Takaki Hashiguchi

Extramammary Paget's Disease/Carcinoma Successfully Treated with a Combination Chemotherapy: Report of Two Cases

We have treated two patients with extramammary Pagets disease/carcinoma (EMPD/C), a 62‐year‐old woman and a 78‐year‐old man. In both patients, lymph nodes in the areas of the bilateral inguinal, external iliac arteries, and abdominal aorta were affected. After surgery, they underwent 5 courses of systemic combination chemotherapy at 4‐week intervals to residual or recurrent lymph node metastasis. Each course consisted of 3.5 mg mitomycin C and 50 mg epirubicin (day 1), 0.6 mg vincristine (days 1 and 7), 30 mg cisplatin (days 1, 2, and 3), and 350 mg 5‐fluorouracil (days 3, 4, 5, 6, and 7). The affected lymph nodes in both patients subsided in response to the chemotherapy. Positron emission tomography (PET) scans confirmed the complete remission of lymph node metastasis in Case 1. In Case 2, they were reduced by more than 90% on computed tomography (CT) scans. Adverse effects included leukocytopenia, vomiting, hypesthesia, and constipation, all of which disappeared after the completion of chemotherapy. While surgery with wide local excision is the treatment of choice in patients with EMPD/C, there is currently no standardized treatment for advanced cases with metastasis. We describe two patients with EMPD/C whose metastatic lesions responded well to this combination of chemotherapy.

Estrogen Dermatitis: A Dendritic-Cell-Mediated Allergic Condition

Background: Most estrogen dermatitides are induced by local or systemic contact dermatitis where dendritic cells are central, and tamoxifen has a blocking effect on dendritic cells. Methods: We present 5 cases of estrogen dermatitis in which the clinical features were prurigo, urticaria, acneiform eruption and annular erythema. Results: Tamoxifen was effective in 3 of 4 cases. Three of 4 biopsy specimens showed the formation of Langerhans cell nests in the epidermis and hair follicles and perivascular infiltration of CD4+ and CD8+ lymphocytes in the dermis. Conclusion: These results suggest that a dendritic-cell-mediated allergic mechanism is involved in estrogen dermatitis.

Three Cases of Polyarteritis Nodosa Cutanea and a Review of the Literature

We describe three cases of polyarteritis nodosa cutanea (PNC) showing necrotizing arteritis and only cutaneous lesions without systemic symptoms or visceral involvement for eleven, six, and three years after the onset of the disease. Since it was first described, there has been continuous controversy as to whether PNC progresses to systemic PN. Some cases have been described which had begun with a cutaneous lesion and progressed to the systemic form 19 and 18 years after the onset of the disease, so we believe that long term follow‐up of this disease is essential.

Mutations in the ED1 gene in Japanese families with X-linked hypohidrotic ectodermal dysplasia

Abstract: X‐linked hypohidrotic ectodermal dysplasia (XLHED; OMIM 305100) is characterized by sparse hair, abnormal teeth and decreased sweating as a result of abnormal development of the sweat glands. Mutations in the ED1 gene, which encodes ectodysplasin‐A (EDA), are responsible for XLHED. Ectodysplasin‐A, a ligand for the EDA receptor, plays an important role in epidermal morphogenesis. We identified ED1 mutations including three novel mutations by sequencing genomic DNAs from eight unrelated Japanese XLHED families. Data from all reported mutations revealed that codon 156 in the furin subdomain is the most frequent site of change in EDA.

Primary squamous cell carcinoma of the frontal sinus

We report a 74‐year‐old Japanese man with squamous cell carcinoma (SCC) originating in the frontal sinus. It presented as a cutaneous nodule on his right forehead. Magnetic resonance imaging (MRI) revealed invasion of the anterior wall of the ethmoid sinus, the frontal bone, and possibly the meninx by a frontal sinus carcinoma. Despite right fronto craniotomy with en bloc resection followed by two courses of radiation therapy and chemotherapy with 5‐fluorouracil and nedaplatin or TS‐1 he died of disease‐related causes 20 months later. Herein, we present a detailed description of this patient and a review of the published work.

