OBJECTIVE: Cutaneous Squamous Cell Carcinoma (cSCC), a tumor with a significantly increasing incidence, is mostly diagnosed in the head region, where tumors have a worse prognosis and a higher risk of metastases. The presence of metastases reduces specific five-year survival from 99% to 50%. As the risk of occult metastases does not exceed 10%, elective dissection of the tributary parotid and neck lymph nodes is not recommended. METHODS: We retrospectively analyzed a group of 12 patients with cSCC of the head after elective dissections of regional (parotid and cervical) nodes by means of superficial parotidectomy and selective neck dissection. RESULTS: We diagnosed occult metastases neither in the cervical nor parotid nodes in any patient. None were diagnosed as a regional recurrence during the follow-up period. CONCLUCION: Our negative opinion on elective parotidectomy and neck dissection in cSCC of the head is in agreement with the majority of published studies. These elective procedures are not indicated even for tumors showing the presence of known (clinical and histological) risk factors for lymphogenic spread, as their positive predictive value is too low. Elective parotidectomy is individually considered as safe deep surgical margin. If elective parotidectomy is planned it should include only the superficial lobe. Completion parotidectomy and elective neck dissection are done in rare cases of histologically confirmed parotid metastasis in the parotid specimen. Preoperatively diagnosed parotid metastases without neck involvement are sent for total parotidectomy and elective selective neck dissection. Cases of clinically evident neck metastasis with no parotid involvement, are referred for comprehensive neck dissection and elective superficial parotidectomy. The treatment of concurrent parotid and cervical metastases includes total conservative parotidectomy and comprehensive neck dissection. LEVEL OF EVIDENCE: How common is the problem? Step 4 (Case-series) Is this diagnostic or monitoring test accurate? (Diagnosis) Step 4 (poor or non-independent reference standard) What will happen if we do not add a therapy? (Prognosis) Step 4 (Case-series) Does this intervention help? (Treatment Benefits) Step 4 (Case-series) What are the COMMON harms? (Treatment Harms) Step 4 (Case-series) What are the RARE harms? (Treatment Harms) Step 4 (Case-series) Is this (early detection) test worthwhile? (Screening) Step 4 (Case-series).

• Klíčová slova
• Cutaneous squamous cell carcinoma, Elective neck dissection, Elective parotidectomy, Occult metastasis, Skin cancer,
• MeSH
• krční disekce metody   MeSH
• lidé MeSH
• nádory hlavy a krku * chirurgie   patologie   MeSH
• nádory kůže * chirurgie   patologie   MeSH
• nádory příušní žlázy * chirurgie   patologie   MeSH
• retrospektivní studie MeSH
• spinocelulární karcinom * patologie   MeSH
• staging nádorů MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

INTRODUCTION: Solid organ transplant recipients (SOTRs) are believed to have an increased risk of metastatic cutaneous squamous cell carcinoma (cSCC), but reliable data are lacking regarding the precise incidence and associated risk factors. METHODS: In a prospective cohort study, including 19 specialist dermatology outpatient clinics in 15 countries, patient and tumor characteristics were collected using standardized questionnaires when SOTRs presented with a new cSCC. After a minimum of 2 years of follow-up, relevant data for all SOTRs were collected. Cumulative incidence of metastases was calculated by the Aalen-Johansen estimator. Fine and Gray models were used to assess multiple risk factors for metastases. RESULTS: Of 514 SOTRs who presented with 623 primary cSCCs, metastases developed in 37 with a 2-year patient-based cumulative incidence of 6.2%. Risk factors for metastases included location in the head and neck area, local recurrence, size > 2 cm, clinical ulceration, poor differentiation grade, perineural invasion, and deep invasion. A high-stage tumor that is also ulcerated showed the highest risk of metastasis, with a 2-year cumulative incidence of 46.2% (31.9%-68.4%). CONCLUSIONS: SOTRs have a high risk of cSCC metastases and well-established clinical and histologic risk factors have been confirmed. High-stage, ulcerated cSCCs have the highest risk of metastasis.

