Frequency and prognosis of associated malignancies in 504 patients with lymphomatoid papulosis.

BACKGROUND: Lymphomatoid papulosis (LyP) can be associated with other haematological malignancies (HM), but reported percentages vary from 20% to over 50%. OBJECTIVE: To evaluate the frequency and prognostic significance of associated HM and non-HM in LyP patients. METHODS: In this multicentre cohort study, the complete Dutch LyP population was included from the Dutch Cutaneous Lymphoma Registry between 1985 and 2018. Clinical and histopathological information was retrieved from every individual patient. RESULTS: After a median follow-up of 120 months (range, 6-585), an associated HM was observed in 78/504 (15.5%) patients. Most common associated HM were mycosis fungoides (MF; n = 31) and anaplastic large-cell lymphoma (ALCL; n = 29), while 19 patients had another HM of B-cell (n = 14) or myeloid origin (n = 5). Even after a 25-year follow-up period, percentages of associated HM did not exceed 20%. Thirty-nine of 465 patients (8.4%) without a prior or concurrent associated HM developed an associated HM during follow-up, after a median of 68 months (range of 3-286 months). Nine of 78 patients died of associated HM, including 6/22 patients developing extracutaneous ALCL, while all patients with associated MF or skin-limited ALCL had an excellent prognosis. Compared with the general population, LyP patients showed an increased risk (relative risk, 2.8; 95% confidence intervals, 2.4-3.3) for non-HM, in particular cutaneous squamous cell carcinoma, melanoma and intestinal/lung/bladder cancer. CONCLUSIONS: An associated HM was reported in 15.5% of the LyP patients, particularly MF and ALCL. Although the frequency of associated HM is lower than suggested and the prognosis of most patients with associated HM is excellent, a small subgroup will develop aggressive disease, in particular extracutaneous ALCL. Furthermore, LyP patients have a higher risk of developing other malignancies. Clinicians should be aware of these risks, and LyP patients require close monitoring.

No radiographic wrist damage after treatment to target in recent-onset juvenile idiopathic arthritis.

BACKGROUND: To evaluate radiographic progression of patients with new-onset juvenile idiopathic arthritis (JIA) in response to an early, tightly-controlled, treatment-to-target. METHODS: Patients with JIA participating in the BeSt-for-Kids-study, randomized to 3 treatment strategy arms, were eligible if at least 1 conventional wrist-radiograph was available. Bone damage as reflected by carpal length was assessed using the Poznanski-score. The BoneXpert-method was used to determine the Bone Age (BA, > 5 years) and bone mineral density (BMD) of the wrist. These scores were evaluated over time and compared between the treatment arms and mean JADAS10-score using linear mixed models corrected for age and symptom duration. RESULTS: In 60 patients, 252 radiographs were analysed. Baseline age and symptom duration were different between the arms. No difference in comparison to the healthy reference population was found at baseline for the Poznanski-score (IQR varying from - 0,82; 0.68), nor for BA (varying from - 0.88 to 0.74). Baseline BMD was statistically significantly lower in arm 3 (initial treatment with etanercept and methotrexate) (- 1.48; - 0.68) compared to arm 1 (- 0.84; - 0.04) and arm 2 (- 0.93; 0.15). After treatment to target inactive disease, the Poznanski-scores and the BA remained clinically unchanged, while the BMD in arm 3 improved (p < 0.05 vs arm 1). CONCLUSIONS: Recent-onset JIA patients, treated-to-target aimed at inactive disease, showed no signs of radiographic wrist damage (Poznanski-score, BA or BMD) either at baseline or at follow-up, irrespective of treatment arm. A lower BMD at baseline in arm 3, initially treated with methotrexate and etanercept, improved significantly after treatment. TRIAL REGISTRATION: NTR, NL1504 (NTR1574). Registered 01-06-2009.

Preliminary Definitions for Sacroiliac Joint Pathologies in the OMERACT Juvenile Idiopathic Arthritis Magnetic Resonance Imaging Score (OMERACT JAMRIS-SIJ).

