Reconstruction of Moderately and Severely Atrophic Scalp-A Multicentric Experience in Surgical Treatment of Patients Irradiated for Tinea Capitis in Childhood and Surgical Algorithm.

Background and Objectives: Before the introduction of griseofluvin, the use of X-ray radiation was the treatment of choice for tinea capitis. More than half a century later various types of tumors have been found to be associated with childhood irradiation due to tinea capitis, most commonly cancers of the head and neck, as well as brain tumors. The often unusually aggressive and recurrent nature of these tumors necessitates the need for repeated surgeries, while the atrophic skin with an impaired vascular supply due to radiation often poses an additional challenge for defect reconstruction. We present our experience in the surgical treatment of such patients. Materials and Methods: This is a retrospective cohort study. In this study, 37 patients treated for acquired defects of the scalp with a history of irradiation therapy due to tinea capitis in childhood were included in this study, 24 male and 13 female patients. The mean age at the first appointment was 60.6 ± 7.8, with the youngest included patient being 46 and the oldest being 75 years old. Patients' characteristics, surgical treatment, and complications were analyzed and a reconstructive algorithm was developed. Results: Local flaps were used for reconstruction in 34 patients, direct sutures were used in 10 patients and 20 patients received split-thickness skin grafts for coverage of both primary and secondary defects for reconstruction of flap donor sites. One regional flap and one dermal substitute covered by an autologous skin graft were also used for reconstruction. Complications occurred in 43.2% of patients and were significantly associated with the presence of comorbidities (p = 0.001), aseptic bone necrosis (p = 0.001), as well as skin atrophy in frontal, occipital, and parietal region (p = 0.001, p = 0.042 and p = 0.001, respectively). A significant correlation between major complications and moderate skin atrophy was found only in the parietal region (p = 0.026). Conclusions: Unfortunately, many protocols developed for scalp reconstruction are not applicable in the setting of severe or diffuse scalp skin atrophy associated with high tumor recurrence rate and radiation-induced vascular impairment, such as in tinea capitis patients in Serbia. An algorithm has been developed based on the authors' experience in managing these patients.

Basal cell carcinomas of the scalp after radiotherapy for tinea capitis: Clinicopathological study in a case series of 96 patients with analysis of 427 tumours.

BACKGROUND/OBJECTIVES: Low-dose X-ray radiotherapy to treat tinea capitis during childhood is a well-known risk factor for scalp basal cell carcinomas (BCCs). Post-radiotherapy BCCs are often multiple, and it has been suggested that they display more aggressive features. Our main objective was to study the clinicopathological aspects of post-radiotherapy BCCs to evaluate their biological behaviour and identify features that may differ from other BCCs. METHODS: We performed an observational, retrospective study assessing multiple clinical and pathological characteristics of patients with post-radiotherapy BCCs. RESULTS: We studied 96 patients with 427 post-radiotherapy scalp BCCs. Post-radiotherapy BCCs were often multiple (median of 4 lesions/patient, ranging from 1 to 54). Significant comorbidities included a high incidence of thyroid disease and meningiomas. Recurrences were observed in 23% of patients, but there may be confounding factors, such as referral bias, heterogenous treatment modalities and occurrence of new tumours due to field effect. We found a high incidence of infundibulocystic BCCs (in 14.6% of patients and corresponding to 5.4% of the total number of tumours), trichoblastomas (5.2%) and neurofibromas of the scalp (10%). CONCLUSIONS: This study is consistent with the occurrence of multiple lesions (sometimes numerous) and a relatively high tendency for recurrence in post-radiotherapy BCCs, as suggested by previous studies. We also found a high incidence of the infundibulocystic variant and a higher risk of follicular tumours and neurofibromas, which suggests that radiotherapy may influence the type of differentiation of BCCs and contribute to induce neoplasms of different cell lines.

Gender Differences in Psychosocial Outcomes of Hair Loss Resulting from Childhood Irradiation for Tinea Capitis.

