Cases Of Actinic Keratosis Research Articles

A Multistep Voriconazole-Related Phototoxic Pathway May Lead to Skin Carcinoma: Results From a French Nationwide Study

Voriconazole long-term therapy is suspected to induce cutaneous squamous cell carcinoma (SCC), as suggested by 18 case reports worldwide and 3 retrospective studies. To better characterize the natural history of these potentially voriconazole-associated tumors, a nationwide call for notification of skin cancers and other skin lesions observed between 2002 and 2012 in patients treated by voriconazole was launched in France. A multidisciplinary committee evaluated voriconazole involvement in each case. Nineteen SCCs were reported. The committee determined the likelihood of voriconazole involvement to be high in 15 cases, intermediate in 2, and low in 2. In the 17 patients with high/intermediate likelihood of voriconazole involvement, the mean time between voriconazole initiation and SCC diagnosis was 39 ± 18 months (range, 28-84 months), and was shorter in transplant recipients (35 vs 45 months, P < .05). Cumulative mean duration of voriconazole therapy at SCC diagnosis was 35 months (range, 7-63 months). A multistep process was noted in 14 of 17 patients: acute phototoxicity during the first year of voriconazole therapy (mean time, 6 months [range, 0-18 months]), actinic keratosis (AK) of the same sun-exposed skin area in the second/third year (mean, 30 months [range, 11-57 months]), followed by SCC during the third year or later. Five cases of AK without SCC and 37 cases of other skin lesions were also reported. Our results suggest that long-term voriconazole prescription may be associated with a multistep phototoxic process involving acute skin lesions followed by AK then by SCC. Discontinuation of voriconazole should be strongly considered in patients experiencing chronic phototoxicity.

Significance of Cyclooxygenase 2, EZH-2 Polycomb Group and p53 Expression in Actinic Keratosis and Squamous Cell Carcinomas of the Skin

The development and progression of squamous cell carcinoma (SCC) of the skin is characterized by an accumulation of molecular changes. The aim of this study was to investigate the association of the immunohistochemical expression of cyclooxygenase-2 (COX-2), enhancer of zeste homolog 2 (EZH-2), and p53 in actinic keratosis (AK) and SCC and detect any differences between invasive and preinvasive squamous epidermal lesions. Forty-three cases with AK, 38 with SCC, and 9 with SCC arising on AK (SCC/AK) were studied. For COX-2 immunostaining, weak or no reaction was associated with AK (58.10% of cases), whereas moderate or strong reaction with SCCs (34.2% and 39.5%, respectively). Furthermore, 88.9% of the "mixed" SCC/AK specimens demonstrated moderate reaction (χ2 = 29.924, P < 0.0001). For EZH-2 immunostaining, a weak or no reaction was observed in 62.8% of AK cases, whereas a moderate reaction was observed in 42.1% of SCCs and 77.8% of "mixed" SCC/AK cases (χ2 = 18.91, P = 0.001). Weak immunoreactivity of p53 was associated with AK (58.1%), moderate with SCC (44.7%), and strong with SCC/AK lesions (66.7%) (χ2 = 15.999, P = 0.003). COX-2, p53, but mainly EZH-2 immune expression seems to be strongly associated with the biological potential of squamous epidermal cells and seems to be differentiating SCC by comparison to AK of the skin. The value of the combined expression of these markers is worth being further investigated as an additional tool for diagnostic, prognostic, and possibly, therapeutic use.

Aldehyde dehydrogenase 1 expression in basal cell carcinoma, actinic keratosis and Bowen’s disease

Aldehyde dehydrogenase (ALDH) is an enzyme responsible for oxidizing aldehydes to carbonic acids. ALDH1 is an isoform that is thought to be a stem cell marker as it is highly expressed in the stem cells of various organs. However, its expression in basal cell carcinoma (BCC), actinic keratosis (AK) and Bowen’s disease (BD) of the skin has not yet been analyzed. Twenty-five consecutive operative cases each of BCC, AK and BD, as well as 10 normal skin tissues were assessed for ALDH1 expression by immunohistochemistry. In normal skin, ALDH1 expression was observed in the suprabasal cells of the follicular infundibulum, inner cells of the outer root sheath and sebocytes. BCC cases (88%) showed no or focal-positive immunoreactivity for ALDH1. Focal immunopositivity for ALDH1 was observed in 44% of AK cases, while the remaining cases were ALDH1-negative. By contrast, diffuse positive immunoreactivity for ALDH1 was observed in 64% of BD cases. Differential expression patterns of ALDH1 in AK and BD may reflect the distinct cells of origin of these two conditions. Moreover, a low ALDH1 expression in BCC may also reflect the possible origin of BCC, the basal cells of the outer root sheath.

