Multiple Skin Cancers Research Articles

Basal Cell Carcinoma with Adnexal Differentiation, a Rare Entity and Challenging Histopathology Presentation. Case Report

We report an 88 year-old male with a history of multiple non-melanoma skin cancers who presented for Mohs micrographic surgery with a biopsy proven infiltrative and nodular basal cell carcinoma located on the right posterior ear. During Mohs surgery, frozen sections revealed a typical nodular BCC on stage 1. However, on stage 2, frozen section showed nodular aggregates of regular cuboidal cells with pale cytoplasm with areas mimicking multi-nucleated giant cells. Deeper permanent sections were consistent with BCC with adnexal differentiation. This histopathological presentation of basal cell carcinoma is uncommon and we sought to report the clinical and pathological features of this case.

Xeroderma pigmentosum clinical practice guidelines.

Xeroderma pigmentosum (XP) is a genetic photosensitive disorder in which patients are highly susceptibe to skin cancers on the sun-exposed body sites. In Japan, more than half of patients (30% worldwide) with XP show complications of idiopathic progressive, intractable neurological symptoms with poor prognoses. Therefore, this disease does not merely present with dermatological symptoms, such as photosensitivity, pigmentary change and skin cancers, but is "an intractable neurological and dermatological disease". For this reason, in March 2007, the Japanese Ministry of Health, Labor and Welfare added XP to the neurocutaneous syndromes that are subject to government research initiatives for overcoming intractable diseases. XP is one of the extremely serious photosensitive disorders in which patients easily develop multiple skin cancers if they are not completely protected from ultraviolet radiation. XP patients thus need to be strictly shielded from sunlight throughout their lives, and they often experience idiopathic neurodegenerative complications that markedly reduce the quality of life for both the patients and their families. Hospitals in Japan often see cases of XP as severely photosensitive in children, and as advanced pigmentary disorders of the sun-exposed area with multiple skin cancers in adults (aged in their 20-40s), making XP an important disease to differentiate in everyday clinical practice. It was thus decided that there was a strong need for clinical practice guidelines dedicated to XP. This process led to the creation of new clinical practice guidelines for XP.

Association of Multiple Primary Skin Cancers With Human Immunodeficiency Virus Infection, CD4 Count, and Viral Load

Persons with human immunodeficiency virus (HIV) have a 2.8-fold higher risk than HIV-uninfected persons of nonmelanoma skin cancer (NMSC), defined as basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Individuals with a prior NMSC history are at increased risk for subsequent NMSC, but the magnitude of risk and its relation to HIV disease-related factors, including CD4 count and viral load (VL), are unknown. To better understand how laboratory markers currently used to evaluate HIV disease progression may be associated with subsequent NMSC risk. This cohort study analyzed 455 HIV-infected and 1945 HIV-uninfected patients, all of them members of the Kaiser Permanente Northern California (KPNC) health care plan, diagnosed with at least 1 NMSC from 1996-2008 to determine risk of subsequent NMSCs in relation to CD4 count and VL. All participants were white, non-Hispanic persons 18 years or older who had had at least 1 NMSC during the 1996-2008 period. Participants entered the cohort at their first NMSC diagnosis and were observed through 2008. Incidence rates were calculated and adjusted hazard ratios were estimated using extended Cox regression models with recent CD4 count and VL analyzed as time-changing covariates. Measured CD4 count, VL, and subsequent NMSC (BCC and SCC). The cohort comprised 455 HIV-infected participants (13 [3%] women) and 1952 HIV-uninfected participants (154 [8%] women). Median duration of observation was 4.6 years, and 16.5% (n = 390) either died (n = 35) or lost KPNC membership status (n = 355) without having a subsequent primary NMSC. Compared with HIV-uninfected persons, HIV-infected individuals were slightly younger (mean age, 52.5 vs 55.5 years), more likely men (97% vs 92%), more likely to have smoked (57% vs 45%), and less likely to be overweight/obese (50% vs 61%). The small observed differences by HIV status in matching characteristics (ie, age and sex) resulted from the restriction of the original cohort to those with at least 1 NMSC. Compared with uninfected individuals, those with HIV infection with a recent biomarker of more severe immune deficiency (CD4 count <200 cells/mL) had a 44% increased risk of subsequent NMSC overall and a 222% increase risk of SCC in particular, suggesting that subsequent SCC risk is associated with immune dysfunction. HIV-infected persons compared with HIV-uninfected persons were are at higher risk for subsequent new SCC but not BCC, with a dose-response relationship between risk and lower CD4 counts and higher VLs. Subsequent new primary SCCs had a strong association with lower CD4 and higher VL among HIV-infected persons, suggesting that immune dysfunction might contribute to increased SCC risk. Clinical implications include targeted monitoring for SCC among HIV-infected individuals, particularly those with low CD4 counts or high VLs.

