Masahito Yasuda

Amalgam tattoo of the oral mucosa mimics malignant melanoma

Figure 1. Clinical features: A blue-black macule was seen on the floor of the oral cavity adjacent to a restored tooth with dental filling. Dear Editor, Amalgam pigmentation, generally called amalgam tattoo, is a pigmented lesion on the oral mucosa. Amalgam is the most commonly used dental restorative material for dental fillings because it is inexpensive and relatively easy to manipulate during placement. Amalgam is characterized by its initial pliability and it can be easily packed to fill any irregular space. It then forms a hard, durable compound with bacteriostatic effects. Amalgam fillings are made of a mixture of several metallic particles, especially mercury, silver and tin. Clinically, amalgam tattoos appear as blue, black or dark gray asymptomatic, flat macules on the oral mucosa, located adjacent to a restored tooth, most commonly on the gingival surfaces. A pigmented mucosal lesion requires an extensive differential diagnosis, particularly with malignant melanoma. A 63-year-old woman had received treatment to her teeth many years ago. When she received dental scaling 2 months prior, an asymptomatic pigmented lesion on the oral mucosa was pointed out by a dentist. Over the next 2 months, the lesion considerably enhanced. She was referred for evaluation of an asymptomatic pigmented lesion on the oral mucosa. Physical examination revealed a 9 mm · 6 mm blueblack macule, with irregular borders on the left floor of the mouth (Fig. 1). Regional lymphadenopathy was not noted. Adjacent to the pigmented lesion, a tooth restored with a dental filling was confirmed (Fig. 1). The results of routine laboratory tests including hematology, liver and renal functions as well as C-reactive protein levels were within normal limits. X-rays did not show the presence of metallic particles in the mucosa. With the main differential diagnoses of malignant melanoma and amalgam tattoo, the lesion was completely excised.

Prognostic significance of L-type amino acid transporter 1 (LAT1) expression in cutaneous melanoma.

Amino acid transporters play a crucial role in the development and invasiveness of cancer cells. However, it remains unclear whether or not the expression of L-type amino acid transporter 1 (LAT1) has prognostic significance in patients with cutaneous melanoma. A total of 128 patients with cutaneous melanoma were evaluated. Tumor sections were stained by immunohistochemistry for LAT1, CD98, Ki-67, and microvessel density determined by CD34 and p53. We also analyzed 30 specimens of patients with melanocytic nevi as negative controls. LAT1 and CD98 were highly expressed in 58% (75/128) and 75% (97/128), respectively. The rates of positivity for LAT1 in the melanocytic nevi were 0% (0/30). The expression of LAT1 was associated significantly with tumor thickness, T factor, CD98 expression, cell proliferation (Ki-67), and microvessel density (CD34). By Spearman’s rank test, LAT1 expression was correlated with CD98, Ki-67, and CD34. By univariate analysis, tumor thickness, ulceration, disease staging, LAT1, and CD34 showed a significant relationship with overall survival and disease-free survival. Furthermore, a multivariate analysis confirmed that LAT1 was an independent prognostic factor for predicting a poor prognosis. This study had a small sample size. LAT1 can serve as a significant prognostic factor to predict a poor outcome and it may therefore play an important role in the aggressiveness of cutaneous melanoma.

Circumscribed palmar hypokeratosis on both hands: distinct keratin expression in multiple depressed lesions

usually composed of spindle cells. Monomorphic epithelioid morphology as in our case is extremely unusual, and must be distinguished from epithelioid cell malignant tumours such as carcinoma, epithelioid haemangioendothelioma or angiosarcoma and melanoma. An accurate diagnosis may be impossible unless reliable immunohistochemistry is available and particularly HHV-8 nuclear immunostaining of tumour cells. Additional support may be obtained through the PCR identification of HHV-8 viral sequences in the skin lesions, although immunohistochemistry or in situ hybridization are the best techniques in this setting as they can localize HHV8 labelling specifically in tumour cells and not in normal or inflammatory cells. This evolutionary pattern, and particularly the progressive loss of HHV-8 immunoreactivity in a monomorphic pure epithelioid tumour, has not been to our knowledge previously described in the literature. Because anaplasia means loss of differentiation, our case is paradigmatic of the progressive morphological and functional dedifferentiation of KS, and supports both the appropriateness of the term ‘anaplastic’ and the value of HHV-8 immunostaining as a marker of evolving dedifferentiation for this unusual subtype of KS.

