Basal Cell Carcinoma of the Scrotum: Clinicopathologic Analysis of 10 Cases

Background

Basal cell carcinoma (BCC) located on the scrotum is rare.

To analyze clinical and pathologic features, discuss therapeutic strategies, and identify prognostic factors of scrotal BCC in Chinese patients.

Between 2000 and 2010, 10 patients with scrotal BCC were diagnosed and treated at our institution. A review was performed using the clinical records and dermatopathologic slides of these patients.

The median patient age was 70. Skin lesions presented as red nodules and brownish plaques. All patients were treated using wide excision without adjuvant therapy. After an average follow-up of 47 months, eight patients were in good health without any relapse. One patient developed left inguinal lymph node metastasis at 21 months that was successfully treated using bilateral inguinal lymphadenectomy. One patient developed bilateral pulmonary metastasis at 48 months and was palliatively treated with chemotherapy. The clinical and histopathologic risk factors predisposing to metastasis were large primary neoplasms; a long period of misdiagnosis; and infiltrating, morpheaform, spiky, irregular outline pathologic patterns.

BCC of the scrotum is rare. It can metastasize after a long period of initial therapy. Long-term surveillance including a complete metastatic examination is recommended for these patients.

Dermoscopy of Small Basal Cell Carcinoma: Study of 100 Lesions 5 mm or Less in Diameter

Read more [J Dermatol Surgery]

No Association between Infections, HLA Type and Other Transplant-related Factors and Risk of Cutaneous Squamous Cell Carcinoma in Solid Organ Transplant Recipients.

Acta Derm Venereol. 2012 Feb 1;
Ingvar A, Smedby KE, Lindelöf B, Fernberg P, Bellocco R, Tufveson G, Höglund P, Adami J

Recipients of solid organ transplants are at a markedly increased risk of cutaneous squamous cell carcinoma (SCC). We investigated potential associations between post-transplant infections, HLA type, and other transplant-related factors and risk of SCC, taking immuno-suppressive treatment into account. A population-based case-control study was conducted. All patients who developed SCC during follow-up (1970-1997) were eligible as cases (n = 207). Controls (n = 189) were individually matched to the cases on age and calendar period of transplantation. Detailed exposure information was collected through an extensive, blinded review of medical records. Odds ratios were computed with conditional logistic regression. There were no significant associations with any infectious agents, or with number and timing of infections, specific HLA-type, donor characteristics, or other transplant characteristics and risk of post-transplant SCC. These results suggest that risk of post-transplant SCC is neither closely related to specific post-transplant infectious disorders, nor to the infectious load or specific HLA types.
Read more [Acta Derm Venereol]

Incidental Gastric Signet-ring Cell Carcinoma Metastasis to the Skin in Basal Cell Carcinoma.

Acta Derm Venereol. 2012 Feb 1;
Nakamura Y, Satomi K, Noguchi M, Shibata-Ito M, Fujisawa Y, Kawachi Y, Otsuka F

Read more [Acta Derm Venereol]

Eccrine Poromatosis Associated with Polychemotherapy.

Acta Derm Venereol. 2012 Feb 1;
Fujii K, Aochi S, Takeshima C, Ohtsuka M, Hamada T, Asagoe K, Aoyama Y, Morizane S, Iwatsuki K

Eccrine poroma frequently occurs as a solitary tumour, and only a few reports have described the occurrence of multiple lesions. Multiple eccrine poromas, or eccrine poromatosis, may occur in patients who have undergone radiotherapy and/or polychemotherapy. We report here four cases of multiple eccrine poromas in patients who were either undergoing, or had undergone, intensive chemotherapy (from 6 months to 16 years prior to onset). Three patients had non-Hodgkin's lymphoma and one had malignant fibrous histiocytosis. The number of lesions varied from 3 to > 20 in each patient, and all the lesions occurred on non-irradiated skin. The histopatho-logical features were consistent with those of eccrine poroma, Pinkus type. In addition to radiation therapy, intensive chemotherapy may play a role in the pathogenesis of multiple eccrine poromas even many years after treatment.
Read more [Acta Derm Venereol]

Clinical Manifestations of Cutaneous Metastases: A Review with Special Emphasis on Cutaneous Metastases Mimicking Keratoacanthoma

Read more [Amer J Clin Dermatol]

A patient with neviod basal cell carcinoma syndrome treated successfully with photodynamic therapy: case report and review of the literature.(CASE REPORTS)(Case study)

ABSTRACT Nevoid basal cell carcinoma syndrome (NBCCS) is a genetic disorder characterized by multiple basal cell carcinomas (BCCs) in addition to skeletal abnormalities and other neoplasms. Difficulty lies in treating the large number of BCCs that develop in these patients. The authors report a

Publication: Journal of Drugs in Dermatology
Read more [Drugs in Dermatology]

Rapid wound re-epithelialization and basal cell carcinoma clearance after Mohs micrographic surgery with postoperative photodynamic therapy.(Clinical report)

ABSTRACT Background: Methyl aminolevulinic acid photodynamic therapy (MAL-PDT) has antitumor activity and may promote wound healing. Superficial and nodular basal cell carcinomas (BCCs) have been successfully treated with MAL-PDT in prior reports. In vitro and animal studies have shown more rapid

Publication: Journal of Drugs in Dermatology
Read more [Drugs in Dermatology]

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

Abstract

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.

Treatment of folliculitis decalvans with tacrolimus ointment

Abstract

Folliculitis decalvans is an embarrassing and challenging disease with no established treatment guidelines. In this paper, we described four patients with this disease treated successfully with Tacrolimus ointment. All of them showed significant control of the condition, stopping inflammatory lesions and progression of the disease, although weak transitory outbreaks of inflammatory lesions were observed in some cases. Alopecia and tufted hairs remained unchanged. The discontinuation of the therapy produced rapid relapses in all cases. Close monitoring of these patients is recommended due to the potential risk of malignant transformation of the disease.

Microarray analysis reveals increased expression of ΔNp63α in seborrhoeic keratosis

Summary

Background  Seborrhoeic keratoses (SKs) are very common benign epidermal lesions without malignant potential. Ultraviolet radiation, old age and viruses are well-known risk factors for disease development. However, the pathomechanisms of SK are not fully understood.

