Angiosarcomas (AS) are rare vascular malignancies that arise either de novo as primary tumors or secondary to irradiation or chronic lymphedema. The cytogenetics of angiosarcomas are poorly ...characterized. We applied array-comparative genomic hybridization as a screening method to identify recurrent alterations in 22 cases. Recurrent genetic alterations were identified only in secondary but not in primary AS. The most frequent recurrent alterations were high level amplifications on chromosome 8q24.21 (50%), followed by 10p12.33 (33%) and 5q35.3 (11%). Fluorescence in situ hybridization analysis in 28 primary and 33 secondary angiosarcomas (31 tumors secondary to irradiation, 2 tumors secondary to chronic lymphedema) confirmed high level amplification of MYC on chromosome 8q24.21 as a recurrent genetic alteration found exclusively in 55% of AS secondary to irradiation or chronic lymphedema, but not in primary AS. Amplification of MYC did not predispose to high grade morphology or increased cell turnover. In conclusion, despite their identical morphology, secondary AS are genetically different from primary AS and are characterized by a high frequency of high level amplifications of MYC . This finding may have implications both for the diagnosis and treatment of these tumors.
Background: High IMP3 expression is correlated with a worse outcome. Until now, there have been no data about IMP3 expression and clinical outcome for high-risk localisation of squamous cell ...carcinoma of the skin (cSCC). Methods: One-hundred twenty-two patients with cSCC of the lip and ear were included, and IMP3 expression in the tumours was immunohistochemically assessed in different evaluation approaches. Subsequently, subgroups were analysed in a matched pair approach and correlated with clinical pathologic parameters. In the following, different IMP3 analysis methods were tested for clinical suitability. Results: We found a significant correlation between IMP3 expression and risk for lymph node metastasis, local relapse, and progression-free survival. Conclusions: On basis of our data, we suggest a prognostic benefit cutoff value for high (>50%) and low (<50%) IMP3 expression. Thus, IMP3 expression has a high scientific potential for further studies and could potentially be used as a prognostic marker in diagnostic and therapeutic decision-making.
Abstract OBJECTIVES : Basosquamous carcinoma (BSC) is a rare tumor entity, and the most common onset is in the head and neck region (BSC-HN). The data on diagnosis, treatment, and especially risk ...assessment concerning disease course and outcome are deficient or inconsistent. This study aimed to evaluate risk factors for local relapse (LR) and lymph node metastasis (LNM) and their impact on progression-free survival (PFS). MATERIALS AND METHODS: In a retrospective monocentric study, patients with BSC-HN treated between 1999 and 2011 were analyzed regarding clinical and histologic characteristics. Prognostic parameters for LR, LNM, and PFS were evaluated. In total, 89 patients (55 male, 34 female, mean age of 71.8 years) with a mean follow-up time of 47.7 months (range 12-112) were included. RESULTS: LR occurred in four patients (4.5%), LNM occurred in five patients (5.6%). Patients with LNM had a significantly shorter PFS time (16.1 months) compared with patients without LNM (154.2 months; P < .001). Tumor depth and size (T classification), incomplete resection, localization at the ear, deep maximal vertical infiltration, muscle and vessel invasion all showed significant ( P < .05) associations with LR, LNM, and shorter PFS time. BSC showed more histologic features of basal cell carcinoma (BCC), especially with regard to BerEP4 expression. CONCLUSION: While histology shows some typical characteristics of BCC, the biologic behavior and aggressiveness of BSC are similar to those of cutaneous squamous cell carcinoma. This is the first study to show that LR and, especially, LNM indicate a higher risk of an unfavorable outcome.
