Gulsen Kandiloglu

Accuracy in melanoma detection: A 10-year multicenter survey

BACKGROUND Early excision is the only strategy to reduce melanoma mortality, but unnecessary excision of benign lesions increases morbidity and healthcare costs. OBJECTIVE To assess accuracy in melanoma detection based on number-needed-to-excise (NNE) values over a 10-year period. METHODS Information was retrieved on all histopathologically confirmed cutaneous melanomas or melanocytic nevi that were excised between 1998 and 2007 at participating clinics. NNE values were calculated by dividing the total number of excised lesions by the number of melanomas. Analyses included changes in NNE over time, differences in NNE between specialized clinical settings (SCS) versus non-specialized clinical settings (NSCS), and patient factors influencing NNE. RESULTS The participating clinics contributed a total of 300,215 cases, including 17,172 melanomas and 283,043 melanocytic nevi. The overall NNE values achieved in SCS and NSCS in the 10-year period were 8.7 and 29.4, respectively. The NNE improved over time in SCS (from 12.8 to 6.8), but appeared unchanged in NSCS. Most of the effect on NNE in SCS was due to a greater number of excised melanomas. Higher NNE values were observed in patients younger than 40 years and for lesions located on the trunk. LIMITATIONS No data concerning the use of dermatoscopy and digital monitoring procedures were collected from the participating centers. CONCLUSION Over the 10-year study period, accuracy in melanoma detection improved only in specialized clinics maybe because of a larger use of new diagnostic techniques such as dermatoscopy.

Liposarcoma of soft tissue: MRI findings with pathologic correlation

ObjectiveTo evaluate the MRI findings of liposarcomas of different histologic types and correlate these with the histopathologic features.DesignThe MR images of seven liposarcomas were reviewed retrospectively to assess the tumor size, location, margination, signal characteristics and enhancement patterns in different histologic types.PatientsSeven liposarcomas comprising three well-differentiated, two myxoid and two pleomorphic types were evaluated.Results and conclusionAll tumors showed well-defined and mostly lobulated margins. The well-differentiated liposarcomas were composed mainly of fat with septations or nodules, were hyperintense on T2-weighted images, and demonstrated faint enhancement or no enhancement following intravenous contrast. Myxoid liposarcomas were homogeneous or mildly heterogeneous and a pseudocapsule was present in one case. Pleomorphic types showed a markedly heterogeneous internal structure. Both myxoid and pleomorphic lesions-showed moderate or marked heterogeneous enhancement after contrast administration. Well-differentiated liposarcomas may be differentiated from other types of the tumor by their largely lipomatous appearance. The malignancy grade increases in parallel with tumor heterogeneity and contrast enhancement.

Magnetic resonance imaging of intramuscular haemangiomas with emphasis on contrast enhancement patterns

Fifteen patients with intramuscular haemangiomas were evaluated with magnetic resonance imaging (MRI). Phleboliths were demonstrated by plain films or CT in six cases, which are characteristic for haemangioma. MRI showed intermediate or slightly high signal intensity on T1-weighted spin-echo images, and overall extremely bright signal on T2-weighted images. Twelve patients had a heterogeneous signal intensity and serpentine pattern on all sequences. A draining vessel was identified in a patient with histologically confirmed diagnosis of arteriovenous type of hemangioma. In three cases with localized small lesions, the MR appearance on T1 and T2-weighted conventional spin-echo sequences was homogenous. Two of the three showed a serpentine pattern on contrast enhanced images. In a patient with a soft tissue mass suspected of representing a haemangioma, MRI may provide more specific information, regarding the characteristics and extent of the lesion than other imaging techniques. In small localized lesions, contrast enhanced MRI may also offer significant advantage, making the identification of serpentine pattern possible which is a characteristic morphological feature of haemangioma.