Digital Gangrene in Systemic Lupus Erythematosus

Digital ulcers and gangrene are common skin manifestations of connective tissue diseases, especially systemic sclerosis, although they are relatively rare in systemic lupus erythematosus. We describe here three patients with digital gangrene and systemic lupus erythematosus. None of the patients showed high disease activity of systemic lupus erythematosus at the time the digital gangrene developed. Two patients were positive for anti-RNP antibodies; however, no symptoms of other collagen diseases were present. One patient had anti-phosphatidylserine/prothrombin complex antibodies, and the other had anti-cardiolipin beta2 glycoprotein I antibodies and lupus anticoagulant at low titre. All patients showed narrowing or occlusion of radial and/or ulnar arteries in addition to digital arteries. Although a complication of anti-phospholipid syndrome is considered to be a possible cause, there may be unidentified causes other than thrombosis, atherosclerosis, overlap syndrome and vasculitis.

Spatial expressions of fibronectin and integrins by human and rodent dermal fibroblasts

Background  Human skin shows various morphological characteristics, depending on the body site. As these distinct phenotypes have been explained on the basis of the variance in epidermal keratinocytes and the presence of skin appendages, the spatial distinction of the dermal components has not been fully elucidated.

A Novel Chromosomal Translocation Associated With COL1A2-PDGFB Gene Fusion in Dermatofibrosarcoma Protuberans: PDGF Expression as a New Diagnostic Tool

Importance Dermatofibrosarcoma protuberans (DFSP) is a rare skin cancer that develops in the deep dermis to subcutaneous adipose tissues. A COL1A1-PDGFB gene fusion, leading to the constitutive expression of PDGFB, is the tumorigenic mechanism in most DFSP cases. Objectives To evaluate the specificity of PDGFB expression as a diagnostic marker of DFSP and to determine whether other pathomechanisms (ie, gene fusions) exist in patients with DFSP without the COL1A1-PDGFB fusion gene. Design, Setting, and Participants All patients with DFSP registered in the pathologic database of the University of the Ryukyus from January 1, 1997, through December 31, 2013, and Gunma University from January 1, 1996, through December 31, 2011, were included in this analysis. Samples were obtained from 30 patients presenting with DFSP tumors. We examined the clinicopathologic characteristics and the expression of PDGFB, PDGFRβ, PDGFRα, CD34, nestin, factor XIIIa, fibronectin, α-smooth muscle actin, S-100 protein, and Ki-67 in 30 DFSP cases and 48 non-DFSP mesenchymal tumor cases by immunohistochemical analysis. We then analyzed tumor tissues for the presence of the COL1A1-PDGFB fusion gene. We also tested whether other genes enriched in fibroblasts formed fusion products with PDGFB by reverse transcription-polymerase chain reaction analysis, using gene-specific primers. Main Outcomes and Measures We aimed to analyze tumor tissues for the presence of the COL1A1-PDGFB fusion gene to investigate expression of PDGFB in DFSP tumors. Results PDGFB expression was detected in 28 (93%) of 30 patients with DFSP. PDGFB was not homogenously expressed in DFSP tumor cells, whereas CD34 and nestin were often expressed throughout the tumor mass. In 1 DFSP tumor, the COL1A1-PDGFB fusion gene was not detected even though PDGFB was expressed. We identified a novel COL1A2-PDGFB fusion gene in this tumor. Conclusions and Relevance Our findings indicate that PDGFB protein is expressed in most DFSP tumors and may be a useful diagnostic tool when used in conjunction with CD34 and nestin expression analysis. These PDGFB expression data, in addition to our discovery of a novel PDGF fusion gene, strongly support the concept that DFSP is a PDGFB-dependent tumor type.

