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Cases with low level JAK2 V617F mutations are increasingly detected; however, the clinical interpretation of the low allele JAK2 burden may be challenging. The aim of this study is to analyze and compare the bone marrow morphology and peripheral blood findings in the low level JAK2 V617F allele burden (≤15% of JAK2) and high JAK2 V617F mutation burden patients (>15% JAK2). In total, 122 JAK2 V617F positive cases with concomitant bone marrow biopsies and peripheral blood findings were re-evaluated (62 low and 60 high level JAK2 V617F positive). Within the low burden group, normal looking megakaryocytes (p = 0.0005) were more frequently found, compared with those with no atypia (p = 0.0003), their number was more frequently not increased (p = 0.009), and they did not form clusters (p = 0.001). We found statistically significant difference in the number of platelet (p = 0.0003) and hematocrit levels (p = 0.032) when comparing the JAK2 V617F

Non-Hodgkin lymphomas are most frequently classified based on the lineage marker expression. However, lymphomas with aberrant marker expression as well as monoclonal IgH/IgΚ and TCR gene rearrangements may co-exist which can be misleading and confusing. Primary CD20 negative diffuse large B-cell lymphomas (DLBCL) represent a rare entity, and they account for 1% to 3% of cases. However, some CD20 negative DLBCLs could not be classified into known variants, creating both diagnostic and therapeutic dilemma’s. Primary CD20 negative DLBCL are more likely to have a non-germinal centre subtype, a higher proliferation index, more frequent extra-nodal involvement, a poorer response, and poorer prognosis to conventional treatment compared to CD20 positive DLBCL. A 66- year-old postmenopausal lady, presented with palpable, bilateral neck lymphadenopathy and difficulty swallowing. She also had left leg lymphoedema, poor appetited, fatigue and weight loss. Her symptoms lasted approximately 1 month. After histological, immunohistochemical and clonality analysis of the lymph node the patient was diagnosed with primary nodal CD20 and PAX-5 negative DLBCL with dual immunoglobulin light-chain kappa ( IgK) and T-cell receptor ( TCR) gene rearrangement. This unusual and unique case presented a diagnostic challenge because it was CD20 and PAX-5 negative, had dual IgK and TCR gene rearrangement and, it could not be classified within the known and well established CD20 negative DLBCL variants. Describing such cases emphasises the fact that lymphomas unclassifiable within known variants of CD20 negative DLBCL do exist and that range and heterogeneity of CD20 negative DLBCL continues to evolve, and pathologist should be aware of these uncommon, atypical mature B-cell neoplasms.

Objective: To evaluate donor site morbidity of the serratus anterior free flap (SAFF) in head and neck reconstruction. Methods: The Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire (0 no disability to 100 most severe disability) was applied to 20 patients (M: 16; F: 4) who underwent ablative surgery and reconstruction of the head and neck using a SAFF. Applications, as well as the donor site, recipient site and flap-related complications, were evaluated. Results: SAFF was mainly used for tongue (n = 11; 55.0%) and pharyngeal reconstruction after a laryngopharyngectomy (n = 4; 20.0%). The majority of patients presented with stage IV disease (n = 12; 60%) and had undergone previous radiotherapy (n = 14; 70%). Our free flap survival rate was 88.9% and the pectoralis major muscle flap (PMMF) was used in 5 patients as a salvage option to reconstruct pharyngeal defects. The mean/median DASH score was 21.6/19.9 (healthy norm 10.1), indicating only mild to moderate disability. However, free flap failure and the additional harvest of PMMF multiplies donor site morbidity since it was associated with a 3- and 2.6-times higher DASH score (46.0 vs. 15.5; p = 0.039 and 39.9 vs. 15.47; p = 0.081). Conclusions: The SAFF represents a versatile flap for head and neck reconstruction with low donor site morbidity.

Purpose: We conducted an outcome analysis on surgically treated laryngeal squamous cell carcinoma (LSCC) patients. Methods: A multicenter retrospective study with 352 patients was analyzed. A new nomogram that incorporates age, T- and N-classification, and treatment was created. Results: Recurrence was observed in 65 (18.5%) patients after a mean time of 16.5 months. After 60 months, 91 (25.9%) of patients developed secondary primary tumors (SPT), most commonly in the lungs (n = 29; 8.2%) followed by other head and neck cancers (n = 21; 6.0%). Notably, the mean time to occurrence of secondary head and neck cancers was twice that of lung cancer (101.1 vs. 47.5 months). Conclusion: Recurrent disease is less common in LSCC patients and appears much earlier than SPT. Because one in every four laryngeal cancer patients develops SPTs within 5–10 years, long-term care and follow-up, including imaging studies, are highly recommended. The nomogram was useful for estimating survival.