Mohs micrographic surgery under general anesthesia for multiple skin cancer removal

Mohs micrographic surgery under general anesthesia for multiple skin cancer removal

MITF suppression by CH5552074 inhibits cell growth in melanoma cells.

Although treatment of melanoma with BRAF inhibitors and immune checkpoint inhibitors achieves a high response rate, a subset of melanoma patients with intrinsic and acquired resistance are insensitive to these therapeutics, so to improve melanoma therapy other target molecules need to be found. Here, we screened our chemical library to identify an anti-melanoma agent and examined its action mechanisms to show cell growth inhibition activity. We screened a chemical library against multiple skin cancer cell lines and conducted ingenuity pathway analysis (IPA) to investigate the mechanisms of CH5552074 activity. Suppression of microphthalmia-associated transcription factor (MITF) expression levels was determined in melanoma cells treated with CH5552074. Cell growth inhibition activity of CH5552074 was evaluated in MITF-dependent melanoma cell lines. We identified an anti-melanoma compound, CH5552074, which showed remarkable cell growth inhibition activity in melanoma cell lines. The IPA results suggested that CH5552074-sensitive cell lines had activated MITF. In further in vitro studies in the melanoma cell lines, a knockdown of MITF with siRNA resulted in cell growth inhibition, which showed that CH5552074 inhibited cell growth by reducing the expression level of MITF protein. These results suggest that CH5552074 can inhibit cell growth in melanoma cells by reducing the protein level of MITF. MITF inhibition by CH5552074 would be an attractive option for melanoma treatment.

Incidence and Implications of Skin Cancers in Cancercare Manitoba Chronic Lymphocytic Leukemia (CLL) Clinic Patients