• Klíčová slova
• immunosuppression, organ transplantation, skin cancer, squamous cell carcinoma,
• MeSH
• dospělí MeSH
• incidence MeSH
• invazivní růst nádoru MeSH
• lidé středního věku MeSH
• lidé MeSH
• lokální recidiva nádoru epidemiologie   MeSH
• nádory hlavy a krku epidemiologie   patologie   MeSH
• nádory kůže * epidemiologie   patologie   MeSH
• příjemce transplantátu statistika a číselné údaje   MeSH
• prospektivní studie MeSH
• rizikové faktory MeSH
• senioři MeSH
• spinocelulární karcinom * epidemiologie   MeSH
• staging nádorů MeSH
• transplantace orgánů * škodlivé účinky   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• Geografické názvy
• Evropa epidemiologie   MeSH

The term metastatic carcinoma to cervical lymph nodes from an unknown primary includes a small group of tumors that present themselves with metastases to the cervical nodes, and in which diagnostic methods do not reveal the primary source of these metastases. Histologically, in most cases, these are metastases of squamous cell carcinoma. Carcinomas of unknown primary metastatic to cervical nodes account for < 5% of carcinomas of unknown primary and < 5% of head and neck cancers. The optimal treatment has not yet been defined. In the absence of distant metastases, the intention of treatment is curative. Patients are treated mostly with combined approaches including surgery, radiotherapy, or concomitant chemoradiotherapy. Radiotherapy is part of the treatment algorithm in most of the referenced works and includes irradiation of the mucosal sites of the pharyngeal axis as a potential localization of the primary tumor and unilateral or, more often, bilateral irradiation of the neck. Due to the higher risk of late toxicities observed, individualization of irradiated volumes based on the extent of the disease or other clinical parameters is a rational way to reduce these risks. Purpose: The presented work discusses the treatment options for patients with metastatic carcinoma to cervical lymph nodes from an unknown primary. Furthermore, the work reports on the high effectiveness of curative radiotherapy in this group of tumors.

• Klíčová slova
• Chemoradiotherapy, carcinoma of unknown primary, concurrent chemoradiotherapy, curative radiotherapy,
• MeSH
• krk patologie   MeSH
• lidé MeSH
• lymfatické uzliny patologie   MeSH
• nádory hlavy a krku * terapie   patologie   MeSH
• nádory neznámé primární lokalizace * patologie   MeSH
• retrospektivní studie MeSH
• spinocelulární karcinom * terapie   patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

INTRODUCTION: The aim of this study is to assess the impact of lymph node ratio (LNR) and number of positive lymph nodes (NPLN) on mortality and recurrence rates in patients with laryngeal squamous cell carcinoma. MATERIALS AND METHODS: We conducted a retrospective multicenter international study involving 24 Otorhinolaryngology-Head and Neck Surgery divisions. Disease-specific survival (DSS) and disease-free survival (DFS) were evaluated as the main outcomes. The curves for DSS and DFS according to NPLN and LNR were analyzed to identify significant variations and establish specific cut-off values. RESULTS: 2507 patients met the inclusion criteria. DSS and DFS were significantly different in the groups of patients stratified according to LNR and NPLN. The 5-year DSS and DFS based on LNR and NPLN demonstrated an improved ability to stratify patients when compared to pN staging. CONCLUSION: Our data demonstrate the potential prognostic value of NPLN and LNR in laryngeal squamous cell carcinoma.

• Klíčová slova
• laryngeal cancer, lymph node, lymph node metastasis, lymph node ratio, oncology,
• MeSH
• dlaždicobuněčné karcinomy hlavy a krku patologie   MeSH
• lidé MeSH
• lymfadenektomie MeSH
• lymfatické metastázy patologie   MeSH
• lymfatické uzliny * patologie   MeSH
• nádory hlavy a krku * patologie   MeSH
• poměr lymfatických uzlin MeSH
• prognóza MeSH
• retrospektivní studie MeSH
• staging nádorů MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