Objectives  To detect and characterize the genes that are involved in the pathogenesis of SK.

Methods  We performed a gene expression study using paired lesional and nonlesional skin samples from patients with SK.

Results  We identified and validated 19 differentially expressed genes in SK. Of these 19 genes, we focused on p63 transcription factor, which plays a pivotal role in epidermal development by regulating its transcriptional programme. We found by immunofluorescence that the expression of ΔNp63α, the most abundantly expressed p63 isoform, was significantly increased in SK as compared with normal skin. Moreover, siRNA-mediated knockdown of ΔNp63 led to the downregulation of 11 genes, including a member of the tensin family TNS4. Chromatin immunoprecipitation assay revealed that TNS4 was a target gene of p63.

Conclusions  We identified upregulated genes in SK using genome-wide cDNA microarray and elucidated the functional contribution of p63 to the disease transcriptome by gene-silencing assay. Taken together, these data may provide a novel insight into the molecular basis of these benign skin lesions.

Glutathione S-transferase genotype is associated with sensitivity to psoralen–ultraviolet A photochemotherapy

Summary

Background  There is marked interpatient variation in responses to psoralen–ultraviolet A (PUVA) photochemotherapy. Identification of molecular biomarkers of PUVA sensitivity may facilitate treatment predictability. The glutathione S-transferases (GSTs) influence cutaneous defence against UV radiation-induced oxidative stress and are therefore candidate biomarkers of PUVA sensitivity. Several human GSTs, including GSTM1 and GSTT1, are polymorphic, and null polymorphisms have been associated with increased UVB erythemal sensitivity and skin cancer risk. PUVA also increases skin cancer risk.

Objectives  To investigate the effect of GST genotype on PUVA sensitivity.

Methods  We investigated GST genotype in patients starting PUVA (n = 111) and the effects of 8-methoxypsoralen (8-MOP) on antioxidant response element (ARE)-regulated gene expression in mammalian cells.

Results  Lower minimal phototoxic doses (MPD) (P = 0·022) and higher serum 8-MOP concentrations (P = 0·052) were seen in GSTM1-null allele homozygotes compared with patients with one or two active alleles. In a subset of patients with psoriasis (n = 50), the GSTM1 genotype was not associated with PUVA outcomes, although MPD [hazard ratio (HR) 1·37; 95% confidence interval (CI) for HR 1·15–1·64] and GSTT1-null (HR 2·39; 95% CI for HR 1·31–4·35) and GSTP1b (HR 1·96; 95% CI for HR 1·10–3·51) genotypes were associated with clearance of psoriasis in this patient group. Exposure of mammalian cells to 8-MOP induced gene expression via the ARE, a regulatory sequence in promoters of cytoprotective genes including GSTs, suggesting that these genes may be implicated in 8-MOP metabolism.

Conclusion  The polymorphic human GSTs are associated with PUVA sensitivity. Further studies are required to examine the clinical relevance of these preliminary findings.

Psoriasis: an evidence-based update. Report of the 9th Evidenced Based Update Meeting, 12 May 2011, Loughborough, U.K.

Summary

The Centre of Evidence Based Dermatology, University of Nottingham, U.K. holds an annual Evidence Based Update (EBU) Meeting focused on important dermatological topics, which have in the past included eczema, urticaria, blistering disorders, skin infections, skin cancer and hair disorders. These one-day meetings aim to summarize the most recent evidence in the form of systematic reviews and recently completed clinical trials. This year, the 9th EBU meeting took place in Loughborough, U.K. on 12 May 2011 and was devoted to psoriasis. The latest updates on topical treatments, nail psoriasis, genetics and clinical implications, rational use of biologics, new and unpublished studies on combination of phototherapy and biologics for psoriasis, and on treatments of palmoplantar pustular psoriasis were discussed by a panel of renowned international speakers.

Mammalian target of rapamycin (mTOR) inhibitors slow skin carcinogenesis, but impair wound healing

Summary Background  Recent studies suggest that patients on mammalian target of rapamycin (mTOR) inhibitors experience a reduction in cutaneous carcinogenesis by an estimated 50% or more compared with calcineurin inhibitors. While randomized trials are running, organ transplant recipients are frequently switched from calcineurin inhibitors to mTOR inhibitors when cutaneous carcinogenesis increases.

Objectives  To slow carcinogenesis in our patient, a heart transplant recipient with a neuropathic diabetic foot syndrome who had developed cutaneous carcinogenesis at a rate of more than 20 squamous cell carcinomas (SCC) annually.

Methods  The patient’s immunosuppression was switched from the calcineurin inhibitor ciclosporin to the mTOR inhibitor everolimus.

Results  Carcinogenesis slowed to six SCC annually; however, he developed recalcitrant diabetic foot ulcers which were purely neuropathic and nonangiopathic, and a limb-threatening fistulating necrotic erysipelas of the right leg. Both sites responded poorly to antibiotic therapy, offloading and debridement. This skin fistula became chronic and some toes were at risk for minor amputation. In view of the propensity for mTOR inhibitors to impair would healing, immunosuppression was switched back to ciclosporin. All wounds healed rapidly, but skin carcinogenesis rose to former levels.

Conclusions  This case impressively illustrates the clinical dilemma for mTOR inhibitor use where benefit in carcinogenesis is counterbalanced by impairment in wound healing. Changes in immunosuppressive regimens should thus be made on an individual basis with careful consideration of the relative risks.

The use of the Dermatology Life Quality Index in patients with malignant carcinoid syndrome

Read more [Brit J Dermatol]

Lip cancer: retrospective analysis of 181 cases

Summary

Background: In Germany little data on the epidemiology and histology of lip cancers are available, as lip cancers are commonly pooled together with head and neck tumors.

Patients and methods: Retrospective analysis of 181 patients with malignant tumors of the lips with respect to gender, location, histology, risk factors and comorbidity.

