Repeated Occurrences of Basal Cell Cancer in Patients With Inflammatory Bowel Disease Treated With Immunosuppressive Medications.

INTRODUCTION: There are limited data on repeated basal cell cancer (BCC) occurrences among patients with inflammatory bowel disease (IBD), especially the impact of continuing immunosuppressive medications. METHODS: We conducted a retrospective cohort study of 54,919 patients with IBD followed in the Veterans Affairs Healthcare System. We identified patients who had an incident BCC after their IBD diagnosis. We defined patients' exposure based on their IBD medications use as follows: (i) only aminosalicylate (5-ASA) use, (ii) only active thiopurine (TP) use, (iii) past TP use (discontinued >6 months ago) and no antitumor necrosis factor (TNF) use, (iv) anti-TNF use after previous TP use, (v) only anti-TNF use, and (vi) active anti-TNF and TP use. The outcome of interest was the repeated occurrence of BCC. Adjusted and unadjusted hazard ratios with 95% confidence intervals were used to estimate the risk of repeated BCC occurrence. RESULTS: A total of 518 patients developed BCC after their IBD diagnosis. The numbers of repeated BCC occurrences per 100 person-years were 12.8 (5-ASA use only), 34.5 (active TP use), 19.3 (past TP use and no anti-TNF use), 25.4 (anti-TNF use after previous TP use), 17.8 (only anti-TNF use), and 22.4 (active anti-TNF and TP use). Compared with 5-ASA use alone, only active TP use was associated with an increased risk for repeated BCC occurrence (adjusted hazard ratio 1.65, 95% confidence interval 1.24-2.19; P = 0.0005). However, the increased risk was no longer present for other exposure categories. DISCUSSION: Among IBD patients who developed an incident BCC while taking a TP and continued it, there was an increased risk of repeated BCC occurrences.

Immunity drives TET1 regulation in cancer through NF-κB.

Ten-eleven translocation enzymes (TET1, TET2, and TET3), which induce DNA demethylation and gene regulation by converting 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), are often down-regulated in cancer. We uncover, in basal-like breast cancer (BLBC), genome-wide 5hmC changes related to TET1 regulation. We further demonstrate that TET1 repression is associated with high expression of immune markers and high infiltration by immune cells. We identify in BLBC tissues an anticorrelation between TET1 expression and the major immunoregulator family nuclear factor κB (NF-κB). In vitro and in mice, TET1 is down-regulated in breast cancer cells upon NF-κB activation through binding of p65 to its consensus sequence in the TET1 promoter. We lastly show that these findings extend to other cancer types, including melanoma, lung, and thyroid cancers. Together, our data suggest a novel mode of regulation for TET1 in cancer and highlight a new paradigm in which the immune system can influence cancer cell epigenetics.

Basal-like Breast Cancers: From Pathology to Biology and Back Again.

Human breast cancers referred to as "basal-like" are of interest because they lack effective therapies and their biology is poorly understood. The term basal-like derives from studies demonstrating tumor gene expression profiles that include some transcripts characteristic of the basal cells of the normal adult human mammary gland and others associated with a subset of normal luminal cells. Elucidating the mechanisms responsible for the profiles of basal-like tumors is an active area of investigation. More refined molecular analysis of patients' samples and genetic strategies to produce breast cancers de novo from defined populations of normal mouse mammary cells have served as complementary approaches to identify relevant pathway alterations. However, both also have limitations. Here, we review some of the underlying reasons, including the unifying concept that some normal luminal cells have both luminal and basal features, as well as some emerging new avenues of investigation.

Decision tree analysis to stratify risk of de novo non-melanoma skin cancer following liver transplantation.

PURPOSE: Non-melanoma skin cancer (NMSC) is the most common de novo malignancy in liver transplant (LT) recipients; it behaves more aggressively and it increases mortality. We used decision tree analysis to develop a tool to stratify and quantify risk of NMSC in LT recipients. METHODS: We performed Cox regression analysis to identify which predictive variables to enter into the decision tree analysis. Data were from the Organ Procurement Transplant Network (OPTN) STAR files of September 2016 (n = 102984). RESULTS: NMSC developed in 4556 of the 105984 recipients, a mean of 5.6 years after transplant. The 5/10/20-year rates of NMSC were 2.9/6.3/13.5%, respectively. Cox regression identified male gender, Caucasian race, age, body mass index (BMI) at LT, and sirolimus use as key predictive or protective factors for NMSC. These factors were entered into a decision tree analysis. The final tree stratified non-Caucasians as low risk (0.8%), and Caucasian males > 47 years, BMI < 40 who did not receive sirolimus, as high risk (7.3% cumulative incidence of NMSC). The predictions in the derivation set were almost identical to those in the validation set (r2 = 0.971, p < 0.0001). Cumulative incidence of NMSC in low, moderate and high risk groups at 5/10/20 year was 0.5/1.2/3.3, 2.1/4.8/11.7 and 5.6/11.6/23.1% (p < 0.0001). CONCLUSIONS: The decision tree model accurately stratifies the risk of developing NMSC in the long-term after LT.