Cilj rada: Analizirati funkcionalni i onkološki ishod bolesnika s ranim stadijem karcinoma grkljana, liječenih frontolateralnom laringektomijom. Bolesnici i metode: U retrospektivno istraživanje uključeno je 45 kirurški liječenih bolesnika s ranim stadijem karcinoma grkljana. Funkcionalni ishod uključivao je procjenu respiratorne i fonatorne funkcije, te akta gutanja. Respiratorna funkcija grkljana smatrana je primjerenom u slučaju nepostojanja stenoza i uspješnog dekanilmana. Za evaluaciju glasa korištene su GRBAS skala, Voice Handicap Index 30 upitnik i spektralna akustična analiza glasa. Akt gutanja procjenjivan je na osnovu anamnestičkih podataka i fiberlaringoskopskog pregleda. Onkološki ishod prikazan je Kaplan-Meierovim krivuljama ukupnog preživljenja (overall survival), preživljenja bez bolesti (disease free survival) i preživljenja vezanog uz bolest (disease specific survival). Rezultati: Od ukupno 45 bolesnika, 3 su bila ženskog, a 42 muškog spola. Medijan dobi iznosio je 64 godine (raspon 44-79). Svi su se tumori nalazili u glotičkoj regiji, te su svrstani u T1 (60%) ili T2 (40%) klasifikaciju bolesti. Postoperativna radioterapija primijenjena je u 15 (33,3%) bolesnika zbog limfovaskularne invazije tumora ili R1 resekcijskih rubova. Svi su bolesnici imali urednu respiratornu funkciju te uredno izvršen dekanilman. Kod niti jednog bolesnika nismo verificirali poremećaj gutanja. Analiza fonatorne funkcije pokazala je umjerene teškoće bolesnika vezane uz kvalitetu glasa. Procjenom onkološkog ishoda utvrđeno je da je petogodišnje preživljenje vezano uz bolest iznosilo 100%, petogodišnje ukupno preživljenje 93,3%, dok je petogodišnje preživljenje bez bolesti iznosilo 86,7%. U sklopu praćenja bolesnika (medijan 86,2 mjeseca), dva su bolesnika razvila lokalni, a jedan regionalni recidiv bolesti. Zaključak: Iako noviji modaliteti liječenja nude bolji funkcionalni ishod što se najviše očituje u kvaliteti glasa, frontolateralna laringektomija nudi podjednak onkološki ishod i vrijedna je alternativna kirurška opcija u pomno izabranim slučajevima.

(1) Objective: To evaluate long-term functional outcome in patients who underwent primary or salvage total laryngectomy (TL), TL with partial (TLPP), or total pharyngectomy (TLTP), and to establish a new scoring system to predict complication rate and long-term functional outcome, (2) Material and Methods: Between 1993 and 2019, 258 patients underwent TL (n = 85), TLPP (n = 101), or TLTP (n = 72). Based on the extent of tumor resection, all patients were stratified to (i) localization I: TL, II: TLPP, III: TLTP and (ii) surgical treatment (A: primary resection, B: salvage surgery). Type and rate of complication and functional outcome, including oral nutrition, G-tube dependence, pharyngeal stenosis, and voice rehabilitation were evaluated in 163 patients with a follow-up ≥ 12 months and absence of recurrent disease, (3) Results: We found 61 IA, 24 IB, 63 IIA, 38 IIB, 37 IIIA, and 35 IIIA patients. Complications and subsequently revision surgeries occurred most frequently in IIIB cases but rarely in IA patients (57.1% vs. 18%, p = 0.001 and 51.4% vs. 14.8%, p = 0.002), respectively. Pharyngocutaneous fistula (PCF) was the most common complication (33%), although it did not significantly differ among cohorts (p = 0.345). Pharyngeal stenosis was found in 27% of cases, with the highest incidence in IIIA (45.5%) and IIIB (72.7%) patients (p &lt, 0.001). Most (91.1%) IA patients achieved complete oral nutrition compared to only 41.7% in class IIIB patients (p &lt, 0.001). Absence of PCF (odds ratio (OR) 3.29, p = 0.003), presence of complications (OR 3.47, p = 0.004), and no need for pharyngeal reconstruction (OR 4.44, p = 0.042) represented independent favorable factors for oral nutrition. Verbal communication was achieved in 69.3% of patients and was accomplished by the insertion of voice prosthesis in 37.4%. Acquisition of esophageal speech was reached in 31.9% of cases. Based on these data, we stratified patients regarding the extent of surgery and previous treatment into subgroups reflecting risk profiles and expectable functional outcome, (4) Conclusions: The extent of resection accompanied by the need for reconstruction and salvage surgery both carry a higher risk of complications and subsequently worse functional outcome. Both factors are reflected in our classification system that can be helpful to better predict patients’ functional outcome.

