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Xeroderma pigmentosum in eastern Turkey: A review of 15 cases
Abstract
Aim: To determine the demographic and clinical characteristics of xeroderma pigmentosum (XP). XP is a rare autosomal recessive disease that is characterized by cellular hypersensitivity to ultraviolet radiation, development of cancers at an early age, severe actinic changes, and photophobia. Materials and methods: In the dermatology clinic of Yüzüncü Yi{dotless}l University, Van, Turkey, 15 patients who were diagnosed with XP were seen between April2004 and May 2010. They were evaluated according to their age, sex, family history, parental relationships, age at onset of skin lesions, presence of cutaneous malignancy, and neurological and ophthalmologic involvement. Results: The patients consisted of 8 males (53.33%) and 7 females (46.67%), and their ages ranged from 4 to 25 years (mean: 12.13). In 2 sibling cases, there was no parental consanguinity. Parental consanguinity was present in all of the other 13 cases (86.67%). The mean age at the onset of skin lesions was 1.4 years. Neurological involvement was not seen in any of the cases, but ophthalmologic involvement was seen in all of the cases. Skin malignancy was detected in 6 patients and actinic keratosis, keratoacanthoma, and multiple ulcers were observed in some of the patients. Conclusion: XP is an inherited disorder and mostly affects the skin. Clinical signs and symptoms usually develop over time. In this series, malignancy developed in 40% of the patients during the follow-up period. This study is a large case series in which XP is clinically assessed.
... [1][2][3] Although there are a few number of reports describing benign skin tumors in the setting of XP, 1,2,[4][5][6] in most series no association has been emphasized. 3,[7][8][9][10][11][12][13][14][15][16][17][18] The aim of this study is to evaluate 24 XP patients with respect to the development of benign skin tumors, precancerous lesions, and malignant skin tumors with their distinct clinical and histopathological features during a long follow-up period. Moreover, we reviewed the literature focusing on skin tumors arising in XP patients and compared our results with other studies. ...
... 23 These rates are compatible with the further data in the literature describing the higher rate of nonmelanoma skin cancer development compared to melanoma development ( Table 2). [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] In our study, F I G U R E 7 Keratoacanthoma-like follicular lesion (patient 19 in Table 1) (Table 1). It was previously reported that the frequency of cutaneous malignancies may vary from one complementation group to the other; predominantly SCC and BCC in group C, melanoma in group D, and BCC in group E and XP variant. ...
... It was previously reported that the frequency of cutaneous malignancies may vary from one complementation group to the other; predominantly SCC and BCC in group C, melanoma in group D, and BCC in group E and XP variant. 9 However, in our study, a clinical heterogeneity in XP-V patients' skin tumor profile was noted, even though they were from the same family; In most of the XP series benign skin tumors were neither investigated nor observed 3,[7][8][9][10][11][12][13][14][15][16][17][18] and only a few studies described particular benign tumors in XP patients 1,2,4-6 ( Table 2). Seborrheic keratosis was only noted in three adult XP patients in our series. ...
Background
Xeroderma pigmentosum (XP) is a rare genodermatosis with a propensity to develop malignant skin tumors lifelong.
Methods
In this retrospective study, 24 XP patients were evaluated with regard to frequency and clinicopathological features of benign and malignant skin tumors.
Results
Seventeen patients had at least one malignant skin tumor diagnosed; basal cell carcinoma in 13 patients (n = 72), basosquamous carcinoma in three patients (n = 4), squamous cell carcinoma in six patients (n = 13), keratoacanthoma in three patients (n = 15) and melanoma in six patients (n = 18). Most melanomas (n = 15) were in‐situ lesions. Several benign skin tumors were noted such as tricholemmoma (n = 1), trichoepithelioma (n = 1), trichoblastoma (n = 1), follicular infundibulum tumor (n = 1), keratoacanthoma‐like follicular lesion (n = 1), adnexal tumors with folliculosebaceous (n = 1) and tricholemmal differentiation (n = 1) and neurofibroma (n = 1). Benign vascular proliferations, including pyogenic granulomas (n = 8), widespread telangiectasias and senile angioma‐like lesions were also observed in 3, 5 and 5 patients, respectively.
