Takeshi Fukumoto

High expression of Mcl-1L via the MEK-ERK-phospho-STAT3 (Ser727) pathway protects melanocytes and melanoma from UVB-induced apoptosis.

Ultraviolet (UV) B is a major factor in melanomagenesis. This fact is linked to the resistance of melanocytes to UVB‐induced apoptosis. In this study, we characterized the involvement of Mcl‐1L in the regulation of UVB‐induced apoptosis in melanocytes and in melanoma cells. In melanocytes, apoptosis was not evident at 24 h after UVB irradiation. The Mcl‐1L expression increased after UVB irradiation, and the high Mcl‐1L expression continued for at least 24 h. This UVB‐dependent increase in Mcl‐1L was mediated by the MEK‐ERK‐pS‐STAT3 (STAT3 phosphorylated at Ser727) pathway. The Ser727 phosphorylation facilitated nuclear localization of STAT3. In melanoma cells, the expression levels of Mcl‐1L varied depending on the cell line. WM39 melanoma cells expressed high levels of Mcl‐1L via the MEK‐ERK‐pS‐STAT3 pathway and were resistant to UVB‐induced apoptosis without up‐regulation of Mcl‐1L. In melanocytes and in WM39 cells, transfection with Mcl‐1 siRNA promoted UVB‐induced apoptosis. Immunohistochemical studies showed that melanoma cells in in situ lesions expressed high amounts of Mcl‐1L. These results indicate that the high expression of Mcl‐1L mediated by the MEK‐ERK‐pS‐STAT3 pathway protects melanocytes and melanoma cells from UVB‐induced apoptosis.

Folic acid-induced anaphylaxis showing cross-reactivity with methotrexate: a case report and review of the literature.

Case report A 42-year-old, otherwise healthy, woman developed generalized urticaria and dyspnea 2 h after taking a folic acid-containing supplement. She was treated with intravenous hydrocortisone in an emergency hospital on February 10, 2007. She was referred to our clinic to determine the cause. Two years prior to this episode she had taken folic acid for 2 months without any symptoms. Laboratory tests revealed normal levels of serum immunoglobulin E (IgE) (123 U/mL; normal, < 300 U/mL) and folic acid (7.7 ng/mL; normal, > 3.1 ng/mL). Her liver function and blood cell counts were normal. IgE radioallergosorbent tests showed that her serum had no specific IgE against any pollen or food. She could safely ingest ordinary foods that contained folic acid.

Malignant melanoma with bone marrow involvement diagnosed from hypercalcemia: Development of a neural cell adhesion molecule stain.

Dear Editor, Hypercalcemia is a life-threatening complication in patients with cancer, but rarely in patients with malignant melanoma. We report a case of a malignant melanoma associated with bone marrow involvement, which was referred to us because of hypercalcemia. Neural cell adhesion molecule (NCAM) is a protein expressed in malignant melanoma. Some reports suggested that NCAM potentiates cellular invasion and metastasis of melanoma cells, although its function in melanoma progression remains unclear. In this case, immunohistochemical observation revealed dynamic changes in NCAM expression with strong expression in bone marrow metastases. A 29-year-old man presented with back pain. He had no relevant medical history. A physical skin examination revealed a black nodule on his right abdomen that had persisted for 1 year (Fig. 1a). Laboratory findings revealed mild leukocytosis, lactate dehydrogenase level of 357 IU/L (normal, 115–217), calcium level of 4.01 mmol/L (normal, 2.2–2.5) and phosphorus level of 0.326 mmol/L (normal, 0.77–1.5). His parathyroid hormone (PTH) level was in the low-normal range at 6 ng/L (normal, 15–65); his PTH-related peptide (PTH-rP) level was lower than normal. Other hormone levels were normal. Computed tomography showed multiple spinal fractures. Magnetic resonance imaging showed osteolysis with non-traumatic

Mucosal lichen sclerosus/lichen planus overlap syndrome with cutaneous lesions of lichen sclerosus

In 1994, Marren et al. proposed the new concept of mucosal lichen sclerosus (LS)/lichen planus (LP) syndrome, referring to the simultaneous presence of vulvar LS and oral lichenoid lesions [1]. The two important points of the concept of this syndrome are that: 1) the oral lichenoid lesions should be regarded as LS, or at least a distinct group, when associated with vulvar LS: and 2) that careful attention to malignant transformation is required not only for the vulvar LS but also for the oral LP. [...]

