Clinical and pathological features of Merkel cell carcinoma: A 4-year follow-up observational retrospective study in Spain.

BACKGROUND: Merkel cell carcinoma (MCC) is a malignant skin cancer with a 5-year survival rate of approximately 50%. Knowledge of MCC has increased in recent years mostly due to improved diagnosis techniques. In Spain there is lack of information regarding the incidence and tumour characteristics, and the treatment approaches are not standardised. The objective of this study was to provide information of the clinical and epidemiological characteristics of MCC patients in Spain. METHODS: Retrospective, observational study involving 192 patients from 25 Spanish hospitals. Evaluated variables included overall survival and incidence rate of Merkel cell polyomavirus, in patients diagnosed from 2012 to 2016. RESULTS: The Spanish incidence rate was estimated 0.32/100,000 inhabitants/year, with variations according to geographical regions, being slightly higher in areas with greater sunlight exposure. In total, 61.5% of tumours showed expansive growth (progressive growth of the tumour), 78.6% showed localisation in UV-exposed skin. 97.4% of patients were diagnosed by excisional biopsy. Surgery was the first line treatment in 96.6% of patients, radiotherapy in 24.6%, and chemotherapy in 6.3%. These treatments were not mutually exclusive. Median overall survival was 38.3 months (78.4% at 12 months and 60% at 24 months). MCPyV was present in 33.8% of patients. CONCLUSION: The incidence of MCC in Spain is one of the highest in Europe, with a slight predominance in men. The sample has shown that a biopsy is available for diagnosis in most cases. Moreover, the treatment is surgical when the tumour is localized and is associated with lymphadenectomy, and/or it is radiotherapy if widespread.

Cutaneous Lymphadenoma Is a Distinct Trichoblastoma-like Lymphoepithelial Tumor With Diffuse Androgen Receptor Immunoreactivity, Notch1 Ligand in Reed-Sternberg-like Cells, and Common EGFR Somatic Mutations.

The term "cutaneous lymphadenoma" was coined in this journal for an unusual lymphoepithelial cutaneous adnexal neoplasm, possibly with immature pilosebaceous differentiation. Some authors further proposed that cutaneous lymphadenoma was an adamantinoid trichoblastoma. However, although a hair follicle differentiation is widely accepted, the fact that this is a lymphoepithelial tumor is not appropriately explained by the trichoblastoma hypothesis. Our goal was to further clarify the phenotypic and genotypic features of cutaneous lymphadenoma in a series of 11 cases. Histologically, a lobular architecture surrounded by a dense fibrous stroma was present in all cases. The lobules were composed of epithelial cells admixtured with small lymphocytes and isolated or clustered large Reed-Sternberg-like (RS-L) cells. The epithelial cells were diffusely positive for the hair follicle stem cell markers CK15, PHLDA1, and for androgen receptor. No immunostaining for markers of sebaceous differentiation was found. Intraepithelial lymphocytes were predominantly CD3+, CD4+, FoxP3+ T cells. RS-L cells showed both strong Jagged-1 and Notch1 cytoplasmic immunostaining. Androgen-regulated NKX3.1 nuclear immunostaining was present in a subset of large intralobular cells in all cases. Double immunostaining showed coexpression of NKX3.1 and CD30 in a subset of RS-L cells. No immunostaining for lymphocytic or epithelial markers was present in RS-L cells. EGFR, PIK3CA, and FGFR3 somatic mutations were found by next-generation sequencing in 56% of the cases. We consider that cutaneous lymphadenoma is a distinct benign lymphoepithelial tumor with androgen receptor and hair follicle bulge stem cell marker expression, RS-L cell-derived Notch1 ligand, and common EGFR gene mutations.

Biological and prognostic differences between symptomatic colorectal carcinomas and those detected by screening.