Results: There were 90 women and 91 men with a mean age of 71 years. 98 had a tumor on the upper lip and 83 patients on the lower lip. Tumors of the upper lip showed a slight female preference (61%). In contrast lower lip cancer was more common (64%) in men. Histological analysis revealed that in both regions nodular basal cell carcinomas as well as squamous cell carcinomas (NOS) are the most common subtypes. Vertical tumor thickness of squamous cell carcinomas was in most cases smaller than 6 mm (n = 71) and only in 4 cases was a tumor thickness of >6 mm detected. Altogether, 57% of the patients reported a high to very high sun exposure.

Conclusions: In comparison to previous studies we found a weaker preference for women for tumors of the upper lip and also a weaker preference for men for tumors of the lower lip. The causes remain unclear, but could be causally related to an increased life expectancy and/or changed risk profile.

Two cases of scleredema with pituitary–adrenocortical neoplasms: An underrecognized skin complication

Read more [J Dermatology (Япония)]

Cutaneous Horn: A Malignant Lesion? A Brief Review of the Literature

Read more [J Dermatol Surgery]

Cutaneous leishmaniasis mimicking inflammatory and neoplastic processes: a clinical, histopathological and molecular study of 57 cases

Background: Cutaneous leishmaniasis displays considerable variation in its histopathological and clinical presentation. Clinically, it progresses from a papule into a painless ulcerated and crusted nodule/papule. Microscopically, it progresses from sheets of amastigote-filled histiocytes to granulomatous inflammation.

Methods: The study was conducted on 145 skin biopsies from untreated patients with histopathological and/or clinical suspicion of cutaneous leishmaniasis in Lebanon, Syria and Saudi Arabia (1992–2010). The pre-biopsy clinical diagnosis and demographic data were collected. Biopsies were evaluated for the major microscopic pattern, and the parasitic index (PI) was also determined. Diagnosis was confirmed by polymerase chain reaction (PCR) followed by molecular sub-speciation.

Results: Of the 145 patients, 125 were confirmed as cutaneous leishmaniasis by PCR. Eighteen cases presented with a pre-biopsy clinical diagnosis other than cutaneous leishmaniasis that ranged from dermatitis to neoplasm. Of the 125 cases, 57 showed a major histopathological pattern other than cutaneous leishmaniasis. Identification of amastigotes was equivocal (PI ≤1) in 38 of the 57 cases. Of interest, all the 18 cases with a pre-biopsy clinical diagnosis other than cutaneous leishmaniasis also showed atypical histopathology for cutaneous leishmaniasis.

Conclusions: The manifestations of cutaneous leishmaniasis are broad and may mimic other inflammatory and neoplastic diseases. Pathologists and dermatologists should be aware of such pitfalls and can utilize PCR to confirm the diagnosis of leishmaniasis.

Saab J, Fedda F, Khattab R, Yahya L, Loya A, Satti M, A-G Kibbi, Houreih MA, Raslan W, El-Sabban M, Khalifeh I. Cutaneous leishmaniasis mimicking inflammatory and neoplastic processes: a clinical, histopathological and molecular study of 57 cases.

Cutaneous myoepithelioma arising within hidradenoma of the scalp

A 62-year-old man presented with a 2-year history of a 2-cm cystic mass involving his occiput. There had been recent enlargement, and the clinical impression was that of a pilar cyst. Histopathological sections showed a partially dermal solid and cystic proliferation. The tumor contained areas of glandular differentiation with cuboidal to columnar cells lining luminal and cystic spaces. A concurrent spindle cell proliferation was seen interspersed between glands and also formed broad, cellular sheets of cells. The stroma was sclerotic and without chondroid or myxoid elements. Immunohistochemistry showed that the spindled cells expressed S100 protein, cytokeratin and smooth muscle myosin. The immunohistochemical profile and the relationship with ductal elements supported myoepithelial differentiation. The proliferation warranted the diagnosis of myoepithelioma arising from a hidradenoma, which to our knowledge has not been previously described. In addition to discussing this case, we provide a brief review of epithelial–myoepithelial neoplasms encountered in the skin.

Jakate K, Wong K, Sirbovan J, Hanna W. Cutaneous myoepithelioma arising within hidradenoma of the scalp.

Human herpesvirus 8-associated lymphoma mimicking cutaneous anaplastic large T-cell lymphoma in a patient with human immunodeficiency virus infection

Primary effusion lymphoma, a human herpesvirus 8 (HHV8)-associated lymphoma, is uncommon, and it is usually seen in human immunodeficiency virus (HIV)-infected patients. It presents as a body cavity-based lymphomatous effusion, but several cases of the so-called solid primary effusion lymphoma presenting as solid tumors without associated lymphomatous effusion have been reported. They have similar clinical, histopathological and immunophenotypical features. Most of them have a B-cell genotype. This suggests the solid variant may represent a clinicopathological spectrum of primary effusion lymphoma. We report a case of HHV8-associated lymphoma histopathologically and immunophenotypically mimicking cutaneous anaplastic large cell lymphoma. The patient was a 31-year-old HIV-seropositive man presenting with skin nodules over his right thigh. Biopsy of the nodules showed anaplastic large cells infiltrating the dermis. These malignant cells strongly expressed CD3, CD30 and CD43. Cutaneous anaplastic large T-cell lymphoma was initially diagnosed, but further tests, including immunoreactivity for HHV8 protein and clonal rearrangements of immunoglobulin genes, confirmed the diagnosis of HHV8-associated B-cell lymphoma with aberrant T-cell marker expression. This case provides an example of solid primary effusion lymphoma mimicking cutaneous anaplastic large T-cell lymphoma and highlights the importance of HHV8 immunohistochemistry and molecular tests in the diagnosis of HHV8-associated lymphoma with a cutaneous presentation.

Li M-F, Hsiao C-H, Chen Y-L, Huang W-Y, Lee Y-H, Huang H-N, Lien H-C. Human herpesvirus 8-associated lymphoma mimicking cutaneous anaplastic large T-cell lymphoma in a patient with human immunodeficiency virus infection.

Cytokeratin 10-negative nested pattern enables sure distinction of clonal seborrheic keratosis from pagetoid Bowen's disease

Background: The histopathologic pattern of clonal seborrheic keratosis (SK) is quite similar to the nested pattern of pagetoid Bowen's disease [squamous cell carcinoma in situ (SCCIS)], and differentiation between the two can be challenging, especially when only small pieces are available for interpretation.

