Human Papillomavirus-Associated Giant Clear Cell Acanthoma and Squamous Cell Carcinoma: A Rare Case Report and Literature Review.

Clear cell acanthoma (CCA) and squamous cell carcinoma (SCC) represent distinct entities within dermatological oncology, each posing unique diagnostic and therapeutic challenges. CCA is a rare, benign epidermal growth, often not associated with human papillomavirus (HPV) infection, whereas SCC, a more aggressive form of skin cancer, has been linked to both ultraviolet (UV) exposure and HPV. Understanding the co-occurrence of these conditions in a single patient can enhance diagnostic accuracy and therapeutic outcomes. We report a 64-year-old male who underwent an operation for a verruciform lesion in the right groin, which was diagnosed as HPV-positive CCA alongside keratinised SCC. A literature search across January 2024 revealed limited evidence directly linking HPV to CCA, suggesting a need for further investigation. The speculative association between HPV and CCA warrants deeper exploration, especially considering the potential for HPV to contribute to lesion development through indirect mechanisms. The coexistence of CCA and SCC in an elderly patient presents a unique clinical scenario. This emphasises the need for vigilant diagnosis and tailored treatment strategies, highlighting the gap in understanding the pathogenesis of CCA, particularly its potential association with HPV. Further research is crucial for elucidating the complex interactions governing these conditions and for developing targeted interventions.

Acantoma de células claras. Estudio clínico de 70 pacientes / Clear Cell Acanthoma: A Series of 70 Cases

Antecedentes y objetivo El acantoma de células claras (ACC) es una lesión poco frecuente caracterizada histológicamente por la presencia de acantosis epidérmica a expensas de queratinocitos de citoplasma claro. Aunque se han descrito muchos casos clínicos de forma individual, se han publicado pocas series de pacientes con ACC. Nuestro objetivo fue analizar las características clínicas del ACC en nuestra población. Material y métodos Estudio retrospectivo de los pacientes con ACC diagnosticados en el Hospital Universitario de Bellvitge en Barcelona, España, entre 1995-2021. Se revisaron las historias clínicas para obtener los siguientes datos: edad, sexo, localización, número de lesiones, diámetro, tiempo de evolución, características clínicas de los tumores, diagnóstico clínico de sospecha y el tratamiento realizado Resultados Setenta pacientes con ACC fueron incluidos en el estudio (30 mujeres y 40 varones, edad media 62 años, DE 13). La mediana del tiempo de evolución fue de dos años, rango intercuartílico (RIQ) 4 y la del diámetro 6 mm, RIQ 5. Una paciente presentó lesiones múltiples. Las lesiones se localizaron en las extremidades inferiores en 57 pacientes (81%), en la cara posterior del tronco en ocho (11%), la cara anterior del tronco en cuatro (5%) y en las extremidades superiores en uno (1%). Se planteó el diagnóstico clínico de ACC en 40% de los pacientes atendidos por dermatólogos. Conclusiones El aspecto clínico característico del ACC es el de una lesión cupuliforme eritematosa con punteado vascular y collarete epidérmico. La proporción de ACC diagnosticados clínicamente ha mejorado respecto a series antiguas, quizás por un mayor conocimiento clínico de la entidad y un mayor uso de la dermatoscopia (AU)

Background and objective Clear cell acanthoma (CCA) is an uncommon lesion histologically characterized by the presence of epidermal acanthosis with keratinocytes containing clear cytoplasm. Although many single cases of CCA have been described, few case series have been published. The aim of this study was to describe the clinical characteristics of CCA in our practice setting. Material and methods Retrospective study of patients diagnosed with CCA at Hospital Universitario de Bellvitge in Barcelona, Spain, between 1995 and 2021. We conducted a chart review to record age, sex, number and location of lesions, diameter, time since onset, clinical characteristics, suspected clinical diagnosis, and treatment. Results Seventy patients (30 women and 40 men) with a mean (SD) age of 62 (13) years were diagnosed with CCA during the study period. Median (interquartile range) time since onset was 2 (4) years and median lesion diameter was 6 (5) mm. One woman had multiple lesions. Lesions were located on the lower extremities in 57 patients (81%), the posterior aspect of the trunk in 8 (11%), the anterior aspect of the trunk in 4 (5%), and the upper extremities in 1 (1%). CCA was clinically suspected in 40% of patients seen by dermatologists. Conclusions CCA presents as an erythematous, dome-shaped lesion with pinpoint vessels and an epidermal collarette. The accuracy of clinical diagnosis has improved relative to earlier series, possibly due to a better clinical understanding of this lesion and a greater use of dermoscopy (AU)

