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This article provides an overview of tumoural melanosis (TM), a rare condition characterized by the regression of cutaneous melanoma. The authors present four cases of TM from Greece and discuss the clinical, dermatoscopic, and histopathologic characteristics of the condition. They highlight the importance of clinicopathologic correlation in diagnosing TM and recommend aggressive management due to the poor outcomes associated with the condition. Dermatoscopic findings, such as "peppering," whitish or pinkish structureless areas, and blue/grey areas, can assist in the diagnosis of TM. The article includes images to illustrate the cases and provide visual examples of the diagnostic findings. [Extracted from the article]

A letter to the editor is presented which discusses a patient with eccrine syringofibroadenomia.

Background -- Aim: HER2 and TOP2A gene status are of prognostic/predictive relevance and are broadly determined with fluorescent in situ hybridization (FISH). For this purpose, probes against (A) 17p11.1-q11.1 (>5Mb, CENtromere), (B) 17q12 (600Kb, including HER2 among other genes), and (C) 17q21-22 (500Kb, similarly including TOP2A) are used, and gene pathology is determined by B/A and C/A signal ratios according to consensus cut-offs. However, chromosome 17 (chr17) and 17q pathology is complex and may be misinterpreted by this approach, especially in cases with low copy gains. Herein, we profiled A, B and C signals in 1027 adjuvantly treated, early breast cancer patients. Methods: Maximal A, B, C copy numbers (raw FISH data) were submitted to hierarchical clustering as continuous variables. Clusters were compared with clinicopathological parameters, conventional FISH ratios, and were evaluated for their prognostic significance (overall survival, OS) with respect to tumor Ki67 status (13% cut-off), TopoIIa protein (5% cut- off) and ER/PgR positivity (1% cut-off). Results: Clustered values resulted into 832 (81%) putatively chr17 stable tumors (ABClow) and 195 17q unstable tumors. Out of these, 43 (4%) had possible chr17 gain (ABChigh), 30 (3%) HER2/TOP2A gain (BChigh), and 122 (12%) HER2 gain (Bhigh). Unstable 17q was more frequent in Ki67 high, ER/PgR negative, high-grade tumors, and were almost exclusively present in luminal-HER2 and HER2-enriched tumors (all Pearson's p's<0.001). Concordance of ABChigh, BChigh and Bhigh with the respective classical CEN17, HER2/TOP2A and HER2 gains was overall <50%, but it was 93-100% in high copy cases. Significant interactions of ABChigh, BChigh and Bhigh copy profiles with Ki67 status (Wald's p = 0.007) and TopoIIa immunopositivity (Wald's p = 0.018) were observed. Among patients with low Ki67 tumors, 5- year survival rates were 95% Bhigh, 90% ABClow, 88% ABChigh and 63% BChigh (BChigh vs. ABClow, HR=3.65, 95%CI 1.32-10.09, p = 0.013), while among patients with high Ki67, no such difference was observed. Similarly, patients with TopoIIa negative - BChigh tumors were associated with shorter OS (HR = 2.63, 95%CI 1.06-6.48, p = 0.036) compared to ABClow tumors. By contrast, the interaction observed between copy profiles and ER/PgR status (Wald's p = 0.011) was in the opposite direction. Among patients with ER/PgR negative tumors, those with BChigh and ABChigh tumors survived longer than those with ABClow tumors (HR = 0.29, 95%CI 0.12-0.73, p = 0.008); no such difference was observed in ER/PgR positive tumors. Conclusions: Profiles of 17p11-q11, 17q12 and 17q21-22 copies according to broadly used FISH probes reveal distinct subgroups of breast cancer with possibly different versions of chromosomal instability that are only partially concordant with classical CEN17, HER2 and TOP2A gain status. The prognostic significance of these profiles seems to depend on tumor proliferation and hormonal status, as well as on the extent of the affected areas on 17q. Validation of these profiles for prospective application may aid in a more accurate assessment of early high-risk breast cancer patients. [ABSTRACT FROM AUTHOR]

