Search

Inguinal lymph node dissection (ILND) for skin cancer is associated with a high incidence of wound complications. The traditional skin approaches are associated with a high risk of wound/flap necrosis of the inguinal skin, which leads to wound dehiscence and wound infection. We report a novel approach for ILND without inguinal skin incision for patients with invasive extramammary Paget disease (EMPD) to minimize the wound complications inherent in conventional ILND. We totally performed this procedure in 3 patients with invasive EMPD with inguinal nodal metastases. No patient had complications, including flap necrosis, wound dehiscence, or wound infection. Our novel surgical approach would retain the vascular supply because there was no inguinal skin incision, preventing postoperative wound complications. In addition, ILND was easily performed with satisfactory exposure of the surgical field. However, the number of patients was small and the follow-up period was short. Further evaluation of a larger case series with longer follow-up is essential to investigate the effect, safety, and indications for this novel approach., (© 2015 Wiley Periodicals, Inc.)

Background: The importance of the genetic background of melanoma cells to the individual susceptibility to treatment has become apparent. In Caucasians, BRAF mutations are frequently detected in lesions on the skin of younger patients compared to NRAS and KIT mutations. However, clinical and pathological characteristics associated with BRAF, NRAS and KIT mutations have not been fully evaluated in East Asians., Objective: To clarify clinical and pathological characteristics associated with BRAF, NRAS and KIT mutations in Japanese melanoma patients., Methods: Clinical data were retrospectively collected from 11 hospitals in Japan. BRAF, NRAS and KIT mutations were evaluated with polymerase chain reaction and Sanger sequencing. The relationships between these gene mutations and pathological and clinical findings were analyzed., Results: The number of cases examined was 171 (primary: 135, metastases: 11, paired: 25), and all were Japanese patients. The detection rates of BRAF, NRAS and KIT mutations were 30.4%, 12.3% and 12.9%, respectively. Compared with the wild type, the presence of BRAF mutations was significantly associated with younger age (median, 50.0 years vs. 70.0 years, p<0.001). BRAF mutation was frequently detected in the lesions of the scalp (80%; 4/5), trunk (72.0%; 18/25), extremities (56.7%; 17/30) and neck (44.4%; 4/9), and the least prevalent were the face (22.2%; 2/9), nail (12.5%; 3/24), palm or sole (8.9%; 4/45) and mucosa (0%). NRAS mutations were prevalent in the face (33.3%) and palm or sole (20.0%), and the median age of these patients was 70.5 years. A KIT mutation was observed in the nail apparatus (25%), palm or sole (15.6%) and mucosa (18.2%). The median age of the patients with a KIT mutation was 63.0 years. Heterogeneity of mutations between primary and metastatic lesions was detected in six of 25 cases (24%). Solar elastosis was identified in 12 of 71 cases (15.3%), among which four cases harbored BRAF(V600E) (2 cases), BRAF(V600K), NRAS(Q61K) or NRAS(Q61L), respectively., Conclusion: Some clinical characteristics associated with BRAF, NRAS and KIT mutations were observed in Japanese patients, and we observed both similarities to and differences from those of Caucasians. Our findings could provide useful information in efforts to clarify the tumor genesis of malignant melanomas., (Copyright © 2015 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.)