Background:We previously conducted a population-based study on chronic lymphocytic leukemia (CLL) in Manitoba, which showed that second cancers are twice as common and skin cancers eight times as common in this disease, as compared to an age- and sex-matched control population and patients with follicular lymphoma. It is postulated that this is related to immunosuppression, secondary to the disease and chemo-immunotherapy. Here we set out to investigate rates and types of skin cancers in CLL patients and how these influence the outcome of CLL patients.Methods: Newly diagnosed CLL patients attending the CancerCare Manitoba CLL Clinic from the January 1st, 2002 until December 31st, 2012 were selected for this study. Patients were followed until December 31, 2014. Cox Proportional Hazard models were constructed to predict hazard’s ratios (HR) and 95% confidence intervals (95% CI) for survival as well as risk of non-cutaneous malignancies. Association between skin cancer and CLL prognostic markers were investigated by Fisher’s Exact test, Student’s t-test and logistic regression analysis. P-value <0.05 was considered statistically significant. Statistical analysis was performed using SAS Studio 3.5.Results: There were 582 CLL patients in this study. The median age was 67 years (range 36-99 years) with a M:F ratio of 1.6:1. This compares with a median age of 71.5 years and a M:F ratio of 1.3:1 in the Manitoba CLL population. The median follow-up for the study was 5.8 years (range 0.1-13.0 years).There were 131 (23%) CLL patients with at least one skin cancer; 73 (56%) had their first skin cancer before the diagnosis of CLL and 58 (44%) after. Rates of first skin cancer diagnoses were constant before CLL diagnosis (5.2 per 1000 CLL cases), but began to increase three years prior to the CLL diagnosis (10.2 per 1000 CLL cases) and continued to increase after the CLL diagnosis (22.7 per 1000 CLL cases).There were a total of 368 skin cancers; 208 (57%) were basal cell carcinomas (BCC), 92 (25%) were squamous cell carcinomas (SCC), 47 (13%) were Bowen's disease, 18 (5%) were melanomas, and three (1%) were Merkel cell carcinomas. Interestingly, multiple skin cancers with varying histologies occurred in almost half the patients. When the total number of skin cancers/year was assessed, the number started to increase seven years before the CLL diagnosis and continued to increase yearly after the CLL diagnosis.Within the follow-up period, 154 (27%) patients died, with the major causes of death being CLL and second malignancies. However, the presence of skin cancers did not appear to influence survival. There were a total of three deaths due to skin cancers; two patients died of melanoma and one from BCC. However, the presence of a skin cancer, in CLL cases without a history of a solid tumor, increased the risk of a non-cutaneous malignancy by seven-fold (HR 7.55, 05% CI 3.92 - 14.53, p<0.0001).The presence of a skin cancer prior to the diagnosis of CLL did not predict CLL aggressiveness at diagnosis, as evaluated by Rai stage, Zap-70 or CD38 status, immunoglobulin levels or IGHV mutational status. However, for those patients developing their first skin cancer after the CLL diagnosis, the risk of developing a skin cancer correlated with the unmutated IGHV status (HR 1.54, 95% CI 1.01 - 2.34, p=0.0462) and baseline CD38 positivity (HR 1.58, 95% CI 1.02 - 2.44, p=0.0405). Interestingly, the risk of developing skin cancer was not increased by chemotherapy.Discussion: In summary, with a median follow-up of 5.8 years, 23% of patients had a skin cancer, half before the diagnosis of CLL and half after the CLL diagnosis. The incidence of skin cancers increased prior to the diagnosis of CLL, indicating that immunosuppression possibly preceded the diagnosis of CLL by years. The increased risk of developing skin cancers in patients with unmutated IGHV and CD38 positivity indicates that CLL patients with a more aggressive disease are more likely to develop skin cancer, probably due to a more pronounced immune deficiency. The diagnosis of skin cancer in CLL patients was associated with a seven-fold increased risk of developing a solid tumour. These results underscore the need for close monitoring and active surveillance of CLL patients for skin and other cancers throughout their disease course, by clinicians experienced in skin and other malignancies. DisclosuresNo relevant conflicts of interest to declare.

Management of Skin Cancer in the High-Risk Patient.

Skin cancer is the most common of human cancers and outnumbers all other types of cancer combined in the USA by over threefold. The majority of non-melanoma skin cancers are easily treated with surgery or locally destructive techniques performed under local anesthesia in the cost-effective outpatient setting. However, there is a subset of "high-risk" cases that prove challenging in terms of morbidity, mortality, adjuvant treatment required, as well as overall cost to the health care system. In our opinion, the term "high risk" when applied to skin cancer can mean one of three things: a high-risk tumorwith aggressive histologic and/or clinical features with an elevated risk for local recurrence or regional/distant metastasis, ahigh-risk patientwith the ongoing development of multiple skin cancers, and ahigh-risk patientbased onimmunosuppression. We have recently proposed classifyingNMSC as a chronic diseasein a certain subset of patients. Although no consensus definition exists for a chronic disease in medicine, there are three components that are present in most definitions: duration of at least 1year, need for ongoing medical care, and functional impairment and/or alteration of activities of daily living (ADLs) and quality of life (QOL). Immunosuppression can refer to exogenous (organ or stem cell transplant patients,) or endogenous (HIV, leukemia, lymphoma, genodermatoses with DNA mismatch repair problems or other immunosuppression) causes. These patients are at risk for high-risk tumors and/or the development of multiple tumors.

A case of multiple skin cancers in a patient with oculocutaneous albinism type 2

A case of multiple skin cancers in a patient with oculocutaneous albinism type 2

Filaggrin genotype does not determine the skin's threshold to UV-induced erythema

Filaggrin genotype does not determine the skin's threshold to UV-induced erythema

Abstract 1782: Post-translational regulation of cyclins by Aspirin through 26S proteasome: Implications in chemoprevention

