Prevalence, clinical features, and survival outcome trends of 627 patients with primary cutaneous lymphoma over 29 years: a retrospective review from single tertiary center in Korea.

The relative frequency of primary cutaneous lymphoma (PCL) subtypes shows wide variation across different geographical regions. This retrospective study was conducted in a tertiary referral center located in Korea to describe the relative frequency, demographics, survival outcomes, and temporal trend in PCL. A total of 627 PCL cases diagnosed between January 1994 and December 2022 were included. The majority of PCL cases (87.2%) were of T-/NK-cell lineage (CTCL), while the remaining cases (12.8%) were B-cell lineage lymphomas (CBCL). The prevalence of mycosis fungoides (MF) in CTCL increased significantly over time, while other CTCL subtypes, including primary cutaneous extranodal NK/T-cell lymphoma and subcutaneous panniculitis-like T-cell lymphoma (SPTCL), decreased in frequency. Notably, the prevalence of CD4-positive small/medium T-cell lymphoproliferative disorder showed a substantial increase over time. Primary cutaneous marginal zone lymphoma was consistently the commonest CBCL subtype. Survival analysis demonstrated that CTCL had a more favorable 5-year overall survival (OS) than CBCL. OS rate of MF, SPTCL, and primary cutaneous peripheral T-cell lymphoma, NOS improved significantly over time. This study provides comprehensive insights into the dynamic change in the relative frequency and overall survival of PCL subtypes over time.

Risk of major adverse cardiovascular events and all-cause mortality among patients with psoriatic disease treated with tumor necrosis factor-α and interleukin-12/23 inhibitors: a nationwide population-based cohort study in Korea.

PURPOSE: Few studies have investigated the impact of biologics on the risk of major adverse cardiovascular events (MACEs) among Korean patients with psoriatic diseases. We compared the risk of MACEs and all-cause mortality among patients with psoriatic disease treated with tumor necrosis factor (TNF)-α and interleukin (IL)-12/23 inhibitors in Korea. METHODS: Patients with psoriatic disease prescribed with TNF-α and IL-12/23 inhibitors since 2016 were selected from the Korean National Health Insurance Service (NHIS) Database. Follow-up data for MACEs and all-cause mortality between 2016 and 2020 were collected. A total of 2886 individuals were included, including 1987 IL-12/23 inhibitor users and 899 TNF-α inhibitor users. RESULTS: Compared with IL-12/23 inhibitor users, TNF-α inhibitor users had a higher prevalence of dyslipidemia and a significantly higher risk of all-cause mortality but not MACE. After controlling for age, female TNF-α inhibitor users had a significantly increased risk of all-cause mortality. Meanwhile, after controlling for sex, TNF-α inhibitor users aged 60 years or older demonstrated a significantly elevated risk of all-cause mortality. In conclusion, No statistically significant difference in MACE risk was observed between patients who used TNF-α and IL-12/23 inhibitors. Nevertheless, the use of IL-12/23 inhibitors, especially among older and female patients, resulted in a lower overall mortality.

Clinicopathological characteristics and prognosis of Merkel cell carcinoma: a single-center retrospective study in Korea.

BACKGROUND: Merkel cell carcinoma (MCC) is an aggressive neuroendocrine tumor of the skin with high mortality. However, its clinical characteristics in Asian patients remain uncertain owing to its low incidence. OBJECTIVE: To analyze the clinicopathological features of MCC and identify factors associated with its prognosis. METHODS: The medical records of 62 patients with MCC were retrospectively reviewed. Data on clinical features, survival outcomes, prognostic factors, histopathology and immunohistochemical profile of the patients were collected and analyzed. Merkel cell polyomavirus status was evaluated using immunohistochemistry. RESULTS: The incidence of MCC significantly increased over time. The mean duration of follow-up was 51.2 months, with an overall 5-year survival of 80.6%. More female patients with MCC were identified than male patients (1.3:1). Approximately half of the patients had stage I disease at the time of initial presentation. The primary tumor was frequently located in the lower extremities (40.3%), followed by the head and neck (32.3%), upper extremities (22.6%), and the trunk (4.8%). Male sex was associated with poorer overall survival (p = 0.003). Post-resection adjuvant radiotherapy significantly improved the overall survival (p = 0.023). Sentinel lymph node biopsy during surgery ameliorated the progression-free survival (p = 0.036) in patients with stage I or II cancer. Lymphovascular and perineural invasion were associated with a poor prognosis. Old age, immunohistochemical profiles, and Merkel cell polyomavirus-positivity were not associated with prognosis. CONCLUSION: Post-surgical adjuvant radiotherapy and sentinel lymph node biopsy significantly improve the course of MCC.

