Multiple persistent keratoacanthomas: Treatment with oral etretinate

Multiple keratoacanthomas (KAs) of the Ferguson-Smith type represent a rare and distinctive disease for which treatment is difficult and often unrewarding. Two patients with multiple KAs of this variety, who were successfully treated with oral etretinate, are described. Our cases support the conclusion that oral retinoids have to be added to the treatment modalities for this entity. Use of oral retinoids is particularly recommended when the number of lesions is very high or when the development of new lesions is severely disabling.     

The "sins" of the fathers: self-healing squamous epithelioma in Scotland.

BACKGROUND: A review is presented of the recent progress made in mapping of the hereditary skin disease "Ferguson-Smith multiple self-healing squamous epithelioma." METHODS: The use of founder effects in an autosomal dominant disease is reviewed as applied to gene mapping efforts. RESULTS: A common haplotype among Scottish families segregating Ferguson-Smith disease allowed the narrowing of the candidate gene interval and the identification of several possible disease-associated genes. CONCLUSION: The gene for Ferguson-Smith multiple self-healing squamous epithelioma lies in a narrow region on chromosome 9q, along with several other important hereditary skin disease loci.     

Multiple keratoacanthoma centrifugum marginatum

Keratoacanthoma centrifugum marginatum (KCM) is a rare variant of keratoacanthoma characterized by a progressive peripheral growth with concomitant central healing. We report here a case of multiple KCM of the lower legs in a 48-year-old man. The lesions had progressively evolved over 3 years. They were multiple asymptomatic and confluent annular plaques of 5 to 20 cm, having papulo-nodular with hyperkeratotic and crusted borders and cicatricial center. Within the centers were numerous firm and pigmented minipapules of 1 to 2 mm. The typical clinical aspect, together with characteristic histological features confirmed the diagnosis of KCM. Herein we will highlight the clinical and histological features of KCM, as well as the different effective treatments. We will also briefly discuss KCM among the other types of keratoacanthomas.     

Keratoacanthoma centrifugum marginatum—A rare variant of keratoacanthoma: Case report and literature review

Keratoacanthoma centrifugum marginatum (KCM) is a rare variant of keratoacanthoma and is characterized by progressive peripheral growth with accompanying central healing. Here, we report a case of multiple KCM. A 53-year-old man presented with multiple erythematous papulonodules on both upper limbs and neck for >2 years. His skin lesions enlarged in an annular manner with central residual cribriform scarring that eventually formed confluent plaques (2–8 cm in diameter) with elevated hyperkeratotic borders. Skin biopsy of a developed matured nodule on the right forearm was consistent with that of classical keratoacanthoma. KCM was diagnosed on the basis of clinical and pathological presentation. Low-dose acitretin (0.7 mg/kg/day) was administered and the skin lesions improved significantly within 3 months after the treatment. In this case, we present the clinical and histological features of KCM and discuss the different effective treatment modalities.     

Severe exacerbation of multiple self‐healing squamous epithelioma (Ferguson–Smith disease) with radiotherapy,which was successfully treated with acitretin

We describe the challenging case of a patient presenting with extensive, eruptive mid‐facial squamous cell carcinomas (SCCs) and keratoacanthomas (KAs) consequent to radiotherapy. Our patient had a personal and family history of multiple KAs and SCCs. Multiple self‐healing squamous epithelioma, otherwise known as Ferguson–Smith disease, was diagnosed. This case presented a therapeutic challenge to preserve tissue and avoid severe facial disfigurement. We found oral acitretin to be the treatment of choice.     

Ineffectiveness of radiotherapy for the treatment of keratoacanthoma centrifugum marginatum: A case report

Keratoacanthoma centrifugum marginatum (KCM) is a rare variant of keratoacantoma (KA). Although KCM shares histological and clinical features with KA, KCM has no tendency of spontaneous regression, and presents with progressive peripheral expansion with a bank‐shaped outer wall and concurrent central healing. As such, early diagnosis and proper treatment of the patient are required. However, because of its rarity, previous reports are insufficient to evaluate which treatment should be selected. Here, we report a case of KCM that responded to radiotherapy, but relapsed 6 months later.     