Methods: Eleven examples of clonal SK and 13 examples of pagetoid SCCIS were examined histopathologically (tabulating necrotic keratinocytes, suprabasal mitoses, infiltrate, parakeratosis housing plump nuclei, crowding of nuclei) and immunohistochemically (using Ki-67, bcl-2, cytokeratin 7 and cytokeratin 10). Sensitivity, specificity, p-values (Fisher's exact test, two-tailed) and positive/negative likelihood ratios (+LR/−LR) were calculated.

Results: Significant differences were seen with regard to crowding (p = 0.0009) and mitoses (p = 0.0006); however, only complete absence of necrotic keratinocytes or of crowding appeared to be diagnostically convincing for a diagnosis of clonal SK (−LR < 0.01). Significant differences were also seen with bcl-2 (p = 0.0005) and cytokeratin 10 antibodies (p < 0.00001). Both markers displayed a typical nested pattern in clonal SK, nests being bcl-2-positive and cytokeratin 10-negative. Cytokeratin 10-negative nests were the most convincing criterion for differentiation between clonal SK and pagetoid SCCIS (+LR > 10, −LR < 0.01).

Conclusions: The most reliable marker to distinguish clonal SK from pagetoid SCCIS is cytokeratin 10 when it spares nests. Other criteria that assist in the differential diagnosis are bcl-2 expression, absence of crowding and of mitoses.

Böer-Auer A, Jones M, Lyasnichaya OV. Cytokeratin 10-negative nested pattern enables sure distinction of clonal seborrheic keratosis from pagetoid Bowen's disease.

Use of proliferation rate, p53 staining and perforating elastic fibers in distinguishing keratoacanthoma from hypertrophic lichen planus: a pilot study

Background: Distinguishing keratoacanthoma (KA) and hypertrophic lichen planus (LP) histopathologically can be difficult, and the challenge is compounded by the tendency of KA to arise in association with hypertrophic LP.

Methods: In this pilot study, we compared 18 cases each of KA and hypertrophic LP for proliferation index (MIB-1), p53 staining and the presence of perforating elastic fibers (elastic Verhoeff-van Gieson) to determine the utility of these staining modalities in distinguishing KA from hypertrophic LP.

Results: Proliferation index in KA compared to hypertrophic LP is 88.2 (mean positive MIB-1 cells/×100 field), SD = 56.6 and 47.3, SD = 68.4, respectively. p53 staining in KA compared to hypertrophic LP is 251 (mean positive cells/×100 field), SD = 117 and 158, SD = 119, respectively. Fifteen of eighteen (83%) keratoacanthomata demonstrate perforating elastic fibers compared to 1/18 (6%) for hypertrophic LP.

Conclusion: Proliferation index is not significantly different between KA and hypertrophic LP (p = 0.059). Expression of p53 is increased in KA over hypertrophic LP (p = 0.024). The presence of perforating elastic fibers in KA is significantly different from hypertrophic LP (p < 0.0001) and suggests that elastic Verhoeff-van Gieson staining may be of practical benefit in distinguishing KA from hypertrophic LP in difficult cases.

Bowen AR, Burt L, Boucher K, Tristani-Firouzi P, Florell SR. Use of proliferation rate, p53 staining and perforating elastic fibers in the distinction of keratoacanthoma and hypertrophic lichen planus: a pilot study.

Solar cheilosis: An ominous precursor: Part II. Therapeutic perspectives

The differential diagnosis of SC includes malignant, premalignant, metastatic, inflammatory, and eczematoid disorders, along with photodermatoses and a few rare but important disorders of the lower lip. Current treatment options include topical, ablative, and surgical therapies. Several clinical challenges are also addressed, including the issue of obtaining a high-yield diagnostic biopsy specimen while minimizing patient morbidity, field-directed treatment for SC, and strategies for combination therapy.
Read more [JAAD]

P-cadherin expression in Merkel cell carcinomas is associated with prolonged recurrence-free survival

Abstract

Background:  Merkel cell carcinoma (MCC) is a highly aggressive skin cancer, associated with advanced age, immunosuppression and Merkel cell polyomavirus (MCV) infections. As development and progression of cancer can be promoted by changes in cell adhesion proteins, we have previously analyzed homo- and heterotypic cell-cell contacts of normal Merkel cells and MCCs and obtained indications for cadherin switching.

Objectives:  The aim of this study was to examine the prevalence and prognostic relevance of E-, N- and P-cadherin in MCCs.

Methods:  Paraffin-embedded MCC samples (n=148) from 106 different patients were analysed by double-label immunostaining and immunofluorescence microscopy. MCV status was determined by real time PCR. The cadherin repertoire and MCV status were correlated to clinical data, including tumour stage and recurrence-free survival.

Results:  Ninety-one percent of all MCC were positive for N-cadherin whereas only 61.6% or 70.3% expressed E- or P-cadherin. P-cadherin was significantly more frequent in primary tumours than in lymph node metastases (81.9% vs. 40.9%, p=0.0002). Patients with P-cadherin-positive primary tumours were in earlier tumour stages at initial diagnosis (p=0.0046). Both in log-rank tests (p=0.0474) and in multiple Cox regression analysis including age, sex, immunosuppression, stage at initial diagnosis and MCV status (HR=0.193, p=0.0373), patients with P-cadherin-positive primary MCCs had significantly prolonged recurrence-free survival (mean: 25.2 vs. 10.6 months; median: 9.0 vs. 4.0 months). MCV DNA was detected in 78.2% of all MCC, more frequently in P-cadherin-positive ones (p=0.0008).

Conclusion:  P-cadherin expression in MCCs predicts prolonged recurrence-free survival and may therefore indicate favourable prognosis.

Desmoplastic trichoepithelioma with perineural involvement: a series of seven cases.

