Pleomorphic dermal sarcoma presenting in a child with Li-Fraumeni syndrome: A case report and review of the literature.

Pleomorphic dermal sarcoma (PDS) is an uncommon malignant soft-tissue tumor that occurs mostly in elderly patients, with only 5% of cases occurring in children. However, pediatric patients with Li-Fraumeni syndrome (LFS) can develop several types of cancer, particularly sarcomas. Here, we describe a young LFS patient who presented with early-onset PDS and review the literature.

Clinical characteristics and survival analysis of cutaneous metastases in a single tertiary centre in Korea.

BACKGROUND: Cutaneous metastasis (CM) refers to the spread of malignancy to the skin. CM is perceived as an advanced stage. It might be the first sign of a primary cancer or an indicator of recurrence. OBJECTIVES: To identify primary cancers associated with CMs and perform a survival analysis according to advanced stage of cutaneous metastasis at a single tertiary centre in Korea. METHODS: A total of 219 patients from Samsung Medical Center from January 2009 to April 2020 were retrospectively analysed to identify cases with biopsy-proven CMs. According to advanced stage of metastasis, patients were divided into three stages, CM only (CMO), CM with lymph node metastasis (CM/LM) and CM with distant metastasis (CM/DM), to analyse clinical characteristics and survival rate. RESULTS: The most common CM from primary cancer was breast cancer, followed by lung cancer, stomach cancer, colorectal cancer and others. When all primary cancers were included, the median survival period was 4.82 years for the CMO stage, 2.15 years for the CM/LM stage and 0.80 years for the CM/DM stage, with a tendency to deteriorate with advancing stage. At 1- and 3-year after occurrence of CM, the CM/DM stage showed a significantly poorer survival rate than the other two stages. CONCLUSIONS: This study showed a median survival period of 22 months for CM patients overall. Breast cancer has greater accessibility to the skin than other cancers. Therefore, breast cancer can metastasize to the skin without involving lymph nodes or other sites.

The long-term risk of lymphoma and skin cancer did not increase after topical calcineurin inhibitor use and phototherapy in a cohort of 25,694 patients with vitiligo.

BACKGROUND: Topical calcineurin inhibitors have been used to treat vitiligo, either alone or in combination with phototherapy; however, the long-term safety of these agents remains controversial. OBJECTIVE: To investigate the risk of lymphoma and skin cancer in vitiligo patients who received topical calcineurin inhibitors or phototherapy. METHODS: A multicenter retrospective cohort study of 25,694 vitiligo patients who received topical calcineurin inhibitors or phototherapy for 6 weeks or more between 2001 and 2019 was performed. Cumulative doses of topical calcineurin inhibitors and total phototherapy sessions were determined. Outcomes were the development of lymphoma or skin cancer after enrollment, confirmed through chart review and pathology reports. RESULTS: During 95,203 person-years, 13 cases of lymphoma, 22 of actinic keratosis, 15 of nonmelanoma skin cancer, and 5 of melanoma were observed. The risk of lymphoma and skin cancer was not significantly increased by topical calcineurin inhibitor dose or phototherapy sessions. The interaction between the topical calcineurin inhibitors and phototherapy was not associated with an increased risk of skin cancer. LIMITATIONS: Retrospective study, individual follow-up duration less than 4 years, and no adjustment for comorbidities and medication history. Not generalizable to other races. CONCLUSION: The long-term risk of skin cancer or lymphoma was not associated with the use of topical calcineurin inhibitors, phototherapy, and both treatments in combination in patients with vitiligo.

Duration of Oral Antibiotics Administration for Cetuximab-Induced Acneiform Eruption.