Selective in situ protein expression profiles correlate with distinct phenotypes of basal cell carcinoma and squamous cell carcinoma of the skin.

Non-melanoma skin cancer is the most common malignancy that shows increasing incidence due to our cumulative exposure to ultraviolet irradiation. Its major subtypes, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) differ in pathobiology, phenotype and clinical behavior, which must be reflected at the molecular level. In this study, protein expression profiles of BCC and SCC were tested in tissue microarrays and correlated with that of actinic keratosis, Bowen's disease, seborrheic keratosis and normal epidermis by detecting 22 proteins involved in cell interactions, growth, cell cycle regulation or apoptosis. The significantly more reduced collagen XVII, CD44v6, pan-Desmoglein levels and more evident E-Cadherin delocalization in BCC compared to SCC correlated with the de novo dermal invasion of BCC against the progressive invasion from in situ lesions in SCC development. EGFR was also expressed at a significantly higher level in SCC than in BCC. The upregulated cell communication protein connexin43 in BCC could contribute to the protection of BCC from metastatic invasion. Elevated cell replication in BCC was underlined by the increased topoisomerase IIα and reduced p21(waf1) and p27(kip1) positive cells fractions compared to SCC. Compared to differentiated keratinocytes, caspase-8 and -9 were equally upregulated in skin carcinoma subtypes for either mediating apoptosis induction or immune escape of tumor cells. Hierarchical cluster analysis grouped SCC and actinic keratosis cases exclusively together in support of their common origin and malignant phenotype. BCC cases were also clustered fully together. Differentially expressed proteins reflect the distinct pathobiology of skin carcinoma subtypes and can serve as surrogate markers in doubtful cases.

CD10 Expression in Cutaneous Squamous Cell Carcinoma and Its Precursor Lesions: Evaluation Using Tissue Microarray

CD10 Expression in Cutaneous Squamous Cell Carcinoma and Its Precursor Lesions: Evaluation Using Tissue Microarray

Reduced P53 staining in actinic keratosis is associated with squamous cell carcinoma: A preliminary study

Background:Actinic keratosis (AK) is a cutaneous neoplasm caused by prolonged sun exposure, and may progress into squamous cell carcinoma (SCC). The p53 gene plays a central role in the development of SCC, and mutations in this gene are found in 90% of SCC and up to 100% of AK cases.Objective:To identify AK cases that are highly susceptible to developing SCC.Materials and Methods:Fifty-six AK cases were classified into two groups: AK adjacent to “normal” skin and AK adjacent to SCC. The groups were compared based on epithelial atypia, inflammation, solar elastosis, histopathological AK classification and p53 protein expression.Results:Of the 56 AK cases analyzed, 23% were associated with SCC. The types of AK observed were classified as follows: common, hypertrophic, atrophic, acantholytic, pigmented and bowenoid. SCC was associated with common and hypertrophic AK, and p53 staining was observed in 78% of AK cases. The mean difference in p53 immunopositivity between common AK cases associated with SCC (17%) and not associated with SCC (45.4%) was significant (p=0.011).Conclusions:Hypertrophic and common AK are associated with SCC, and the low percentage of p53 immunopositivity in the common type indicates a greater probability of developing into SCC.