Amiloidosis cutánea primaria del oído externo: una entidad peculiar, inusual y benigna / Primary cutaneous amyloidosis of the external ear: A peculiar, unusual and benign entity

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Prostatic inflammation enhances basal-to-luminal differentiation and accelerates initiation of prostate cancer with a basal cell origin.

Chronic inflammation has been shown to promote the initiation and progression of diverse malignancies by inducing genetic and epigenetic alterations. In this study, we investigate an alternative mechanism through which inflammation promotes the initiation of prostate cancer. Adult murine prostate epithelia are composed predominantly of basal and luminal cells. Previous studies revealed that the two lineages are largely self-sustained when residing in their native microenvironment. To interrogate whether tissue inflammation alters the differentiation program of basal cells, we conducted lineage tracing of basal cells using a K14-CreER;mTmG model in concert with a murine model of prostatitis induced by infection from the uropathogenic bacteria CP9. We show that acute prostatitis causes tissue damage and creates a tissue microenvironment that induces the differentiation of basal cells into luminal cells, an alteration that rarely occurs under normal physiological conditions. Previously we showed that a mouse model with prostate basal cell-specific deletion of Phosphatase and tensin homolog (K14-CreER;Pten(fl/fl)) develops prostate cancer with a long latency, because disease initiation in this model requires and is limited by the differentiation of transformation-resistant basal cells into transformation-competent luminal cells. Here, we show that CP9-induced prostatitis significantly accelerates the initiation of prostatic intraepithelial neoplasia in this model. Our results demonstrate that inflammation results in a tissue microenvironment that alters the normal prostate epithelial cell differentiation program and that through this cellular process inflammation accelerates the initiation of prostate cancer with a basal cell origin.

[New aspects of the pathogenesis and classification of basal-like breast carcinoma].

New approaches to the molecular classification of breast cancer are considered. Particular emphasis is placed on its basal-like type that belongs to the most aggressive and prognostically unfavorable forms of tumor. The origin of this type of breast cancer is the subject of intense debate in the scientific community. There are three basic theories that basal-like breast carcinoma may arise from the stem or myoepithelial cells and through dedifferentiation via epithelial-mesenchymal transformation. The theory of its origin from stem/progenitor cells is most valid and proven.

Comparative vaccine-specific and other injectable-specific risks of injection-site sarcomas in cats.

OBJECTIVE: To compare associations between vaccine types and other injectable drugs with development of injection-site sarcomas in cats. DESIGN: Case-control study. ANIMALS: 181 cats with soft tissue sarcomas (cases), 96 cats with tumors at non-vaccine regions (control group I), and 159 cats with basal cell tumors (control group II). PROCEDURES: Subjects were prospectively obtained from a large pathology database. Demographic, sarcoma location, basal cell tumor, and vaccine and other injectable history data were documented by use of a questionnaire and used to define case, control, and exposure status. Three control groups were included: cats with sarcomas at non-vaccine sites, cats with basal cell tumors, and a combined group of cats with sarcomas at non-vaccine sites and cats with basal cell tumors. χ(2) tests, marginal homogeneity tests, and exact logistic regression were performed. RESULTS: In the broad interscapular region, the frequency of administration of long-acting corticosteroid injections (dexamethasone, methylprednisolone, and triamcinolone) was significantly higher in cases than in controls. In the broad rear limb region, case cats were significantly less likely to have received recombinant vaccines than inactivated vaccines; ORs from logistic regression analyses equaled 0.1, with 95% confidence intervals ranging from 0 to 0.4 and 0 to 0.7, depending on control group and time period of exposure used. CONCLUSIONS AND CLINICAL RELEVANCE: This case-control study measuring temporal and spatial exposures efficiently detected associations between administrations of various types of vaccines (recombinant vs inactivated rabies) and other injectable products (ie, long-acting corticosteroids) with sarcoma development without the need to directly measure incidence. These findings nevertheless also indicated that no vaccines were risk free. The study is informative in allowing practitioners to weigh the relative merits and risks of commonly used pharmaceutical products.

Squamous cell and basal cell carcinoma of the skin in relation to radiation therapy and potential modification of risk by sun exposure.

