Konjonktiva tümörlerinde tanı ve tedavi
Diagnosis and treatment in conjunctival tumors
Yazar: ŞENAY ALİEVA HASANOVA
Danışman: PROF. DR. KAAN GÜNDÜZ
Ankara Üniversitesi / Tıp Fakültesi / Göz Hastalıkları Ana Bilim Dalı
Derece: Tıpta Uzmanlık, 2008
Konu: Göz Hastalıkları = Eye Diseases

Özet:
Benign konjonktiva tümörleri genç popülasyonda daha sık görülürkenpremalign-malign konjonktiva tümörleri eriskin ve yaslı popülasyonda daha sıkgörülmektedir. Konjonktiva tümörlerinin klinik özellikleri dikkate alınarakbiyomikroskopik muayene ile ön tanı konulabilmekte ve etkin tedavi seçeneği ilebasarılı sonuçlar elde edilebilmektedir. Benign ve premalign-malign konjonktivatümörleri arasında kesin ayırım histopatolojik inceleme ile yapılmaktadır.Benign konjonktiva tümörlerinde TEB ile etkin tedavi sağlanmaktadır.Premalign-malign konjonktiva tümörlerinde geçmiste kullanılan enükleasyon veegzenterasyon gibi agresif tedavi seçenekleri yerine günümüzde TEB'e ek olarakuygulanan kriyoterapi, alkol epitelyektomi ve topikal MMC gibi yöntemleri tercihedilmektedir. Tedavi seçimini etkileyen faktörler arasında: tümörünün benign veyapremalign-malign klinik özellikleri tasıması, tümörün yerlesim yeri ve yaygınlığı(kornea, göziçi ve orbitaya invazyon olup olmaması), histopatolojik inceleme sonrasıtümörün histopatolojik özellikleri, cerrahi sınırlarda tümöral hücre mevcudiyeti,diğer gözün durumu, hastanın yası, genel sağlık durumu ve hastanın tercihi yeralmaktadır.Bu çalısmada, toplam 209 konjonktiva tümörü olan olgunun klinik özellikleri,uygulanan tedavi, histopatolojik sonuçları, gelisen nüks ve nüks tedavisi incelendi.Arastırmaya dahil edilen olguların 109'u kadın (%52.2), 100'ü (%47.8) erkek idi.Hastaların yas ortalaması 52.1±20.1 yıl iken ortalama izlem süresi 72.8 hafta idi.Klinik ve patolojik değerlendirme sonucunda hastaların 60'ında (%28.7) benign,149'unda (%71.3) ise premalign-malign konjonktiva tümörü saptandı. Premalignmalignkonjonktiva tümörlerinde benign konjonktiva tümörlerine göre yas ortalamasıistatistiksel olarak daha yüksek idi.Benign konjonktiva tümörü olan olguların 31'i (%51.7) kadın, 29'u (%48.3)erkek idi. Benign konjonktiva tümörü olan olguların 23'ü (%38.2) nevüs, 8'i (%13.3)papillom, 4'ü (%6.7) limbal dermoid, 4'ü (%6.7) lenfanjiom, 1'i (%1.7) piyojenikgranülom, 1'i (%1.7) epibulber koristom, 1'i (%1.7) psödoepitelyomatöz hiperplazi,1'i (%1.7) kapiller hemanjiom, 13'ü (%21.6) tümör içermeyen dokular ve 4'ü (%6.7)dejenerasyon, grubunda yer almaktaydı. Konjonktiva nevüsü olan olguların yasortalaması diğer benign konjonktiva tümörlerine göre istatistiksel anlamlı olarakdaha düsük idi (21.5±14.3yıl). Papillom erkeklerde kadınlara göre daha sıkgörülmekteyken (%75) diğer benign konjonktiva tümörlerinde cinsiyet açısındanistatistiksel olarak anlamlı bir fark görülmedi. Benign konjonktiva tümörlerinden 8olgu (%13.3) izleme alınırken 52 olguya (%86.7) TEB veya subtotal eksizyonelbiyopsi cerrahisi uygulandı.Premalign-malign konjonktiva tümörü olan olguların 78'i (%52.3) kadın ve71'i (%47.7) erkek idi. Premalign-malign konjonktiva tümörü olan olguların42'sinde (%28.2) K?N, 72'sinde (%48.3) YHK, 8'inde (%5.4) PEM, 15'inde (%10.1)MM, 2'sinde (%1.3) RLH ve 10'unda (%6.7) malign lenfoma mevcuttu. PEM'litoplam 8 (%5.4) olgudan 2 (%25) olguda PEM ve MM birlikte görüldü. Premalignmalignkonjonktiva tümörlerinde tedavi olarak, 43 olguda (%30) TEB+Kriyo+AE,28 olguda (%19) TEB+Kriyo, 20 olguda (%14) TEB+Kriyo+AE+MMC, 10 olguda(%7) TEB+AE, 7 olguda (%5) TEB+Kriyo+AE+AMT, 7 olguda (%5)TEB+Kriyo+Str-90, 7 olguda (%5) TEB+Kriyo+MMC, 6 olguda(%4)TEB+KriyoAE+Str-90, 6 olguda (%4) TEB+Kriyo+RT, 2 olguda (%1)TEB+Kriyo+KT, 4 olguda (%3) enükleasyon ve 3 olguda (%2) ekzenterasyonuygulandı. Histopatolojik incelemede 29 olguda (%20.3) cerrahi sınırlar pozitif, 61olguda (%42.6) cerrahi sınırlar negatif iken 53 olguda (%37.1) cerrahi sınırlarbelirtilmemis idi.Birinci nüks görülme oranı %34.3 (49/143) idi. YHK'da birinci nüks %45.8iken MM'da %41.2 idi. K?N grubunda nüks gelismedi. Yas ilerledikçe 1. nüksgelisme ihtimali de istatistiksel anlamlı olarak artmaktaydı. Tümör büyüklüğü,cinsiyet ve tümör lokalizasyonu ile 1.nüks arasında istatistiksel olarak anlamlı birbirliktelik saptanmadı. Birinci nüks tedavisi olarak 24 olguda (%49)TEB+Kriyo+AE+MMC, 9 olguda (%18) TEB+Kriyo+AE, 8 olguda (%5)TEB+Kriyo+MMC, 2 olguda (%4) TEB+Kriyo+AE+AMT, 1 olguda (%2) TEB+AE,3 olguda (%6) enükleasyon ve 2 olguda (%4) ekzenterasyon uygulandı.Histopatolojik incelemede 6 olguda (%12.2) cerrahi sınırlar pozitif, 18 olguda(%36.7) cerrahi sınırlar negatif iken 25 olguda (%51.1) cerrahi sınırlar belirtilmemisidi.?kinci nüks görülme oranı %11.2 (16/143) idi. YHK'da ikinci nüks oranı%18.1 ve MM'da %11.8 olarak bulundu. Yas, tümör büyüklüğü, cinsiyet, tümörlokalizasyonu ile ikinci nüks arasında istatistiksel olarak anlamlı bir birlikteliksaptanmadı. ?kinci nüks tedavisi olarak 6 olguda (%38) TEB+Kriyo+AE+MMC, 4olguda (%25) TEB+Kriyo+AE, 4 olguda (%25) TEB+Kriyo+MMC, 1 olguda (%6)TEB+AE ve 1 olguda (%6) TEB+Kriyo+AE+AMT uygulandı. ?kinci nüks tedavisonrası 5 olguda (%31.3) cerrahi sınırlar pozitif iken 11 olguda (%68.7) cerrahisınırlar negatif idi.Üçüncü nüks görülme oranı %3.5 (5/143) idi. Üçüncü kez nüks edenolguların 4'ü YHK iken 1 olgu MM idi.Cerrahi sınırlarda tümöral hücre mevcudiyeti ve yas nüks açısından riskfaktörü olarak bulundu. ?ki malign lenfomalı hastada sistemik tutulum ve 1 malignmelanomlu hastada rejyonel lenf bezi pozitif idi. ?zlem süresince hiçbir hastadaexitus gelismedi.Sonuç olarak, benign konjonktiva tümörlerinde TEB ile etkin tedavisağlanmaktadır. Premalign-malign konjonktiva tümörlerinin tedavisinde TEB'e ekolarak uygulanan kriyoterapi, alkol epitelyektomi ve topikal MMC ile nüksoranınında azalma ve uzun dönemde basarılı sonuçlar elde edilmektedir. Yaygınmalign konjonktiva tümörlerinde AMT oküler yüzey rekonstrüksiyonu açısındangereklidir. Yaygın ve göziçi invazyonu gösteren malign konjonktiva tümörlerindeenükleasyon; orbita invazyonu gösteren malign tümörlerde ise ekzenterasyonuygulanmaktadır.Anahtar sözcükler: benign konjonktiva tümörleri, premalign-malignkonjonktiva tümörleri, total eksizyonel biyopsi, kriyoterapi, alkol epitelyektomi,topikal mitomisin C, stronsyum-90, amnion membran transplantasyonu,enükleasyon, ekzenterasyon, cerrahi sınırlar, nüks.

