Purpose: To evaluate the efficacy and toxicities of skin-directed radiotherapy (RT) in primary cutaneous T-cell lymphoma (CTCL). Materials and Methods: We retrospectively analyzed 57 CTCL lesions treated with skin-directed RT between January 2000 and December 2022. Lesions were categorized into three distinct groups: early-stage disease treated with local RT, advanced-stage disease treated with local RT, and advanced-stage disease treated with total skin electron beam therapy (TSEBT). Treatment outcomes, including response rates, recurrence patterns, and local progression probability, were assessed for each group. Results: Mycosis fungoides (MF) constituted 90.9% of the advanced-stage pathologies, while CD4+ primary cutaneous small/medium T-cell lymphoproliferative disorder was common in the early stage lesions (55%). Median RT doses were 30.6 Gy, 27 Gy, and 32 Gy for the local RT with early stage, the local RT with advanced stage, and TSEBT with advanced stage, respectively. The complete response rates were high across the groups: 95.5%, 70.8%, and 90.9%, respectively. Seven local recurrences (29.2%) occurred in the local RT group with advanced stage, while seven patients (63.6%) in the TSEBT group experienced local failure. All recurrences were observed in lesions and patients with MF. Acute toxicities were mainly grade 1 or 2, with no grade 3 or higher events. No significant association between RT dose and local progression rates in MF lesions was found. Conclusion Skin-directed RT in CTCL is effective for local control and well-tolerated with less toxicity.

Stevens-Johnson syndrome (SJS) and acute generalized exanthematous pustulosis (AGEP) are 2 distinct entities that can overlap within the spectrum of severe cutaneous adverse reaction (SCAR). AGEP is a self-limiting and drug-induced eruption characterized by sudden onset of sterile pustules, erythema, and sometimes fever. SJS, in contrast, is a severe form of SCAR that causes blistering and necrosis of the skin and mucosal membranes, often leading to significant morbidity and mortality. However, there are cases where patients may present with symptoms that overlap between AGEP and SJS, making it challenging to differentiate the 2 conditions. This report describes a 70-year-old male with nontuberculous mycobacterium tenosynovitis in the left hand, coinfected with methicillin-resistant coagulase-negative Staphylococcus and Klebsiella oxytoca. After administration of additional antibiotics, the patient developed fever and erythematous macules with purpuric centers on the trunk and the extremities. Further examination revealed marked leukocytosis and elevated C-reactive protein levels. Skin biopsy histopathology showed subcorneal intraepidermal pustule formation with neutrophil infiltration. The patient’s clinical course improved after cessation of the culprit drugs and treatment with a high-dose systemic steroid. This case highlights the rare occurrence of SJS/AGEP overlap and underscores the importance of prompt diagnosis and appropriate management of these SCAR.

Purpose: To evaluate the efficacy and toxicities of skin-directed radiotherapy (RT) in primary cutaneous T-cell lymphoma (CTCL). Materials and Methods: We retrospectively analyzed 57 CTCL lesions treated with skin-directed RT between January 2000 and December 2022. Lesions were categorized into three distinct groups: early-stage disease treated with local RT, advanced-stage disease treated with local RT, and advanced-stage disease treated with total skin electron beam therapy (TSEBT). Treatment outcomes, including response rates, recurrence patterns, and local progression probability, were assessed for each group. Results: Mycosis fungoides (MF) constituted 90.9% of the advanced-stage pathologies, while CD4+ primary cutaneous small/medium T-cell lymphoproliferative disorder was common in the early stage lesions (55%). Median RT doses were 30.6 Gy, 27 Gy, and 32 Gy for the local RT with early stage, the local RT with advanced stage, and TSEBT with advanced stage, respectively. The complete response rates were high across the groups: 95.5%, 70.8%, and 90.9%, respectively. Seven local recurrences (29.2%) occurred in the local RT group with advanced stage, while seven patients (63.6%) in the TSEBT group experienced local failure. All recurrences were observed in lesions and patients with MF. Acute toxicities were mainly grade 1 or 2, with no grade 3 or higher events. No significant association between RT dose and local progression rates in MF lesions was found. Conclusion Skin-directed RT in CTCL is effective for local control and well-tolerated with less toxicity.

