Melanoma risk after in vitro fertilization: A review of the literature.

BACKGROUND: The role of female sex hormones in the pathogenesis of malignant melanoma (MM) remains controversial. Although melanocytes appear to be hormonally responsive, the effect of estrogen on MM cells is less clear. Available clinical data does not consistently demonstrate that increased endogenous hormones from pregnancy or increased exogenous hormones from oral contraceptive pills and hormone replacement affect MM prevalence and outcome. OBJECTIVE: We sought to examine potential associations between in vitro fertilization (IVF) and melanoma. METHODS: A literature review was conducted. Primary outcomes were reported as associations between IVF and melanoma risk compared with the general population. Secondary outcomes included associations stratified by type of IVF regimen and subgroup, such as parous versus nulliparous patients. RESULTS: Eleven studies met our inclusion criteria. Five studies found no increased risk for MM among IVF users compared with the general population. Two studies found an increase in MM in clomiphene users, and 4 studies found an increase in MM among patients who were gravid or parous either before or after IVF. CONCLUSION: The reviewed studies do not reveal consistent patterns of association between IVF and MM among all infertile women. However, the data indicates a potential increased risk for MM in ever-parous patients treated with IVF. High-quality studies including a large number of MM cases that control for well-established MM risk factors are needed to adequately assess the relationship between IVF and MM, particularly among ever-parous women.

The risk of melanoma and hematologic cancers in patients with psoriasis.

BACKGROUND: The risk of melanoma and hematologic cancers in patients with psoriasis is controversial. OBJECTIVE: We sought to assess the risk of melanoma and hematologic cancers in patients with psoriasis, and the association with different treatments. METHODS: We used case-control and retrospective cohort designs to determine melanoma or hematologic cancer risk in patients with psoriasis. Risk with treatment type was assessed using Fisher exact test. RESULTS: Patients with psoriasis had 1.53 times greater risk of developing a malignancy compared with patients without psoriasis (P < .01). There were no significant differences in malignancy risk among patients treated with topicals, phototherapy, systemics, or biologic agents. Patients with psoriasis and malignancy did not have significantly worse survival than patients without psoriasis. LIMITATIONS: It is possible that patients developed malignancy subsequent to the follow-up time included in the study. CONCLUSION: Patients with psoriasis may experience an elevated risk of melanoma and hematologic cancers, compared with the general population. The risk is not increased by systemic or biologic psoriasis therapies.

Impact of Socioeconomic Status and Ethnicity on Melanoma Presentation and Recurrence in Caucasian Patients.

OBJECTIVES: The impact of ethnicity and the socioeconomic status (SES) among Caucasians is not well studied. Here, we examine the impact of income on melanoma presentation and prognosis within a Caucasian cohort, accounting for ethnicity, as some reports suggest increased melanoma incidence in Ashkenazi Jewish (AJ) BRCA mutation carriers. METHODS: We studied prospectively enrolled primary melanoma patients at New York University. SES data were estimated using United States' Census Bureau data and patient zip codes. We evaluated associations between ethnicity, SES, and baseline characteristics using the χ² test and multivariate logistic regression. We compared survival distributions using Kaplan-Meier curves, log-rank tests, and Cox proportional hazard ratios. RESULTS: Of the 1,339 enrolled patients, AJ represented 32% (n = 423). Apart from AJ being older at presentation (p < 0.001), no significant differences were observed in baseline characteristics between ethnic groups. Patients with a median household income (MHI) lower than the median of the cohort were significantly more likely to present with advanced stages (p < 0.001) compared to patients with a higher MHI. Shorter overall (p = 0.016) and post-recurrence survival (p = 0.042) was also observed in patients from lower-income households. CONCLUSION: Data suggest that disparities in melanoma presentation in Caucasians stratify according to income independent of ethnic background.

Pregnancy and melanoma.

Malignant melanoma is the most common malignancy during pregnancy, and is diagnosed during childbearing age in approximately one-third of women diagnosed with melanoma. The impact of hormonal changes during pregnancy and from iatrogenic hormones on melanoma is controversial. Women undergo immunologic changes during pregnancy that may decrease tumor surveillance. In addition, hormone receptors are found on some melanomas. In spite of these observations, the preponderance of evidence does not support a poorer prognosis for pregnancy-associated melanomas. There is also a lack of evidence that oral contraceptives or hormone replacement therapy worsens melanoma prognosis.

Nevi and pregnancy.

