Necrobiotic xanthogranuloma with paraproteinemia; an atypical case.

Necrobiotic xanthogranuloma (NXG) is a rare marker for paraproteinemia. An 86-year-old woman had a one year history of large red-yellow to brown annular plaques involving all limbs. Biopsies showed a non-palisading granuloma with numerous multinucleated giant cells showing prominent elastophagocytosis and extensive areas of necrobiosis throughout the entire dermis. Complete loss of elastic fibers was observed in the central atrophic area of an annular plaque. Small vascular thromboses were also present. Laboratory findings revealed paraproteinemia of IgG-lambda type. Immunohistochemical staining detected the presence of roughly equal numbers of IgG-lambda-and IgG-kappa-staining plasma cells in the dermis. We diagnosed NXG with paraproteinemia with monoclonal gammopathy (IgG-lambda type) of unknown significance.

Keratin and filaggrin expression in keratoacanthoma.

To clarify the histogenesis of keratoacanthoma, we studied keratin (K) expression in keratoacanthoma (KA) using 10 different anti-keratin antibodies against K1, K7, K8, K10, K14, K15, K16, K17, K18 and K19 and anti-filaggrin (filament aggregating protein) antibody. In the centre of KA, K1 and K10 expressions were declined, and K14 and K16 were detected in the tumour cells, suggesting differentiation towards the outer root sheath beneath the orifice of the sebaceous duct. These results suggest that KA differentiates towards the outer root sheath beneath the opening of the sebaceous duct.

A case of Adamantiades-Behçet disease with ischemic optic neuritis (posterior optic neuropathy).

Adamantiades-Behçet disease (ABD) may present with cutaneous and ophthalmologic findings. A 29-year old woman complained of fever and general fatigue, along with erythema nodosum and vesiculo-pustular lesions on the legs, acneiform lesions, genital ulcerations and painful oral ulcers. She also complained of reduced visual acuity, visual disturbance and blurred vision in the left eye. Her left visual acuity was 6/20. Light reflex in the left eye was reduced. The relative afferent pupillary defect (RAPD) was positive in the left eye where a central scotoma was present. The vitreous was clear; the optic disc, macula, retina and iris were all normal. Uveitis was not observed. The patient was diagnosed with ischemic optic neuritis (posterior optic neuropathy) with ABD. Histopathological findings taken from a blister on the leg showed subepidermal bulla, dense dermal neutrophil infiltration, and extravasation of erythrocytes, suggesting leukocytoclastic vasculitis. She was treated orally with high-dose corticosteroids (methylprednisolone 500 mg/d) for three days. Her general condition and ophthalmic symptoms resolved completely. Optic neuropathy with ABD is very rare; we know of two previous cases [1, 2] of ABD with ischemic posterior optic neuritis.

Cytokeratin and filaggrin expression in nevus comedonicus.

To elucidate the pathogenesis of abnormal keratinization in nevus comedonicus, we performed an immunohistochemical study using antikeratin and antifilaggrin (filament-aggregating protein) antibodies. There were no significant differences between nevus comedonicus and normal skin in cytokeratin expression. Although filaggrin was only detected in the granular layer in open comedones, filaggrin was detected in both superficial cells and also intermediate cells in closed comedones, suggesting that filaggrin is involved in the formation of closed comedones. The disorder of terminal differentiation related to filaggrin may play a role in the pathogenesis of abnormal keratinization in nevus comedonicus.

Pinkus tumor may originate from intraepidermal eccrine ducts and proliferate in the dermis.

To clarify the histopathogenesis of Pinkus tumor (fibroepithelial basal cell carcinoma, FEBCC), we have studied cytokeratin (CK) expression in FEBCC using ten different anti-keratin antibodies against CK 1, 7, 8, 10, 14, 15, 16, 17, 18 and 19. Tumor nests consisted of two epithelial components: duct-like structures and basaloid cells of anastomosing strands. In duct-like structure, CK 1, 10, 14, 16, 17 and 19 were detected. CK expression of duct-like structure showed the hyperproliferative state of eccrine intraepidermal ducts. In basaloid cells of anastomosing strands, CK 14 and 17 were detectable. These results suggested that duct-like structure originates from the intraepidermal duct and proliferates to spread in the dermis.

Cytokeratin expression in trichilemmal carcinoma suggests differentiation towards follicular infundibulum.

