Histopathological predictor of the progression from actinic keratosis to squamous cell carcinoma: quantitative computer-aided image analysis.

BACKGROUND: The current histopathological classifications for actinic keratosis (AK) are subjective, and histopathological factors predicting the progression into invasive squamous cell carcinoma (SCC) remain unclear. OBJECTIVES: To quantitatively assess the histopathological findings of AK and to investigate the predisposing factors for malignant transformation of AK. METHODS: A total of 502 AK specimens were retrospectively reviewed. The AK lesions were divided into the atrophic, intermediate, hypertrophic and bowenoid types. Histopathological features were quantitatively analysed using computer-aided image analysis. RESULTS: The epidermal thickness excluding the horny layer increased with statistical significance (P < 0.001) in order of atrophic, intermediate, hypertrophic and bowenoid type. The proportion of keratinocytic atypia was not significantly different among subtypes, except for the bowenoid type. Five of 498 cases were confirmed to develop into SCC. Bowenoid type, epidermal thickening and higher proportion of keratinocytic atypia were significantly associated with progression to invasive SCC in univariate analysis (OR = 12.571, 95% CI: 1.392-113.57; OR = 1.004, 95% CI: 1.001-1.007; OR = 1.069, 95% CI: 1.011-1.130, respectively). In multivariate analysis, only the proportion of keratinocytic atypia was an independent predisposing factor for progression to invasive SCC (OR = 1.069; 95% CI: 1.011-1.130). CONCLUSIONS: Histopathological subtypes based on the essential change of the epidermis well correlated with the actual epidermal thickness excluding the horny layer. The overall severity of keratinocytic atypia might be an independent risk factor for malignant transformation of AK.

Proton pump inhibitors as a possible cause of vitiligo: an in vivo and in vitro study.

BACKGROUND: Vitiligo is an acquired depigmentation disorder of melanocytes. Recently, some clinical reports have suggested that proton pump inhibitors (PPIs) may worsen vitiligo, but their effects on melanocytes have yet to be elucidated. OBJECTIVE: We investigated the effect of PPIs on melanogenesis in vivo and in vitro. METHODS: We examined the effect of PPIs on melanogenesis in B16 murine melanoma cells by measuring melanin content and tyrosinase (TYR) activity. TYR and tyrosinase-related protein-1 (TRP-1) were monitored by western blotting. Finally, a PPI was applied to zebrafish embryos to investigate its in vivo effect on pigmentation. RESULTS: In agreement with our clinical experience of worsened vitiligo after PPI treatment, PPIs decreased both melanin content and TYR activity. Western blotting showed that PPIs decreased TYR and TRP-1 protein levels. In the zebrafish test, PPIs inhibited body pigmentation in a dose-dependent manner. CONCLUSION: These results suggest that the functional inhibition of melanization by PPIs may induce or aggravate vitiligo lesions in genetically predisposed patients.

Clinical characteristics and risk of melanoma development from giant congenital melanocytic naevi in Korea: a nationwide retrospective study.

BACKGROUND: Giant congenital melanocytic naevi (GCMN) are known risk factors for the development of melanoma. However, melanoma risk among Asians is rarely evaluated. OBJECTIVES: To evaluate the clinical characteristics and risk of melanoma development from GCMN in Koreans, we performed a nationwide retrospective cohort study in Korea. GCMN were defined as those comprising ≥5% body surface area in children or measuring ≥20cm in adults. METHODS: In total, 131 patients with GCMN were enrolled, with a mean age of 10·3years (range: birth-70years). RESULTS: The posterior trunk was the most common site (67, 51·1%), followed by lateral trunk, anterior trunk, legs, both anterior and posterior trunk, buttocks, and arms. Satellite naevi were present in 69 cases (52·7%), and axial areas were more commonly involved in patients with satellite naevi than in those without satellite lesions. Atypical features such as rete ridge elongation and bridges were seen, and, among these, pagetoid spread and ballooning cell changes were more common in patients <4years old. Proliferative nodules were found in three cases. Melanomas had developed in three of 131 patients (2·3%; a 6-year-old girl, a 14-year-old girl and a 70-year-old man), and the incidence rate was 990 per 100000 person-years. Melanomas in these three patients consisted of two cutaneous melanomas and one extracutaneous meningeal melanoma. CONCLUSIONS: We should be aware of melanoma development from GCMN, and lifelong follow-up is required due to the risk of melanoma arising in GCMN.

