Kathryn J. Martires

Psoriasis and the Risk of Depression in the US Population: National Health and Nutrition Examination Survey 2009-2012

IMPORTANCE Psoriasis is a risk factor for depression. Depression may also trigger or exacerbate psoriasis. The relationship between psoriasis and depression, however, remains to be fully explored. OBJECTIVE To investigate the association between psoriasis and major depression in the US population. DESIGN, SETTING, AND PARTICIPANTS Population-based study using participants in the National Health and Nutrition Examination Survey from 2009 through 2012. MAIN OUTCOMES AND MEASURES Diagnosis of major depression based on the Patient Health Questionnaire-9. RESULTS We identified 351 (2.8%) cases of psoriasis and 968 (7.8%) cases of major depression among 12,382 US citizens included in our study. Fifty-eight (16.5%) patients with psoriasis met criteria for a diagnosis of major depression. The mean (SD) Patient Health Questionnaire-9 score was significantly higher among patients with a history of psoriasis than those without psoriasis (4.54 [5.7] vs 3.22 [4.3], P < .001). Psoriasis was significantly associated with major depression, even after adjustment for sex, age, race, body mass index, physical activity, smoking history, alcohol use, history of myocardial infarction (MI), history of stroke, and history of diabetes mellitus (OR, 2.09 [95% CI, 1.41-3.11], P < .001). Interaction term analyses involving patients with a history of both psoriasis and a cardiovascular event, specifically MI or stroke, did not reveal a synergistically increased risk of major depression (psoriasis and MI: OR, 1.09 [95% CI, 0.28-3.60], P = .91; psoriasis and stroke: OR, 0.67 [95% CI, 0.12-3.66], P = .63). In adjusted multivariable models, the risk of major depression was not significantly different between patients with limited vs extensive psoriasis (OR, 0.66 [95% CI, 0.18-2.44], P = .53). CONCLUSIONS AND RELEVANCE Self-reported history of psoriasis was independently associated with major depression as assessed by a validated screening tool, even when controlling for comorbidities. History of cardiovascular event did not modify the risk of major depression for patients with psoriasis. The severity of psoriasis was unrelated to the risk of major depression. Therefore, all patients with psoriasis, regardless of severity, may be at risk for major depression.

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

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.

Prognostic Factors, Treatment, and Survival in Dermatofibrosarcoma Protuberans

Importance There is limited information regarding the influence of patient demographics, tumor characteristics, and treatment type on the survival of patients with dermatofibrosarcoma protuberans (DFSP). Objective To assess prognostic factors and to evaluate the influence of treatment modality on overall survival of patients with DFSP. Design, Setting, and Participants We examined DFSP using data for 3686 patients with histologically confirmed cases of DFSP diagnosed between 1972 and 2012 from the 18 US regional registries of the National Cancer Institutes Surveillance, Epidemiology, and End Results (SEER) Program, with linkage to demographic data from the US Census Bureau for median household income (MHI). The analysis was performed in February 2016. Main Outcomes and Measures The primary outcome measures were tumor characteristics, prognostic factors, and overall survival in months. Results There were 3686 cases of DFSP examined. Older age (hazard ratio [HR], 1.08; 95% CI, 1.06-1.10; P < .001), male sex (HR, 1.97; 95% CI, 1.09-3.55; P = .03), and tumor size (HR, 1.09; 95% CI, 1.01-1.18; P = .04) were significantly associated with poorer overall survival in a controlled analysis. Older age (odds ratio [OR], 1.01; 95% CI, 1.00-1.02; P = .01), male sex (OR, 1.95; 95% CI, 1.57-2.42; P < .001), and black race (OR, 1.78; 95% CI, 1.37-2.32; P < .001) were associated with larger (≥3.0 cm) tumors at presentation. Treatment modality did not influence overall survival; however, differences in patient characteristics affected the treatment received. Older age at presentation (OR, 1.02; 95% CI, 1.01-1.03; P =.01), black race (OR, 1.82; 95% CI, 1.13-2.92; P = .01), large tumor size (OR, 1.15; 95% CI, 1.09-1.21; P < .001), and head or neck location (OR, 4.63; 95% CI, 2.66-8.07; P <.001) increased the likelihood of a patient receiving surgery and radiation over surgery alone. In addition, white patients (OR, 0.51; 95% CI, 0.30-0.87; P=.01), women (OR, 0.53; 95% CI, 0.36-0.78; P <.001), and patients with a higher MHI (OR, 1.27; 95% CI, 1.11-1.46; P <.001) were more likely to receive Mohs micrographic surgery (MMS) over excision. Conclusions and Relevance Age at diagnosis, male sex, and DFSP tumor size appear to be important prognostic factors. Treatment modality did not significantly influence survival; however, patient and tumor characteristics influence treatment modality.