Evaluation of Artificial Intelligence-Assisted Diagnosis of Skin Neoplasms: A Single-Center, Paralleled, Unmasked, Randomized Controlled Trial.

TRIAL DESIGN: This was a single-center, unmasked, paralleled, randomized controlled trial. METHODS: A randomized trial was conducted in a tertiary care institute in South Korea to validate whether artificial intelligence (AI) could augment the accuracy of nonexpert physicians in the real-world settings, which included diverse out-of-distribution conditions. Consecutive patients aged >19 years, having one or more skin lesions suspicious for skin cancer detected by either the patient or physician, were randomly allocated to four nondermatology trainees and four dermatology residents. The attending dermatologists examined the randomly allocated patients with (AI-assisted group) or without (unaided group) the real-time assistance of AI algorithm (https://b2020.modelderm.com#world; convolutional neural networks; unmasked design) after simple randomization of the patients. RESULTS: Using 576 consecutive cases (Fitzpatrick skin phototypes III or IV) with suspicious lesions out of the initial 603 recruitments, the accuracy of the AI-assisted group (n = 295, 53.9%) was found to be significantly higher than those of the unaided group (n = 281, 43.8%; P = 0.019). Whereas the augmentation was more significant from 54.7% (n = 150) to 30.7% (n = 138; P < 0.0001) in the nondermatology trainees who had the least experience in dermatology, it was not significant in the dermatology residents. The algorithm could help trainees in the AI-assisted group include more differential diagnoses than the unaided group (2.09 vs. 1.95 diagnoses; P = 0.0005). However, a 12.2% drop in Top-1 accuracy of the trainees was observed in cases in which all Top-3 predictions given by the algorithm were incorrect. CONCLUSIONS: The multiclass AI algorithm augmented the diagnostic accuracy of nonexpert physicians in dermatology.

Clinical characteristics and long-term outcomes of 97 Korean patients with mycosis fungoides.

BACKGROUND: Mycosis fungoides (MF) shows racial and regional differences in terms of clinical features. The availability of therapeutic options as well as drugs differs from one country to another. There are only limited data on the clinical characteristics and treatment experience of MF from South Korea. METHODS: Medical records of 97 patients with MF were retrospectively analyzed to investigate clinical features, survivals, and prognostic factors. Assessment of prognostic variables was done using univariate Cox proportional hazard models. RESULTS: Median age at time of diagnosis was 45 years. The median time from onset of skin lesion to diagnosis of MF was 36 months with a median follow-up period of 96 months. A number of clinical variants of MF were observed. Treatment mainly consisted of narrow-band UVB, systemic retinoids, methotrexate, chemotherapy, and regional radiotherapy. Complete remission was observed in 78% of patients with records on their clinical course. About 12% experienced disease progression. No clinical prognostic factor apart from TNM staging was identified. CONCLUSION: Despite delay in diagnosis, most cases of MF in Korea were diagnosed in early stages. Prognosis of our patients was more favorable than those of other geographic regions as reported in previous studies. Good response to treatment, consisting mainly of phototherapy and radiation therapy, and relatively indolent clinical behavior of disease were observed in this homogeneous cohort of Korean patients with MF.

Assessment of deep neural networks for the diagnosis of benign and malignant skin neoplasms in comparison with dermatologists: A retrospective validation study.