Progress in understanding the neuronal SNARE function and its regulation.

Vesicle budding and fusion underlies many essential biochemical deliveries in eukaryotic cells, and its core fusion machinery is thought to be built on one protein family named soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE). Recent technical advances based on site-directed fluorescence labelling and nano-scale detection down to the single-molecule level rapidly unveiled the protein and the lipid intermediates along the fusion pathway as well as the molecular actions of fusion effectors. Here we summarize these new exciting findings in context with a new mechanistic model that reconciles two existing fusion models: the proteinaceous pore model and the hemifusion model. Further, we attempt to locate the points of action for the fusion effectors along the fusion pathway and to delineate the energetic interplay between the SNARE complexes and the fusion effectors.

Spitz naevus is rare in Korea.

BACKGROUND: Spitz naevi have not been widely studied in Asians. AIM: To compare the epidemiology and clinicopathological features of Spitz naevi in Koreans with lesions in western countries. METHODS: In total, 80 Spitz naevi in 77 patients diagnosed over 10 years at 17 university hospitals in Korea were analysed. RESULTS: The relative incidence of Spitz naevus vs. MM was 1 vs. 10.9. In most patients (75%) the Spitz naevi had been present for > 6 months. The size of the lesion was relatively large. Histologically, most of the lesions (54%) were the dermal type and pigmentation was common (49% of lesions). Immunohistochemical study found that all of the 34 lesions were positive for S-100 protein but only 14 (47%) were positive for HMB-45. CONCLUSION: Spitz naevus is rare in Korea. The lesions were more commonly larger, pigmented, and of the dermal type than reported in western countries.

Expression of the c-erb-B2 and p53 protein in gallbladder carcinomas.

Gallbladder carcinoma is the most common malignancy of the biliary tract in Korea and known to be more common in East Asia and Latin America than in Europe and North America. However, their exact histopathological characteristics and carcinogenesis are not well-elucidated. A total of 71 cases of gallbladder carcinomas, two cases of gallbladder dysplasia and 20 cases of gallbladder adenoma were immunohistochemically studied to evaluate the expression of c-erb-B2 and p53 proteins in the light of their relationship with various prognostic factors. Thirty-three gallbladder carcinomas (46.5%) showed positive staining for c-erb-B2, but none of the dysplasia and adenoma were positive (p<0.05). c-erb-B2 was stained in the cell membrane of the cancer cells. Adjacent normal mucosa was negative for c-erb-B2 staining. Forty-eight gallbladder carcinomas (67.6%) showed positive staining in the nucleus for p53 protein. None of the cases with dysplasia, adenoma, and normal mucosa stained positive for p53 protein. There was no significant correlation between c-erb-B2 and p53 expression and age, gender, histological tumor grade, and tumor stage. In the multivariate analysis, tumor stage approached statistical significance (p=0.05), but c-erb-B2 and p53 expression was not significant (p=0.14 and p=0.29, respectively). The mean survival periods of the c-erb-B2 positive and negative groups were 26 months and 52 months, respectively (p=0.02). However, the mean survival periods of the p53 protein positive and negative patients were 34 months and 35 months, respectively (p=0.45). In conclusion, our results suggest that c-erb-B2 and p53 protein expression is strongly associated with neoplastic progression in gallbladder carcinomas, and that c-erb-B2 expression identifies patients with a worse prognosis.

Sensory perineuritis presented as a mononeuritis multiplex associated with livedo vasculitis.

We report a 52-year-old patient affected by a mononeuritis multiplex and livedo vasculitis. Sural nerve biopsy showed mild thickening of the perineurium, vascular alterations with inflammatory cell infiltration in the perineurium, and remarkable loss of large and small myelinated fibers. A therapeutic trial of acetylsalicylic acid, danazol, and dipyridamole controlled the skin lesion without improvement of nerve conduction studies.

Complete remission of hypereosinophilic syndrome after interferon-alpha therapy: report of a case and literature review.