Recent studies have linked hair loss due to childhood irradiation for tinea capitis, a fungal infection of the scalp, to adverse psychosocial and health outcomes in women. However, no study to date has examined gender differences in the outcomes of this type of hair loss. The current study aimed to investigate gender differences in health and psychosocial outcomes of hair loss resulting from childhood irradiation for tinea capitis, and to identify the risk factors associated with depression in both men and women. Medical records held at the archives of the Israel National Center for Compensation of Scalp Ringworm Victims were retrospectively reviewed for 217 women and 105 men who received maximum disability compensation due to severe hair loss resulting from irradiation for tinea capitis. We found that women were at increased risk of developing psychosocial symptoms, including depression. Gender emerged as a significant predictor of depression, distinct from other predictors, such as marital status, age at radiation, exposure to verbal and physical bullying, low self-esteem, social anxiety, and physical health problems. Thus, the psychosocial needs of patients, particularly female patients, who were irradiated for tinea capitis during childhood need to be taken into account by the healthcare professionals treating them.

Multiple Basal Cell Carcinomas of the Scalp After Radiotherapy: Genomic Study in a Case With Latency Period Over 80 Years.

ABSTRACT: Basal cell carcinoma (BCC) has been linked mostly to ultraviolet radiation exposure, but ionizing radiation has also been implicated in the genesis of a subset of BCCs occurring after radiotherapy. We present a 93-year-old woman with 4 BCCs of the scalp after radiotherapy for tinea capitis, diagnosed after a latency period of over 80 years. The largest lesion was located on the right temporal region and corresponded to a BCC of mixed type, with nodular, infiltrative, and micronodular components. We performed genomic study with array comparative genomic hybridization in samples from each BCC, which revealed more imbalances in the largest lesion than in the remaining ones, correlating with its higher histological complexity. Furthermore, this was the only lesion presenting loss at 2p22.3, where is mapped the BIRC6 gene associated with regulation of apoptosis, and loss at 16q24.3, where is mapped FANCA gene, responsible for DNA repair and maintenance of chromosome stability. Despite these differences, there were aberrations shared by all tumor samples, suggesting a common genetic signature. Our report describes, to the best of our knowledge, the longest latency period between exposure to radiotherapy and the diagnosis of BCC. The genomic study showed imbalances common to all tumor samples but also differences that could explain their heterogeneity in terms of histological subtype and biological potential. In addition, these differences could also be a consequence of different times in the evolution of the lesions at the moment of presentation, thus having a diverse combination of accumulated genomic imbalances.

Basal cell carcinomas of the scalp after radiotherapy for tinea capitis in childhood: A genetic and epigenetic study with comparison with basal cell carcinomas evolving in chronically sun-exposed areas.

BACKGROUND: Basal cell carcinoma (BCC) has been mostly associated with sun exposure, but ionizing radiation is also a known risk factor. It is not clear if the pathogenesis of BCC, namely at a genomic and epigenetic level, differs according to the underlying triggering factors. OBJECTIVE: The present study aims to compare genetic and epigenetic changes in BCCs related to ionizing radiation and chronic sun exposure. METHODS: Tumor samples from BCCs of the scalp in patients submitted to radiotherapy to treat tinea capitis in childhood and BCCs from sun-exposed areas were analysed through array comparative genomic hybridization (array-CGH) and methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) to detect copy number alterations and methylation status of specific genes. RESULTS: Genomic characterization of tumor samples revealed several copy number gains and losses in all chromosomes, with the most frequent gains observed at 2p, 6p, 12p, 14q, 15q, 18q, Xp and Yp, and the most frequent losses observed at 3q, 14q, 16p, 17q, 22q, Xp, Yp and Yq. We developed a statistical model, encompassing gains in 3p and 16p and losses in 14q and 20p, with potential to discriminate BCC samples with sporadic aetiology from BCC samples that evolve after radiotherapy in childhood for the treatment of tinea capitis, which presented statistical significance (P = 0.003). Few methylated genes were detected through MS-MLPA, most frequently RARB and CD44. CONCLUSIONS: Our study represents a step forward in the understanding of the genetic mechanisms underlying the pathogenesis of BCC and suggests potential differences according to the underlying ris k factors.

Childhood Exposure to Low to Moderate Doses of Ionizing Radiation and the Risk of Vascular Diseases.

