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.

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.

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.

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.

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.

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.

Patients' experience of psoriasis in the genital area.

BACKGROUND: Psoriasis in the genital area is often neglected, although it bothers a substantial number of patients. OBJECTIVE: To study both the role of the physician in the treatment of genital psoriasis and the symptom intensity of these lesions as experienced by the patients. METHODS: A detailed self-administered questionnaire (containing items on the role of the physician and genital symptom intensity, range 0-10) was filled in by members of the Dutch Psoriasis Society. RESULTS: Data of 277 patients with genital psoriasis were analyzed. A total of 45.8% did not discuss the presence of genital psoriasis with their physician, 25% believed that the physician paid sufficient attention to genital lesions, and 67.8% never applied treatment for genital lesions. Mean symptom intensity ranged from 2.4 to 5.1, all scores being significantly higher for women compared to men. Severe symptoms were present in up to 43.5% of patients. Of these patients, up to 38.1% did not discuss the symptoms with their physician. CONCLUSION: The consultation rate for genital lesions is low, while numerous patients report a significant burden of disease.

HPV-related (pre)malignancies of the female anogenital tract in renal transplant recipients.

Renal transplantations (RTs) are performed routinely in many countries. After RT, the administration of lifelong immunosuppressive therapy is required. As a consequence, renal transplant recipients (RTRs) have a high risk to develop virus-associated (pre)malignancies, such as Human papillomavirus (HPV) related anogenital (pre)malignancies. It is known that the majority of the RTRs are infected with HPV and that these women have a 14-fold increased risk of cervical cancer, up to 50-fold of vulvar cancer and up to 100-fold of anal cancer. Often, treatment of these lesions requires concessions and may be suboptimal as radiation therapy and extensive surgery may damage the renal transplant. Therefore, prognosis may be compromised due to inadequately treated malignancies. Especially for these immunocompromised patients prevention is of utmost importance. Yearly cervical cancer screening for RTRs is advised, but appears to be executed poorly. For the future, optimizing screening and prevention of anogenital (pre)malignancies is an important issue for women after RT. This review gives a broad overview of all aspects regarding HPV-related (pre)malignancies of the female anogenital tract in RTRs.

Quality of life and sexual health in patients with genital psoriasis.

BACKGROUND: Knowledge about quality of life and sexual health in patients with genital psoriasis is limited. OBJECTIVES: We studied quality of life and sexual function in a large group of patients with genital psoriasis by means of validated questionnaires. In addition, we evaluated whether sufficient attention is given by healthcare professionals to sexual problems in patients with psoriasis, as perceived by the patients. METHODS: A self-administered questionnaire was sent to 1579 members of the Dutch Psoriasis Association. Sociodemographic patient characteristics, medical data and scores of several validated questionnaires regarding quality of life (Dermatology Life Quality Index) and sexual health (Sexual Quality of Life Questionnaire for use in Men, International Index of Erectile Function, Female Sexual Distress Scale and Female Sexual Function Index) were collected and analysed. RESULTS: This study (n = 487) shows that psoriasis has a detrimental effect on quality of life and sexual health. Patients with genital lesions reported even significantly worse quality of life than patients without genital lesions (mean ± SD quality of life scores 8·5 ± 6·5 vs. 5·5 ± 4·6, respectively, P < 0·0001). Sexual distress and dysfunction are particularly prominent in women (reported by 37·7% and 48·7% of the female patients, respectively). Sexual distress is especially high when genital skin is affected (mean ± SD sexual distress score in patients with genital lesions 16·1 ± 12·1 vs. 10·1 ± 9·7 in patients without genital lesions, P = 0·001). The attention given to possible sexual problems in the psoriasis population by healthcare professionals is perceived as insufficient by patients. CONCLUSIONS: In addition to quality of life, sexual health is diminished in a considerable number of patients with psoriasis and particularly women with genital lesions have on average high levels of sexual distress. We underscore the need for physicians to pay attention to the impact of psoriasis on psychosocial and sexual health when treating patients for this skin disease.