Hypereosinophilic syndrome (HES) is a multisystem disease with a significant mortality rate. It is characterized by peripheral blood eosinophilia and infiltration of eosinophils into many organs including skin. We describe a patient with cutaneous, pulmonary, and gastric symptoms of HES. He was first treated with systemic and topical corticosteroids, antihistamines, and photochemotherapy. Therapy was switched to interferon-alpha, because we had to consider side effects of corticosteroids and no significant improvement had been achieved. During the period of usage of interferon-alpha for 50 weeks, his symptoms of HES nearly cleared. There has been no recurrence in the eight months since the discontinuation of interferon-alpha therapy.

Eruptive vellus hair cyst in a patient with pachyonychia congenita.

Pachyonychia congenita is characterized by symmetrical nail dystrophy, palmoplantar keratoderma, oral leukokeratosis, and follicular hyperkeratosis. In addition to these features, multiple cutaneous cysts of various kinds have been described. We report a case of pachyonychia congenita associated with eruptive vellus hair cyst.

Colchicine treatment in a patient with neutrophilic dermatosis associated with rheumatoid arthritis.

Neutrophilic dermatoses (ND) are characterized by epidermal and dermal infiltrates of polymorphonuclear leukocytes (PMN), without any infectious or other detectable agents as a cause. We describe a case of ND, which very rapidly improved upon colchicine treatment. The patient was a 67-year-old female with an 8-month history of dusky-red, tender, swollen plaques and nodules with superimposed vesicles and bullae on the buttocks, hands, and ankles associated with rheumatoid arthritis. The diagnosis of ND was made on the basis of the clinical and histopathological features of the skin lesions. She was treated with 0.6 mg of oral colchicine twice daily. Within one week, the erythematous plaques and arthralgia began to recede and disappeared within four weeks. In our case, colchicine seemed to improve the signs and symptoms of ND and appeared to be more effective than the other drugs we had used.

Sweet's syndrome with abscess-like lesions in a patient with acute myelogenous leukemia.

We describe a 49-year-old man with acute myelogenous leukemia associated with Sweet's syndrome and abscess-like lesions mimicking an infectious disease. Although blisters may be included in the clinical spectrum, frank non-infectious abscesses have not been reported as far as we know. Clinicians should be familiar with this clinical and histopathologic variant of Sweet's syndrome. It is mandatory to make every effort to find an infectious cause for abscesses before a diagnosis of Sweet's syndrome is made.

Epstein-Barr virus-associated recurrent necrotic papulovesicles with repeated bacterial infections ending in sepsis and death: consideration of the relationship between Epstein-Barr virus infection and immune defect.

The disease of Epstein-Barr virus (EBV) -associated recurrent necrotic papulovesicles is a distinct clinicopathologic entity different from classic hydroa vacciniforme (HV). A few patients have been reported as atypical HV with systemic involvement, development of lymphoma, and poor prognosis. We describe a patient with recurrent necrotic papulovesicles and multiple varioliform scars in both sun-exposed and covered areas. In contrast to cases of previously reported atypical HV, our patient suffered from repeated bacterial infections on various sites ending in sepsis and death, but without malignant transformation. EBV was detected in the lymphoid cells from the skin lesions by anti-latent membrane protein (LMP) antibody and in situ hybridization. We suggest that the repeated bacterial infections in this case raise the possibility of an association of EBV infection with increased susceptibility to bacterial infections.

Genetic associations of IL1RN polymorphisms with metabolic syndrome in a Korean population.

Metabolic syndrome (MetS) is rapidly growing into one of the major public health issues worldwide. Interleukin 1 receptor antagonist (IL1Ra) functions as a competitor of proinflammatory cytokines and has an important role in metabolic functions, including insulin secretion. To identify the relationship between the interleukin 1 receptor antagonist gene (IL1RN) and MetS, we genotyped nine single nucleotide polymorphisms (SNPs) in the gene using direct sequencing in 66 MetS patients and 346 normal subjects in the Korean population. Among the nine polymorphisms, after adjusting for age and sex, rs928940 (G>T) showed a significant association with MetS in the codominant ( P= 0.023) and recessive models ( P= 0.011). Also, rs315952 (C>T) exhibited a significant association with MetS in the codominant model ( P= 0.046). The results suggest that the IL1RN polymorphisms may be associated with MetS in the Korean population.