Conclusions
Similar to many reports, basal cell carcinoma was found to be the most common malignant skin tumor. The high prevalence of benign adnexal tumors of follicular differentiation, some of them showing mixed histopathological features and various vascular proliferations in our series raises the question of whether they indicate a formerly undescribed association with XP.
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... Akdeniz N. y cols. 2012 reportaron la incidencia de neoplasias cutáneas en un 40% todas encontradas en la exposición al sol con mayor frecuencia en la cara 8,10,11 . ...
... Las conjuntivas sufren una alteración grave con xerosis, congestión conjuntiva crónica, hiperemia, telangiectasias, y manchas pigmentarias que con el tiempo pueden epidermizarse. Los párpados pueden presentar ectropión, lo que agrava el pronóstico ocular, la gravedad se debe a la aparición de tumores benignos y sobre todo malignos y melanomas de localización palpebral, límbica o conjuntival, lo que compromete el pronóstico funcional y vital 8,9,11 . ...
... 2014 se encuentran en el 14-40% de los casos de xerodermia pigmentosa, sobre todo en los grupos: A, B, D mientras que Akdeniz N. y cols. 2012 observaron una incidencia de 20% -30% de los casos con una edad de aparición neurológica que va desde el periodo infantil hasta la segunda década de la vida 1,9,11 . ...
La xerodermia pigmentosa (XP) es un trastorno autosómico recesivo. Se presenta con manifestaciones cutáneas como aparición de machas, pecas, eritema, vesículas, carcinomas y melanomas en zonas expuestas la radicación solar que incluyen piel y mucosas. Además de lesiones oculares como fotofobia, conjuntivitis, ulceras , ceguera y en ciertos casos alteraciones neurológicas. Se presenta dos casos clínicos de pacientes con diagnostico de xerodermia pigmentosa con manifestaciones cutáneas, oftalmológicas y orales. El objetivo de este artículo es presentar las manifestaciones orales que se presentan en la xerodermia pigmentosa , su diagnóstico precoz, tratamiento y prevención de las mismas. Palabras claves: xerodermia pigmentosa, melanoma, cáncer, manifestaciones orales.
... XP is a hereditary autosomal recessive disorder, with a prevalence of 1:1,000,000 in the USA and 1:100,000 in Japan [1]. The prevalence is higher in Middle Eastern countries such as Turkey, Israel, and Syria because of the high frequency of consanguineous marriages [11,16]. Recent Turkish Demographic and Health Surveys reported the rate of consanguineous marriages as 22-24% in Turkey [17]. ...
... Recent Turkish Demographic and Health Surveys reported the rate of consanguineous marriages as 22-24% in Turkey [17]. In a demographic study among patients with XP by Akdeniz et al. [16], the parental consanguinity rate was 86.7%, which is consistent with previous reports by Khatri [20]. The parents of the present patient were first cousins, and they were heterozygous carriers of the relevant mutation. ...
Background: Xeroderma pigmentosum is an extremely serious genetic disorder defined by sensitivity to sunlight, resulting in sunburn and pigment changes. If patients are not completely protected from ultraviolet radiation, xero-derma pigmentosum is characterized by a greatly increased risk of sunlight-induced cutaneous neoplasms. There is no standard therapy for skin cancer of xeroderma pigmentosum. However, immune checkpoint inhibitors were reported to increase response rates and improve outcomes and life expectancy in patients with various cancers, including squamous cell carcinoma in xeroderma pigmentosum. In this paper, we report on a patient with xeroderma pigmentosum from a consanguineous family with recurrent facial chemotherapy-resistant squamous cell carcinoma lesions treated successfully with an anti-programmed cell death protein 1 monoclonal antibody in both relapses.