In the Tinea Capitis Study (Israel, 1966-2011), we assessed the association between childhood exposure to low to moderate doses of ionizing radiation (IR) to the head and neck and the development of vascular diseases (ischemic heart disease, carotid artery stenosis, and stroke) in adulthood. The study included 17,734 individuals from the Tinea Capitis cohort (7,408 irradiated in childhood and 10,326 nonirradiated), insured by Israel's largest health provider. Individual dosimetry was estimated based on measurements made on a head phantom and original treatment records. The mean doses were 1.5, 0.09, 0.78, and 0.017 Gy to brain, thyroid, salivary gland, and breast, respectively. Data on vascular diseases was abstracted from computerized medical records. Using Poisson regressions, we examined the association of radiation with morbidity. Any vascular disease was reported for 2,221 individuals. Adjusted for age, sex, socioeconomic status, smoking, hypertension, and diabetes, exposure to IR increased the risk of developing any vascular diseases (relative risk (RR) = 1.19, 95% confidence interval (CI): 1.09, 1.29), stroke (RR = 1.35, 1.20, 1.53), carotid artery stenosis (RR = 1.32, 1.06, 1.64), and ischemic heart disease (RR = 1.12, 1.01, 1.26). The risk of developing vascular diseases was positively associated with dose and inversely associated with age at exposure. In conclusion, the results indicate that early exposure to low to moderate doses of IR increases the risk of cerebro- and cardiovascular impairments.

Does Severity of Hair Loss Matter? Factors Associated with Mental Health Outcomes in Women Irradiated for Tinea Capitis in Childhood.

Hair loss resulting from childhood irradiation for tinea capitis has been linked to mental health effects in women. However, the association of hair loss severity with mental health in this population is unknown. To address this gap, this study examined the association between hair loss severity and mental health outcomes in women irradiated for tinea capitis in childhood as well as the factors that contribute to these outcomes. Medical records, held at the archives of the Israel National Center for Compensation of Scalp Ringworm Victims, were retrospectively reviewed for 2509 women who received compensation for full or partial alopecia resulting from irradiation for tinea capitis. Mental health outcomes were determined by the number of mental health conditions reported. The results show that among women with more hair loss, risk was increased for a range of mental health problems, especially social anxiety (RR 2.44, 95% CI 2.09-2.87). Hair loss severity emerged as a significant predictor of mental health, adding to the effects of other predictors such as family, social and physical health problems (ß = 0.13, 95% CI 0.27, 0.56). The effects of hair loss severity on mental health outcomes were mediated by women's negative social experiences (indirect = 0.72, 95% bias-corrected confidence interval, 0.53-1.08). Healthcare professionals supporting women with hair loss after irradiation for childhood tinea capitis should be alert to a history of severe levels of hair loss.

Cancer incidence after childhood irradiation for tinea capitis in a Portuguese cohort.

OBJECTIVES: Our aim was to compare cancer incidence in a cohort exposed in childhood (1950-63) to a therapeutic dose of radiation in the North of Portugal and followed-up until the end of 2012, with the incidence rates for the same age and sex in the general population. METHODS: A population-based North Region cancer registry (RORENO) was used to assess which members of the cohort developed cancer. The association between radiation exposure and overall and specific cancer sites was evaluated using standardised incidence ratios (SIR). RESULTS: Over the full follow-up period, 3357 individuals of the 5356 original tinea capitis (TC) cohort (63%) were retrieved in the RORENO, and 399 new cancer cases were identified, representing an increased risk of 49% when compared with the general population (SIR = 1.49; 95% CI: 1.35-1.64). The risk was slightly higher in males than in females (SIR = 1.65; 95% CI: 1.43-1.89 vs SIR = 1.35; CI = 1.17-1.55). The risk was slightly higher in the individuals exposed to a higher radiation dose (SIR = 1.78; 95% CI: 1.22-2.51 for ≥630 R vs SIR = 1.46; 95% CI: 1.31-1.62 for 325-475 R). In females, there was an excess cancer risk in all cancers with the higher radiation dose (SIR = 2.00; 95% CI: 1.21-3.13 for ≥630 R vs SIR = 1.30; 95% CI: 1.11-1.51 for 325-475 R) which was not observed in males, and for combined dose categories significantly raised SIRs for thyroid and head and neck cancer, suggesting a possible higher radiosensitivity of females. An increased risk was also observed for some cancers located far from the irradiated area. CONCLUSIONS: The results suggest an association between radiation exposure and later increased cancer risk for cancers located near the radiation exposed area, mainly thyroid, and head and neck cancers. Further studies are necessary to disentangle possible non-radiation causes for distant cancers increased risk. ADVANCES IN KNOWLEDGE: This paper shows a possible association between childhood X-ray epilation and increased risk of cancer which was not previously investigated in the Portuguese TC cohort.

