Basal Cell CarcinomaInformation for Patients and the Public
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Non Melanoma Skin Cancer
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MeSH term: Carcinoma, Basal Cell
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This list of publications is regularly updated (Source: PubMed).
Skin Cancer: Squamous and Basal Cell Carcinomas.
FP Essent. 2019; 481:17-22 [PubMed] Related Publications
Skin cancer incidence in rural workers at a reference hospital in western Paraná.
An Bras Dermatol. 2019 Mar-Apr; 94(2):157-163 [PubMed] Free Access to Full Article Related Publications
OBJECTIVE: To analyze the incidence and profile of rural workers who were diagnosed with skin cancer at a reference service in Cascavel, western Paraná, in the last five years (2011-2016).
METHODS: This retrospective cross-sectional study was carried out through a review of the anatomopathological reports of rural workers diagnosed with skin cancer at Cascavel Oncology Center (CEONC), in Cascavel. The following variables were collected: year of diagnosis, age, gender, injury location and histological subtype.
RESULTS: A total of 681 cases of malignant epithelial neoplasia were identified, with a higher frequency in the 61-70 age group. Data analysis showed an increase of about 210% in the occurrence of skin cancers in the last 5 years. The cephalic region was the most affected, and the most common histological subtype was nodular basal cell carcinoma. There was no association between gender and location.
STUDY LIMITATIONS: This is a retrospective study and analysis of a secondary data bank.
CONCLUSION: This study is a regional estimation of the incidence of cutaneous neoplasms and provides evidence of a considerable increase in the number of diagnoses in rural workers from western Paraná, Brazil. Moreover, it is possible to conclude that the sample group studied is at risk of developing skin cancer.
A technical note for the use of small-diameter cannula for lipoaspiration technique in aesthetic reconstructive post-oncological surgery.
J Biol Regul Homeost Agents. 2019 May-Jun,; 33(3):1011-1013 [PubMed] Related Publications
Metatypical Basal Cell Carcinoma: A 6-Year Retrospective Study.
Skinmed. 2019; 17(1):24-28 [PubMed] Related Publications
Investigation of Interleukin-17 Gene Polymorphisms and Serum Levels in Patients with Basal Cell Carcinoma of the Skin.
Iran J Immunol. 2019; 16(1):53-61 [PubMed] Related Publications
OBJECTIVE: To investigate the association of two IL-17 gene polymorphisms (rs2275913 and rs763780), as well as IL-17 serum levels with susceptibility to Basal Cell Carcinoma (BCC) of skin.
METHODS: Two hundred subjects with BCC and 200 healthy controls were recruited. DNA was extracted from peripheral blood leukocytes and genotypes were determined using PCR-RFLP methods. Serum levels were assessed by ELISA.
RESULTS: At position rs2275913 in IL-17A, the frequencies of GG, AG and AA genotypes were 99 (49.5%), 76 (38%) and 25 (12.5%) in patients and 97 (48.5%), 84 (42%) and 19 (9.5%) in the control group. The distribution of AA, GA and GG genotypes at position rs763780 in IL-17F were 166 (83%), 34 (17%) and 0 (0%) in patients and 158 (79%), 40 (20%) and 2 (1%) in the control group. Haplotype analysis by Arlequin software package revealed that GA haplotype was the most frequent haplotype in both groups. No significant differences were found in alleles, genotypes, and haplotypes frequencies between study groups at both positions (P>0.05). While no difference in IL-17 serum levels was observed between individuals with different genotypes, statistical analysis showed higher IL-17A serum levels, but not IL-17F, in patients compared to controls (0.65 ± 0.11 and 0.03 ± 0.02 pg/ml), respectively, (P<0.001).
CONCLUSION: Our findings do not support the association of rs763780 and rs2275913 gene polymorphisms in IL-17gene with susceptibility of Iranians with BCC. Increased IL-17A serum levels may still play a role in pathogenesis of BCC.
Multiple basal cell carcinomas in a patient with myotonic dystrophy type 1.
BMJ Case Rep. 2019; 12(3) [PubMed] Article available free on PMC after 08/03/2020 Related Publications
Automated detection of nonmelanoma skin cancer using digital images: a systematic review.