BACKGROUND: Epidemiologic studies consistently find enhanced risk of basal cell carcinoma of the skin among individuals exposed to ionizing radiation, but it is unclear whether the radiation effect occurs for squamous cell carcinoma. It is also not known whether subgroups of individuals are at greater risk, eg, those with radiation sensitivity or high ultraviolet radiation exposure. METHODS: We analyzed data from a case-control study of keratinocyte cancers in New Hampshire. Incident cases diagnosed in 1993-1995 and 1997-2000 were identified through a state-wide skin cancer surveillance system, and controls were identified through the Department of Transportation and Center for Medicare and Medicaid Service Files (n = 1121 basal cell carcinoma cases, 854 squamous cell carcinoma cases, and 1049 controls). RESULTS: We found an association between history of radiation treatment and basal cell carcinoma. The association was especially strong for basal cell carcinomas arising within the radiation treatment field (odds ratio = 2.6; 95% confidence interval = 1.5-4.3), and among those treated with radiation therapy before age 20 (3.4; 1.8-6.4), those whose basal cell carcinomas occurred 40 or more years after radiation treatment (3.2; 1.8-5.8), and those treated with radiation for acne (11; 2.7-49). Similar age and time patterns of risk were observed for squamous cell carcinoma, although generally with smaller odds ratios. For basal cell carcinoma, early exposure to radiation treatment was a risk factor largely among those without a history of severe sunburns, whereas for squamous cell carcinoma, radiation treatment was a risk factor primarily among those with a sun-sensitive skin type (ie, a tendency to sunburn). CONCLUSIONS: Radiation treatment, particularly if experienced before age 20, seems to increase the long-term risk of both basal and squamous cell carcinomas of the skin. These risks may differ by sun exposure or host response to sunlight exposure.

Skin cancers at the National University Hospital of Cotonou from 1985 to 2004.

BACKGROUND: Skin cancer is the most common form of cancer occurring in adults in Europe and the USA. A low incidence has been reported in the black American population and in Africa, however. This study investigates the incidence of melanoma and epidermoid and basocellular carcinoma at Cotonou in Benin. METHODS: Over 20 years, 19 patient records were collected, 16 of which were the subject of a retrospective epidemiologic study. RESULTS: The main characteristic of skin cancer in the Department of Dermatology, Cotonou, Benin was its extreme rarity. The frequency was 0.00066%, with a male to female ratio of 1.28 and a mean age of 54.81 years. The mean ages at diagnosis for epidermoid carcinoma, melanoma, and basocellular carcinoma were 61.66, 59.40, and 54.56 years, respectively. The mean duration of epidermoid carcinoma was 6-10 times longer than that of melanoma and basocellular carcinoma. Of the 16 patients included in the study, five were albinos. In this group, the frequency was 31.25%. DISCUSSION: The extreme rarity of skin cancers in our series cannot be the result of recruitment bias alone. It reflects the actual situation. All of our cases of melanoma were in a plantar location. This inconsistency with other studies is probably a result of the size of our series. The duration of disease in our cases of carcinoma was comparable with the results obtained in a previous study in Dakar, Senegal. In our study, oculocutaneous albinism was the main preneoplastic factor. CONCLUSION: This study confirms the low incidence of skin cancer in the black population, the fact that basocellular carcinoma affects a relatively young population, and the predilection of melanoma for acral locations in black individuals.

Deconstructing the molecular portrait of basal-like breast cancer.

Gene-expression profiling has revealed several molecular subtypes of breast cancer, which differ in their pathobiology and clinical outcomes. Basal-like tumors are a newly recognized subtype of breast cancer, which express genes that are characteristic of basal epithelial cells, such as the basal cytokeratins, and are associated with poor relapse-free and overall survival. However, the genetic and epigenetic alterations that are responsible for the biologically aggressive phenotype of these estrogen receptor-negative and HER2/ErbB2-negative tumors are not well understood, thereby hindering efforts to develop targeted therapies. Here, we focus on new insights into the molecular pathogenesis of basal-like breast cancer and explore how these discoveries might impact the treatment of these poor-prognosis tumors.

Multicenter case-control study of risk factors associated with development of vaccine-associated sarcomas in cats.

OBJECTIVE: To determine whether particular vaccine brands, other injectable medications, customary vaccination practices, or various host factors were associated with the formation of vaccine-associated sarcomas in cats. DESIGN: Prospective multicenter case-control study. ANIMALS: Cats in the United States and Canada with soft tissue sarcomas or basal cell tumors. PROCEDURE: Veterinarians submitting biopsy specimens from cats with a confirmed diagnosis of soft tissue sarcoma or basal cell tumor were contacted for patient medical history. Time window statistical analyses were used in conjunction with various assumptions about case definitions. RESULTS: No single vaccine brand or manufacturer within antigen class was found to be associated with sarcoma formation. Factors related to vaccine administration were also not associated with sarcoma development, with the possible exception of vaccine temperature prior to injection. Two injectable medications (long-acting penicillin and methyl prednisolone acetate) were administered to case cats more frequently than to control cats. CONCLUSIONS AND CLINICAL RELEVANCE: Findings do not support the hypotheses that specific brands or types of vaccine within antigen class, vaccine practices such as reuse of syringes, concomitant viral infection, history of trauma, or residence either increase or decrease the risk of vaccine-associated sarcoma formation in cats. There was evidence to suggest that certain long-acting injectable medications may also be associated with sarcoma formation.