OBJECTIVE: To develop definitions for the assessment of magnetic resonance imaging (MRI) pathologies of the sacroiliac joints (SIJ) in juvenile idiopathic arthritis. METHODS: An Outcome Measures in Rheumatology (OMERACT) consensus-driven methodology consisting of iterative surveys and focus group meetings within an international group of rheumatologists and radiologists. RESULTS: Two domains, inflammation and structural, were identified. Definitions for bone marrow edema, joint space inflammation, capsulitis, and enthesitis were derived for joint inflammation; sclerosis, erosion, fatty lesion, and ankylosis were defined for assessing structural joint changes. CONCLUSION: Preliminary consensus-driven definitions for inflammation and structural elements have been derived, underpinning the ongoing development of the OMERACT Juvenile Arthritis MRI SIJ scoring system (OMERACT JAMRIS-SIJ).

Evaluation of treatment results in multifocal primary cutaneous anaplastic large cell lymphoma: report of the Dutch Cutaneous Lymphoma Group.

BACKGROUND: There is no consensus on the treatment of multifocal primary cutaneous anaplastic large cell lymphoma (C-ALCL). Radiotherapy (RT) and methotrexate (MTX) are the current treatment options, but their efficacy is unknown. Recently, targeted therapies showed promising results in C-ALCL, and may therefore be an attractive first choice of treatment. OBJECTIVES: To assess the efficacy of conventional treatment strategies for patients with multifocal C-ALCL, and to define which patients may require novel targeted therapies. METHODS: In this multicentre study, treatment was evaluated in patients initially presenting (n = 24) or relapsing with multifocal C-ALCL (n = 17; 23 relapses). Distinction was made between patients with five or less lesions (n = 36) and more than five lesions (n = 11). RESULTS: Treatments most commonly used were RT (n = 21), systemic chemotherapy (n = 9) and low-dose MTX (n = 7) with complete response rates of 100%, 78% and 43%, respectively, and an overall response rate of 100%, 100% and 57%, respectively. Four patients showed complete spontaneous regression. In total, 16 of 24 patients (67%) first presenting with multifocal C-ALCL relapsed, including all five patients initially treated with CHOP (cyclophosphamide, hydroxydaunorubicin, oncovin and prednisone). Compared with patients presenting with two to five skin lesions, patients presenting with more than five lesions had a higher chance of developing extracutaneous relapse (56% vs. 20%) and more often died of lymphoma (44% vs. 7%). CONCLUSIONS: Patients with five or less lesions should be treated with low-dose RT (2 × 4 Gy). Maintenance low-dose MTX (20 mg weekly) is a suitable option in patients with more than five lesions. Targeted therapies may be considered in rare patients who are refractory to MTX or patients developing extracutaneous disease.

A comparison of three treatment strategies in recent onset non-systemic Juvenile Idiopathic Arthritis: initial 3-months results of the BeSt for Kids-study.

BACKGROUND: Combination therapy with prednisone or etanercept may induce earlier and/or more improvement in disease activity in Disease Modifying Anti Rheumatic Drug (DMARD) naïve non-systemic Juvenile Idiopathic Arthritis (JIA) patients. Here we present three months clinical outcome of initial treatments of the BeSt-for-Kids study. METHODS: Included patients were randomized to either: 1. initial DMARD-monotherapy (sulfasalazine (SSZ) or methotrexate (MTX)), 2. Initial MTX / prednisolone-bridging, 3. Initial combination MTX/etanercept. Percentage inactive disease, adjusted (a) ACR Pedi30, 50 and 70 and JADAS after 6 and 12 weeks of treatment (intention to treat analysis) and side effects are reported. RESULTS: 94 patients (67% girls, 32 (arm 1), 32 (arm 2) and 30 (arm 3) with median (InterQuartileRange) age of 9.1 (4.7-12.9) years were included. 38% were ANA positive, 10 had oligo-articular disease, 68 polyarticular JIA and 16 psoriatic arthritis. Baseline median (IQR) ACRpedi-scores: VAS physician 49 (40-58) mm, VAS patient 54 (37-70) mm, ESR 6.5 (2-14.8)mm/hr, active joint count 8 (5-12), limited joint count 3 (1-5), CHAQ score 0.88 (0.63-1.5). In arm 1, 17 started with MTX, 15 with SSZ. After 3 months, aACR Pedi 50 was reached by 10/32 (31%), 12/32(38%) and 16/30 (53%) (p = 0.19) and aACR Pedi 70 was reached by 8/32 (25%), 6/32(19%) and 14/30(47%) in arms 1-3 (p = 0.04). Toxicity was similar. Few serious adverse events were reported. CONCLUSION: After 3 months of treatment in a randomized trial, patients with recent-onset JIA achieved significantly more clinical improvement (aACRPedi70) on initial combination therapy with MTX / etanercept than on initial MTX or SSZ monotherapy. TRIAL REGISTRATION: NTR1574 . Registered 3 December 2008.

