Riei Kamo

Applicability of radiocolloids, blue dyes and fluorescent indocyanine green to sentinel node biopsy in melanoma

Patients with primary cutaneous melanoma underwent sentinel node (SN) mapping and biopsy at 25 facilities in Japan by the combination of radiocolloid with gamma probe and dye. Technetium‐99m (99mTc)‐tin colloid, 99mTc‐phytate, 2% patent blue violet (PBV) and 0.4% indigo carmine were used as tracers. In some hospitals, 0.5% fluorescent indocyanine green, which allows visualization of the SN with an infrared camera, was concomitantly used and examined. A total of 673 patients were enrolled, and 562 cases were eligible. The detection rates of SN were 95.5% (147/154) with the combination of tin colloid and PBV, 98.9% (368/372) with the combination of phytate and PBV, and 97.2% (35/36) with the combination of tin colloid or phytate and indigo carmine. SN was not detected in 12 cases by the combination method, and the primary tumor was in the head and neck in six of those 12 cases. In eight of 526 cases (1.5%), SN was detected by PBV but not by radiocolloid. There were 13 cases (2.5%) in which SN was detected by radiocolloid but not by PBV. In 18 of 36 cases (50%), SN was detected by radiocolloid but not by indigo carmine. Concomitantly used fluorescent indocyanine green detected SN in all of 67 cases. Interference with transcutaneous oximetry by PVB was observed in some cases, although it caused no clinical trouble. Allergic reactions were not reported with any of the tracers. 99mTc‐tin colloid, 99mTc‐phytate, PBV and indocyanine green are useful tracers for SN mapping.

Dermatofibrosarcoma protuberans with atrophic appearance at early stage of the tumor

We report a case of dermatofibrosarcoma protuberans (DFSP) which had looked like an atrophic plaque on the face for 20 years and been diagnosed as morphea. At the late stage after subsequent development of a nodule, histopathological examinations including immunohistochemical stainings revealed the final diagnosis of DFSP. While DFSP is given typical “protuberant” morphology, our case indicates that DFSP sometimes appears as a non‐protuberant lesion. Some reported variants of non‐protuberant DFSP are suspected to be preceding features at the early stage of DFSP before the protuberant feature occurs. We should take this preprotuberant stage of DFSP into consideration of different diagnoses with non‐protuberant lesions. Histopathological examination and immunohistochemical stainings are necessary for an accurate and early diagnosis of DFSP.

Induction of cytotoxic T cells as a novel independent survival factor in malignant melanoma with percutaneous peptide immunization.

BACKGROUND Malignant melanoma (MM) often shows multiple chemo-resistance, leading to poor prognosis of the patients. Therapeutic anti-cancer vaccination may be a feasible way to prolong the survival of patients. We have demonstrated that application of antigenic peptides via the tape-stripped, horny layer-removed skin, known as percutaneous peptide immunization (PPI), induces tumor cell-specific cytotoxic T lymphocytes (CTLs) in rodents and humans. OBJECTIVE To evaluate clinical significance of PPI in advanced MM patients. METHODS We performed PPI in 59 patients undergoing advanced MM with Melan-A, tyrosinase, MAGE-2, MAGE-3 and gp-100 peptides based on HLA typing in individuals. The induction of CTLs was assessed by the tetramer or pentamer flow cytometry in 35 patients. Patients showing positive CTL responses to all antigens were defined as complete responder (n=18), and those showing negative responses to at least one applied antigen were classified as incomplete responder (n=17). The primary endpoint of the study was overall survival (OS). For statistical analysis, log-rank test, univariate and multivariate Cox proportional hazard model were used. RESULTS OS of the complete responders was longer than that of the incomplete responders (median survival time: 55.8 vs 20.3 months, log rank P=0.089). A hazard ratio for the complete responders relative to the incomplete responders was 0.23 (95% confidence interval: 0.06-0.93, P=0.039) in a multivariate Cox proportional hazard model. CONCLUSION The induction of CTLs was a novel independent survival factor, and the induction of peptide-specific CTLs by PPI contributes to the prolonged survival and represents an impact on therapeutic approaches in MM. Unique trial number: UMIN000005706.

Dermoscopic features of pigmentation in Laugier-Hunziker-Baran syndrome.