INTRODUCTION: Few studies have been conducted to establish the relationship between colorectal cancer screening programmes and survival adjusting by stage and, to determine whether there are differences, at a biological level, between the tumours of asymptomatic and symptomatic patients. Accordingly, the aim of this study is to evaluate clinical, biological and survival differences between symptomatic colorectal tumours and those detected by screening. STUDY METHOD: A prospective cohort study was performed of patients subjected to surgical intervention during the period 2010-2012, at different hospitals in Spain. In every case, clinical, pathological, biological and survival-related variables were obtained. RESULTS: A total of 2634 patients from the CARESS-CCR cohort were analysed; of these, 220 were diagnosed through screening. The asymptomatic patients were younger, had a higher Body Mass Index (BMI), a lower degree of perineural invasion and a less advanced T stage and nodular stage, and the tumour was frequently located on the right side of the colon. All of these differences were statistically significant. The serum tumour marker carbohydrate antigen 19.9 (CA 19.9) was found more frequently in the symptomatic patients (p < 0.05). However, no significant differences were found regarding the markers of tumour biology: Ki67 (proliferation), CD105 (angiogenesis) and the Terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End Labeling (TUNEL) assay (apoptosis). The patients with asymptomatic tumours had a lower mortality at five years than those diagnosed presenting symptoms. CONCLUSIONS: The detection method employed influenced the survival of patients with colorectal cancer and there were no significant biological differences between the study groups.

Clinical-pathological characteristics and short-term follow-up associated with proliferation, apoptosis and angiogenesis in a prospective cohort of patients with colorectal tumours.

We investigate the clinical and pathological features related to variations in colorectal tumour apoptosis, proliferation and angiogenesis and the influence of the latter in short-term mortality (2 years); 551 tumour samples from a prospective cohort of patients with colorectal cancer were examined and tumour biology markers were determined as follows: percentage of apoptotic cells, by the terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End Labeling technique; Ki-67 antigen, as a cell proliferation marker and density of microvessels (as a marker of angiogenesis). An increase in the percentage of cellular apoptosis is significantly related to the presence of poorly differentiated tumours, with vascular invasion (p < 0.001). The CD105 angiogenesis marker is not related to any clinical-pathological parameter except that of higher frequency in older patients (p = 0.03). Ki-67 is more frequently expressed in tumours with less nervous invasion (p = 0.05). Neither apoptosis nor angiogenesis present any significant association with short-term survival. The only marker clearly related to 2-year survival is Ki-67, which is shown to be a good prognostic factor in the multivariate analysis (hazard ratio = 0.49; 95% confidence interval = 0.27-0.90). Therefore, in a prospective cohort of colorectal cancer patients, only Ki-67 is a marker of good prognosis in short-term follow-up.

The role and prognostic value of apoptosis in colorectal carcinoma.

BACKGROUND: Alterations to apoptosis are a common occurrence in human tumours. The aim of our study was to determine the influence of apoptotic variations on the carcinogenesis and prognosis of colorectal carcinomas (CRCs). METHODS: A TUNEL assay was performed on archival material from 103 colorectal carcinomas, 26 adenomas and 20 samples of normal epithelia. RESULTS: The number of apoptotic cells was higher in CRCs (1.09 ± 0.13) than in adenomas (0.38 ± 0.23, p = 0.059) and normal epithelium (0.06 ± 0.04, p = 0.001). In addition, the apoptotic index (AI) was greater in metastatic disease (stage IV) than in other stages (p = 0.017). No relationship was found between apoptotic rates and age, gender or tumour grade. However, patients with tumours that showed higher AI values had a significantly lower disease-free survival (DFS) and overall survival (OS) than those with tumours that had lower AIs (p = 0.020 and p = 0.027). In a multivariate Cox proportional hazards model, AI remained a significant independent predictor of survival. CONCLUSIONS: We conclude that disregulated apoptosis is an important event during CRC development and progression. Higher AIs are associated with more aggressive tumours and a poorer prognosis for patients with CRC.

Detection methods predict differences in biology and survival in breast cancer patients.

BACKGROUND: The aim of this study was to measure the biological characteristics involved in tumorigenesis and the progression of breast cancer in symptomatic and screen-detected carcinomas to identify possible differences. METHODS: For this purpose, we evaluated clinical-pathological parameters and proliferative and apoptotic activities in a series of 130 symptomatic and 161 screen-detected tumors. RESULTS: After adjustment for the smaller size of the screen-detected carcinomas compared with symptomatic cancers, those detected in the screening program presented longer disease-free survival (RR = 0.43, CI = 0.19-0.96) and had high estrogen and progesterone receptor concentrations more often than did symptomatic cancers (OR = 3.38, CI = 1.72-6.63 and OR = 3.44, CI = 1.94-6.10, respectively). Furthermore, the expression of bcl-2, a marker of good prognosis in breast cancer, was higher and HER2/neu expression was lower in screen-detected cancers than in symptomatic cancers (OR = 1.77, CI = 1.01-3.23 and OR = 0.64, CI = 0.40-0.98, respectively). However, when comparing prevalent vs incident screen-detected carcinomas, prevalent tumors were larger (OR = 2.84, CI = 1.05-7.69), were less likely to be HER2/neu positive (OR = 0.22, CI = 0.08-0.61) and presented lower Ki67 expression (OR = 0.36, CI = 0.17-0.77). In addition, incident tumors presented a shorter survival time than did prevalent ones (RR = 4.88, CI = 1.12-21.19). CONCLUSIONS: Incident carcinomas include a variety of screen-detected carcinomas that exhibit differences in biology and prognosis relative to prevalent carcinomas. The detection method is important and should be taken into account when making therapy decisions.