Keratoacanthoma centrifugum marginatum arising in vitiligo: a case report

Keratoacanthoma centrifugam marginatum (KCM) is a rare variant of the Keratoacanthoma (KA) form of squamous cell carcinoma with only 30 cases reported to date. We report a case of KCM arising in a long-standing vitiligo lesion chronically exposed to sunlight. Over years, the vitiligo lesions gradually evolved into sclerotic plaques and subsequently KCM developed in one of the plaques.     

Analysis of microsatellite instability and loss of heterozygosity in keratoacanthoma

We analyzed microsatellite instability (MSI) and loss of heterozygosity (LOH) at 17 microsatellite markers located on chromosomes 2p, 3p, 5q, 6q, 9p, 9q, 17p and 18q in 19 randomly selected keratoacantomas (KAs), in one cutaneous lesion that histologically could not unequivocally be differentiated from squamous cell carcinoma, and in one patient with multiple KAs of longstanding duration. The goals of our study were to determine whether, in a similar manner to some visceral carcinomas, genomic instability could be detected in KAs and to clarify whether molecular analysis might be useful to further characterize KA. MSI was observed in 2 of 21 cases (9.5%) at 5 of 17 loci examined. In one patient with a solitary KA, the presence of MSI and a family history of visceral malignant tumours suggested that the patient might have belonged to a family with Muir-Torre syndrome. In one other MSI ⁺ KA, a definite differential diagnosis in relation to squamous cell carcinoma could not be established. In addition, one sample displayed LOH at 2 of 17 loci analysed whereas in the patient with multiple KAs, LOH at one locus was the only alteration found. In conclusion, the low frequency of MSI and LOH detected in our study suggests that these genetic events are uncommon in KA unless it is associated with a familial disease (e.g. Muir-Torre syndrome) or it has more aggressive histological features. Received: 12 August 1996     

Array comparative genomic hybridization of keratoacanthomas and squamous cell carcinomas: different patterns of genetic aberrations suggest two distinct entities

Keratoacanthoma (KA) is a benign keratinocytic neoplasm that spontaneously regresses after 3-6 months and shares features with squamous cell carcinomas (SCCs). Furthermore, there are reports of KAs that have metastasized, invoking the question of whether KA is a variant of SCC (Hodak et al., 1993). To date, no reported criteria are sensitive enough to discriminate reliably between KA and SCC, and consequently there is a clinical need for discriminating markers. Our previous study analyzed 132 KAs and 29 SCCs and revealed significantly different regions of genomic aberrations using chromosomal comparative genomic hybridization (CGH). In the present study, we applied array CGH to investigate 98 KAs and 22 SCCs from the above samples. The result shows that all KAs and SCCs have some degree of genetic aberrations. The distribution of numbers of aberrant clones per sample differed significantly between KAs and SCCs (P<0.02), which also demonstrated recurrent aberrations that differed significantly (P<0.001), as illustrated by unsupervised cluster analysis. Classifiers for clinicopathological parameters of KAs were established based on t-test statistics and permutation tests. Tumor size, fibrosis, and inflammation, which are related to the developmental stages of KAs, showed significant (t-test, permutation test) associations with aberrations of selected genomic regions. This suggests chromosomal instability during the whole life cycle of KAs.     

Spontaneous resolution of keratoacanthoma centrifugum marginatum

Keratoacantnoma centrifugum marginatum (KCM) is a rare variant of keratoacantnoma, with > 40 cases reported world wide. Spontaneous resolution of KCM is very rare. To our knowledge, this is the first case of KCM with spontaneous resolution as documented by serial photographs.     

Multiple keratoacanthomas: a case report with evidence of regression with thymic hormone

A case of multiple keratoacanthomas (KAs) arising on sun-damaged skin in a 63-year-old male is reported. The patient showed a moderate elevation of the T-helper/T-suppressor ratio. Therapy with thymic hormone appeared to improve the condition.     