Laugier-Hunziker-Baran syndrome (LHBS) is a rare, acquired, benign disorder of hyperpigmentation often involving the acral regions and the oral and genital mucosa and is frequently associated with longitudinal melanonychia. Because the lesions of LHBS often resemble various other mucocutaneous hyperpigmentary diseases such as Peutz-Jeghers syndrome, Addison’s disease, and malignant melanoma, detailed examination for systemic involvement is required for differentiation from these disorders. Dermoscopy is a useful noninvasive technique for more accurate diagnosis of various cutaneous pigmented lesions, and therefore it should also be applied to the lesions of LHBS, but the dermoscopic features of this disease are not well described. We report here a case of LHBS with results of detailed dermoscopic findings of the pigmented lesions.

Codeine Phosphate—Induced Hypersensitivity Syndrome:

OBJECTIVE To report a case of drug-induced hypersensitivity syndrome related to codeine phosphate. CASE SUMMARY A 19-year-old Japanese man was prescribed codeine phosphate 10 mg 3 times daily and several other drugs for cold symptoms. About 20 days later, an erythematous, maculopapular rash appeared and progressed to erythroderma; a spiking fever also developed. He had splenomegaly and generalized lymphadenopathy on admission. Laboratory examinations showed atypical lymphocytosis, eosinophilia, and increased liver enzyme values. The platelet count slowly decreased after admission. The increased numbers of megakaryocytes in bone marrow and platelet-associated immunoglobulin (Ig) G antibodies in serum were compatible with a diagnosis of immune thrombocytopenic purpura. A significant increase in IgG antibodies to human herpesvirus 6 (HHV6) and transient viremia were helpful in diagnosing hypersensitivity syndrome. The results of patch tests were positive for codeine phosphate. An objective causality assessment revealed that an adverse drug event was probable. DISCUSSION Codeine is an opioid analgesic. Severe adverse cutaneous reactions rarely occur. As of March 3, 2004, our case is, to our knowledge, the first report of hypersensitivity syndrome attributed to codeine phosphate. Drug-induced hypersensitivity syndrome is an acute, potentially life-threatening, idiosyncratic adverse reaction caused mainly by aromatic anticonvulsants. It is characterized by the triad of fever, skin rash, and internal organ involvement. Reactivation of HHV6 is involved in the pathogenesis of this syndrome and may have also caused the immune thrombocytopenic purpura in our patient. CONCLUSIONS Codeine phosphate may rarely be associated with hypersensitivity syndrome. Clinicians should be aware that the potentially fatal syndrome can be caused by various drugs.

Chromoblastomycosis caused by Fonsecaea nubica: First report from Japan.

Dear Editor, Chromoblastomycosis, a major deep fungal infection showing pink to dark red colored, slightly elevated, scaly lesion on the skin, is known to be caused conventionally by Fonsecaea (F.) pedrosoi. Recently, this species has been reclassified into F. pedrosoi sensu stricto, F. monophora, F. multimorphosa, F. nubica and F. brasiliensis based on results of molecular biological studies instead of from a morphological approach to the strain. We report the first case of chromoblastomycosis caused by F. nubica found in Japan. A 66-year-old Vietnamese man, who had lived in Japan for 20 years, came to our hospital with a refractory wound on the right thigh. He had injured his thigh with scrap wood in a garbage dump in Osaka approximately 18 months prior. He had no significant past history, and had generally been healthy. On physical examination, a well-defined, irregularly shaped, reddish brown plaque, 10 cm 9 5 cm in size, with partial ulceration and surrounded by atrophic scar was evident on the right thigh (Fig. 1a). A skin biopsy obtained from the erythematous part exhibited epithelioid histiocytes and multinucleated giant cells containing sclerotic cells histologically (Fig. 1b,c). Fungal culture showed a black–gray velvety colony (Fig. 1d,e). and the smear specimens revealed both Cladosporium and Rhinocladiella type conidia (Fig. 1f,g). The internal transcribed spacer (ITS) region of rDNA was directly sequenced from polymerase chain reaction product and the sequence was registered as LC030180 at the DNA Data Bank of Japan. Phylogenetic tree analysis by neighbor-joining method was performed with known sequences of Fonsecaea (a) (d) (f) (g)

A Case of Ileoileal Intussusception Caused by Metastatic Pedunculated Tumor of Cutaneous Angiosarcoma

Cutaneous angiosarcoma is a rare aggressive vascular tumor that occurs in elderly patients and is usually located on the head and face. Metastases often develop in the cervical lymph nodes, lungs, bone, liver and spleen. There have been no reports of ileoileal intussusception due to metastatic tumor from cutaneous angiosarcoma. We reported a case of cutaneous angiosarcoma in a 67‐year‐old Japanese male accompanied with ileoileal intussusception due to metastatic angiosarcoma. We assume that the metastatic tumor in the small intestine was metastasized hematogeneously from cutaneous angiosarcoma, resulting in the formation of nodules and the rapid growth of a pedunculated tumor as a forerunner of the ileoileal intessusception.