P53 Protein expression in eccrine poroma and porocarcinoma

The role of p53 mutation has been shown in different human malignancies, including various skin cancers. In this study, we examined p53 protein expression in 25 eccrine poromas and 11 porocarcinomas by immunohistochemistry. P53 expression was observed in 88% (22 of 25) of eccrine poromas and 73% (8 of 11) of porocarcinomas. In eccrine poromas, percentage of cells reactive for p53 was less than 5% (low expresser) in 6 cases, 5 to 50% (moderate expresser) in 14 and greater than 50% (high expresser) in 2 cases. In terms of intensity, 13 cases showed weak staining, 8 moderate, and 1 case showed strong reactivity. On the other hand, 2 cases of porocarcinoma were low expresser, 2 were moderate and 4 were high expresser. All of the high expressers had also strong staining.This study has demonstrated that eccrine poromas showed significant p53 expression as much as porocarcinomas and, therefore, p53 positivity cannot be accepted as a valuable parameter for malignancy. P53 gene may involve in the carcinogenetic pathway of porocarcinoma but it is likely that other oncogenes may also have a role.

Granulomatous skin lesions, severe scrotal and lower limb edema due to mycobacterial infections in a child with complete IFN-γ receptor-1 deficiency.

Interferon-γ receptor-1 (IFNγR1) deficiency is caused by mutations in the IFNγR1 gene and is characterized mainly by susceptibility to mycobacterial disease. Herein, we report an 8-month-old boy with complete recessive IFNγR1 deficiency, afflicted by recurrent mycobacterial diseases with Mycobacterium bovis, Mycobacterium tuberculosis, Mycobacterium avium intracellulare and Mycobacterium fortuitum. Genetic analysis showed a homozygous mutation (106insT) in the IFNγR1 gene leading to complete IFNγR1 deficiency. In addition, he had atypical mycobacterial skin lesions caused by M. avium intracellulare and developed scrotal and lower limb lymphedema secondary to compression of large and fixed inguinal lymphadenopathies. Hematopoietic stem cell transplantation was performed from a matched unrelated donor at 5 years of age; however, he died at 9 months post-transplant. To our knowledge, the patient is the first case with IL-12/IFN-γ pathway defect and severe lymphedema. We have also reviewed and summarized the literature related with IFNγR1 deficiency.

Clinicopathological characteristics and mutation profiling in primary cutaneous melanoma.

Background:The incidence of mutations in malignant melanoma varies remarkably according to the subtype of melanoma, and this in itself is affected by racial and geographical factors. Studies screening melanoma case series for different types of mutations are relatively rare. Method:The authors analyzed the frequency of various somatic point mutations of 10 genes in 106 primary cutaneous melanoma cases. The mutations (BRAF, NRAS, KIT, CDKN2A, KRAS, HRAS, PIK3CA, STK11, GNAQ, CTNNB1) were evaluated with real-time PCR-based PCR-Array through allele-specific amplification, and the results were correlated with various clinicopathological characteristics. Results:Mutations were found in 64.2% of the melanomas overall. BRAF (42.5%), NRAS (15.1%), and CDKN2A (13.2%) were the 3 most common mutations. BRAF and NRAS mutations were more frequent in nodular and superficial spreading melanomas (P < 0.001). Associations with BRAF mutation were as follows: male gender [odds ratio (OR) = 2.4], younger age (OR = 2.7), superficial spreading (OR = 15.6) and nodular melanoma (OR = 9.5), trunk localization (OR = 6.3), and intermittent sun exposure (OR = 4.6). A considerable percentage of V600K (44.4%) mutations were found among the BRAF mutations, whereas KIT mutations (3.8%) were less frequent. Multiple mutations were detected in 13.2% of the melanomas. The most common co-occurrences were in the BRAF, NRAS, and CDKN2A genes. Conclusions:The authors analyzed 10 somatic mutations in the main subtypes of primary cutaneous melanomas from the western region of Turkey. Mutations were found in 64.2% of the melanomas overall. The most common mutations were in the BRAF and NRAS genes. In addition to other less common mutations, a notable number of multiple mutations were encountered. The multiplicity and concurrence of mutations in this study may provide further study areas for personalized targeted therapy.