Novel molecular techniques including markers of laryngeal carcinogenesis could improve the difficult diagnosis of a wide array of laryngeal polypoid changes. The case reported herein shows that not every clinically diagnosed vocal fold polyp is a benign lesion as mostly considered in the literature. Further assessment including carcinogenesis markers detected a nest of micro-invasive squamous cell carcinoma. Therefore, we recommend biopsy backed up with immunohistochemical analysis whenever there is a suspicious polypoid formation in order to exclude or confirm a malignant transformation because of the possibility of multi-focal growth in the active laryngeal epithelium., Sažetak. Nove molekularne tehnike, uključujući markere laringealne karcinogeneze, mogu pridonijeti diferencijalnoj dijagnozi širokog spektra polipoidnih promjena grkljana. Prikazujemo slučaj koji ukazuje na to da nije svaka klinički dijagnosticirana polipoidna lezija glasnica benigna kao što se obično navodi u literaturi jer smo daljnjom imunohistokemijskom obradom otkrili žarište mikroinvazivnog planocelularnog karcinoma. Stoga kod svake polipoidne tvorbe grkljana preporučujemo biopsiju popraćenu imunohistokemijskom analizom markera kako bi se potvrdila ili isključila maligna transformacija zbog poznate sklonosti multifokalnom rastu u aktivnom epitelu grkljana.

Maligni tumori usne šupljine spadaju u češće tumore glave i vrata, te čine 2-3% svih tumora u ljudskom organizmu. Dijelovi svijeta, većinom Azijskog kontinenta (Indija, Pakistan, Kina, Tajvan) imaju incidenciju veću od 10/100.000 stanovnika, dok većina zemalja Europe, a time i Hrvatska, imaju incidenciju od oko 4-7/100.000 stanovnika i stopu mortaliteta od oko 2/100.000 stanovnika. Češće je zahvaćena muška populacija, obično iznad pedesete godine života. Omjer učestalosti obzirom na spol je 2-5:1. Etiologija nije još u potpunosti razjašnjena, ali uz genetsku predispoziciju, nekoliko rizičnih čimbenika povećava se rizik od zloćudnog oboljenja. Najsnažnije se ističu pušenje i konzumacija alkohola, te posebice njihov sinergijski učinak. U manjem postotku slučajeva karcinom se javlja uz prisutnu infekciju humanim papiloma virusom (HPV tip 16). Različite navike poput žvakanja duhana pomiješanog s lišćem betela, nasjeckanim Areka orahom i prahom gašenoga vapna, objašnjavaju pojačanu učestalost ovoga tipa karcinoma u azijskim zemljama. Dijagnoza se postavlja na osnovu anamnestičkih podataka, znakova bolesti, kliničkoga pregleda, te patohistološke analize bioptiranog tumora. U svrhu precizne anatomske lokalizacije tumora i uvida u proširenost bolesti, primjenjuje se slikovna dijagnostika (CT i/ili MR glave i vrata). Dijagnostiku je potrebno, posebno u slučajevima uznapredovalih tumora, upotpuniti slikovnim metodama susjednih regija (CT toraksa i abdomena) ili cijelog tijela (PET/CT) radi isključivanja udaljenih metastaza ili sekundarnog primarnog tumora. Ultrazvuk vrata i citološka analiza punktata suspektnih limfnih čvorova, metode su izbora za dokaz regionalne proširenosti bolesti. Na temelju kliničke obrade određuje se stadij bolesti prema međunarodnoj TNM klasi- fikaciji, nakon čega slijedi odluka o liječenju.

Renal clear cell metastatic carcinoma of the larynx is an extremely rare diagnosis with poor survival. The objective of this short review is to provide insight into current state of literature on this rare neoplasm. Additionally we include the case of a patient with metastatic process of the thyroid cartilage that was treated with novel targeted therapies which enabled prolonged survival and good quality of life. These findings support their inclusion in treatment protocols of patients with metastatic renal clear cell carcinoma of the larynx, especially in those refusing surgery which is the main treatment option in literature so far., Metastaza svjetlostaničnog karcinoma bubrežnih stanica u grkljan izuzetno je rijetka dijagnoza s lošim preživljavanjem. Cilj je ovog kratkog preglednog članka pružiti uvid u trenutno stanje literature o ovoj rijetkoj novotvorini. Uz to uključujemo i slučaj pacijenta s metastatskim procesom tiroidne hrskavice koji je liječen novim ciljanim terapijama koje su omogućile produljeno preživljavanje i dobru kvalitetu života. Ova otkrića potkrepljuju njihovo uključivanje u protokole liječenja pacijenata sa svjetlostaničnim metastatskim karcinomom grkljana, posebno kod pacijenata koji odbijaju kirurško liječenje, što je dosad glavni modalitet liječenja prema dostupnoj literaturi.

Novel molecular techniques including markers of laryngeal carcinogenesis could improve the difficult diagnosis of a wide array of laryngeal polypoid changes. The case reported herein shows that not every clinically diagnosed vocal fold polyp is a benign lesion as mostly considered in the literature. Further assessment including carcinogenesis markers detected a nest of micro-invasive squamous cell carcinoma. Therefore, we recommend biopsy backed up with immunohistochemical analysis whenever there is a suspicious polypoid formation in order to exclude or confirm a malignant transformation because of the possibility of multi-focal growth in the active laryngeal epithelium., Sažetak. Nove molekularne tehnike, uključujući markere laringealne karcinogeneze, mogu pridonijeti diferencijalnoj dijagnozi širokog spektra polipoidnih promjena grkljana. Prikazujemo slučaj koji ukazuje na to da nije svaka klinički dijagnosticirana polipoidna lezija glasnica benigna kao što se obično navodi u literaturi jer smo daljnjom imunohistokemijskom obradom otkrili žarište mikroinvazivnog planocelularnog karcinoma. Stoga kod svake polipoidne tvorbe grkljana preporučujemo biopsiju popraćenu imunohistokemijskom analizom markera kako bi se potvrdila ili isključila maligna transformacija zbog poznate sklonosti multifokalnom rastu u aktivnom epitelu grkljana.