Background: Although extramammary Paget's disease (EMPD) mostly presents as intraepithelial carcinoma, we sometimes encounter patients with invasive EMPD (iEMPD) who have lymph node metastasis and may develop distant metastasis. Although sentinel lymph node biopsy (SLNB) is widely accepted for various cancers, there is no large study that has assessed its role in iEMPD., Objective: The main objective of this study is to assess the role of SLNB in patients with iEMPD., Materials and Methods: We retrospectively collected data on 151 iEMPD patients treated from 1998 to 2012 in 11 institutes in Japan. All 151 patients received curative surgery for their primary tumor and none of them had distant metastasis. SLNB was performed on the 107 patients without lymphadenopathy to determine their LN status. The 44 other patients with lymphadenopathy underwent one of the following procedures to determine their LN status: SLNB in 22 cases, immediate LN dissection in 21, and LN biopsy in 1., Results: Compared to those without lymphadenopathy, patients with lymphadenopathy had advanced primary tumors (nodule in the primary tumor, thicker tumor, deeper invasion level, and lymphovascular invasion). The rate of LN metastasis in patients with lymphadenopathy was 80%, compared to 15% in patients without lymphadenopathy who underwent SLNB. Compared to those with negative SLN, patients with positive SLN had advanced primary tumors (nodule in the primary tumor, deeper invasion level, and lymphovascular invasion). Multivariate analysis revealed that dermal invasion (odds ratio 5.8, p=0.04) and lymphovascular invasion (odds ratio 18.0, p=0.0023) were independent factors associated with SLN positivity. Notably, there was no difference in survival between patients with or without SLN metastasis (p=0.71). On the other hand, patients with lymphadenopathy showed worse survival than those with positive SLN (p=0.045)., Conclusion: Clinical lymphadenopathy was strongly correlated with pathological LN metastasis and also associated with worse survival than absence of lymphadenopathy. The rate of occult LN metastasis detected by SLNB was 15%. Survival was not affected by SLN status even when an advanced primary tumor was present in patients with positive SLN. Our results raise the possibility that SLNB and subsequent LN dissection improved the survival of patients with early stage lymphatic spread. Our study indicates that SLNB should be considered for iEMPD if lymphadenopathy is not apparent., (Copyright © 2015 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.)

Basal cell carcinoma (BCC) is a common malignant skin tumor. However, BCC that arise at the umbilicus is rare. We present three cases of umbilical BCC. Each BCC was excised at a different depth level, and all deep surgical margins were negative. All patients had no evidence of local recurrence or metastasis during the follow-up periods (12, 24, and 52 months). Reviewing the reported cases of umbilical BCC, the BCC cells did not seem to invade into the umbilical scar in most cases, and the deepest invasion levels of tumor cells were up to the middle layer of the subcutaneous tissue. However, the dermatological surgeons have to consider the possibility of surgical excision down to and including the umbilical attachment to the peritoneum, and intraoperative margin assessment should be necessary to avoid the risk of excessive or incomplete excision., (© 2014 Japanese Dermatological Association.)

Subungual melanoma (SUM) is rare and represents approximately 2-3% and 20% of all cutaneous melanomas in Caucasians and Asians, respectively. Amputation has usually been performed for invasive SUM; however, not all invasive SUMs invade or attach to the distal phalanx. To investigate the possibility of non-amputative surgery for patients with invasive SUM, the distances between the deepest base of the melanoma cells and the bony surface in the surgical specimens of invasive SUM were measured. Thirty surgical specimens of invasive SUM were retrospectively reviewed. The contents of the specimens were as follows: 14 first toes, 10 thumbs, three second fingers, two third fingers, and one fifth finger. Four specimens showed bone invasion, and the tumor was attached to the bone in four specimens. The tumor-to-bone distance exceeded 0.9 mm in all the specimens with thicknesses <4 mm. In the non-ulcerated SUMs (nine specimens), only one SUM specimen showed bone attachment. There was a higher likelihood of bone attachment or invasion when tumor thickness (TT) exceeded 4 mm (Pearson chi-square test, P = 0.009; Fisher exact test, P = 0.004; student t test, 0.033). Univariate and multivariate analysis also revealed that thick TT had a statistically significant affect (odds ratio 1.807 and 1.865, 95% CI 1.11-3.01 and 1.11-3.13, P = 0.023 and 0.018). Non-amputative surgery may be possible for SUM tumors that are of intermediate-thickness. However, there has been little evidence demonstrating survival with non-amputative surgery for invasive SUM. A large, randomized, prospective clinical study is required to address this issue., (© 2014 Japanese Dermatological Association.)