Abstract Recent studies have shown that, regular use aspirin for 5 years or more, decreases the occurrence of cancer of the colon, skin, breast, prostate and lung tissues. However, the mechanism of its anti-cancer effects are not completely understood. We hypothesized that Aspirin's chemo preventive action may involve proteins important in the regulation of cell cycle. Using multiple colon and skin cancer cells, we studied whether aspirin modulates the expression of cyclin B1. Cyclin B1 is a regulatory protein involved in mitosis and promotes the passage of cell cycle from G2 to M phase. Cyclin B1 along with Cyclin dependent Kinase 1(CDK1) regulates chromosomal condensation, nuclear envelope break down and spindle pole assembly in early mitosis. We demonstrate that, in HT-29 human colon and Sk-Mel 28 skin cancer cells, aspirin dose dependently decreased the levels of cyclin B1. This was further confirmed using immunofluorescence studies. To determine the involvement of proteases, we determined whether the lactacystin, a 26S proteasomal inhibitor, would reverse the inhibitory effect of aspirin on cyclin B1. We observed that pretreatment of cells with lactacystin completely reversed the decrease in levels of cyclin B1 in aspirin treated cells. Transfection of the DDK tagged cyclin B1 into HT-29 cells were carried out to establish whether the decrease observed occurs through a nuclear independent and post-translational mechanism. We observed that, aspirin significantly decreased the exogenously transfected DDK tagged cyclin B1 protein. Our results, for the first time show that anticancer effects of aspirin may occur through cyclin B1 degradation mediated by 26S proteasomes. Citation Format: Rakesh Dachineni, Guoqiang Ai, Hemachand Tummala, Jayarama B. Gunaje. Post-translational regulation of cyclins by Aspirin through 26S proteasome: Implications in chemoprevention. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1782. doi:10.1158/1538-7445.AM2015-1782

Generation of Xeroderma Pigmentosum-A Patient-Derived Induced Pluripotent Stem Cell Line for Use As Future Disease Model.

Xeroderma pigmentosum group A (XP-A) is a genetic disorder in which there is an abnormality in nucleotide excision repair that causes hypersensitivity to sunlight and multiple skin cancers. The development of central and peripheral neurological disorders not correlated to ultraviolet light exposure is associated with XP-A. The genes responsible for XP-A have been identified and a XPA knockout mouse has been generated. These knockout mice exhibit cutaneous symptoms, but they do not show neurological disorders. The mechanism of pathogenesis of neurological disorders is still unclear and therapeutic methods have not been established. Therefore, we generated XP-A patient-derived human induced pluripotent stem cells (XPA-iPSCs) to produce in vitro models of neurological disorders. We obtained iPSC lines from fibroblasts of two patients carrying different mutations. Drugs screened using XPA-iPSC lines can be helpful for treating XP-A patients in Japan. Additionally, we revealed that these iPSCs have the potential to differentiate into neural lineage cells, including dopaminergic neurons, which decrease in XP-A patients. Our results indicate that expression of the normal XPA gene without mutations is not required for generation of iPSCs and differentiation of iPSCs into neural lineage cells. XPA-iPSCs may become useful models that clarify our understanding of neurological pathogenesis and help to establish therapeutic methods.

Family history of skin cancer is associated with increased risk of cutaneous squamous cell carcinoma.

The contribution of family history to cutaneous squamous cell carcinoma (SCC) risk has not been systematically quantified. To examine the association between self-reported family history of skin cancer and SCC risk. Cases (n = 415) with a pathology-verified SCC and 415 age-, gender-, and race-matched controls were identified within a large integrated health care delivery system. Family history and skin cancer risk factors were ascertained by survey. Odds ratios (ORs) for associations of SCC with family history of skin cancer were estimated using conditional logistic regression adjusted for environmental and innate SCC risk factors. Any known family history of skin cancer was associated with a four-fold higher risk of SCC, adjusting for known environmental and innate SCC risk factors (OR, 4.0; confidence interval [CI]: 2.5-6.5). An unknown family history of skin cancer showed similar risk for SCC (OR, 3.9; CI: 2.4-6.5). In models including skin cancer type, the strongest association was for family history of basal cell carcinoma (OR, 9.8; CI: 2.6-36.8) and for multiple skin cancer types (OR, 10.5; CI: 3.7-29.6). Family history of skin cancer is an important independent risk factor for cutaneous SCCs.

