Tessin Watanabe

Intralymphatic histiocytosis with granuloma formation associated with orthopaedic metal implants.

A 75‐year‐old man presented with a 1‐year history of asymptomatic reddish‐brown nodules on his left knee, in which orthopaedic metal implants had been inserted for a transformation‐related knee joint disorder. Histopathological examination revealed typical features of mixed cell granuloma with many dilated lymphatics that contained many histiocytes from the upper dermis to subcutaneous fat tissue. Results of qualitative analysis of biopsy specimens by energy‐dispersive X‐ray spectroscopy were positive for molybdenum, which was one of the constituents of the metal implant. We describe the first observation of intralymphatic histiocytosis with granuloma formation in the skin occurring in a patient bearing orthopaedic metal implants for a transformation‐related knee joint disorder.

A morphological study of granulomas induced by subcutaneous injection of leuprorelin acetate

Leuprorelin acetate‐induced granulomas in subcutaneous injection sites have been occasionally reported, but there have been no detailed morphological examinations. Histopathology of leuprorelin acetate‐induced granulomas in six patients was studied, and one of them was evaluated by electron microscopy. Study using haematoxylin and eosin staining revealed that there were many intracytoplasmic vacuoles in the granulomas and degeneration of fat tissue. Ultrastructurally, electron‐lucent spherical bodies (microcapsules of leuprorelin acetate products) were observed in the granuloma cells. Needle‐shaped crystalloid structures in lipid droplets (degenerated lipid droplets) were observed in the granuloma cells and fat tissue. Degeneration of fat tissues caused by leuprorelin acetate is one of main factors responsible for granuloma formation.

Multiorgan involvement in Sweet's syndrome.

A 59-year-old man who had been hospitalized for endoscopic excision of untreated early gastric cancer (stage 1A) presented with a 1-week history of high fever and indurated painful erythemas on the nape of the neck and the right ear. The gastric cancer had been diagnosed 4 months before, and the patient was hospitalized for endoscopic excision. At the time the eruption first appeared, a diagnosis of myelodysplastic syndrome had been made by a haematologist. The erythemas had gradually appeared on the patient s face, the dorsa of both hands and the left ear during the course of 1 week. Physical examination revealed indurated erythemas with superficial pustules on the patient s face (Fig. 1) and his dorsal hand and finger appeared gangrenous. There were a few reddish nodules on both conjunctiva and swelling on the lower jaw. Laboratory investigations showed pancytopenia, with a red blood cell count of 2.26 · 10 ⁄ L (normal range 1.5– 6.5 · 10 ⁄ L), haemoglobin 79 g ⁄ L (13.0–18.0), white blood cell count of 2.8 · 10 ⁄ L with 66% polymorphonuclear leucocytes (4–11 · 10 ⁄ L and 40–60%) and platelet count of 105 · 10 ⁄ L (150–400 · 10 ⁄ L). Serum granulocyte colony-stimulating factor (G-CSF) was raised at 122 pg ⁄ mL (normal, < 10 pg ⁄ mL). Skin biopsies taken from the lesions on the patient s face and hands revealed a high level of neutrophil infiltration with marked dermal oedema but without any signs of vasculitis (Fig. 2). No microorganisms grew on cultures. These findings led to the diagnosis of Sweet s syndrome (SS). Chest X-ray and computed tomography scan revealed right lower pulmonary infiltrates. Sonography of the lower jaw revealed swelling of the submandibular gland. As there were no signs of another disease (e.g. sarcoidosis, tuberculosis), the pulmonary infiltrates and swelling of the submandibular gland were likely to be related to SS. The patient was started on oral prednisolone 40 mg ⁄ day and sulfamethoxazole–trimethoprim 1 g ⁄ day. The skin lesions gradually improved, but the treatment had no effect on the pulmonary infiltrates or the swelling of the lower jaw. The patient was then given pulse treatment with methylprednisolone (1000 mg ⁄ day), and the symptoms were dramatically improved. After the pulse treatment, the dosage of oral prednisolone was gradually tapered from 60 mg ⁄ day, but when it reached 35 mg ⁄ day, the patient developed a high fever and reduced consciousness. Although the symptoms indicated involvement of the meninges, infectious brain meningitis (due to infection with viruses, tuberculosis or other bacteria) was excluded by the results of cerebrospinal fluid investigations and