Conditioned medium from cultured human keratinocytes has growth stimulatory properties on different human cell types.

Evidence for growth-stimulatory properties of keratinocyte-conditioned medium (KCM) on human fibroblasts, endothelial cells, keratinocytes, smooth muscle cells, and a mouse fibroblast cell line (3T3 cells) is presented. On human fibroblasts KCM caused an increase of over 400% in DNA synthesis as revealed by 3H-thymidine incorporation and autoradiography. The proliferative effect was comparable to that of platelet-derived growth factor (PDGF), but was not inhibited by PDGF antibodies and exceeded that of transforming growth factor-alpha (TGF-alpha), epidermal growth factor (EGF), insulin-like growth factor-I (IGF-I), and basic fibroblast growth factor (bFGF). Furthermore, KCM was found to stimulate smooth muscle cells, keratinocytes, and endothelial cells more potently than PDGF, EGF/TGF-alpha, and bFGF, respectively. KCM was also potent in stimulating thymidine incorporation in 3T3 cells, whereas EGF showed a twenty-fold weaker stimulatory effect. Because keratinocytes have been shown to secrete TGF-alpha, which binds to the EGF receptor, binding of factors in KCM to the EGF receptor was assayed. The displacement of radiolabeled EGF by KCM corresponded to a low concentration of EGF (0.5 ng/ml), implying that the growth-stimulatory effect of KCM was not mediated via activation of EGF receptors. Taken together, these results suggest the presence of hitherto unidentified growth-stimulatory factor(s), expressed and secreted by cultured human keratinocytes.     

Are keratoacanthomas variants of squamous cell carcinomas? A comparison of chromosomal aberrations by comparative genomic hybridization

Keratoacanthoma (KA) is a benign keratinocytic neoplasm that usually presents as a solitary nodule on sun-exposed areas, develops within 6-8 weeks and spontaneously regresses after 3-6 months. KAs share features such as infiltration and cytological atypia with squamous cell carcinomas (SCCs). Furthermore, there are reports of KAs that have metastasized, invoking the question of whether or not KA is a variant of SCC. To date no reported criteria are sensitive enough to discriminate reliably between KA and SCC, and consequently there is a clinical need for discriminating markers. We screened fresh frozen material from 132 KAs and 37 SCCs for gross chromosomal aberrations by using comparative genomic hybridization (CGH). Forty-nine KAs (37.1%) and 31 SCCs (83.7%) showed genomic aberrations, indicating a higher degree of chromosomal instability in SCCs. Gains of chromosomal material from 1p, 14q, 16q, 20q, and losses from 4p were seen significantly more frequently in SCCs compared with KAs (P-values 0.0033, 0.0198, 0.0301, 0.0017, and 0.0070), whereas loss from 9p was seen significantly more frequently in KAs (P-value 0.0434). The patterns of recurrent aberrations were also different in the two types of neoplasms, pointing to different genetic mechanisms involved in their developments.     

Keratoacanthoma centrifugum marginatum: a rare atypical variant of keratoacanthoma

Keratoacanthoma centrifugum marginatum (KCM) is an extremely rare variant of keratoacanthoma (KA), with about 30 cases reported since it was first described in 1962. Clinically, KA is an exoendophytic lesion of 10-25 mm with a horn-filled crater that resolves spontaneously within 6 months. In contrast, KCM is characterized by a larger diameter continuous centrifugal spread, concurrent central atrophy and lack of spontaneous remission. Histologically, KCM is similar to KA, with a central keratin-filled crater, overhanging lips of epithelium, a sharp outline between the tumour nests and stroma, and lack of anaplasia and stroma desmoplasia. We describe a 63-year-old agricultural worker with a 9-month history of a multinodular tumour, 70-75 mm in size, on his right hand. The clinical diagnosis of KCM was confirmed by histological examination. Local radiotherapy proved effective, with no recurrence during a 4-year follow-up.     