In the European Organization for Research and Treatment of Cancer (EORTC) classification 2 types of primary cutaneous large B-cell lymphoma (PCLBCL) are distinguished: primary cutaneous follicle ...center cell lymphomas (PCFCCL) and PCLBCL of the leg (PCLBCL-leg). Distinction between both groups is considered important because of differences in prognosis (5-year survival > 95% and 52%, respectively) and the first choice of treatment (radiotherapy or systemic chemotherapy, respectively), but is not generally accepted. To establish a molecular basis for this subdivision in the EORTC classification, we investigated the gene expression profiles of 21 PCLBCLs by oligonucleotide microarray analysis. Hierarchical clustering based on a B-cell signature (7450 genes) classified PCLBCL into 2 distinct subgroups consisting of, respectively, 8 PCFCCLs and 13 PCLBCLsleg. PCLBCLs-leg showed increased expression of genes associated with cell proliferation; the proto-oncogenes Pim-1, Pim-2, and c-Myc; and the transcription factors Mum1/IRF4 and Oct-2. In the group of PCFCCL high expression of SPINK2 was observed. Further analysis suggested that PCFCCLs and PCLBCLs-leg have expression profiles similar to that of germinal center B-cell–like and activated B-cell–like diffuse large B-cell lymphoma, respectively. The results of this study suggest that different pathogenetic mechanisms are involved in the development of PCFCCLs and PCLBCLs-leg and provide molecular support for the subdivision used in the EORTC classification.
Abstract Background Cutaneous angiosarcoma of the head and neck (cAS-HN) is a rare malignancy with poor survival. Most of the histological markers and grading were not proven to be significant for ...prediction of outcomes in cAS-HN. This study aimed to find prognostic clinical features and histologic markers for cAS-HN. Material and methods We retrospectively analysed primary cAS-HN's seen in a single institution between 1980 and 2009. Clinical data and specific histologic characteristics were assessed. Outcome parameters were analysed using uni- and multivariate statistics. Results 80 patients (mean age 71.4 (SD 14.4) years, average follow-up time 55.3 (SD 74.4) months) were included. 5-year DSS rate was 62%. Univariate analysis revealed the extent of primary tumour (affecting more than one anatomical region), incomplete resection and initial metastatic disease as significant ( p < 0.05) predictors for unfavourable disease specific survival (DSS) rates and time. Multivariate analysis confirmed age over 70 years, incomplete resection and initially distant metastasis influencing outcome adversely. Analysis of specific histological markers in 37 cases found patterns of growth (solid areas greater than 80%) associated with better survival ( p = 0.011). Conclusion In conclusion age, number of affected regions, initial metastasis, complete initial resection and pattern of growth significantly affected mortality rates.
Background There is a growing body of literature that has enhanced our understanding of the biology of primary cutaneous diffuse large B-cell lymphoma (PCDLBCL) including in the context of gene ...profiling studies. Recent studies have demonstrated an activated proliferation profile associated with leg type lymphoma including overexpression of proto-oncogenes PIM1, PIM2, and cMYC, and the transcription factors MUM1 and OCT2. Although gene profiling is very useful in understanding the molecular basis of diffuse large B-cell lymphoma (LBCL), it is not practical from a routine diagnostic perspective. In this regard, the purpose of the study was to further define an armamentarium of easily applied immunohistochemical stains to accurately prognosticate PCDLBCL. Methods In all, 35 patients with PCDLBCL, 14 of follicle center and 21 of leg type, were analyzed using antibodies against CD5, CD138, BCL2, BCL6, OCT2, MUM1, FOXP1, and cMYC. Findings were correlated with clinical data. Results All cases stained negative for CD5 and CD138. Both subtypes differed in distinct staining patterns for BCL6, BCL2, OCT2, MUM1, and FOXP1. Staining for BCL2, OCT2, and/or MUM1 was associated with poor, and BCL6 with a favorable prognosis. Expression of cMYC was irrespective of prognosis or subtype, whereas ulceration or primary manifestation on the leg or multiple lesions was indicative for worse prognosis. Limitations Case number was a limitation. Conclusion Discriminating PCDLBCL supports the validity of the World Health Organization/European Organization for Research and Treatment of Cancer classification. To identify risk factors in patients with PCDLBCL we recommend thorough evaluation of clinical presentation and exploratory staining pattern for BCL2, BCL6, MUM1 and OCT2.