BACKGROUND: The diagnostic performance of convolutional neural networks (CNNs) for diagnosing several types of skin neoplasms has been demonstrated as comparable with that of dermatologists using clinical photography. However, the generalizability should be demonstrated using a large-scale external dataset that includes most types of skin neoplasms. In this study, the performance of a neural network algorithm was compared with that of dermatologists in both real-world practice and experimental settings. METHODS AND FINDINGS: To demonstrate generalizability, the skin cancer detection algorithm (https://rcnn.modelderm.com) developed in our previous study was used without modification. We conducted a retrospective study with all single lesion biopsied cases (43 disorders; 40,331 clinical images from 10,426 cases: 1,222 malignant cases and 9,204 benign cases); mean age (standard deviation [SD], 52.1 [18.3]; 4,701 men [45.1%]) were obtained from the Department of Dermatology, Severance Hospital in Seoul, Korea between January 1, 2008 and March 31, 2019. Using the external validation dataset, the predictions of the algorithm were compared with the clinical diagnoses of 65 attending physicians who had recorded the clinical diagnoses with thorough examinations in real-world practice. In addition, the results obtained by the algorithm for the data of randomly selected batches of 30 patients were compared with those obtained by 44 dermatologists in experimental settings; the dermatologists were only provided with multiple images of each lesion, without clinical information. With regard to the determination of malignancy, the area under the curve (AUC) achieved by the algorithm was 0.863 (95% confidence interval [CI] 0.852-0.875), when unprocessed clinical photographs were used. The sensitivity and specificity of the algorithm at the predefined high-specificity threshold were 62.7% (95% CI 59.9-65.1) and 90.0% (95% CI 89.4-90.6), respectively. Furthermore, the sensitivity and specificity of the first clinical impression of 65 attending physicians were 70.2% and 95.6%, respectively, which were superior to those of the algorithm (McNemar test; p < 0.0001). The positive and negative predictive values of the algorithm were 45.4% (CI 43.7-47.3) and 94.8% (CI 94.4-95.2), respectively, whereas those of the first clinical impression were 68.1% and 96.0%, respectively. In the reader test conducted using images corresponding to batches of 30 patients, the sensitivity and specificity of the algorithm at the predefined threshold were 66.9% (95% CI 57.7-76.0) and 87.4% (95% CI 82.5-92.2), respectively. Furthermore, the sensitivity and specificity derived from the first impression of 44 of the participants were 65.8% (95% CI 55.7-75.9) and 85.7% (95% CI 82.4-88.9), respectively, which are values comparable with those of the algorithm (Wilcoxon signed-rank test; p = 0.607 and 0.097). Limitations of this study include the exclusive use of high-quality clinical photographs taken in hospitals and the lack of ethnic diversity in the study population. CONCLUSIONS: Our algorithm could diagnose skin tumors with nearly the same accuracy as a dermatologist when the diagnosis was performed solely with photographs. However, as a result of limited data relevancy, the performance was inferior to that of actual medical examination. To achieve more accurate predictive diagnoses, clinical information should be integrated with imaging information.

Clinicopathological and survival analyses of primary cutaneous angiosarcoma in an Asian population: prognostic value of the clinical features of skin lesions.

BACKGROUND: Primary cutaneous angiosarcoma (CA) is a rare but aggressive tumor with a high rate of local recurrence. This study was designed to analyze the clinicopathological features of primary CA and identify factors of cutaneous manifestations associated with the prognosis of angiosarcoma. METHODS: Medical records of 55 patients with primary CA were retrospectively analyzed to investigate clinical features, survivals, and prognostic factors. Anatomical location of tumor was classified to the scalp, face, and neck, and sites outside the head and neck. RESULTS: Primary CA presented cutaneous nodules (31/55, 47.2%), patches (13/55, 23.6%), and indurated plaques (11/55, 20.0%). Nodular lesion was significantly more common in CA on the scalp compared to CA on sites outside the scalp. Histologically, tumors presenting as nodular lesions on the scalp was predominantly composed of solid sheets of large pleomorphic cells, whereas non-nodular lesions composed of tumor cells between collagen bundles forming irregular vascular spaces. Cutaneous angiosarcoma on the scalp showed a worse prognosis compared to CA on sites outside the scalp. Patients presenting clinical morphology with nodules and multiple skin lesions showed significantly reduced overall survival (OS). CONCLUSION: In primary CA, location on the scalp, morphology with nodules, and multiplicity of skin lesions significantly affected survival outcomes.

Keratinocytic Skin Cancer Detection on the Face Using Region-Based Convolutional Neural Network.