Localization of cellular neurothekeoma with magnetic resonance microscopy Imaging

change for 7 months. Pigmented epithelioid melanocytoma usually presents as a solitary, pigmented, dome-shaped nodule and has a predilection for the extremities and trunk. However, it rarely develops on oral and genital mucosae. It is characterized by medium to large heavily pigmented epithelioid melanocytes arranged as solitary units between the collagen bundles of the dermis. It requires differentiation from tumors like Spitz nevus, blue nevus, malignant blue nevus and malignant melanoma. In contrast to PEM, Spitz nevus is sparsely pigmented, and shows nested features in the reticular dermis. Moreover, Kamino bodies are occasionally found, and immunoreactivity for HMB-45 is negative in Spitz nevus. The presence of epithelioid cells is the most characteristic feature of PEM differentiating from blue nevus, which is mostly composed of spindled or dendritic cells. Malignant blue nevus can be differentiated by its high-grade cellular atypia, brisk mitotic activity, necrosis and increased Ki-67 immunoreactivity. Malignant melanoma can be easily differentiated by its typical pagetoid activity along the dermoepidermal junction, cellular pleomorphism, significant mitotic activity, infiltrating margins and peripheral inflammation. To our knowledge, PEM occurring on the genital mucosa has been rarely reported in the published work. Herein, we report a sporadic case of PEM found on the glans penis, a rare location, of a teenage boy without clinical evidence of the Carney complex. CONFLICT OF INTEREST: None.

Importance of sentinel lymph node biopsy in Merkel cell carcinoma

Dear Editor, Merkel cell carcinoma (MCC) is a rare aggressive skin cancer that occurs as a subcutaneous mass and is often definitively diagnosed by pathological examination. In elderly persons it has a tendency to develop on the head and neck, which are exposed to the sun. Patients with MCC have a poor outcome characterized by locoregional and distant relapse. The importance of multidisciplinary treatment of MCC based on its staging has been reported, and the use of sentinel lymph node biopsy (SLNB) as a tool for staging and for guidelines has been proposed. We report on a 44-year-old Japanese man with MCC in the left lower leg, in which he noticed a subcutaneous mass around April 2008. The mass gradually enlarged. He had the tumor removed at the previous clinic in August the same year. The mass was diagnosed as MCC by histopathological examination. Neither his medical history nor family history was contributory. He was referred to our department in September the same year. At presentation, he had an operative scar approximately 3 cm long in the left lower leg (Fig. 1a). The popliteal lymph nodes and inguinal lymph nodes were not enlarged. An image with a loupe revealed a round tumor 1.5 cm in diameter. The tumor extended from the dermis to the subcutaneous tissue. There were tumor cells in the surgical margin (Fig. 1b). Histopathological diagnosis was MCC (Fig. 1c,d). Immunohistochemical staining revealed that the cells were positive for CAM5.2 and AE1 ⁄AE3. CK20 was positive and appeared as a perinuclear dot-like pattern (keratin button). These findings were consistent with MCC. Image examinations revealed no lymph node or distant metastases (Fig. 2). Magnetic resonance imaging showed only operative changes in the left lower leg.

Onychocytic matricoma as an underrecognized benign mimicker of subungual malignant melanoma and Bowen's disease

Figure 1. (a) The nail plate of the ring finger with non-homogeneous brown pigmentation. (b) Dermoscopic findings: vague irregular longitudinal lines over a light brown background, nail scales (dashed blue circle), white dots (yellow circles) and splinter hemorrhage (red arrow). (c) Gross view of the specimen. (d–g) Histopathological findings. (d) Scan magnification: apparent acanthosis of the nail matrix and the nail bed. The blue box indicates the location of (e), the yellow box (f) and the red box (g) (hematoxylineosin [HE], original magnification 910). (e) Thickened nail plate with parakeratosis (HE, 9100). (f) Squamous eddy-like structures in pre-keratogenous zone (PKZ) cells (HE, 9200). (g) A keratinous cyst-like structure formed by a nest of pre-keratogenous and keratogenous zone (KZ) in concentric arrangements with nail plate in the center (HE, 9200).