Recommendations for treatment in folliculotropic mycosis fungoides: report of the Dutch Cutaneous Lymphoma Group.

BACKGROUND: Folliculotropic mycosis fungoides (FMF) is an aggressive variant of mycosis fungoides (MF) and generally less responsive to standard skin-directed therapies (SDTs). Recent studies distinguished indolent (early-stage FMF) and more aggressive (advanced-stage FMF) subgroups. The optimal treatment for both subgroups remains to be defined. OBJECTIVES: To evaluate initial treatment results in patients with early- and advanced-stage FMF. METHODS: A study was undertaken of 203 patients (84 early-stage, 102 advanced-stage, 17 extracutaneous FMF) included in the Dutch Cutaneous Lymphoma Registry between 1985 and 2014. Type and results of initial treatment were retrieved from the Dutch Registry. Main outcomes were complete remission (CR); sustained complete remission; partial remission (PR), > 50% improvement; and overall response (OR; CR + PR). RESULTS: Patients with early-stage FMF were treated with nonaggressive SDTs in 67 of 84 cases resulting, respectively, in CR and OR of 28% and 83% for monotherapy topical steroids, 0% and 83% for ultraviolet B (UVB), and 30% and 88% for psoralen plus ultraviolet A (PUVA). In patients with advanced-stage FMF these SDTs were less effective (combined CR and OR 10% and 52%, respectively). In patients with advanced-stage FMF local radiotherapy (CR 63%; OR 100%), total skin electron beam irradiation (CR 59%; OR 100%) and PUVA combined with local radiotherapy (CR 5%, OR 75%) were most effective. CONCLUSIONS: The results of the present study demonstrate that not all patients with FMF should be treated aggressively. Patients with early-stage FMF may benefit very well from standard SDTs also used in early-stage classic MF and have an excellent prognosis.

Risk factors for second primary melanoma among Dutch patients with melanoma.

BACKGROUND: Patients with melanoma are at increased risk of developing subsequent primary melanomas. Knowledge about risk factors for these subsequent primaries is scarce. More evidence may help clinicians in tailoring surveillance schedules by selecting patients who could benefit from intensified surveillance. OBJECTIVES: To identify risk factors for a second primary cutaneous melanoma. METHODS: Possible risk factors for a second primary melanoma were assessed in 1127 patients with cutaneous melanoma who were diagnosed between 2003 and 2011 and completed a baseline questionnaire. Additional data were extracted from the Netherlands Cancer Registry and medical files. RESULTS: Fifty-three patients were diagnosed with a second melanoma during a median follow-up time of 6·3 years. The 5-year cumulative risk was 3·7% and the conditional cumulative risk was 4·6% in years 5-10 after diagnosis. In multivariable analyses, the risk of a second melanoma increased with older age at diagnosis [hazard ratio (HR) 1·03 per year; 95% confidence interval (CI) 1·00-1·06], a high naevus density (HR 7·16, 95% CI 2·89-17·75) and working outside for > 10 years (HR 2·88, 95% CI 1·38-6·03). Patients with invasive melanoma (> 1 mm) had a decreased risk compared with patients with melanoma in situ (HR 0·35, 95% CI 0·13-0·93). CONCLUSIONS: Besides phenotypic characteristics, cumulative sun exposure seemed to increase the risk of a second melanoma. Patients with melanoma in situ may need to be offered follow-up, which is currently not advised. As the risk of a second melanoma did not decline in years 5-10 after diagnosis, a subgroup of patients may need a longer follow-up than is currently advised.