Lipomas are common, benign, small-sized, soft-tissue tumors. However, giant lipomas are uncommon and the tumor size can cause pain and nerve compression syndrome. The axilla is an extremely rare location for development of giant lipomas. We report two cases of axillary giant lipoma. A 47-year-old man (case 1) and a 42-year-old woman (case 2) presented with a large mass in the axillary region. Case 2 had tenderness in the shoulder and numbness in the upper arm. Magnetic resonance imaging of each tumor showed a homogenous soft-tissue mass in the axillary region, suggestive of lipoma. In case 2, the tumor extended from the axilla to the supraclavicular region and split and compressed the neurovascular bundle. Each lesion was successfully excised surgically without serious complications and recurrence. In case 2, the tenderness and numbness disappeared. Histologically, each lesion was composed of multilobulated, mature adipose cells, which led to a diagnosis of benign lipoma. Axillary giant lipoma is preferably excised surgically to avoid damage caused by tumor compression to the major vessels or nerves, to offer better local control and to establish a correct final diagnosis., (© 2014 Japanese Dermatological Association.)

B-Myb (Mybl2) is a member of the Myb gene family of transcription factors involved in the control of cell growth, differentiation, and apoptosis. The effects of B-Myb on keratinocyte proliferation and differentiation have not yet been clarified. The present study was performed to examine the role of B-Myb in proliferation and differentiation of the spontaneously immortalized human skin keratinocyte cell line HaCaT and normal human keratinocytes with formation of a stratified epidermoid structure in air-liquid interface three-dimensional culture. B-Myb was expressed specifically in undifferentiated normal keratinocytes and downregulated during differentiation. The constitutive overexpression of B-Myb in HaCaT cells during air exposure-induced differentiation resulted in an undifferentiated phenotype, i.e., thickening of the stratified layers, suppression of differentiation marker expression, and retention of proliferative activity with activation of cell cycle regulatory proteins in the S and G2/M phases. In contrast, suppression of B-Myb caused their downregulation and constrained proliferation with retention of differentiation capacity. These findings suggested that B-Myb plays an important role in maintenance of the undifferentiated phenotype of keratinocytes in the basal epidermal layer.

Mucoepidermoid carcinoma (MEC) usually originates from the salivary glands. However, there has been no report on mucoepidermoid carcinoma of the columella. In this study, we report the case of a high-grade MEC of the columella that was successfully reconstructed after surgical resection with bilateral nasolabial flaps set up in a sandwich shape and an auricular cartilage graft. A 66-year-old man presented with a nodule on the columella. Histological findings were suggestive of a high-grade mucoepidermoid carcinoma. Wide excision was performed, and the defects of the columella and the nasal floor were reconstructed with bilateral nasolabial flaps set up in a sandwich shape and an auricular cartilage graft. The postoperative cosmetic result was good with excellent tissue texture. The reconstructed columella had an appropriate, not bulky, width as well as satisfactory height and depth. This reconstructive technique is particularly useful for correcting the large defect of the columella with nasal septum and/or nasal floor defects., (© 2013 Japanese Dermatological Association.)

We describe a female neonate with large flaccid pustules on her trunk and extremities. Cultures were negative, and a Wright-stained smear of pustule contents showed numerous eosinophils (>90%). The pustules resolved without leaving pigmentation after 2 weeks. We diagnosed this case as sterile transient neonatal pustulosis., (© 2012 Wiley Periodicals, Inc.)

Proliferation and differentiation in the epidermis must be tightly regulated. This regulation is known to involve a range of transcription factors, including pituitary tumor transforming gene 1 (PTTG1), a ubiquitously distributed transcription factor that regulates keratinocyte proliferation and differentiation. Psoriasis is a common but refractory skin disorder, the pathophysiology of which is characterized by hyperproliferation and impaired differentiation in the epidermis. The present study was conducted to clarify the less well-known roles of PTTG1 in the pathophysiology of psoriasis, focusing on its relationship with tumor necrosis factor-α (TNF-α), which is a critical mediator of the disease. The levels of PTTG1 expression were increased in the psoriatic epidermis. Overexpression of PTTG1 resulted in the overproduction of TNF-α, and TNF-α itself had an inductive effect on PTTG1 expression, suggesting that their expression may involve autoinduction. Moreover, overexpression of PTTG1 involved augmented the expression of cyclin A and B1 proteins in both cultured keratinocytes and the psoriatic epidermis. Therefore, enhanced expression of PTTG1 in the psoriatic epidermis may result in aberrant regulation of the cell cycle and impaired differentiation via the interplay between PTTG1 and TNF-α.