PURPOSE: To evaluate the effectiveness and toxicity of curative (chemo)radiotherapy in patients with metastatic carcinoma to cervical lymph nodes from an unknown primary. METHODS: Retrospective study of 90 consecutive patients, treated with curative radiotherapy from 2003 to 2018 (median age 59 years; current/former smokers 76%) was conducted. The distribution of nodal staging was as follows: N1: 12%, N2a: 21%, N2b: 43%, N2c: 10%, N3: 13%. In 62% of patients, neck dissection was performed before radiotherapy. Concomitant chemotherapy was given to 64% of patients. RESULTS: The median follow-up of surviving patients was 86 months. The median total radiotherapy dose achieved was 70 Gy. The 5‑ and 10-year locoregional control were 84% in both cases, while 5‑ and 10-year distant control were 90% and 89%, respectively. A primary tumor in the head and neck area was detected in only 2 patients. No patient had an initial failure in the pharyngeal axis or contralateral cervical nodes. The 5‑ and 10-year overall survival were 55% and 42%, respectively. Severe early toxicity occurred in 71%; severe late toxicity in 33% of patients. Multivariate analysis demonstrated N‑status (hazard ratio [HR] 2.424; 95% confidence interval [CI] 1.121-5.241; p = 0.024) and comorbidity scores assessed by ACE-27 (Adult Comorbidity Evaluation; HR 3.058; 95% CI 1.489-6.281; p = 0.002) as two independent prognostic factors for overall survival. CONCLUSION: The results of our work study demonstrate the high effectiveness of curative (chemo)radiotherapy on the pharyngeal axis and bilateral cervical nodes with long-term locoregional and distant control in 3/4 of the treated patients. N‑status and comorbidity scores were shown as strong prognostic factors influencing overall survival.

• Klíčová slova
• ACE-27, Carcinoma of unknown primary, Chemoradiotherapy, Curative radiotherapy, Prognostic Factors,
• MeSH
• dospělí MeSH
• karcinom * patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lymfatické metastázy patologie   MeSH
• lymfatické uzliny patologie   MeSH
• nádory hlavy a krku * patologie   MeSH
• nádory neznámé primární lokalizace * terapie   patologie   MeSH
• retrospektivní studie MeSH
• staging nádorů MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Head and neck cancer is the sixth most common cancer across the globe. This is generally associated with tobacco and alcohol consumption. Cancer in the pharynx majorly arises through human papillomavirus (HPV) infection, thus classifying head and neck squamous cell carcinoma (HNSCC) into HPV-positive and HPV-negative HNSCCs. Aberrant, mesenchymal-epithelial transition factor (c-MET) signal transduction favors HNSCC progression by stimulating proliferation, motility, invasiveness, morphogenesis, and angiogenesis. c-MET upregulation can be found in the majority of head and neck squamous cell carcinomas. c-MET pathway acts on several downstream effectors including phospholipase C gamma (PLCγ), cellular Src kinase (c-Src), phosphotidylinsitol-3-OH kinase (PI3K), alpha serine/threonine-protein kinase (Akt), mitogen-activated protein kinase (MAPK), and wingless-related integration site (Wnt) pathways. c-MET also establishes a crosstalk pathway with epidermal growth factor receptor (EGFR) and contributes towards chemoresistance in HNSCC. In recent years, the signaling communications of c-MET/HGF in metabolic dysregulation, tumor-microenvironment and immune modulation in HNSCC have emerged. Several clinical trials have been established against c-MET/ hepatocyte growth factor (HGF) signaling network to bring up targeted and effective therapeutic strategies against HNSCC. In this review, we discuss the molecular mechanism(s) and current understanding of c-MET/HGF signaling and its effect on HNSCC.

• Klíčová slova
• C-MET, Chemoresistance, EGFR, Head and neck squamous cell carcinoma, Hepatocyte growth factor, Monoclonal antibody,
• MeSH
• chemorezistence genetika   MeSH
• energetický metabolismus MeSH
• hepatocytární růstový faktor metabolismus   MeSH
• imunita MeSH
• lidé MeSH
• management nemoci MeSH
• náchylnost k nemoci MeSH
• nádorové biomarkery MeSH
• nádorové mikroprostředí genetika   imunologie   MeSH
• nádory hlavy a krku etiologie   metabolismus   patologie   terapie   MeSH
• protokoly antitumorózní kombinované chemoterapie škodlivé účinky   terapeutické užití   MeSH
• protoonkogenní proteiny c-met metabolismus   MeSH
• signální transdukce * MeSH
• výsledek terapie MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• hepatocytární růstový faktor MeSH
• HGF protein, human MeSH Prohlížeč
• MET protein, human MeSH Prohlížeč
• nádorové biomarkery MeSH
• protoonkogenní proteiny c-met MeSH