Predictors of functional disability in mild cognitive impairment and dementia.

OBJECTIVE: Knowledge about factors predicting functional disability in mild cognitive impairment (MCI) and dementia would help health care providers to identify those patients who are at high risk of functional disability. Previous research is scarce and focused on only a small number of possible predictors. The aim of this study was to identify predictors of functional disability in patients with MCI and dementia. STUDY DESIGN: Cross-sectional cohort study. MAIN OUTCOME MEASURES: Data from patients who visited a memory clinic between 2011 and 2015 were evaluated. The Disability Assessment for Dementia (DAD) was used to assess functional disability. Patients diagnosed with MCI or dementia and with a DAD score available were included. This led to the inclusion of 474 patients. Univariate analyses with a broad range of variables were performed to detect factors that had a significant relationship to the DAD score. Age, gender and variables with a p-value of 0.1 or lower in the univariate analyses were taken into a multivariable analysis. This multiple linear regression analysis was performed to determine which variables were independently associated with the DAD score. MAIN RESULTS: Our multivariable model explained 42% of the variance in the DAD score. Independent predictors of the DAD score were age (B=0.03, 95%CI=0.002-0.05), gender (B=-0.43, 95%CI=-0.78 to -0.07), score on the Clinical Dementia Rating scale (CDR) (B=1.53, 95%CI=1.07-1.99 for CDR 1, B=2.93, 95%CI=2.28-3.58 for CDR 2, B=3.96, 95%CI=2.65-5.27 for CDR 3) and level of physical activity (B=0.56, 95%CI=0.05-1.07). CONCLUSION: Older age, male gender, higher CDR score and lower levels of physical activity are independent predictors of functional disability in MCI and dementia.

Rare vulvar malignancies; incidence, treatment and survival in the Netherlands.

OBJECTIVE: To describe trends in incidence, treatment and survival of patients with basal cell carcinomas and melanomas of the vulva. Also to compare survival of vulvar and cutaneous melanoma patients. METHODS: All women with a vulvar malignancy between 1989 and 2012 were selected from the Dutch Cancer Registry (n=6436). Standardized incidence rates, estimated annual percentage change (EAPC) and 5-year relative survival rates were calculated for basal cell carcinomas (BCCs) and melanomas. Patients with vulvar melanomas were matched to women with cutaneous melanomas on period of diagnosis, age, Breslow thickness, tumour ulceration, lymph node status and distant metastases. Differences in survival were evaluated using Kaplan-Meier curves and the log rank test. RESULTS: 489 women were diagnosed with a BCC and 350 with a melanoma of the vulva. The EAPC in incidence for melanomas was 0.2% and 1.1% for BCCs. Eighty-six percent of patients with BCC underwent surgical treatment in 1989-2006 and 95% in 2005-2012. Forty-five percent with BCC and 79% with melanoma were treated in a referral centre. Five-year relative survival for BCCs was 100% and for melanomas survival increased from 37% (95%CI 28-47%) in 1989-1999 to 45% (95%CI: 37-54%) in 2000-2012. Five years after diagnosis survival of women with vulvar melanoma was 15% lower compared to matched cutaneous melanoma patients (p=0.002). CONCLUSION: No trends in age-adjusted incidence have been observed but more patients with BCC received surgical treatment over time. Having had vulvar BCC did not affect life expectancy. Well-known prognostic factors explained most of the differences in survival between cutaneous and vulvar melanoma patients, however a difference of 15% remained unexplained.

Vocal fold hyalinosis in Urbach-Wiethe disease, a rare cause of hoarseness.