The membrane EGFR (mEGFR) protein overexpression in the head and neck squamous cell carcinoma (SCC) is considered to cause increased EGFR activity which adds to tumorigenicity and therapy resistance. The mEGFR upon stimulation can translocate to the nucleus nuclear EGFR (nEGFR) where it has been associated with poor prognosis and worse survival in many cancers. The relevance of differentially located EGFR proteins in laryngeal lesions has not been studied enough and remains unclear. Aim of our study was to examine nEGFR and mEGFR protein expression as well as EGFR gene status and cell cycle proliferation markers in the laryngeal polyps, dysplasia, and SCC using immunohistochemistry and in situ hybridization. There was significantly higher frequency of strong nEGFR between SCC, dysplasia, and polyps (P

Rationale: The aim of this case is to emphasize the need to include nerve traction in the differential diagnosis of nerve deficits associated with Vernet syndrome. This mechanism of injury has been described only once, but must not be overlooked and should be considered and included as a possible cause in diagnostic algorithms. Patient concerns: A patient presenting with dysphagia, extreme hoarseness, and limited shoulder movement after head injury was admitted to the emergency department. Diagnoses: Multidisciplinary evaluation was performed, and nerve traction-induced Vernet syndrome was established as a running diagnosis. Interventions: Intensive swallowing and speech exercises, assisted by a specialist, were performed. Outcomes: Swallowing and speech exercises significantly and objectively improved the patient's swallowing and voice, with mild hoarseness of voice remaining as the main symptom. Spectral acoustic analysis went from a voice pitch of 163.77 Hz to normal (187.77 Hz), jitter improved from 17.87% to 0.86% and shimmer values decreased from 39.86% to 19.60%. Breathiness during phonation measuring 2.91% was reduced to 1.08% and appropriate average intensity of voice (63.95 dB) was achieved. Initial dysphagia and fluid retention in the right piriform sinus, along with tracheal aspiration, were not observed in control fiberoptic endoscopic evaluation of swallowing. Lessons: According to our knowledge and literature data, this is the second reported case of posttraumatic Vernet syndrome without radiologically confirmed jugular foramen fracture, induced by nerve traction. Such patients need a prompt multidisciplinary approach in diagnosis and timely posttraumatic rehabilitation therapy for favorable clinical evolution and retrieval of nerve function.

Cilj: Cilj rada je prikazati slučaj s višestrukim rijetkim komplikacijama laringokele. Prikaz slučaja: Prikazujemo slučaj 71-godišnje pacijentice s višestrukim komplikacijama laringokele. Pacijentica se prvi put javlja u kliniku za otorinolaringologiju i kirurgiju glave i vrata KBC-a Rijeka u veljači 2008. te biva podvrgnuta traheotomiji zbog epizode akutnog epiglotitisa. Godinu dana kasnije pacijentica se vraća na kliniku zbog odinofagije i disfagije. Postavlja se dijagnoza parafaringealnog apscesa te se on incidira i drenira. Godine 2010. pacijentica biva ponovno hospitalizirana zbog mase na vratu te se započinje s dijagnostikom. Nekoliko dana kasnije pacijentica se otpušta, ali se ubrzo samoinicijativno vraća na kliniku dispnoična. Učini se magnetska rezonancija vrata i postavi se dijagnoza laringokele koju se liječi kirurškom ekstirpacijom. Zaključak: Naša pacijentica prezentira se nizom zanimljivih i vrlo rijetkih komplikacija koje čine ovaj slučaj vrijednim prikazivanja. Pretpostavljamo da je pacijentica u ovom slučaju laringokelu razvila zbog traheotomije 2008. godine. Pretražujući literaturu, pronašli smo samo jedan slučaj koji povezuje traheotomiju s nastajanjem laringokele. Nadalje, laringokela je pacijentici uzrokovala po život opasnu opstrukciju dišnog puta, što je samo po sebi vrlo rijetka komplikacija. Možemo pretpostaviti da bi ranija dijagnoza i adekvatno liječenje omogućilo ovoj pacijentici da izbjegne sve komplikacije te se nadamo kako će ovaj slučaj podići svijest o laringokeli i smanjiti incidenciju komplikacija u budućnosti., Objective: The aim of this case report is to present a case with multiple rare laryngocele complications. Case review: This case report follows a 71-year-old female patient with multiple complications following the formation of a laryngocele. The patient first arrives at the Otorhinolaryngology, head and neck surgery clinic in February 2008 and undergoes a tracheotomy for acute epiglottitis. A year later, the patient returns to the clinic complaining about odynophagia and dysphagia. A diagnosis of parapharyngeal abscess is made and the patient is treated with incision and drainage. In 2010 the patient is re-hospitalized for a neck formation and a diagnostic procedure is initiated. A few days later, the patient is discharged, but soon returns to the hospital dyspnoeic. Magnetic resonance imaging of the neck is performed, and a diagnosis of laryngocele is made. The patient undergoes surgical extirpation of the laryngocele. Conclusion: The patient in this case has an interesting combination of rare complications which makes this case worth representing. Firstly, we assume that this patient has developed a laryngocele following a tracheostomy. We were able to find only one case of post-tracheostomy laryngocele formation in the literature. Secondly, the laryngocele caused this patient a life threating airway obstruction which is in itself a very rare complication. We can speculate that an earlier diagnosis and treatment could have saved the patient of all the complication she had, and we hope this case can contribute to lower the incidence of laryngocele complications in the future.