Exclusive Development of a Single Type of Keratinocyte Skin Cancer: Evidence from an Australian Population–Based Cohort Study

Whether susceptible people develop both basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) or one type exclusively during life is unknown. We investigated this in an Australian community cohort of 1,191 adults aged 25-75 years by recording all new BCCs and SCCs for 16 years in people with no previous keratinocyte cancer. Among those who developed multiple skin cancers, age- and sex-specific incidence rates per 100,000 were calculated for those who developed BCC exclusively, SCC exclusively, or BCC and SCC. Corresponding relative risks (and 95% confidence intervals) were estimated by Poisson regression. During follow-up, 116 people developed multiple keratinocyte cancers: 65 (56%) developed BCC exclusively (range 2-8 per person); 18 (16%) developed SCC exclusively (2-5 per person); and 28% developed both types. Of the 116, 88 had a BCC first, of whom 74% subsequently developed only BCCs, and 28 had SCC first, of whom 64% subsequently developed only SCCs. Incidence rates did not differ by sex in the BCC-only, SCC-only, or mixed groups, but they increased significantly with age especially in the SCC-only group. These findings suggest that the majority of people are prone to develop one type rather than a mix of keratinocyte cancers.

Development of effective skin cancer treatment and prevention in xeroderma pigmentosum.

Xeroderma pigmentosum (XP) is a rare, recessively transmitted genetic disease characterized by increasingly marked dyspigmentation and xerosis (dryness) of sun-exposed tissues, especially skin. Skin cancers characteristically develop in sun-exposed sites at very much earlier ages than in the general population; these are often multiple and hundreds or even thousands may develop. Eight complementation groups have been identified. Seven groups, XP-A…G, are associated with defective genes encoding proteins involved in the nucleotide excision DNA repair (NER) pathway that recognizes and excises mutagenic changes induced in DNA by sunlight; the eighth group, XP-V, is associated with defective translesion synthesis (TLS) bypassing such alterations. The dyspigmentation, xerosis and eventually carcinogenesis in XP patients appear to be due to their cells' failure to respond properly to these mutagenic DNA alterations, leading to mutations in skin cells. A subset of cases, especially those in some complementation groups, may develop neurological degeneration, which may be severe. However, in most XP patients, in the past the multiple skin cancers have led to death at an early age due to either metastases or sepsis. Using either topical 5-fluorouracil or imiquimod, we have developed a protocol that effectively prevents most skin cancer development in XP patients.

Sarcoma-like Tumor of Head and Neck Skin

A group of tumors referred to as atypical fibroxanthoma (AFX) and pleomorphic dermal sarcoma (PDS) predominantly occur in sun-damaged skin of the elderly, particularly in the head and neck region. Although this group of tumors is often regarded as of mesenchymal phenotype, the matter of histogenesis has not been entirely resolved. Evans H and Smith JL reported in 1980 that prognosis was not significantly different irrespective of whether there was a definite squamous cell carcinoma component or not, supporting a view that these are all carcinomata in nature (sarcomatoid carcinoma [SC]). There are a number of clinicopathologic studies of AFX in the literature but information on morphologically similar sarcoma-like tumors with immunohistochemical evidence of epithelial differentiation is sparse. One hundred sarcoma-like tumors (SLTs) of head and neck skin of the elderly, treated by surgical excision, were studied. Clinical information was obtained, and pathology reports and hematoxylin and eosin sections were reviewed to document size (maximum dimension), extent of invasion, mitotic count, vascular and perineural invasion, margin status, ulceration, necrosis, and the presence of actinic keratosis in adjacent/overlying skin. Immunostains examined included: pan-cytokeratins (CKs) (AE1/AE3, MNF116), high-molecular weight CKs (34βE12, CK5/6, CK14), p63, and melanocytic (S100, Melan A, HMB-45, MITF), vascular (CD31, CD34), and muscle markers (SMA, desmin, h-caldesmon) to exclude melanoma and definite sarcoma entities. The tumors were divided into AFX/PDS (G1), the SC group, which was subdivided into SLT with only p63 positivity (G2a) and SLT with CK positivity regardless of p63 status (G2b), and SLT with a minor morphologic squamous cell carcinoma component (G3). Clinicopathologic findings of each group were compared, in relation to outcomes. Age at diagnosis ranged from 51 to 96 years (median, 79 y), with M:F=11.5:1. There were 53 tumors in G1 (19AFX, 34PDS), 37 in G2 (25 in G2a, 12 in G2b), and 10 in G3. There was no statistically significant difference in clinical and pathologic parameters or survival among all 3 groups. CKs and p63 expression, size, extent of invasion, vascular invasion, perineural invasion, mitotic count, and ulcer did not affect outcome, whereas margin status and necrosis did by both univariate and multivariate analysis and by only univariate analysis, respectively. Sixty patients had multiple nonmelanomatous skin cancers. Actinic keratosis was observed in overlying/adjacent epidermis in 51 cases. Eight patients had prior radiotherapy to head skin cancers; 1 patient developed 2 separate tumors (G1 and G3) after radiotherapy. Four patients died of tumor (1 G1, 2 G2b, and 1 G3); of these, 3 cases had positive margin, and 1 had narrow margin. Our results have shown similarities of various clinicopathologic parameters between AFX/PDS and SC, raising the possibility that both entities are related, and some of the former entities may represent complete dedifferentiation (complete loss of epithelial phenotype) with a gain of mesenchymal phenotype. In addition, the difference between AFX and PDS appears to be the extent of invasiveness (stage) rather than a different histogenesis. Further investigations are needed. However, from a practical point of view, efforts should be made to excise this group of tumors with clear margins, as margin status appears to be the most important prognostic factor regardless of the presence or absence of epithelial differentiation.