Infliximab for severe colitis associated with nivolumab followed by ipilimumab

Dear Editor, Therapeutic strategies for melanoma have improved with the development of immune checkpoint inhibitors (ICI), such as nivolumab and ipilimumab. Because nivolumab and ipilimumab have non-redundant signaling pathways, the efficacy of combination therapy (concurrent/sequential administration) of nivolumab and ipilimumab has been studied, and combination therapy was found to have high efficacy, albeit with highgrade or high-frequency immune-related adverse effects (irAE). Therefore, irAE management is important. Here, we report a Japanese patient with severe colitis associated with combination therapy involving nivolumab followed by ipilimumab, which was successfully treated with infliximab. The patient was a 77-year-old Japanese woman with a history of stage IIIc (pT4bN3M0) melanoma on her right toe without BRAF V600E mutation, who developed liver, pulmonary and skin metastases (Fig. 1a,b). Although she received 12 cycles of nivolumab (nine cycles of 2 mg/kg every 3 weeks; three cycles of 3 mg/kg every 2 weeks), the lesions persisted. Therefore, ipilimumab (3 mg/kg every 3 weeks) was

Rare case of vascular malformations in both skin and brain: Case report and published work review

Solitary venous malformation (VM) of the skin, previously known as cavernous hemangioma, is frequently observed in the dermatological field, but multiple acquired VM are rare. We present a case of multiple VM of the skin associated with multiple cerebral cavernous malformations (CCM) in a 70‐year‐old Japanese woman. In addition, we summarize seven reported similar cases, including the present case. That some reports have described concomitant VM of the skin and CCM, together with the present case, suggests a tight relationship or a common pathogenetic pathway between these two diseases.

Concomitant confluent and reticulated papillomatosis and acanthosis nigricans in an obese girl with insulin resistance successfully treated with oral minocycline: Case report and published work review

Concomitant confluent and reticulated papillomatosis (CRP) and acanthosis nigricans (AN) is rare. We present a case of concomitant CRP and obesity‐associated AN in a 12‐year‐old obese Japanese girl. Curiously, oral minocycline therapy, which has been shown to be effective for CRP, was effective against both CRP and AN. Possible mechanisms by which minocycline could have improved skin lesions of CRP and obesity‐associated AN are discussed. In addition, reports of concomitant CRP and obesity‐associated AN are reviewed. CRP and obesity‐associated AN share common clinicopathological features and some reports have described concomitant CRP and obesity‐associated AN. Together with the observation that skin lesions of CRP and obesity‐associated AN in the present case responded to oral minocycline therapy, these facts suggest a tight relationship or a common pathogenetic pathway between these pathologies.

Acquired dermal melanocytosis confined to the palm with a review of published cases of acquired dermal melanocytosis on the hands.

Acquired dermal melanocytosis (ADM) classically occurs on the face. However, extrafacial ADM including palmar ADM has been reported on rare occasions. We present the first report of ADM confined to the palm without ADM lesions in other regions in a 30‐year‐old Japanese woman. The patient presented with several interspersed macules up to 1 cm in diameter with poorly defined margins, containing faint slate‐gray spots 1–2 mm in diameter, on the left palm near the first and second fingers and on the palmar side of the first finger near the metacarpophalangeal joint. These slate‐gray spots were prominent on and around palmar creases and on wrinkles on the metacarpophalangeal joint. The patient was right hand‐dominant. Histopathological examination revealed scattered spindle‐shaped cells with melanin granules and melanophages in the upper to middle dermis. Pigment‐bearing spindle‐shaped cells were demonstrated to be dermal melanocytes because of positive staining for Melan‐A after melanin removal. We review the published work for ADM on the hands.