BACKGROUND: Lipoid proteinosis is an autosomal recessive disorder characterized by hyalin deposits in the skin and mucosa of the upper aerodigestive tract; currently, no treatment exists. Nearly all patients experience hoarseness and speech difficulties, due to hyalin deposition in the vocal folds and diminished mobility in infiltrated lips, tongue, and palate. METHODS: We describe a patient with extensive hyalin plaques on the vocal folds, which resulted in near-aphonic hoarseness. Hyalin deposits in the vocal folds and skin were treated with laser resection. RESULTS: Both the vocal folds and skin improved in appearance, with smoother surface epithelium. However, the patient's speech remained impaired, due to extensive hyalin plaques in the mouth, tongue, and lips. The voice improved only temporarily. CONCLUSIONS: Laser resection of hyalin plaques in the vocal folds and skin is a feasible treatment for lipoid proteinosis. However, speech may remain severely limited, due to impaired tongue and lip movement.

EULAR-PReS points to consider for the use of imaging in the diagnosis and management of juvenile idiopathic arthritis in clinical practice.

To develop evidence based points to consider the use of imaging in the diagnosis and management of juvenile idiopathic arthritis (JIA) in clinical practice. The task force comprised a group of paediatric rheumatologists, rheumatologists experienced in imaging, radiologists, methodologists and patients from nine countries. Eleven questions on imaging in JIA were generated using a process of discussion and consensus. Research evidence was searched systematically for each question using MEDLINE, EMBASE and Cochrane CENTRAL. Imaging modalities included were conventional radiography, ultrasound, MRI, CT, scintigraphy and positron emission tomography. The experts used the evidence obtained from the relevant studies to develop a set of points to consider. The level of agreement with each point to consider was assessed using a numerical rating scale. A total of 13 277 references were identified from the search process, from which 204 studies were included in the systematic review. Nine points to consider were produced, taking into account the heterogeneity of JIA, the lack of normative data and consequent difficulty identifying pathology. These encompassed the role of imaging in making a diagnosis of JIA, detecting and monitoring inflammation and damage, predicting outcome and response to treatment, use of guided therapies, progression and remission. Level of agreement for each proposition varied according to the research evidence and expert opinion. Nine points to consider and a related research agenda for the role of imaging in the management of JIA were developed using published evidence and expert opinion.

Cutaneous hyperpigmentation induced by doxycycline: a case series.

Cutaneous hyperpigmentation is a well-known side effect of tetracyclines, but doxycycline-induced cutaneous hyperpigmentation has only been described in one patient with a therapeutic dosage of doxycycline, and in one patient using suprapharmacological doses. We describe four patients with cutaneous hyperpigmentation in previously unaffected skin, and speculate that this was due to treatment with doxycycline in therapeutic doses. After cessation of therapy, the hyperpigmentation diminished in all four patients, illustrating the need for recognition and timely cessation of therapy.

Cervicovaginal HPV infection in female renal transplant recipients: an observational, self-sampling based, cohort study.

Immunosuppressive treatment of organ transplant recipients is associated with an increase in the occurrence of human papillomavirus (HPV) related anogenital (pre)malignancies. This cohort study investigated the genotype-specific prevalence of HPV infections in a large cohort of female renal transplant recipients (RTRs). Participants self-collected a cervicovaginal sample for detection and genotyping of HPV. Besides, they completed a questionnaire regarding sociodemographic variables, medical data and sexual behavior. Anogenital screening was offered to all HPV-positive participants. A total number of 218 female RTRs was included. The prevalence of mucosal HPV infections was 27.1% and 17.4% for high risk HPV in particular. The studied cohort showed a broad range of HPV genotypes and multiple HPV genotypes were found in 27.1% of HPV-positive patients. Seven participants were identified with occult premalignant anogenital lesions. In conclusion, this study shows a high point-prevalence of HPV in female RTRs (age-matched West-European general population: 9-10%) with a shift in the distribution of genotypes as compared with the general population. Moreover, a substantial number of patients with occult premalignancies was identified. The introduction of self-sampling for HPV positivity can help in early detection of (pre)malignant anogenital lesions in this vulnerable population.