BMC Med Imaging. 2019; 19(1):21 [PubMed] Article available free on PMC after 08/03/2020 Related Publications
METHODS: Eight databases (PubMed, Google Scholar, Embase, IEEE Xplore, Web of Science, SpringerLink, ScienceDirect, and the ACM Digital Library) were searched to identify diagnostic studies of NMSC using image-based machine learning models. Two reviewers independently screened eligible articles. The level of evidence of each study was evaluated using a five tier rating system, and the applicability and risk of bias of each study was assessed using the Quality Assessment of Diagnostic Accuracy Studies tool.
RESULTS: Thirty-nine studies were reviewed. Twenty-four models were designed to detect basal cell carcinoma, two were designed to detect squamous cell carcinoma, and thirteen were designed to detect both. All studies were conducted in silico. The overall diagnostic accuracy of the classifiers, defined as concordance with histopathologic diagnosis, was high, with reported accuracies ranging from 72 to 100% and areas under the receiver operating characteristic curve ranging from 0.832 to 1. Most studies had substantial methodological limitations, but several were robustly designed and presented a high level of evidence.
CONCLUSION: Most studies of image-based NMSC classifiers report performance greater than or equal to the reported diagnostic accuracy of the average dermatologist, but relatively few studies have presented a high level of evidence. Clinical studies are needed to assess whether these technologies can feasibly be implemented as a real-time aid for clinical diagnosis of NMSC.
Epidemiological evidence of carcinogenicity of sunbed use and of efficacy of preventive measures.
J Eur Acad Dermatol Venereol. 2019; 33 Suppl 2:57-62 [PubMed] Related Publications
Association of sunbed use with skin cancer risk factors in Europe: an investigation within the Euromelanoma skin cancer prevention campaign.
J Eur Acad Dermatol Venereol. 2019; 33 Suppl 2:76-88 [PubMed] Related Publications
OBJECTIVES: To investigate the association of sunbed use with nevus count, atypical nevi, lentigines and suspicion of skin cancer.
METHODS: To ensure reliability of the data, we defined inclusion and exclusion criteria for countries' eligibility for the risk analysis. Multivariate logistic regression models (including age, gender, education, skin type, family history of melanoma, personal history of skin cancer, any sun exposure and any sunscreen use) were used to calculate summary odds ratios (SORs) of each clinical endpoint for ever sunbed use.
RESULTS: Overall, 227 888 individuals from 30 countries completed the Euromelanoma questionnaire. After the data quality check, 16 countries were eligible for the multivariate analysis, for a total of 145 980 participants (64.8% females; median age 43 years; 62.3% highly educated; 28.5% skin type I-II; 11.0% ever sunbed use). Ever sunbed use was independently associated with nevus count >50 [SOR = 1.05 (1.01-1.10)], atypical nevi [SOR = 1.04 (1.00-1.09)], lentigines [SOR = 1.16 (1.04-1.29)] and suspicion of melanoma [SOR = 1.13 (1.00-1.27)]. Conversely, no significant association was found between ever sunbed use and suspicion of NMSC [SOR = 1.00 (0.91-1.10)].
CONCLUSIONS: Indoor tanning is significantly associated with well-recognized risk factors for melanoma (including high nevus count, presence of atypical nevi and lentigines) as well as suspicion of melanoma within the Euromelanoma screenees. In order to reduce the prevalence of melanoma risk factors, avoidance/discontinuation of sunbed use should always be encouraged, especially but not exclusively for individuals with high-risk phenotypes.
Sunbeds and carcinogenesis: the need for new regulations and restrictions in Europe from the Euromelanoma perspective.
J Eur Acad Dermatol Venereol. 2019; 33 Suppl 2:104-109 [PubMed] Related Publications
Infrared and Raman Spectroscopic Studies of Molecular Disorders in Skin Cancer.
In Vivo. 2019 Mar-Apr; 33(2):567-572 [PubMed] Article available free on PMC after 08/03/2020 Related Publications
MATERIALS AND METHODS: Human malignant melanoma and basal cell carcinoma biopsies were used for the investigation. Fourier transform infrared (FT-IR), Raman spectroscopy, and scanning electron microscopy were utilized. Spectral differences between healthy, basal cell carcinoma and melanoma tissues were recorded.
RESULTS: The FT-IR bands of v
CONCLUSION: Vibrational spectroscopy highlighted increased glycosylation in melanoma.
