Prognostička vrijednost izraženosti koštanoga morfogenetskoga proteina 6 u planocelularnim karcinomima usne šupljine [Prognostic significance of bone morphogenetic protein 6 (BMP6) expression in oral squamous cell carcinoma]

Introduction: Bone morphogenetic proteins, BMPs, are growth and differentiation factors, originally isolated as molecules which in vivo stimulate ectopic bone and cartilage formation. Overexpression of BMP6 has been shown in various malignant tumors. However, the prognostic significance of its expression in oral squamous cell carcinoma (OSCC) is still unknown. Immunohistochemistry and semiquantitative analyses were performed in order to determine the level of BMP6 in OSCC, thus correlating it with clinical and histological prognostic parameters, disease recurrence and survival. Patients and methods: The study included 120 patients with clinically T1-3N0 OSCC,who were treated primary surgically, between January 1, 2003 and December 31, 2008. Results: There were 99 (82,5%) males and 21 (17,5%) females, with an average age of 59 years. Five-year disease-specific survival rate for the whole cohort was 79,4%. Twenty patients had died during the follow-up, while 100 patients were censored. Patients with tumors smaller than 2,1 cm determined histologically showed higher incidence of strong BMP6 expression. No statistically significant corellation was detected between the level of BMP6 expression and other clinico-pathological factors. Similarly, the expression of BMP6 was neither associated with disease recurrence nor was it associated with patient's survival. Conclusions: Accordingly, routine analysis of BMP6 expression for predicting the biological behaviour of OSCC is not justified. The level of BMP6 expression cannot be considered as a prognostic factor in OSCC. In multivarite model, positive surgical margin, moderate tumor cell differentiation and metastatic cervical lymph nodes located at levels 4 and/or 5 were independent predictors of survival

Lymphatic drainage patterns of head and neck cutaneous melanoma: does primary melanoma site correlate with anatomic distribution of pathologically involved lymph nodes?

The aim of this study was to analyse patterns of metastatic spread from cutaneous head and neck melanoma, which are said to be highly variable. The medical records of 145 patients with pathologically proven metastatic melanoma were reviewed retrospectively. The location of pathologically positive lymph nodes was compared with clinically predicted spread, and patients with metastatic disease in areas outside of predicted drainage patterns were considered aberrant. There were 33 curative and 73 elective neck dissections. 21 of 77 patients undergoing parotidectomy had positive results for metastases. Clinical prediction proved to be correct in 33 of 45 cases (73.3%). Two patients with lateralized melanomas were initially seen with contralateral metastases. Six of 45 patients (13.3%) developed contralateral metastases after neck dissection. Patients with clinical involvement of the parotid gland were at high risk of occult neck disease (40%). Patients undergoing neck dissection for primaries originating in face, forehead, coronal scalp, periauricular area, and upper neck should be considered for parotidectomy. Patients with posterior scalp and posterior neck primaries should be considered for selective neck dissection in conjunction with posterior lymphadenectomy. In patients with coronal scalp and periauricular primaries, a complete neck dissection including parotidectomy is the recommended approach

Prognostički značaj zračenjem inducirane limfopenije kod bolesnika s rakom prostate visokog rizika

Lymphopenia is a known side-effect of radiotherapy but, being usually asymptomatic, its clinical value is just recently being recognized in the light of immunotherapy revival. Here we present clinical and laboratory data of 9 high-risk prostate patients that underwent whole pelvis radiotherapy combined with hormonal therapy. All patients experienced haematological toxicity during their treatment, with lymphopenia being the most profound. In addition, all of them were asymptomatic as regards to observed lymphopenia. After median follow up of 17 months 8/9 patients are still receiving hormonal treatment and have no evidence of their disease. The only patient with relapse discontinued hormonal therapy upon completion of radiotherapy. Therefore, we could not show any detrimental effect of observed lymphopenia on the outcome of these 9 patients.Limfopenija je poznata nuspojava zračenja, međutim, kako je obično asimptomatska, njen klinički značaj je tek odnedavno prepoznat s obzirom na rastući interes za imunoterapijom. Predstavljamo kliničke i laboratorijske podatke 9 bolesnika s rakom prostate visokog rizika kod kojih je provedeno zračenje zdjelice u kombinaciji s hormonskom terapijom. Kod svih bolesnika je zabilježena hematološka toksičnost; limfopenija je bila najviše izražena. Sve opažene limfopenije su bile asimptomatske. Nakon medijana praćenja od 17 mjeseci 8 od 9 bolesnika je bez znakova bolesti te još primaju hormonsku terapiju. Jedini bolesnik s relapsom bolesti je prestao dobivati hormonsku terapiju po završetku zračenja. Sukladno navedenom, nismo uspjeli pokazati štetan učinak opažene limfopenije na ishod liječenja ovih 9 bolesnika