Necrotizing Soft-Tissue Infection Caused by Both Candida glabrata and Streptococcus agalactiae

dronate and zoledronic acid. No established guidelines exist for dosing of zoledronic acid in children. Our patient’s severe symptomatic hypocalcemia may have been dose related and/or related to his severe osteopenia. He received 4 mg (0.1 mg/kg) of zoledronic acid, which has been safely used in multiple patients with osteopenia treated by one of us (J.E.H.). Two recent case series of zoledronic acid therapy used to treat a small number of children with osteoporosis or localized bone disease and evidence of active resorption have used initial doses of 0.0125 to 0.025 mg/kg. Owing to the risk for osteopenia and osteoporosis, patients with RDEB should be screened for bone mineral density with dual-energy x-ray absorptiometry. Low serum calcium and 25-hydroxyvitamin D levels should be treated with vigorous supplementation and exercise programs to prevent development of osteopenia. Caution should be used when choosing a zoledronic acid dose: an initial low dose (0.025-0.05 mg/kg) should be considered for patients with severe osteopenia to prevent hypocalcemia, and treatment should be repeated every 3 to 6 months. Further studies of the safest and most effective oral and/or intravenous doses of bisphosphonates in children are needed.

Epstein-Barr Virus-Infected Malignant T/NK-Cell Lymphoma in a Patient with Hypersensitivity to Mosquito Bites

We report an autopsy case of Epstein-Barr virus (EBV)-infected malignant lymphoma in a young male who had hypersensitivity to mosquito bites. The autopsy revealed multiple confluent lymphoma lesions in the lungs, and on the right leg irregular-shaped skin ulcers were seen. The left pleural effusion also contained a large number of lymphoma cells. The lymphoma cells were determined as T/NK-cell type cells by immunohistochemistry. EBV DNA was detected most intensively in the lungs and EBV-encoded small RNAs-positive lymphoma cells were also observed in the lungs at a high frequency. EBV latent membrane protein-1 expression and a high Ki-67 labeling indices were noted in the lymphoma cells of the lung lesions. These findings indicate that the development of the malignant lymphoma was associated with the proliferation of EBV-infected lymphoma cells, and the cells that infiltrated the whole the body, especially the lungs, caused the patients death.

Novel morphological study of solar lentigines by immunohistochemical and electron microscopic evaluation

Solar lentigines (SL) are hyperpigmented lesions generally seen in elderly people. Their pathogenesis has not been completely elucidated. We examined 75 cases of SL using routine histopathology and immunohistochemistry. In addition, seven cases were evaluated by electron microscopy. Histopathologically, we observed vacuolar changes in the dermoepidermal junction in 85% of the cases. Dermal melanophages were seen in 77% of the cases. The immunohistochemical expression rates in the epidermis for cytokeratin (CK)15, CK14, CK10, p63 and nestin were 76%, 100%, 100%, 100% and 17%, respectively. In 58 cases showing dermal melanophages, expression rates of CD163 and factor XIIIa on melanophages were 79% and 83%, respectively. Double positivity for both proteins was identified in 44 cases (75%). Ultrastructurally, vacuolar structures were seen in the cytoplasm of basal cells and upper dermis in all cases examined. We observed elimination processes of damaged basal keratinocytes, which were probably produced by ultraviolet (UV) irradiation, into the papillary dermis. The segregated damaged cell bodies containing melanin granules seemed to be phagocytosed by poorly immunostimulatory macrophages labeled immunohistochemically by CD163 and factor X IIIa, contributing to prolonged pigmentation of SL. In addition, repeated basal keratinocyte damages may be in association with altered CK and p63 expression patterns in the constituent cells of SL.

A case of symmetrical drug-related intertriginous and flexural exanthema induced by loflazepate ethyl

associated infusion reactions. Mt Sinai J Med 2005; 72: 250–256. 4 De Rycke L, Baeten D, Kruithof E, Van den Bosch F, Veys EM, De Keyser F. Infliximab, but not etanercept, induces IgM anti-double-stranded DNA autoantibodies as main antinuclear reactivity: biologic and clinical implications in autoimmune arthritis. Arthritis Rheum 2005; 52: 2192–2201. 5 Atzeni F, Turiel M, Capsoni F, Doria A, Meroni P, Sarzi-Puttini P. Autoimmunity and anti-TNF-a agents. Ann N Y Acad Sci 2005; 1051: 559–569. 6 Eriksson C, Engstrand S, Sundqvist KG, Rantapää-Dahlqvist S. Autoantibody formation in patients with rheumatoid arthritis treated with anti-TNF a. Ann Rheum Dis 2005; 64: 403–407. 7 De Bandt M, Sibilia J, Le Loët X et al. Systemic lupus erythematosus induced by anti-tumor necrosis factor alpha therapy: a French national survey. Arthritis Res Ther 2005; 7: R545–R551. 8 Egner W. The use of laboratory tests in the diagnosis of SLE. J Clin Pathol 2000; 53: 424–432. 9 Ramos-Casals M, Brito-Zerón P, Muñoz S et al. Autoimmune diseases induced by TNF-targeted therapies: analysis of 233 cases. Medicine (Baltimore) 2007; 86: 242–251.