Changes in the moles of pregnant women are frequently attributed to pregnancy, but recent studies suggest that pregnancy does not induce significant physiologic changes in nevi. It is common for nevi on the breasts and abdomen to grow with normal skin expansion, but studies that have examined melanocytic nevi on the backs or lower extremities have found no significant changes in size during pregnancy. Several studies have also investigated the belief that moles darken during pregnancy and have found insufficient evidence to support this idea. Dermoscopically, transient changes have been identified, but none are suggestive of melanoma. Results vary in terms of histologic changes seen in samples taken from pregnant women, but all authors agree that any histopathologic features consistent with melanoma should be viewed as melanoma and not attributed to pregnancy. Biopsy specimens should be obtained promptly from any changing mole that would raise concern for malignancy in a nonpregnant patient. Such procedures can be performed safely during pregnancy.

Acral melanocytic lesions in the United States: Prevalence, awareness, and dermoscopic patterns in skin-of-color and non-Hispanic white patients.

BACKGROUND: Acral lentiginous melanoma has increased mortality compared with other melanoma subtypes and disproportionately affects ethnic minorities. Acral melanocytic lesions have not been well studied in diverse populations of the United States. OBJECTIVE: We sought to assess the prevalence, awareness, and dermoscopic patterns of acral melanocytic lesions in skin-of-color and non-Hispanic white patients. METHODS: We prospectively examined the palms and soles of 1052 patients presenting to dermatology clinics in New York, NY, and Miami, FL, from October 2013 to April 2015. RESULTS: Acral melanocytic lesions were observed in 36% of our cohort. Skin-of-color patients were more likely to have acral melanocytic lesions than non-Hispanic white patients (P < .01). Acral melanocytic lesions correlated with increased mole counts, particularly on non-Hispanic white patients. The majority of lesions demonstrated benign dermoscopic patterns. We observed 2 lesions with the parallel ridge pattern in our cohort, both found to be atypical nevi on biopsy specimen. Patients often lacked awareness of the presence of their lesions. LIMITATIONS: Interobserver variability in assessing dermoscopic patterns is a limitation. CONCLUSIONS: Melanocytic lesions of the palms and soles are common, particularly in a cohort of multiple ethnicities from the United States. Dermoscopy of acral lesions is an important clinical tool for diagnosis and management of these lesions.

CD30+ lymphoproliferative disorder with spindle-cell morphology.

Lymphomatoid papulosis (LyP) is classified as a CD30+ primary cutaneous lymphoproliferative disease. The phenotypic variability along the spectrum of CD30+ lymphoproliferative diseases is highlighted by the distinct histologic subtypes of LyP types A, B, C, and the more recently described types D, E, and F. We report the case of an elderly woman with a clinical presentation and histopathologic findings consistent with LyP, whose atypical CD30+ infiltrate uniquely demonstrated a spindle-cell morphology. To our knowledge, this is the first reported case of LyP characterized by CD30+ spindle-shaped cells, and may represent a new and distinct histologic variant of LyP.

Primary cutaneous smoldering adult T-cell leukemia/ lymphoma.

HTLV-1 is a virus that is endemic in southwesternJapan and the Caribbean and has been implicatedin the development of ATLL. ATLL, which is anuncommon malignant condition of peripheralT-lymphocytes, is characterized by four clinicalsubtypes, which include acute, lymphomatous,chronic, and smoldering types, that are based onLDH levels, calcium levels, and extent of organinvolvement. We present a 52-year- old woman withpruritic patches with scale on the buttocks and withtender, hyperpigmented macules and papules oftwo-years duration. Histopathologic examinationwas suggestive of mycosis fungoides, laboratoryresults showed HTLV-I and II, and the patient wasdiagnosed with primary cutaneous ATLL. We reviewthe literature on HTLV-1 and ATLL and specifically theprognosis of cutaneous ATLL. The literature suggeststhat a diagnosis of ATLL should be considered amongpatients of Caribbean origin or other endemicareas with skin lesions that suggest a cutaneousT-cell lymphoma, with clinicopathologic features ofmycosis fungoides. Differentiation between ATLLand cutaneous T-cell lymphoma is imperative as theyhave different prognoses and treatment approaches.

Eosinophilic dermatosis of hematologic malignancy.

We report a 68-year-old woman with chroniclymphocytic leukemia, who developed numerous,pruritic, edematous, and vesicobullous skin lesionsof the face and extremities over the course of severalmonths. The diagnosis of eosinophilic dermatosis ofhematologic malignancy (EDHM) was made basedon the clinical history and histopathologic features.Owing to the possible link between EDHM and amore aggressive underlying CLL, she was startedagain on chemotherapy. This case serves as areminder that, although the precise pathogenesis ofEDHM remains unclear, the paraneoplastic disorderis the result of immune dysregulation. Patientswho develop EDHM should undergo prompthematologic/oncologic evaluation.

