WikiDer > B-hujayrali limfa limiti

Chet zonasi B-hujayrali limfomalar
Boshqa ismlar	Marginal zona limfomalari (MZL)
EMZL infiltratsion buyrak to'qimasi.
Turlari	Ekstranodal marginal zonasi limfoma, taloq marginal zonasi limfoma va tugunli marginal zonasi limfoma.

Chet zonasi B-hujayrali limfomalar, shuningdek, nomi bilan tanilgan chekka zona limfomalari (MZLlar), heterojen guruhdir limfomalar dan kelib chiqqan zararli o'zgarish ning chekka zona B hujayralari.^[1] B chegara zonasi hujayralari tug'ma limfoid hujayralar odatda tezkor o'rnatish orqali ishlaydi IgM antikor immunitet reaktsiyalari ga antijenler yuqumli moddalar va shikastlangan to'qimalar tomonidan taqdim etilganlar kabi.^[2] Ular limfotsitlar ning B-hujayra kelib chiqadigan va etuk bo'lgan chiziq ikkilamchi limfoid follikulalar va keyin ga o'ting chekka zonalar ning shilliq qavat bilan bog'langan limfoid to'qima (ya'ni MALT), the taloq, yoki limfa tugunlari. Mukozaga bog'langan limfoid to'qima - bu kichik kontsentratsiyalarning tarqoq tizimi limfoid to'qima turli xil shilliq osti membranasi saytlari tanasi kabi oshqozon-ichak trakti, og'iz, burun bo'shlig'i, tomoq, qalqonsimon bez, ko'krak, o'pka, tuprik bezlari, ko'z, teri va inson taloq.^[3]

2016 yilda Jahon sog'liqni saqlash tashkiloti MZLlarni uch xil turga ajratdi. Ekstranodal marginal zona limfomalari (EMZL) ekstranodal to'qimalarda rivojlanadigan MZLlardir. Ko'pgina EMZLlar MALTda rivojlanadi va ko'pincha mukozaga bog'langan limfoid to'qimalarining ekstranodal MZL deb nomlanadi yoki sodda qilib aytganda, MALT limfomalari. Dalakning chekka zonasi limfomalari (SMZL) - bu dastlab taloq, suyak iligi va qon bilan chegaralangan MZLlar.^[1] Tugunli marginal zona limfomalari (NNMZ) - dastlab limfa tugunlari bilan chegaralangan MZLlar, ilikva qon.^[1] Ushbu MZLlarning barchasi zararli B-hujayralarni o'z ichiga olgan bo'lsa-da, ular nafaqat o'z ichiga olgan to'qimalarda, balki ularning hujayralarida ham farqlanadi patofiziologiya, klinik prezentatsiyalar, prognozlar va davolash usullari.^[1][4]

MZLlar 5-17% ni tashkil qiladi Xodkin bo'lmagan limfomalar ekstradodal, taloq va tugun shakllari bilan barcha MZLlarning 50-70%, ~ 20% va ~ 10% ni tashkil qiladi.^[5] Uchta MZL subtipasi keksa yoshdagi odamlarda (65-68 yosh) tez-tez uchraydi va asemptomatik simptomlarsiz odamlarda dastlab davolanishi mumkin bo'lgan befarq kasalliklardir. hushyor kutish strategiya. Biroq, NMZL boshqa pastki turlarga qaraganda ancha yomon uzoq muddatli natijalarga olib keladi^[1] va har qanday MZL subtipasi kam foizlarda, ayniqsa, ko'proq agressiv limfomaga o'tishi mumkin diffuz katta B-hujayrali limfoma.^[6] MZLning o'ziga xos xususiyatlaridan biri shundaki, ko'p holatlar surunkali immunitet tizimining doimiy simulyatsiyasi bilan bog'liq yallig'lanish hamrohlik qiladi infektsiyalar^[7] yoki otoimmun kasalliklar.^[8] Ba'zi yuqumli kasalliklar bilan bog'liq MZL holatlari patogenlar ushbu infektsiyalarni keltirib chiqaradigan yoki ular bilan bog'liq bo'lgan patogenlarga yo'naltirilgan davolash orqali davolash mumkin.^[7]