BACKGROUND: Acneiform eruption is the most common cutaneous adverse event associated with cetuximab. As it can affect quality of life and adversely affect chemotherapy schedule, additional medical care is required. OBJECTIVES: To investigate the adherence to and the duration of antibiotic administration to treat cetuximab-induced acneiform eruption. METHODS: Medical data of patients who were referred to the Department of Dermatology were reviewed from January 2013 to June 2018. Dermatologists assessed the severity of acneiform eruption and prescribed tetracycline-class antibiotics according to the severity every 2 or 4 weeks. We investigated the duration and amount of oral antibiotic administration and analyzed the factors that may affect the control of acneiform eruption statistically. RESULTS: A total of 207 of 267 patients referred to the Department of Dermatology showed acneiform eruption; 124 patients were treated with minocycline, 34 patients with doxycycline, 27 patients with both, and 22 patients with topical agents. The mean duration of oral antibiotic medication was 82.7 days. A statistical analysis of the factors that prolonged the use of antibiotics for more than 90 days showed that male and younger age were risk factors. Shorter time interval from starting cetuximab to starting antibiotics was associated with longer duration of antibiotic use, statistically. CONCLUSIONS: Cetuximab-induced acneiform eruption can be well controlled with tetracycline-class antibiotics in about 3 months. It can last longer in male and younger patients. The sooner and the more severe it appears, the longer it can last.

Development of evidence-based consensus on critical issues in the management of patients with vitiligo: A modified Delphi study.

BACKGROUND/PURPOSE: Vitiligo remains a major challenge in dermatology. However, much of the treatment remains unclear, because little evidence is available. We sought to answer some critical questions pertaining to management of vitiligo patients. METHODS: A modified Delphi process among 31 vitiligo experts was conducted. A total of 12 clinical vitiligo treatment questions without clear answers were collected via a vote. To address each question, two members performed systematic literature reviews and prepared draft statements along with the levels of evidence and strength of recommendation. After reviewing the draft, all expressed their extent of agreement from 1 (strong disagreement) to 9 (strong agreement) for each item. The drafts were revised to reflect suggested comments. Discussion continued until all members agreed with the ultimate decision. RESULTS: The consensus process was completed after five rounds. We identified the best answers to 12 key questions, including issues on long-term phototherapy, systemic and topical corticosteroids, topical calcineurin inhibitors, immunosuppressants, excimer laser treatment, and surgical interventions. CONCLUSION: This consensus would complement current guidelines and aid both physician and patient decision-making in the treatment of vitiligo.

Effect of photobiomodulation therapy on radiodermatitis in a mouse model: an experimental animal study.

This study aimed to evaluate the effect of photobiomodulation (PBM) for prevention of radiodermatitis in an irradiated mouse model and compare the efficacy of PBM using 633- or 830-nm wavelengths. Irradiated mice were randomly distributed into three groups: A (633 nm), B (830 nm), and C (without PBM). On post-irradiation days 7 and 21, we compared acute damage and recovery in treated skin samples to non-irradiated skin using H&E, Masson's trichrome, anti-CD45 and PCNA immunohistochemistry, and a TUNEL assay. Grade 3 radiodermatitis was evident only in group C. Compared with that in group C, the skin in groups A and B had significantly less epidermal hyperplasia, inflammatory cell infiltration, and thinner dermis on day 7 and less inflammatory cell infiltration, fewer apoptotic cells, and thinner dermis on day 21. However, there was no significant difference between groups A and B. This study indicates PBM could prevent severe radiodermatitis by reducing epidermal and dermal damage, inflammation, and apoptosis. There was no difference in PBM efficacy between the 633- and 830-nm wavelengths.

Permanent Chemotherapy-Induced Alopecia in Patients with Breast Cancer: A 3-Year Prospective Cohort Study.