Prognostic factors in head and neck mucoepidermoid carcinoma: experience at a single institution based on 64 consecutive patients over a 28-year period

Mucoepidermoid carcinoma (MEC) is the most common malignancy of the salivary glands. The clinical behaviour of MEC is largely unpredictable, ranging from indolent tumour growth to highly aggressive metastatic spread. The objective of this study was to determine the clinicopathological predictors of recurrence and survival in patients with head and neck MEC. The medical records of 64 patients who underwent surgical treatment for head and neck MEC between 1982 and 2010 were reviewed. The main outcome measures were disease-free survival (DFS) and overall survival (OS). Clinicopathological parameters evaluated were age, sex, anatomical subsite, histological grade, tumour stage, tumour size, adjuvant therapy, and nodal and margin status. For the entire cohort, the 5-year DFS was 82.8% and the 5-year OS was 67.2%. Histological grade and tumour subsite were statistically significant predictors of OS. Furthermore, tumour stage and nodal status were statistically significant predictors with respect to OS. Advanced tumour stage, high histological grade, submandibular/sublingual localization, and positive nodal status were independent predictors of the prognosis in patients with head and neck MEC. Further studies into the molecular biology of MEC are needed in order to provide new therapeutic strategies for patients with locally aggressive and highly metastatic carcinomas

Pleomorphic Adenoma in Ectopic Salivary Gland Tissue in the Neck

A case of pleomorphic adenoma originating from ectopic salivary gland tissue (ESGT) of the upper neck is reported. A 34-year-old male patient was referred to our Department for a painless swelling in the right submandibular region. Preoperative evaluation (clinical examination, fine-needle aspiration cytology (FNAC) and imaging studies) was performed and the finding was that of a pleomorphic adenoma in ESGT. A modified »S« incision with extension to the submandibular region was performed and the tumour was extirpated. The histopathological report confirmed our initial diagnosis. No recurrence was obtained during a four-year follow-up period. Isolated neck mass may be overlooked as ectopic salivary gland tissue neoplasm (ESGTN). Proper preoperative assessment and optimal surgical treatment are the keys for successful management of these rare tumours. The distinction between metastatic lesion from a head and neck tumour and ESGTN may present considerable diagnostic problem. A review of the literature on ESGT and associated tumours with emphasis on clinical features, diagnosis and treatment is also presented

Dileme u radioterapiji/kemoterapiji bolesnika s metastazama u limfne čvorove na vratu tumora nepoznatoga primarnog sijela

SAŽETAK Incidencija karcinoma nepoznatoga primarnog sijela s metastazama u limfne čvorove glave i vrata je niska te prema literaturi varira između 2 i 9%, te je u daljnjem padu zbog sve preciznije dijagnostike. Histološki, najčešći su planocelularni karcinomi. Osim općega fizikalnog pregleda s osobitim usmjerenjem na područje glave i vrata, nužan je endoskopski pregled s vizualizacijom nazofarinksa, orofarinksa, larinksa i hipofarinksa te radiološka slikovna obrada (CT i/ili MR te u slučaju indikacije PET/CT). Kirurško liječenje najstarija je, no još uvijek vrlo važna metoda liječenja ovih bolesnika te je preferirana opcija inicijalnog liječenja. S druge strane, primarna radioterapija predstavlja važnu opciju liječenja za tumore glave i vrata, posebno u bolesnika koji nisu kandidati za kirurško liječenje, a kod bolesnika s uznapredovalim nalazom na vratu (N2-3) preporučuje se kombinirati je s kemoterapijom. Nakon inicijalnog kirurškog liječenja i patohistološkog nalaza N2 ili N3 bolesti, radioterapija s kemoterapijom ili bez nje indicirana je u svih bolesnika, a može se razmotriti i kod onih sa statusom N1. Neovisno radi li se o primarnoj ili adjuvantnoj radioterapiji, opseg polja zračenja i nadalje je kontroverzna tema. Opcije liječenja se kreću od operativnog liječenja ipsilateralne strane vrata bez adjuvantnog liječenja, operativnog liječenja s adjuvantnom primjenom (kemo)radioterapije do primarnog liječenja – zračenja obje strane vrata i svih mjesta potencijalnog sijela primarnog tumora. Ranije je u smjernicama zagovaran agresivniji pristup koji je uključivao radioterapiju cijelog volumena ždrijela (nazofarniks, orofarinks i hipofarinks) i grkljana te obje strane vrata. S vremenom je primjetan pomak prema poštednijem liječenju, najčešće u smislu operativnog liječenja metastaza na vratu s primjenom adjuvantne ipsilateralne radioterapije, bez zračenja čitave sluznice ždrijela i grkljana. Najvažniji parametri u odluci o primjeni konkomitantne kemoterapije jesu proboj čahure limfnog čvora i resekcija R1/2