An immunohistochemical study of cytokeratins (CK) in a case of trichilemmal carcinoma (TLC). CK expression showed the presence of CK 1, 10, 14 and 17, suggesting that TLC differentiates toward follicular infundibulum. In a comparison of CK expression between TLC and trichilemmoma, the absence of CK 15 and 16 in TLC may be related to transformation from trichilemmoma to TLC. Trichilemmal carcinoma (TLC) is a rare cutaneous tumor, and is considered as a malignant counterpart of trichilemmoma. The histogenesis of TLC remains unclear. The features of TLC resemble the outer root sheath. Monoclonal antibodies against cytokeratin (CK) are crucial markers for evaluating the origin of epithelial tumors and the stage of differentiation. To elucidate the origin and the stage of differentiation of TLC, an immunohistochemical study of CK was performed using nine different anti-keratin antibodies against CK1, 7, 8, 10,14,16,17, 18 and 19.

Cutaneous dermoid cyst: cytokeratin and filaggrin expression suggesting differentiation towards follicular infundibulum and mature sebaceous gland.

We experienced two cases of cutaneous dermoid cysts (DC). To elucidate the histogenesis of DC, we have studied cytokeratin (CK) expression in DC using ten different anti-keratin antibodies against CK1, 7, 8, 10, 14, 15, 16, 17, 18 and 19, and anti-filaggrin (filament aggregating protein) antibody. In the cyst wall of DC, CK1 and 10 were expressed in suprabasal layer, and CK14 was limited to the basal layer. In sebaceous gland-like structures, CK14 was detected in sebaceous acinus, and CK17 was detected in sebaceous duct. The other CKs were not detected. Filaggrin was intensely detected in the granular layer in the cyst wall of DC. CK expression profile of DC was similar to follicular infundibulum and sebaceous gland. These results suggested that DC differentiates towards follicular infundibulum and mature sebaceous gland.

A case of epidermotropic metastatic malignant melanoma with multiple nodular lesions of the scalp.

Epidermotropic metastatic malignant melanoma (EMMM) is a form of metastatic malignant melanoma that has dermal cell nests with epidermotropism and specific histopathological features. We report a patient with eight nodular lesions of the scalp with histopathological findings compatible with EMMM. The tumors developed one year before consultation and increased in size simultaneously. The histopathological findings of all eight tumors were very similar. The tumor cells were located mainly in the dermis and partly in the basal layer of the epidermis. They contained melanin pigments and were positive for anti-HMB45 antibody. The tumors did not respond to combination chemotherapy with dacarbazine, nimustine, vincristine, and interferon-beta. Therefore, all the tumors were surgically removed. No local relapse, distant metastasis or re-elevation of plasma 5-S-cysteinyldopa was identified during nine months of follow-up. Histopathologically, all eight tumors lacked apparent vascular invasion, which may be related to a slow clinical course of the present case.

Atelocollagen sponge and recombinant basic fibroblast growth factor combination therapy for resistant wounds with deep cavities.

Recent advances in bioengineering have introduced materials that enhance wound healing. Even with such new tools, some deep ulcers surrounded by avascular tissues, including bone, tendon, and fascia, are resistant to various therapies and easily form deep cavities with loss of subcutaneous tissue. Atelocollagen sponges have been used as an artificial dermis to cover full-thickness skin defects. Topical recombinant human basic fibroblast growth factor has been introduced as a growth factor to induce fibroblast proliferation in skin ulcers. We applied these materials in combination in two patients with deep resistant wounds: one with a cavity reaching the mediastinum through a divided sternum and one with deep necrotic wounds caused by electric burns. These wounds did not respond to the topical basic fibroblast growth factor alone. In contrast, the combination therapy closed the wounds rapidly without further surgical treatment. This combination therapy is a potent treatment for resistant wounds with deep cavities.

Relapse of dermatomyositis after 10 years in remission following curative surgical treatment of lung cancer.

A 55-year-old woman with dermatomyositis and small cell lung cancer was successfully treated with surgery followed by combination chemotherapy in 1987. She had been in remission without further immunosuppressive therapy for 10 years. However, myositis with cutaneous manifestations specific for dermatomyositis relapsed when the patient was 69 years old. Intensive examinations revealed no neoplasm, and she responded to a moderate dose of systemic corticosteroids. This case suggests a long-lasting autoimmune abnormality in dermatomyositis and that a neoplasm is an important factor in eliciting an occult dermatomyositis.

Extra nodal NK/T-cell lymphoma nasal type that responded to DeVIC combination chemotherapy.

We report a 76-year-old woman with extra nodal NK/T-cell lymphoma nasal type (ENKL). She had large tumors on her left leg with inguinal lymphadenopathy and gastric tumors. The tumor cells showed angiocentric growth with necrosis. Immunohistologically, the tumor cells from the skin lesion expressed CD2, cytoplasmic CD3, CD56, and T-cell intracellular antigen-1 (TIA-1), but not surface CD3, CD19, and TdT. The gastric tumor cell, also expressed cytoplasmic CD3, CD45RO and CD56. She was diagnosed as having ENKL (stage IV of Ann Arbor). The tumors responded remarkably well to radiation therapy followed by multi-drug resistance independent DeVIC (carboplatin, etoposide, ifosfamide, and dexamethasone) combination therapy. After two series of this therapy, no tumors were detected in clinical, histopathological, endoscope and computerized tomogram (CT) examinations. However, she suddenly died of brain stem metastasis three months later. Although there may be a limitation of effects on metastasis of tumors in the central nervous system, radiation and DeVIC combination therapy is a potent therapeutic method for ENKL.