BACKGROUND: Although chemotherapy-induced alopecia (CIA) is considered temporary, some patients report persistent alopecia several years after chemotherapy. There is, however, a paucity of long-term prospective data on the incidence and impact of permanent CIA (PCIA). The objective of our study was to estimate the long-term incidence of PCIA in a cohort of patients with breast cancer whose hair volume and density were measured prior to chemotherapy and who were followed for 3 years after chemotherapy. MATERIALS AND METHODS: Prospective cohort study of consecutive patients ≥18 years of age with postoperative diagnosis of stage I-III breast cancer expected to receive adjuvant chemotherapy at the outpatient breast cancer clinic at the Samsung Medical Center in Seoul, Korea, from February 2012 to July 2013 (n = 61). Objective hair density and thickness were measured using a noninvasive bioengineering device. RESULTS: The proportion of participants who had PCIA at 6 months and 3 years was 39.5% and 42.3%, respectively. PCIA was characterized in most patients by incomplete hair regrowth. Patients who received a taxane-based regimen were more likely to experience PCIA compared with patients with other types of chemotherapy. At a 3-year follow-up, hair thinning was the most common problem reported by study participants (75.0%), followed by reduced hair volume (53.9%), hair loss (34.6%), and gray hair (34.6%). CONCLUSION: PCIA is a common adverse event of breast cancer adjuvant cytotoxic chemotherapy. Clinicians should be aware of this distressing adverse event and develop supportive care strategies to counsel patients and minimize its impact on quality of life. IMPLICATIONS FOR PRACTICE: Knowledge of permanent chemotherapy-induced alopecia, an under-reported adverse event, should lead to optimized pretherapy counseling, anticipatory coping techniques, and potential therapeutic strategies for this sequela of treatment.

The concept of nail matrix onychodermis (onychomatricodermis) in the nail unit: Histology and elastin immunohistochemistry.

BACKGROUNDS: We previously demonstrated the presence of onychodermis below nail matrix and nail bed. Because nail matrix is a producer of nail plate, we hypothesized that onychodermis below nail matrix could be the nail counterpart of follicular dermal papilla. In this study, we sought to further characterize histologic, histochemical, and immunohistochemical features of nail matrix onychodermis. METHODS AND RESULTS: Hematoxylin and eosin slides of 10 polydactyly nail units and 10 nail matrix biopsies from children and adults were reviewed. In polydactyly nail units, the onychodermis beneath nail matrix was characterized by onychofibroblasts showing abundant cytoplasm, and this area was slightly separated from the undersurface of the nail matrix. Nail matrix biopsy specimens also showed similar histology in the nail matrix onychodermis. Alcian blue stain demonstrated mucin deposition in onychofibroblasts within the nail matrix onychodermis. Immunohistochemically, elastin was rarely expressed in the nail matrix onychodermis while it was strongly expressed in the dermis of other areas of polydactyly nail units. Elastin was not expressed in follicular dermal papilla of terminal hair follicles of the scalp. CONCLUSION: Our findings demonstrate the presence and localization of nail matrix onychodermis (onychomatricodermis). Our study also demonstrates similar elastin expression patterns in the onychomatricodermis and follicular dermal papilla.

Clinicopathologic features of 28 cases of nail matrix nevi (NMNs) in Asians: Comparison between children and adults.

BACKGROUND: Clinical distinction between nail matrix nevus (NMN) and subungual melanoma (SUM) can be challenging. More precise delineation of the clinicodermoscopic characteristics specific for NMNs is needed. OBJECTIVE: We sought to analyze the clinicopathologic features of childhood and adult NMNs and to propose clinicodermoscopic features that can aid in differentiating NMNs from SUM. METHODS: We retrospectively reviewed clinical, dermoscopic, and histologic findings of patients (20 children and 8 adults) in whom NMN was diagnosed between 2012 and 2015. RESULTS: Except for 2 cases of total melanonychia, the affected nails demonstrated longitudinal melanonychia sharply demarcated from the adjacent nail plate. Melanonychia was wider among children than among adults (P = .002). Nail dystrophy was more frequent in wider lesions (P = .028). Hutchinson's sign was observed in pediatric cases at the hyponychium and/or proximal nailfold cuticles. All hyponychial pigmentations demonstrated a longitudinal brush pigmentation pattern under dermoscopy. LIMITATIONS: This was a retrospective study of Asians in a single center. CONCLUSION: Our study is the largest case series to date of biopsy-confirmed NMNs. It highlighted important clinicodermoscopic differences between pediatric and adult NMNs. We propose that in pediatric cases of longitudinal melanonychia presenting as a sharply demarcated pigment band of even width, the presence of Hutchinson's sign with longitudinal brush pigmentation may favor a diagnosis of NMN over SUM.

Mutational profiling of acral melanomas in Korean populations.