Desmoplastic trichoepithelioma is a benign follicular tumor occurring most commonly within facial skin of young and middle aged women, morphologically characterized by a superficial dermal proliferation of basaloid cells growing in narrow strands embedded in a desmoplastic stroma with associated small keratinizing cysts. Desmoplastic trichoepithelioma must be distinguished from other benign epithelial proliferations such as syringoma, microcystic adnexal carcinoma, and infiltrating basal cell carcinoma. Among morphological features useful in that distinction, perineural involvement is considered a feature indicative of malignancy. We present a series of seven desmoplastic trichoepitheliomas with otherwise typical presentation and morphology, nevertheless demonstrating epithelium present in the perineural spaces of adjacent small dermal nerves. Patients ranged in age from 14 to 66 years (mean 44 years). All seven tumors were restricted to dermis, showed strands of basaloid epithelium in desmoplastic stroma, and contained CK20-positive cells. Additionally, five of five examined tumors displayed diffuse expression of p75 neurotrophin receptor. Five patients were followed-up clinically (follow-up time range: 2 months - 4 years). No tumor recurrence was observed in any of these patients. We postulate that perineural involvement is an unusual feature of desmoplastic trichoepithelioma that should not be equated with malignancy or lead to unnecessary over-treatment.

Atopic Dermatitis and Risk of Skin Cancer: A Danish Nationwide Cohort Study (19772006)

Read more [Amer J Clin Dermatol]

Ultraviolet A1 phototherapy: a British Photodermatology Group workshop report

Summary

Whole-body ultraviolet (UV)A1 (340–400 nm) phototherapy was first introduced 30 years ago, but is currently available in the UK in only three dermatology departments. A workshop to discuss UVA1 was held by the British Photodermatology Group in May 2009, the aim of which was to provide an overview of UVA1 phototherapy and its role in practice, and to identify areas in which further studies are required. The conclusions were that UVA1 phototherapy is an effective treatment in several inflammatory skin diseases, including localized scleroderma and atopic eczema (AE); however, deficiencies and limitations exist in the published evidence base. For most diseases, such as AE, other treatments also exist, which are generally more effective than UVA1. However, for some diseases, particularly morphoea, the evidence of efficacy is stronger for UVA1 than for other treatments. Acute adverse effects of UVA1 are minimal. The risk of long-term adverse effects, particularly skin cancer, is unknown. Medium to high doses of UVA1 are needed for efficacy in most situations, but the equipment to deliver such doses is large, expensive and difficult to install. UVA1 is currently underprovided, and the recommendation of the workshop is that more tertiary centres should have access to UVA1 phototherapy in the UK.

Effect of non-steroidal anti-inflammatory drugs on the histology of basal cell carcinomas.

Eur J Dermatol. 2012 Jan 12;
Husein-El Ahmed H, Aneiros-Fernandez J, Gutierrez-Salmeron MT, Aneiros-Cachaza J, Naranjo-Sintes R

Background: Aggressive histology is not rare in BCC. Large studies from referral centers report incidences of aggressive histology BCC ranging from 2.5- 44%. These aggressive BCC are characterized by subclinical extension, invasive behavior, local recurrence and challenging treatment. Objectives: To examine the association between non-steroidal anti-inflammatory drug (NSAID) use and the different histological subtypes of basal cell carcinoma (BCC). Methods: The design was a nested case-control study. The two population-based cohorts were of patients with a primary BCC diagnosis during January and May 2010 (n=136) and NSAID use in the 15 years prior to baseline. All the lesions were excised and analyzed to determinate the histological subtype of BCC as aggressive or non-aggressive. Odds ratios (ORs) and 95% confidence intervals (CIs), using conditional logistic regression, were calculated with the SPSS software to estimate the association of aggressive histological subtypes of BCC and use of NSAID. We controlled the potential confounding factors. Results: The rate of non-aggressive BCC associated with exposure to NSAID was increased (OD: 0.34; 95% CI: 0.14-0.84) after adjusting for covariants. Limitations: our sample is small. We collected data regarding use of NSAID over a wide time ranges, so that we are unable to propose when the potential benefits of NSAID on the histology of BCC would happen. Conclusion: According to our data, NSAID exposure is associated with a decreased risk of aggressive BCC.
Read more [European J Dermatol]

Pulsed Dye Laser and Pulsed Dye Laser–Mediated Photodynamic Therapy in the Treatment of Dermatologic Disorders

Background

The pulsed dye laser (PDL) is used for treating cutaneous vascular disorders. Recent reports have also shown its effectiveness in conditions of other etiologies, although the precise mechanisms of action are unknown. PDL has also been used in photodynamic therapy (PDT) for many dermatologic conditions. We review the broad array of disorders that can be effectively managed using the PDL.

A review of the literature on the application of the PDL and PDL-mediated PDT in dermatologic disorders. A literature-based search was performed using PubMed from 1997 to 2010. Search terms included: “pulsed dye laser,” “pulsed dye laser photodynamic therapy,” and “pulsed dye laser indications.”

The PDL was initially designed for cutaneous vascular disorders. Recent investigations have demonstrated successful results when treating malignant, inflammatory, viral, and collagenous conditions. Side effects, including pain, purpura, edema, and postinflammatory hyperpigmentation, were mild, well tolerated, and transient.

PDL is accepted as first-line therapy for vascular disorders including port-wine stains, telangiectasias, and hemangiomas. PDL causes selective photothermolysis of dermal vasculature. This mechanism also allows it to be applicable for disorders of other etiologies. Recent studies suggest that the PDL may induce cytokine expression and collagen formation, further increasing its applicability in dermatology.

Malignant nodular hidradenoma treated with Mohs micrographic surgery.

Cutis. 2011 Oct; 88(4): 173-4
Lane JE, Kent DE

Read more [Cutis]

Large facial basal cell carcinoma treated with multimodal combination therapy.