Dermatomyositis, clinically presenting with cutaneous ulcers, with histopathologic evidence of perforating collagenosis.

Dermatomyositis is a systemic, autoimmune diseasewith a variety of clinical features that often includemyositis and characteristic cutaneous findings. Asubset of patients with dermatomyositis developcutaneous ulcers, often in the setting of vasculitis orvasculopathy. We present a case of dermatomyositiswith cutaneous ulcers that show perforatingcollagenosis on histopathologic examination.Acquired reactive perforating collagenosistypically occurs in the setting of diabetes mellitus,chronic renal failure, and other pruritic conditions,and this case represents a rare association withdermatomyositis, which may ultimately be helpful inelucidating the pathophysiology of this perforatingdisorder.

Melanoma in patients with chronic lymphocytic leukemia and non-Hodgkin lymphoma.

BACKGROUND: The relationship between melanoma and chronic lymphocytic leukemia (CLL) or non-Hodgkin lymphoma (NHL) has been minimally investigated. OBJECTIVE: The objective of this study was to examine the incidence of melanoma in patients with a history of CLL or NHL, and their associated mortality. METHODS: Cohorts of Kaiser Permanente Southern California members with a history of CLL and NHL were identified. Age-adjusted incidence density rates of melanoma among patients with CLL or NHL were compared with rates of melanoma among the general population of Kaiser Permanente Southern California patients. The mortality of patients with melanoma was examined using Cox proportional hazards modeling. RESULTS: The age-adjusted incidence rate per 100,000 person-years for melanoma among patients with either CLL or NHL was 107 (95% confidence interval 84.4-129.6) versus 25.9 among the general population (95% confidence interval 84.4-129.6, P < .001). Patients with melanoma and a history of CLL or NHL had 2.46 greater odds of death compared with those without CLL or NHL (95% confidence interval 1.77-3.41). LIMITATIONS: This study was retrospective in nature; the International Classification of Diseases, Ninth Revision codes used may contain diagnostic errors; and only overall survival was used in our analysis. CONCLUSIONS: Patients with a history of CLL or NHL have a higher incidence of melanoma. Patients with CLL or NHL who are subsequently given the diagnosis of melanoma have a higher mortality than patients with melanoma without a preceding diagnosis of CLL.

Characterization of primary cutaneous CD8+/CD30+ lymphoproliferative disorders.

CD30 primary cutaneous lymphoproliferative diseases include both lymphomatoid papulosis (LyP) and primary cutaneous anaplastic large cell lymphoma (PCALCL). The neoplastic cell of most primary CD30 lymphoproliferative disorders is CD4 positive. The terminology LyP "type D" has been used to describe a growing number of cases of LyP with a predominantly CD8 infiltrate. PCALCL with a CD8 phenotype has also been described, which presents a particularly difficult diagnostic and management challenge, given the difficulty in distinguishing it histologically from other cytotoxic lymphomas such as primary cutaneous aggressive epidermotropic CD8 cytotoxic T-cell lymphoma and CD8 gamma/delta and natural killer/T-cell lymphoma. We report 7 additional cases of these rare cutaneous CD8/CD30 lymphoproliferative disorders. We also present a unique case of CD8/CD30 LyP with histologic similarities to LyP type B. In all 7 of our cases of CD8 LyP and CD8 anaplastic large cell lymphoma, we found focal to diffuse MUM-1 positivity. We propose that MUM-1 may represent an adjunctive marker for CD8 lymphoproliferative disease. Finally, we review the current literature on cases of CD8 LyP and PCALCL. For the 106 cases examined, we found similar clinical and histologic features to those reported for traditional CD4CD30 LyP and PCALCL.

Factors affecting academic leadership in dermatology.

Although prior studies have examined methods by which to recruit and retain academic dermatologists, few have examined factors that are important for developing academic leaders in dermatology. This study sought to examine characteristics of dermatology residency programs that affect the odds of producing department or division chairs/chiefs and program directors (PDs). Data regarding program size, faculty, grants, alumni residency program attended, lectures, and publications for all accredited US dermatology residency programs were collected. Of the 103 programs examined, 46% had graduated at least 1 chair/chief, and 53% had graduated at least 1 PD. Results emphasize that faculty guidance and research may represent modifiable factors by which a dermatology residency program can increase its graduation of academic leaders.

Sarcoidosis.