Novonastali uvećani čvor vrata je čest razlog posjete liječniku, a dijagnostika i liječenje ponekad uključuju specijaliste različitih specijalnosti. Anamneza i fizikalni pregled ključni su koraci u početku evaluacije i daljnjeg usmjeravanja bolesnika na odgovarajuće dijagnostičke ili terapijske postupke. Diferencijalna dijagnoza je vrlo široka, te dobno ovisna, pa je stoga bitno utvrditi radi li se o mogućem upalnom stanju, kongenitalnoj ili neoplastičnoj patologiji. U većini slučajeva dijagnostički postupak uključuje ultrazvuk s mogućom citološkom punkcijom tvorbe ili se čine druge slikovne pretrage poput CT-a ili MRI. U specifičnim slučajevima izvodi se biopsija tvorbe. Liječenje ovisi o uzroku.

Objective: The aim of the study was to investigate the expression of ribonuclear protein IMP3 in laryngeal carcinogenesis, together with other biomarkers of carcinogenesis (Ki-67, p53 and cyclin D1), and to evaluate their predictive values. Methods: The study included 153 patients divided into three groups: 68 operated for primary invasive laryngeal squamous cell carcinoma (LSCC) ; 41 with precancerous lesions of atypical and abnormal hyperplasia ; 44 with hyperplastic laryngeal nodule without atypia. Tissue microarray technique was used for immunohistochemical analysis. Results: All markers showed statistically significant differences between the three groups.The percentage of IMP3 positive cells is statistically significantly higher in LSCC group in comparison to precancerosis and control group. The percentage of Ki-67 positive cells is statistically significantly higher in LSCC group in comparison to precancerosis and control group. The percentage of p53 positive cells in LSCC group is statistically significantly higher than the control group and higher, but not statistically significant, than the precancerosis group. The percentage of cyclin D1 positive cells is statistically significantly higher in LSCC group than in precancerosis group and higher, but not statistically significant, than in the control group. All analyzed markers have good predictive values (AUC &gt ; 0.6), but the percentage of IMP3 positive cells is the only statistically significant marker in predicting whether the patient has LSCC or not. Conclusion: Expression of Ki-67 and pronouncedly IMP3 generally follow the same pattern where control and precancerosis are similar and LSCC significantly differs, as opposed to p53 and cyclin D1. This implies that, if precancerosis is radically surgically treated before the transformation of molecular phenotype takes place (increase in IMP3 and Ki- 67 expression, further increase in p53 and re- increase in cyclin D1 expression, all coinciding with malignant transformation), we can consider the case clinically “most probably solved”. IMP3 expression increase possibly has an important diagnostic, therapeutic (in terms of the need for additional therapy after surgery) and prognostic value. Further studies on the exact molecular mechanisms behind it are, of course, needed.

Simple Summary Salivary bypass tubes (SBT) have been introduced in order to reduce the risk of pharyngocutaneous fistula (PCF) after laryngectomy with pharynx reconstruction. Although the current literature is rather heterogenous, our meta-analysis demonstrates a favorable effect of SBT insertion on PCF formation in patients after laryngopharyngectomies. Abstract To evaluate the effect of salivary bypass tube (SBT) usage on the occurrence of pharyngocutaneous fistula (PCF) in patients after a laryngopharyngectomy, a total of 20 studies, published between 1988 and 2021, were identified including 2946 patients. We performed a meta-analysis assessing the risk of PCF occurrence in patients after SBT application compared to those without. PCF occurred in 26.8% of cases (669/2496) and SBT was applied in 33.0% of patients (820/2483). There was an overall trend towards lower PCF rates when using SBTs (22.2% vs. 35.3%; p = 0.057). We further selected five studies, comprising 580 patients who underwent laryngopharyngectomies, for meta-analysis showing that application of SBT reduced the risk of PCF formation (OR 0.46; 95% CI 0.18–1.18; p = 0.11). The meta-analysis demonstrates a beneficial effect of SBT insertion on PCF formation in patients after laryngopharyngectomy.

