No abstract

In the histopathological diagnosis of cutaneous tumors, the differential diagnosis of squamous cell carcinoma (SCC) with crateriform architecture and keratoacanthoma (KA) is often difficult so an accurate understanding of the biological features and the identification of reliable markers of SCC and KA are crucial issues. Insulin-like growth factor 2 mRNA-binding protein-3 (IGF2BP3, also known as IMP3) is thought of as a bona fide oncofetal protein, which is overexpressed and is involved in cell proliferation, migration, and invasion in several kinds of tumors. However, the role of IMP3 in cutaneous SCC and KA has not been well studied. Therefore, we focused on studying the biological functions of IMP3 in SCC and KA. In human skin SCC cell lines, HSC-1 and HSC-5, and the human keratinocyte cell line, HaCaT, IMP3 mRNA levels were significantly higher than that of normal human skin. The knockdown of IMP3 expression reduced the proliferation of HSC-1, and significantly reduced invasion by HSC-1 and HSC-5. In contrast, the knockdown of IMP3 did not significantly affect invasion by HaCaT cells. In immunohistochemical studies of SCC and KA tissues, the Ki-67 labeling index (LI) of the suprabasal cell layer was significantly higher in SCC, compared with KA tissues and the tumor-free margin (TFM) adjacent to SCC and KA. Most SCC tissues stained strongly positive for IMP3, but KA tissues and TFM were mostly negative for IMP3. The Ki-67 LI of the IMP3-positive group was significantly higher than that of the IMP3-negative group in the suprabasal cell layer of SCC. These results suggest that IMP3 plays an important role in proliferation and, more significantly, in the invasion of SCC, and may be a suitable marker for the histopathological diagnosis of SCC with a crateriform architecture and KA. Furthermore, IMP3 may potentially be a new therapeutic target for SCC.

The terminal complement inhibitor eculizumab was shown to improve myasthenia gravis-related symptoms in the 26-week, phase 3, randomized, double-blind, placebo-controlled REGAIN study (NCT01997229). In this 52week sub-analysis of the open-label extension of REGAIN (NCT02301624), eculizumab's efficacy and safety were assessed in 11 Japanese and 88 Caucasian patients with anti-acetylcholine receptor antibody-positive refractory generalized myasthenia gravis. For patients who had received placebo during REGAIN, treatment with openlabel eculizumab resulted in generally similar outcomes in the Japanese and Caucasian populations. Rapid improvements were maintained for 52 weeks, assessed by change in score from open-label extension baseline to week 52 (mean [standard error]) using the following scales (in Japanese and Caucasian patients, respectively): Myasthenia Gravis Activities of Daily Living (−2.4 [1.34] and − 3.3 [0.65]); Quantitative Myasthenia Gravis (−2.9 [1.98] and − 4.3 [0.79]); Myasthenia Gravis Composite (−4.5 [2.63] and − 4.9 [1.19]); and Myasthenia Gravis Quality of Life 15-item questionnaire (−8.6 [5.68] and − 6.5 [1.93]). Overall, the safety of eculizumab was consistent with its known safety profile. In this interim sub-analysis, the efficacy and safety of eculizumab in Japanese and Caucasian patients were generally similar, and consistent with the overall REGAIN population.

