Synchronous laryngeal cancer.

Multiple primary cancers are usually defined as primary malignant tumors of different histological origins in one person. Synchronous cancers are defined as two or more primary cancers diagnosed in the same patient at the same time or within six months after identifying the first tumor, and those cancers that develop at more than a six-month interval are termed as metachronous multiple primary cancers. Our study comprised of a patient with synchronous laryngeal cancer with double localizations. The case was solved through surgical excision of the tumors. Histopathological and immunohistochemistry examinations revealed synchronous laryngeal cancer. Laryngeal cancer should usually be managed through surgical resection, followed by oncological treatment.

Clinical Characteristics and Local Histopathological Modulators of Endometriosis and Its Progression.

Endometriosis (E) and adenomyosis (A) are associated with a wide spectrum of symptoms and may present various histopathological transformations, such as the presence of hyperplasia, atypia, and malignant transformation occurring under the influence of local inflammatory, vascular and hormonal factors and by the alteration of tumor suppressor proteins and the inhibition of cell apoptosis, with an increased degree of lesion proliferation. MATERIAL AND METHODS: This retrospective study included 243 patients from whom tissue with E/A or normal control uterine tissue was harvested and stained by histochemical and classical immunohistochemical staining. We assessed the symptomatology of the patients, the structure of the ectopic epithelium and the presence of neovascularization, hormone receptors, inflammatory cells and oncoproteins involved in lesion development. Atypical areas were analyzed using multiple immunolabeling techniques. RESULTS: The cytokeratin (CK) CK7+/CK20- expression profile was present in E foci and differentiated them from digestive metastases. The neovascularization marker cluster of differentiation (CD) 34+ was increased, especially in areas with malignant transformation of E or A foci. T:CD3+ lymphocytes, B:CD20+ lymphocytes, CD68+ macrophages and tryptase+ mast cells were abundant, especially in cases associated with malignant transformation, being markers of the proinflammatory microenvironment. In addition, we found a significantly increased cell division index (Ki67+), with transformation and inactivation of tumor suppressor genes p53, B-cell lymphoma 2 (BCL-2) and Phosphatase and tensin homolog (PTEN) in areas with E/A-transformed malignancy. CONCLUSIONS: Proinflammatory/vascular/hormonal changes trigger E/A progression and the onset of cellular atypia and malignant transformation, exacerbating symptoms, especially local pain and vaginal bleeding. These triggers may represent future therapeutic targets.

Influence of tumor topography on clinical-morphological profile of laryngeal malignancies.

AIM: Laryngeal cancers are redoubtable because they are still diagnosed in advanced stages which results in poor survival and the decline of life quality. The authors intend to identify if the tumor topography influences clinical behavior, the morphological profile and therapeutic strategy. PATIENTS, MATERIALS AND METHODS: The study group included 188 patients with laryngeal malignancies diagnosed and treated in an Ear, Nose and Throat (ENT) Department. The patients have been divided into four groups according to the tumor topography and extension. Three categories of parameters were defined (epidemiological, clinical, and morphological) and analyzed comparatively between the four groups using filter scales and the χ² (chi-squared) correlation test. RESULTS: Epidemiological parameters (sex, age, socio-economic status) showed no significant differences between the four groups. Clinical parameters (symptoms, lymphadenopathies, surgical procedures, and hospitalization) instead registered significant differences between the four groups. Morphological parameters (longitudinal diameter, transverse diameter, shape, gross aspect, histopathological aspect, grade, local invasion - pT, lymph node invasion - pN, metastases - pM and tumor stage), excepting shape, registered too significant differences between the four groups. The analysis of the whole set of parameters in each group revealed different, distinct profiles for each of the topographic groups, especially for glottic and large tumors. Our results concerning the entire series of tumors ranged in the limits of variation of each of the parameters observed in the literature. CONCLUSIONS: Our study revealed that tumors placed in different regions of the larynx have distinct profiles from epidemiological, clinical, and morphological points of view. However, the profile of our entire group of tumors proved to be comparable with the literature data.

HPV and Other Risk Factors Involved in Pharyngeal Neoplasm-Clinical and Morphopathological Correlations in the Southwestern Region of Romania.