The aim of study was to investigate the expression of the proliferation factor Ki-67 and its relationship with histological grade, cancer stage, and treatment outcome in squamous cell carcinoma of the larynx. Samples from 78 patients with laryngeal cancer were analysed retrospectively. Paraffin sections of tumors were immunohistochemically stained for Ki-67 expression. The patients were divided in two groups according to the proliferative factor values (a low Ki-67 index group - Ki-67≤34 and high Ki-67 index group-Ki-67 >34). Statistical analysis of the data shows significant correlation among histological tumor grade and the value of the Ki-67 proliferative index. There was no correlation between tumoral Ki-67 expression and diagnosis, stage of the disease, or treatment outcome. In conclusion, Ki-67 expression in laryngeal cancer is not the most reliable marker for making precise diagnosis and predicting the clinical course.

Objective The aim of the study was to perform a pathohistological and immunohistochemical analysis of squamous cell (SC) carcinogenesis markers on epithelial linings of vocal cord polyps. The vocal box, being a heavily burdened organ with intensive cell renewal and regenerative processes, is therefore a favourable environment for constant epithelial growth and hyperplasia. In our ongoing projects on laryngeal carcinogenesis and research on laryngeal tissue, we encountered atypia on diagnosed nodules and polyps that are usually considered as benign formations, resulting from the above-mentioned cell renewal and regeneration, which lead to further investigation. The purpose was to see if changes in molecular markers of SC carcinogenesis follow, or, may appear in immunohistochemical (IHC) analysis, before histological atypia in standard haematoxylin-eosin (HE) staining, and contribute in early diagnosis of potentially suspect polyps. Methods After classical pathohistological (PH) analysis on HE slides, IHC analysis of EGFR, cyclin D1, p53, Ki-67, and IMP3 was performed on tissue microarrays of laryngeal tissue (50 samples), ranging from normal to hyperplastic lesions with no atypia (34 samples), low-grade atypia (11 samples), and high-grade atypia (5 samples). Results This study established an increase and correlation of EGFR, cyclin D1, p53, Ki-67 and IMP3 IHC expressions with pathohistological findings of dysplasia in glottic polypoid lesions. Low and high-grade dysplasia had statistically higher percentages of EGFR-positive cells than normal epithelium and simple hyperplasia (SH) (low vs. normal/SH P = 0.007; high vs. normal/SH P = 0.001). High-grade dysplasia had statistically more positive cells than low-grade dysplasia (P = 0.004), and low-grade dysplasia had statistically more positive cells than specimens without atypia (P = 0.007). The percentage of positive cells was statistically higher for cyclin D1, p53 and Ki-67 in high-grade dysplasia versus low-grade dysplasia (cyclin D1 P = 0.011, p53 P = 0.002; Ki-67 P = 0.026; respectively) and versus normal epithelium and SH (cyclin D1 P = 0.003; p53 P = 0.001; Ki-67 P = 0.002; respectively). An increase of IMP3-positive cells with an increase of atypical changes in the laryngeal epithelium, from superficial towards basal layers was noticed, contrary to the usually seen positivity pattern of SC carcinogenesis markers from basal to superficial layers. A statistically significant difference of IMP3 IHC staining between the pathohistological groups (P = 0.003) was recorded. Conclusion Only polyps that present with simple hyperplasia as the greatest mucosal change can be considered as benign formations. Pathohistologically detected atypia in polypoid changes of vocal cords, confirmed by molecular atypia with an increase of SC carcinogenesis markers, suggest their inclusion in studies of laryngeal carcinogenesis. Our results suggest that in problematic cases IHC analysis could be of interest in detection of biological aggressiveness in polypoid laryngeal tissue and beneficiary for polyp patients’ follow-up. Further research of laryngeal carcinogenesis markers and their meaning in fibrovascular polyps is of interest.

Cilj: Ispitati povezanost srednjeg volumena trombocita - MPV (engl. mean platelet volume) s kliničkim stadijem karcinoma grkljana te s histološkim značajkama karcinoma koje mogu činiti podlogu patofiziologije promijenjenog broja te volumena trombocita. Materijali i metode: Retrospektivno su analizirani laboratorijski i klinički podaci 76 pacijenata s patohistološki potvrđenim planocelularnim karcinomom grkljana. Podijelom po kliničkoj TNM klasifikaciji dobivene su dvije skupine: rani i kasni karcinom grkljana. Nadalje, pacijenti su podijeljeni u grupe prema stupnju diferencijacije stanica karcinoma, kao i po prisutnosti vaskularne invazije. Rezultati: Statistički značajna razlika između skupina ranog i kasnog karcinoma u demografskim podacima i podatku o pušenju nije pronađena. Usporedba MPV vrijednosti pokazala je značajnu razliku (P= 0,003) između skupina ranog i kasnog karcinoma grkljana. Nadalje, usporedba istih skupina ukazala je na povećan broj trombocita u skupini kasnog karcinoma grkljana (P, Aim: This study aimes to investigate alteration of MPV (mean platelet volume) in laryngeal cancer. The hypothesis is that different clinical stages of laryngeal cancer and histological characteristics may be the basis of the pathophysiological changes in size and number of platelets. Materials and methods: Laboratory and clinical data were analysed retrospectively from 76 patients with laryngeal squamous cell carcinoma. Two main groups were formed upon TNM clasification: early stage and advanced stage laryngeal cancer. Furthermore, the patients were subdivided according to cancer degree of differentiation and presence of blood vessel invasion. Results: Statisticly significant difference between early and advanced stage cancer in the demographic and smoking data was not found. The comparison of MPV values showed statistically significant difference (P=0,003) between early and advanced laryngeal cancer. Furthermore, platelet values were significantly higher in the advanced group (P