[Translated article] Clear Cell Acanthoma: A Series of 70 Cases / Acantoma de células claras. Estudio clínico de 70 pacientes

Background and objective Clear cell acanthoma (CCA) is an uncommon lesion histologically characterized by the presence of epidermal acanthosis with keratinocytes containing clear cytoplasm. Although many single cases of CCA have been described, few case series have been published. The aim of this study was to describe the clinical characteristics of CCA in our practice setting. Material and methods Retrospective study of patients diagnosed with CCA at Hospital Universitario de Bellvitge in Barcelona, Spain, between 1995 and 2021. We conducted a chart review to record age, sex, number and location of lesions, diameter, time since onset, clinical characteristics, suspected clinical diagnosis, and treatment. Results Seventy patients (30 women and 40 men) with a mean (SD) age of 62 (13) years were diagnosed with CCA during the study period. Median (interquartile range) time since onset was 2 (4) years and median lesion diameter was 6 (5)mm. One woman had multiple lesions. Lesions were located on the lower extremities in 57 patients (81%), the posterior aspect of the trunk in 8 (11%), the anterior aspect of the trunk in 4 (5%), and the upper extremities in 1 (1%). CCA was clinically suspected in 40% of patients seen by dermatologists. Conclusions CCA presents as an erythematous, dome-shaped lesion with pinpoint vessels and an epidermal collarette. The accuracy of clinical diagnosis has improved relative to earlier series, possibly due to a better clinical understanding of this lesion and a greater use of dermoscopy (AU)

Antecedentes y objetivo El acantoma de células claras (ACC) es una lesión poco frecuente caracterizada histológicamente por la presencia de acantosis epidérmica a expensas de queratinocitos de citoplasma claro. Aunque se han descrito muchos casos clínicos de forma individual, se han publicado pocas series de pacientes con ACC. Nuestro objetivo fue analizar las características clínicas del ACC en nuestra población. Material y métodos Estudio retrospectivo de los pacientes con ACC diagnosticados en el Hospital Universitario de Bellvitge en Barcelona, España, entre 1995-2021. Se revisaron las historias clínicas para obtener los siguientes datos: edad, sexo, localización, número de lesiones, diámetro, tiempo de evolución, características clínicas de los tumores, diagnóstico clínico de sospecha y tratamiento realizado. Resultados Setenta pacientes con ACC fueron incluidos en el estudio (30 mujeres y 40 varones, edad media: 62 años, DE: 13). La mediana del tiempo de evolución fue de 2 años, rango intercuartílico (RIQ): 4 y la del diámetro 6mm, RIQ: 5. Una paciente presentó lesiones múltiples. Las lesiones se localizaron en las extremidades inferiores en 57 pacientes (81%), en la cara posterior del tronco en 8 pacientes (11%), la cara anterior del tronco en 4 pacientes (5%) y en las extremidades superiores en un paciente (1%). Se planteó el diagnóstico clínico de ACC en el 40% de los pacientes atendidos por dermatólogos. Conclusiones El aspecto clínico característico del ACC es el de una lesión cupuliforme eritematosa con punteado vascular y collarete epidérmico. La proporción de ACC diagnosticados clínicamente ha mejorado respecto a series antiguas, quizás por un mayor conocimiento clínico de la entidad y un mayor uso de la dermatoscopia (AU)

Clear Cell Acanthoma: A Series of 70 Cases. / Acantoma de células claras. Estudio clínico de 70 pacientes.

BACKGROUND AND OBJECTIVE: Clear cell acanthoma (CCA) is an uncommon lesion histologically characterized by the presence of epidermal acanthosis with keratinocytes containing clear cytoplasm. Although many single cases of CCA have been described, few case series have been published. The aim of this study was to describe the clinical characteristics of CCA in our practice setting. MATERIAL AND METHODS: Retrospective study of patients diagnosed with CCA at Hospital Universitario de Bellvitge in Barcelona, Spain, between 1995 and 2021. We conducted a chart review to record age, sex, number and location of lesions, diameter, time since onset, clinical characteristics, suspected clinical diagnosis, and treatment. RESULTS: Seventy patients (30 women and 40 men) with a mean (SD) age of 62 (13) years were diagnosed with CCA during the study period. Median (interquartile range) time since onset was 2 (4) years and median lesion diameter was 6 (5) mm. One woman had multiple lesions. Lesions were located on the lower extremities in 57 patients (81%), the posterior aspect of the trunk in 8 (11%), the anterior aspect of the trunk in 4 (5%), and the upper extremities in 1 (1%). CCA was clinically suspected in 40% of patients seen by dermatologists. CONCLUSIONS: CCA presents as an erythematous, dome-shaped lesion with pinpoint vessels and an epidermal collarette. The accuracy of clinical diagnosis has improved relative to earlier series, possibly due to a better clinical understanding of this lesion and a greater use of dermoscopy.