Graft-versus-host disease (GVHD) is a frequent complication of bone marrow transplantation (BMT) that can be classified as acute or chronic. Characteristic cutaneous manifestations of acute GVHD, which generally occurs within 3 months following BMT, include maculopapular exanthema and perifollicular papular lesions. Psoriasiform skin eruption as a manifestation of acute GVHD is rare. We report the case of a 4-year-old boy who developed a generalized psoriasiform eruption shortly after undergoing an allogeneic BMT. Histologic features of both psoriasis and acute GVHD were present.

Loricrin is a major component of the epidermal cornified cell envelope, and is expressed only in terminally differentiated keratinocytes. This cell differentiation-specific expression pattern suggests specific regulatory mechanisms for activation and suppression of loricrin gene transcription in differentiated keratinocytes. Here, we identified a regulatory element in the proximal promoter region of the loricrin gene involved in suppression of its expression in keratinocytes. A database search indicated that this sequence contained a POU transcription factor binding motif. Electrophoretic mobility shift assay revealed that Oct-1, Oct-6, and Oct-11 actually bind to the motif. Constructs with point mutations in the POU-binding motif showed increased reporter activity, indicating that the POU factors negatively regulate loricrin gene transcription. Cotransfection experiments suggested that Oct-6 and Oct-11 suppress loricrin gene transcription in a cooperative manner with AP-1 and Sp1. Furthermore, in vitro experiments indicated that the Oct-6 and Oct-11 can physically associate with both AP-1 factors and Sp1/Sp3. These findings indicate that Oct-6 and Oct-11 contribute to the regulation of loricrin gene transcription via interaction with AP-1 factors and Sp1/Sp3.

The standard technique using lymphoscintigraphy, blue dye and a gamma probe has established a reliable method for sentinel node biopsy for skin cancer. However, the detection rate of cervical sentinel lymph nodes (SLN) is generally lower than that of inguinal or axillary SLN because of the complexity of lymphatic drainage in the head and neck region and the "shine-through" phenomenon. Recently, indocyanine green fluorescence imaging has been reported as a new method to detect SLN. We hypothesized that fluorescence navigation with indocyanine green in combination with the standard technique would improve the detection rate of cervical sentinel nodes. We performed cervical sentinel node biopsies using the standard technique in 20 basins of 18 patients (group A) and using fluorescence navigation in combination with the standard technique in 12 basins of 16 patients (group B). The mean number of sentinel nodes was two per basin (range, 1-4) in group A and three per basin (range, 1-5) in group B. The detection rate of sentinel nodes was 83% (29/35) in group A and 95% (36/38) in group B. The false-negative rate was 6% (1/18 patients) in group A and 0% in group B. Fluorescence navigation with indocyanine green may improve the cervical sentinel node detection rate. However, greater collection of data regarding the usefulness of cervical sentinel node biopsy using indocyanine green is necessary., (© 2013 Japanese Dermatological Association.)

Non-melanoma skin cancer is the most frequently occurring type of cancer worldwide and is caused by epidermal carcinogenesis and malignant progression that involve dysregulated expression of proto-oncogenes and tumor suppressor genes. The proto-oncogene pituitary tumor-transforming gene 1 (PTTG1) is a ubiquitously expressed transcription factor that can promote enhanced proliferation of cultured epidermal keratinocytes. To investigate the potential roles of PTTG1 in epidermal carcinogenesis and malignant progression, the expression of PTTG1 was analysed by immunohistochemistry along with Ki67, keratin 10 (K10) and p53 in tissue samples of cutaneous squamous cell carcinomas (SCC), actinic keratoses (AK) and Bowen's disease (BD). Expression levels of PTTG1 were compared among these disease groups to test for correlations with proliferation, differentiation capacity or the existence of mutated tumor suppressor genes in each disease group. In each disease group, the expression levels of PTTG1 correlated positively with those of Ki67, although the differentiation status, measured by K10 expression, did not show any correlation. In contrast, the existence of mutated p53 proteins showed a positive correlation only in the SCC group. Moreover, the expression levels of PTTG1 in SCC did not correlate with known prognostic factors such as TNM staging or tumor thickness. These results suggest that PTTG1 may represent a proliferation marker associated with mutated p53 proteins but is not an informative predictor of poor clinical outcomes in SCC., (© 2013 John Wiley & Sons A/S.)

