Yayoi Niimi

Mast Cells in Basal Cell Carcinoma Express VEGF, IL-8 and RANTES

Background: Basal cell carcinoma (BCC) is the most common malignant tumor of the skin. Although an increase in mast cell infiltration was observed in BCC lesions, definite evidence of an active role of mast cells in the pathogenesis of BCC is still lacking. BCC is accompanied by cellular infiltrates. Moreover, the stroma in the BCC lesions is characterized by an increased number of mast cells and increased vascularity. The aim of this study was to elucidate the probable role of mast cells in BCC, especially focusing on the relationship between mast cells and lymphocytic infiltration as well as angiogenesis. Methods: We examined the expression and distribution of VEGF, IL-8 and RANTES in 16 nodular BCC lesions by immunohistochemistry. We also examined the lymphocyte subset, and the correlation between VEGF expression and microvessel density in the BCC lesion. mRNA expression of IL-8 and RANTES was examined by the reverse transcriptase-polymerase chain reaction. Results: T cells, especially CD4+/CD45RO+ memory T cells were the predominant infiltrating lymphocyte population in BCC lesions. An increased number of tryptase+ cells (mast cells) was found in the stroma. VEGF+/IL-8+/RANTES+ cells were also found abundantly in the stroma of all BCC lesions. The number of VEGF+, IL-8+ and RANTES+ cells was significantly higher than that in controls. By immunohistochemistry of serial sections, tryptase+ cells were found to express VEGF, IL-8 or RANTES. Messenger RNA expression of IL-8 and RANTES was also observed in the BCC lesions. Conclusion: This study suggests that mast cells may play an active role in the angiogenesis of BCC through the production of VEGF and IL-8. Furthermore, mast cells may also regulate lymphocytic infiltration through the production of IL-8 and RANTES.

Epidermolysis Bullosa Acquisita: Incidence in Patients With Basement Membrane Zone Antibodies

We examined the incidence of epidermolysis bullosa acquisita in patients with circulating basement membrane zone antibodies. Serum samples from 100 sequential patients with basement membrane zone antibodies were tested by indirect immunofluorescence against 1 mol/L sodium chloride split skin and by Western immunoblot against epidermal and dermal extracts of skin. Ninety-two (92%) serum samples stained only the epidermal side of split skin, 5 (5%) stained only the dermal side, and 3 (3%) stained both sides. Four of the 5 serum samples with dermal staining but none of the serum samples with epidermal or combined staining reacted with the 290-kd epidermolysis bullosa acquisita antigen by Western immunoblot. These results indicate that approximately 5% of unselected patients with basement membrane zone antibodies have epidermolysis bullosa acquisita or bullous lupus erythematosus rather than bullous pemphigoid.

Increased expression of matrix metalloproteinase-2, matrix metalloproteinase-9 and matrix metalloproteinase-13 in lesional skin of bullous pemphigoid.

Background: Matrix metalloproteinase (MMP)-2, MMP-9 and MMP-13 can degrade type IV collagen which is the major component of the basement membrane zone (BMZ). In bullous pemphigoid (BP), the separation occurs within the BMZ. Objective: To evaluate the involvement of MMPs in the pathogenesis of BP, we examined the expression of MMP-2, MMP-9 and MMP-13 in the lesional skin of BP patients. Methods: The expression of MMP-2, MMP-9, MMP-13, tissue inhibitors of metalloproteinase (TIMP)-1 and TIMP-2 was analyzed by immunohistochemistry in the lesional skin of BP patients in comparison with that in normal human skin. Next, the cellular sources of MMP-2, MMP-9 and MMP-13 were analyzed by double immunohistochemistry. Finally, the levels of these MMPs in the serum and blister fluid of BP patients were measured by ELISA. Results: The number of cells expressing MMP-2, MMP-9 and MMP-13 were significantly increased in the lesional skin of BP patients as compared to that in normal skin. Although the number of cells expressing TIMP-1 and TIMP-2 were also increased in the lesional skin of BP patients as compared to that in normal skin, the ratio of MMPs to TIMPs in the lesional skin of BP patients was high (2.4:1). T cells comprised the major source of MMP-2, MMP-9 and MMP-13, while a proportion of mast cells and eosinophils also expressed these MMPs. Furthermore, marked expression of MMP-2 was detected in the epidermal keratinocytes. The levels of these MMPs in the blister fluid were significantly greater than those in the serum. Conclusion: These results suggest that MMP-2, MMP-9 and MMP-13 may be involved in the mechanism of blister formation in BP and that besides infiltrating inflammatory cells, structural cells like epidermal keratinocytes may also participate in the induction of blister formation in BP.

Sebaceous Carcinoma of the Nose with a Regional Metastasis Following False-negative Sentinel Lymph Node Biopsy

A recent large-scale retrospective study has revealed that the frequency and aggressiveness of extraocular sebaceous carcinoma is comparable with that of the periocular counterpart (1) and a signiflcant number of extraocular sebaceous carcinomas show regional and widespread métastases (2). However, sentinel lymph node (SLN) biopsy has seldom been used for identifying regional nodal metastasis in extraocular sebaceous carcinoma. We report here the case of a nasal sebaceous carcinoma which was excised in combination with SLN biopsies showing no tumour cells. However, 6 months after surgery, a metastasis to the submental lymph node was detected. The efticacy of SLN biopsy in extraocular sebaceous carcinoma is discussed.