Pseudotumor formation and serum ions after large head metal-on-metal stemmed total hip replacement. Risk factors, time course and revisions in 706 hips.

INTRODUCTION: The incidence and natural course of pseudotumors in metal-on-metal total hip arthroplasties is largely unknown. The objective of this study was to identify the true incidence and risk factors of pseudotumor formation in large head metal-on-metal total hip arthroplasties. MATERIALS AND METHODS: Incidence, time course and risk factors for pseudotumor formation were analysed after large femoral head MoM-THA. We defined a pseudotumor as a (semi-)solid or cystic peri-prosthetic soft-tissue mass with a diameter ≥2 cm that could not be attributed to infection, malignancy, bursa or scar tissue. All patients treated in our clinic with MoM-THA's were contacted. CT scan, metal ions and X-rays were obtained. Symptoms were recorded. RESULTS: After median follow-up of 3 years, 706 hips were screened in 626 patients. There were 228 pseudotumors (32.3 %) in 219 patients (35.0 %). Pseudotumor formation significantly increased after prolonged follow-up. Seventy-six hips (10.8 %) were revised in 73 patients (11.7 %), independent risk factors were identified. Best cutoff point for cobalt and chromium was 4 µg/l (68 and 77 nmol/l). CONCLUSIONS: This study confirms a high incidence of pseudotumors, dramatically increasing after prolonged follow-up. Risk factors for pseudotumors are of limited importance. Pain was the strongest predictor for pseudotumor presence; cobalt chromium and swelling were considered poor predictors. Cross-sectional imaging is the main screening tool during follow-up.

CD226 (DNAM-1) is associated with susceptibility to juvenile idiopathic arthritis.

OBJECTIVES: Juvenile idiopathic arthritis (JIA) is considered a complex genetic autoimmune disease. We investigated the association of genetic variants previously implicated in JIA, autoimmunity and/or immunoregulation, with susceptibility to JIA. METHODS: A genetic association study was performed in 639 JIA patients and 1613 healthy controls of northwest European descent. Ninety-three single nucleotide polymorphisms (SNP) were genotyped in a candidate gene approach. Results of the entire JIA patient group (all subtypes) were compared with results obtained, alternatively, with a clinically homogeneous patient group including only oligoarticular and rheumatoid factor (RF) negative polyarticular JIA patients (n=493). Meta-analyses were performed for all SNPs that have been typed in other Caucasian JIA cohorts before. RESULTS: SNPs in or near PTPN22, VTCN1, the IL2-IL21 region, ANKRD55 and TNFA were confirmed to be associated with JIA (p<0.05), strengthening the evidence for involvement of these genes in JIA. In the majority of these replicated SNPs, effect sizes were larger when analysing a homogeneous patient cohort than when analysing all subtypes. We identified two novel associations with oligoarticular and RF-negative polyarticular JIA: CD226 rs763361 (OR 1.30, 95% CI 1.12 to 1.51, p=0.0006) and CD28 rs1980422 (OR 1.29, 95% CI 1.07 to 1.55, p=0.008). Meta-analyses including reported studies confirmed the association of both SNPs with susceptibility to JIA (OR 1.16, p=0.001 and OR 1.18, p=0.001, for rs763361 and rs1980422, respectively). CONCLUSIONS: The CD226 gene has been identified as novel association with JIA, and a SNP near CD28 as a suggestive association. Both genes are probable candidate risk factors, since they are involved in costimulation of T cells.

Limited role for histopathological examination of re-excision specimens of completely excised melanomas.

