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BACKGROUND: Clinical factors associated with vitiligo in patients receiving anti-programmed cell death-1 (PD-1) remain unknown. OBJECTIVE: To better characterize the occurrence of vitiligo in patients receiving anti-PD-1. METHODS: The present single-center ambispective cohort study included patients with melanoma treated with anti-PD-1. Progression-free survival, overall survival, and objective tumor response were compared between patients with and those without vitiligo using Kaplan-Meier curves and the log-rank test. Demographic and clinical factors associated with vitiligo were evaluated using multivariate logistic regression. RESULTS: Of the 457 patients included in the study, vitiligo developed in 85 patients. The clinical presentation of vitiligo consisted of the presence of ovalar and multiple flecked white macules, mainly located on chronic sun-exposed areas. The presence of vitiligo was associated with a significant improvement in overall survival and progression-free survival (P < .001). A Cox proportional hazards model estimation demonstrated markedly improved survival in patients with vitiligo compared with those without vitiligo (aHR [overall survival], 0.20; 95% CI, 0.12-0.33; P < .001; and aHR [progression-free survival], 0.33; 95% CI, 0.23-0.47; P < .001). In the multivariate logistic regression analyses, men showed an independent increased risk of the development of vitiligo (odds ratio, 1.66). In contrast, the presence of pulmonary metastases was found to be an independent factor associated with a reduced risk of the development of vitiligo (odds ratio, 0.50). LIMITATIONS: Single-center ambispective cohort. CONCLUSION: Vitiligo in patients receiving anti-PD-1 for advanced melanoma is associated with a better outcome. A gender effect associated with the development of vitiligo will need further investigation.

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BACKGROUND: Traditionally, most cutaneous nevi show a gradient of HMB45 (human melanoma black 45) and negative PRAME (preferentially expressed antigen in melanoma) immunostaining, while melanomas often show irregularly positive, diffusely positive or completely negative HMB45 expression, and PRAME immunopositivity. However, we have occasionally observed benign halo nevi with loss of HMB45 gradient, raising diagnostic consideration for melanoma. The purpose of this study was to elucidate the expression pattern of HMB45 and PRAME in nevi with the halo phenomenon (NHP). METHODS: PRAME and HMB45 staining patterns in 20 cases of NHP and 16 cases of conventional nevi were evaluated using light microscopy. An HMB45 gradient was defined as immunopositivity in only superficial melanocytes. HMB45 aberrant expression consisted of superficial and deep immunopositivity. RESULTS: Aberrant HMB45 expression was observed in 10 of 20 NHP (50%). A gradient of HMB45 staining was seen in most conventional nevi, with only one showing focal weak expression in the deep dermis (6.3%). All cases of NHP and conventional nevi showed essentially negative immunostaining by PRAME. CONCLUSION: Aberrant HMB45 expression in NHP is not uncommon and may be a diagnostic pitfall. Negative PRAME immunostaining may be a reassuring finding to help differentiate halo nevus from malignant melanoma.

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RESEARCH QUESTION: Is the spatiotemporal phenomenology of the cytoplasmic halo during fertilization related to embryonic competence? DESIGN: Time-lapse images from 1009 zygotes were retrospectively analysed from 560 patients who underwent IVF with minimal stimulation and single vitrified-warmed blastocyst transfer between April 2017 and March 2018. Halo presence and morphokinetics were monitored and compared relative to embryo quality, blastocyst expansion and ongoing pregnancy. RESULTS: Halo was observed in 88% of fertilized oocytes. Embryos derived from zygotes without halo had significantly higher rates of rapid cleavage (P = 0.0004), cell fusion (P = 0.0028) and asymmetrical division (P = 0.0002) compared with those derived from zygotes with halo. Multivariate logistic regression analysis had significantly higher developmental rates compared with the expanded blastocyst stage in embryos displaying a halo, regardless of its distribution (adjusted odds ratio 0.435; P = 0.0004). Prolonged halo time intervals were significantly correlated with increased asymmetrical division at first cell division (P = 0.0412, P = 0.0088, respectively) and decreased developmental rates to expanded blastocyst stage (P = 0.0062, P = 0.0020, respectively). Additionally, prolonged presence of the cytoplasmic halo was associated with a decreased ongoing pregnancy rate (adjusted odds ratio 0.871; P = 0.006). Poor sperm quality and decreased oocyte diameter were correlated with absence of the cytoplasmic halo (P = 0.0477, P < 0.0001, respectively) or prolonged halo presence (P = 0.0139, P = 0.0002, respectively). CONCLUSIONS: Halo presence and morphokinetics are associated with cleavage patterns, development to blastocyst stage and ongoing pregnancy rate after single blastocyst transfer. Halo morphokinetics seems to reflect sperm and oocyte quality. Cytoplasmic halo might be valuable predictor for refining selection of more developmentally competent blastocysts.