Cutis. 2011 Oct; 88(4): 182-4
Rubenzik MK, Schwartz LR, Humphreys TR

Large basal cell carcinomas (BCCs) with mixed intratumoral histology can present treatment challenges. Although a single treatment modality may be appropriate for some portions of the tumor, it may prove to be inadequate or overly aggressive for others. We describe a patient with a large facial BCC who was referred to our clinic for Mohs micrographic surgery. Biopsies revealed both noduloinfiltrative and superficial patterns. To excise the tumor completely would have been disfiguring, and topical therapy alone would have been inadequate. A multimodal approach using Mohs micrographic surgery to excise the central nodular portion and topical imiquimod to treat the surrounding superficial portion resulted in an excellent clinical outcome. This approach, which minimizes morbidity by capitalizing on the benefits of various techniques, can be applied to any BCC demonstrating distinct nodular and superficial portions.
Read more [Cutis]

Porokeratosis in Singapore: An Asian perspective

ABSTRACT

Porokeratosis is a rare disorder of skin keratinisation characterised by a cornoid lamella. We reviewed its associations with immunosuppression and phototherapy, as well as the risks of malignant progression. This is a retrospective review on all cases of porokeratosis seen at the National Skin Centre, Singapore, between 2000 and 2010. A total of 94 patients were reviewed. Clinical and histological diagnoses were confirmed in 63% patients. Most patients were Chinese (89%) with a mean age of 51.6 years. The male to female ratio was 1.4:1. The four main clinical variants were classical porokeratosis of Mibelli (56%), disseminated superficial actinic porokeratosis (DSAP) (18%), disseminated superficial porokeratosis (DSP) (11%), and linear porokeratosis (13%). Phototherapy-induced porokeratosis, seen in three patients, is rare. Seven cases of porokeratosis occurred in patients who were immunosuppressed. Progression of porokeratosis to malignancy is uncommon and was observed in three patients. The most common treatments included cryotherapy (26.5%) as well as topical steroids or retinoids (38.1%). A good response, defined as clear or almost clear lesions, occurred in 16% patients. The most common presentation of porokeratosis in our review was a middle-aged male patient with an asymptomatic lesion of porokeratosis of Mibelli over the extremities. No particular immunosuppressive drug was implicated. Porokeratosis associated with ultraviolet phototherapy or malignancy is rare. Progression of porokeratosis to malignancy arose in the disseminated variants, with a possible correlation with age. This is the largest institutional retrospective review of porokeratosis to date and highlights the major epidemiological characteristics of this condition.

Rare case of basal cell carcinoma arising in a nevus sebaceous on the upper arm

Read more [J Dermatology (Япония)]

Resistance of Sézary Cells to TNF-α-Induced Apoptosis Is Mediated in Part by a Loss of TNFR1 and a High Level of the IER3 Expression

Abstract

Failure to execute an apoptotic program is one of the critical steps and a common mechanism promoting tumorogenesis. Immediate early responsive gene 3 (IER3) has been shown to be upregulated in several cancers. IER3 is a stress induced gene, which upregulation leads to reduction in production of reactive oxygen species (ROS) protecting malignant cells from apoptosis. We observed that malignant lymphocytes from patients with Sézary syndrome (SzS) were resistant to pro-apoptotic dose of tumor necrosis factor-α (TNF-α). The aim of this study was to investigate the role of IER3 in the mechanism of such resistance. CD4+ CD26- lymphocytes from the peripheral blood of patients with SzS and healthy controls were negatively selected using CD4 and CD26 magnetic beads and analyzed for expression of TNFR1, TNFR2, IER3 expression, and ROS production in response to TNF-α at an apoptotic dose. Sézary cells with a higher level of IER3 expression retained their viability to TNF-α. IER3 upregulation correlated with a decrease level of intracellular ROS and low TNFR1 expression on malignant cells. Targeting IER3 could be of interest for the development of future therapeutic strategies for patients with SzS.

Xeroderma pigmentosum complementation group G patient with a novel homozygous missense mutation and no neurological abnormalities

Abstract

We describe an unusual xeroderma pigmentosum (XP) patient with a mutation in XP complementation group G, representing only the third reported Japanese XP-G patient. A 40-year-old male (XP3HM), born from consanguineous parents experienced sun sensitivity and pigmentary changes of sun-exposed skin since childhood. He developed a squamous cell carcinoma on his lower lip at the age of 40. He has neither neurological abnormalities nor Cockayne syndrome. The primary fibroblasts of the patient were hypersensitive to killing by UV (D0=0.6 J/m2) and the post-UV unscheduled DNA synthesis was 8% of normal. Host cell reactivation complementation analysis implicated XP complementation group G. We identified a novel homozygous mutation (c.194T>C) in a conserved portion of the XPG(ERCC5) gene, resulting in a predicted amino acid change; p.L65P. We confirmed that this genetic change reduced DNA repair thus linking this mutation to increased skin cancer.

Cutaneous Manifestations of DOCK8 Deficiency Syndrome [Observation]

Background  Mutations in the dedicator of cytokinesis 8 gene (DOCK8) cause a combined primary immunodeficiency syndrome that is characterized by elevated serum IgE levels, depressed IgM levels, eosinophilia, sinopulmonary infections, cutaneous viral infections, and lymphopenia. Many patients with DOCK8 deficiency were previously thought to have a variant of Job's syndrome. Distinguishing between DOCK8 deficiency and Job's syndrome, also referred to as autosomal dominant hyper-IgE syndrome, on the basis of clinical findings alone is challenging. The discovery of the DOCK8 mutation has made it possible to differentiate the cutaneous manifestations of these hyper-IgE syndromes.

Observations  Twenty-one patients from 14 families with confirmed homozygous or compound heterozygous mutations in DOCK8 were evaluated. Clinical findings included dermatitis, asthma, food and environmental allergies, recurrent sinopulmonary infections, staphylococcal skin abscesses, and severe cutaneous viral infections. Malignant neoplasms, including aggressive cutaneous T-cell lymphoma, anal and vulvar squamous cell carcinomas, and diffuse large B-cell lymphoma, developed in 5 patients during adolescence and young adulthood.

Conclusions  DOCK8 deficiency and Job's syndrome share several clinical features, including elevated serum IgE levels, dermatitis, recurrent sinopulmonary infections, and cutaneous staphylococcal abscesses. However, the presence of recalcitrant, widespread cutaneous viral infections, asthma, and food and environmental allergies, as well as the absence of newborn rash and coarse facies, favors the clinical diagnosis of DOCK8 deficiency. Rates of malignancy and overall mortality in patients with DOCK8 deficiency were higher than in those with Job's syndrome, highlighting the value of distinguishing between these conditions and the importance of close monitoring for neoplasia.