The Dutch melanoma guideline advises to examine one central block of the re-excision scar in case of a complete primary excision. To increase the evidence for this recommendation, we re-evaluated how often residual melanoma was found in re-excision specimens of a large series of completely excised melanomas. Of 1,209 Dutch melanoma cases, pathology reports of primary excisions were reviewed. Presence of melanoma in the margins was scored. All melanomas with a complete primary excision were included and pathology reports of re-excisions were reviewed. Presence of residual melanoma in the re-excision specimen and the number of blocks were scored. Slides of re-excision specimens containing residual melanoma were reviewed. Eventually, in four out of 812 melanomas (0.5 %) with a complete primary excision, residual melanoma was found in the re-excision specimen. The free margins of the primary melanomas in these cases ranged from 0.5-3.5 mm. In one case, the margin for melanoma in situ was 0.2 mm. In <1 % of initially completely excised melanomas, residual melanoma was found in the re-excision specimen. Histopathological examination of these re-excision specimens may not be cost-efficient. Our findings even imply that a re-excision could safely be omitted in selected cases of completely excised melanomas.

Impact of mitotic activity on the pathological substaging of pT1 cutaneous melanoma.

BACKGROUND: In the transition from the sixth to the seventh edition of the American Joint Committee on Cancer (AJCC) melanoma staging system, mitotic activity was incorporated, while Clark level of invasion was abandoned. OBJECTIVES: To investigate the effect of this change on the pathological tumour (pT)1 substaging of primary cutaneous melanomas and the possible clinical implications. METHODS: Patients with pT1 melanomas, diagnosed in the period January 2003 to March 2011, were selected from a population-based cohort study on cutaneous melanoma in the eastern part of the Netherlands. The pT1 melanomas were systematically reviewed by an expert pathologist and classified according to both the sixth and the seventh editions of the AJCC staging system. The shift of melanomas between pT1 substages, classified according to the two staging systems, was determined. RESULTS: In total, 260 pT1 melanomas were included. Overall 28% (57/207) of all pT1a melanomas shifted to pT1b when classified according to the new seventh staging classification, because of the presence of mitoses. Some 32% (17/53) of all pT1b melanomas shifted to pT1a. The percentage of pT1b melanomas relative to all pT1 melanomas increased from 20% to 36%. CONCLUSIONS: The addition of mitotic activity to the pathological staging system, according to the seventh edition of the AJCC staging system, resulted in a considerable change in the classification of thin cutaneous melanomas. This shift has clear clinical implications, as it is advised in the Dutch guideline that patients with pT1b melanoma should be offered a sentinel lymph node biopsy.

New insights into the aetiology of scrotal cancer, a nationwide case-control study in the Netherlands.

BACKGROUND: Although scrotal cancer is traditionally regarded as an occupational disease, there is increasing evidence that factors which are involved in cutaneous and genital carcinogenesis might play a role in the carcinogenesis of scrotal cancer. OBJECTIVE: This exploratory study aimed to detect exposures that might have an aetiological relation with scrotal cancer. METHODS: A nationwide population-based case-control study was conducted in the Netherlands. The patients were identified through the Netherlands cancer registry. Controls were recruited among acquaintances of the cancer registry registrars. The participants completed a questionnaire that included questions on occupational exposures, naked sunbathing, use of sunbeds, skin diseases and their treatments, treatments for cancer and sexually transmitted diseases. Age-adjusted odds-ratios (ORs) were calculated. RESULTS: Forty-seven scrotal cancer patients and 125 controls completed the questionnaire. The patients were categorized according to histology of the scrotal tumours. Having had a skin disease (OR = 6.3, 95% CI = 1.8-22), especially psoriasis (OR = 8.7), increased the risk of squamous cell carcinomas (SCC) of the scrotum. A previous cancer diagnosis may affect the risk of scrotal basal cell carcinomas (BCC; OR = 4.9, 95% CI = 0.9-27.3). Furthermore, an association between the number of sexual partners and the occurrence of scrotal sarcoma was found. CONCLUSION: Scrotal SCCs may be related with skin diseases or skin disease treatments. Having had cancer may be a risk factor for a BCC of the scrotum. Scrotal sarcomas seem to be correlated with the number of sexual partners. This study suggests that scrotal cancer has characteristics of both cutaneous and genital carcinogenesis.