Squamous Neoplasia of the Scrotum

The current epidemiology and clinicopathologic features of squamous cell carcinoma (SCC) of the scrotum are largely unknown because of its low incidence. We describe the histopathologic features, immunohistochemistry, and human papillomavirus (HPV) status of 29 patients with scrotal SCC. The mean age at presentation was 55 years (range, 30 to 74 y). White to black ratio was 1.9:1. There was no predominant occupation, with the majority being white-collar professionals. Clinical history of condylomas was present in 5 patients, and 7 patients had a history of multiple skin cancers including melanoma, basal cell carcinoma, and other SCCs. Other comorbidities included human immunodeficiency virus infection (n=2), kidney transplant (n=1), leukemia/lymphoma (n=2), hidradenitis suppurativa (n=1), chronic scrotal infections with abscess (n=1), inflamed epidermal inclusion cyst (n=1), and lichen planus (n=1). One patient had a history of regular tanning bed use. Morphologically, the majority was usual type (n=17), followed by basaloid (n=7) and warty (n=5). Nineteen cases were in situ, and 10 were invasive. Three patients had inguinal lymphadenopathy; in 1, metastasis was confirmed. Suprabasal nuclear staining for Ki67 was considered positive. For p16, a continuous band of nuclear and cytoplasmic staining was considered positive, and a noncontinuous or absence of staining was considered negative. p16 was positive in 10 cases; high-risk HPV was confirmed in 7 cases. Ki67 was positive in 8/17 (47%) usual, 6/7 (85.7%) basaloid, and 3/5 (60%) warty type. p53 was positive in 5/17 (29.4%) usual, 2/7 (28.6%) basaloid, and 1/5 (20%) warty type. All patients were treated with local excision only; 13 had positive margins. Three patients were treated with imiquimod after local excision. The median follow-up was 30 months. Three patients recurred and were treated with re-excision; 1 patient received radiotherapy. Overall, the morphologic, immunohistochemical, and HPV studies show that, similar to SCC of the vulva or penis, the SCC of the scrotum can be divided into 2 major groups. Group 1 (38.5%): positive for p16 and elevated Ki67. This group is associated with HPV infection and displays predominantly a basaloid or warty morphology, although a number of them are of usual type. Group 2 (61.5%): negative for p16. This group has variable Ki67 expression, is consistently negative for HPV, and displays predominantly usual-type morphology. SCC of the scrotum in the United States currently affects primarily white-collar professionals. The majority present with in situ lesions, and the high rate of positive margins at first excision suggests that they are clinically ill-defined lesions. No longer are occupational exposures to carcinogens the major etiology of scrotal SCC. Rather in contemporary times, common risk factors include HPV infection, immunocompromised states, and chronic scrotal inflammatory conditions.

Non-melanoma skin cancer is reduced after switch of immunosuppression to mTOR-inhibitors in organ transplant recipients.