Histopathology of Basal Cell Carcinoma After Treatment With Vismogedib
J Drugs Dermatol. 2019; 18(2):136-138 [PubMed] Related Publications
Superficial Radiation Therapy: A Viable Nonsurgical Option for Treating Basal and Squamous Cell Carcinoma of the Lower Extremities
J Drugs Dermatol. 2019; 18(2):130-134 [PubMed] Related Publications
Long-term recurrence rates of whole specimen intraoperative frozen section analysis in basal cell carcinomas of the face with WIFSA.
J Surg Oncol. 2019; 119(7):903-908 [PubMed] Related Publications
MATERIALS AND METHODS: All patients with a facial BCC receiving excision with WIFSA between 1992 and 2007 were evaluated. Recurrence rates were examined for primary BCC (pBCC), recurrent BCCs (rBCC), and the different histological subtypes. The accuracy of WIFSA was assessed by comparing with formalin-fixed paraffin-embedded section analysis.
RESULTS: A total of 1140 patients with 1265 BCCs underwent excision with WIFSA, with a median and maximum follow-up of 10 and 25.3 years, respectively. Of all tumors, 90.0% were primary. Excisions were radical after an average of 1.4 excision rounds;5, 10, and 15-year recurrence rates for pBCCs are 3.3%, 5.1%, and 7.3%, respectively. An aggressive growth pattern and rBCCs are associated with more recurrences. The accuracy of WIFSA is 98.4%.
CONCLUSIONS: WIFSA provides a highly accurate analysis and has a low recurrence rate for primary BCCs. The increasing recurrence rates over time imply 5 years of follow-up may be insufficient.
Erectile Dysfunction Medications and Skin Cancer: An Analysis in US Veterans.
Urology. 2019; 126:116-120 [PubMed] Related Publications
METHODS: This was a retrospective database review using the Department of Veterans Affairs Informatics and Computing Infrastructure database. Veterans Affairs Informatics and Computing Infrastructure was searched 19 years for Veterans who received PDE5i treatment of erectile dysfunction. A non-PDE5i group of Veterans was selected for comparison analysis. Follow-up time, outpatient clinic visits and incidence of malignant melanoma (MM), and basal cell carcinoma (BCC) were measured in both groups.
RESULTS: A total of 2.55 million Veterans were included in this study (1.27 million in each group). Mean age of the PDE5i group and non-PDE5i group was 59.2 years (standard deviation [SD] ± 10.8) and 58.7 (SD ± 10.8), respectively. Mean follow-up time for the PDE5i group was 8.9 years (SD ± 4.2) and 8.5 years (SD ± 4.3) for non-PDE5i group. Odds ratio for malignant melanoma and BCC in the PDE5i group was 1.25 (confidence interval 95%, 1.22-1.28, P <.0001) and 1.49 (confidence interval 95%, 1.46-1.51, P <.0001), respectively. PDE5i users showed more mean outpatient visits/year (8.9 SD ± 9.50) compared to non-PDE5i users (5.9 SD ± 10.0; P <.0001).
CONCLUSION: Veterans prescribed PDE5is to treat erectile show a minimal increased risk of MM and a greater risk of BCC compared to non-PDE5i users. PDE5i users visited outpatient VA clinics at a higher rate than non-PDE5i users in this study. These findings suggest confounding variables are likely involved in the relationship between skin cancers and PDE5i use. PDE5i drugs remain a safe treatment for erectile dysfunction.
Study of skin neoplasms in a university hospital: integration of anatomopathological records and its interface with the literature.
An Bras Dermatol. 2019 Jan-Feb; 94(1):42-46 [PubMed] Article available free on PMC after 08/03/2020 Related Publications
OBJECTIVE: To retrospectively evaluate the incidence, prevalence and profile of basal cell carcinoma, squamous cell carcinoma and cutaneous melanoma in Campos dos Goytacazes and region.
METHODS: In total, 2,207 histopathological reports of a local reference hospital were analyzed between January 2013 and December 2015, of which 306 corresponded to the neoplasms studied.
RESULTS: Of the 306 reports evaluated, 232 basal cell carcinomas (75.9%), 55 squamous cell carcinomas (18%) and 19 cutaneous melanomas (6.5%) were identified. The face was the most involved anatomical site (58.8%) and women (51%) were the most affected gender. The temporal analysis revealed a decrease in the overall incidence of 3.4% from 2013 to 2014 and 5.4% from 2014 to 2015. There was a 10.1% increase in basal cell carcinomas and 38% in melanomas in this period; however, there was a decrease in the number of squamous cell carcinomas of 14.8% during the studied years.