The proportion of acral melanoma (AM) is much higher in Asian populations than in Caucasian populations. Although mutational profiles associated with AM have been discovered in Caucasian populations, knowledge of its genetic alterations in Asian populations is limited. To describe the molecular nature of AM in Korean patients, we performed mutational profiling of AM and matched normal tissues in patients. Fifty-one formalin-fixed paraffin-embedded AM samples and 32 matched pairs from patients' saliva DNA were analysed by next-generation sequencing. Only mutations confirmed via digital droplet PCR or in BRAF, KIT and NRAS, the most frequently altered cancer genes in cutaneous melanoma, were considered as positive. The relationship between mutational status and clinicopathological features were examined. Of the 47 AM patients screened, alteration of BRAF, NRAS and KIT genes was observed in 6.4%, 4.3% and 8.5%, respectively. We also tested matched normal tissues of patients to identify tumor-specific mutations. Examination of the mutational profile in a cohort of 28 primary melanomas and matched normal controls found BRAF mutations in two cases (7.1%), KIT mutations in three cases (10.7%) and CTNNB1 mutations in one case (3.6%). The BRAF, NRAS and KIT mutation status did not correlate with clinicopathological characteristics. Our results show that KIT, NRAS and BRAF hotspot mutations occur at a low frequency in Korean populations. We also observed a case with the CTNNB1 mutation, which raises the possibility that other pathways are associated with AM development.

CD13 is a marker for onychofibroblasts within nail matrix onychodermis: Comparison of its expression patterns in the nail unit and in the hair follicle.

BACKGROUND: We previously demonstrated the presence of onychodermis, a specialized mesenchymal cell population beneath the nail matrix and proximal nail bed demonstrating CD10 expression. We hypothesize that the onychodermis could be the nail analog of the follicular dermal papilla, which is known to express CD13. We compare CD13 expression patterns between specialized mesenchymes of nail and hair, and compare these findings with CD10 expression patterns. METHODS: CD10 and CD13 immunohistochemistry was performed on polydactyly and adult cadaveric nail units, and on hair follicles in scalp nevus sebaceus excision specimens. RESULTS: CD10 and CD13 were expressed in the mesenchyme below the nail matrix and nail bed. Stronger CD13 expression was observed in the mesenchyme containing onychofibroblasts below the nail matrix compared with that below the nail bed. CD10 was expressed in the dermal sheath of terminal hair follicles, but it was expressed in the dermal sheath and follicular dermal papilla of primitive hair follicles within nevus sebaceus lesions. CD13 was expressed in the dermal sheath and dermal papilla of terminal and primitive hair follicles. CONCLUSION: CD13 may be a marker for onychofibroblasts within nail matrix onychodermis. We demonstrate CD13 expression in the specialized mesenchymes of both nail and hair.

Surgical excision margin for primary acral melanoma.

BACKGROUND AND OBJECTIVES: This study aimed to evaluate treatment outcomes of acral melanoma (AM) based on the excision margin. METHODS: A retrospective cohort study was conducted for patients with primary AM, analyzing recurrence rates, local and in-transit recurrence-free survival (LITRFS), disease-free survival (DFS), and melanoma-specific survival (MSS). RESULTS: Data from 129 patients of AM were analyzed. In 53 patients with thin AM (thickness ≤1 mm), neither recurrence nor mortality occurred regardless of whether the excision margin was >1 cm or not. Seventy-six patients had thick AM (thickness >1 mm), including 36 treated with a <2 cm excision margin and 40 with a 2 cm margin. Multivariate analyses revealed that a 2 cm margin was associated with a reduced rate of local recurrence (HR, 0.120; P-value = 0.023) and LITR (HR, 0.187; P-value = 0.013) compared with a <2 cm margin. DFS and MSS did not differ between the two groups. CONCLUSIONS: Thin AM were successfully treated with a 1 cm excision margin. For thick AM, a 2 cm excision margin provided improved local control, compared with a <2 cm margin; however, this benefit did not translate into a survival gain. J. Surg. Oncol. 2016;114:933-939. © 2016 Wiley Periodicals, Inc.