Background: Melanomas developing on anatomic sites other than the trunk and extremities have a special pathogenetic and mutational profile, morphologic characteristics and biologic behaviour. Objective: By retrospectively screening the databases of our centres, we aimed to investigate the dermatoscopic morphology of early scalp melanoma, including in situ and invasive tumours with a Breslow thickness up to 1 mm. Methods: The databases of three specialized centres for skin cancer diagnosis and management in Greece were retrospectively evaluated to retrieve dermatoscopic images of scalp melanomas. Patients' age and sex were recorded, as well as the precise location of the tumour, using 6 possible sub‐locations: frontal, parietal, occipital, temporal, nuchal scalp and vertex. The dermatoscopic images were evaluated by 3 independent investigators for the presence of pre‐defined criteria. The dermatoscopic criteria included in the evaluation were selected based on available literature and were categorized in 2 groups: 'classic melanoma criteria' and 'lentigo maligna (LM) criteria'. Results: Of 38 melanomas, 37 (97.4%) displayed brown colour and 23 (60.5%) displayed additional grey or blue colour. The most frequent dermatoscopic criteria were regression (18/38, 47.4%), grey dots/globules (17/38, 44.7%), atypical network (16/38, 42.1%), obliterated follicles (16/38, 42.1%) and angulated lines (15/38, 39.5%). Of 38 melanomas, 28 (73.7%) displayed at least 1 classic melanoma criterion plus at least 1 LM criterion. Of the remaining melanomas, 8 (21.1%) displayed only classic melanoma criteria, 1 (2.6%) only LM criteria and 1 (2.6%) did not exhibit any of the evaluated criteria. Conclusions: This study demonstrates that early scalp melanoma combines classic with LM criteria in terms of colours and structures. [ABSTRACT FROM AUTHOR]

Background: The dermoscopic features of classic patch stage mycosis fungoides (MF) have been described, but data on plaque and tumoral stage as well as rarer MF subtypes is limited. Objective: To evaluate dermoscopic morphology and dermoscopic‐pathological correlations of classic MF stages and investigate dermoscopic features of MF variants. Methods: Patients with histopathologically confirmed lesions of classic MF (patch, plaque and tumoral stage) or folliculotropic, erythrodermic and poikilodermatous MF were included. Standardized evaluation of dermoscopic pictures of the included MF variants and comparative analysis and dermoscopic‐pathological correlation assessment of different stages of classic MF were performed. Results: A total of 118 instances were included (75 classic MF, 26 folliculotropic MF, 9 erythrodermic MF and 8 poikilodermatous MF). Linear/linear‐curved vessels and white scales in the skin furrows were significantly associated with patch‐stage MF, while clustered dotted vessels were related to plaque‐stage MF and peripheral linear vessels with branches, ulceration and red globules separated by white lines to tumour‐stage MF. Moreover, patchy white scales were significantly more common in patches and plaques compared to tumours, whereas focal bright white structureless areas were related to plaque and tumoral stage. Vessels histopathologically corresponded to dilated vascular structures in the dermis, orange structureless areas to either dermal hemosiderin (patch/plaque stage) or dense cellular infiltration (tumours), bright white lines/structureless areas to dermal fibrosis and ulceration to loss of epidermis. The main dermoscopic findings of folliculotropic MF were lack of hairs, dilated follicles and follicular plugs, while erythrodermic MF was mainly characterized by linear/dotted vessels, patchy white scales and focal orange structureless areas and poikilodermatous MF by focal white and brown structureless areas, white patchy scales and brown reticular lines. Conclusion: Dermoscopy may allow a more precise characterization of classic MF and reveal clues suggestive of the main MF variants. [ABSTRACT FROM AUTHOR]

Background: Concomitant administration of radiation therapy (RT) and chemotherapy with cisplatin (CCRT) is considered standard treatment in patients with locally advanced nasopharyngeal cancer (LA-NPC). The role of induction chemotherapy (IC) when followed by CCRT in improving locoregional control remains controversial. Patients and methods: Totally, 141 eligible patients with LA-NPC were randomized to either three cycles of IC with cisplatin 75 mg/m2, epirubicin 75 mg/m2 and paclitaxel (Taxol) 175 mg/m2 (CEP) every 3 weeks followed by definitive RT (70 Gy) and concomitant weekly infusion of cisplatin 40 mg/m2 (investigational arm, 72 patients) or to the same CCRT regimen alone (control arm, 69 patients). Results: Sixty-two patients (86%) received three cycles of IC. No difference between the arms was observed in the number of patients who completed RT (61 versus 64, P = 018). Overall and complete response rates were very similar in the two arms and so were 3-year progression-free and overall survival rates. Grade III or IV toxic effects from IC were infrequent, apart of alopecia. Mucositis, weight loss and leukopenia were the most prominent side-effects from CCRT. Conclusion: IC with three cycles of CEP when followed by CCRT did not significantly improve response rates and/or survival compared with that of CCRT alone. [ABSTRACT FROM PUBLISHER]