Patients belonging to xeroderma pigmentosum (XP) complementation group C comprise one‐third of all XP patients. Only four major reports compiled larger groups of XP‐C patients from southern Europe ...(12 pts), North America (16 pts) and Africa (14 and 56 pts) as well as their genetic background (46 XPC mutations). We identified 16 XP‐C patients from Germany. Interestingly, only five patients exhibited severe sun sensitivity. The mean age of XP diagnosis was 9.4 years, and the median age of the first skin cancer was 7 years. Neurological symptoms were absent in all but two patients. Primary fibroblasts from all 16 patients showed reduced post‐UV cell survival (mean: 50% vs 93% in normal cells) and reduced reactivation of an UV‐treated luciferase reporter gene (mean: 6.4% vs 30.7% in normal cells). XPC mRNA expression was also greatly reduced compared with normal cells (mean: 14.3%; range 8.3–25.7%) except in XP47MA (274.1%). All patients carried homozygous XPC mutations. Four mutations have been described previously: c.1747_1748delTG (found in 4/16), c.567 C>T (4/16), c.1839 C>T (1/16) and a complex insertion/deletion mutation in exon 9 (1/16). The novel frameshift mutations c.446_447delAG (2/16), c.1525insA (1/16) and c.2271delC (1/16) lead to truncated XPC proteins as does the novel nonsense mutation c.843C>T (1/16). XP47MA carries an interesting mutation (c.2538_2540delATC; p.Ile812del) resulting in an in‐frame single amino acid deletion. This mutation results in a classical XP phenotype, a non‐functional XPC protein, but elevated XPC mRNA expression. Our study indicates that extrinsic factors may contribute to XP‐C symptom severity due to nonsense‐mediated message decay.
Head and neck mucosal melanoma (HNMM) is a rare tumor with a poor outcome. The objective of this study was to assess outcome and prognostic factors for a cohort of patients treated in a head and neck ...cancer center. In addition, a case series on sentinel lymph node biopsy (SLNB) was included to evaluate it as a method for staging the node-negative neck.
A retrospective study design was chosen, and 50 patients who were treated from 1973 to 2015 in our institution for primary HNMM were included. The Kaplan–Meier method was used to estimate survival rates. Uni- and multivariate analyses were used to study the influence of possible risk factors on the patients' outcome. These risk factors included patient demographics, tumor characteristics, and treatment modalities.
All patients were treated surgically and 50% received adjuvant treatment. The median disease specific survival (DSS) was 38 months, with a 5-year survival rate of 44%. Positive surgical margin (p = 0.004) and distant failure (p = 0.005) were associated with a worse DSS. The median disease-free survival (DFS) was 27 months, with a 5-year disease-free rate of 12%. Only tumor depth >5 mm (p = 0.002) was associated with a worse DFS. Five clinically node-negative patients received SLNB and only the two SLN-positive individuals suffered from distant failure. Radiotherapy, chemotherapy, and AJCC/UICC stage had no influence on any outcome measure.
Positive surgical margin and distant failure are the only independent prognostic factors for DSS. Tumor depth can predict distant failure. SLNB may be a valuable staging tool for the node-negative neck.
Abstract Introduction In patients with squamous cell carcinoma (SCC) of the lip, occurrence of lymph node metastasis (LNM) is more frequent than in other cutaneous head and neck SCCs. The aim of this ...study was to identify predictive factors for LNM in SCC of the lip and to establish a prediction model identifying patients at high LNM risk. Materials and methods Tumor characteristics of 326 patients with lip SCC were analyzed retrospectively to assess differences between the LNM group and controls. Using binary logistic and Cox regression analysis, a prediction model for LNM was calculated. Results Lymph node metastasis occurred in 26 (8%) patients. Regression analysis revealed tumor extent, tumor depth and grading as the most important factors in the correct classification of LNM in 94.2% of patients. A prediction model taking tumor depth and grading into account allowed for stratification of patients into high and low risk groups (sensitivity 92.3%, specificity 78.3%, negative predictive value 99.2%). Conclusions Our new prediction model was able to identify patients with lip cancer who had a high risk of LNM with a good level of accuracy. This algorithm is easy to apply as part of the decision process for elective and selective lymph node dissection in SCC of the lip.
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