Abstract 5531: Lumican as a novel differential diagnostic maker for Bowen's disease and actinic keratosis

Abstract BACKGROUND: Lumican is a member of the small leucine-rich proteoglycan (SLRP) family and regulates the assembly and diameter of collagen fibrils in the extracellular matrix in human tissue. Mice homozygous for a null mutation in lumican display corneal opacification and skin laxity. Recent studies have shown that lumican is expressed in various types of malignant tumors including breast, colorectal, and pancreatic cancer, and osteosarcoma and malignant melanoma, and that it plays an important role in the growth of tumors. However, little has been studied about the expression pattern and role of lumican in non-melanoma skin cancer. In this study, we examined the expression levels of lumican in in situ lesions of squamous cell carcinoma (SCC) of the skin, actinic keraotsis and Bowen's disease, to discover whether lumican can be used as a novel differential diagnostic marker for such skin tumors, particularly for bowenoid actinic keratosis and Bowen's disease in sun-exposed areas of the body. Bowenoid actinic keratosis and Bowen's disease are often difficult to distinguish in both the clinical setting and commonly prepared pathological specimens. Furthermore, invasive SCC arising in actinic keratosis is considered low-risk clinically, while Bowen's disease with invasion is considered high-risk. Thus, it is important to distinguish between actinic keratosis and Bowen's disease, and reliable differential markers for these diseases are required.METHOD: Twenty-nine cases of actinic keratosis, including 4 of the bowenoid sub-type, and 37 cases of Bowen's disease, including 6 in sun-exposed areas of the body, were selected from among patients undergoing surgical resection at the Department of Dermatology at the Nippon Medical School from 2006 to 2010. We evaluated lumican expression and mRNA in these cases using immunohistochemistry and in situ hybridization analysis, respectively. RESULTS: Immunohistochemical analysis indicated that Lumican was expressed in 34 of 37 patients with Bowen's disease (91.8%), but was not detected in any of the cases of actinic keratosis. In situ hybridization analysis revealed that lumican mRNA was expressed in the cytoplasm of immunohistochemically lumican-positive tumor cells in Bowen's disease. CONCLUSION: These findings suggest that lumican plays an important role in the pathogenesis of Bowen's disease and will be a useful marker for the differential diagnosis between Bowen's disease and actinic keratosis, particularly for bowenoid actinic keratosis and Bowen's disease occurring in sun-exposed areas of the body. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5531. doi:1538-7445.AM2012-5531

Ber‐EP4 is a useful marker for follicular germinative cell differentiation of cutaneous epithelial neoplasms

Ber-EP4 is a monoclonal antibody that recognizes 34-kDa and 39-kDa non-covalently linked glycopolypeptides expressed by most human epithelial cells and carcinomas. In this study, we performed immunohistochemical staining of 31 cases of basal cell carcinoma (BCC); 20 cases of trichoblastoma (TB), including ten cases of nodular type, eight cases of cribriform type (trichoepithelioma) and two cases of columnar type (desmoplastic trichoepithelioma); 16 cases of actinic keratosis (AK); and 10 cases each of Bowen's disease, poroma and seborrheic keratosis. Six cases of BCC and AK were co-lesions of both neoplasms. In normal skin tissue, Ber-EP4 reacted positively with the secretory portion of eccrine glands and follicular germinative cells at the lower end of catagen hairs. Neoplastic cells in 97% of cases with BCC reacted positively with Ber-EP4 in at least 5% of neoplastic cells. Those in 90% with nodular type TB and 50% with trichoepithelioma also reacted positively in at least 5% of neoplastic cells. No cases of poroma, seborrheic keratosis, AK or Bowen's disease were immunohistochemically positive for Ber-EP4 in neoplastic cells. In all six cases with co-lesions of BCC and AK, neoplastic cells of BCC reacted positively with Ber-EP4 and those of AK were negative. Immunohistochemical examination using the Ber-EP4 antibody is a useful tool for diagnosing neoplasms with follicular germinative differentiation, such as TB, TE or BCC, and for differentiating those from squamous cell carcinoma in situ, poroma or seborrheic keratosis.