A total of 30 archival cases of male breast carcinoma were studied immunohistochemically for the expression of CD34 antigen. An obvious CD34 staining was found in three cases. By adding the original CD34-positive case, recently published as unique CD34-stained male breast carcinoma, the number of positive cases comes to four. This case was classified as an invasive papillary carcinoma of solid conformation, whereas the three other cases were invasive ductal carcinomas, not otherwise specified. The aim of this study is to establish whether the CD34 positivity, observed in the case of papillary subtype, was a case-specific finding. CD34 expression in the male breast carcinoma, according to our findings, seems to be neither a feature presented exclusively by a singular case nor a specific immunophenotype characterising a special type. The presence or preservation of CD34 antigen in four totally male breast carcinomas may be considered as a novel finding that supports a relationship between these tumours and the progenitor CD34-positive stem cells, committed to the organogenesis of mammary gland. In this context we hypothesise an origin of male breast carcinoma from the stem cells expressing or not the CD34 antigen according to their stage of differentiation. [ABSTRACT FROM AUTHOR]

Purpose: RACGAP1 is a Rac GTPase-activating protein involved in cell growth regulation, cell transformation and metastasis. The aim of the present study was to explore the prognostic and/or predictive significance of RACGAP1 mRNA expression on disease-free survival (DFS) and overall survival (OS) in high-risk early breast cancer patients and compare it to that of Ki67 protein expression and to the Nottingham prognostic index (NPI). Methods: A total of 595 high-risk breast cancer patients were treated in a two-arm trial evaluating postoperative dose-dense sequential chemotherapy with epirubicin followed by CMF with or without paclitaxel. RNA was extracted from 314 formalin-fixed paraffin-embedded primary tumor tissue samples followed by one-step quantitative RT-PCR for assessing RACGAP1 mRNA expression. Results: High RACGAP1 mRNA expression (above the median) was associated with poor DFS (log-rank, p = 0.002) and OS ( p < 0.001). High histological grade, as well as high Ki67 protein expression, was more frequent in the high-expression group of RACGAP1. Results of the Cox multivariate regression analysis revealed that high RACGAP1 mRNA expression independently predicted poor overall survival (Wald's p = 0.008). High Ki67 protein expression was also an adverse prognostic factor for death ( p = 0.016), while high NPI score values were not. Conclusions: High RACGAP1 mRNA expression, as assessed by qRT-PCR, was found to be of adverse prognostic significance in high-risk early breast cancer patients treated with dose-dense sequential chemotherapy. The utility of RACGAP1 mRNA expression in patient selection for treatment with aggressive chemotherapy regimens should be further explored and validated in larger cohorts. [ABSTRACT FROM AUTHOR]

Background Hypothesising that cancer of unknown primary (CUP) may harbour unique characteristics, we present a translational study of the immunohistochemical expression and clinical correlation of key PTEN/AKT pathway molecules. Patients and methods We collected 100 paraffin-embedded CUP tissue blocks. We studied using tissue microarrays the expression of PTEN, phospho-AKT, Cyclin D1, p21, phospho-RPS6. From the percentage of staining tumour cells and the literature, we selected cut-offs to classify the expression of each biomolecule. We correlated IHC expression with clinical data. Results PTEN, pAKT, and pRPS6 showed frequent expression. At univariate analysis, high IHC expression of pAKT and pRPS6 displayed statistically significant association with worse survival. Prognosis was worse upon concurrent high IHC expression of pMAPK and pAKT {median overall survival = 8 months [95% confidence interval (CI) 5.3–10.7] versus 17 months [95% CI 13.1–20.9]}. In multivariate analysis, high p21 was associated with better survival (risk ratio [RR] = 0.34 [95% CI 0.16–0.73], P = 0.005). High expression of pAKT (RR = 2.39 [95% CI 1.23–4.66], P = 0.01) or pRPS6 (RR = 2.76 [95% CI 1.31–5.84], P = 0.008) was associated with worse survival. Conclusions p21 expression conferred favourable prognosis, while high pAKT or pRPS6 expression predicted worse prognosis. Concurrent MAPK and pAKT expression had a marked adverse impact on survival. [ABSTRACT FROM AUTHOR]

Background Despite improvement in therapeutic techniques, patients with early-stage laryngeal cancer still recur after treatment. Gene expression prognostic models could suggest which of these patients would be more appropriate for testing adjuvant strategies. Materials and methods Expression profiling using whole-genome DASL arrays was carried out on 56 formalin-fixed paraffin-embedded tumor samples of patients with early-stage laryngeal cancer. We split the samples into a training and a validation set. Using the supervised principal components survival analysis in the first cohort, we identified gene expression profiles that predict the risk of recurrence. These profiles were then validated in an independent cohort. Results Gene models comprising different number of genes identified a subgroup of patients who were at high risk of recurrence. Of these, the best prognostic model distinguished between a high- and a low-risk group (log-rank P < 0.005). The prognostic value of this model was reproduced in the validation cohort (median disease-free survival: 38 versus 161 months, log-rank P = 0.018), hazard ratio = 5.19 (95% confidence interval 1.14–23.57, P < 0.05). Conclusions We have identified gene expression prognostic models that can refine the estimation of a patient's risk of recurrence. These findings, if further validated, should aid in patient stratification for testing adjuvant treatment strategies. [ABSTRACT FROM AUTHOR]