Oropharyngeal squamous cell carcinoma (OPSCC) development is strongly associated with risk factors like smoking, chronic alcohol consumption, and the living environment, but also chronic human papilloma virus (HPV) infection, which can trigger cascade cellular changes leading to a neoplastic transformation. The prevalence of these factors differs among different world regions, and the prevention, diagnosis, and prognosis of OPSCC are highly dependent on them. We performed a retrospective study on 406 patients diagnosed with OPSCC in our region that were classified according to the tumor type, localization and diagnosis stage, demographic characteristics, risk factors, and histological and immunohistochemical features. We found that most of the patients were men from urban areas with a smoking habit, while most of the women in our study were diagnosed with tonsillar OPSCC and had a history of chronic alcoholism. During the immunohistochemical study, we analyzed the tumor immunoreactivity against anti-p16 and anti-HPV antibodies as markers of HPV involvement in tumor progression, as well as the correlation with the percentage of intratumoral nuclei immunomarked with the anti-Ki 67 antibody in serial samples. We observed that the percentage of Ki67-positive nuclei increased proportionally with the presence of intratumoral HPV; thus, active HPV infection leads to an increase in the rate of tumor progression. Our results support the implementation of strategies for OPSCC prevention and early diagnosis and can be a starting point for future studies aiming at adapting surgical and oncological treatment according to the HPV stage for better therapeutic results.

Cutaneous Malignant Melanoma Metastatic to the Larynx and Trachea: A Case Report and Review of the Literature.

Malignant melanoma rarely develops in mucous membranes. Statistical data show that approximately 0.6-9.3% of patients with cutaneous malignant melanoma will develop metastases in the upper aerodigestive tract mucosa, and within these metastatic sites, the least common are the laryngeal and tracheobronchial ones. This exceedingly rare clinical entity has no clear treatment recommendations; radical surgery does not seem to benefit the patient in term of life expectancy. We present the case of a 56-year-old male patient diagnosed with laryngeal and tracheobronchial melanoma metastases. Prior to admission to our clinic the patient had a personal history of malignant melanoma of the nuchal region operated on 7 years ago, malignant melanoma of the gallbladder and metastatic left axillary polyadenopathy for which he underwent surgical treatment 3 months prior. Histopathological and immunohistochemical reports established the diagnosis of laryngeal metastasis of malignant melanoma. Genetic molecular analysis was positive for B-Raf (BRAF) gene and hence Vemurafenib was administered, with a favorable outcome at the one-year follow-up. Nevertheless, there are currently no clear universally accepted guidelines for the treatment of laryngeal melanoma, mainly due to the rarity of this clinical entity. We conducted a review of similar cases reported in the literature. Interestingly, reviewing the cases reported in the literature, it appears that laryngeal metastases of a primary cutaneous melanoma are more common in men, with an average time to metastasis of 4.3 years.

Nasal polyposis from cystic fibrosis in children - the experience of a single center.

BACKGROUND: Cystic fibrosis (CF) is the most common monogenic disease, characterized by clinically notable polymorphism. Respiratory disease is the main factor that influences the disease outcome and prognosis of the patient with CF, bacterial infections being responsible for severe exacerbations and rhinosinusitis a difficult complication, besides lung disease. AIM: The aim of the paper was to present a case series of CF-associated nasal polyposis and our management experience, providing new data for nasal and sinus complications. PATIENTS, MATERIALS AND METHODS: Patients attending the National Cystic Fibrosis Center, Timisoara, Romania, were evaluated for nasal polyposis. Besides clinical examination, endoscopy, and computed tomography (CT) was performed for comprehensive evaluation. Patients with persistent symptoms or with complicated sinusitis underwent surgical approach. RESULTS: Fourteen (18.18%) children were diagnosed with nasal polyposis and had surgery, with positive outcomes. One patient received Omalizumab for an associated, uncontrolled asthma with a subsequent substantial effect with the significant polyp reduction and lack of recurrence. CONCLUSIONS: Even if extremely difficult to manage, complicated nasal polyposis CF related might have an improved outcome and better life quality.

Kaposi's sarcoma of the larynx: case series.

