Genomic profiling with whole-exome sequencing revealed distinct mutations and novel pathways in Asian melanoma.

The clinical characteristics of malignant melanoma are highly variable between patient populations of different ethnicities. To explore the underlining genetic variations, we reviewed the clinical data of 242 malignant melanoma cases from Taiwan and among them submitted formalin-fixed paraffin-embedded tissue samples from 37 patients for whole-exome sequencing to identify the mutational signatures, tumor mutation burden and specific gene mutations. The genomic profiles and clinical outcomes were compared with the information derived from the publicly available TCGA and TGEN databases. Mutation signature 12 was the dominant signature in Taiwanese patients and represented approximately 45% of the mutation signatures observed. In contrast, mutation signature 7 was the most prominent among cases available in the TCGA database. Common gene mutations found in the TCGA melanoma dataset were not frequently found in melanomas from Taiwanese patients. There were a significant number of specific gene mutations that exclusively occurred in acral subtype but not in non-acral subtype melanomas, and vice versa. While certain common mutations form a shared core of genetic features, there appear to be specific genetic pathways that are involved in the occurrence of melanomas that grow in non-UV-exposed areas. Our findings have shed light on the tumorigenesis pathways involved in malignant melanoma.

Investigation of Prognostic Features in Primary Cutaneous and Soft Tissue Angiosarcoma After Surgical Resection: A Retrospective Study.

Primary cutaneous and soft tissue angiosarcoma is a rare but highly aggressive malignancy. To date, surgical resection is the mainstay of treatment, but poor prognosis is expected. To investigate whether there are factors associated with poor prognosis after surgical resection and to develop a treatment guideline for current therapy, we retrospectively collected data on 28 patients who underwent surgery as initial treatment and reviewed patient demographics, tumor characteristics, disease courses, and prognoses from September 1996 to May 2013. Of these 28 patients, 17 (60.7%) were men and the mean age at first diagnosis was 66.57 ± 18.57 years. Anatomically, 17 (60.7%) tumors were in the scalp and 11 (39.3%) were in other sites of the body. Of the 28 patients, 23 (82.1%) had achieved negative surgical margins, 24 (85.7%) received adjuvant radiation therapy, and 17 (60.7%) received adjuvant chemotherapy. Twenty-one patients (75%) died during a mean follow-up time of 35.86 ± 28.91 months, and all deaths were caused by angiosarcoma. The 5-year overall survival rate was 17.86%. Sixteen (57.1%) patients had locoregional tumor recurrence, and 20 (71.4%) had distant metastases, with a median of 9.17 (range, 1.9-98.07) months to recurrence or metastasis. Possible predictors of poor prognosis (P < 0.05) in terms of disease-free survival after surgical resection were male sex, cardiovascular disease, smoking, and scalp angiosarcomas, those in terms of overall survival were older than 70 years, male sex, cardiovascular disease, smoking, scalp angiosarcomas, distant metastases, and not receiving adjuvant chemotherapy. In conclusion, although multimodal treatments are used, the overall prognosis after surgical resection is still poor, especially for patients with the above predictive factors. An early diagnosis and complete resection of the primary tumor with or without adjuvant radiotherapy and chemotherapy are suggested for a potential better outcome. For those who have a diffuse lesion pattern with the involvement of vital structures, recurrence, or metastasis, palliative resection could be an alternative treatment choice.

Clinicopathology of Immunoglobulin G4-Related Chronic Sclerosing Sialadenitis: A Single-Center Study.

OBJECTIVES: To investigate the clinicopathologic characteristics of patients with immunoglobulin G4-related chronic sclerosing sialadenitis (IgG4-RCSS), a recently recognized disease. STUDY DESIGN: Case series with chart review and pathology study. SETTINGS: Tertiary care hospital. SUBJECTS AND METHODS: We evaluated chronic sialadenitis specimens obtained over 11 years using pathologic examination and IgG4 immunohistochemistry staining. The specimens were assigned a revised diagnosis of IgG4-RCSS or chronic sialadenitis not otherwise specified, and clinicopathologic data from each group were compared. RESULTS: Of the 84 patients, 21 were diagnosed with IgG4-RCSS and 63 with chronic sialadenitis not otherwise specified. IgG4-RCSS patients were older (68.2 ± 13.9 vs 54.2 ± 15.8 years, P = .001), predominantly male (85.7% vs 61.9%, P = .036), and more likely to present with painless swelling (75% vs 44.3%, P = .001) and bilateral involvement (52.4% vs 6.3%, P < .001). Ratio of IgG4-positive plasma cells to IgG-positive plasma cells in IgG4-RCSS tissues was 0.81 ± 0.14. The mean value of serum IgG4 in IgG4-RCSS patients was 918.8 mg/dL. CONCLUSION: IgG4-RCSS is more common in older male patients and frequently presents with bilateral involvement. Informing head and neck surgeons of the clinical features of IgG4-RCSS and promoting a combined approach of clinical evaluation, imaging, and biopsy can improve the accuracy of preoperative diagnoses.

Clinical Manifestation, Diagnosis, and Surgical Treatment of Chronic Radiation Ulcers Related to Percutaneous Coronary Intervention.

Chronic radiation ulcers that develop after cardiac catheterization have become common recently because of the rapid increase in the use of diagnostic and interventional cardiac catheterization procedures. However, their diagnosis and treatment remain difficult. We encountered 10 patients with National Cancer Institute grade 4 radiation ulcers related to prolonged percutaneous coronary intervention. Data of these 10 patients, including clinical presentations and treatments, were collected and analyzed. A quality-of-life questionnaire was administered to the patients preoperatively and postoperatively. Most of the lesions (8/10 patients) were located on the back. All of the patients received prolonged cardiac catheterization lasting for more than 3 hours, at least once, and all of the coronary artery lesions showed chronic total or near-total occlusion. The surgical procedures included complete resection of the lesion followed by fasciocutaneous flap coverage (9/10) or skin grafting (1/10). The mean ± SD follow-up time was 23.3 ± 19.79 months, and the wounds in all the patients healed well without complications. After the surgery, the symptoms reduced and the quality of life improved significantly according to the scores in the quality-of-life questionnaire. In conclusion, the early diagnosis of chronic ulcers related to prolonged percutaneous coronary intervention depends on careful history taking and a highly suspicious clinical presentation. For National Cancer Institute grade 4 radiation ulcers, complete resection and immediate reconstruction with flaps or grafts may improve the symptoms and achieve reliable wound coverage without complications.