Paraneoplastic pemphigus presenting as mild cutaneous features of pemphigus foliaceus and lichenoid stomatitis with antidesmoglein 1 antibodies

Herein, we report a case of paraneoplastic pemphigus with mild skin features of pemphigus foliaceus and lichenoid stomatitis associated with B-cell lymphoma. A 49-year-old man presented with scattered blisters and erosions on the trunk along with mucosal blisters and erosions. Skin biopsy showed subcorneal acantholytic bulla and oral mucosal biopsy demonstrated lichenoid dermatitis. Direct immunofluorescence showed cell surface deposits of IgG and C3. Indirect immunofluorescence identified circulating IgG autoantibodies to the cell surfaces of normal human skin and also on the transitional epithelium of rat bladder. Enzyme-linked immunosorbent assay using recombinant baculoproteins showed positive antidesmoglein 1 autoantibodies (index 46) but negative antidesmoglein 3 autoantibodies (index 8). Immunoblot analysis using normal human epidermal extract detected BP230 and the 190 kDa periplakin, while immunoprecipitation using radiolabeled cultured keratinocyte immunoprecipitated BP230 and the 210 kDa envoplakin. We consider that the skin lesion was produced by humoral immunity whereas the oral lesion was produced by cellular immunity.

Type 2 segmental manifestation of disseminated superficial actinic porokeratosis in a 7-year-old girl

We report here a rare case of porokeratosis in which two different clinical types of porokeratosis (linear porokeratosis and disseminated superficial actinic porokeratosis) coexisted. A 7-year-old girl developed a centrifugal lesion on her left abdomen at the age of 2, disseminated superficial actinic porokeratosis on her face at the age of 3 after ultraviolet exposure, and linear porokeratosis on her left body at the age of 5. Histological findings corresponded with cornoid lamella. She was treated with topical maxacalcitol ointment and cryotherapy with considerable improvement. The combination of different types of porokeratosis in one individual is rare. We consider that this case may represent a type 2 segmental manifestation of disseminated superficial actinic porokeratosis.

Basal cell carcinoma arising on a chronic lymphedematous leg

We describe a case of an 82‐year‐old Japanese woman with basal cell carcinoma (BCC) on the leg with secondary chronic lymphedema due to treatment for uterine cancer. Sparse tumor nests with remarkable edema of the dermis in the nodule appeared to be influenced by the chronic lymphedema. However, it remains inconclusive whether or not the tumorigenesis of the BCC was associated with chronic lymphedema in this case.

Coexistence of acquired perforating dermatosis and bullous pemphigoid: three cases.

Both acquired perforating dermatosis (APD) and bullous pemphigoid (BP) are associated with a wide variety of systemic and cutaneous disorders [1, 2]. However, coexistence of APD and BP has never been reported. Herein, we describe three patients with coexisting BP and APD. The patients had several common features, suggesting that this condition is a new and unique clinical presentation associated with BP.Patient 1 was a 65-year-old male who presented with a three-month history of pruritic skin lesions [...]

Leg ulcer in a patient with 49, XXXXY syndrome

Figure 1. The right lower leg shows ulceration and pigmentation with marked edema. Dear Editor, The 49, XXXXY syndrome, first reported in 1960 by Fraccaro et al., is a supernumerary X chromosome aneuploidy syndrome with an approximate incidence of 1 in every 10 000–85 000 male births. Recently, the 49, XXXXY syndrome has been distinguished from Klinefelter’s syndrome (47, XXY) because of some dissimilarities in the clinical features of 49, XXXXY syndrome such as distinct facial feature abnormalities, eunuchoid habitus, multiple skeletal anomalies and genital abnormalities. There is also a variable degree of mental impairment, speech problems, and cardiac defects or renal anomalies in affected individuals. There have been very few reports on the dermatological findings of people with 49, XXXXY syndrome. Herein, we describe leg ulcers in a patient with 49, XXXXY syndrome. A 47-year-old Japanese man was referred to our outpatient clinic. He had had refractory ulcers on his lower legs for several years and an 8-year history of deep vein thrombosis (DVT) of the lower extremities. He was prescribed warfarin potassium at a dose of 3 mg ⁄day. He had exhibited mental retardation since childhood and his family history was not significant except for Addison’s disease in his mother. Physical examination revealed irregularly bordered ulcers (22 mm · 14 mm and 10 mm · 10 mm in size) with adjoining edema, erythema and pigmentation on the right leg (Fig. 1), eunuchoid habitus (height 173 cm, weight 73.5 kg), abnormal facial features (epicanthus, hypertelorism, broad nasal bridge and irregular teeth alignment), sparse body hair, and small penis and testes (Fig. 2). X-ray examination revealed cubitus valgus, radioulnar synostosis, genu valgum, kyphosis, and clinodactyly of the small fingers. Laboratory test results showed that the patient’s white blood cell count was 9500 ⁄lL and his C-reactive protein level was 6.14 mg ⁄dL. Other laboratory test results of the complete blood count and routine

Pretibial dystrophic epidermolysis bullosa with localized cutaneous amyloidosis: coincidental or secondary amyloidosis?

Here, we describe the case of a patient with pretibial dystrophic epidermolysis bullosa (PDEB) with amyloid deposition. The patient was a 40‐year‐old Japanese woman who presented a blistering eruption in the pretibial area with flat violaceous‐brown lichenoid papules. The histology of the blister revealed a subepidermal bulla with antibodies bound to basement membrane antigens on the blister roof by immunoflourescent mapping. Electron microscopy revealed a blister cleavage plane below the lamina densa. The histology of the lichenoid papules showed amyloid deposition in the papillary dermis. Because it was confined to just beneath the bulla base of the blister specimen, the amyloid deposition may have been derived from degenerated keratinocytes induced by damage to the epidermal–dermal junction due to blister formation in PDEB in this case. PDEB, in general, is often misdiagnosed as lichen amyloidosis; however, some PDEB cases could actually be associated with amyloid deposition.