Neurofibromatosis type I (NF1) is associated with typical hypervascular tumors, including neurofibroma, glioma, malignant peripheral nerve sheath tumors (MPNST) and glomus tumors. Previously, we and other groups reported that neurofibromas showed high-level expression of vascular endothelial growth factor (VEGF), a potent angiogenic factor involved in neovascularization. However, the molecular mechanism underlying the upregulation of VEGF in neurofibromas remains unclear. In this study, we examined the effects of Nf1 gene silencing on VEGF expression in Schwann cell and non-Schwann cell line and the upstream mTOR-HIF-1α - VEGF pathway in Schwann cell line. The results indicated that Nf1 gene silencing by lentiviral-mediated RNA interference resulted in elevated expression of VEGF, HIF-1α and phosphorylated mTOR at the protein level. The results obtained from Nf1 gene silencing in murine Schwann cell line analogously suggest that NF1 gene haploinsufficiency in human tumor Schwann cells may directly elicit upregulation of VEGF expression without the tumor microenvironment by activation of the mTOR-HIF-1α - VEGF pathway. We also showed that interleukin-6 is upregulated in Nf1 gene knock-down Schwann cells at the protein level., (© 2013 John Wiley & Sons A/S.)

Loricrin is a major component of the epidermal cornified cell envelope and is expressed only in terminally differentiated keratinocytes. This cell differentiation-specific expression pattern suggests specific regulatory mechanisms for activation of loricrin gene transcription in differentiated keratinocytes. Here, we identified a positive regulatory element in the proximal promoter region of the loricrin gene involved in activation of its expression in differentiated keratinocytes. A database search indicated that this sequence contained a GATA-3 binding motif. Constructs with point mutations in the GATA-3 binding motif showed decreased reporter activity, indicating that GATA-3 positively regulates loricrin gene transcription. Western blotting analysis indicated that GATA-3 is more abundant in differentiated than in undifferentiated keratinocytes. Cotransfection experiments indicated that GATA-3 activates transcription of the loricrin gene in a cooperative manner with c-Fos and Sp1. These findings indicate that GATA-3 contributes to keratinocyte differentiation-specific activation of loricrin gene transcription via interaction with c-Fos and Sp1., (© 2012 John Wiley & Sons A/S.)

The benefit of a sentinel lymph node (SLN) biopsy and adjuvant therapy for patients with thick (>4 mm) melanoma has not been well studied in the Asian population. We examined the benefit of an SLN biopsy and adjuvant therapy on prognosis in Japanese patients with thick melanoma. A review of the melanoma database collected from 26 institutions in Japan identified 291 patients with thick melanoma between 2005 and 2010. Univariate and multivariate analyses were performed to evaluate the factors predictive of the overall survival (OS) and the disease-free survival (DFS). Of the 242 patients with thick melanoma who underwent an SLN biopsy, the results for 96 (40%) were positive. On multivariate analysis, increased Breslow thickness (relative risk, 1.11; 95% confidence interval, 1.05-1.17; P=0.0002) and SLN metastasis (2.14; 1.04-4.43; P=0.040) were associated with a poor OS. Increased Breslow thickness (1.11; 1.04-1.18; P =0.0018), ulceration (3.11; 1.25-7.72; P=0.014), satellitosis (3.89; 1.62-9.31; P=0.0023), and SLN metastasis (2.24; 1.16-4.36; P=0.017) were associated with DFS. Adjuvant chemotherapy had no impact on either OS or DFS. Adjuvant use of a monthly dermal injection of interferon-β (IFN-β) was associated with a improvement in both OS (0.34; 0.17-0.67; P=0.0022) and DFS (0.42; 0.20-0.86; P=0.018). An SLN biopsy provided useful prognostic information and the adjuvant use of IFN-β improved both OS and DFS in Japanese patients with thick melanoma. These results were consistent with those of previous studies carried out on a white population. Therefore, we suggest that an SLN biopsy and adjuvant IFN should be considered for patients with thick melanoma irrespective of the Breslow thickness or ethnicity.