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Halo nevi (HN), also known as Sutton's nevi or leukoderma acquisitum centrifugum, are nevomelanocytic nevi surrounded by a rim of depigmentation. A 9-year-old female presented with an asymptomatic solitary flesh-colored 0.75-cm-sized papule surrounded by depigmentation on the right cheek 1 month ago. The excisional biopsy demonstrated molluscum contagiosum and decreased basal layer pigmentation on Fontana-Masson stain. The halo phenomenon is often associated with an acquired nevus cell nevus, but has also been associated with a congenital nevus cell nevus, non-neuroectodermal lesions such as angiomas, seborrheic keratoses, lichen planus, sarcoid, psoriasis, involuting flat warts, and histiocytoma. Our patient had an unusual association of molluscum contagiosum with the halo phenomenon. We suppose that the halo phenomenon in this patient might have been provoked by the molluscum contagiosum virus. A halo nevus-like appearance suggests the possibility of disease other than nevus. In such cases, skin biopsy is required for confirmation.

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Halo phenomenon of nevus may be observed as a circular reaction, although it is unusual around tumors. A 29-year-old woman presented with a pigmented lesion on the cheek since three years. She noted whitening of the skin around the lesion almost after a year following its appearance. Dermatologic examination revealed a pigmented nodular lesion with a hypopigmented halo on the left infraorbital region. The clinical impression was halo nevus, whereas basal cell carcinoma (BCC) was considered in dermatoscopic differential diagnosis. The diagnosis was infiltrative-type BCC histopathologically. The persistence of a perilesional halo around an enlarging pigmented lesion should be carefully examined with accompanying dermatoscopic findings even in young patients for early diagnosis of tumoral lesions.

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Melanocytic nevi represent a widespread cutaneous finding. Nevertheless, the presence of mycosis fungoides and melanocytic nevi in the same location is an extremely rare event. We report the case of a patient affected by mycosis fungoides and treated with PUVA therapy, with complete remission of the disease. Eight years after therapy discontinuation, he presented epidermal scaling and an erythematous perinevic halo on 3 old melanocytic lesions, the clinical aspect of which was highly suggestive for Meyerson nevi. The histological and immunohistochemical examination of an excised melanocytic lesion revealed histological features consistent with the diagnosis of mycosis fungoides superimposed on junctional melanocytic nevi. The finding of patches of mycosis fungoides superimposed on melanocytic nevi is a rare event; the confounding clinical appearance with eczematous changes around a pre-existing nevus may recall the halo dermatitis known as Meyerson phenomenon; this highlights the importance of clinical and histological examination to make the correct diagnosis of dermatological diseases.

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Depigmented halos surrounding cutaneous lesions have been the common description of many diseases, including benign melanocytic nevus, acquired blue nevi, malignant melanoma and neurofibromatosis. To the best of our knowledge, a halo around seborrheic keratosis has not been reported in the Korean dermatologic literature, and only two cases have been described abroad. Though vitiligo is known to be frequently associated with this halo phenomenon, the exact etiopathogenesis of vitiligo and the halo phenomenon is still unknown. Herein, we report on a case of halo seborrheic keratosis in a patient with vitiligo.