Significance of myofibroblast appearance in squamous cell carcinoma of the oral cavity on the occurrence of occult regional metastases, distant metastases, and survival

The aim of the present study was to assess the frequency of appearance of stromal myofibroblasts in patients with oral squamous cell carcinoma (OSCC) and to further clarify whether myofibroblasts influence tumour suppression or progression. Surgical resection specimens from 152 patients with cT1-T3N0 OSCC were analysed. The frequency of myofibroblasts within the tumour stroma was assessed immunohistochemically and compared with other clinical and histopathological factors. The immunohistochemical reaction for alpha-smooth muscle actin showed positive cells in the stroma of 84.2% of OSCC (n=128). An increased presence of myofibroblasts in the tumour stroma was significantly correlated with T stage (P=0.019), the presence of occult neck metastasis (P<0.001), regional recurrence (P=0.037), and distant metastasis (P=0.008). There was also an association between the presence of myofibroblasts and patient survival (P=0.009). The presence of myofibroblasts was not associated with local recurrence, tumour cell differentiation, mode of invasion, or bone invasion. The results of this study suggest that myofibroblast proliferation facilitates tumour invasion, the occurrence of occult neck disease, and distant metastasis. The survival rate was poorer in patients with abundant myofibroblasts. Further investigations on tumour-associated stroma at the invasive front are needed in order to establish new diagnostic markers and therapeutic strategies

Prognostic significance of bone morphogenetic protein 6 (BMP6) expression in oral squamous cell carcinoma

Uvod: Koštani morfogenetski proteini (BMP, od eng. bone morphogenetic proteins) su čimbenici rasta i diferencijacije koji su prvotno izolirani iz kosti, kao molekule koje potiču ektopično stvaranje kosti i hrskavice in vivo. Iako je BMP6 pojačano izražen u različitim zloćudnim tumorima, nije poznata prognostička vrijednost njegove izraženosti u planocelularnom karcinomu usne šupljine. Ovim su istraživanjem metode imunohistokemije i semikvantitativne analize upotrijebljene za određivanje izraženost BMP6 u planocelularnom karcinomu usne šupljine. Dobiveni rezultati su korelirani s kliničkim i histološkim prognostičkim parametrima, pojavom recidiva bolesti i preživljenjem bolesnika. Ispitanici i metode: Istraživanje je uključilo 120 bolesnika s karcinomom usne šupljine kliničkog stadija T1-T3N0 koji su primarno kirurški liječeni u razdoblju od 1. siječnja 2003. do 31. prosinca 2008. godine. Rezultati: Ispitivana skupina brojila je 99 (82,5%) muškaraca i 21 (17,5%) ženu, prosječne dobi 59 godina. Prosječno petogodišnje preživljenje bilo je 79,4%. Tijekom praćenja je od osnovne bolesti umrlo 20 bolesnika, a 100 ih je cenzurirano. BMP6 je bio izražen u 109 (90,8%) tumora. Bolesnici s tumorima histološkog promjera do 2,1 cm imali su statistički značajno češće prisutan snažan izražaj BMP6. Stupanj izraženost proteina BMP6 nije bio povezan s drugim kliničkim ili histološkim čimbenicima. Jednako tako, izraženost BMP6 nije povezana s pojavom recidiva bolesti, i nije povezana s duljinom preživljenja. Zaključci: S obzirom na to da jačina izraženosti BMP6 ne ovisi o biološkom ponašanju tumora, rutinsko određivanje njegove izraženosti u karcinomu usne šupljine, metodom imunohistokemije, nije opravdano. Među pokazateljima kojima je dokazana multivarijatna povezanost s preživljenjem, statistički značajne i međusobno nezavisne značajke su umjerna zrelost tumora, pozitivan rub resekcije te zahvaćenost područja vrata 4 i/ili 5.Introduction: Bone morphogenetic proteins, BMPs, are growth and differentiation factors, originally isolated as molecules which in vivo stimulate ectopic bone and cartilage formation. Overexpression of BMP6 has been shown in various malignant tumors. However, the prognostic significance of its expression in oral squamous cell carcinoma (OSCC) is still unknown. Immunohistochemistry and semiquantitative analyses were performed in order to determine the level of BMP6 in OSCC, thus correlating it with clinical and histological prognostic parameters, disease recurrence and survival. Patients and methods: The study included 120 patients with clinically T1-3N0 OSCC,who were treated primary surgically, between January 1, 2003 and December 31, 2008. Results: There were 99 (82,5%) males and 21 (17,5%) females, with an average age of 59 years. Five-year disease-specific survival rate for the whole cohort was 79,4%. Twenty patients had died during the follow-up, while 100 patients were censored. Patients with tumors smaller than 2,1 cm determined histologically showed higher incidence of strong BMP6 expression. No statistically significant corellation was detected between the level of BMP6 expression and other clinico-pathological factors. Similarly, the expression of BMP6 was neither associated with disease recurrence nor was it associated with patient's survival. Conclusions: Accordingly, routine analysis of BMP6 expression for predicting the biological behaviour of OSCC is not justified. The level of BMP6 expression cannot be considered as a prognostic factor in OSCC. In multivarite model, positive surgical margin, moderate tumor cell differentiation and metastatic cervical lymph nodes located at levels 4 and/or 5 were independent predictors of survival