Cathepsin K expression in basal cell carcinoma

Cathepsin K is a cysteine protease with strong collagenolytic and elastolytic properties. Recently, cathepsin K expression in tumour cells of malignant melanoma and in the stromal cells of squamous cell carcinoma of the skin has been reported to play an important role in tumour progression. However, its expression profile in basal cell carcinoma (BCC) has not yet been clarified. The aim of this study is to examine the expression profile of cathepsin K in both the tumour cells and the peritumoural stromal cells of BCC in comparison with its expression in normal skin. Fifty consecutive operative cases of BCC, 10 cases of actinic keratosis, 10 cases of Bowen's disease and five normal skin tissues were assessed for cathepsin K expression by immunohistochemical methods. In normal skin, cathepsin K expression was observed in the stratum corneum, mature sebaceous cells and outer root sheath of the hair follicles. Cathepsin K was expressed in the tumour cells of all BCC cases, in which 90% showed diffuse expression (>51% of tumour cells), as well as in the peritumoural stromal cells in all BCC cases. Focal cathepsin K expression was observed in the tumour cells of Bowen's disease (2/10 cases), but not in any of actinic keratosis (0/10 cases). Cathepsin K expression may contribute to tumour invasion and peculiar histopathological features, such as fibromucinous stroma around the tumour nests by mediating extracellular matrix degradation in BCC.

The expression of p53 and cox-2 in basal cell carcinoma, squamous cell carcinoma and actinic keratosis cases

The aim of this study was to investigate p53 and COX-2 expressions in basal cell carcinoma, squamous cell carcinoma and actinic keratoses, and to determine a possible relationship. 50 basal cell carcinoma, 45 squamous cell carcinoma and 45 actinic keratosis cases were evaluated. The type of tumor in basal cell carcinoma and tumor differentiation in squamous cell carcinoma were noted and the paraffin block that best represented the tumor was chosen. Immunostaining by p53 and COX-2 was performed on sections of the paraffin blocks. p53 expression was observed in 98% of basal cell carcinoma, 88.9% of squamous cell carcinoma and all actinic keratosis cases. p53 expression was also noted in non-dysplastic appearing epithelium in actinic keratosis cases. COX-2 expression was seen in 90, 100 and 88.9% of the basal cell carcinoma, squamous cell carcinoma and actinic keratosis groups, respectively. Skin appendages, inflammatory cells and vascular structures were also stained by COX-2 besides tumor tissue. COX-2 expression increased by the p53 expression increase in basal cell carcinoma and squamous cell carcinoma. p53 and COX-2 expressions were not related in terms of tumor type in the BCC and were not related in terms of differentiation in SCC. The existence of p53 expression in actinic keratosis cases has supported the idea that p53 plays a role in the early steps of carcinogenesis in skin cancers. The fact that the expression of COX-2 increases in line with the increase of p53 expression in basal cell carcinoma and squamous cell carcinoma cases indicates that COX-2 expression may be affected by p53.

Detection of human papillomavirus DNA in feline premalignant and invasive squamous cell carcinoma

Squamous cell carcinoma (SCC) is the most common malignant cutaneous and oral neoplasm of cats. Papillomavirus (PV) DNA has been identified in a proportion of feline Bowenoid in situ carcinomas (BISCs), cutaneous SCCs and a single oral SCC, but its exact role in the pathogenesis remains unknown. In humans, it has been suggested that ultraviolet (UV) light and human PV (HPV) may act as cofactors in cutaneous SCC carcinogenesis. Little is known about the influence of UV light on PV prevalence in feline cutaneous lesions, including actinic keratosis (AK). Additionally, PV prevalence in noncutaneous feline lesions, including oral SCC, is largely not known. This study aimed to determine the presence of PV in 84 cats with premalignant and invasive SCC from cutaneous and noncutaneous sites using polymerase chain reaction and to investigate an association with UV light. Papillomaviral DNA was amplified from two of 12 cases of AK, seven of 22 BISCs, nine of 39 cutaneous SCCs and two of 35 non-cutaneous SCCs. Of the PV DNA sequenced, 50% was most similar to HPV of the genus Betapapillomavirus, while the other 50% was most similar to Felis domesticus PV type 2. Exposure to UV was not associated with an increase in PV for cutaneous SCC. The results of this study suggest that in the cat, HPV DNA may be detectible within a higher percentage of squamous lesions than previously demonstrated, UV exposure may not be a confounder for PV presence, and noncutaneous lesions may have a low prevalence of PV.