Kaposi's sarcoma (KS) represents a type of cancer that usually arises on the skin and very rarely in other organs. KS-associated herpesvirus (KSHV), also known as human herpesvirus-8 (HHV-8) commonly arises in patients with acquired immunodeficiency syndrome (AIDS). Laryngeal involvement of KS is very rare. Our study comprised of three cases with laryngeal KS. All cases were solved through surgical excision of the tumor. Histopathological and immunohistochemistry examinations revealed laryngeal KS. Laryngeal KS should be managed through surgical resection, followed by oncological treatment.

Current approach of juvenile nasopharyngeal angiofibroma: a case series.

Juvenile nasopharyngeal angiofibroma (JNA) is a rare benign tumor that affects predominantly males and is known by its highly vascular character. We have performed a 3-year retrospective study of patients with JNA surgically treated within the third ENT Department of Prof. Dr. Dorin Hociota Institute of Phonoaudiology and Functional ENT Surgery, Bucharest, Romania. In all the cases, the patients were investigated both clinically and through medical imaging before surgery and all tumors were embolized. Our study comprised of eight cases, of which seven were solved by endoscopic endonasal approach and one case was treated through a combined endonasal-external approach. JNA should always be managed through a multidisciplinary team (MDT) approach in centers with adequate experience, to gain favorable results.

Current approach to branchial remnants in the neck.

Congenital branchial fistulas and cysts are an interesting subject in cervical pathology. There are congenital malformations with late expression in young adults that require correct diagnosis and appropriate treatment. We review essential notions of cervical embryology to understand the mechanism of occurrence of these malformations and their clinical expression. The most common cases present vestiges from the second branchial arch, with the appearance of a cystic tumor or a fistulous orifice on the anterior edge of the sternocleidomastoid muscle, at the level of the hyoid bone. Performant imagery is mandatory for appropriate diagnosis, so we recommend a cervical computed tomography (CT) scan or cervical magnetic resonance imaging (MRI) to evaluate the relations with great vessels of the neck or other lesions. The treatment implies complete surgical excision because otherwise there is a high risk of recurrence of the lesion. The differential diagnosis includes cystic lymphangioma, dermoid cyst, tuberculous adenopathy, cystic hygroma, lateral cervical cystic metastases. Histological examination is mandatory for a definite diagnosis. Also, there is a small percentage of malignancy of these malformations, but it is very important to check that all the histological diagnostic criteria for a primary branchiogenic carcinoma are accomplished. Therefore, although it is a benign cystic cervical pathology, the diagnosis and treatment must be made very accurately for a complete cure, and this review aims to summarize the current approach to branchial remnants of the neck.

Benign tumors of the superficial lobe of the parotid gland.

Tumors of the parotid gland are a rare occurrence among head and neck tumors (only 3-8%), and the vast majority are benign. Most benign tumors of the parotid gland are pleomorphic adenoma (PA), followed by Warthin's tumor (WT) and they occur in the superficial lobe. The only reasonable treatment is considered to be total tumor removal, but the appropriate surgical approach remains a matter of controversy. Over time, it went from enucleation to superficial parotidectomy (SP) and then to extracapsular dissection (ECD). SP is often considered to be the "gold standard"; however, the risk of intraoperative damage to the facial nerve (FN) cannot be ignored. Lately, ECD - which does not expose the main trunk of the FN - has been regarded as a safe technique for the treatment of small benign parotid tumors. PATIENTS, MATERIALS AND METHODS: The study retrospectively reviewed all parotidectomies for benign parotid tumors of the superficial lobe performed in the Department of ENT, Municipal Emergency Clinical Hospital, Timisoara, Romania, between January 2014 and December 2018. The following patient data were collected: age; sex; follow-up duration; extension of the resection; use of FN monitoring and lesion features, including position, pathology, and size. Preoperative investigation protocol included a computed tomography (CT) scan to assess the size and location of the tumor helping the treatment planning. The same surgical team performed both standard SP and ECD for the treatment of these tumors. All cases were confirmed as benign parotid tumors. Recurrences of any kind and tumors involving the deep lobe of the gland were excluded from the study. All patients underwent a macroscopically complete resection of the tumor. The main outcome was the postoperative complications in the two groups. Data regarding these complications were recorded on follow-up visits at one, six, 12 and 24 months. RESULTS: Ninety-five patients with benign parotid tumors were operated by the same surgical team at the Department of ENT, Municipal Emergency Clinical Hospital, Timisoara, between January 2014 and December 2018 but only 89 (38 men and 51 women) met the follow-up criteria and were included in the study. Sixteen (18%) patients underwent ECD, and 73 (82%) patients underwent SP as a primary intervention. The mean lesion size for ECD group was 2.0±0.9 cm and 4.2±1.7 cm in the SP group, and it was statistically significant (p<0.05). As expected, the most common type of tumor was PA but the distribution between the groups was different: in the SP group, PA represents 83% (61∕73) of cases but only 44% (7∕16) of cases in the ECD group. Median follow-up time was comparable in the two groups - 33±8 months for the ECD group and 39±11 months for the SP group. There were also differences between the two groups regarding the postoperative complication rate. There were significantly more transient and permanent FN paralysis, transient and permanent great auricular nerve (GAN) dysfunctions and Frey's syndrome (FS) in the SP group. CONCLUSIONS: A comparison between ECD and SP as surgical procedures for the treatment of benign tumors of the parotid seems inappropriate as their indications do not overlap. ECD showed similar effectiveness and fewer side effects than SP and can be considered the treatment of choice for small, superficial and/or marginal tumors located in the lateral lobe of the parotid gland.