Echoes from the past- changing associations between brain tumors and ethnicity.

BACKGROUND: cranial X radiation therapy was the standard of care for treating dermatological conditions until the 1960s, when its association to cancer and particularly high rates of brain tumors was discovered. This study examines associations found between incidence of brain tumor and ethnicity. METHODS: This study analyzed two cohorts who underwent examination at age 17 and were followed by linkage to the national cancer registry. The first cohort included 376,336 participants born in 1948-1959 (when treatment with cranial X radiation was standard care for treating tinea capitis), and the second 474,923 participants born in 1960-1971. RESULTS: In the first cohort, ethnicity was strongly associated with the incidence of brain tumor (BT), with higher incidence observed among patients with origins in North Africa or the Middle East. This effect was ablated in the second cohort, and a significant decrease in the rate of meningiomas was noted. CONCLUSION: The association of brain tumor with ethnicity was present only during the period when treatment with cranial X radiation was the standard of care for TC in Israel, therefore it is most likely that radiation exposure was a confounding factor, and that ethnic susceptibility for brain cancer was not causative in these cohorts.

Indurated purple plaques on the scalp.

Cutaneous epithelioid angiosarcoma is a rare neoplasm of vascular endothelial cell origin that can mimic a cutaneous lymphoma, metastatic carcinoma, or Kaposi sarcoma. It is one of the most malignant cutaneous tumors and early diagnosis is essential, as the tumor metastasizes quickly. We describe a 75-year-old man who presented with three tender, indurated violaceous plaques on his scalp. Biopsy revealed a poorly circumscribed infiltrate extending into the subcutaneous fat, composed of atypical epithelioid cells lining vascular spaces. We provide a brief review of the clinical presentation, histopathologic features, differential diagnosis, and management of this rare tumor.

Basal cell carcinoma induced by therapeutic radiation for tinea capitis-clinicopathological study.

AIMS: An increased prevalence of aggressive histological subtypes, such as micronodular and morpheaform, has been seen, irrespective of the clinical course, in basal cell carcinoma (BCC) following irradiation for tinea capitis. The aim of this study was to assess the histopathological features of BCCs among patients irradiated for tinea capitis and correlate them with the clinical course. METHODS AND RESULTS: The medical records and BCC biopsy specimens of individuals who were previously irradiated for tinea capitis were reviewed. Demographic data and clinical characteristics were retrieved. Biopsy specimens were evaluated for histological subtype classification and additional histopathological features. A telephone survey was conducted to assess the clinical behaviour of the tumours. Thirty-one patients (17 male; 14 female) were included. The average age at time of first biopsy was 56 years. The total number of lesions was 185, with 80% of subjects showing multiple lesions. The nodular subtype was the most prevalent, followed by superficial, micronodular and mixed tumours. One-third of the BCCs could be classified as aggressive histologically. Stromal fibroplasia and melanin deposits were common. There was no mortality related to BCC. None of the 17 patients who completed the survey had evidence of local invasiveness or metastases. CONCLUSIONS: BCCs following radiation therapy for tinea capitis show unique histological characteristics related to aggressive behaviour. These aggressive features did not reflect the clinical behaviour in the current cohort.

TERT promoter mutations: a genetic signature of benign and malignant thyroid tumours occurring in the context of tinea capitis irradiation.