Basic fibroblast growth factor treatment for skin ulcerations in scleroderma.

We report the use of topical application of recombinant human basic fibroblast growth factor (rhbFGF) to successfully treat therapy-resistant, chronic leg ulcers in scleroderma. Endothelial cell FGF receptors are directly stimulated by bFGF; also, bFGF promotes the regeneration of capillary-rich granulation tissue. We conclude that topical bFGF may be a powerful new pharmacologic tool for treating severe skin ulcers.

A case of a large dermatofibrosarcoma protuberans successfully treated with radiofrequency ablation and transcatheter arterial embolization.

We present a large dermatofibrosarcoma protuberans on a 52 years-old woman's back that was successfully treated with transcatheter arterial embolization and radiofrequency ablation. The tumor developed on her back at the age of 14. Surgical treatment was not complete, and it relapsed at age 17 and again at age 24. The tumor enlarged to over 20x20x10 cm and flooded intermittently. The tumor cells with atypical nuclei were CD34 positive and proliferated in a storiform pattern. These findings were compatible with dermatofibrosarcoma protuberans. She was treated with blood transfusion for severe anemia. Two large feeding arteries were embolized, and the bottom of the tumor was treated with radiofrequency ablation. The tumor reduced in volume by more than 50%. It was then surgically removed and reconstructed with a free mesh skin graft. The combination pretreatment enabled radical resections of a large DFSP without severe complications.

Drug eruption caused by azathioprine: value of using the drug-induced lymphocytes stimulation test for diagnosis.

Azathioprine (AZA) is an immunosuppressant commonly used for organ transplantation and autoimmune diseases. Allergic side effects of AZA are rare, and reported allergic skin eruptions from AZA are very limited in Japan. We report AZA-induced drug eruption that developed in two cases of systemic scleroderma with polymyositis. One case presented with Stevens-Johnson syndrome, and the other had systemic papular erythema. The stimulation indices of the drug-induced lymphocyte stimulation test (DLST) for AZA in these two patients were as high as 2,180% and 430%, respectively, but those of healthy volunteers were under 120% without nonspecific suppression of lymphocyte proliferation. Other drugs used simultaneously were ruled out by patch and challenge tests. The challenge test for Stevens-Johnson syndrome type drug allergy is very risky. DLST is a good diagnostic tool for AZA allergy, especially for severe drug allergy cases.

Primary cutaneous follicle center cell lymphoma of the scalp successfully treated with anti CD20 monoclonal antibody and CHOP combination therapy with no subsequent permanent loss of hair.

We present a primary cutaneous follicle center cell lymphoma (PCFCCL) patient who was successfully treated with Rituximab, a new anti-CD20 monoclonal antibody. A thirty-two-year-old male developed two asymptomatic tumors on the scalp. Histopathologically, the tumors were composed of diffuse and nodular infiltration of centrocytes and centroblasts. Immunohistopathologically, the tumor cells stained positively with anti-CD20 antibody and anti-kappa antibody, but not with anti-CD5, anti-CD10, or anti-Bcl-2 antibody. Radiation therapy is effective in treating PCFCCL; however, it usually results in the permanent loss of hair. This patient was treated with Rituximab and CHOP, and achieved a complete remission. He has had no recurrence in more than 12 months and no permanent loss of hair on the scalp.

Bilateral scalp necrosis with giant cell arteritis.

We present a patient with bilateral scalp necrosis caused by giant cell arteritis (temporal arteritis). A 67-year-old woman, who had been treated with 5 mg of oral prednisolone every other day for polymyalgia rheumatica, developed painful egg-sized regions of necrosis on both of her temples. Doppler pulsemetory revealed bilateral obstruction of the temporal arteries. Biopsy revealed ischemic necrosis of the skin and necrotic angiitis of the temporal arteries with giant cell infiltration. Bilateral stenosis of the internal carotid arteries and moderate retinal bleeding were revealed by angiography. Daily administration of prednisolone (20 mg/day) with intravenous and topical limaprost alphadex markedly improved her condition. The ulcers reepithelized without surgical treatment. There are few reports of bilateral scalp necrosis. Rapid and complete obstruction of the temporal artery may result in this condition. Simultaneous development of two ulcerative lesions in the ventro-parietal cranial regions is thought to correspond to systemic arterial involvement, including involvement of the internal carotid arteries.