Condyloma and coincidental epidermodysplasia verruciformis acanthoma positive for human papillomavirus-14 and -21.

Epidermodysplasia verruciformis (EDV) is a rare genodermatosis that predisposes individuals to persistent infection with ß-human papillomavirus (HPV) genotypes. The term EDV acanthoma may be applied to lesions with incidental findings of EDV-defining histopathological features without clinical signs of EDV. We report a case of HPV-14- and -21-positive EDV acanthoma arising in association with condyloma in a female patient with a history of low-grade squamous intraepithelial lesion of the cervix positive for high-risk HPV (non-16/18), chronic kidney disease, and systemic lupus erythematosus. The patient had no family or personal history of EDV, but the patient was on immunosuppressive therapy with mycophenolate mofetil and prednisone. A biopsy specimen from one of the perianal lesions revealed histopathologic changes consistent with EDV in the setting of condyloma. Molecular testing showed HPV-14 and -21, which supported the coexistence of condyloma with EDV acanthoma.

Eczematoid clear cell acanthoma of the nipple/areola: the first case reported in China and literature analysis / 中华皮肤科杂志

Objective:To investigate clinical manifestations, pathological features and diagnosis of eczematoid clear cell acanthoma of the nipple/areola.Methods:The clinical manifestations, histopathological features, special staining results and immunohistochemical features of a case of eczemtoid clear cell acanthoma of the nipple/areola firstly reported in China were analyzed, and compared with those of similar cases in foreign literature.Results:The female patient presented with recurrent pruritic rashes on the left nipple and areola for over 2 years. Skin examination showed hypertrophic skin on the left nipple and areola, and scattered erythema, hypopigmented macules and hyperpigmented macules on the areola, which were covered with a few crusts and scales. Histopathological examination of the skin lesions showed focal epidermal crusts and scales, focal parakeratosis, extended and fused rete ridges, thickened spinous layer, focal spongiosis, clear cell clumps in the spinous cell layer, telangiectasia in the superficial dermis, with infiltration of a few eosinophils and neutrophils. Periodic acid-Schiff staining showed positive results, and immunohistochemical staining revealed positive reaction for epithelial membrane antigen. Topical treatment with triamcinolone acetonide and econazole cream was effective, and topical application of 3% boric acid solution could alleviate exudation. During the 6-month follow-up, the patient experienced intermittent recurrence twice, and responded well to the above treatment.Conclusions:Eczematoid clear cell acanthoma of the nipple/areola has unique clinical and pathological features, revealing that it′s a new subtype of clear cell acanthoma. Pathological examination is the gold standard for its diagnosis.

Practice and analysis of clinical pharmacist participating in the treatment of a case of acanthoma caused by navulizumab / 中国药房

This paper reports the clinical pharmacist participated in the diagnosis and treatment of a patient with acanthoma caused by nivolumab. This patient developed acanthoma 2 weeks after medication， involving scalp， neck， trunk， back of hand， sole of foot and other parts， with moderate pruritus. The clinical pharmacist determined it as “yes” according to the causality evaluation method of adverse reactions. After reviewing the literature， clinical pharmacists found that acanthoma caused by immune checkpoint inhibitors was more commonly seen in male elderly patients with malignant melanoma， and mainly involved the trunk， extremities and hands. Under the general principle of considering the effectiveness， safety， economy and accessibility of therapeutic drugs， the clinical pharmacist finally decided to give the patient a comprehensive treatment scheme of Halometasone cream for external use + oral administration of Retinoic acid capsules + oral administration of Ebastine tablets after discussion with the doctor， with maximum respect for the patient’s wishes，and continued to use navulizumab for immunotherapy. At the same time， pharmaceutical care and psychological counseling were conducted by clinical pharmacist. Finally， the patient successfully completed the treatment， and the acanthoma gradually subsided after the end of navulizumab treatment. The diagnosis and treatment process of this patient indicated that the participation of clinical pharmacists is helpful to improve the continuity and safety of immunotherapy.