Use of tanning devices and risk of basal cell and squamous cell skin cancers.

Use of artificial tanning devices that emit UV radiation, such as tanning lamps and tanning beds, has become increasingly popular in the United States. Although an excess risk of nonmelanoma skin cancers might be predicted from this exposure, little epidemiologic data exist. We conducted a population-based, case-control study that included 603 basal cell carcinoma (BCC) case patients, 293 squamous cell carcinoma (SCC) case patients, and 540 control subjects. Study participants were interviewed in person to obtain information on tanning device use, sun exposure history, sun sensitivity, and other risk factors for skin cancer. Overall, any use of tanning devices was associated with odds ratios of 2.5 (95% confidence interval [CI] = 1.7 to 3.8) for SCC and 1.5 (95% CI = 1.1 to 2.1) for BCC. Adjustment for history of sunburns, sunbathing, and sun exposure did not affect our results. Our findings suggest that the use of tanning devices may contribute to the incidence of nonmelanoma skin cancers. They highlight the need to further evaluate the potential risks of BCC and SCC that are associated with tanning lamp exposure and the appropriate public health response.

Carcinoma basocelular con diferenciación mioepitelial / Basall cell carcinoma with myoepithelial differentiation

Presentamos un nuevo caso de carcinoma basocelular con diferenciación micepitelial en un varón de 71 años. La tumoración, de 2,5 cm, estaba localizada en el ala nasal izquierda. Se trataba de un carcinoma basocelular típico que infiltraba en profundidad, alcanzando el tejido muscular. En algunas áreas del tumor el citoplasma de las células neoplásicas se hacía homogéneo y eosinofilico, desplazando el núcleo a la periferia. Estas células eran idénticas a las llamadas células hialinas descritas en tumores mixtos y mioepiteliomas de glándula salival y piel. En el estudio inmunohistoquímico presentaban una franca positividad para la actína muscular específica (HHF35) y más débil para la desmína. Ultraestructuralmente la eosinofilia citoplasmática estaba determinada por la presencia de abundantes filamentos finos de tipo actína que desplazaban los escasos tonofilamentos a la periferia. Estas células cumplían todos los criterios para ser etiquetadas como mioepiteliales. En la literatura sólo se han descrito siete casos de carcinoma basocelular con esta peculiar diferenciación (AU)

Trichoepithelioma papulosum multiplex.

Trichoepithelioma papulosum multiplex is an uncommon autosomal dominant disorder in which multiple trichoepitheliomas are seen. Its cause may be a defective tumor suppressor gene. Studies have mapped this gene to the 9p21 locus. However, there is a parallel or identical syndrome of multiple trichoepitheliomas and cylindromas. Within a given family, some members may have cyclindromas whereas others may have trichoepitheliomas or a combination of both. Although preliminary evidence suggests a different gene is responsible, it is possible that TPM may be caused by more than two independent genes, with some cases of TPM due to impairment of the gene for cylindromatosis. This entity, as well as other disorders with multiple appendageal tumors, may require clarification and distinction from TPM.

Desmoplastic trichilemmoma arising within a nevus sebaceus.

A 74-year-old man presented with a tumor on his scalp that he had since birth. The authors observed a verrucous pink crusted plaque. The tumor was clinically diagnosed as nevus sebaceus and was removed. Histopathologic study showed, arising from nevus sebaceus, a lobular neoplasm with the classic features of trichilemmoma. Desmoplasia was present in the center of the trichilemmomatous area. This description is typical of a special, uncommon type of trichilemmoma that histologically mimics invasive carcinoma.

Recurrent trichofolliculoma of the upper eyelid margin.

We report a woman who had a recurrent trichofolliculoma on the upper eyelid margin. Only three cases of this benign tumor on the eyelid have been reported, and no recurrence in this location had been noted in the literature. The lesion, present for 6 years, had been excised twice previously (3 and 4 years before), recurred, and had been injected with a steroid preparation 2 years earlier. Lashes, both normal-looking and immature, arose from the center area of this lesion, and telangiectatic vessels were on its surface. Full-thickness wedge resection was used to excise the lesion completely. Complete primary excision of trichofolliculoma is important, and local steroid preparations should not be used.