Importance: Detection of cutaneous cancer on the face using deep-learning algorithms has been challenging because various anatomic structures create curves and shades that confuse the algorithm and can potentially lead to false-positive results. Objective: To evaluate whether an algorithm can automatically locate suspected areas and predict the probability of a lesion being malignant. Design, Setting, and Participants: Region-based convolutional neural network technology was used to create 924 538 possible lesions by extracting nodular benign lesions from 182 348 clinical photographs. After manually or automatically annotating these possible lesions based on image findings, convolutional neural networks were trained with 1 106 886 image crops to locate and diagnose cancer. Validation data sets (2844 images from 673 patients; mean [SD] age, 58.2 [19.9] years; 308 men [45.8%]; 185 patients with malignant tumors, 305 with benign tumors, and 183 free of tumor) were obtained from 3 hospitals between January 1, 2010, and September 30, 2018. Main Outcomes and Measures: The area under the receiver operating characteristic curve, F1 score (mean of precision and recall; range, 0.000-1.000), and Youden index score (sensitivity + specificity -1; 0%-100%) were used to compare the performance of the algorithm with that of the participants. Results: The algorithm analyzed a mean (SD) of 4.2 (2.4) photographs per patient and reported the malignancy score according to the highest malignancy output. The area under the receiver operating characteristic curve for the validation data set (673 patients) was 0.910. At a high-sensitivity cutoff threshold, the sensitivity and specificity of the model with the 673 patients were 76.8% and 90.6%, respectively. With the test partition (325 images; 80 patients), the performance of the algorithm was compared with the performance of 13 board-certified dermatologists, 34 dermatology residents, 20 nondermatologic physicians, and 52 members of the general public with no medical background. When the disease screening performance was evaluated at high sensitivity areas using the F1 score and Youden index score, the algorithm showed a higher F1 score (0.831 vs 0.653 [0.126], P < .001) and Youden index score (0.675 vs 0.417 [0.124], P < .001) than that of nondermatologic physicians. The accuracy of the algorithm was comparable with that of dermatologists (F1 score, 0.831 vs 0.835 [0.040]; Youden index score, 0.675 vs 0.671 [0.100]). Conclusions and Relevance: The results of the study suggest that the algorithm could localize and diagnose skin cancer without preselection of suspicious lesions by dermatologists.

CD30-positive cutaneous extranodal natural killer/T-cell lymphoma: clinicopathological features and survival outcomes.

BACKGROUND: The prognostic value of CD30 expression in cutaneous extranodal natural killer/T-cell lymphoma is controversial. METHODS: Clinicopathological features, survival outcomes, and prognostic implications of CD30 were retrospectively analyzed in 55 patients with cutaneous extranodal natural killer/T-cell lymphoma. We classified patients into (i) primary cutaneous extranodal natural killer/T-cell lymphoma and (ii) cutaneous extranodal natural killer/T-cell lymphoma secondary to nasal disease depending on the primary tumor site. RESULTS: CD30+ cutaneous extranodal natural killer/T-cell lymphoma was more common in patients with cutaneous extranodal natural killer/T-cell lymphoma secondary to nasal disease than in those with primary cutaneous disease. CD30+ cases were more likely to present nodular lesions or cellulitis-like swelling than CD30- cases. Histologically, CD30+ cutaneous extranodal natural killer/T-cell lymphoma predominantly comprised large tumor cells compared with CD30- cases. However, the clinical morphology and tumor cell size were not associated with survival outcomes. CD30 expression was associated with better survival outcomes in patients with cutaneous extranodal natural killer/T-cell lymphoma secondary to nasal disease. CONCLUSION: CD30+ cutaneous extranodal natural killer/T-cell lymphoma presented peculiar clinicopathological features and had more favorable disease course in patients with cutaneous dissemination from nasal disease.

Primary cutaneous extranodal natural killer/T-cell lymphoma presenting as bilateral erythematous patches on the arms.

Natural killer/T-cell lymphoma is a rare, Epstein-Barr virus-associated type of cytotoxic lymphoma thatpresents mainly in the nasal cavity and its vicinity. Very few cases of primary cutaneous extranodal natural killer/T-cell lymphoma have been reported till date. All the previously reported cases of primary cutaneous extranodalnatural killer/T-cell lymphoma presented as lesions resembling cellulitis, subcutaneous nodules or ulcers. We report a rare case which presented as erythematous and purpuric round patches on the arms and was finally diagnosed as primary cutaneous extranodalnatural killer/T-cell lymphoma, following a skin biopsy. The atypical patchy lesions presented a diagnostic challenge. We herein describe this clinically novel atypical patch-like presentation of primary cutaneous extranodalnatural killer/T-cell lymphoma together with the key histopathologic features and highlights of the previously reported cases.

The Glutathione Derivative, GSH Monoethyl Ester, May Effectively Whiten Skin but GSH Does Not.