A Frameshift Mutation of the ED1 Gene in Sibling Cases with X-Linked Hypohidrotic Ectodermal Dysplasia

X-linked hypohidrotic ectodermal dysplasia (XLHED; MIM 305100) is characterized by the absence or hypoplasia of hair, teeth, and sweat glands. The ED1 gene was identified as a responsive gene for XLHED. The patients were 2 Japanese brothers. Both had the same mutation in exon 1 of the ED1 gene, i.e. C deletion at nucleotide 49, which induced a frameshift starting from amino acid 17 and made a stop codon at amino acid 56, encoding the transmembrane site. The mutation caused the extracellular domain of ectodysplasin A to be completely absent. Their mother had a heterozygous allele; she congenitally lacked 1 tooth, and incisors appeared conical in form.

Extramammary Paget’s disease with prominent signet-ring cells

Figure 2. Histopathological examination showed prominent signet-ring cells invaded in the epidermis and dermis (HE stain, original magnification ·200). Figure 1. Photograph showing indurated erythematous lesions on the lower abdomen, scrotum and penis. Dear Editor, Extramammary Paget’s disease (EMPD), characterized histologically by the intraepidermal proliferation of Paget cells, is a relatively common skin cancer. Signet-ring cells are neoplastic cells with abundant cytoplasm; their nuclei are eccentrically located. Primary cutaneous signet-ring cell carcinoma (SRCC), mammary Paget’s disease and EMPD are primary carcinomas of the skin exhibiting signet-ring morphology. We encountered a 63-year-old man with EMPD on the scrotum and lower abdomen comprised primarily of signet-ring cells. One year prior to his current admission to our hospital, he noticed an erythematous plaque in his genital region. Skin biopsy, positron emission tomography (PET) and computed tomography (CT) of the whole body were performed elsewhere and a non-specific diagnosis of adenocarcinoma was made based on biopsy findings. PET and CT study detected a metastatic liver lesion. After 6-month treatment with tegafur and cisplatin he was referred to our hospital. Examination revealed an irregularly-shaped erythematous lesion with induration involving his scrotum, penis and lower abdomen, showing a trunk-like distribution (Fig. 1). Although this type of distribution is often observed in a retrograde metastatic lesion from inguinal lymph nodes, his inguinal lymph nodes were not palpable nor detected by PET and CT. Biopsy specimens from his scrotum and lower abdomen disclosed prominent signet-ring cells with mucinous cytoplasm both in the epidermis and dermis. Signet-ring cells are distributed prominently in the dermis (Fig. 2). Lymphatic invasion was revealed by staining with D2-40, a specific marker for lymph vessels (Fig. 3). The invasion level of tumor cells and the distribution of signet-ring cells are evenly seen in the lesion. Immunohistochemical examination showed that the cells were positive for carcinoembryonic antigen

Tungsten granuloma attributable to a piece of lawn-mower blade

We report a patient with a foreign-body granuloma induced by a metal fragment from a lawn-mower blade. As the patient did not remember the injury and histological examination of the initial biopsy showed necrobiosis but no foreign-body reaction, diagnosis was difficult. Computed tomography (CT) indicated that the foreign body was a small piece of metal; X-ray microanalysis of the excised specimen showed it to be composed primarily of tungsten. A 59-year-old man presented with a 3-month history of a subcutaneous tumour on his left cheek (Fig. 1). The tumour measured 20 · 30 mm, with an erythematous surface. The lesion was hard and elastic without pain or tenderness, and had poor mobility. Histological examination of a biopsy specimen taken from the lesion showed degeneration of collagen fibres surrounded by lymphocytic and histiocytic infiltrates in the dermis. We initially suspected infectious granuloma. However, results of cultures for bacteria and fungi and PCR for Mycobacterium tuberculosis were negative. Before total surgical excision, we performed a CT scan, which showed a piece of metal at the centre of the tumour (Fig. 2). Histological examination of the site showed necrobiotic degeneration of collagen fibres with granulomatous inflammation consisting of lymphocytes, histiocytes, and numerous neutrophils. A sinus partially lined by epidermis was seen in the upper dermis over a cavity in which the metal