Clinical significance of langerhans cells in squamous cell carcinoma of the larynx.

Langerhans cells (LCs) may be involved in the immunosurveillance against tumors as antigen-presenting cells. Our objective has been to determine the relevance of LC in progression of larynx squamous cell carcinomas and their relationship with different subpopulations of tumor-infiltrating cells. LCs were investigated by immunohistochemical methods using anti-CD1 antibody. LCs were detected in most of the primary tumors studied (44 out of 50) and also in metastases (6 out of 10) and recurrences (2 out of 3), but we did not find any statistical association between number of LCs and clinical-pathological parameters or survival. However, the number of LCs was increased in patients with evident infiltration of lymphocytes, mainly cytotoxic T cells. We can conclude that although LCs did not show clinical utility as prognostic marker, they may play a role in releasing an active immune response in larynx carcinomas, according to their ability to present antigens to sensitized T cells.

Clusterin expression is associated with decreased disease-free survival of patients with colorectal carcinomas.

AIMS: It has been demonstrated that increased clusterin expression is involved in malignant progression and that anticlusterin treatment leads to selective apoptosis. The aim of this study was to determine the clinicopathological significance of clusterin expression in human colorectal carcinomas. METHODS AND RESULTS: The expression of clusterin was examined in 31 adenomas and 103 colorectal carcinomas. Normal epithelial cells were always negative for clusterin expression, but clusterin expression was present in 16% (5/31) of adenomas and this percentage increased in colorectal carcinomas (30%, 31/103). Immunopositivity always presented an apical cytoplasmic pattern. The expression level of clusterin did not correlate with age, gender, grade or stage. However, its expression was significantly associated with a decrease in disease-free survival (P < 0.05). In a multivariate Cox proportional hazards model, clusterin expression remained a significant independent predictor. CONCLUSIONS: Clusterin expression may have a role in colonic carcinogenesis and may help identify patients with more aggressive tumours who may benefit from targeted therapy.

Prognostic implications of emergency admission and delays in patients with breast cancer.

INTRODUCTION: This study evaluates clinical-pathological characteristics and survival rates associated with emergency admission and delays in diagnosis and treatment of 411 consecutive breast cancer patients. MATERIALS AND METHODS: Emergency admission and first symptom-first hospital visit delay were significantly associated with advanced tumor stages but only in the former case with short disease-free survival (RR 2.5, CI 95% 1.5-4.2). RESULTS: Brief diagnostic delays were significantly associated with advanced disease stage and poor survival rates (RR 2.04; CI 95% 1.08-3.82) probably because sicker patients receive prompt medical attention.

Solitary colonic polypoid ganglioneuroma.

This short report discusses a case of solitary colonic polypoid ganglioneuroma associated with melanosis coli in a woman with no systemic manifestations. To our knowledge this is the first ganglioneuroma reported in the literature in association with melanosis coli. The nature and significance of this event remains unclear, although this may be coincidental due to the laxative intake. Further investigation is necessary to clarify this point. The interest of this case lies moreover in the rarity of this entity and its endoscopic and histologic resemblance to sessile polyps frequent in the clinical practice.

Simultaneous chromophobe renal cell carcinoma and squamous renal cell carcinoma.

Chromophobe renal cell carcinoma (CHRC) is a neoplasm of the kidney with clinicopathologic peculiarities that seems to be of better prognosis than conventional renal cell carcinoma. Classical and eosinophilic types are the two histological variants recorded. Also, it has been described in association with carcinoma of collecting ducts, conventional renal cell carcinoma and sarcomatoid renal cell carcinoma. Squamous renal carcinoma is a very rare neoplasm with a malignant course. We describe a case of simultaneous chromophobe renal cell carcinoma with squamous cell carcinoma, finding which, to the best of our knowledge, has not previously been reported.