Genital psoriasis: a questionnaire-based survey on a concealed skin disease in the Netherlands.

BACKGROUND: Psoriatic lesions may involve nearly all sites of the body. Involvement of the genital skin is frequently classified as part of intertriginous psoriasis without special awareness and treatment for this presentation of the disease. Gaining knowledge about the frequency of the involvement of genital skin in these patients will improve the overall care for patients with psoriasis. OBJECTIVES: We studied the prevalence of genital psoriasis in the Netherlands and epidemiological characteristics of this specific presentation of the disease. Furthermore, we studied the relation between flexural and genital psoriasis. PATIENTS/METHODS: A self-administered questionnaire was sent to all 5300 members of the Dutch Psoriasis Society. Sociodemographic patient characteristics and disease-related data (such as localization of psoriatic lesions, involvement of the genitalia, age at onset of genital psoriasis and severity of genital psoriatic lesions) were collected and analysed. RESULTS: A response rate of 37% was achieved. Almost 46% of the responding patients with psoriasis, that is 16.5% of all potential responders (n = 5300), report genital involvement at some time during the course of their disease. The genitalia can become affected at any age. Many patients with current genital involvement (38%) do not have the flexural skin affected. CONCLUSIONS: A large part of patients with psoriasis suffer from genital psoriasis, which was not associated with flexural involvement in at least one third of them. More attention to the genital region is required in the current standard treatment of both male and female psoriatic patients at any age.

Incidence of cancer in first-degree relatives of basal cell carcinoma patients.

There is evidence to suggest that genetic factors play an important role in the development of basal cell carcinomas (BCCs), and that skin neoplasms might be a sign for a genetic predisposition to cancer. We investigated whether the incidence of visceral and skin malignancies among first-degree relatives of BCC-patients was increased. Postal questionnaires were sent to 249 BCC-patients, who were divided into two groups (young = BCC under the age of 51 years and older = BCC over the age of 50 years), and asked them about cancer in their first-degree relatives. The reported numbers of cancer among the relatives were compared with the expected numbers based on sex and age-specific population-based incidence rates. The accuracy of the reported diagnoses was verified. A total of 157 BCC-patients reported 277 malignancies in 1,272 relatives. The incidence of the following cancers was higher than expected in relatives from young BCC-patients: bone and soft tissue (O/E = 3.91; 95% CI: 1.43-8.66), skin (O/E = 2.13; 95% CI: 1.30-3.29) and digestive tract (O/E = 1.59; 95% CI: 1.10-2.23). In relatives of older BCC-patients, only the incidence of digestive tract cancer was higher than expected (O/E = 1.44; 95% CI: 1.08-1.89). Diagnoses that were verified turned out to be accurate in 87% of the cases. This study suggests that the risk of certain cancers, particularly that of the digestive tract, in first-degree relatives of BCC-patients is increased. These findings may indicate a genetic predisposition to both skin and visceral malignancies in this patient group.

[Lichen sclerosus]. / Lichen sclerosus.

Lichen sclerosus is a chronic disorder of skin and mucosa which affects patients of all age groups, particularly women, but also men. It is most commonly seen on the female genital skin, but it also occurs on extragenital areas. Most patients complain of itching and, less frequently, a burning sensation, dyspareunia, dysuria and painful defecation are reported. The cause of lichen sclerosus is largely unknown. However, it has been suggested that a genetic predisposition to inflammatory disorders, an immunological constitution, hormonal influences and local factors might play a role. Anogenital lichen sclerosus is associated with an increased incidence of malignancies, especially vulvular squamous-cell carcinomas. The life-time risk of developing this carcinoma is about 5%. Extragenital lichen sclerosus and lichen sclerosus in children do not seem to be correlated with malignancy. Potent local corticosteroids form the mainstay of treatment for lichen sclerosus. The condition is characterised by remissions and exacerbations. Long-term follow-up is required for the early diagnosis of malignant changes.