Glutathione in its reduced form (GSH) is an antioxidant and also is involved in pheomelanin formation. Thus, it has been long believed that GSH has a skin whitening effect. However, its actual or direct effect is unproven. We evaluated the anti-melanogenic effects of GSH and its derivatives in vitro. We examined change of melanogenesis and its related proteins by GSH itself and its derivatives, including GSH monoethyl ester (GSH-MEE), GSH diethyl ester (GSH-DEE) and GSH monoisopropyl ester (GSH-MIPE) in Melan-A cells, Mel-Ab cells, and B16F10 cells. GSH and GSH-MEE did not display cytotoxic activity, but GSH-MIPE and GSH-DEE did. Intriguingly, GSH itself had no inhibitory effect on melanin production or intracellular tyrosinase activity. Rather, it was GSH-MEE and GSH-MIPE that profoundly reduced the amount of melanin and intracellular tyrosinase activity. Thus, GSH-MEE was selected as a suitable candidate skin-whitening agent and it did not alter melanogenesis-associated proteins such as microphthalmia-associated transcription factor (MITF), tyrosinase, tyrosinase-related protein (TRP)-1, and TRP-2, but it did increase the amount of suggested pheomelanin and suggested pheomelanin/eumelanin ratio. GSH-MEE was effective for anti-melanogenesis, whereas GSH itself was not. GSH-MEE could be developed as a safe and efficient agent for the treatment of hyperpigmentation skin disorders.

Facial swelling: an atypical presentation of cutaneous lymphoma.

BACKGROUND: Cutaneous lymphomas (primary and secondary lymphomas involving the skin) are a heterogeneous group with various clinical manifestations, histological features, and prognoses. METHODS: We describe eight cases of cutaneous lymphoma presenting with facial swelling. RESULTS: Our case series included three cases of primary cutaneous extranodal natural killer/T-cell lymphoma, one case of secondary cutaneous extranodal natural killer/T-cell lymphoma, one case of subcutaneous panniculitis-like T-cell lymphoma, one case of cutaneous CD4+ small/medium pleomorphic T-cell lymphoma, and two cases of peripheral T-cell lymphoma (unspecified). CONCLUSIONS: This collection of cases and literature review emphasizes the need for clinical suspicion of cutaneous lymphoma in the differential diagnosis of patients with refractory facial swelling.

Relative Frequency, Clinical Features, and Survival Outcomes of 395 Patients with Cutaneous Lymphoma in Korea: A Subgroup Analysis per 10-year Period.

Long-term changes in the relative frequency of cutaneous lymphoma (CL) have not been investigated in Asian populations. The aim of this study was to investigate the relative frequency, clinical characteristics, and survival outcomes of CL in Korean patients, and to evaluate the changes in relative frequency of CL over a 20-year period. The present retrospective cohort study included 395 patients, of whom 289 had primary CL and 106 secondary CL, seen at a tertiary referral hospital in Seoul, Korea. Primary CL included T-/NK-cell linage lymphoma (CTCL, 85.1%) and B-cell lineage lymphoma (CBCL, 14.9%). The relative frequency of CBCL increased over time, as shown by a decrease in the CTCL/CBCL ratio from 10.3 in 1994 to 2003 to 4.5 in 2004 to 2013. CTCL was more commonly associated with multiple and extensive skin lesions than CBCL. Extranodal NK/T-cell lymphoma and subcutaneous panniculitis-like T-cell lymphoma were commonly associated with extensive skin lesions. The 5-year overall survival rate for all patients with primary CL was 81%.

Cutaneous anaplastic large-cell lymphoma (ALCL): A comparative clinical feature and survival outcome analysis of 52 cases according to primary tumor site.

BACKGROUND: Cutaneous anaplastic large-cell lymphoma (ALCL) is primary extranodal or secondary to nodal disease. OBJECTIVE: We sought to analyze clinical features and survival outcomes by primary tumor site in patients with cutaneous ALCL. METHODS: Clinical features, survival outcomes, and prognostic factors of 52 patients with primary or secondary cutaneous ALCL to primary nodal disease were retrospectively evaluated using medical records. RESULTS: Although skin lesion characteristics did not significantly differ between groups, the head and neck location was more common in primary cutaneous ALCL, whereas cutaneous lesion extent was greater in secondary cutaneous ALCL. Skin lesion extent in primary cutaneous ALCL was indicative of extracutaneous dissemination development and skin lesion relapse. Neither anaplastic lymphoma kinase expression nor clinical stage affected skin lesion characteristics in secondary cutaneous ALCL. Patients with primary rather than secondary cutaneous ALCL demonstrated better survival outcomes. The skin lesion extent and location on the leg were associated with the tendency toward a poorer prognosis in primary cutaneous ALCL. The secondary cutaneous ALCL prognosis was not influenced by skin lesion characteristics. LIMITATIONS: This was a retrospective study in a single institution. CONCLUSION: Survival outcomes and prognostic factors in cutaneous ALCL differed by primary tumor site.