Cancer Risk in Patients With Chronic Urticaria: A Population-Based Cohort Study [Evidence-Based Dermatology: Study]

Objective  To investigate the relative risk of cancer among patients with chronic urticaria in the Taiwanese population.

Design  Retrospective population-based cohort study.

Setting  The National Health Insurance Research Database of Taiwan from January 1, 1996, through December 31, 2008.

Participants  A total of 12 720 patients with chronic urticaria, with long-term antihistamine use and no history of malignant tumors, autoimmune diseases, atopy, or allergic diseases.

Main Outcome Measure  Relative cancer risk calculated by standardized incidence ratios.

Results  There were 704 cancers among chronic urticaria patients. An increased risk of cancer (standardized incidence ratio, 2.2; 95% CI, 2.0-2.3), especially hematologic malignant tumor (4.1; 3.1-5.4), was observed. The relative risk of cancer varied by age and was highest among those aged 20 to 39 years in comparison with the general population. Most cancer cases were detected within the first year of diagnosis. The risk of non-Hodgkin lymphoma was greatest (standardized incidence ratio, 4.4; 95% CI, 3.0-6.1) among the hematologic cancers.

Conclusions  Patients with chronic urticaria are at increased risk of cancer, especially hematologic malignant tumors. Further studies are needed to delineate the associations.

Consensus Guidelines for the Management of Plaque Psoriasis [Consensus Statement]

The Canadian Guidelines for the Management of Plaque Psoriasis were reviewed by the entire National Psoriasis Foundation Medical Board and updated to include newly approved agents such as ustekinumab and to reflect practice patterns in the United States, where the excimer laser is approved for psoriasis treatment. Management of psoriasis in special populations is discussed. In the updated guidelines, we include sections on children, pregnant patients or pregnant partners of patients, nursing mothers, the elderly, patients with hepatitis B or C virus infections, human immunodeficiency virus–infected patients, and patients with malignant neoplasms, as well as sections on tumor necrosis factor blockers, elective surgery, and vaccinations.

High Frequency of Genital Lichen Sclerosus in a Prospective Series of 76 Patients With Morphea: Toward a Better Understanding of the Spectrum of Morphea [Study]

Objective  To compare the frequency of genital lichen sclerosus (LS) in patients with morphea with that of control patients.

Design  A prospective multicenter study.

Setting  Four French academic dermatology departments: Strasbourg, Montpellier, Tenon Hospital Paris, and Henri Mondor Hospital Créteil.

Patients  Patients were recruited from November 1, 2008, through June 30, 2010. Seventy-six patients with morphea and 101 age- and sex-matched controls, who underwent complete clinical examination, were enrolled.

Interventions  A complete clinical examination and, if deemed necessary, a cutaneous biopsy.

Main Outcome Measure  The frequency of genital LS.

Results  There were 58 women and 18 men (a 3:1 ratio) with a median age of 59 years. Mean (range) age at diagnosis was 54 (13-87) years. Forty-nine patients had plaque morphea, 9 had generalized morphea, and 18 had linear morphea. Three patients (3%) in the control group and 29 patients (38%) with morphea had LS (odds ratio, 19.8; 95% CI, 5.7-106.9; P < .001). Twenty-two patients with plaque morphea (45%) and only 1 patient with linear morphea (6%) had associated genital LS.

Conclusions  Genital LS is significantly more frequent in patients with morphea than in unaffected individuals. Forty-five percent of patients with plaque morphea have associated LS. Complete clinical examination, including careful inspection of genital mucosa, should therefore be mandatory in patients with morphea because genital LS bears a risk of evolution into squamous cell carcinoma and thus needs treatment with topical corticosteroids.

A study of pathogenesis of Acanthosis nigricans and its clinical implications

Neerja Puri

Indian Journal of Dermatology 2011 56(6):678-683

Background: Acanthosis nigricans (AN) is a dermatosis characterized by thickened, hyperpigmented plaques, typically on the intertriginous surfaces and neck. Common in some populations, its prevalence depends on race. Clinicians should recognize AN; it heralds disorders ranging from endocrinologic disturbances to malignancy. In this review, we discuss the pathogenesis of AN and its clinical implications and management. Materials and Methods: We selected 30 patients for the study. Diagnosis of associated disorders was established by history, physical examination, body mass index (BMI), hormone measurements by radioimmunoassays of thyroidnfunction tests, free testosterone, 17 (OH) progesterone, dehydroepiandrosterone sulfate (DHEAS), cortisol, gonadotropins, prolactin, immunoreactive insulin, and C-peptide levels. Results and Discussion: In our study, the flexural involvement (flexures of groins, knees and elbows) was seen in 40% patients, lip involvement was seen in 6.6% patients, and dorsal involvement was seen in 3.3% patients each. Increased serum testosterone levels were seen in 13.3% patients and increased DHEAS levels were seen in 20% patients. Regarding the types of AN, obesity induced AN or pseudo-AN was seen 70% patients, syndromic AN was seen in 23.35% patients and malignant AN was seen in 6.6% patients. The commonest histopathological feature of patients with AN was hyperkeratosis, seen in 100% patients, papillomatosis was seen in 90% patients, dermal infiltrate of lymphocytes and plasma cells was seen in 60% patients, horn pseudocysts were seen in 30% patients, and irregular acanthosis was seen in 26.6% patients.
Read more [Indian J Dermatol]

Primary cutaneous leiomysarcoma

Shubhangi Vinayak Agale, Sumit Grover, Rahul Zode, Shilpa Hande

Indian Journal of Dermatology 2011 56(6):728-730

Primary cutaneous leiomyosarcoma of the skin is a rare soft tissue neoplasm, accounting for about 2-3% of all superficial soft tissue sarcomas. It arises between the ages of 50 and 70 years, and shows a greater predilection for the lower extremities. Clinically, it presents with solitary, well-circumscribed nodule and, microscopically, consists of fascicles of spindle-shaped cells with "cigar-shaped" nuclei. Local recurrence is known in this tumor. We document a case of primary cutaneous leiomyosarcoma in a 77-year-old man and discuss the histological features and immunohistochemical profile of this uncommon neoplasm.
Read more [Indian J Dermatol]

Topical photodynamic therapy significantly reduces epidermal Langerhans cells during clinical treatment of basal cell carcinoma

Abstract

Background:  Topical photodynamic therapy (PDT) is a widely applied treatment for basal cell carcinoma (BCC). PDT-induced immunosuppression leading to ineffective anti-tumour immune responses may be a factor in treatment failure.

