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.     

A case of Ferguson-Smith type multiple keratoacanthomas associated with keratoacanthoma centrifugum marginatum: response to oral acitretin

Keratoacanthoma centrifugum marginatum (KCM) is a rare entity, usually classified as solitary keratoacanthoma (KA). The Ferguson-Smith type is the most common form of multiple KAs. Because development of multiple KAs and KCM in a single patient has rarely been reported, this association presents a therapeutic challenge. We report a 46-year-old man with Ferguson-Smith multiple KAs and KCM, who was successfully treated with acitretin.     

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—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.     

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

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.     

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 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.     

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.     

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.     

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.     

Keratinocyte-releasable stratifin functions as a potent collagenase-stimulating factor in fibroblasts

Termination of wound healing requires a fine balance between collagen deposition and its hydrolysis. To dissect the underlying control mechanisms for this process, we established a keratinocyte/fibroblast co-culture system and subsequently demonstrated more than a 10-fold increase in collagenase expression in fibroblasts co-cultured with keratinocytes relative to that of control cells. This finding was further confirmed in fibroblasts grown in a keratinocyte/fibroblast collagen-GAG gel. The efficacy of keratinocyte-derived collagenase stimulatory factors on collagenase activity was evaluated, and the results showed that only conditioned medium derived from fibroblasts co-cultured with keratinocytes was able to break down markedly type I collagen to its one-quarter and three-quarter fragments of both alpha (alpha1 and alpha2) and beta (beta1.1 and beta1.2) chains. The results of a dose-response experiment showed that keratinocyte-conditioned medium (KCM) stimulates the expression of collagenase mRNA by dermal fibroblasts in a concentration-dependent fashion. In a similar experiment, the results of a time-response experiment revealed that KCM treatment increases the expression of collagenase mRNA in dermal fibroblasts as early as 6 h and reaches its maximum level within 24-48 h. Considering that this keratinocyte-releasable factor has a potent collagenase stimulatory effect on fibroblasts, which favors the resolution of accumulated type I and type III collagen found in fibrotic tissue, we referred to this protein as a keratinocyte-derived anti-fibrogenic factor (KDAF). In a series of chromatography experiments and a direct trypsin digestion of the proteins and subsequent peptide mapping, a keratinocyte-derived collagenase-stimulating factor turned out to be a releasable form of stratifin, also known as 14-3-3 sigma protein. To validate this finding, stratifin cDNA was cloned into a pGEX-6P-1 expressing vector and more than 50 mg of recombinant stratifin was generated and used to treat fibroblasts with various concentrations for 24 h. The results of northern analysis showed a remarkable dose-response increase in the expression of collagenase mRNA in stratifin-treated fibroblasts relative to that of the control. This finding was consistent with that obtained from collagenase activity assay. In conclusion, we identified a keratinocyte-releasable form of stratifin in KCM that mimics the collagenase stimulatory effect of KCM for dermal fibroblasts. This finding suggests that stratifin is likely to be, at least, one of the KDAFs found in KCM.     

Keratoacanthoma centrifugum marginatum arising from a scar after skin injury.

Among the variants of solitary keratoacanthoma, keratoacanthoma centrifugum marginatum (KCM) is characterized by the lack of a tendency toward spontaneous remission and by continuous centrifugal spread. We describe a case of KCM arising from the scar after an old skin injury. The lesion appeared on the dorsum of the right hand, grew peripherally for 30 months, and became a tumor with a multinodular margin and central atrophy. A biopsy specimen from the edge of the tumor showed features resembling typical solitary keratoacanthoma.     

A case of multiple keratoacanthoma centrifugum marginatum: response to oral etretinate

The patient was a 48-year-old man who had a history of colonic polyps. About 18 months before, a dark reddish nodule had appeared on his right forearm. By peripheral growth, this lesion had formed a crateriform prominence with central healing. Similar symptoms multiplied and expanded, the largest being about the size of a child's head. Given both the clinical and histologic evidence, a diagnosis of keratoacanthoma centrifugum marginatum (KCM) was made. Oral etretinate was administered, and an involution of verrucous plaque began after 4 weeks. After 8 weeks, the lesions faded, leaving pigmentation in some areas. This is a rare disorder, only 30 such cases having been reported worldwide, and the present case was the third in which oral etretinate was found to be effective.     