Abstract:
Although benign conjunctival tumors are seen more frequently in youngpopulation; premalignant-malignant conjunctival tumors are seen more frequently inadults and elderly population. Early diagnosis can be made based on biomicroscopicexamination of conjunctival tumors? clinical characters and successful results can beobtained with effective treatment option. Definite discrimination, between benignand premalignant-malignant conjunctival tumors, is obtained byhistopathological examination.Effective treatment for benign conjunctival tumors is obtained with totalexcisional biopsy (TEB). Nowadays; aggressive treatment options, such asenucleation and exenteration, which were used in the past, gave way to cryotherapy,alcohol epitheliectomy and topical mitomycin C (MMC) which are used in additionto TEB. The factors that affect treatment selection are whether the tumor has benignor premalignant-malignant clinical feature, site and extention (whether there is aninvasion to the cornea or intraocular or orbita) of the tumor, histopathologic featuresof the tumor after the histopathologic examination, tumoral cell presence in thesurgical border, situation of the other eye, age and general health state of the patientand patient?s choice.In this study, clinical features of totally 209 patients with conjunctivaltumors, treatment methods employed, histopathologic results, recurrence rates andmanagement of the recurrences were examined. 109 (52.2%) of the patients werewomen and 100 (47.8%) of them were men. Mean follow-up was 72.8 weeks,whereas mean age of the patients was 52.1±20.1. According to clinical andpathological assessment; 60 patients (28.7%) were diagnosed as benign conjunctivaltumor and 149 patients (71.3%) were diagnosed as premalignant-malignantconjunctival tumor. Mean age of patientsts with premalignant-malignant conjunctivaltumor was statistically larger than mean age of patients with benign conjunctivaltumor.31 of patients with benign conjunctival tumors were women (51.7%) and29 of them were men (48.3%). Among the patients with benign conjunctival tumors,23 patients (38.2%) had nevus, 8 patients (13.3%) had papilloma, 4 patients (6.7%)had limbal dermoid, 4 patients (6.7%) had lymphangioma, 1 patient (1.7%) hadpyogenic granuloma, 1 patient (1.7%) had epibulbar choristoma, 1 patient (1.7%) hadpseudoepitheliamatous hyperplasia, 1 patient (1.7%) had capillary hemangioma, 13patients (21.6%) had nontumoral tissue and 4 patients (6.7%) had degeneration.Mean age of patients with conjunctival nevus was statistically lower than otherbenign conjunctival tumors (21.5±14.3 years). No statistically significant differencewas found about sex, among other benign conjunctival tumors; whereas papillomawas seen in men more frequently than women (75%). TEB or subtotal excisionalbiopsy were done in 52 patients (86.7%) who have benign conjunctivaltumor, whereas other 8 patients, who have benign conjunctival tumor, (13.3%) werefollowed up.78 patients with premalignant-malignant conjunctival tumor (52.3%) werewomen and 71 patients (47.7%) were men. Among the patients with premalignantmalignantconjunctival tumor, 42 patients (28.2%) had conjunctival intraepithelialneoplasia (CIN), 72 patients (48.3%) had squamous cell carcinoma (SCC), 8 patients(5.4%) had primary acquired melanosis (PAM), 15 patients (10.1%) had malignantmelanoma (MM), 2 patients (1.3%) had reactive lymphoid hyperplasia (RLH) and 10patients (6.7%) had malignant lymphoma. PAM and MM were seen together in 2(25%) of 8 patients (5.4%) who had PAM. In the treatment of premalignantmalignantconjunctival tumors total excisional biopsy+cryotherapy+alcoholepitheliectomy (TEB+Cryo+AE) were applied in 43 patients (%30), total excisionalbiopsy+cryotherapy (TEB+Cryo) were applied in 28 patients (19%), total excisionalbiopsy+cryotherapy+alcohol