Cystic hygroma of the neck - case report.

Cystic hygromas (CHs) are benign congenital malformations of the lymphatic system mainly diagnosed in small children aged less than two years old. They may give a multitude of local, sometimes severe complications. The most used method of treatment is surgical removal. In this paper, we present the case of a CH of a 13-year-old boy, localized in the right lateral region of the neck, diagnosed through magnetic resonance imaging (MRI), with excellent results of the surgical treatment.

Neck synovial sarcoma: case presentation.

Head and neck synovial sarcoma (HNSS) is a rare tumor with a few case reports or case series being published in the literature. We present the case of a 68-year-old patient admitted to our department for management of a palpable neck mass. After initial investigation and due to major problems of differential diagnosis, there was performed a wide excision of the tumor. Histopathology examination revealed an HNSS.

Giant pleomorphic sarcoma of the tongue base - a cured clinical case report and literature review.

Pleomorphic sarcoma of the tongue base is an extremely rare pathology finding. Our review of current databases returned fewer than 10 articles available free full text on this subject. We review the current state of art management guidelines for this type of tumor. Our case presented surprisingly a favorable evolution despite the huge dimensions, the tumor type, and associated pathology. The patient received radiation therapy and oncological treatment followed by revision surgery consisting of partial glossectomy for the residual tumor. Histological examination of the operatory specimen showed a residual tumor of pleomorphic sarcoma type, with clear margins. The evolution was without relapse after 18 months.

Involvement of inflammatory cells in chronic rhinosinusitis with nasal polyps.

Inflammation plays an important role in the pathogenesis of nasal polyps. Understanding the biomolecular action mechanisms of inflammatory elements can contribute to improving the prognosis of these lesions. The study analyzed the distribution and immunohistochemically quantified eosinophils [eosinophil major basic protein (BMK-13)], lymphocytes [cluster of differentiation (CD) 4, CD8, CD20] and plasmocytes (CD138) in both the epithelial and stromal compartment in relation to composite scores, which included specific histopathological parameters for 50 sinonasal polyps. Inflammatory elements predominated at stromal level, the high histological composite scores being frequently associated with increased expression of inflammatory elements. Also, the numerical distribution of inflammatory elements indicated positive linear relations within the groups BMK-13∕CD8 and CD4∕CD20∕CD138, and a negative linear relation between the two groups. This aspect can support the existence of alternative or sequential pathogenic mechanisms involved in the pathogenesis of sinonasal polyps, and the results obtained can be used for a better stratification of patients in order to optimize the therapy.

Latest advances in chronic rhinosinusitis with nasal polyps endotyping and biomarkers, and their significance for daily practice.