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A 39-year-old man with poliosis of his lower eyelid lashes visited our clinic. He reported that his symptoms began with a few central lashes and then spread along the adjacent lashes during the ensuing 2 weeks. A pigmented nevus, approximately 4 mm in diameter, was identified just above the white lashes without surrounding skin depigmentation. No specific findings were identified with regard to the patient's general health or serologic and radiologic testing. Excisional biopsy of the pigmented nevus was performed. On histopathologic examination, infiltration of the dermis by numerous lymphocytes and melanophages was observed. The poliosis was ultimately diagnosed as a presenting sign of the halo phenomenon in the regressive stage of a melanocytic nevus.

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A 39-year-old man with poliosis of his lower eyelid lashes visited our clinic. He reported that his symptoms began with a few central lashes and then spread along the adjacent lashes during the ensuing 2 weeks. A pigmented nevus, approximately 4 mm in diameter, was identified just above the white lashes without surrounding skin depigmentation. No specific findings were identified with regard to the patient's general health or serologic and radiologic testing. Excisional biopsy of the pigmented nevus was performed. On histopathologic examination, infiltration of the dermis by numerous lymphocytes and melanophages was observed. The poliosis was ultimately diagnosed as a presenting sign of the halo phenomenon in the regressive stage of a melanocytic nevus.

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STUDY DESIGN: Retrospective study. PURPOSE: First, to examine the association between bone mineral density (BMD) and the halo phenomenon, and second, to investigate risk factors predisposing to the halo phenomenon and its correlation with clinical outcomes. OVERVIEW OF LITERATURE: The few in vivo studies regarding the relationship between pedicle screw stability and BMD have shown conflicting results. METHODS: Forty-four female patients who underwent spine fusion surgery due to spinal stenosis were included in this study. The halo phenomenon and fusion state were evaluated through plain radiographs performed immediately after surgery and through the final outpatient follow-up examination. BMD, osteoarthritis grade in the hip and knee joints, and surgical outcome were also evaluated. RESULTS: BMD was not related to the halo phenomenon, but age, absence of osteoarthritis in the knee, and non-union state were found to be significant risk factors for the halo phenomenon. However, the radiological halo phenomenon did not correlate with clinical outcome (visual analogue scale for back pain and leg pain). CONCLUSIONS: The halo phenomenon is a simple phenomenon that can develop during follow-up after pedicle screw fixation. It does not influence clinical outcomes, and thus it is thought that hydroxyapatite coating screws, expandable screws, cement augmentation, and additional surgeries are not required, if their purpose is to prevent the halo phenomenon.

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STUDY DESIGN: Retrospective study. PURPOSE: First, to examine the association between bone mineral density (BMD) and the halo phenomenon, and second, to investigate risk factors predisposing to the halo phenomenon and its correlation with clinical outcomes. OVERVIEW OF LITERATURE: The few in vivo studies regarding the relationship between pedicle screw stability and BMD have shown conflicting results. METHODS: Forty-four female patients who underwent spine fusion surgery due to spinal stenosis were included in this study. The halo phenomenon and fusion state were evaluated through plain radiographs performed immediately after surgery and through the final outpatient follow-up examination. BMD, osteoarthritis grade in the hip and knee joints, and surgical outcome were also evaluated. RESULTS: BMD was not related to the halo phenomenon, but age, absence of osteoarthritis in the knee, and non-union state were found to be significant risk factors for the halo phenomenon. However, the radiological halo phenomenon did not correlate with clinical outcome (visual analogue scale for back pain and leg pain). CONCLUSIONS: The halo phenomenon is a simple phenomenon that can develop during follow-up after pedicle screw fixation. It does not influence clinical outcomes, and thus it is thought that hydroxyapatite coating screws, expandable screws, cement augmentation, and additional surgeries are not required, if their purpose is to prevent the halo phenomenon.

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