Ekstranodal marginal zona lenfoma

EMZLlar MZL shaklidir, unda zararli marginal zonalar B hujayralari dastlab oshqozonning MALT to'qimalariga (barcha EMZL ning 50-70%) yoki kamroq tez-tez kirib boradi. qizilo'ngach, ingichka ichak, yo'g'on ichak, to'g'ri ichak, kon'yunktiva ko'zning, burun yo'llari, tomoq, o'pka bronxlar, vulva, qin, teri, ko'krak, timus bezi, miya pardalari (ya'ni membranalar) miya va orqa miyayoki boshqa organlar.^[7][9] Ushbu EMZLlar ishtirok etgan organ (lar) ga qarab subtiplarga bo'linadi. Masalan, oshqozonning EMZLi birlamchi oshqozon EMZL deb ataladi. Pastki turidan qat'i nazar, ushbu EMZLlar o'xshashdir patofizyolojik (ya'ni tartibsiz) fiziologik jarayonlar kasallikka olib keladigan) va histopatologik (ya'ni mikroskopik kasallikning xususiyatlari to'qimalar). Shu bilan birga, subtipalar taqdimot, rivojlanish, zo'ravonlik, davolash va qo'zg'atuvchi omillarga ko'ra farqlanadi. Keyingi ikki bo'limda barcha EMZL subtiplarida uchraydigan umumiy patofiziologik va gistopatologik xususiyatlar tasvirlangan. Har bir EMZL subtipiga xos xususiyatlar ushbu ikki qismga amal qiladi.

Patofiziologiya

EMZL rivojlanishida ko'plab omillar paydo bo'ladi. Kam miqdordagi holatlarda kasallik gematologik malignite, xususan leykemiya yoki Sjogren sindromi kabi turli xil otoimmün kasalliklarga ega bo'lgan oilada tarixga ega bo'lgan bemorlarda ko'payib boradi. qizil yuguruk eritematozi. Merzga uchragan genetik, umumiy atrof-muhit va boshqa hali aniqlanmagan omillar EMZL rivojlanish xavfining ortishi mumkin.^[10] Ko'pgina EMZL holatlarini boshlashning yana bir muhim omili bu surunkali infeksiya yoki otoimmun reaktsiya natijasida kelib chiqqan surunkali yallig'lanishdir. Surunkali yallig'lanish, B hujayralarini qayta tiklashga undaydi immunoglobulin og'ir zanjirli lokus ular kodlashlari uchun B hujayrasi retseptorlari shikastlangan muammolar va / yoki yallig'lanish asosida yotadigan yuqumli vositalar tomonidan taqdim etilgan g'ayritabiiy antijenlarni tan oladigan. Ushbu qayta tashkil etish natijasida B hujayralari anormal antijenlarga ta'sir o'tkazib, chekka B hujayralarining xususiyatlarini oladi va haddan tashqari ko'payadi.^[11] Natijada, bu B hujayralari bosqichma-bosqich o'sib boradi xromosoma anormalliklari, gen mutatsiyalarva / yoki ularning yomon xulqli bo'lishiga yordam beradigan tartibga solinmagan genlar. EMZLda aniqlangan genomik anormalliklarga va o'ziga xos EMZL subtiplarida paydo bo'lish chastotasiga quyidagilar kiradi.