Giant congenital blue nevus (GCBN) is rare and usually occurs on the scalp. Malignant blue nevus (MBN) is also rare and has a poor prognosis. We report a case of MBN arising in a GCBN on the back. There have been three previous reports of MBN associated with GCBN on the trunk; our case had the earliest onset of MBN arising in a GCBN., (© 2012 Wiley Periodicals, Inc.)

Background and Objectives: Although sentinel lymph node (SLN) biopsy using radioisotope (RI) and blue dye (BD) achieved a high detection rate, approximately 5% of melanomas with negative SLNs develop nodal metastasis. We tested a new lymphatic navigation method using indocyanine green fluorescence imaging (ICG-FI) to detect such "occult" SLNs., Methods: Thirty-four skin cancer patients received SLN biopsy with the following three methods: RI (99Tc-tin colloid), BD (2% patent blue), and ICG (0.5% indocyanine green). Lymph nodes detected by any of the three methods were counted as SLNs., Results: ICG-FI detected more SLNs in 8 out of the 34 cases (24%). The average numbers of SLNs detected by ICG-FI, RI, and BD were 2.18, 1.76, and 1.73, respectively. Interestingly, ICG-FI not only detected more SLNs in one basin (ICG-FI: 1.64, RI: 1.50, and BD: 1.51 SLNs per basin), but also detected additional SLNs in other basins (ICG-FI: 1.32, RI: 1.18, and BD: 1.15 basins per case)., Conclusion: ICG-FI detected SLNs more efficiently than did the conventional methods, and these "occult" SLNs may offer an explanation for some false-negative cases. We recommend using ICG-FI in addition to a conventional method to reduce the risk of overlooking these "occult" SLNs., (Copyright © 2012 Wiley Periodicals, Inc.)

Subcutaneous panniculitis-like T-cell lymphoma is an uncommon form of CD8-positive cytotoxic T-cell lymphoma of the skin that predominantly affects the subcutaneous tissue and is extremely rare in early childhood (<3 yrs). Here, we present an early pediatric case with an indolent form of subcutaneous panniculitis-like T-cell lymphoma occurring at 12 months old. The subcutaneous nodules gradually disappeared spontaneously, and the girl showed excellent prognosis with no aggressive treatment., (© 2012 Wiley Periodicals, Inc.)

Background: Inguinal lymphocele is a well-known complication of inguinal lymph node dissection. Isosulfan blue has been used to identify and treat lymphoceles arising from lymphatics injured during surgery of the groin. However, the preventive use at the time of lymph node dissection has not been reported., Objectives: We evaluated the potential role of intraoperative injection of isosulfan blue during inguinal lymph node dissection for the prevention of postoperative lymphocele., Methods: We performed 43 conventional inguinal lymph node dissections (group A) and 7 inguinal lymph node dissections using isosulfan blue injection around the dissected inguinal region (group B) to identify lymphatic leakage intraoperatively., Results: Lymphoceles were observed in 13 of 43 dissections (30.23%) in group A and in 0 of 7 dissections (0%) in group B. The number of detected injured lymphatics ranged from 0 to 6 (mean 3.3) in group B. The mean postoperative lymphatic drainage output was less in group B than in group A. The mean number of days of suction catheter insertion was 4.43 days in group B, and 7.98 days in group A., Conclusions: The technique during inguinal lymph node dissection presented herein is useful for the prevention of postoperative lymphocele., (Copyright © 2011 Wiley Periodicals, Inc.)

The linear arrangement of discoid lupus erythematosus is uncommon. Here, we report a 6-year-old Japanese girl with linear discoid lupus erythematosus following the lines of Blaschko on her face and neck. Topical tacrolimus treatment improved the eruptions. The present case also indicated the important role of epidermal and dermal cells as well as immune cells in the pathogenesis of cutaneous lupus erythematodes., (© 2010 Wiley Periodicals, Inc.)