First‐genetic analysis of atypical phenotype of pseudoxanthoma elasticum with ocular manifestations in the absence of characteristic skin lesions

C. Baykal* Department of Dermatology and Venereology, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey *Correspondence: C. Baykal. E-mail: baykalc@istanbul.edu.tr References 1 Sachs C, Lipsker D. The molluscum pendulum necklace sign in tuberous sclerosis complex. a case series. A pathognomonic finding? J Eur Acad Dermatol Venereol 2017. https://doi.org/10.1111/jdv.14357. 2 Barbato MT, Criado PR, Silva AK, Averbeck E, Guerine MB, S a NB. Association of acanthosis nigricans and skin tags with insulin resistance. An Bras Dermatol 2012; 87: 97–104. 3 J o zwiak S, Schwartz RA, Janniger CK, Michałowicz R, Chmielik J. Skin lesions in children with tuberous sclerosis complex: their prevalence, natural course, and diagnostic significance. Int J Dermatol 1998; 37: 911–917. 4 Northrup H, Krueger DA, International Tuberous Sclerosis Complex Consensus Group. Tuberous sclerosis complex diagnostic criteria update: recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference. Pediatr Neurol 2013; 49: 243–254.

Coexistence of mucosa-associated lymphoid tissue lymphoma and systemic sclerosis showing positive for anticentromere antibody and anti-RNA polymerase III antibody: A case report and published work review

tions 4 months prior to the consultation and was treated with oral antibiotics at another clinic. However, new eruptions emerged, resulting in a swelling on the left facial side. Clinically, actinomycosis, external dental fistula and sporotrichosis were considered as differential diagnoses, but they were atypical. Histological examination of the nodule at the gonial angle revealed the infiltration of neutrophils, lymphocytes, and histiocytes and granulation tissue with capillary vessels and fibroblasts. Gram and Grocott stains were negative, and blood test findings were normal. Bacterial culture of the tissue was identified as Acinetobacter lwoffii, mycobacterial and fungal cultures were negative. Computed tomography revealed high-density fat tissue in the left cheek. The patient confirmed having undergone thread-lifting (SpringThread ; 1st SurgiConcept, Tourcoing, France) 5 months prior to symptom onset. Accordingly, we diagnosed this case as skin ulcers induced by infection due to SpringThread. The left cheek swelling improved after the removal of the infected sutures(Fig. 1c,d) and the ulcers healed leaving a scar (Fig. 1e,f). Thread-lifting is a procedure for facial lifting achieved by leaving a special thread with cog in the subcutaneous tissue. It is often used in the field of cosmetic dermatology for lifting up sagged cheeks and the lower jaw. Different commercial materials and several thread-lifting techniques are available. In our case, the X-tosis method was performed by crossing two threads into a V-shape at the temple. The former clinic used SpringThread, which comprises polyester sutures with silicon cogs attached in every direction. The effect of SpringThread is considered long term because the threads are non-absorbable. However, the patient should be monitored for infection in the long term. We found four cases of infection induced by threadlifting, with a similar unilateral infection in three cases. The period of onset after treatment varied (longest, 6 years). The cheek, nasolabial fold and temple are the most common infection sites because the sutures are usually left there, and suture removal is necessary for healing. Mycobacterium infections were observed in three cases and A. lwoffii, which is considered normal skin flora, was identified only in ours. Patients may visit a dermatology department for treatment rather than a cosmetic dermatology clinic for initial treatment because infection due to thread-lifting can occur after a long period. In these cases and in cases such as ours with characteristic unilateral ulcers on the face, obtaining cosmetic treatment history is imperative to avoid treatment delays and infection worsening. Doctors must alert their patients to the importance of infection control during the thread procedure, and threads be removed after treatment, if the above symptoms occur.