Two cases of dyshidrosiform pemphigoid with different presentations.

We report two cases of dyshidrosiform pemphigoid (DP) with different presentations. One patient was a 65‐year‐old Japanese man, who had been diagnosed with dyshidrosis and had been treated before visiting our hospital. When we stopped all treatments, the vesicles increased and spread to the trunk and limbs. We made a diagnosis of vesicular pemphigoid (VP) that was concomitant with or transformed from DP. Using Western blotting, the sera reacted with antigens with molecular weights of 60 and 180 kDa. The 60‐kDa antigen has not been found previously in the sera of patients with VP. The other patient was a 94‐year‐old Japanese woman, who presented with redness and swelling with bullae on the palmoplantar areas. Five days later, areas of oedematous erythema, as seen in prototypical bullous pemphigoid (BP), developed on the limbs. Study of the distribution of the BP antigen may elucidate the mechanisms involved in localized forms of BP such as DP.

Bowen's disease involving the urethra.

Bowens disease developing on mucous or mucocutaneous regions is clinically called erythroplasia of Queyrat. We report herein a 56‐year‐old male with Bowens disease extending from the penis shaft to the glans penis, and urethral meatus. Physical examination revealed bright red velvety plaques on the prepuce and glans penis and an irregularly pigmented scaly lesion on the dorsum of his penis shaft. Histopathological findings of both lesions were compatible with those of Bowens disease, supporting the concept that erythroplasia of Queyrat and Bowens disease should be regarded as one clinicopathologic entity. A partial penectomy was finally performed, because tumor cells were pathologically observed in the mucous epithelium of the urethra. Although several therapeutic modalities exist for Bowens disease on the external genitalia, treatment options are limited when Bowens disease extends to the urethral meatus. We discussed the recent therapeutic modalities in genital Bowens disease.

Decreased expression of class III β-tubulin is associated with unfavourable prognosis in patients with malignant melanoma.

Class III &bgr;-tubulin (TUBB3) has been recognized as being associated with resistance to taxane-based regimens in several cancers. However, little is known about the clinicopathological significance of TUBB3 expression in patients with cutaneous malignant melanoma. The aim of this study was to examine the prognostic significance of TUBB3 expression in cutaneous malignant melanoma. A total of 106 patients with surgically resected cutaneous malignant melanoma were assessed. Tumour sections were immunohistochemically stained for TUBB3, Ki-67 and microvessel density with CD34. TUBB3 was highly expressed in 80% (85/106) of patients. No statistically significant relationship was observed between the high expression of TUBB3 and any variables. On univariate analysis, ulceration, disease stage, TUBB3 and CD34 revealed a significant relationship with overall survival and progression-free survival. Multivariate analysis confirmed that a low TUBB3 expression was an independent prognostic factor for poor prognosis of cutaneous malignant melanoma. The decreased expression of TUBB3 could be a significant marker for predicting unfavourable prognosis in patients with cutaneous malignant melanoma.

Reactive proliferation of endothelial cells and pericytes associated with arteriovenous malformation

Arteriovenous malformation (AVM) is a structural vascular abnormality with no proliferation of cellular components. We report on a 53‐year‐old man who presented with a 15‐year history of a progressively enlarging nodule on his lower lip. A dark‐reddish, easy‐bleeding nodule diagnosed as AVM was resected to reduce the volume and troublesome bleeding. Histologically, the nodule revealed that the proliferating cellular area was composed of endothelial cells and pericytes in addition to the area of dilated vessels. We speculated that the cell proliferation developed secondary to AVM. We also discuss the histological differential diagnosis of spindle cell hemangioma and pseudo‐Kaposi’s sarcoma.