• Xromosoma translokatsiyalari: 1) uzun (yoki "q") qo'lning translokatsiyasi xromosoma 11 x 21-pozitsiyada 21-xromosomaning q qo'li bilan 21-pozitsiyada (t (11; 18) (q21; q21) translokatsiya deb belgilangan) oshqozonning 24%, o'pkaning 38% va kamdan-kam hollarda boshqa EMZL subtipalarida uchraydi. Ushbu translokatsiya .ning bir qismini joylashtiradi API2 ning bir qismi bo'lgan gen MALT1 yaratish uchun gen termoyadroviy gen bu Api2-Malt1-ni kodlaydi birlashma oqsili. Bu ximerik oqsil a ning doimiy faollashuviga yordam beradi transkripsiya omili, NF-DB. NF-DB hayotni oshiradigan turli xil genlarning ekspressionini boshqaradi, sitokin ishlab chiqarish va hujayralarning boshqa xavfli potentsial xatti-harakatlari. 2) t (14; 18) (q32; q21) translokatsiyasi ko'z adneksiyasining 7 foizida, o'pkaning 6 foizida va kamdan-kam hollarda EMZLning boshqa holatlarida sodir bo'ladi. Bu Malt1 ning haddan tashqari ta'sirlanishiga olib keladi. Ushbu protein bilvosita inhibe qiladi dasturlashtirilgan hujayralar o'limi hujayraning omon qolish muddatini uzaytirish va NF-kB faollashishiga yordam beradi. 3) A t (1; 14) (p22; q32) ("p" xromosomaning qisqa qo'lini bildiradi) translokatsiya o'pkaning -9%, oshqozonning -4% va kamdan kam hollarda EMZLda sodir bo'ladi. . Ushbu translokatsiya .ning haddan tashqari ifodasini keltirib chiqaradi BCL10 gen. Bcl10 oqsili NF-kB faollashishiga yordam beradi. 4) t (3; 14) (p13; q32) translokatsiyasi EMZLning kamdan-kam holatlarida uchraydi va uning haddan tashqari ta'sirlanishiga olib keladi. FOXP1 gen. FoxP1 oqsilining hosil bo'lishini rag'batlantiradi transkripsiya omillari kabi PRDM1, IRF4va XBP1 plazma hujayralari uchun B hujayralarining pishib etishiga yordam beradi. 5) uchta translokatsiya, t (1; 14) (p21; q32), t (5; 14) (q34; q32), t (9; 14) (p24; q32) va t (X; 14) (p11) .4; q32), kamdan-kam hollarda EMZLda uchraydi, ammo ularning malignitani oshirishga ta'siri noma'lum.^[12]
• Genlarning inaktivatsiyasi va mutatsiyalari: 1) Faolsizlantirish yoki TNFAIP3 23-pozitsiya (ya'ni 6q23 o'chirilishi) haqida xromosomada 6 yo'qolishi yoki uning mutatsiyasi asosan ko'z adneksi, tuprik bezi va qalqonsimon bez EMZLda uchraydi. TNFAIP3 inaktivatsiya odatda yuqoridagi xromosoma translokatsiyasiga ega bo'lmagan hollarda sodir bo'ladi. Ushbu genning mahsuloti, o'sma nekrozi faktori, alfa ta'siridagi oqsil 3, NF-kB aktivatsiyasini susaytiradi. 2) Funktsiya yutug'i mutatsiyalar MYD88 gen okzular adneksaning EMZL holatlarida ~ 5% da uchraydi. Ushbu genning mahsuloti, miyeloid differentsiatsiyasi birlamchi javob 88, doimiy ravishda NF-kB ni faollashtiradi va STAT3 va AP1 transkripsiya omillari.^[12] 3) inaktivlovchi mutatsiyalar NOTCH1 (Barcha holatlarning 8%) va NOTCH2 (Barcha holatlarning 8%) genlar EMZLda uchraydi. Ushbu genlarning mahsulotlari hujayra yuzasi retseptorlari o'zlarining faollashtiruvchi ligandlari bilan bog'langanda hujayra yadrosiga o'tadigan va B hujayralarining rivojlanishi, ko'payishi, omon qolishi va migratsiyasini boshqaruvchi genlarning faollashishiga hissa qo'shadigan oqsillar.^[13]

Ko'pgina EMZL subtiplari yuqumli kasalliklar yoki ularning xavfli rivojlanishiga hissa qo'shishi mumkin bo'lgan otoimmun kasalliklar bilan bog'liq. Ushbu EMZL subtiplari haqida quyidagi Jadvalda xabar berilgan; ular ishtirok etgan to'qimalar; EMZL pastki turlarini rivojlanishiga asos bo'lishi mumkin bo'lgan yuqumli moddalar / otoimmun kasalliklar; ushbu yuqumli kasalliklar / otoimmun kasalliklarni ularning malignanligi bilan bog'laydigan dalillarning kuchi; yuqumli razvedka / otoimmun kasallik bilan bog'liq bo'lgan EMZL subtipi bilan kasallanish (ya'ni foiz); va ba'zilari ximerik genlar EMZL subtipining neoplastik B hujayralari bilan ifodalangan.