Scattered atypical melanocytes with hyperchromatic nuclei in the nail matrix: diagnostic clue for early subungual melanoma in situ.

BACKGROUND: The lack of highly specific clinical and histopathological criteria has contributed to the delay in diagnosis of subungual melanoma in situ in its early stages. METHODS: Eighteen cases of subungual melanoma in situ, the largest series reported to date, were analyzed to characterize the clinical and histopathological findings of early stages of subungual melanoma in situ along with five cases of nail matrix nevus and five cases of subungual lentigo serving as histologic control. RESULTS: Clinically, longitudinal melanonychia was present in all 18 cases of subungual melanoma in situ, consisting of irregular dark brown to black streaks within a brown background with (11 cases) or without Hutchinson's sign. Histopathologically, variable shaped and sized, hyperchromatic nuclei surrounded by retraction artifact were present in all cases. Nine cases showed a significant increase in the number of atypical melanocytes with marked nuclear atypia, while the rest of the cases showed less noticeable changes in nail matrix including lower density of melanocytes and/or mild nuclear atypia. In 15 cases, the nuclear enlargement in some of the melanocytes was greater than two times that of the neighboring matrix cells. In the remaining three cases, the nuclei were enlarged to a much lesser degree. All cases displayed areas of haphazard and uneven distribution of solitary melanocytes and, although not observed in all cases, some degree of pagetoid spread was present in majority of the cases. In contrast, nail matrix nevi showed well-formed nests consisting of relatively monomorphous melanocytes with abundant cytoplasm and subungual lentigos consisted of subtle increase in the number of dendritic melanocytes in solitary units within the lower layers of the nail matrix. CONCLUSION: Increase in the number of scattered atypical melanocytes with large hyperchromatic nuclei in a partial nail matrix may provide a diagnostic clue to subungual melanoma in situ in concert with its clinical suspicion.

Cutaneous Lymphoma in Korea: A Nationwide Retrospective Study.

The epidemiological and clinicopathological features of cutaneous lymphoma may vary by geographical area. However, only a few large-scale epidemiological studies of cutaneous lymphoma have been performed, mainly in the USA and Europe. This aim of this study was to determine the recent characteristics of cutaneous lymphoma in Korea according to the WHO/EORTC classification. A total of 422 patients with newly diagnosed cutaneous lymphoma from January 2009 to December 2013 comprising 293 cases of mature T-cell and natural killer (NK)-cell lymphoma and 39 cases of mature B-cell lymphoma were retrospectively reviewed. The incidence of mature B-cell lymphoma was lower in Korea than in Europe and the USA. Diffuse large B-cell lymphoma was more prevalent in Korea than in Western countries. The incidence of extranodal NK/T-cell lymphoma, nasal-type was higher in Korea than in Western countries and Japan.

Acquired Bilateral Dyspigmentation on Face and Neck: Clinically Appropriate Approaches.

Facial dyspigmentation in Asian women often poses diagnostic and therapeutic challenges. Recently, a distinctive bilateral hyperpigmentation of face and neck has occasionally been observed. This study was performed to investigate the clinico-pathological features of this dyspigmentation as well as proper treatment approaches. We retrospectively investigated the medical records including photographs, routine laboratory tests, histopathologic studies of both lesional and peri-lesional normal skin and patch test of thirty-one patients presented acquired bizarre hyperpigmentation on face and neck. The mean age of patients was 52.3 years and the mean duration of dyspigmentation was 24.2 months. In histologic evaluations of lesional skin, a significantly increased liquefactive degeneration of basal layer, pigmentary incontinence and lymphocytic infiltration were noted, whereas epidermal melanin or solar elastosis showed no statistical differences. Among 19 patients managed with a step-by-step approach, seven improved with using only topical anti-inflammatory agents and moisturizer, and 12 patients gained clinical benefit after laser therapy without clinical aggravation. Both clinical and histopathologic findings of the cases suggest a distinctive acquired hyperpigmentary disorder related with subclinical inflammation. Proper step-by-step evaluation and management of underlying subclinical inflammation would provide clinical benefit.