Case presentation: A 7-year-old Turkish male was referred to our oncology department for recurring squamous cell carcinoma after local excision of the tumor over his nose. The lesion was a rapidly growing lesion, measuring 8 × 4 cm in size. Physical examination revealed that he also had hemorrhagic crusted plaques and nodules over both eyelids and upper lip, with multiple hypo-and hyperpigmented punctate lesions all over his body. After two more cycles of chemotherapy, progressive disease was noted, and a new lesion on the right eyelid caused blurred vision. Anti-programmed cell death protein 1 antibody treatment was planned with concomitant radiotherapy. He received nivolumab every 3 weeks for 4 months, improving his vision. No new lesions or active complaints have been observed in the current situation, and complete remission has been achieved. On the last admission, the patient was clinically diagnosed with xeroderma pigmentosum. Owing to the condition's genetic heterogeneity, whole-exome sequencing was performed with Ion Proton next-generation sequencing platform, and the c.2250 + 1G>A splice site mutation of the XPC gene was detected in the homozygous state.
Conclusions: The clinical report emphasizes the importance of clinical awareness and crucial early diagnosis of xeroderma pigmentosum and presents a novel causative homozygous c.2250 + 1G>A splice site mutation. Our case proves that next-generation sequencing is an effective method for the rapid diagnosis and determination of xero-derma pigmentosum genetic etiology.
... XP is known as an autosomal recessive disorder consisting of mucocutaneous and ocular hypersensitivity to UV radiation with malignant transformers, in some cases by progressive neurological problems 11 . There is no gender or race predilection for XP 10 . ...
... and 1/40.000 in Japan 1 . XP is more common because of the high frequency of intermarriages 11 . But in our case, a history of consanguinity was not identified. ...
Background/Aim : Xeroderma pigmentosum (XP) is an autosomal recessive skin disease. Affected patients have skin problems, oral mucosa and neurologic symptoms. In these patients, erythematous, hyperpigmented or malignant skin lesions may occur in the sun-exposed areas. Leukoplakia, erythroplakia, and squamous cell carcinoma of the tip of the tongue and lips are common oral lesions associated with XP.
Case report : Treatment of the disease included protection from ultraviolet radiation, topical application to treat actinic keratitis, and multidisciplinary approaches by physicians.
Conclusions : Even though USG in dentistry is not very common, it is a non-invasive, cost-effective, readily available and repeatable diagnostic imaging method. Thus, USG should take place as a routine diagnostic tool in dentistry, especially for patients who are medically compromised.
... A study by Baykal et al reported six cases of BCC. 11 While the most common malignant skin tumor was reported to be squamous cell carcinoma in a review article that included 830 published XP cases from 1874 to 1982 12 and in other several studies, they also reported squamous cell carcinoma was the commonest 19,20 which was in agreement with our study because we reported six cases of squamous cell carcinoma. We also reported one unusual case having both skin malignancies (squamous cell carcinoma and BCC). ...
Xeroderma pigmentosum (XP) is a rare autosomal recessive genetic disease. This disease predisposes patients to early-onset skin cancers, like squamous cell carcinoma and basal cell carcinoma. This was a 5-year experience. Here, we report nine pediatric cases of XP in which two patients had basal cell carcinoma and six patients had squamous cell carcinoma. We have also reported one case in which both skin malignancies were present. The subjects included seven boys and two girls, while seven subjects were from consanguineous marriages, and the average age was 9.4 years. All the patients had ulcerative budding tumor lesions on the face (eye, nose, chin, cheek, and forehead) and scalp. Squamous cell carcinoma is a common cutaneous malignancy related to XP in our study. Prevention is based on the early diagnosis of XP, skin photo-protection, screening and early treatment of lesions, and genetic counseling.
... [3] Actinic damage occurs between 1 and 2 years. [7] The most common types of cancer found in XP patients are basal cell carcinoma and SCC, mostly involving the face, head, and neck. [8] SCC in the scalp tends to have an aggressive course. ...
Xeroderma pigmentosum is a rare autosomal-recessive disorder that appears in early childhood. Squamous cell carcinoma is not uncommon in patients with xeroderma pigmentosum and mostly involving the face, head, neck, and scalp. However, squamous cell carcinoma of the scalp may exhibit an aggressive course.