OBJECTIVE: The aim of this study is to evaluate the frequency and molecular characteristics of TERTp mutations in thyroid adenomas and carcinomas occurring in the low-dose radiation exposure tinea capitis setting. DESIGN AND METHODS: Twenty-seven patients with 34 well-differentiated thyroid carcinomas and 28 patients with 29 follicular adenomas diagnosed in a Portuguese tinea capitis cohort were studied. Blood samples were obtained from all the patients. Screening for TERTp mutations was performed by PCR amplification followed by Sanger sequencing. A series of 33 sporadic thyroid adenomas was used as control. RESULTS: TERTp mutations were detected in six of the 28 patients with adenoma (21.4%) and in four of the 27 patients with carcinoma (14.8%). Three tumours (two carcinomas and one adenoma) had the tandem mutation -124/-125 GG>AA (30.0%), whereas the remaining seven had the -124G > A. The 20.7% frequency of TERTp mutations in adenomas contrasts with the absence of mutations in the adenomas from the control group and from most series on record, whereas the one found in carcinomas (11.8%) is similar to those reported in the literature for sporadic carcinomas. CONCLUSION: TERTp mutations, including the tandem mutation -124/-125 GG>AA not described previously in thyroid tumours, appear to represent a genetic signature for thyroid tumours in patients submitted to low-dose X-ray irradiation. The high frequency of TERTp mutations in the adenomas of our cohort contrasts with their absence in sporadically occurring, as well as in adenomas of the Chernobyl series.

Thyroid and parathyroid tumours in patients submitted to X-ray scalp epilation during the tinea capitis eradication campaign in the North of Portugal (1950-1963).

Tinea capitis attained epidemical proportions in the fifth and sixth decades in Portugal, as in other countries. Before starting the utilization of griseofulvin in 1959, the best approach to treat tinea capitis infection was X-ray scalp epilation combined with topical antimycotic ointments. A long-term side effect of this therapy is thyroid disease, namely thyroid cancer; data on parathyroid lesions (hyperplasia, adenoma and carcinoma) are scarce. We observed clinically 1,375 individuals irradiated in childhood for tinea capitis treatment in the North of Portugal with the main purpose of evaluating thyroid and parathyroid tumours as possible sequelae of the irradiation treatment. For each individual, a cervical ultrasound and a serum calcium measurement were proposed. Fine needle aspiration cytology was suggested whenever ultrasound thyroid nodules presented suspicious features. We observed a 54 % frequency of thyroid nodules and a 2.8 % frequency of thyroid carcinoma (38/1,375). Nineteen of the 38 (50 %) carcinomas were diagnosed by us, whereas the remaining 19 carcinomas had been diagnosed and treated prior to our observation. The carcinomas were significantly more frequent in women than in men. Benign excised lesions were also significantly more frequent in women and in patients irradiated at younger ages. Seven women, considered asymptomatic until our clinical observation, had laboratory signs of hyperparathyroidism. The data we have obtained, namely high thyroid cancer frequency, corroborate previous data from childhood irradiated cohorts and highlight the need for the close follow-up of these populations in order to identify and treat early undiagnosed head and neck lesions. No evidence of increased parathyroid disease was found in this cohort of head and neck X-irradiated patients.

Mitochondrial D310 D-Loop instability and histological subtypes in radiation-induced cutaneous basal cell carcinomas.

BACKGROUND: Basal cell carcinoma (BCC) is the most frequent skin cancer. An elevated prevalence of BCC has been associated with radiation, namely after the Tinea capitis epilation treatment, being these tumors described as more aggressive. Mitochondrial DNA (mtDNA) mutations have been reported in many human tumors, but their occurrence in BCC is poorly documented. OBJECTIVE: The purpose of this work was to evaluate BCC histological subtypes in individuals subjected to X-ray epilation for Tinea capitis treatment when compared to non-irradiated patients. Moreover we also wanted to evaluate mitochondrial D-Loop instability in both groups of BCCs in order to compare the frequency of D-Loop mutations in post-irradiation BCC versus sporadic BCC. METHODS: 228 histological specimens corresponding to BCCs from 75 irradiated patients and 60 non-irradiated patients were re-evaluated for histological subtype. Subsequently, we sequenced the D-Loop 310 repeat in blood, oral mucosa, tumor lesions and, whenever available, non-tumoral adjacent tissue from these patients. RESULTS: The infiltrative subtype of BCC, considered to be more aggressive, was significantly more frequent in irradiated patients. BCC D-Loop D310 mutation rate was significantly higher in irradiated BCCs than in the non-irradiated ones. Moreover, it was associated with a higher irradiation dose. The presence of mtDNA heteroplasmy in patients' blood was associated with a higher mutation rate in the BCCs suggesting that a more unstable genotype could predispose to mtDNA somatic mutation. CONCLUSIONS: Our results suggest that radiation-induced BCCs may be considered to be more aggressive tumors. Further studies are needed to clarify the role of mtDNA D-Loop mutations in tumors from irradiated patients.