Gistopatologiya

The histopatologik (ya'ni mikroskopik) EMZLni tekshirish jarohatlar odatda hujayralarning noaniq tugunli yoki tarqoq shaklini ochib beradi. Ushbu jarohatlardagi zararli hujayralar turli nisbatlarda morfologiya kichik va o'rta kattalikdagi limfotsitlar, sentrosit- B hujayralari singari, sentroblast- B hujayralari singari, monotsit- B hujayralari singari, plazma hujayrasi- B hujayralari va / yoki katta B hujayralari kabi. Katta B hujayralari hujayralardan boshqa, past darajadagi malign morfologiyalar bilan aniq ajralib turadigan taniqli varaqlarni hosil qilganda, kasallik ancha tajovuzkor malignitaga o'tishi mumkin, diffuz katta B-hujayrali limfoma. Ushbu transformatsiya ~ 18% bemorlarda o'rtacha EMZL tashxisidan keyin 4-5 yil davomida sodir bo'ladi.^[21] Immunofenotiplash yoki bu shikastlanishlardagi neoplastik katta B hujayralari ularning ekspresyon ekanligini ko'rsatadi CD20 lekin emas CD3 sirt membranasi B hujayrasi marker oqsillari. Hujayralar deyarli har doim ifoda etadi BCL2 va ifoda etishi mumkin MNDA (~ 70% holatlar), CD23 (~ 33% holatlar) va CD5 (~ 20% holatlarda) marker oqsillari, ammo ifoda etmaydi velosiped D1 marker oqsil.,^[21] T-hujayra belgisi, CD10, yoki BCL6.^[1]

Subtipalar, diagnostika, davolash va prognoz

Ular ishtirok etgan organlarga asoslangan turli xil EMZL subtipalari mavjud. Ushbu subtiplarning deyarli barchasi zararlangan organning shilliq qavati bilan bog'langan limfoid to'qimalarida uchraydi va ko'pincha ta'sirlangan organning MALT limfomalari deb nomlanadi (masalan, oshqozon MALT limfomasi). Ammo, bu limfomalar, shuningdek, ta'sirlangan organning asosiy EMZL (masalan, asosiy oshqozon EMZL) deb nomlanadi. Ushbu ikkala atama bu kichik tiplar uchun ishlatilgan bo'lsa-da, EMZL boshlang'ich (a'zo bo'lgan) EMZL subtipi dastlab ushbu to'qimalarda ishlab chiqilganligi va ular bilan chegaralanib qolishi mumkinligini ko'rsatishni afzal ko'radi. Ammo, taxminan 30% holatlar boshqa joylarda, asosan limfa tugunlarida va kamdan-kam hollarda tarqaladi ilik. Ushbu pastki tipdagi xavfli B-hujayralar qonda ham aylanishi mumkin, ammo bu juda kam uchraydi. EMZL subtipidan yoki uning boshqa to'qimalarga tarqalishidan qat'i nazar, ushbu limfomalar uchun prognoz yaxshi, 5 yillik umumiy omon qolish 86% dan 95% gacha.^[14][6]

Birlamchi oshqozon

Helicobacter pylori ko'pincha oshqozon yarasini keltirib chiqaradigan bakteriyalar bo'lib, birlamchi oshqozon EMZL ning asosiy sababi hisoblanadi