We present a 28-year-old man with a one-year history of cutaneous lesions in old scars and tattoos with concomitant subcutaneous nodules and myopathy. A skin biopsy specimen showed cutaneous sarcoidosis. We discuss the multiple aspects of this case, which represent unique presentations of this systemic disease as well as review isomorphic and isotopic responses.

Patterns of cancer screening in primary care from 2005 to 2010.

BACKGROUND: Cancer screening recommendations vary widely, especially for breast, prostate, and skin cancer screening. Guidelines are provided by the American Cancer Society, the US Preventive Services Task Force, and various professional organizations. The recommendations often differ with regard to age and frequency of screening. The objective of this study was to determine actual rates of screening in the primary care setting. METHODS: Data from the National Ambulatory Medical Care Survey were used. Only adult visits to non-federally employed, office-based physicians for preventive care from 2005 through 2010 were examined. Prevalence rates for breast, pelvic, and rectal examinations were calculated, along with the rates for mammograms, Papanicolaou smears, and prostate-specific antigen tests. Factors associated with screening, including age, race, smoking status, and insurance type, were examined using t tests and chi-square tests. RESULTS: In total, 8521 visits were examined. The rates of most screening examinations and tests were stable over time. Clinical breast examinations took place significantly more than mammography was ordered (54.8% vs 34.6%; P<.001). White patients received more mammography (P=.031), skin examinations (P<.010), digital rectal examinations (P<.010), and prostate-specific antigen tests (P=.003) than patients of other races. Patients who paid with Medicare or private insurance received more screening than patients who had Medicaid or no insurance (P<.010). CONCLUSIONS: Current cancer screening practices in primary care vary significantly. Cancer screening may not follow evidence-based practices and may not be targeting patients considered most at risk. Racial and socioeconomic disparities are present in cancer screening in primary care.

The role of skin trauma in the distribution of morphea lesions: a cross-sectional survey of the Morphea in Adults and Children cohort IV.

BACKGROUND: Skin trauma may play a role in the development of morphea lesions. The association between trauma and the distribution of cutaneous lesions has never been examined to our knowledge. OBJECTIVE: We sought to determine whether patients enrolled in the Morphea in Adults and Children (MAC) cohort exhibit skin lesions distributed in areas of prior (isotopic) or ongoing (isomorphic) trauma. METHODS: This was a cross-sectional analysis of the MAC cohort. RESULTS: Of 329 patients in the MAC cohort, 52 (16%) had trauma-associated lesions at the onset of disease. Patients with lesions in an isotopic distribution had greater clinical severity as measured by a clinical outcome measure (mean modified Rodnan Skin Score of 13.8 vs 5.3, P = .004, 95% confidence interval 3.08-13.92) and impact on life quality (mean Dermatology Life Quality Index score 8.4 vs 4.1, P = .009, 95% confidence interval 1.18-7.50) than those with an isomorphic distribution. Most frequent associated traumas were chronic friction (isomorphic) and surgery/isotopic. LIMITATIONS: Recall bias for patient-reported events is a limitation. CONCLUSION: Of patients in the MAC cohort, 16% developed initial morphea lesions at sites of skin trauma. If these findings can be confirmed in additional series, they suggest that elective procedures and excessive skin trauma or friction might be avoided in these patients.

Antitumorigenic potential of STAT3 alternative splicing modulation.

Signal transducer and activator of transcription 3 (STAT3) plays a central role in the activation of multiple oncogenic pathways. Splicing variant STAT3ß uses an alternative acceptor site within exon 23 that leads to a truncated isoform lacking the C-terminal transactivation domain. Depending on the context, STAT3ß can act as a dominant-negative regulator of transcription and promote apoptosis. We show that modified antisense oligonucleotides targeted to a splicing enhancer that regulates STAT3 exon 23 alternative splicing specifically promote a shift of expression from STAT3α to STAT3ß. Induction of endogenous STAT3ß leads to apoptosis and cell-cycle arrest in cell lines with persistent STAT3 tyrosine phosphorylation compared with total STAT3 knockdown obtained by forced splicing-dependent nonsense-mediated decay (FSD-NMD). Comparison of the molecular effects of splicing redirection to STAT3 knockdown reveals a unique STAT3ß signature, with a down-regulation of specific targets (including lens epithelium-derived growth factor, p300/CBP-associated factor, CyclinC, peroxisomal biogenesis factor 1, and STAT1ß) distinct from canonical STAT3 targets typically associated with total STAT3 knockdown. Furthermore, similar in vivo redirection of STAT3 alternative splicing leads to tumor regression in a xenograft cancer model, demonstrating how pharmacological manipulation of a single key splicing event can manifest powerful antitumorigenic properties and validating endogenous splicing reprogramming as an effective cancer therapeutic approach.