Here, we present a huge squamous cell carcinoma of the scalp in a three-years-old child with xeroderma pigmentosum. In addition, we illustrate the challenges of a child with xeroderma pigmentosum who grows up in a sunny environment where the possibility of early onset of squamous cell carcinoma is extremely high in any suspected skin lesion.
In xeroderma pigmentosum patients, squamous cell carcinoma of the scalp can present early and tends to be unusually aggressive. In sunny areas, proper education to the patient and their parents about ultra-violet light protection and early recognition of any suspicious lesion could be life-saving.
Background
Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder presenting with an inability to repair UV‐induced DNA damage. This can lead to the development of neoplasms affecting multiple organ systems, with onset often in childhood. Unfortunately, no cure currently exists for XP, and management strategies focus on sun protection and early intervention for malignancies. Although most skin problems in XP patients are UV induced, various oral lesions are also described. However, the literature has not extensively characterized the oral manifestations and their prognostic significance.
Methods
We conducted a comprehensive review to evaluate the prevalence and nature of oral mucosal lesions in pediatric XP patients.
Results
Our literature search yielded 130 pediatric XP patients with oral involvement and 210 associated tumoral or non‐tumoral lesions. Squamous cell carcinoma was the most common type of oral mucosal tumor reported, with other malignancies including basal cell carcinoma, melanoma, angiosarcoma, fibrosarcoma, and trichilemmal carcinoma.
Conclusion
Given the potential morbidity and mortality associated with oral mucosal tumors in XP patients, our study aims to raise awareness of these manifestations. Early diagnosis and treatment are crucial for managing these lesions effectively, and routine oral exams should be considered a critical component of dermatological evaluations for XP patients, especially in the pediatric age group.
The lariat branch point sequence (BPS) is crucial for splicing of human nuclear pre-mRNA yet BPS mutations have infrequently been reported to cause human disease. Using an inverse RT–PCR technique we mapped two BPS to the adenosine residues at positions À4 and À24 in intron 3 of the human XPC DNA repair gene. We identified homozygous mutations in each of these BPS in two newly diagnosed Turkish families with the autosomal recessive disorder xeroderma pigmentosum (XP). Cells from two severely affected children in family A harbor a homozygous point mutation in XPC intron 3 (À9 T to A), located within the downstream BPS. Using a real-time quantitative reverse transcriptase–polymerase chain reaction (QRT–PCR) assay, these cells expressed no detectable (<0.1%) normal XPC message. Instead they expressed an XPC mRNA isoform with deletion of exon 4 that has no DNA repair activity in a host cell reactivation (HCR) assay. In contrast, in cells from three mildly affected siblings in family B, the BPS adenosine located at the À24 position in XPC intron 3 is mutated to a G. Real-time QRT–PCR revealed 3–5% of normal XPC message. These cells from family B had a higher level of HCR than cells from the severely affected siblings in family A, who had multiple skin cancers. Mutations identified in two BPS of the XPC intron 3 resulted in alternative splicing that impaired DNA repair function, thus implicating both of these BPS as essential for normal pre-mRNA splicing. However, a small amount of normal XPC mRNA can provide partial protection against skin cancers.
We present the case of an 8 year-old girl in a developing country with significant corneal scarring and multiple cutaneous skin lesions in sun-exposed areas. Neuro-developmental delay had been present since 3 months of age, and taken as a whole the consensus was that this clinical picture was consistent with Xeroderma Pigmentosum (XP). We highlight the difficulties encountered due to the lack of diagnostic and treatment modalities for this child, and offer a brief review of XP, including emerging treatments that show potential.
to evaluate the probable presence of otorhinolaryngological pathology accompanied by head and neck region skin findings in patients with Xeroderma pigmentosum.
a total of 19 patients with Xeroderma pigmentosum were investigated for otorhinolaryngological findings. The patients gave their anamnesis and underwent physical examination, audiological tests and endoscopic examination.
various malignancies developed in 14 patients on the sun-exposed areas of the head and neck region. Multiple malignancies were found in six of them. There was no other pathological condition secondary to this rare clinical entity.
Xeroderma pigmentosum causes skin lesions. Some otolaryngological findings such as rhinitis, sinusitis etc. were thought to be coincidental.