STUDY LIMITATIONS: Some samples of cutaneous fragments had no identification of the anatomical site of origin.
CONCLUSION: Research that generates statistical data on cutaneous tumors produces epidemiological tools useful in the identification of risk groups and allows the adoption of more targeted and efficient future prevention measures.
Extremity nevus count is an independent risk factor for basal cell carcinoma and melanoma, but not squamous cell carcinoma.
J Am Acad Dermatol. 2019; 80(4):970-978 [PubMed] Related Publications
OBJECTIVE: We sought to examine the association between extremity nevus count and the risk of melanoma and keratinocyte cancers.
METHODS: We evaluated prospective cohorts of 176,317 women (the Nurses' Health Study, 1986-2012 and the Nurses' Health Study 2, 1989-2013) and 32,383 men (Health Professionals Follow-up Study, 1986-2012). Information on nevus count (none, 1-5, 6-14, ≥15) on the extremity was collected at baseline.
RESULTS: There were 1704 incident cases of melanoma, 2296 incident cases of squamous cell carcinoma, and 30,457 incident cases of basal cell carcinoma, with a total of 4,655,043 person-years for melanoma and 4,267,708 person-years for keratinocyte cancers. The presence of an extremity nevus was associated with an increased risk of melanoma in all anatomic areas and increased risk of basal cell carcinoma (BCC). Individuals with ≥15 nevi had the highest risk of melanoma and BCC compared to those without any extremity nevi (melanoma hazard ratio 2.79 [95% confidence interval 2.04-3.83]; BCC HR 1.40 [95% confidence interval 1.32-1.49]). No significant association was observed for squamous cell carcinoma.
LIMITATIONS: Limitations of our study included self-reported nevus count and detection bias.
CONCLUSIONS: Extremity nevus count is a helpful clinical marker in risk-stratifying individuals for BCC and melanoma on all body sites.
Koebner phenomenon: pemphigus vulgaris following Mohs micrographic surgery.
Dermatol Online J. 2019; 25(1) [PubMed] Related Publications
Assessment of quality of life using Skindex-16 in patients with advanced basal cell carcinoma treated with vismodegib in the STEVIE study.
Eur J Dermatol. 2018; 28(6):775-783 [PubMed] Related Publications
A systematic review on the use of cryotherapy versus other treatments for basal cell carcinoma.
Dermatol Online J. 2018; 24(11) [PubMed] Related Publications
OBJECTIVE: To determine the efficacy and adverse events profile of cryotherapy for the treatment of basal cell carcinoma compared to other therapeutic options or non-intervention.
METHODS: We systematically searched PubMed, OVID, Cochrane Library, EMBASE, CINHAL, and CANCERLIT databases for the following terms: "cryotherapy", AND "basal cell carcinoma", OR "cryosurgery" OR "cryoablation" up to April 2018. Two independent reviewers screened the results and extracted the data. Study endpoints included basal cell carcinoma recurrence, cosmetic outcome, and healing time. Study quality was assessed using the Jadad scale.
RESULTS: Six clinical studies met our inclusion criteria. The efficacy and safety of cryotherapy alone or with curettage in the treatment of primary superficial and nodular basal cell carcinoma was comparable to photodynamic therapy and surgery, respectively. Cryotherapy was inferior to radiation in terms of recurrence rate. Most patients had better cosmetic outcomes with photodynamic therapy and surgery compared to cryotherapy alone, and cryotherapy with curettage.
CONCLUSION: Current available data suggests equivalent efficacy of cryotherapy alone compared to photodynamic therapy or surgery, but inferior to radiotherapy. More studies are necessary to draw definitive conclusions.
A trichogenic tumor with aggressive features initially diagnosed as basal cell carcinoma.
Dermatol Online J. 2018; 24(9) [PubMed] Related Publications
Basal cell carcinoma with intravascular invasion: A case report and review of the literature.
Dermatol Online J. 2018; 24(10) [PubMed] Related Publications
Skin Cancer Associated Genodermatoses: A Literature Review.