5-Aminolevulinic acid-mediated photodynamic therapy to superficial malignant skin tumors using Super Lizer

Photodynamic therapy (PDT) using topically applied 5-aminolevulinic acid (ALA) has become a generally accepted treatment modality for superficial malignant skin tumors. However, the costly excimer-dye laser, diode laser and light-emitting diode (LED) frequently used to administrate PDT are impractical to use in most dermatology clinics. This study evaluated the effectiveness of ALA-mediated PDT using a Super Lizer (Tokyo Iken, Tokyo, Japan) equipped with band-pass filters in 38 patients with superficial malignant skin tumors (33 cases of actinic keratosis and five cases of Bowen's disease). Twenty-one cases (18 cases of actinic keratosis and three cases of Bowen's disease) were successfully treated, and the other 17 cases (15 cases of actinic keratosis and two cases of Bowen's disease) showed partial remission after single or repeated administration of PDT. PDT repeated three times at weekly intervals was more effective against actinic keratosis than randomly repeated procedures. The Super Lizer is easy to handle and move, and is less expensive than other known machinery and is useful for PDT in dermatology, especially under the protocol of three times at weekly intervals for the treatment of actinic keratosis.

The incidence of Demodex species in skin biopsy specimens diagnosed as actinic keratosis and nonmelanoma skin cancer.

Background: The most common types of skin cancers include basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), which are grouped as non-melanoma skin cancers. Actinic keratosis (AK) is a precancerous lesion that may develop into SCC. The pilosebaceous follicle mites, Demodex folliculorum and Demodex brevis, inhabit most commonly and densely certain facial skin areas where BCC and SCC also develops most frequently. Objective: Determine the prevalence of Demodex species in skin biopsy specimens diagnosed as SCC, BCC, and AK. Method: Specimens of the patients whose reports were available were studied in terms of Demodex. The specimens were stained using Hematoxylin and Eosin, and evaluated for Demodex species positivity. Results: There were Demodex species in seven (38.9%) out of 18 AK cases, 12 (31.6%) out of 38 SCC cases, and 26 (44.8%) out of 58 BCC cases of this study. The rate of Demodex species in patients diagnosed SCC, BCC, and AK was found to be rather high. Conclusion: Demodex species should also be evaluated in the follow-up of the treatment of patients in SCC, BCC, and AK group.

Benign lip lesions. A 10-year retrospective study

This paper aims to present a retrospective analysis of a cohort of patients with benign lip lesions managed over the last decade at the Department of Maxillofacial Surgical Oncology of Theagenio Cancer Hospital of Thessaloniki. It aims to highlight the substantial clinical and histological diversity of the lesions, as well as to present an epidemiological analysis for the specific cohort/population. During the period 1995-2004 a total of 420 patients were managed for lip lesions. Of these, 280 were malignant and 116 benign. A total of 24 cases of actinic keratosis were added in the latter group. Of the benign lesions, the commonest were haemangiomas (19.28%), actinic keratosis (17.14%), intradermal naevus (14.28%), fibroma (9.28%), papilloma (7.85%), mild and moderate dysplasia (7.85%) and mucocele (7.14%). The group included 17 different histological types of benign lesions. The most frequent site of presentation was the lower lip (56.42%). Post-operative follow-up ranged from 6 months to 2 years (average 15.5 months). There was a single case of recurrence during follow-up. Benign lip lesions do not usually pose a problem for the clinician and their surgical management is straightforward. Accurate auditing and detailed statistical analysis aid in disease prevention and help avoid errors in diagnosis and management.

The Keratin-14 Expression in Actinic Keratosis and Squamous Cell Carcinoma: Is This a Prognostic Factor for Tumor Progression?