Objective:  To examine the impact of topical PDT on leucocyte trafficking following clinical treatment of BCC.

Methods:  Superficial BCC in eight white Caucasian patients were treated with methyl aminolaevulinate (MAL)-PDT. Biopsies for immunohistochemical assessment were taken from BCC pre-PDT, 1h and 24h post-PDT and from untreated healthy skin.

Results:  Treatment of BCC with MAL-PDT produced a rapid neutrophil infiltration, commencing by 1h and significantly increased at 24h post-PDT (p<0.05 compared to baseline). An associated increase in the number of blood vessels expressing E-selectin was observed at 1h and 24h post-PDT (both p<0.05 compared to baseline). In contrast, the number of epidermal Langerhans cells fell sharply by 1h post-PDT, and remained significantly reduced at 24h post-PDT (both p<0.05 compared to baseline).

Conclusions:  Reduction of Langerhans cells during clinical treatment of BCC might potentially impact negatively on anti-tumour responses through reduced activation of tumour-specific effector cells. Investigation of modified PDT protocols with the aim to minimise immunosuppressive effects whilst maintaining anti-tumour efficacy is warranted.

Validation of self-reported erythema: comparison of self-reports, researcher assessment and objective measurements in sun worshippers and skiers

Abstract

Background  Most epidemiological data of sunburn related to skin cancer have come from self-reporting in diaries and questionnaires. We thought it important to validate the reliability of such data.

Objective  To validate the quality of self-reported erythema by sun worshippers and skiers, and to validate the ability to determine erythema visually compared with objectively measured erythema.

Methods  The skin in a group of sun worshippers in Tenerife and of skiers in Austria was closely monitored over a week. The participants used a diary to record any erythema assessed on different skin sites and underwent a twice daily skin examination by researchers who assessed erythema on the same sites. Lastly, the erythema assessment was validated by objective measurements.

Results  We found that the participants’ agreed with researchers’ assessment of erythema in only 57–61% of cases, and that the researchers detected up to 28% more of the objectively measured erythema than the participants did. We also found that, even for the trained eye (researchers), it was difficult to detect an increase in erythema as only 71–91% of those cases with an increase >15 in measured erythema percentage were detected in the evening. Possibly, detection was impeded by a simultaneous increase in pigmentation.

Conclusion  Self-assessment of erythema from diaries is unreliable. Erythema is considerably underestimated and possibly neglected. Even for the trained eye, it can be difficult to detect erythema.

Identification and Characterization of Tumor-Initiating Cells in Human Primary Cutaneous Squamous Cell Carcinoma

Identification and Characterization of Tumor-Initiating Cells in Human Primary Cutaneous Squamous Cell Carcinoma

Journal of Investigative Dermatology 132, 401 (February 2012). doi:10.1038/jid.2011.317

Authors: Girish K Patel, Carole L Yee, Atsushi Terunuma, William G Telford, Nga Voong, Stuart H Yuspa & Jonathan C Vogel

Identification of an mtDNA Mutation Hot Spot in UV-Induced Mouse Skin Tumors Producing Altered Cellular Biochemistry

Identification of an mtDNA Mutation Hot Spot in UV-Induced Mouse Skin Tumors Producing Altered Cellular Biochemistry

Journal of Investigative Dermatology 132, 421 (February 2012). doi:10.1038/jid.2011.320

Authors: Jana Jandova, Alex Eshaghian, Mingjian Shi, Meiling Li, Lloyd E King, Jaroslav Janda & James E Sligh

A Humanized Stromal Bed Is Required for Engraftment of Isolated Human Primary Squamous Cell Carcinoma Cells in Immunocompromised Mice

A Humanized Stromal Bed Is Required for Engraftment of Isolated Human Primary Squamous Cell Carcinoma Cells in Immunocompromised Mice

Journal of Investigative Dermatology 132, 284 (February 2012). doi:10.1038/jid.2011.284

Authors: Girish K Patel, Carole L Yee, Stuart H Yuspa & Jonathan C Vogel

A New Xenotransplantation Model Reveals Tumor-Initiating Cells in Cutaneous Squamous Cell Carcinoma

A New Xenotransplantation Model Reveals Tumor-Initiating Cells in Cutaneous Squamous Cell Carcinoma

Journal of Investigative Dermatology 132, 261 (February 2012). doi:10.1038/jid.2011.327

Author: Adam Glick

What is the cause of retraction spaces associated with basal cell carcinoma?

Read more [J Cutaneous Pathology]

Automatic dirt trail analysis in dermoscopy images

Background

Basal cell carcinoma (BCC) is the most common cancer in the US. Dermatoscopes are devices used by physicians to facilitate the early detection of these cancers based on the identification of skin lesion structures often specific to BCCs. One new lesion structure, referred to as dirt trails, has the appearance of dark gray, brown or black dots and clods of varying sizes distributed in elongated clusters with indistinct borders, often appearing as curvilinear trails.

In this research, we explore a dirt trail detection and analysis algorithm for extracting, measuring, and characterizing dirt trails based on size, distribution, and color in dermoscopic skin lesion images. These dirt trails are then used to automatically discriminate BCC from benign skin lesions.

For an experimental data set of 35 BCC images with dirt trails and 79 benign lesion images, a neural network-based classifier achieved a 0.902 are under a receiver operating characteristic curve using a leave-one-out approach.

Results obtained from this study show that automatic detection of dirt trails in dermoscopic images of BCC is feasible. This is important because of the large number of these skin cancers seen every year and the challenge of discovering these earlier with instrumentation.