Quantitative changes in skin composition parameters due to chemotherapy in breast cancer patients: a cohort study.

The objective of this study is to evaluate objective changes in water content, sebum content, transepidermal water loss (TEWL), and melanin due to breast cancer chemotherapy, and their association with subjective symptoms. Prospective cohort study of 61 patients 18 years of age or older with a postoperative diagnosis of stage I-III breast cancer, who received adjuvant chemotherapy between February and September 2012 at an outpatient breast cancer clinic in Korea. Objective skin parameters, measured using a noninvasive bioengineering device, and patient-reported dryness and dullness were assessed before chemotherapy, after two cycles of chemotherapy, and 1, 3, and 6 months after completion of chemotherapy. Water content (-6.5 %), sebum (-75.5 %), and TEWL (-22.4 %) significantly decreased during chemotherapy compared to pre-chemotherapy levels (all p values <0.001). These parameters were lowest at 1 month after completion of chemotherapy and recovered thereafter but did not return to baseline levels after 6 months of follow-up. Melanin increased during chemotherapy with respect to pre-chemotherapy levels (8.4 %; p < 0.001) but decreased from the first month after completion of chemotherapy through the end of follow-up (-17.1 %; p < 0.001). The patterns of skin changes were similar in patients with or without hormone therapy. Most of patients reported dryness (57.9 %) and dullness (49.1 %) after chemotherapy, and patient-reported dryness was significantly associated with decreased sebum content. Chemotherapy-induced substantial changes in objective skin composition parameters. These changes persisted after 6 months from completion of chemotherapy and were associated with patient-reported symptoms. Additional research is needed to translate these findings into interventions for improving the dermatologic quality of life of breast cancer patients undergoing chemotherapy.

Histopathological analysis of the progression pattern of subungual melanoma: late tendency of dermal invasion in the nail matrix area.

Subungual melanoma is a rare subtype of melanoma that usually originates and spreads from the nail matrix. Because of its poor prognosis and short matrix-to-bone distance, amputation has been traditionally performed. Recently, conservative surgery has been attempted for early subungual melanoma, but the evidence supporting this practice is sparse. As little is known about the progression pattern of subungual melanoma, further advances on the subject may provide better guidance on the optimal surgical approach. Histopathology slides, clinical records, and photographs of 23 cases of subungual melanoma were reviewed. For all cases, each area of the nail unit-proximal nail fold, nail matrix, nail bed, and/or hyponychium-in longitudinal sections was available for histological examination. Growth pattern, dermal invasion, and thickness were assessed in each area of the nail unit. There were five cases of melanoma in situ. Eighteen cases showed dermal invasion in at least one area of the nail unit. There were no cases showing dermal invasion in the nail matrix area only. In four cases, dermal invasion involved areas of the nail unit other than the nail matrix. In 14 cases, dermal invasion involved the nail matrix area as well as other areas of the nail unit. Except for one case, the nail matrix area showed thinner dermal invasion compared with dermal invasion in other areas of the nail unit. In conclusion, dermal invasion of subungual melanoma in the nail matrix area tends to occur later than other areas of the nail unit. Longitudinal incisional biopsy is necessary to accurately evaluate melanoma invasion. The findings of this study suggest that conservative surgical treatment for early subungual melanoma may be justified as the nail matrix area, an area of thin dermis and close proximity to the underlying bone, appears to be more resistant to invasion.

The effectiveness of early treatment in segmental vitiligo: retrospective study according to disease duration.

Segmental vitiligo (SV) is usually characterized by a unilateral-dermatomal distribution, earlier onset and rapid progression followed by stabilization. The response to phototherapy in patients with SV is limited. We evaluated the treatment response in 39 cases of SV according to disease duration. Ten cases (50.0%) of Group 1 (duration ≤ 5 months) and five cases (26.3%) of Group 2 (duration > 5 months) showed more than 50% repigmentation. Contrary to previous reports, patients in our study responded well to medical treatments like oral steroids, topical calcineurin inhibitors and phototherapy when treated early after onset. The results suggest that early treatment is important.