Actinic keratosis (AK) is an incipient form of cutaneous squamous cell carcinoma (SCC). We determined if the pattern of expression of keratin-14 (K14) is a factor for tumor progression in AK and SCC. Eighteen sections from the tissues of 16 patients were stained with anti-K14 antibody and p16(INK4a). Among the 16 patients, 4 were diagnosed with both SCC and AK at the same site, but AK developed first and SCC developed subsequently. Thus, SCC may have evolved from AK. The other 12 patients were only diagnosed with AK. In all of the AK and SCC tissues, basement membranes showed positive staining for K14. However, strong reactivities were shown in the spinous and granular layers and focuses of dermal invasion in the SCC tissues developed from AK. Two and 3 of the 12 AK cases had moderately positive reactions for K14 in the spinous and granular layers, respectively. Also, all SCC tissues except one had moderate-to-strong reactions in the basal, spinous, and granular layers for p16(INK4a). Two of the 12 AK cases had weak-to-moderate positive reactions in the basal, spinous, and horny layers for p16(INK4a). The results of our study advance our understanding of the pathogenesis of SCC developing from AK. The results also indicate a differential role in the control of K14 in normal epithelia, AK, and SCC. K14 expression in the spinous and granular layers may be a prognostic factor for tumor progression of AK.

Expressão de marcadores de proliferação celular e apoptose no carcinoma espinocelular de pele e ceratose actínica

Skin cancer is the most frequent type of human cancer and has shown an increase in its incidence. In many cases, before the onset of the carcinoma, there might be a precursor lesion--actinic keratosis, which can develop into squamous cell carcinoma. Studies have been carried out in order to determine the parameters that have prognostic significance in predicting those tumors which have more aggressive behavior. To evaluate the expression of markers of cell proliferation (PCNA, Ki-67) and apoptosis (p53,Bcl-2) in patients with squamous cell carcinoma and actinic keratosis. We studied samples from 30 patients, ten patients of squamous cell carcinoma, ten with actinic keratosis and ten lesion-free samples from blepharoplasty. p53 protein was expressed in all cases with different quantitative patterns. Bcl-2 was expressed at low intensity in six cases of actinic keratosis in the skin from blepharoplasty and negative in cases of squamous cell carcinoma. PCNA showed intense expression in all samples. Ki-67 showed variable expression in cases of keratosis and carcinoma and negative in the skin from the eyelid. The high expression of Ki-67 associated with low expression of Bcl-2 indicates proliferation in the carcinoma group. Thus, expression of p53 and Bcl-2 in patients with actinic keratosis indicates cell immortalization.

Actinic keratosis associated with squamous and basal cell carcinomas: an evaluation of neoplastic progression by a standardized AgNOR analysis

In an attempt to investigate the neoplastic progression in different stages of actinic keratosis (AK), a standardized AgNOR analysis was performed in 94 cases of AK, 35 of which were associated with squamous cell carcinoma (SCC) or basal cell carcinoma (BCC), and in 31 cases of SCC and 22 cases of BCC. The cases were subdivided into low- and high-AgNOR-expressing (AgNOR status) AK by using the mean area of AgNORs per cell (NORA) value (3.996 micro(2)) as the cut-off. In AK samples, a progressive increase of the mean NORA value from Stage I to Stage IV was encountered. In addition, a significantly higher mean NORA value was found in the AK cases associated with SCC, in comparison to those without SCC; by contrast, no significant differences in the mean NORA value were noted between AK cases with or without BCC. A highly significant association between a high AgNOR quantity and the coexistence of SCC was encountered in AK; no association was appreciable between the AgNOR quantity and the co-occurrence of BCC. Moreover, when the co-existence of SCC in AK was considered as the reference point, the AK cases associated with SCC mostly (95.5%) presented a high AgNOR quantity (high sensitivity), but only 57.6% of cases without SCC displayed a low AgNOR quantity (low specificity). Additionally, our data document that the standardised AgNOR analysis represents a strong negative predictor for the association between SCC and AK. Indeed, a low AgNOR quantity mostly is associated with AK cases without SCC.