Eruptive disseminated Spitz naevi: dermatoscopic features

Eruptive disseminated Spitz naevi is a rarely reported condition. Although the dermatoscopic features of nondisseminated, solitary forms of Spitz naevi are well known, there are no reports describing the dermatoscopic features of eruptive disseminated variant. We report an additional case and describe the dermatoscopic features. Two patterns were observed. In all pink lesions, the vascular pattern was seen, composed of dotted, linear or comma‐like vessels located at the centre of the meshes of the reticular depigmentation. In all brown lesions, we observed only the reticular pattern, which is quite interesting as the reticular pattern is a rare feature of Spitz naevi. This observation may be a special feature particularly seen in the eruptive disseminated variant. A superficial black network also accompanied reticular pattern in some lesions. In dichromatic lesions, both patterns were observed in different areas of the body.

BRAF-V600 Mutation Heterogeneity in Primary and Metastatic Melanoma: A Study With Pyrosequencing and Immunohistochemistry.

Background:The BRAF-V600 mutation is the most common mutation in cutaneous melanomas and is currently considered a target mutation when planning treatment for metastatic melanoma patients. Various techniques are used to determine the mutation status. The aim of this study was to determine the BRAF-V600 mutation status in primary and metastatic foci of melanoma cases and the consistency between the results of immunohistochemical and molecular methods. Methods:A total of 48 primary or metastatic cases were included in the study. Pyrosequencing was used as the molecular method and the VE1 antibody for immunohistochemical evaluation when determining the BRAF-V600 mutation. Results:The BRAF-V600 mutation was found in 75 of the 96 tumors (78.1%) from the 48 cases. V600E and V600K were present in 60 and 10 tumors, respectively, whereas V600R and V600M were present in 2 tumors and V600G in 1 tumor. There was no mutation in 5 metastases (12.8%) of the 39 cases with a V600 mutation in the primary tumor and no mutation in the primary tumor of 2 of the 36 cases (5.6%) with the V600 mutation in the metastasis. Fifty-six tumors were immunohistochemically positive where a V600E mutation was detected with pyrosequencing. Wild-type tumors (n = 20) and tumors with non-V600E mutations (n = 15) on pyrosequencing were immunonegative with VE1. The sensitivity and specificity of immunohistochemistry were 93.3% and 97.2%, respectively. Conclusions:In conclusion, BRAF-V600 mutation inconsistencies of up to 14.5% can be seen between the primary and metastatic foci in melanoma cases. These findings should be taken into account when planning targeted therapy and deciding on treatment responsiveness/unresponsiveness. An immunohistochemical method can be used as the first step to detect a BRAF-V600 mutation but additional molecular methods should be used when immunohistochemistry results are negative.

Public health education in Ege University Medical Faculty: Developing a community-oriented model

Background: Ege University Medical Faculty (EUMF) introduced a community-oriented curriculum in 2001. Aims: To evaluate the new public health education program in EUMF curriculum. Method: The study adopted triangulated methods. Quantitatively, a comparison of the students who were exposed to a community-oriented curriculum (Year 4 in 2007) was made with the students who were exposed to the traditional curriculum (Year 4 in 2005) in terms of their assessment of their achievement of our learning objectives. A total of 255 students in 2005 (80.7%) and 243 students in 2007 (81.5%) were surveyed using a questionnaire. Qualitatively, five focus group- and five individual interviews were performed with the 2007 cohort. Results: Except the one related to teamwork (p > 0.05) all learning objectives yielded significantly higher scores in the 2007 cohort than in the 2005 cohort (p < 0.05). The qualitative analysis supported the achievement of objectives in the 2007 cohort. The students appreciated the relevance of public health education with clinical subjects and interactive methods, but criticized didactic lectures and written assignments. Conclusions: A community-oriented approach is more effective in achieving a holistic approach to health problems. Improving community-based activities and assessment methods would be more successful in integrating population health into medical training.

Generalized pustular eruptions due to terbinafine

Terbinafine, a widely used antifungal agent, may rarely cause cutaneous side effects with an incidence of 2.7%. Generalized pustular eruptions are quite uncommon but severe adverse cutaneous reactions of terbinafine have been reported. The main pustular eruptions due to terbinafine include acute generalized exanthematous pustulosis and drug induced pustular psoriasis. In this report, two cases of acute generalized exanthematous pustulosis and one case of generalized pustular psoriasis triggered with terbinafine are presented.