Genetic alterations in thyroid tumors from patients irradiated in childhood for tinea capitis treatment.

OBJECTIVE: Exposure to ionizing radiation at young age is the strongest risk factor for the occurrence of papillary thyroid carcinoma (PTC). RET/PTC rearrangements are the most frequent genetic alterations associated with radiation-induced PTC, whereas BRAF and RAS mutations and PAX8-PPARG rearrangement have been associated with sporadic PTC. We decided to search for such genetic alterations in PTCs of patients subjected in childhood to scalp irradiation. DESIGN: We studied 67 thyroid tumors from 49 individuals irradiated in childhood for tinea capitis scalp epilation: 36 malignant (12 cases of conventional PTC (cPTC), two cPTC metastases, 20 cases of follicular variant PTC (FVPTC), one oncocytic variant of PTC and one follicular carcinoma) and 31 follicular thyroid adenomas. METHODS: The lesions were screened for the BRAF(V600E) and NRAS mutations and for RET/PTC and PAX8-PPARG rearrangements. RESULTS: BRAF(V600E) mutation was detected in seven of 14 (50%) cPTC and two of 20 FVPTC (10%) (P=0.019). NRAS mutation was present in one case of FVPTC (5%). RET/PTC1 rearrangement was found, by RT-PCR, in one of 17 cases (5.9%) and by fluorescence in situ hybridization in two of six cases (33%). PAX8-PPARG rearrangement was not detected in any carcinoma. None of the follicular adenomas presented any of the aforementioned genetic alterations. CONCLUSIONS: The prevalence of BRAF(V600E) mutation in our series is the highest reported in series of PTCs arising in radiation-exposed individuals. The prevalence of RET/PTC1 rearrangement fits with the values recently described in a similar setting.

[Cutaneous carcinoma induced by radiotherapy: a report of 31 cases]. / Carcinomes cutanés induits par la radiothérapie: a propos de 31 cas.

BACKGROUND: Depilatory radiotherapy was used in the sixties as a treatment for ringworm in Tunisia. Subsequently some of these patients developed radio-induced carcinomas of the scalp. AIM: To present the epidemiological, clinical, pathological,therapeutic features and out come of radio-induced cutaneous carcinomas. METHODS: We conducted a retrospective study performed in the dermatology department of the La Rabta hospital of Tunis over a 6- year-period recording all histologically confirmed carcinomas in patients irradiated in childhood for tinea capitis. RESULTS: Thirty one patients were included with 49 tumors: 47 basal cell carcinomas and 2 squamous cell carcinomas. The average latent period between the irradiation and the appearance of the carcinomas was of 35.7 years. The average age was 53 years. A male predominance was noted, with a sex ratioM/F of 6.75. Clinically, basal cell carcinomas were nodular in all cases. Surgery was indicated in 90% of cases. Cryosurgery and radiotherapy were used respectively in 1 and 2 patients. CONCLUSION: Our study shows that radio-induced cutaneous carcinomas are widely dominated by basal cell carcinoma. They arise, approximately, ten years earlier than carcinoma in patients with no history of scalp irradiation. However X-ray exposure does not seem to influence clinical or histological presentation, therapeutic modalities nor prognosis of these tumors. The prognosis of radioinduced cutaneous carcinomas was globally similar to that of other cutaneous carcinomas with same histological type and equivalent degree of invasion.

The mass campaign to eradicate ringworm among the Jewish community in Eastern Europe, 1921-1938.

Between the years 1921 and 1938, 27,600 children were irradiated during a mass campaign to eradicate ringworm among the Jewish community in East Europe. The ringworm campaign was the initiative of the American Jewish Joint Distribution Committee together with the Jewish health maintenance organization OZE (The Society for the Protection of Jewish Health). We describe this campaign that used x-rays to eradicate ringworm and its mission to enhance public health among Jewish communities in Eastern Europe during the period between the world wars. We discuss the concepts behind the campaign, the primary health agents that participated in it, and the latent medical ramifications that were found among children treated for ringworm, many years after treatment--pathologies that can be linked to the irradiation they received as children. Our research is based on historical archival materials in the United States, Europe, and Israel.