Prognostic significance of bone morphogenetic protein 6 (BMP6) expression in oral squamous cell carcinoma

Uvod: Koštani morfogenetski proteini (BMP, od eng. bone morphogenetic proteins) su čimbenici rasta i diferencijacije koji su prvotno izolirani iz kosti, kao molekule koje potiču ektopično stvaranje kosti i hrskavice in vivo. Iako je BMP6 pojačano izražen u različitim zloćudnim tumorima, nije poznata prognostička vrijednost njegove izraženosti u planocelularnom karcinomu usne šupljine. Ovim su istraživanjem metode imunohistokemije i semikvantitativne analize upotrijebljene za određivanje izraženost BMP6 u planocelularnom karcinomu usne šupljine. Dobiveni rezultati su korelirani s kliničkim i histološkim prognostičkim parametrima, pojavom recidiva bolesti i preživljenjem bolesnika. Ispitanici i metode: Istraživanje je uključilo 120 bolesnika s karcinomom usne šupljine kliničkog stadija T1-T3N0 koji su primarno kirurški liječeni u razdoblju od 1. siječnja 2003. do 31. prosinca 2008. godine. Rezultati: Ispitivana skupina brojila je 99 (82,5%) muškaraca i 21 (17,5%) ženu, prosječne dobi 59 godina. Prosječno petogodišnje preživljenje bilo je 79,4%. Tijekom praćenja je od osnovne bolesti umrlo 20 bolesnika, a 100 ih je cenzurirano. BMP6 je bio izražen u 109 (90,8%) tumora. Bolesnici s tumorima histološkog promjera do 2,1 cm imali su statistički značajno češće prisutan snažan izražaj BMP6. Stupanj izraženost proteina BMP6 nije bio povezan s drugim kliničkim ili histološkim čimbenicima. Jednako tako, izraženost BMP6 nije povezana s pojavom recidiva bolesti, i nije povezana s duljinom preživljenja. Zaključci: S obzirom na to da jačina izraženosti BMP6 ne ovisi o biološkom ponašanju tumora, rutinsko određivanje njegove izraženosti u karcinomu usne šupljine, metodom imunohistokemije, nije opravdano. Među pokazateljima kojima je dokazana multivarijatna povezanost s preživljenjem, statistički značajne i međusobno nezavisne značajke su umjerna zrelost tumora, pozitivan rub resekcije te zahvaćenost područja vrata 4 i/ili 5.Introduction: Bone morphogenetic proteins, BMPs, are growth and differentiation factors, originally isolated as molecules which in vivo stimulate ectopic bone and cartilage formation. Overexpression of BMP6 has been shown in various malignant tumors. However, the prognostic significance of its expression in oral squamous cell carcinoma (OSCC) is still unknown. Immunohistochemistry and semiquantitative analyses were performed in order to determine the level of BMP6 in OSCC, thus correlating it with clinical and histological prognostic parameters, disease recurrence and survival. Patients and methods: The study included 120 patients with clinically T1-3N0 OSCC,who were treated primary surgically, between January 1, 2003 and December 31, 2008. Results: There were 99 (82,5%) males and 21 (17,5%) females, with an average age of 59 years. Five-year disease-specific survival rate for the whole cohort was 79,4%. Twenty patients had died during the follow-up, while 100 patients were censored. Patients with tumors smaller than 2,1 cm determined histologically showed higher incidence of strong BMP6 expression. No statistically significant corellation was detected between the level of BMP6 expression and other clinico-pathological factors. Similarly, the expression of BMP6 was neither associated with disease recurrence nor was it associated with patient's survival. Conclusions: Accordingly, routine analysis of BMP6 expression for predicting the biological behaviour of OSCC is not justified. The level of BMP6 expression cannot be considered as a prognostic factor in OSCC. In multivarite model, positive surgical margin, moderate tumor cell differentiation and metastatic cervical lymph nodes located at levels 4 and/or 5 were independent predictors of survival