Xeroderma pigmentosum (XP) is a rare, usually autosomal recessive disorder related to DNA repair defects. Atypical fibroxanthoma (AFX) is a pleomorphic tumour that occurs infrequently on the limbs and trunk in children, We report a child with XP who presented with AFX of the facial skin and the lower lip, The diagnosis of AFX was confirmed using histological and immunohistochemical techniques. We discuss the possibility that ultraviolet-induced damage might be implicated in the pathogenesis of AFX.
Background
Xeroderma pigmentosum (XP) is an autosomal recessive disorder characterized by a defect in DNA repair and subsequent increased frequency of cutaneous malignant neoplasms, including melanoma. In patients with XP, patient and family education and aggressive UV radiation protection are the primary means of skin cancer prevention. An important secondary measure in decreasing morbidity and mortality in these patients involves early detection of skin cancers, particularly melanomas.Observations
We describe a 39-year-old woman with XP who developed 38 primary melanomas along with 6 squamous cell carcinomas and 70 basal cell carcinomas over a 23-year period. During this time, a 3-fold management approach of total-body cutaneous examination, total-body photography, and dermoscopy was used in the care of the patient. The thickest melanoma had a Breslow thickness of 1.07 mm, and the mean Breslow thickness of her detected melanomas was 0.18 mm. The ratio of benign to malignant biopsied suspicious melanocytic lesions during 23 years of follow-up was 0.9:1. All melanomas were treated using wide local excision, and she had no evidence of local or in-transit metastases of any of her malignant neoplasms at the most recent follow-up examination.Conclusion
Monthly follow-up using total-body cutaneous examinations, total-body photography, and dermoscopy is an important 3-fold secondary management technique for this unique patient, allowing early detection of her melanomas.
A preliminary study of 24 cases of xeroderma pigmentosum (XP) was presented in 1990 and later published in 1992. Since then we have seen 18 further cases.
To study the clinical profile of Libyan cases of XP.
With the help of a special protocol, all 42 cases (23 girls and 19 boys from 29 families) treated and followed between 1981 and 1994 were subjected to detailed analysis.
A history of consanguinity was present in the parents of 39 patients. XP in Libya is characterized by a relatively high incidence (approximately 15-20 per million of the population), early onset of initial manifestations (median age, 12 months) and malignant tumors (median age, 8 years), severe ocular and oral lesions in a high percentage of patients, and early death (median age, 15.5 years). The malignant skin tumors seen were squamous cell carcinoma (SCC) in 23 patients, basal cell carcinoma (BCC) in 17 patients, and basosquamous carcinoma in two patients. Malignant melanoma was not seen, but lentigo maligna was found in one case. SCC of the tongue, carcinoma of the thyroid, and lymphatic leukemia affected individual patients. Subnormal physical growth was observed in six patients, but none of the patients had significant neurologic abnormalities. The results of etretinate therapy in nine patients revealed that it is an effective preventive agent against carcinogenesis, but not a curative one.
Severe ophthalmic manifestations affected a higher percentage of patients at an early age. Malignant melanoma did not develop in any case, except for lentigo maligna in one patient.
Xeroderma pigmentosum (XP) is a rare, usually autosomal recessive disorder related to DNA repair defects. Atypical fibroxanthoma (AFX) is a pleomorphic tumour that occurs infrequently on the limbs and trunk in children. We report a child with XP who presented with AFX of the facial skin and the lower lip. The diagnosis of AFX was confirmed using histological and immunohistochemical techniques. We discuss the possibility that ultraviolet-induced damage might be implicated in the pathogenesis of AFX.