The term chronic rhinosinusitis (CRS) comprises of an assortment of diseases that share a common feature: inflammation of the sinonasal mucosa. The phenotype classification of CRS, based on the presence of polyps, has failed to offer a curative treatment for the disease, particularly in refractory cases. Chronic rhinosinusitis with nasal polyps (CRSwNP) remains a challenging entity. Researchers have made efforts trying to characterize subtypes of the disease according to the endotypes, which are delineated by different immunological pathways, using biomarkers. Even if the inflammatory processes controlling CRSwNP are not fully understood, data suggested that the disease associated with a type 2 inflammatory mechanisms can be also linked to the type 1 or type 3 pathomechanism, being highly heterogeneous. Biomarkers for CRSwNP are proposed, such as: eosinophil count, cytokines, metalloproteinases, bitter and sweet taste receptors, and the nasal microbiome. For endotyping to be clinically applicable and simply determined, biomarkers referring to the intrinsic biomolecular mechanism still need to be found. Precision medicine is becoming the new standard of care, but innovative therapies such as biologics may be rather challenging for the clinicians in their daily practice. This new approach to CRSwNP implies patient selection and a simple algorithm for deciding the right treatment, easy to implement and adjust. Our review points out the ongoing new research on the pathophysiology of CRSwNP, biomarkers and treatment opportunities. It allows clinicians to keep abreast of current evidence-based knowledge and to individualize the management of CRSwNP, especially in refractory cases.

Clinical, ultrasound and histopathological correlation of clinically N0 neck nodes in patients with cancers of the pharynx and larynx.

BACKGROUND: The presence of metastatic cervical adenopathy is essential for treatment planning and prognosis assessment. Treatment of patients with head and neck cancer with clinically negative cervical lymphadenopathy (N0) remains controversial. Neck palpation, as the method used in tumor, node, metastasis (TNM) staging, has limitations and can provide false negative results in some cases. Lymph node metastases are associated with a reduced survival rate but at the same time, neck dissection for the patient with N0 neck is not without risks or complications. OBJECTIVES: In prospective study, we compared palpation, ultrasonography (US) examination of the neck and histopathological examination in patients with cancers of the pharynx and larynx. PATIENTS, MATERIALS AND METHODS: Forty-six patients with cancers of the pharynx and larynx that presented with a N0 neck were prospectively analyzed. They were divided in two groups: 23 patients operated with an external approach including the control of the lymph node areas, and a second group of 23 patients operated using endoscopy and carbon dioxide (CO2) laser, no neck dissection - "watchful waiting policy". All patients have had a flexible endoscopy of the pharynx and larynx, US of the neck and all received surgical treatment for their primary tumor. Imaging was performed in selected cases. All the removed lymph nodes were sent for histopathology. US was also used as a follow-up method. The US features of the examined lymph nodes were: diameters [longitudinal (L) and transverse (T)]; the ratio of the two diameters (L∕T); shape; lymph node area; central hypodensity; regular∕irregular margins; aspect (homogeneous or not). RESULTS: US has detected 25 lymph nodes in the open surgery group and intraoperatively, we excised 31 (sensitivity of 80.6%). Ten lymph nodes showed metastases, with 100% accuracy of US, which have been confirmed both pathologically and immunohistochemically. US in the second group - patients treated with CO2 laser - detected at four patients 10 cervical lymph nodes that did not presented any malignant features. At recurrence alone, the US confirmed 100% presence of nodes metastases. CONCLUSIONS: US was superior to palpation and this method can be recommended as a diagnostic tool in preoperative assessment of patients without palpable metastasis (N0).

Do we know enough about the genetic involvement in laryngeal cancer susceptibility and prognostic outcome?

INTRODUCTION: Advances in molecular biology have opened the door to a wide range of research material through the usage of genetic testing on certain variables within the human genome known as single-nucleotide polymorphisms (SNPs).The purpose of this article is to present a review on the influence variants within SNPs have on the outcome of laryngeal cancer when associated with different variables, such as external toxins or survival rate. Amongst these toxins, the most frequent and most studied have been alcohol and tobacco consumption, with a proven increased rate of overall cancer risk within the aero-digestive tract. MATERIALS AND METHODS: The review was realized utilizing available studies on the subject of genetic polymorphisms analysis of deoxyribonucleic acid (DNA) samples using polymerase chain reaction (PCR) assays and laryngeal cancer published in the PubMed database. RESULTS: Statistical analysis of 262 polymorphisms shows a predominantly positive association between two genetic variants of the human genome (mutant homozygote and heterozygote) and cancer risk with significant influence on patient outcome and survival. Genotype combinations were divided into two categories depending on the individual 'at risk' and 'protective' allele within the loci of each inherited gene block. Amongst the genes involved with aero-digestive cancers, the most studied were those belonging to the xenobiotic metabolism, nucleotide excision repair (NER) and DNA repair pathways. The presence of toxins has a distinct cumulative effect within the genotype-phenotype relationship, which further influences the presence of malignancy depending on the adaptability of each individual genome. CONCLUSIONS: Laryngeal cancer evolution is linked to inherited risk factors found within the genetic code. Most studied were the genes belonging to NER pathways, DNA repair and xenobiotic metabolism, which all favored mutant homozygote and heterozygote variants, as high risk factors. Only five articles focused on overall survival rates with insufficient results to undisputedly predict the risk variants. The consumption of external toxins has a positive effect on the overall cancer risk in consumers. Most articles affirmed further evaluation or replication was needed in a larger scale population to conclusively validate their results.