The incidence of second primary malignancies after gastrointestinal stromal tumor before and after the introduction of imatinib mesylate

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. Imatinib mesylate was FDA-approved in 2002 for the treatment of unresectable and metastatic GISTs and has become the standard of care. Its use has resulted in greatly increased survival rates for patients with GIST. The increased survival in patients with GIST raises concerns about long term effects of therapy, particularly the development of second primary malignancies (SPMs), which has been reported with imatinib treatment of chronic myeloid leukemia. In addition, the diagnosis of GIST itself may pose a risk for the development of SPMs. The purpose of this study was to examine the incidence of SPMs after GIST, particularly before (pre-imatinib era: 1992-2001) and after (imatinib era: 2002-2009), and factors related to the occurrence of SPMs. Data from the NCI’s Surveillance Epidemiology and End Results (SEER) 1992-2009 program was utilized. Standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) for these were calculated using SEER*Stat 8.0.1. Observed incidences were then compared between preimatinib and imatinib eras using Fisher’s exact test. The relationship between the presence of SPMs and each of the variables was examined using logistic regression. There were significantly more patients in the imatinib era alive after follow-up (n=533, 63.99%) than in the pre-imatinib era (n=130, 22.41%, P<0.001). Overall, the rate of SPMs after GIST in the imatinib era was 7.07%, compared with the rate of 1.15% that occurred in the pre-imatinib era (P=0.030). This difference was mainly accounted for by a higher incidence of colon adenocarcinoma in the imatinib era (P=0.023). Renal cell carcinoma also accounted for this difference. In contrast, the rate of melanoma of the skin was significantly lower in the imatinib era compared with the pre-imatinib era (P=0.030). In the pre-imatinib era for melanoma, the SIR was 17.64 (95% CI: 3.64-51.57). Patients with SPMs were significantly older at diagnosis (mean =64.18, SD =12.95) than patients without SPMs (mean =60.63, SD =15.27, P=0.024). Marital status was significantly related to the presence of SPMs (78.26% vs. 65.62%, P=0.0154) with those patients with SPMs more likely to be married compared to those without SPMs. This relationship is most likely due to increased survival. Of note, patients with SPMs had greater number of months of survival (mean =70.83, SD =51.54) than those without SPMs (mean =39.33, SD =37.30, P<0.0001). The findings in our study demonstrate that patients after GIST are at increased risk of developing SPMs and that this risk is increased following the introduction of imatinib in 2002. The increased incidence of SPMs in the era of imatinib could be explained by the increased survival of patients with metastatic GIST and therefore more time to develop SPMs, however, further studies are needed to investigate this mechanism.

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.

Meta-analysis concerning mortality for pregnancy-associated melanoma

pregnancy-associated group had their melanomas diagnosed either during pregnancy or up to 12 months post-partum. As we noted, this timing is consistent with obstetric definitions of ‘pregnancy-associated’ outcomes. Martires et al. asserted that the inclusion of Lens et al. instead of a subsequent report by Johansson et al. resulted in a more negative result than otherwise might have been seen. Both studies used data retrieved from the National Swedish Cancer Register with overlap of dates of melanoma diagnoses. However, only Lens et al. met inclusion criteria in regards to definition of pregnancy-associated melanoma. Johansson et al. defined pregnancy-associated melanoma as a melanoma diagnosed during pregnancy and up to 2 years post-partum which takes the estimates beyond the accepted 1-year post-partum period. Martires et al. also queried our choice of HR for the study by Stensheim et al. We had included the estimate that was not adjusted for anatomic location because not all the other published HRs were adjusted for anatomic location. On repeat analysis using the estimate adjusted for anatomic location, the pooled estimate remained essentially the same (pHR 1.54; 95% CI 1.21–1.96). Our inclusion of the study by Moller et al. where women with pregnancy-associated melanoma were identified through linkage with information on childbirth registered in a hospital, was also questioned. Their subgroup of females with melanomas diagnosed within 1 year of childbirth met our inclusion criteria and so was included. The limitation of missing data is common to registry-based studies. Moller et al. had available information on TNM stage for 72% of melanomas. With adjustment of TNM stage, the HR reduced from 2.06 (1.42–3.01) to 1.92 (1.32–2.79) but remained significant. The stage-adjusted HR was included in the pooled effect estimate in meta-analysis. While quantitative estimates of effect in relation to pregnancy-associated melanoma may vary according to metaanalysis inclusion criteria, we assert that our inclusion criteria were valid to assess this pregnancy-related outcome. Based on our findings and due to the limitations as stated in our manuscript, a precautionary attitude should prevail when managing patients with a pregnancy-associated melanoma.

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.

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

Abstract: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 CD4+CD30+ LyP and PCALCL.

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.

Pigmentation and Pregnancy: Knowing What Is Normal.

Changes in melanocytic nevi during pregnancy are frequently attributed to the new hormonal milieu and are dismissed without concern for malignancy. Recent studies suggest that pregnancy itself does not induce significant change in nevi, and delays in the assessment of changing moles may contribute to the often more advanced nature of melanomas diagnosed during or soon after pregnancy. Nevi on the breasts and abdomen can grow as a result of skin expansion, but studies have found no significant changes in nevi located in more stable areas such as the back or lower extremities. There is also insufficient evidence to support the notion that nevi darken during pregnancy. As such, any changing nevus that would raise concern for malignancy in a nonpregnant patient should do so in a pregnant patient as well. Pregnancy can, however, induce physiologic pigmentary changes that are often worrisome to both patients and physicians. These benign changes include melasma, pigmentary demarcation lines, secondary areola, and linea nigra as well as other less common findings. It is important for physicians to recognize these changes as physiologic to provide adequate reassurance to their patients and avoid unnecessary stress.