Stromelysin-3 expression in the differential diagnosis of dermatofibroma and dermatofibrosarcoma protuberans: comparison with factor XIIIa and CD34.

BACKGROUND: The distinction between dermatofibroma (DF) and dermatofibrosarcoma protuberans (DFSP) is a well-known challenge for dermatopathologists. Immunohistochemical stains have been used to augment routine histological examination to aid in differentiating DF from DFSP. Stromelysin-3 (ST3) is a member of the matrix metalloproteinase (MMP) family, MMP-11, which is expressed in the skin during wound healing and in the stroma of basal cell carcinoma. Recent studies demonstrated that DFs expressed ST3, whereas DFSPs were only rarely ST3 positive. OBJECTIVES: To assess the expression of ST3 in DF and DFSP and to ascertain whether ST3 is superior to factor XIIIa or CD34 in differentiating DF from DFSP, by comparison with factor XIIIa and CD34 expression. METHODS: Immunohistochemical staining was performed on 23 cases of DF and 17 cases of DFSP, using antibodies to ST3, factor XIIIa and CD34. RESULTS: ST3 was expressed in all cases of DF (23 of 23) but only one case showed weakly positive staining in DFSP (one of 17). The mean +/- SD ST3 immunohistochemistry (IHC) score in DF was 4.52 +/- 0.67. The sensitivity of ST3 was 100% and the specificity was 94%. Factor XIIIa was expressed in all cases of DF (23 of 23) and in five of the 17 DFSPs. The mean +/- SD factor XIIIa IHC score in the DFs was 4.43 +/- 0.73. The sensitivity of factor XIIIa was 100% and the specificity was 71%. CD34 was expressed in four of the 23 DFs and 16 of the 17 DFSPs. The mean +/- SD CD34 IHC score in the DFSPs was 4.41 +/- 1.37. The sensitivity of CD34 was 94% and the specificity was 83%. CONCLUSIONS: Immunohistochemical staining with a commercial anti-ST3 antibody can be successfully carried out in routine dermatopathology. We confirmed that ST3 is a positive marker for DF and that ST3 staining might be more reliable than factor XIIIa staining in differential diagnosis of DF and DFSP. As the present study showed that ST3 was not absolutely negative in all cases of DFSP, the combination with CD34 immunostaining could make the distinction more reliable.

Cellulitis due to Escherichia coli in three immunocompromised subjects.

In adults, cellulitis is usually caused by group A streptococci and Staphylococcus aureus. However, in patients with underlying disease, it may be caused by other organisms, such as Acinetobacter, Clostridium septicum, Enterobacter, Haemophilus influenzae, Proteus mirabilis or Escherichia coli. We report three cases of cellulitis of the lower legs where E. coli was the causative bacterial organism. It is important to suspect E. coli as a causative organism if blistering cellulitis occurs, especially in patients with underlying diseases.

Giant congenital multiple patch-like glomus tumors.

Glomus tumors can be classified into solitary and multiple glomus tumors. Congenital multiple glomus tumors are extremely rare, and only 12 cases have been reported in the world literature. We describe the first case with giant congenital multiple patch-like glomus tumors that show partial atrophy.

Nasal-type T/natural killer cell angiocentric lymphoma, Epstein-Barr virus-associated, and showing clonal T-cell receptor gamma gene rearrangement.

Nasal-type T/natural killer (NK) cell lymphoma, which often shows an angiocentric growth pattern, is a distinct clinicopathological entity highly associated with the Epstein-Barr virus (EBV). This tumour has a characteristic immunophenotype, whereas the cytological spectrum is broad. It is known that a clonal T-cell receptor (TCR) gene rearrangement is not found in this tumour. However, it is still unresolved as to whether the finding of a clonal TCR gene rearrangement excludes the diagnosis of nasal-type T/NK cell lymphoma. We describe a case of nasal-type T/NK cell angiocentric lymphoma, EBV-associated, and showing clonal TCR gamma gene rearrangement. The patient died of sepsis 5 months after diagnosis in spite of aggressive chemotherapy.