatment of solitary keratoacanthoma lesion on the nose with intralesional methotrexate as non-surgical therapy.

Mosaic Muir Torre Syndrome: Keratoacanthoma as a Piece of the Puzzle.

ABSTRACT: Lynch syndrome is an inherited condition, which increases the risk of numerous visceral malignancies and cutaneous tumors such as keratoacanthomas and sebaceous tumors. It is typically identified by immunohistochemistry of tissue taken from tumors or through genetic testing with next-generation sequencing. Diagnosing Lynch syndrome becomes more complex when the individual is mosaic for the relevant pathogenic variant. There are very few cases of this reported in the medical literature. It is even more unusual for the diagnosis to be made based on testing of a keratoacanthoma lesion. We report a case where immunohistochemistry of a keratoacanthoma helped make a diagnosis of mosaic Lynch syndrome. We will explore how mosaicism should be considered when a phenotype is strong, even if next-generation sequencing reports no pathogenic or likely pathogenic variant and how lesions such as keratoacanthomas can have a role in the early detection and treatment of future malignancies.

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.

Surgical management of periocular squamous cell carcinoma: case report.

This report describes the case of a 72-year-old female patient admitted to the ophthalmology clinic for a large round-oval tumor with a long-standing keratotic lesion on her lower eyelid, without extending to the free margin of the eyelid. The tumor was excised with a margin in non-tumorous tissue, the nearest being 1 mm away from the tumor at the 12 o'clock position. The surgical process was complicated by the patient's treatment with the anticoagulant rivaroxaban, resulting in increased bleeding during surgery. The histopathological evaluation showed characteristics indicative of a well-differentiated squamous cell carcinoma, more specifically, the keratoacanthoma type. Consequently, it was necessary to extend the excision at the 12 o'clock position by an additional 3 mm. The procedure involved extensive removal of the impacted area and subsequent reconstruction with advancement flaps, supported by histological examination to ensure total excision. In cases of squamous cell carcinoma on the eyelid, multiple sequential excisions are often required to ensure complete removal within safe histological margins, achieving desirable functional and esthetic results.

Computer Image Analysis Reveals C-Myc as a Potential Biomarker for Discriminating between Keratoacanthoma and Cutaneous Squamous Cell Carcinoma.

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, ß-catenin, C-Myc, and CyclinD1, which are critical molecules that play important roles in the Wnt/ß-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.

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.

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.

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.