Acta Derm Venereol. 2019; 99(4):360-369 [PubMed] Related Publications
Reconstruction of Mohs Defects Located in the Head and Neck.
J Craniofac Surg. 2019 Mar/Apr; 30(2):412-417 [PubMed] Related Publications
METHODS: All data were retrieved for patients ≥18 years who underwent multidisciplinary treatment including dermatological MMS and plastic surgical reconstruction at a single tertiary hospital center (2001-2017). Patient characteristics, tumor pathology, surgical specifics, reconstructive modalities, and surgical outcomes were analyzed.
RESULTS: A total of 418 patients were included. Patients were predominantly White, non-Hispanic (97%) and female (58%) with a mean age of 60 ± 13.9 years. Tumor pathology was predominantly basal cell carcinoma in 73% of all cases followed by squamous cell carcinoma in 14%. The nasal aesthetic unit was mostly affected (50%). Local advancement flaps and different types of grafts were used in 51% and 25% of reconstructions, respectively. Complications were observed in 3% and local cancer recurrence in 4% of the patients. Scar revision was needed in 6% of the patients.
CONCLUSION: Reconstruction of facial defects after Mohs micrographic surgery can be challenging due to its technical complexity and aesthetic implications. There were differences in complications in reconstructions performed within the same day versus 1 week, with a majority of complications occurring within same-day Mohs reconstructions. A multidisciplinary structured approach, which incorporates patient-reported outcomes, may be needed to optimize surgical results.
Clinical Characteristics of Basal Cell Carcinoma in African Americans: A 10-Year Retrospective Review at a Single Academic Institution.
Dermatol Surg. 2019; 45(5):660-665 [PubMed] Related Publications
OBJECTIVE: We sought to describe the clinical characteristics of BCC in African Americans treated with Mohs micrographic surgery (MMS).
METHODS: We performed a retrospective case series in an ambulatory referral center at a single academic institution from 2007 to 2017 to characterize BCCs in African Americans treated with MMS.
RESULTS: A total of 17 patients, who identified as black or African American, with 18 BCCs were included for analysis. Patients were predominantly female (82%) with a mean age at diagnosis of 61 years. Seventy-eight percent of tumors were located in the head and neck region with 50% of BCCs located in high-risk areas. The average preoperative and postoperative defect size was 1.78 and 5.90 cm, respectively, with a mean number of 2.2 Mohs stages required for tumor clearance. One patient had Gorlin syndrome.
CONCLUSION: The presented retrospective review adds to limited available reported studies regarding BCC in African Americans to potentially aid in early recognition of these tumors.
Frequent TLE1 Expression in Cutaneous Neoplasms.
Am J Dermatopathol. 2019; 41(1):1-6 [PubMed] Related Publications
Oral Hedgehog Pathway Inhibition as a Means for Ocular Salvage in Locally Advanced Intraorbital Basal Cell Carcinoma.
Dermatol Surg. 2019; 45(1):17-25 [PubMed] Related Publications
OBJECTIVE: To evaluate the evidence for the management of intraorbital basal cell cancer with HPIs.
METHODS: A search to identify evidence for treatment intraorbital basal cell cancers with HPIs to date was performed in PubMed database and OVID using the phrases "basal cell cancer/carcinoma/BCC," "intraorbital," "orbital," "ocular," "periocular," "vismodegib," "GDC-0449," "sonidegib," and "LDE224," in various combinations with Boolean operators "AND" and "OR."
RESULTS: Rigorous clinical trials have previously reported the use of vismodegib and sonidegib in locally advanced and metastatic basal cell carcinoma (BCC). However, specific descriptions of treatment of intraorbital tumors are rarely presented in detail adequate for analysis. Twenty-two cases of intraorbital BCC treated with vismodegib have been described in the literature, and no cases using sonidegib were identified. These vary in quality, but highlight important questions regarding optimal treatment duration, follow-up, and adjunctive therapies. Reports describing locally advanced BCC in various facial and periocular locations, but without specific mention of intraorbital invasion, were excluded.
CONCLUSION: Vismodegib is an attractive eye and vision-sparing option in patients with locally advanced intraorbital basal cell cancer whose other options often include exenteration, radiation, or other radical surgery.
Histologic subtype of treatment failures after noninvasive therapy for superficial basal cell carcinoma: An observational study.
