Arterial Imaging in Digital Gangrenes Associated with Scleroderma-Spectrum Disorders

Objectives: Digital refractory gangrene is rarely found in collagen diseases, including systemic sclerosis and is possibly caused by similar underlying vascular damage in peripheral arterial disease (PAD) such as arteriosclerosis obliterans (ASO) and/or thromboangiitis obliterans (TAO) by unclarified mechanisms other than vasculitis and thrombosis. This study evaluated the radiological imaging in patients with digital gangrene associated with collagen disease and compared the images with those of PAD based on the results of laboratory and histopathological examinations. Methods: Angiography, MR angiography and/or CT angiography were performed on 6 patients with refractory gangrene or extensive ulcers accompanied by scleroderma-spectrum disorders;3 with diffuse systemic sclerosis, 1 with limited systemic sclerosis, 1 with overlap syndrome and 1 with Sj?gren’s syndrome. Results: Although the vascular alterations in collagen diseases were similar to those in PAD, the abnormal image findings (occlusion or stenosis of the arteries with smooth vessel walls) found in collagen diseases did not include atheromatous plaque, which are worm-like vessels that are characteristic of those observed in PAD. Conclusions: Some cases of digital gangrene seen in collagen diseases show similar vascular imaging patterns to those of PAD and comprehensive examinations including arterial imaging can be useful for the diagnosis of these unrecognized vascular changes other than vasculitis or digital thrombosis.

The Disturbance of Melanogenesis and Melanosome Transfer in the Leukoderma Lesions of Extramammary Paget’s Disease

We frequently encounter characteristic color variation including hypopigmentation, hyperpigmentation, and erythema in extramammary Paget’s disease (EMPD) lesions. Owing to unclear hypopigmentation, the lesional border of EMPD can be poorly defined and it is likely insufficient to perform its complete resection. Although the existence of Toker’s cells and lack of lesional bFGF production have been reported to cause hypopigmentation inside of EMPD lesions, exact mechanisms of hypopigmentation in EMPD are not fully explored. We experienced three EMPD patients with obviously hypopigmented EMPD macules and histopathologically confirmed a reduced number of melanocytes on the hypopigmented macules and their loss on the erythematous plaques or nodules. An ultrastructural analysis on the hypopigmented lesions revealed disturbance of melanosome maturation and melanosome transfer to the adherent Pagets’ cell on the basal layer. No Paget’s cells even adhered to remaining melanocytes with dendrites contained matured melanosome and a few number of matured melanosome complexes were observed in basal keratinocytes. In the present study, we hypothesize that severe disturbance of not only melanogenesis but also melanosome transfer to surrounding Paget’s cells and basal keratinocytes may cause characteristic hypopigmentation in EMPD. Future bioanalysis would reveal molecular mechanisms for hypopigmentation in EMPD.

A Rare Case of Severe Muscular Necrosis Due to Extravascular Leakage of Trabectedin—Severe Tissue Damage of Trabectedin Extravasation

Trabectedin is a synthetic antineoplastic drug, binding to the minor groove of DNA and affecting DNA repair pathways, resulting in G2-M cell cycle arrest and apoptosis. Trabectedin has demonstrated high efficacy against various soft tissue sarcomas. However, its extravasation causes serious complications, such as tissue necrosis and a delay in the treatment of underlying diseases. Methods: We experienced a rare case in which trabectedin extravasation caused severe pectoralis major muscle necrosis. A 45-year-old man with multiple lung metastases of follicular dendritic cell sarcoma received 2.15 mg of trabectedin totally through a central venous access device (CVAD) system in the right precordium. Computed tomography showed extensive turbidity of subcutaneous fatty tissue and swelling of the pectoralis major muscle to the upper margin of the liver, and the creatine kinase level was elevated to 759 U/L (reference value from 54 to 286). We performed surgical debridement twice, and the CVAD was concomitantly removed;thereafter, the skin defect was reconstructed with a split skin mesh graft. Results: Histopathology showed extreme degeneration of striated muscle and fatty tissue. Unfortunately, disability of the right arm abducens persisted after treatment because of debridement around the right humerus muscle. Discussion: Several reports have described cases of the extravasation of trabectedin. A few have mentioned severe muscular degeneration similar to that shown in the present case. Because trabectedin is a strong vesicant cytotoxic agent, it is principally administered through a CVAD rather than peripheral vessels and is continued during the nighttime;this can lead to a delay in patients or attending doctors noticing any extravasation. We need to spread appropriate knowledge of this drug and make an effort to prevent severe complications like in the present case.

Successful Combination Therapy of Nivolumab and Radiation for Massive Mucosal Melanoma in Patient with Autoimmune-Myasthenia Gravis, Systemic Lupus Erythematosus and Rheumatoid Arthritis

A 58-year-old woman complicated with autoimmune diseases of myasthenia gravis (MG), rheumatoid arthritis, and systemic lupus erythematosus noticed an irregular black macule on her bilateral major labia, which was diagnosed as malignant melanoma. The melanoma lesion involving the vagina, uterus, and ventral side of rectum was not operable and was treated with nivolumab and concurrent radiotherapy with good control of the MG. This resulted in remarkable tumor shrinkage, possibly due to synergistic effects of both treatments. To our knowledge, few reports have described the effectiveness of combination therapy with nivolumab and radiation for malignant melanoma. The present case showed an enhanced anti-tumor effect with combination therapy.