Primary tonsillar tuberculosis - case report.

We report the case of a 44-year-old male patient with tonsillar tuberculosis (TB) diagnosed in the Department of Ear, Nose & Throat (ENT), "Victor Babes" University of Medicine and Pharmacy, Timisoara, Romania. The patient addressed to our Clinic with intense odynophagia, referred otalgia, sore throat, fever periods and weight loss. During the ENT clinical exam, we identified an enlarged left tonsil, partially covered with yellowish-white plaque, with ulceration and bleeding spots localized on tonsillar inferior pole. A high suspicion of tonsillar malignancy was raised, and a biopsy was performed revealing extrapulmonary TB. Taking into consideration the normal chest X-ray, a primary tonsillar TB diagnosis was established. The patient was addressed to Department of Pneumophthisiology for anti-tuberculous therapy for six months. At the end of the treatment, the patient was symptoms-free.

The role of HPV infection in oropharyngeal cancer.

BACKGROUND: Human papilloma virus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) has been recognized as a distinct disease entity associated with oral HPV infection with high-risk serotypes, mainly among white man at younger age. Lifetime number of oral sex partners of HPV-positive OPSCC patients is the strongest risk factor associated. HPV type 16 is now established as oncogenic and it is the main cause (over the 80%) of this type of OPSCC, followed by HPV 18 (3%). Nowadays, it is reported a dramatic rising of HPV-positive OPSCC, mainly in developed countries, including Australia, Canada, Denmark, Netherlands, Norway, Sweden, Poland, Slovakia, Switzerland, Estonia, France, Japan, United States (US) and United Kingdom. At present, the yearly number of new incidence OPSCC cases given to HPV worldwide has been estimated of 29 000 by the International Agency for Research on Cancer (IARC). If incidence trends continue, the annual number of HPV-positive oropharyngeal cancers is expected to overcome the annual number of cervical cancers by the year 2020, in the US. AIM: The aim of this paper is to review the recent data about several topics including risk factors of HPV-positive OPSCCs, guidelines in diagnostic evaluation, treatment, prognosis and prevention strategies, through prophylactic HPV vaccine on both sexes. Nowadays, HPV detection is a clinical standard of care for oropharyngeal malignancy by reporting tumors as HPV positive or p16 positive.

Head and neck metachronous tumors - clinical, histopathological and immunohistochemical study.

Multiple primary tumors (MPT) represent an important factor affecting the survival of some patients. They present an incidence of about 0.7-11% of all carcinomas developing in any region of the human body, being either synchronous or metachronous. These tumors raise problems of differential diagnosis, with tumoral relapses and distance metastases; also, they involve problems related to chemotherapy, radiotherapy and surgical treatment. In the present paper, we studied a group of 902 patients diagnosed with head and neck tumors admitted to the Ear, Nose & Throat (ENT) Clinic of the Emergency County Hospital of Timisoara, Romania, and we identified 12 patients with metachronous tumors, representing 1.33% of the hospitalized cases. Of the 12 patients with metachronous tumors, a single case was a woman, the other 11 cases being diagnosed in men. Regarding the age of the patients with metachronous tumors, only a single patient was aged less than 60 years old; most of them (nine patients) were aged between 60 and 69 years old, while two patients were aged over 70 years old. Nine patients were alcohol consumers, while 10 (83.33%) patients were smokers of about 20 cigarettes∕day. All the metachronous tumors localized in the head and neck were squamous cell carcinomas. The second primary tumor was identified in the prostate, kidneys, ureter, lungs, salivary gland, thyroid gland, meninges, colon, rectum or skin.