PURPOSE: Prolongation of radiotherapy worsens the results of treatment of head and neck squamous cell carcinoma (HNSCC). The purpose of this study was to identify the prognostic factors most affected by the prolongation of treatment. METHODS: 184 patients with locally advanced HNSCC were treated with curative chemo-radiation using SIB-IMRT from 2008 to 2016 and the influence of radiotherapy time (RTT) in groups of patients according to prognostic factors was retrospectively evaluated. RESULTS: Median overall survival (OS) was 45 months, median disease-free survival (DFS) was 41 months and median local control (LC) was not reached (mean LRC 68 months). In the multivariate analysis the radiotherapy prolongation negatively affected the LC in stage IV patients, T3/T4, in neck nodes positive disease, in oropharyngeal and oral cavity cancers, after neoadjuvant chemotherapy and in men. The RTT effect on DFS was significant in stage IV patients, patients with neck nodes positive disease and oropharyngeal cancer. RTT prolongation decreased OS within the groups of stage IV and grade 3 tumours. CONCLUSION: Prolonged RTT was associated with worsened OS and LRC, especially in stage IV patients and/or neck node positive disease and/or oropharyngeal cancer and we recommend that these patients should be prioritized in treatment gap compensation in radical radiotherapy for locally advanced HNSCC.

• MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory hlavy a krku patologie   radioterapie   MeSH
• radioterapie s modulovanou intenzitou metody   MeSH
• retrospektivní studie MeSH
• riziko MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• staging nádorů MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

OBJECTIVES: This study examined whether palbociclib and cetuximab prolonged overall survival (OS) versus placebo and cetuximab. MATERIALS AND METHODS: In this double-blind, randomized, phase 2 trial (PALATINUS), patients with platinum-resistant, cetuximab-naïve, human papillomavirus-unrelated recurrent/metastatic head and neck squamous-cell carcinoma received cetuximab and either palbociclib (arm A) or placebo (arm B). The primary endpoint was OS; 120 patients were required to have ≥80% power to detect a hazard ratio (HR) of 0.6 (median OS of 10 months in arm A and 6 months in arm B) using a one-sided, log-rank test (P = 0.10). RESULTS: 125 patients were randomized (arm A: 65, arm B: 60). Median follow-up was 15.9 months (IQR, 11.3-22.7). Median OS was 9.7 months in arm A and 7.8 months in arm B (HR, 0.82; 95% CI, 0.54-1.25; P = 0.18). Median progression-free survival was 3.9 months in arm A and 4.6 months in arm B (HR, 1.00; 95% CI, 0.67-1.5; P = 0.50). The most common treatment-related adverse events in arm A were rash (39 patients, 60.9%) and neutropenia (26, 40.6%; three febrile) and in arm B was rash (32, 53.3%). CONCLUSION: There was no significant difference in median OS with palbociclib and cetuximab versus placebo and cetuximab. FUNDING: Pfizer Inc (NCT02499120).

• Klíčová slova
• Cetuximab, Head and neck cancer, Palbociclib, Squamous cell carcinoma,
• MeSH
• cetuximab farmakologie   terapeutické užití   MeSH
• dvojitá slepá metoda MeSH
• lidé středního věku MeSH
• lidé MeSH
• lokální recidiva nádoru MeSH
• metastázy nádorů MeSH
• nádory hlavy a krku farmakoterapie   patologie   MeSH
• piperaziny farmakologie   terapeutické užití   MeSH
• protokoly antitumorózní kombinované chemoterapie farmakologie   terapeutické užití   MeSH
• pyridiny farmakologie   terapeutické užití   MeSH
• spinocelulární karcinom farmakoterapie   patologie   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze II MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• cetuximab MeSH
• palbociclib MeSH Prohlížeč
• piperaziny MeSH
• pyridiny MeSH