Tailgut cysts are rare benign cystic lesions of the retrorectal space. The recommended treatment is complete resection because these cysts have occasionally shown malignant transformation. However, a high index of clinical suspicion is required to reach a diagnosis. We report a 68-year-old man complaining of a subcutaneous mass in his right buttock. Magnetic resonance imaging (MRI) showed a large cystic mass extending 25.7 cm from the pelvis to the buttock. Radiological features indicated a benign cystic tumor, but the level of serum carcinoembryonic antigen (CEA) (87.5 ng/mL) was increased. An incisional biopsy did not define the true histological nature of the lesion and was not useful for surgical planning. Although MRI could not detect malignant changes, the elevated serum CEA indicated malignant degeneration. The patient required a Miles operation for complete resection. Surgical pathology revealed focal areas of high-grade adenomatous and adenocarcinomatous changes in the cyst wall. After surgery, the serum CEA level decreased to below the normal range. The case presented here shows that early malignant degeneration of TGC is difficult to detect by MRI. Thus, a tailgut cyst should be completely removed, even if radiological examination cannot detect malignant features. Measurement of serum CEA may be helpful when the tumor expresses this antigen.

We have demonstrated that dendritic cells (DCs) genetically modified to express tumor-associated antigens (TAAs) with retroviral vectors elicit more potential anti-tumor effect than those loaded with peptides because they can prime antigen-specific CD4+ T cells resulting in production of tumor-specific antibody. In this study, we showed the importance of antigen presentation via a major histocompatibility complex (MHC) class II molecule in cancer immunity against non-membrane bound TAAs such as the melanoma antigen gp100 by using DCs derived from MHC class II-deficient mice (C2KO). DCs were prepared by transduction of gp100 cDNA into haematopoietic progenitor cells obtained from C2KO followed by differentiation with cytokines (C2KO-gp/DCs). When C2KO-gp/DCs were inoculated into immunocompetent mice, the mice scarcely primed the antigen-specific Th1 cells and developed fewer CD8 T cells than did those inoculated with transduced DCs prepared from normal mice. The attenuated anti-tumor effect was also confirmed in a postimmunization setting where, while two of eight control mice eradicated the pre-existing melanoma cell line B16 (25%), no mice inoculated with C2KO-gp/DCs did. These results suggested not only the limitation of current protocols using MHC class I-restricted tumor peptides but also the usefulness of DCs expressing gp100 in vaccine therapy against melanoma.

Recently, low-dose 5-fluorouracil/cisplatin induction concurrent with radiation (chemoradiation) has been reported to be effective for locally advanced squamous cell carcinoma of the otorhinolaryngologic and gynecologic regions. However, to date, this therapeutic option has not been evaluated for squamous cell carcinoma of the skin. We evaluated chemoradiation therapy using cisplatin and 5-fluorouracil in two patients with locally advanced squamous cell carcinoma of the skin. Administration of cisplatin and 5-fluorouracil was conducted concurrently with conventionally fractionated radiation therapy. Cisplatin (patient 1: 4 mg/m(2)/d on days 1 to 5; patient 2: 15 mg/m(2)/d on days 1 to 5) and 5-fluorouracil (patient 1: 400 mg/m(2)/d for 7 days; patient 2: 850 mg/m(2)/d for 5 days) were administered intravenously for 1 hour and for 24 hours, respectively. Patient 1 underwent two courses of chemotherapy with a 3-week interval, and patient 2 underwent a single course of chemotherapy. The primary tumor of both patients showed complete regression, leaving ulceration. In patient 1, the ulceration completely resolved after 3 months. Patient 2 underwent surgical resection and full-thickness skin grafting. A histopathologic examination confirmed complete tumor regression. Neither patient suffered any serious side effects during this treatment. We conclude that chemoradiation using cisplatin and 5-fluorouracil was effective in these two patients with locally advanced squamous cell carcinoma of the skin. Several randomized studies have shown concurrent chemoradiation to be superior to radiation alone. This regimen is an option in managing patients who have unresectable primary tumors or who require preservation of local function.