Purpose: It is well recognized that breast cancer is a heterogeneous disease. The purpose of the current study was to classify patients according to the immunohistochemical phenotype of their tumors in an effort to evaluate the outcome of the respective groups of patients and specifically of those with triple-negative breast cancer (TNBC) following dose-dense sequential adjuvant chemotherapy. Methods: A total of 595 patients with high-risk breast cancer were treated with adjuvant anthracycline-based dose-dense sequential chemotherapy with or without paclitaxel in the context of a randomized study. ER, PgR, HER2, Ki67, EGFR, and CK5 protein expression were evaluated in 298 formalin-fixed paraffin-embedded tumor samples by immunohistochemistry (IHC). HER2 was also evaluated by chromogen in situ hybridization (CISH). HER2 status and Ki67 protein expression differentiated luminal IHC subtypes (luminal B tumors being HER2 and/or Ki67-positive). Results: Among the 298 tumors, the immunohistochemical panel classified 37 (12%) as luminal A, 198 (66%) as luminal B, 27 (9%) as HER2 enriched, and 36 (12%) as TNBC. The median follow-up time was 97 months. Patients with luminal A tumors had the best prognosis, with improved disease-free survival (log-rank, P = 0.033) and overall survival ( P = 0.006) compared with the other three tumor subtypes. The three subtypes had an increased risk for relapse and death compared with luminal A in multivariate analysis, as well. No benefit from paclitaxel treatment was detected in any of the four subtypes or the total cohort. Hierarchical clustering based on mRNA expression of ER, PgR, and HER2 by quantitative RT-PCR identified patient groups that were comparable to the subtypes identified by IHC. Conclusions: The results of this study confirm that triple negative, luminal B and HER2-enriched phenotypes identified by IHC are of adverse prognostic value in high-risk breast cancer patients treated with dose-dense sequential adjuvant chemotherapy. [ABSTRACT FROM AUTHOR]

Although lymphomas involving the prostate gland are rare, they should always be considered in the differential diagnosis. We report a case of primary prostatic NHL in a 70-year-old man presented with hematuria and urinary obstructive symptoms. Routine laboratory tests were within normal limits and prostate-specific antigen (PSA) was 0,01 ng/ml. The patient underwent radical prostatectomy. Histologically, two different coexisting patterns of non-Hodgkin lymphoma, infiltrating the prostatic tissue, were identified. The diagnosis of diffuse large B-cell lymphoma (DLBCL) presenting with an associated low-grade lymphoma of MALT-type was confirmed by immunohistochemistry. The patient received chemotherapy without any complication and has been followed-up for 2 years since surgical resection with no recurrence. The clinicopathologic characteristics of prostatic lymphomas are discussed, while reviewing the current English-language literature. Hippokratia. 2012; 16 (1): 86-89 [ABSTRACT FROM AUTHOR]

The optimal adjuvant treatment for gastric cancer remains controversial. We compared the efficacy of a docetaxel and platinum adjuvant chemotherapy regimen, in patients with high-risk gastric cancer, with that of the same chemotherapy plus radiation therapy (RT). In addition, we evaluated the prognostic and/or predictive value of a panel of molecular markers. Patients with histologically proven, radically resected gastric cancer, stage ≥T3 and/or N+ were randomized to 6 cycles of docetaxel with cisplatin, both at 75 mg/m2 every 3 weeks (arm A) or the same treatment with RT (arm B; 45 Gy). Due to excessive nausea and vomiting, cisplatin was substituted by carboplatin at AUC (area under the curve) of 5 after the first 45 patients (22 group A, 23 group B). The prognostic value of EGFR, ERCC1, HER2, MET/HGFR, MAP-Tau, and PTEN expression was also studied in a subset of 67 patients using immunohistochemistry on tissue microarrays (TMAs). A total of 147 patients were randomized. After a median follow-up of 53.7 months, no differences in overall (OS) and disease-free survival (DFS) were found between the two arms. The most common grade 3/4 toxicities for arms A and B (excluding alopecia) were non-febrile neutropenia (11 and 17%, respectively), febrile neutropenia (9 and 7%) and diarrhea (7 and 4%, respectively). Patients with ERCC1 positive tumors had significantly longer median DFS (33.1 vs. 11.8 months, Wald P = 0.016) and OS (63.2 vs. 18.8 months, Wald P = 0.046). Our results indicate that the addition of RT to platinum/docetaxel adjuvant chemotherapy does not appear to improve survival in high-risk, radically resected gastric cancer. However, the possibility that a benefit by the addition of RT was not detected due to decreased power of the study should not be excluded. [ABSTRACT FROM AUTHOR]