Keratinocyte-conditioned media regulate collagen expression in dermal fibroblasts

Excessive extracellular matrix (ECM) production during dermal wound healing often leads to fibrotic conditions such as keloids and hypertrophic scarring (HSc). Type I collagen is the predominant form of collagen in the human skin and is produced mainly by dermal fibroblasts. It has been suggested that abnormalities in epidermal-dermal interaction can lead to excessive production of collagen by fibroblasts. To identify and further characterize any possible keratinocyte-derived collagen-inhibitory factors (KD-CIFs), we investigated the expression of pro-alpha1(I) collagen at the level of mRNA and protein in human fibroblasts that had been either co-cultured with keratinocytes or treated with keratinocyte-conditioned medium (KCM). Fibroblasts in both groups demonstrated a significant reduction in the steady-state levels of collagen mRNA and protein. Further characterization of KD-CIFs revealed a high-molecular-weight factor (>30 kDa) that showed stable activity at high temperature (56 degrees C) and acidic pH (pH 2). Keratinocyte differentiation did not alter the release of KD-CIFs into KCM. These results provide further evidence that type I collagen expression and synthesis in fibroblasts are regulated by a keratinocyte-releasable factor(s) with an apparent molecular weight between 30 and 50 kDa.     

Differentiated keratinocyte-releasable stratifin (14-3-3 sigma) stimulates MMP-1 expression in dermal fibroblasts

Through the use of a keratinocyte/fibroblast co-culture system, we have recently identified a potent keratinocyte-derived anti-fibrogenic factor (KDAF) for dermal fibroblasts. A sequential chromatography of the active fractions of keratinocyte-conditioned medium (KCM) and peptide mapping of the candidate proteins identified KDAF as being the keratinocyte-releasable 14-3-3 sigma (14-3-3sigma) protein, which is also known as stratifin. In this study, we hypothesize that differentiated, but not proliferating, keratinocytes are the primary source of releasable 14-3-3sigma in conditioned medium. To address this hypothesis, in a longitudinal study, keratinocyte differentiation was induced by growing these cells in a medium consisting of 50% keratinocyte serum-free medium (KSFM) and 50% Dulbecco's modified eagle's medium without any additives for up to 20 d. When KCM was collected every other day and added to fibroblasts, the level of matrix metalloproteinase (MMP)-1 mRNA expression was markedly increased in fibroblasts receiving KCM and this increase was even greater in cells receiving conditioned media collected at later time points relative to that of controls. The results of a western blot analysis further showed a marked increase in the expression of 14-3-3sigma protein in keratinocytes grown in test medium from day 4 to day 10. This finding was consistent with the levels of 14-3-3sigma mRNA expression in differentiated keratinocytes. In contrast to a very high level of 14-3-3sigma mRNA expression seen in keratinocytes, fibroblasts that are highly responsive to14-3-3sigma were unable to express this factor. Interestingly, the level of 14-3-3sigma mRNA expression was markedly higher in keratinocytes co-cultured with fibroblasts relative to that of mono-cultured keratinocytes. In conclusion, this study provides evidence that keratinocytes express a high level of 14-3-3sigma at the levels of mRNA and protein. But the releasable form of 14-3-3sigma protein was only found in conditioned medium derived from differentiated keratinocytes. Further, our recently purified recombinant 14-3-3sigma protein mimics the collagenase stimulatory effect of KCM in dermal fibroblasts.     

The spontaneous resolution of photosensitivity and contact allergy in a patient with chronic actinic dermatitis

Chronic actinic dermatitis (CAD) is an uncommon photodermatosis in which patients typically exhibit photosensitivity together with contact allergy. Improvement of the photosensitivity over time is well recognized in a proportion of patients but the concurrent resolution of contact allergy is rare. We report on a 46-year-old female with longstanding CAD who demonstrated resolution of both of these features.     

A case of febrile ulceronecrotic Mucha-Habermann disease responsive to systemic corticosteroids

Febrile ulceronecrotic Mucha-Habermann disease (FUMHD) is a rare, potentially fatal subtype of pityriasis lichenoides et varioliformis acuta (PLEVA). Herein, we present a rare case of a 14-year-old male without significant past medical history who was diagnosed with FUMHD without a clear inciting factor. He was effectively treated with systemic corticosteroids with complete resolution of symptoms.     

A patient with cupping-related post-inflammatory hyperpigmentation successfully treated with a 1,927 nm thulium fiber fractional laser

Abstract

Post-inflammatory hyperpigmentation is a rare complication following cupping therapy. We report a case of a 26-year-old woman who presented with hyper-pigmented skin lesions on her lower back which was persistent for 6 months following cupping therapy. The 1,927 nm thulium fiber laser (Fraxel re:store Dual, Solta Medical Inc., Hayward, CA) was tested leading to near complete resolution within four sessions.     

Acute dysarthria induced by low dose methotrexate therapy in a patient with erythrodermic cutaneous T-cell lymphoma: an unusual manifestation of neurotoxicity

Neurotoxicity has been associated on rare occasions with methotrexate therapy. We now report the case of a 71-year-old man with erythrodermic cutaneous T-cell lymphoma who developed symptoms of dysarthria and inco-ordination within 1 month of the initiation of oral methotrexate; discontinuation of the therapy then resulted in a gradual resolution of the problems.