Clear Cell Acanthoma with Malignant Cytologic Features: A Case Report and Review of the Literature.

Clear cell acanthoma (CCA) is classically considered a benign epidermal tumor, although rare case reports have described CCA with malignant features. Here, we present a case of a patient with a biopsy proven CCA that regrew post-biopsy and was subsequently completely excised. Histologic examination of the tumor in the excision specimen revealed malignant cytologic features that were not present in the initial biopsy. A review of the literature identified five additional cases of CCA with similar malignant cytologic features. On analysis, common histopathologic characteristics included cellular pleomorphism, increased nuclear-to-cytoplasmic ratio, prominent nucleoli, and atypical mitotic figures. We support the designation of atypical clear cell acanthoma for these entities with features of both CCA and significant cytologic atypia. As none of these cases exhibited clinically aggressive behavior, further study is warranted.

Dermoscopic findings and histopathological correlation in large cell acanthoma.

Since large cell acanthoma (LCA) has many overlapping clinical and histopathological features with other epidermal pigmented tumours, an additional method to differentiate it would be of great clinical significance. A retrospective study was performed on 33 lesions (26 patients) to identify distinct dermoscopic findings of LCA and to describe dermoscopic-histopathological correlations. The results revealed that dermoscopy significantly aids in the distinction of LCA from other epidermal tumours included in the differential diagnosis. Yellow opaque homogeneous background, brown dots, and moth-eaten border are common findings, and prominent skin markings and short white streaks are additional distinguishing features. Several important findings that are common in other diseases are rare in LCA.

Diagnostic Pearls of Vulvar Epidermolytic Acanthoma: Case Report.

Epidermolytic acanthomas (EA) are uncommon benign tumors clinically presenting as single to multiple papules. Histologically, EA display hyperkeratosis, hypergranulosis, acanthosis, and epidermal degeneration-also known as epidermolytic hyperkeratosis (EH). EA may be misdiagnosed as condyloma both clinically and histopathologically when located on the genitalia. Thus, this diagnosis carries a significant psychological burden and must remain in the differential when initially considering genital warts. We utilize the case of a 62-year old female referred to dermatology for a 5-year history of multiple pruritic and hypopigmented vulvar papules-misdiagnosed as genital warts-to highlight the impact of differentiating EA from genital warts. This patient was initially misdiagnosed with common genital warts at her gynecologist's office and treated unsuccessfully for years. A shave biopsy was performed and histology revealed EH, consistent with EA.

Whole-transcriptome sequencing identifies postzygotic ATP2A2 mutations in a patient misdiagnosed with herpes zoster, confirming the diagnosis of very late-onset segmental Darier disease.

An 82-year-old female patient presented with a recent onset of painful skin lesions in unilateral distribution on the abdominal area following the lines of Blaschko; the initial diagnosis of Varicella-Zoster infection was made. However, because the individual lesions appeared as hyperkeratotic papules and were unresponsive to antiviral therapy, a skin biopsy was performed, which revealed hyperkeratosis, suprabasal acantholysis and dyskeratosis with corps ronds and grains, consistent with acantholytic dyskeratotic acanthoma. Since this entity has been associated with Darier disease, whole-transcriptome sequencing by RNA-Seq was performed on RNA isolated from a lesion and from adjacent normal appearing skin, and a recently developed bioinformatics pipeline that can identify both genomic sequence variants and the presence of any of 926 viruses was applied. Two pathogenic missense mutations in the ATP2A2 gene were identified in the lesional but not in normal appearing skin, and no evidence of Varicella-Zoster infection was obtained. These findings confirm the diagnosis of segmental Darier disease due to postzygotic mutations in the ATP2A2 gene, and attest to the power of a novel single-step application of RNA-Seq in providing correct diagnosis in this rare genodermatosis.

Multiple eruptive clear cell acanthomas successfully treated with CO2 laser ablation.