epitheliectomy+mitomycin C (TEB+Cryo+AE+MMC)were applied in 20 patients (14%), total excisional biopsy+alcohol epitheliectomy(TEB+AE) were applied in 10 patients (7%), total excisionalbiopsy+cryotherapy+alcohol epitheliectomy+amniotic membrane transplantation(TEB+Cryo+AE+AMT) were applied in 7 patients (5%), total excisionalbiopsy+cryotherapy+strontium-90 (TEB+Cryo+Str-90) were applied in 7 patients(5%), total excisional biopsy+cryotherapy+mitomycin C (TEB+Cryo+MMC) wereapplied in 7 patients (5%), total excisional biopsy+cryotherapy+alcoholepitheliectomy+strontium-90 (TEB+Cryo+AE+Str-90) were applied in 6 patients(4%), total excisional biopsy+cryotherapy+radiotherapy (TEB+Cryo+RT) wereapplied in 6 patients (4%), total excisional biopsy+cryotherapy+chemotherapy(TEB+Cryo+CT) were applied in 2 patients (1%), enucleation was applied in 4patients (3%) and exenteration was applied in 3 patients (2%). According tohistopathological examination; surgical borders were negative in 61 patients (42.6%),whereas it was positive in 29 patients (20.3%) and unknown in 53 patients (37.1%).Recurrence was noted in 34.3% (49/143) of patients. Primary recurrence wasseen in 45.8% of patients with SCC and in 41.2% of patients with MM. However;there has not been any recurrence in CIN group. Primary recurrence probabilitysignificantly increased with increasing age in statistical analysis. No statisticallysignificant relationship was found between tumor size, sex and tumor localizationwith primary recurrence. As a treatment for recurrence, TEB+Cryo+AE+MMC wereapplied in 24 patients (49%), TEB+Cryo+AE were applied in 9 patients (18%),TEB+Cryo+MMC were applied in 8 patients (5%), TEB+Cryo+AE+AMT wereapplied in 2 patients (4%), TEB+AE were applied in 1 patients (2%), enucleationwas applied in 3 patients (6%) and exenteration was applied in 2 patients (4%).Surgical borders were negative in 18 patients (36.7%) whereas it was positive in 6patients (12.2%) and unknown in 25 patients (51.1%).Second recurrence was seen in 11.2% (16/143) of patients. Second recurrencewas found in 18.1% of patients with SCC and in 11.8% of patients with MM. Nostatistically significant relationship was found between age, tumor size, sex, tumorlocalization with second recurrence. As second recurrence treatment,TEB+Cryo+AE+MMC were applied in 6 patients (38%), TEB+Cryo+AE wereapplied in 4 patients (25%), TEB+Cryo+MMC were applied in 4 patients (25%),TEB+AE were applied in 1 patients (6%) and TEB+Cryo+AE+AMT were applied in1 patients (6%). Surgical borders were negative in 11 patients (68.7%) whereas itwas positive in 5 patients (31.3%) after the secondary recurrence treatment.Third recurrence was observed in 3.5% (5/143) of patients. 1 patient had MMwhereas 4 patient had SCC among the cases who had third recurrence.Tumoral positivity at the surgical borders and patients age were found a riskfactor for recurrence. Systemical involvement was positive in 2 patients withmalignant lymphoma and regional lymph node was positive in 1 patient withmalignant melanoma. During the follow-up period there has not been any cases whodied.Successful results in long term and decrease in recurrence ratio can beobtained with cryotherapy, alcohol epitheliectomy, topical MMC in addition to TEBin premalignant-malignant conjunctival tumor treatment. AMT is essential for ocularsurface reconstruction in widespread malignant conjunctival tumors. Enucleation isused for malignant conjunctival tumors that exhibit widespread and intraocularinvasion; exenteration is used for malignant tumors that exhibit orbital invasion.Key words: benign conjunctival tumors, premalignant-malignantconjunctival tumors, total excisional biopsy, cryotherapy, alcohol epitheliectomy,topical mitomycin C, strontium-90, amniotic membrane transplantation, enucleation,exenteration, surgical borders, recurrence.