Objective To assess whether eculizumab, a terminal complement inhibitor, improves patient‐ and physician‐reported outcomes (evaluated using the myasthenia gravis activities of daily living profile and the quantitative myasthenia gravis scale, respectively) in patients with refractory anti‐acetylcholine receptor antibody‐positive generalized myasthenia gravis across four domains, representing ocular, bulbar, respiratory, and limb/gross motor muscle groups. Methods Patients with refractory anti‐acetylcholine receptor antibody‐positive generalized myasthenia gravis were randomized 1:1 to receive either placebo or eculizumab during the REGAIN study (NCT01997229). Patients who completed REGAIN were eligible to continue into the open‐label extension trial (NCT02301624) for up to 4 years. The four domain scores of each of the myasthenia gravis activities of daily living profile and the quantitative myasthenia gravis scale recorded throughout REGAIN and through 130 weeks of the open‐label extension were analyzed. Results Of the 125 patients who participated in REGAIN, 117 enrolled in the open‐label extension; 61 had received placebo and 56 had received eculizumab during REGAIN. Patients experienced rapid improvements in total scores and all four domain scores of both the myasthenia gravis activities of daily living profile and the quantitative myasthenia gravis scale with eculizumab treatment. These improvements were sustained through 130 weeks of the open‐label extension. Interpretation Eculizumab treatment elicits rapid and sustained improvements in muscle strength across ocular, bulbar, respiratory, and limb/gross motor muscle groups and in associated daily activities in patients with refractory anti‐acetylcholine receptor antibody‐positive generalized myasthenia gravis.

Association of psoriasis with Hashimoto's thyroiditis, Sjö gren's syndrome and dermatomyositisDear Editor, Psoriasis is an autoimmune chronic inflammatory skin disease and has been reported to coexist with other autoimmune diseases such as Hashimoto's thyroiditis, Sj€ ogren's syndrome and dermatomyositis. We describe here the first case of a combination of these four autoimmune diseases.A 52-year-old Japanese woman with Hashimoto's thyroiditis for 6 years visited our department in October 2006. Physical examination revealed edematous erythema on her face, neck, upper back and extremities. Her upper back was covered with itching edematous erythema suggesting shawl sign (Fig. 1a). She had a heliotrope rash on the upper eyelids ( Fig. 1b) and Gottron's sign on the knuckles ( Fig. 1c) with proximal muscle weakness. Abnormal laboratory findings were as follows: creatinine kinase, 187 IU/L (normal range, 50-170); myoglobin, 95 ng/mL (normal range, 0-65); thyroid-stimulating hormone, 7.1 lU/mL (normal, <5); antinuclear antibody, positive with a titer of 1:320; anti-SSA, more than 500 (normal, <7); and antithyroglobulin more than 100 (normal, <0.3). The skin biopsy from a forearm showed subtle vacuolar interface dermatitis with sparse superficial perivascular inflammation with increased mucin (Fig. 1d). The muscle biopsy from the left vastus lateralis muscle did not reveal an apparent muscle degeneration but lymphocyte infiltration of perimysium was found. The labial gland biopsy disclosed tightly aggregated lymphocytes surrounding a duct (>50 in 4 mm 2 ). From these findings, the diagnoses of Hashimoto's thyroiditis, Sj€ ogren's syndrome and dermatomyositis were made. She was treated with 60 mg prednisolone together with levothyroxine sodium hydrate with remarkable effect and gradually tapered off prednisolone.In July 2014, she visited us complaining of erythematic plaques with silvery scales on the face, neck, upper back (Fig. 1e), upper extremities and elbows of 2 months' duration without treatment by prednisolone. The skin biopsy from an elbow showed marked acanthosis of the epidermal ridges with parakeratosis, dilated capillaries and lymphocytic perivascular infiltration in the dermis (Fig. 1f). From the clinical and histological findings, the diagnosis of psoriasis was made. She was treated with topical corticosteroid and vitamin D 3 with remarkable effect. In November 2014, she visited us complaining of myalgia and symmetrical, proximal muscle weakness with a heliotrope rash, elevated creatinine kinase (226 IU/L) and positivity of anti-TIF-1 antibody, whereas psoriasis is well controlled. Being suspected of the recurrence of dermatomyositis, she was treated with 20 mg prednisolone. She is now being tapered off prednisolone together with the addition of 6 mg methotrexate and remains in clinically good condition both for dermatomyositis and psoriasis.Although there have been three reports of the association of psoriasis with Hashimoto's thyroiditis and Sj€ ogren's syndrome, 1-3 there has been no report of the coexis...