Organ transplant recipients are prone to the development of non-melanoma skin cancer. Organ transplant recipients often develop multiple non-melanoma skin cancers and the tumors show an aggressive growth pattern, therefore surgical therapy can be difficult. Switch of the immunosuppressive regimen to mTOR-inhibitors such as everolimus or sirolimus can have an antitumor effect. In a monocentric retrospective study we evaluated organ transplant recipients who presented with non-melanoma skin cancer in the years 2008-2010. Experience with patients who were switched to an mTOR-inhibitor due to non-melanoma skin cancer are reported in detail, and recent clinical studies are reviewed. 60 organ transplant recipients with non-melanoma skin cancer were evaluated. Due to the development of multiple non-melanoma skin cancer within a few years, the immunosuppressive regimen was switched to everolimus in 7 patients and to sirolimus in 5 patients. Eight patients were evaluable for the effect of mTOR-inhibitors on the development of non-melanoma skin cancer; 4 patients had to discontinue the medication with mTOR-inhibitors early due to various side effects. In the year before the switch to mTOR-inhibitors, 8 patients developed 16 squamous cell carcinomas, 3 Basal cell carcinomas and 22 cases of Bowen's disease. All tumors were histologically confirmed. In the year after switch of immunosuppression, the rate of squamous cell carcinomas (n = 2) and Bowen's disease (n = 3), but not of basal cell carcinomas (n = 2) was significantly reduced. Moreover, 5 prospective randomized trials recently have demonstrated a reduced number of non-melanoma skin cancers in organ transplant recipients after switch of the immunosuppressive regimen to mTOR-inhibitors. Switch of the immunosuppressive regimen to mTOR-inhibitors should be considered for organ transplant recipients suffering from multiple non-melanoma skin cancers.

Reconstruction after skin cancer excision through a dermal induction template: our experience

Dermal substitutes offer alternative approaches for wounds of all thicknesses where sufficient donation sites are not available for self-grafts. Several dermal substitutes are described in literature. This study included 20 patients treated with a dermal induction template after the removal of malignant skin cancers situated in various parts of the body. The participants were especially aged patients with multiple skin cancers, and complex clinical conditions, often affected by pathologies such as cardiopathy, diabetes mellitus, and hypercholesterolaemia, and receiving pharmacological multi-therapies, particularly antiplatelets and anticoagulants. In many of these patients, the general complex clinical picture provided significant contraindication for complex reconstructive surgery because of the high risk involved. All patients achieved complete healing about 8 weeks after the first surgery. By using a dermal induction template, it was possible to cover substantial loss of substances without the need of autologous tissue, with smoother and less apparent scar, minor occurrence of hypertrophic and retracted scars, better flexibility of healed skin and therefore a better result from an aesthetic point of view.

Multiple unilateral nonmelanoma skin cancers arising within chronic lymphedema

Multiple unilateral nonmelanoma skin cancers arising within chronic lymphedema

A Mass on the Nasal Dorsum

An elderly manwith a history of multiple skin cancers of the face presented with a 4-month history of a mass on the nasal dorsum. Findings from a biopsy of the lesion performed at an outside facilitywereconsistentwithsquamouscell carcinoma(SCC).Threeyears prior, the patient underwent 2 excisional biopsies of a mass at the same location showing infiltratingmoderately differentiated squamous cell carcinoma with acantholytic and pseudoglandular features. The lesion extended into the papillary dermis at the base of the excision. Therewas no endolymphatic or perineural invasion. A third excision performed later failed to demonstrate any disease. The patient’s other medical problems included diabetesmellitus, coronaryarterydisease,andemphysema.Findings fromaphysical examination were significant for a 3 × 2-cm ulcerative, nodular massof thenasal dorsum(Figure, A). Therewasnopalpable lymphadenopathy in theneck.Computed tomographic imagesof thehead andneck revealeda2.6 × 1.7-cmenhancingmass infiltrating thenasal dorsumwith possible involvement of the anterior nasal septum (Figure, B). The patient underwent an en bloc excision with negativemargins. Multiple areas of necrosis and cutaneous ulcerationwere evident. The tumor consistedof nests, trabeculae, and infiltrating rays of mitotically active cells. Some cells showed foamy, clear cytoplasm,while otherswere basophilic to amphophilic (Figure, C). Extensiveangiolymphatic andperineural invasionwaspresent (Figure, D). Immunohistochemical staining was positive for P63 (nuclear) and EMA and focally positive for CAM 5.2 and CK-7. Staining for HMB-45,CD10, chromogranin-A, S100, andVimentinwasnegative. What is your diagnosis? A B