Keratoacanthoma centrifugum marginatum after photodynamic therapy with good response to oral retinoids and topical 5‐fluorouracil

Keratoacanthoma centrifugum marginatum (KCM) is a rare variant of keratoacanthoma (KA), characterized by progressive peripheral growth, and usually devoid of deep invasion. Different systemic (oral retinoids) or topical treatments have been reported, but there is not a well‐defined therapeutic protocol. We report the case of a KCM developing after photodynamic therapy (PDT) on the right leg of a 64‐year‐old woman. It was treated successfully with oral acitretin combined with topical 5‐Fluorouracil + salicylic acid for 5 months. This is the first case of KCM developing after PDT and successfully treated with oral retinoid combined with topical treatment.     

Keratoacanthoma centrifugum marginatum associated with mechanical trauma: Response to acitretin—A case report and review of the literature

Keratoacanthoma centrifugum marginatum (KCM) is a very rare variant of keratoacanthoma, characterized with progressive centrifugal growth, central healing, and atrophy. Due to its rarity and lack of distinctive histopathological features, KCM often raises diagnostic and therapeutic challenge. We present a case of a 76‐year‐old Caucasian woman with a single large tumor on her right shin that responded to oral retinoids. The patient presented history of local trauma. The tumor developed over the course of 20 months from a scar. To the best of our knowledge, this is the fifth case of KCM associated with mechanical trauma as a possible triggering factor.     

Keratoacanthoma centrifugum marginatum

Keratoacanthoma centrifugum marginatum (KCM) is a rare distinct variant of keratoacanthoma. Based on three personal observations and a review of the literature, the authors describe the clinical and histological features of this neoplasm. Clinically KCM is characterized by the lack of a tendency for spontaneous remission and by continuous centrifugal spread. Histologically there is a subclinical, iceberg-like growth pattern. Like keratoacanthoma, KCM is a highly differentiated, biologically benign, non-metastasizing tumour. The treatment of choice is early excision of the tumour.     

周期素A在皮肤鳞状细胞癌与角化棘皮瘤中的检测

目的通过检测周期素(cyc lin)A在皮肤鳞状细胞癌(SCC)和角化棘皮瘤(KA)中的分布,探讨两者之间的关系。方法采用免疫组化技术检测12例KA和20例SCC皮损中cyc lin A蛋白。结果cyc lin A阳性细胞在KA中主要位于肿瘤的周边部,而在SCC中,呈弥漫性分布;cyc lin A在KA中的平均阳性率(13.2%)与高分化SCC(15.5%)差异无显著性(P>0.05),但与中、低分化SCC(23.4%,33.6%)差异有显著性(P<0.05)。结论cyc lin A在KA与SCC中的分布特点进一步说明了两者的异同,KA是否是SCC的分型尚需进一步探讨;cyc lin A在KA及各型SCC中的阳性率的不同说明cyc lin A可以作为评价皮肤肿瘤增殖程度的一个分子生物学指标。     

Efficacy of oral retinoids for keratoacanthoma centrifugum marginatum

Keratoacanthoma centrifugum marginatum (KCM) is a rare variant of keratoacanthoma. This condition is difficult to diagnose because of its large size and expansive nature and may be diagnosed as a malignant tumor. There are various treatments such as surgery and oral retinoids; however, limited studies have verified their effectiveness. Here, we report a case of KCM on the anterior chest of a 50‐year‐old woman and evaluate the efficacy of oral retinoids. In this case, oral retinoids were highly effective for KCM treatment. A total of 55 cases of KCM, including 54 previously reported cases, were reviewed, and their clinical characteristics and treatment were examined. In this report, 14 of 16 patients were effectively treated with oral retinoids, resulting in a treatment rate of 87.5%. Furthermore, even low‐to‐medium doses were sufficient for treatment and prevention. KCM can be misdiagnosed as a malignant disease based on its clinical features. Due to its large size and expansive nature, a wide excision may be performed; however, because oral retinoids have a very high response rate, an accurate diagnosis will help avoid an unnecessary wide excision.