J Am Acad Dermatol. 2019; 80(4):1022-1028 [PubMed] Related Publications
OBJECTIVE: We sought to evaluate the proportion of patients with a nonsuperficial treatment failure after noninvasive therapy for superficial BCC.
METHODS: An observational study was performed using data from a single blind, noninferiority, randomized controlled trial (March 2008-August 2010) with 5-year follow-up in patients with primary superficial BCC treated with methylaminolevulinate-photodynamic therapy, 5-fluorouracil, or imiquimod. Data were used from 166 adults with a histologically confirmed treatment failure.
RESULTS: A nonsuperficial subtype was found in 64 of 166 treatment failures (38.6%). Proportions with a more aggressive subtype than the primary tumor were 51.3% (38/74) for early and 28.3% (26/92) for later treatment failures (P = .003). The proportion of more aggressive early failures was significantly lower after imiquimod (26.3%) compared with methylaminolevulinate-photodynamic therapy (54.8%, P = .086) and 5-fluorouracil (66.7%, P = .011).
LIMITATIONS: There was limited information on the exact time of occurrence of treatment failures.
CONCLUSION: More aggressive treatment failure recurrences after noninvasive therapy for superficial BCC occur most often within the first 3 months posttreatment, probably indicating underdiagnosis of more aggressive components in the primary tumor rather than transformation.
The diagnostic accuracy of dermoscopy for basal cell carcinoma: A systematic review and meta-analysis.
J Am Acad Dermatol. 2019; 80(5):1380-1388 [PubMed] Related Publications
OBJECTIVE: We sought to systematically investigate the accuracy of dermoscopy for the diagnosis of BCC compared with examination with the naked eye.
METHODS: A systematic review of studies reporting the accuracy of naked eye examination and dermoscopy for the diagnosis of BCC was conducted. A meta-analysis for sensitivity and specificity was performed using a bivariate mixed-effects logistic regression modeling framework.
RESULTS: Seventeen studies were identified. The pooled sensitivity and specificity of dermoscopy for the diagnosis of BCC were 91.2% and 95%, respectively. In studies comparing test performance, adding dermoscopy to naked eye examination improved sensitivity from 66.9% to 85% (P = .0001) and specificity from 97.2% to 98.2% (P = .006). The sensitivity and specificity of dermoscopy were higher for pigmented than nonpigmented BCC. Sensitivity increased when dermoscopy was performed by experts and when the diagnosis was based on in-person dermoscopy as opposed to dermoscopic photographs.
LIMITATIONS: Significant heterogeneity among studies with a medium-to-high risk of bias.
CONCLUSION: Dermoscopy is a sensitive and specific add-on tool for the diagnosis of BCC. It is especially valuable for pigmented BCC.
Skin lesions in organ transplant recipients: a study of 177 consecutive Brazilian patients.
Int J Dermatol. 2019; 58(4):440-448 [PubMed] Related Publications
METHODS: 177 OTR were examined. Skin lesions were categorized into neoplastic, infectious, and inflammatory diseases.
RESULTS: The mean age of OTR was 52 years, the mean age at transplantation was 42.7 years, and kidney was the most common organ transplanted (72%). Skin lesions were found in 147 patients (83%). Cutaneous infections were seen in 106 patients (60%). Warts (30%) had the larger incidence and were associated with azathioprine (P = 0.026), cyclosporine (P = 0.006), and tacrolimus (P = 0.009). Superficial mycoses occurred in 16% of OTR, mostly onychomycosis, which was associated with tacrolimus (P = 0.040). Actinic keratosis (AK) occurred in 31% of patients and cutaneous tumors in 56%. Squamous cell carcinoma (SCC) was the most common tumor type affecting 36% of OTR (n = 64), with invasive SCC predominating over in situ SCC, whereas basal cell carcinoma (BCC) accounted for 17%. Both SCC and BCC were more numerous in patients' skin type I (P < 0.05). SCC was more frequent (36%) in combined kidney and liver recipients (P = 0.004), and BCC was associated with cyclosporine (P = 0.047). Inflammatory complications (acne, alopecia, hypertrichosis, and gingival overgrowth) were observed in 17.5% of patients.
CONCLUSIONS: Organ transplant recipients must be regularly evaluated by dermatologists, who should be alert to the onset of infections and skin (pre)malignant diseases in these patients.