Activation of fibroblast growth factor receptor 3 and oncogene-induced senescence in skin tumours

The activation of oncogenes is an important step in tumorigenesis, and recently, oncogene-induced senescence (OIS) was proposed as a critical barrier against malignant transformation in normal primary cells. The aim of this study was to examine the activation of fibroblast growth factor receptor 3 (FGFR3) as an oncogene product and OIS in human skin tumours. We investigated the activation of FGFR3 and OIS by mutation and immunohistochemical analysis in skin tumours, including seborrhoeic keratosis, actinic keratosis (AK), Bowen's disease (BD), basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Activated point mutations of FGFR3 were identified in four of 22 cases (18%) of seborrhoeic keratosis, but no mutation was detected in the other skin tumours. Twenty-seven of 31 cases (87%) of seborrhoeic keratosis showed moderately to strongly positive expression of the FGFR3 protein, but almost all the other skin tumours were negative. On the other hand, almost all the seborrhoeic keratoses showed negative immunoreactivity for antiphoshohistone H2AX (gamma-H2AX) as a marker of OIS, but 17 of 22 cases (77%) of AK were moderately to strongly positive. Immunoreactivity for gamma-H2AX was significantly greater in AK than in seborrhoeic keratosis, BD, BCC and SCC. The activation of FGFR3 might be a common feature in the tumorigenesis in seborrhoeic keratosis, although the activation does not induce a typical oncogenic signal in keratinocytes. In addition, OIS due to some oncogenic signals rather than activation of FGFR3 might be involved in the early skin carcinogenesis related to chronic ultraviolet radiation exposure.

Cutaneous Squamous Cell Carcinoma and Inflammation of Actinic Keratoses Associated with Sorafenib

Background Sorafenib-induced dermatologic toxicity is common and consists primarily of dry skin, maculopapular rash, hand-foot skin reaction, and alopecia. Cutaneous squamous cell carcinoma (SCC) and inflammation of actinic keratosis (AK) were reported in 2 patients treated with sorafenib (Lacouture et al), but the scope of this observation has not been evaluated. Patients and Methods We reviewed medical records of 131 patients with metastatic renal cell carcinoma treated with single-agent sorafenib at our institution from June 1, 2005, through April 4, 2007. Results We identified 7 cases of cutaneous SCC, 2 cases of SCC keratoacanthoma type, 2 cases of focal squamous atypia, and 3 cases of AKs. The time to development of SCC or AK from the start of sorafenib was 9.3 months (median, 6.5 months; range, 0.9–43 months). Ten of these 14 patients discontinued therapy with sorafenib: 7 patients as a result of disease progression, 2 patients as a result of nondermatologic toxicity, and 1 patient as a result of dermatologic toxicity. Four patients are continuing sorafenib therapy at reduced doses because of diarrhea and fatigue. One patient receiving sorafenib at a 25% dose reduction developed a second invasive SCC lesion on his forearm 6 months after the initial resection. Conclusion These data suggest that there could be an association between sorafenib therapy and the development of cutaneous SCC and inflammation of AK. This adverse event has important therapeutic implications. Full appraisal of this observation in prospective studies is warranted.

Clinical, Histologic, and Immunohistochemical Analyses of Feline Squamous Cell Carcinoma In Situ

Actinic keratosis (AK) and Bowenoid in situ carcinoma (BISC) are two distinct forms of in situ squamous cell carcinoma in felines. They usually occur on different locations and present with specific clinical and histologic features. However, in some cases, these diseases cannot be distinguished either clinically or histopathologically. The aim of the present study was to determine the accuracy of diagnosis based on clinical or histologic criteria alone, and whether immunohistochemistry for papillomavirus or p53 can improve the accuracy of diagnosis. A series of in situ squamous cell carcinoma cases (n = 45) were selected according to their location and initial histologic classification and subsequently classified as AK (n = 22) or BISC (n = 23) according to the clinical criteria and were reevaluated histologically by 2 dermatopathologists. All BISC cases and most of the AK cases (n = 15) were confirmed histologically. In 7 cases clinically classified as AK, this diagnosis was not unanimously confirmed histologically because of the presence of overlapping features. P53 immunoreactivity was observed in 11/14 (79%) confirmed AK cases and in 4/22 (18%) BISC cases, while papillomavirus antigen was not detected in any confirmed AK case but was detected in 11/23 (48%) BISC cases. It was concluded that BISC can usually be reliably diagnosed histologically. The histologic diagnosis of lesions clinically suggestive of AK might sometimes be difficult. Results of immunohistochemistry for p53 and papillomavirus antigen were supportive for a role of sun exposure and papillomavirus in the pathogenesis of AK and BISC, respectively.