Myxoma is a benign tumor composed of primitive connective tissue cells and mesenchymal mucousal stroma. Also referred to as, a gelationus or colloidal tumor. Although rare, it can be found in the atrium of the heart, and it is the most common heart tumor. It has also been described in other body sites, one of which is the bone. We report a case of a 57-year-old female patient, with recurrent headaches located in the area of the right half of the face. Radiological analysis (Multislice Computed Tomography of the paranasal sinuses and viscerocranium) was performed, and a formation of irregular contours, destroying the right zygomatic bone, was described, measuring 25 x 17 x 20 mm in its widest diameters. Its me- dial border was adjacent to the lateral wall of the right maxillary sinus and the cortical bone in this segment was thinned, but preserved. A probatory excision was performed in general anesthesia, and the histopathological finding showed, star-like tumor cells embedded in mucoid stroma and infiltrating the bone. After pathohistological confirmation of myxoma, the tumor was excised in total, using infraorbital surgical approach to the zygomatic bone. During the follow-up, the patient was symptom free, without headaches, and there were no signs of local tumor recurrence. Despite of the fact that myxoma behaves as a benign disease in its nature, it can cause destruction of the tissue in the vicinity of the tumor itself and thus major health issues for the patient. A timely proper diagnosis and the right choice of a surgical treatment can help avoid more extensive surgery procedures, as shown in our case report.

Total laryngectomy, as a consequence of carcinoma of the larynx, results in loss of speech function. Cerebrovascular stroke is the leading cause of reduced speech production ability, and thereby communication difficulties. The case is presented of a 60-year-old male patient who suffered stroke five years after a total laryngectomy. Speech rehabilitation was hampered due to the depressive state of the patient. Although contraindicated, the secondary voice prosthesis was implanted. Only at that moment the patient showed willingness and motivation for speech rehabilitation. The aim of this presentation is to demonstrate that not all neurological disorders are contraindicated for implantation of voice prostheses.

Kliničke manifestacije jetrene bolesti širokog su spektra, počevši od asimptomatskog povišenja jetrenih enzima do mogućeg dramatičnog zatajenja jetre. Bolesnici su dugo vremena bez simptoma, a otkrivaju se u kasnijim fazama bolesti. Loša prognoza i visoki troškovi liječenja uznapredovale jetrene bolesti zahti jevaju rano dijagnosti ciranje bolesti i pravovremeno liječenje. U pristupu bolesniku s povišenim jetrenim enzimima nužna je iscrpna anamneza i detaljan fi zikalni pregled. Pravovremena rana dijagnoza jetrene bolesti može spriječiti razvoj ireverzibilnog oštećenja jetre., Clinical manifestati ons of liver disease are of wide spectra, from asymptomatic elevation of liver enzymes to possible dramatic and progressive liver failure. The liver disease develops subclinically for a long time and the disease is being diagnosed in its later stages. Bad prognosis and high costs of treatment demand early diagnosis and adequate treatment. In the approach to the patient with elevated liver enzymes the most important are detailed medical history and physical exam. Early diagnosis of the liver disease can prevent the development of irreversible liver damage.

Axillary lymph node dissection (ALND) is an important procedure in the staging of breast cancer patients. However, it is associated with a significant morbidity rate. In addition, using early diagnosis a high number of cases with negative lymph nodes can be identified. A lymph node defined as sentinel lymph node (SLN) would be the first to receive tumoral drainage. A less morbid but accurate staining procedure using mapping and SLN biopsy has been introduced. The aim of this study was to estimate the likelihood of additional disease in the axilla after SLN analysis. A total of 259 breast carcinomas and SLN biopsies followed by ALND were examined. The patient median age was 59 years, approximately 75% of them postmenopausal. Tumor size was 1.4 ± 0.8 cm (almost 80% in pT1). SLNs were positive in 59 of 259 (22.8%) carcinomas, 30 (11.6%) with micrometastases (2 mm in SLN ( P = .003), in carcinoma with higher nuclear grade ( P = .044), decreased estrogen receptor (ER; P = .042), and progesterone receptor (PR; P = .042). Finally, lymph node status (pN) following SLN and ALND was found to be significantly associated with tumor size ( P = .006), LVI ( P = .037), PR ( P = .023), and Her-2 status ( P < .001). These results point to detailed analysis of primary tumor and SLN that may increase the precision of patient selection for further axillary surgery or radiotherapy.