Clear cell acanthoma (CCA) is a rare, benign epidermal lesion of clear glycogen-containing keratinocytes. The exact etiology is unknown. Although CCA usually appear as solitary lesions, cases of multiple CCAs have also been described. The rare eruptive CCA variant describes cases with more than 30 lesions.Current therapeutic evidence for the management of multiple CCAs is limited. CO2 laser remains the most widely used laser in clinical practice. However, literature describing its effectiveness on CCA is sparse, and previous reports have described its use for a maximum of three lesions. To our knowledge, this is the first report of successful CO2 laser treatment of the multiple eruptive CCA variant with an excellent cosmetic outcome.Our case adds to the evidence that CO2 laser is an effective treatment for this condition. Particularly in those patients with refractory or multiple eruptive CCAs, or for those who may not tolerate repeated courses of cryotherapy, or who are concerned about scarring and cosmetic outcome.

Non-Invasive Diagnosis of a Facial Tumor Using Dermoscopy and Successful Treatment with 595 nm Pulsed Dye Laser.

Clear cell acanthoma (CCA) is an uncommon, benign epithelial tumor presenting as a well-defined, slow-growing solitary nodule. The diagnosis of CCA is usually based on clinical and histopathological evaluation of the tumor. However, when such type of benign tumor occurs on an exposed area, a biopsy is not always the best diagnostic option since it may leave scar. The recent advent of dermoscopy has offered an accurate and non-invasive method to diagnose CCA without resorting to skin biopsy. A 40-year-old male presented with a shiny, erythematous-to-brown, flattened nodule on the left cheek. Dermoscopic examination revealed a 'string of pearls' vascular pattern, a characteristic dermoscopic feature of CCA. Under the clinical and dermoscopic impression of CCA, a 595 nm pulsed dye laser (PDL) therapy targeting the vascular tissue in the superficial dermis of the lesion was chosen for a minimally invasive treatment. After repeated sessions of PDL, an optimal cosmetic outcome was achieved and no recurrence was recorded during the follow-up period. Herein, we report a case of presumed CCA which was successfully diagnosed and treated by utilizing non-invasive modalities.

Cutaneous acantholytic dyskeratotic acanthoma accompanying syringofibroadenomatous hyperplasia with proliferation of mature sebocytes: A case report.

Acantholytic dyskeratotic acanthoma is a rare variant of epidermal acanthoma. It has a flat, plaque-like structure and is characterized microscopically by acantholysis and dyskeratosis. Eccrine syringofibroadenomatous hyperplasia is benign and likely reactive. It has recently been considered as a hyperplastic process affecting the eccrine ducts rather than the neoplasm because of its pathological heterogeneity and wide clinical associations. In this article, we present the case of 97-year-old Japanese women with a 10-mm wide, painful acantholytic dyskeratotic acanthoma accompanied by syringofibroadenomatous hyperplasia in the right femoral region. Although syringofibroadenomatous hyperplasia is known to occur as a reactive process with various dermatoses and cutaneous tumors, to date, there have been no reports of cases of acantholytic dyskeratotic acanthoma accompanying syringofibroadenomatous hyperplasia. Moreover, this case also includes the unusual finding of an increase in the mature sebocytes in the area of the syringofibroadenomatous hyperplasia.

Variability in the Histopathological Diagnosis of Non-Melanocytic Lesions Excised to Exclude Melanoma.

INTRODUCTION: The differential diagnosis of lesions excised to exclude melanoma include a variety of benign and malignant melanocytic and non-melanocytic lesions. OBJECTIVES: We examined the variability between pathologists in diagnosing non-melanocytic lesions. METHODS: As part of a larger study prospectively examining the diagnosis of lesions excised to exclude melanoma in 198 patients at a primary care skin cancer clinic in Newcastle, Australia, we compared diagnosis made by 5 experienced dermatopathologists, of 44 non-melanocytic lesions in 44 patients aged 22-90. RESULTS: Forty-four lesions (out of 217 in total) were non-melanocytic. Among the 5 pathologists who examined each case there was marked variability in the terminology used to diagnose each case. The most common variability was found between seborrheic keratosis, large cell acanthoma, solar lentigo, and lichenoid keratosis. The diagnosis made by the majority of the pathologists was deemed to be the reference diagnosis. Versus majority diagnosis, 4% of benign lesions were considered malignant, and 7% of malignant diagnoses were considered as benign. CONCLUSIONS: The different terminology adopted and lack of consensus in the diagnosis of these non-melanocytic lesions in this setting suggests that training AI systems using gold standards may be problematic. We propose a new management classification scheme called MOLEM (Management of Lesions Excised to exclude Melanoma) which expands the previously described MPATH-dx to include non-melanocytic lesions.