Purpose: To evaluate the efficacy and toxicities of skin-directed radiotherapy (RT) in primary cutaneous T-cell lymphoma (CTCL). Materials and Methods: We retrospectively analyzed 57 CTCL lesions treated with skin-directed RT between January 2000 and December 2022. Lesions were categorized into three distinct groups: early-stage disease treated with local RT, advanced-stage disease treated with local RT, and advanced-stage disease treated with total skin electron beam therapy (TSEBT). Treatment outcomes, including response rates, recurrence patterns, and local progression probability, were assessed for each group. Results: Mycosis fungoides (MF) constituted 90.9% of the advanced-stage pathologies, while CD4+ primary cutaneous small/medium T-cell lymphoproliferative disorder was common in the early stage lesions (55%). Median RT doses were 30.6 Gy, 27 Gy, and 32 Gy for the local RT with early stage, the local RT with advanced stage, and TSEBT with advanced stage, respectively. The complete response rates were high across the groups: 95.5%, 70.8%, and 90.9%, respectively. Seven local recurrences (29.2%) occurred in the local RT group with advanced stage, while seven patients (63.6%) in the TSEBT group experienced local failure. All recurrences were observed in lesions and patients with MF. Acute toxicities were mainly grade 1 or 2, with no grade 3 or higher events. No significant association between RT dose and local progression rates in MF lesions was found. Conclusion Skin-directed RT in CTCL is effective for local control and well-tolerated with less toxicity.

Purpose: Vascular endothelial growth factor tyrosine kinase inhibitors (TKIs) have been the standard of care for advanced and metastatic clear cell renal cell carcinoma (ccRCC). However, the therapeutic effect of TKI monotherapy remains unsatisfactory given the high rates of acquired resistance to TKI therapy despite favorable initial tumor response. Materials and Methods: To define the TKI-resistance mechanism and identify new therapeutic target for TKI-resistant ccRCC, an integrative differential gene expression analysis was performed using acquired resistant cohort and a public dataset. Sunitinib-resistant RCC cell lines were established and used to test their malignant behaviors of TKI resistance through in vitro and in vivo studies. Immunohistochemistry was conducted to compare expression between the tumor and normal kidney and verify expression of pathway-related proteins. Results: Integrated differential gene expression analysis revealed increased interferon-induced transmembrane protein 3 (IFITM3) expression in post-TKI samples. IFITM3 expression was increased in ccRCC compared with the normal kidney. TKI-resistant RCC cells showed high expression of IFITM3 compared with TKI-sensitive cells and displayed aggressive biologic features such as higher proliferative ability, clonogenic survival, migration, and invasion while being treated with sunitinib. These aggressive features were suppressed by the inhibition of IFITM3 expression and promoted by IFITM3 overexpression, and these findings were confirmed in a xenograft model. IFITM3-mediated TKI resistance was associated with the activation of TRAF6 and MAPK/AP-1 pathways. Conclusions These results demonstrate IFITM3-mediated activation of the TRAF6/MAPK/AP-1 pathways as a mechanism of acquired TKI resistance, and suggest IFITM3 as a new target for TKI-resistant ccRCC.

Stevens-Johnson syndrome (SJS) and acute generalized exanthematous pustulosis (AGEP) are 2 distinct entities that can overlap within the spectrum of severe cutaneous adverse reaction (SCAR). AGEP is a self-limiting and drug-induced eruption characterized by sudden onset of sterile pustules, erythema, and sometimes fever. SJS, in contrast, is a severe form of SCAR that causes blistering and necrosis of the skin and mucosal membranes, often leading to significant morbidity and mortality. However, there are cases where patients may present with symptoms that overlap between AGEP and SJS, making it challenging to differentiate the 2 conditions. This report describes a 70-year-old male with nontuberculous mycobacterium tenosynovitis in the left hand, coinfected with methicillin-resistant coagulase-negative Staphylococcus and Klebsiella oxytoca. After administration of additional antibiotics, the patient developed fever and erythematous macules with purpuric centers on the trunk and the extremities. Further examination revealed marked leukocytosis and elevated C-reactive protein levels. Skin biopsy histopathology showed subcorneal intraepidermal pustule formation with neutrophil infiltration. The patient’s clinical course improved after cessation of the culprit drugs and treatment with a high-dose systemic steroid. This case highlights the rare occurrence of SJS/AGEP overlap and underscores the importance of prompt diagnosis and appropriate management of these SCAR.

Stevens-Johnson syndrome (SJS) and acute generalized exanthematous pustulosis (AGEP) are 2 distinct entities that can overlap within the spectrum of severe cutaneous adverse reaction (SCAR). AGEP is a self-limiting and drug-induced eruption characterized by sudden onset of sterile pustules, erythema, and sometimes fever. SJS, in contrast, is a severe form of SCAR that causes blistering and necrosis of the skin and mucosal membranes, often leading to significant morbidity and mortality. However, there are cases where patients may present with symptoms that overlap between AGEP and SJS, making it challenging to differentiate the 2 conditions. This report describes a 70-year-old male with nontuberculous mycobacterium tenosynovitis in the left hand, coinfected with methicillin-resistant coagulase-negative Staphylococcus and Klebsiella oxytoca. After administration of additional antibiotics, the patient developed fever and erythematous macules with purpuric centers on the trunk and the extremities. Further examination revealed marked leukocytosis and elevated C-reactive protein levels. Skin biopsy histopathology showed subcorneal intraepidermal pustule formation with neutrophil infiltration. The patient’s clinical course improved after cessation of the culprit drugs and treatment with a high-dose systemic steroid. This case highlights the rare occurrence of SJS/AGEP overlap and underscores the importance of prompt diagnosis and appropriate management of these SCAR.