Axillary lymph node dissection (ALND) is an important procedure in the staging of breast cancer patients. A lymph node defined as sentinel lymph node (SLN) would be the first to receive tumoral drainage. The aim of this study was to estimate the likelihood of additional disease in the axilla after SLN mapping. A total of 259 breast carcinomas and SLN biopsies followed by ALND were examined. The patient median age was 59 years, approximately 75% of them postmenopausal. Tumor size was 1.4±0.8 cm (almost 80% in pT1). SLNs were positive in 59 of 259 (22.8%) carcinomas, 30 (11.6%) with micrometastases (2 mm in SLN (p=0.003), in carcinoma with higher nuclear grade (p=0.044), decreased ER (p=0.042), and PR (p=0.042). Finally, lymph node status (pN) following SLN and ALND was found to be significantly associated with tumor size (p=0.006), LVI (p=0.037), PR (p=0.023) and Her-2 status (p

Aims and Background Diffuse large B-cell lymphoma displays striking heterogeneity at clinical, genetic and molecular levels. The International Prognostic Index is useful to predict the outcome of diffuse large B-cell lymphoma patients. However, patients with identical International Prognostic Index values in clinical practice exhibit marked variability in survival, suggesting the presence of significant residual heterogeneity within each category. Since cytokines such as interleukin-6, -8 and -10 play important roles in the pathogenesis of lymphomas, and plasma level of beta2-microglobulin is associated with the outcome of patients with diffuse large B-cell lymphoma, the aim of the present study was to determine whether these parameters combined with the International Prognostic Index would better stratify these patients to predict their prognosis. Patients and Methods The study included 46 untreated diffuse large B-cell lymphoma patients. Results All study parameters (International Prognostic Index, Ann Arbor stage, extra-nodal involvement, performance status, lactate dehydrogenase, beta2-microglobulin, interleukin-6 and -10, and response to therapy) except for patient age and serum interleukin-8 level were associated with overall survival. In addition, the International Prognostic Index was strongly correlated with beta2-microglobulin, interleukin-6, -8 and -10, and when combined these parameters significantly better stratified patients according to survival. On multivariate analysis, therapeutic response to the primary treatment, elevated interleukin-6 and -10 levels, and the International Prognostic Index were significant predictors of overall survival. Conclusions Our data imply that interleukins and beta2-microglobulin evaluation should be used in association with the International Prognostic Index to define prognostic subgroups in diffuse large B-cell lymphoma patients.

Diffuse large B-cell lymphoma displays striking heterogeneity at clinical, genetic and molecular levels. The International Prognostic Index is useful to predict the outcome of diffuse large B-cell lymphoma patients. However, patients with identical International Prognostic Index values in clinical practice exhibit marked variability in survival, suggesting the presence of significant residual heterogeneity within each category. Since cytokines such as interleukin-6, -8 and -10 play important roles in the pathogenesis of lymphomas, and plasma level of beta2-microglobulin is associated with the outcome of patients with diffuse large B-cell lymphoma, the aim of the present study was to determine whether these parameters combined with the International Prognostic Index would better stratify these patients to predict their prognosis. The study included 46 untreated diffuse large B-cell lymphoma patients. All study parameters (International Prognostic Index, Ann Arbor stage, extranodal involvement, performance status, lactate dehydrogenase, beta2-microglobulin, interleukin-6 and -10, and response to therapy) except for patient age and serum interleukin-8 level were associated with overall survival. In addition, the International Prognostic Index was strongly correlated with beta2-microglobulin, interleukin-6, -8 and -10, and when combined these parameters significantly better stratified patients according to survival. On multivariate analysis, therapeutic response to the primary treatment, elevated interleukin-6 and -10 levels, and the International Prognostic Index were significant predictors of overall survival. Our data imply that interleukins and beta2-microglobulin evaluation should be used in association with the International Prognostic Index to define prognostic subgroups in diffuse large B-cell lymphoma patients.

Sentinel lymph node and clinically negative axillary node status was compared with well-known clinicopathological characteristics such as tumor size, histologic and nuclear grade, lymphovascular invasion, steroid receptor, and HER-2 status in patients with breast cancer (pT1 and pT2). Positive sentinel lymph nodes were found in 29 of 100 patients: 19 with metastases detected by hematoxylin and eosin staining and 10 with micrometastases confirmed by immunohistochemistry with cytokeratin. Positive sentinel lymph nodes were present in larger carcinomas ( P < 0.03), more frequently in tumors with negative PR status ( P < 0.037) and evident lymphovascular invasion ( P < 0.002). Lymphovascular invasion was also associated with breast cancer of higher histologic ( P = 0.011) and nuclear grade ( P = 0.039). Tumor size and the presence of lymphovascular invasion were found to be significant predictors of pathologically positive sentinel lymph node in T1 and T2.

Extramedullary plasmacytoma (EMP) of the orbit is an extremely rare tumor, which frequently manifests with nonspecific symptoms. In the case reported, the symptoms of relapsing dacryocystitis appeared before the diagnosis of orbital EMP in a 60-year-old man. Moreover, EMP of the right submandibular gland that had been excised and treated by radiotherapy preceded the orbital lesion by seven years. The present report emphasizes the importance of an extensive medical workup to rule out multiple myeloma or other malignant lymphoproliferative diseases, because their treatment and prognosis are very different. Additionally, it is necessary to consider all tumors that can provoke relapsing dacryocystits.