Xeroderma pigmentosum family G from Van, Turkey had two severely affected children: a son with multiple skin cancers who died at age 10 (XP67TMA), and an 8 y old daughter who began developing skin cancer before 3 y of age (XP68TMA). XP67TMA and XP68TMA cells were hypersensitive to killing by ultraviolet and the post-ultraviolet DNA repair level was 12-16% of normal. Host cell reactivation of an ultraviolet-treated reporter plasmid cotransfected with a vector expressing wild-type XPC cDNA assigned XP67TMA to xeroderma pigmentosum complementation group C. The XPC mRNA level was markedly reduced. Sequencing of the 3.5 kb XPC cDNA from XP67TMA showed a C-T mutation in XPC exon 8 at base pair 1840. This mutation converts the CGA codon of arginine at amino acid 579 to a UGA stop codon resulting in marked truncation of the 940 amino acid xeroderma pigmentosum C protein. Restriction fragment length polymorphism analysis of XPC exon 8 DNA in XP67TMA and XP68TMA showed that both affected children had a homozygous mutation and that both parents had heterozygous normal and mutated sequences at the same position consistent with a history of consanguinity in the family. The mutated allele also contained two XPC single nucleotide polymorphisms. The same mutated XPC allele was reported in an Italian family. Studies of 19 microsatellite markers flanking the XPC gene on chromosome 3 suggest that the XPC allele passed between Italy and Turkey approximately 300-500 y ago. This XPC allele containing a nonsense mutation is associated with severe clinical disease with multiple skin cancers and early death.
Xeroderma pigmentosum (XP) is a rare autosomal recessive inherited disorder caused by a defect in the normal repair of DNA of various cutaneous cell types damaged by exposure to ultraviolet radiation. We present our 7-year experience with 36 XP patients who either visited the Department of Dermatology or were seen in the medical camps arranged in remote areas for patients' welfare, from 1995 to 2001. For ease of discussion we classified all cases into the following subgroups on clinical grounds only: mild, those with light brown freckles on the face alone; moderate, those with dark brown freckles with burning on the face, neck, ears, chest, hands and photophobia but without other associated obvious cutaneous and ocular changes; severe, those with extensive dark brown freckles with burning on the exposed parts as well as on the unexposed parts of the body, i.e. the chest, back, abdomen and arms including other associated cutaneous and ocular changes such as ulcers and malignancy. Of 36 patients, three (8.3%) were classified as mild, nine (25%) moderate and 24 (66.7%) severe; there were 18 males and 18 females, age range 2-30 years (mean 8.9 years). Seventeen patients had cutaneous changes: actinic keratosis, keratoacanthoma, fissures and ulcerative nodules on the exposed parts of the body. Four patients had wide ulcers, along with mass formation and severe pigmentation on the face, neck and head. Twenty-nine patients developed ocular symptoms: photophobia, conjunctivitis, corneal keratitis and lid ulcer. One patient had complete loss of vision. Histopathological findings revealed that six patients had squamous cell carcinoma (SCC) on the face, head, ear or lip. More than one sibling (two to four) was affected in four families. The majority of cases (20/36, 55.6%) were from the Brohi tribe (skin type III), while the remaining cases (16/36, 44.4%) were from the Sindhi population (skin type IV). The large number of XP patients seen in those with skin type III (Brohi tribe) compared with skin type IV (Sindhi population) indicates that the skin type and the race has a considerable value in the pathogenesis of XP. Furthermore, 24 of 36 patients were in the severe group and six of these had SCC. Moreover, no neurological abnormalities were observed in our patients. All patients were treated according to disease severity by prescribing oral antibiotics, local steroids, sunscreens and/or chemotherapy followed by irradiation in malignant cases. Two patients died because of extensive SCC.
Xeroderma pigmentosum (XP) is a rare, autosomal recessive genodermatosis in which affected individuals exhibit sun sensitivity, cutaneous pigment abnormalities, and a high incidence of skin cancers of sun-exposed skin.
We studied the clinical features of 12 XP patients from Turkey, who were followed for 5 years.
Consanguinity was confirmed in 10 cases. The onset of hyperpigmented macules and photosensitivity was between the ages of 6 months and 5 years (average age, 25 months). The first appearance of cutaneous tumors was at 3-28 years of age (average age, 12 years). In nine of the 12 patients, cutaneous malignancies were confirmed histopathologically, and all nine were squamous cell carcinomas. One patient developed both squamous cell carcinoma and malignant melanoma.
This study presents the epidemiological and clinical features of Turkish XP patients. We believe this study will provide new data for further studies in the future.