Purpose: To evaluate the efficacy and toxicities of skin-directed radiotherapy (RT) in primary cutaneous T-cell lymphoma (CTCL). Materials and Methods: We retrospectively analyzed 57 CTCL lesions treated with skin-directed RT between January 2000 and December 2022. Lesions were categorized into three distinct groups: early-stage disease treated with local RT, advanced-stage disease treated with local RT, and advanced-stage disease treated with total skin electron beam therapy (TSEBT). Treatment outcomes, including response rates, recurrence patterns, and local progression probability, were assessed for each group. Results: Mycosis fungoides (MF) constituted 90.9% of the advanced-stage pathologies, while CD4+ primary cutaneous small/medium T-cell lymphoproliferative disorder was common in the early stage lesions (55%). Median RT doses were 30.6 Gy, 27 Gy, and 32 Gy for the local RT with early stage, the local RT with advanced stage, and TSEBT with advanced stage, respectively. The complete response rates were high across the groups: 95.5%, 70.8%, and 90.9%, respectively. Seven local recurrences (29.2%) occurred in the local RT group with advanced stage, while seven patients (63.6%) in the TSEBT group experienced local failure. All recurrences were observed in lesions and patients with MF. Acute toxicities were mainly grade 1 or 2, with no grade 3 or higher events. No significant association between RT dose and local progression rates in MF lesions was found. Conclusion Skin-directed RT in CTCL is effective for local control and well-tolerated with less toxicity.

Stevens-Johnson syndrome (SJS) and acute generalized exanthematous pustulosis (AGEP) are 2 distinct entities that can overlap within the spectrum of severe cutaneous adverse reaction (SCAR). AGEP is a self-limiting and drug-induced eruption characterized by sudden onset of sterile pustules, erythema, and sometimes fever. SJS, in contrast, is a severe form of SCAR that causes blistering and necrosis of the skin and mucosal membranes, often leading to significant morbidity and mortality. However, there are cases where patients may present with symptoms that overlap between AGEP and SJS, making it challenging to differentiate the 2 conditions. This report describes a 70-year-old male with nontuberculous mycobacterium tenosynovitis in the left hand, coinfected with methicillin-resistant coagulase-negative Staphylococcus and Klebsiella oxytoca. After administration of additional antibiotics, the patient developed fever and erythematous macules with purpuric centers on the trunk and the extremities. Further examination revealed marked leukocytosis and elevated C-reactive protein levels. Skin biopsy histopathology showed subcorneal intraepidermal pustule formation with neutrophil infiltration. The patient’s clinical course improved after cessation of the culprit drugs and treatment with a high-dose systemic steroid. This case highlights the rare occurrence of SJS/AGEP overlap and underscores the importance of prompt diagnosis and appropriate management of these SCAR.

Stevens-Johnson syndrome (SJS) and acute generalized exanthematous pustulosis (AGEP) are 2 distinct entities that can overlap within the spectrum of severe cutaneous adverse reaction (SCAR). AGEP is a self-limiting and drug-induced eruption characterized by sudden onset of sterile pustules, erythema, and sometimes fever. SJS, in contrast, is a severe form of SCAR that causes blistering and necrosis of the skin and mucosal membranes, often leading to significant morbidity and mortality. However, there are cases where patients may present with symptoms that overlap between AGEP and SJS, making it challenging to differentiate the 2 conditions. This report describes a 70-year-old male with nontuberculous mycobacterium tenosynovitis in the left hand, coinfected with methicillin-resistant coagulase-negative Staphylococcus and Klebsiella oxytoca. After administration of additional antibiotics, the patient developed fever and erythematous macules with purpuric centers on the trunk and the extremities. Further examination revealed marked leukocytosis and elevated C-reactive protein levels. Skin biopsy histopathology showed subcorneal intraepidermal pustule formation with neutrophil infiltration. The patient’s clinical course improved after cessation of the culprit drugs and treatment with a high-dose systemic steroid. This case highlights the rare occurrence of SJS/AGEP overlap and underscores the importance of prompt diagnosis and appropriate management of these SCAR.