Sebaceous neoplasms occur sporadically or in the setting of Muir-Torre syndrome. The data regarding the correlation of pathologic features and DNA mismatch repair (MMR) staining pattern in sebaceous tumors of the skin are very scanty and based on relatively small series of patients. The goal of this study was to correlate MMR staining pattern with selected morphological features in a series of 145 sebaceous neoplasms (sebaceous adenoma, sebaceoma, and extraocular sebaceous carcinoma) from 136 patients. Cystic change, intratumoral mucin deposits, squamous metaplasia in the absence of keratoacanthoma-like changes, ulceration, intratumoral and peritumoral lymphocytes (in cases without epidermal ulceration), and intertumoral heterogeneity proved to be significantly associated with MMR deficiency. Identification of any of these changes, alone or in combination, should prompt further investigation of the patient to exclude Muir-Torre Syndrome. Our study also confirms the previously published observation that the diagnosis and tumor location are significantly associated with MMR deficiency.

• MeSH
• adenom metabolismus   patologie   MeSH
• DNA vazebné proteiny metabolismus   MeSH
• dospělí MeSH
• homolog 2 proteinu MutS metabolismus   MeSH
• imunohistochemie MeSH
• karcinom metabolismus   patologie   MeSH
• končetiny MeSH
• lidé středního věku MeSH
• lidé MeSH
• mismatch repair endonukleáza PMS2 metabolismus   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• MutL homolog 1 metabolismus   MeSH
• nádory hlavy a krku metabolismus   patologie   MeSH
• nádory mazových žláz metabolismus   patologie   MeSH
• obličej MeSH
• oprava chybného párování bází DNA MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• skalp MeSH
• trup MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• DNA vazebné proteiny MeSH
• G-T mismatch-binding protein MeSH Prohlížeč
• homolog 2 proteinu MutS MeSH
• mismatch repair endonukleáza PMS2 MeSH
• MLH1 protein, human MeSH Prohlížeč
• MSH2 protein, human MeSH Prohlížeč
• MutL homolog 1 MeSH
• PMS2 protein, human MeSH Prohlížeč

Many cancer therapies aim to trigger apoptosis in cancer cells. Nevertheless, the presence of oncogenic alterations in these cells and distorted composition of tumour microenvironment largely limit the clinical efficacy of this type of therapy. Luckily, scientific consensus describes about 10 different cell death subroutines with different regulatory pathways and cancer cells are probably not able to avoid all of cell death types at once. Therefore, a focused and individualised therapy is needed to address the specific advantages and disadvantages of individual tumours. Although much is known about apoptosis, therapeutic opportunities of other cell death pathways are often neglected. Molecular heterogeneity of head and neck squamous cell carcinomas (HNSCC) causing unpredictability of the clinical response represents a grave challenge for oncologists and seems to be a critical component of treatment response. The large proportion of this clinical heterogeneity probably lies in alterations of cell death pathways. How exactly cells die is very important because the predominant type of cell death can have multiple impacts on the therapeutic response as cell death itself acts as a second messenger. In this review, we discuss the different types of programmed cell death (PCD), their connection with HNSCC pathogenesis and possible therapeutic windows that result from specific sensitivity to some form of PCD in some clinically relevant subgroups of HNSCC.

• MeSH
• antitumorózní látky terapeutické užití   MeSH
• apoptóza účinky léků   MeSH
• autofagie účinky léků   MeSH
• chemorezistence MeSH
• dlaždicobuněčné karcinomy hlavy a krku farmakoterapie   genetika   metabolismus   patologie   MeSH
• ferroptóza účinky léků   MeSH
• genetická heterogenita MeSH
• lidé MeSH
• nádorové mikroprostředí MeSH
• nádory hlavy a krku farmakoterapie   genetika   metabolismus   patologie   MeSH
• nekroptóza účinky léků   MeSH
• pyroptóza účinky léků   MeSH
• regulovaná buněčná smrt účinky léků   MeSH
• signální transdukce MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• antitumorózní látky MeSH