Necrotizing fasciitis of the breast and axillary regions

ejd.2012.1838 Auteur(s) : Koji Adachi1 koujiadachi@grape.med.tottori-u.ac.jp, Reiko Tsutsumi1, Yuichi Yoshida1, Tessin Watanabe1, Bin Nakayama2, Osamu Yamamoto1 1 Division of Dermatology, Department of Sensory and Motor Organs 2 Department of Plastic and Reconstructive Surgery, Tottori University, 86 Nishi-cho, Yonago-shi, Tottori 683-8503, Japan Reprints: K. Adachi Necrotizing fasciitis is a rare, soft tissue infection which is characterized by widespread fascial necrosis with relative sparing of [...]

Multiple skin lesions caused by Mycobacterium scrofulaceum infection

ejd.2011.1534 Auteur(s) : Ayako Ito1 ayama813@grape.med.tottori-u.ac.jp, Yuichi Yoshida1, Hiromi Higaki-Mori1, Tessin Watanabe1, Kazue Nakanaga2, Norihisa Ishii2, Osamu Yamamoto1 1 Division of Dermatology, Faculty of Medicine, Tottori University, 86 Nishi-cho, Yonago 683-8503, Japan 2 Leprosy Research Center, National Institute of Infectious Diseases, Tokyo, Japan Mycobacterium (M.) scrofulaceum is a slow-growing, non-tuberculous mycobacterium that is widely distributed in nature and is isolated [...]

Granulomas induced by subcutaneous injection of a luteinizing hormone‐releasing hormone analog: a case report and review of the literature

To the Editor, Both leuprorelin acetate and goserelin acetate are superactive agonist analogs of luteinizing hormone-releasing hormone (LH-RH), administered by subcutaneous injection in Japan, and are frequently indicated for treatment of prostate cancer.1– 3 Leuprorelin acetate products consist of leuprorelin acetate and microcapsules that are made of synthetic biodegradable polymers. There are many fine drug cores containing leuprorelin acetate throughout the polymer matrix.1 On the other hand, goserelin acetate products consist of goserelin acetate and an implant that is made of synthetic biodegradable polymers. Goserelin acetate is dispersed in the implant, which is a stickshaped material of 10 × 1.2 mm or 10 × 1.5 mm in size.2,3 Several cases of leuprorelin acetate-induced granulomas have been reported.3– 9 We have performed detailed histologic examination of six cases of leuprorelin acetate-induced granulomas and pointed out that degeneration of fat tissues caused by leuprorelin acetate is one of main factors responsible for granuloma formation.10 On the other hand, only two cases of goserelin acetate-induced granulomas have been reported. However, detailed histologic examinations have not been performed.8,9 We report here an additional case of goserelin acetate-induced granuloma and describe the first detailed ultrastructural observation. We propose a possible mechanism of granuloma formation induced by subcutaneous injection of LH-RH analogs. A 79-year-old man presented with a 2-month history of a nodule on his abdomen. He had been treated with subcutaneous injections of goserelin acetate for prostate cancer once every 12 weeks for about 3 years. Physical examination revealed a painless, firm subcutaneous nodule of 7 × 2 cm in size on his abdomen. Differential diagnosis included granuloma induced by goserelin acetate, metastatic prostate cancer and sarcoidosis. A skin biopsy was performed. Histopathologic examination showed epithelioid cell granulomatous inflammation. The histiocytes in the granulomas contained a few vacuoles. The number of vacuoles was less than that in the granulomas induced by leuprorelin acetate previously reported.10 In addition, degeneration of fat tissue was observed. Based on these findings, this case was diagnosed as granuloma induced by goserelin acetate. The nodule spontaneously disappeared without any treatment after the biopsy. Transmission electron microscopy (TEM) exhibited two types of round or ovoid bodies in the cytoplasm of histiocytes: one was electron-lucent and the other was electron-dense. The number of electron-lucent bodies was less than that of electrondense bodies. The electron-lucent bodies were about 1–2 μm in diameter and contained minute granules (Fig. 1A). These bodies were similar to the constitution ingredient of microcapsules of leuprorelin acetate-induced granulomas previously observed by TEM. These bodies were smaller than those of leuprorelin acetate-induced granuloma.10 On the other hand, the electron-dense bodies were lipid droplets. Some of these droplets showed various degrees of degeneration (Fig. 1B). The degenerated area was packed by numerous needle-shaped or ellipsoidal-shaped crystalloid structures. Similar crystalloid structures were observed in some lipid droplets of fat cells in the adipose tissue adjacent to the granuloma (Fig. 1C). Based on the morphologic similarity between features of electron-lucent bodies in the histiocytes in leuprorelin acetate-induced granuloma and those in