Sclerotic-type chronic GVHD of the skin: clinical risk factors, laboratory markers, and burden of disease.

Chronic GVHD is one of the most severe complications of allogeneic HSCT. The sclerotic skin manifestations of cGVHD (ScGVHD) result from inflammation and fibrosis of the dermis, subcutaneous tissue, or fascia, leading to significant functional disability. Risk factors and clinical markers associated with ScGVHD remain largely unexamined. By using a single-visit, cross-sectional design, we evaluated 206 patients with cGVHD at the National Institutes of Health. Most patients manifested severe (ie, 63% National Institutes of Health score "severe"), refractory disease (median treatments = 4). ScGVHD was detected in 109 (52.9%) patients. ScGVHD was associated with greater platelet count (P < .001) and C3 (P < .001), and decreased forced vital capacity (P = .013). Total body irradiation (TBI) was associated with development of ScGVHD (P = .002). TBI administered in reduced-intensity conditioning was most strongly associated with ScGVHD (14/15 patients, P < .0001). Patients with ScGVHD had significant impairments of joint range of motion and grip strength (P < .001). Greater body surface area involvement was associated with poorer survival (P = .015). We conclude that TBI, particularly in reduced-intensity regimens, may be an important risk factor for ScGVHD. Widespread skin involvement is associated with significant functional impairment, distressing symptoms, and diminished survival. This trial is registered at http://www.clinicaltrials.gov as NCT00331968.

Risk of subsequent primary malignancies after dermatofibrosarcoma protuberans diagnosis: a national study.

BACKGROUND: Patients frequently live many years after diagnosis of dermatofibrosarcoma protuberans (DFSP). OBJECTIVE: We sought to determine the risk of subsequent primary malignancy (SPM) after DFSP diagnosis. METHODS: Using the Surveillance, Epidemiology, and End Results database (1973-2008) for 3734 patients with DFSP, we compared the risk of developing 14 SPMs (12 most prevalent cancers in the United States plus other nonepithelial and soft tissue) relative to risk in the general population of same sex, race, and age and year of diagnosis. RESULTS: Patients given the diagnosis of DFSP had an overall increased risk of SPM (observed:expected [O:E], 1.20; 95% confidence intervals [CI], 1.04-1.39), with much of the overall increased risk attributable to increased risk of nonepithelial skin cancer (O:E, 9.94; 95% CI, 3.38-22.30). Specifically, female patients with DFSP were at increased risk of other nonepithelial skin cancer (O:E, 14.50; 95% CI, 3.46-38.98), melanoma (O:E, 2.59; 95% CI, 1.02-5.35), and breast cancer (O:E, 1.44; 95% CI, 1.00-2.00). Male patients were not at increased overall risk (O:E, 1.18; 95% CI, 0.96-1.44) of SPM or at increased risk of any specific malignancy (P > .05) adjusted for multiplicity of t tests. LIMITATIONS: Surveillance bias may have led to increased rates and earlier detection of primary malignances in patients with DFSP compared with the general population. Individual data that may reveal shared environmental causes of DFSP and SPM were unavailable. CONCLUSIONS: Patients with DFSP are at increased risk of a number of SPMs.

Prognosis of patients with transected melanomas.

BACKGROUND: The management of melanoma is directly related to Breslow's depth. Biopsying melanomas in a fashion that transects the deep margin precludes an accurate measurement of the true depth. OBJECTIVE: To examine the prognosis of melanomas transected along the deep margins, as well as cases where no residual melanoma was seen on re-excision after transection. METHODS: Records from a cohort of patients at one institution were examined from 1996 through 2007. Patients were considered to have "transected" melanomas if tumor cells were present on the deep margin of the biopsy. Overall survival was determined. RESULTS: Seven hundred fourteen patients were examined. 171 (24%) of all melanomas were transected. 101(59%) of those lacked tumor cells on re-excision. Patients with transected melanomas were older (OR = 1.03, p < .001), and had higher Breslow's depths (OR = 1.21, p < .001) than those without transected tumors. Those with no residual melanoma after transection were younger (OR = 0.98, p = .010) and more likely to have no lymph node involvement (OR = 2.23, p = .037). Neither transection (p = .760), nor lack of residual melanoma on re-excision after transection (p = .793) influenced survival. CONCLUSION: A high number of melanomas are transected at diagnosis, many of which lack visible tumor. The original Breslow's depth of transected melanomas without residual tumor on re-excision accurately predicts survival and prognosis.