Birlamchi oshqozon EMZL, shuningdek, birlamchi oshqozon MALT limfomasi yoki ko'pincha oshqozon MALT lenfomasi deb ataladi, odatda befarq kasallik bo'lib, ~ 10% hollarda boshqa GI traktlari va / yoki GI bo'lmagan trakt joylari ham kiradi. Bemorlar odatda kasallikning dastlabki bosqichida mavjud^[22] kabi turli xil alomatlar bilan ko'ngil aynish, qusish, oshqozon buzilishi, qorinning yuqori qismida og'riq va qonni yo'talayotganida ko'rsatilgandek me'da qon ketishi, qonli ichak harakatlariva / yoki temir tanqisligi anemiyasi. Kamdan kam hollarda bemorlar murojaat qilishadi oshqozon teshilishi yoki B belgilari isitma va tungi terlar. Surunkali kasalligi bo'lgan shaxslar Helicobacter pylori infektsiya ham bo'lishi mumkin halitoz.^[23] Endoskopik lezyonlarni tekshirish va biopsiya^[15] va endoskopik asoslangan ultratovush^[22] yuqori oshqozon-ichak traktining tekshiruvi, ko'pincha oshqozonda pilorik antrium, bu yuzaki mukozal eroziya, sayoz yaralar, tugunlar, kattalashgan rugae, va / yoki oshqozon devorining qalinlashishi.^[15] Gastopatologiya bo'limida birlamchi oshqozon MALT lezyonlarining gistopatologiyasi va marker oqsillari va zararli hujayralar tomonidan bildirilgan genomik anomaliyalar keltirilgan. Birlamchi oshqozon EMZL bilan oshqozon infektsiyasi bog'liq Helicobacter pylori > 80% hollarda yoki bilan Helicobacter heilmannii sensu lato <1% hollarda.^[14] Me'da ko'rsatmalari Helicobactor pylori oshqozon EMZL sabablari quyidagilardan iborat: ijobiy karbamid nafas olish testi; ijobiy najas sinovi an antigen bemorning najasidagi patogenning; ijobiy ureaz testi biopsiya qilingan to'qima namunasida; o'ziga xos xususiyatdan foydalangan holda ijobiy sarum yoki to'liq qon testi antikorlar patogenga qarshi qaratilgan; va qo'zg'atuvchining o'sishi to'qima madaniyati biopsiya qilingan to'qima.^[24] Helicobacter heilmannii sensu lato kamida 11 xilni belgilaydi Helicobactor ularning 5 turi odam oshqozoniga yuqishi ma'lum. Buni aniqlash qiyinroq kechdi Helicobacter heilmannii sensu lato insonning oshqozon kasalligi uchun javobgardir, chunki karbamidning nafas olish testi bu turlarning zararlanishida kamroq ijobiy bo'ladi, ularga qarshi qaratilgan antikorlar odatda mavjud emas va ular madaniy sharoitda o'sishi qiyin. Tashxisi Helicobacter heilmannii sensu lato shuning uchun maxsus kumush rang berish usullarini qo'llagan holda to'qimalarni yoki najas moddalarini organizmni gistologik usulda aniqlashga va keyinchalik DNK va / yoki organizmdagi ba'zi genlarni (ya'ni ureaza A, urease B, issiqlik zarbasi oqsili 60 va / yoki gyraza subbirligi) sekvensiyalashga bog'liq. organizmlar 23sRNK.^[16] Mahalliylashtirilgan davolanish (ya'ni. Ann Arbor bosqichi I va II) Helicobactor pylori- ijobiy birlamchi oshqozon EMZL bir nechta har qanday birini qo'llaydi Helicobacter pylori yo'q qilish protokollari. Ushbu protokollarga a proton-nasos inhibitori (masalan, omeprazol yoki lansoprazol^[25]) ortiqcha har xil narsalardan biri antibiotik kombinatsiyalar (masalan, Klaritromitsin + Amoksitsillin yoki levofloksatsin + nitazoksanid + doksisiklin).^[15] Dori-darmonlarning aniq rejimi alohida holatlarda patogenning ushbu antibiotiklarga ma'lum yoki taxmin qilingan qarshiligiga qarab tanlanadi. Rejim 7-14 kun davomida beriladi va 4 hafta ichida karbamid nafasi yoki najas antigeni tekshiruvi orqali patogen borligini tekshirish orqali tekshiriladi. Agar boshlang'ich rejim patogenni yo'q qila olmasa, bemorlar uch yoki to'rtta dorilarning kombinatsiyasi (masalan, proton-nasosli inhitor +) yordamida ikkinchi rejim bilan davolanadi. vismut subkitrat + tetratsiklin + metronidazol).^[15] Patogenani yo'q qilish 70-95% hollarda muvaffaqiyatli bo'ladi. Yaqinda ketma-ket davolash rejimi (ya'ni proton-nasos inhibitori + amoksitsillin, keyin proton-nasos inhibitori + klaritromitsin +) Tinidazol)> 90% hollarda patogenni yo'q qilish haqida xabar berilgan.^[15] T (11; 18) yoki t (1; 14) xromosoma translokatsiyasini saqlaydigan va shu sababli BIRC3-MALT1 yoki IGH-BCL10 kimerik oqsillarini ifoda etadigan lezyonlari bo'lgan bemorlarda chidamli bo'lish hollari ko'paygan. Helicobactor pylori yo'q qilish protokollari.^[14] Qo'zg'atuvchining yo'q qilinishini boshdan kechirgan bemorlarning taxminan 50-80% 3-28 oy ichida o'zlarining limfomasini remissiya va uzoq muddatli klinik nazoratini rivojlantiradi. Radiatsiya terapiyasi oshqozonga va atrofdagi (ya'ni oshqozon-ichak) limfa tugunlariga muvaffaqiyatli davolash uchun foydalanilgan: a) mahalliylashtirilgan Helicobactor pylori- qo'zg'atuvchisi keltirilgan dori protokollari bilan yo'q qilinmagan ijobiy birlamchi oshqozon EZML; b) mahalliylashtirilgan Helicobactor pylori- oshqozonning EZML salbiy salbiy holatlari; va v) Helicobactor pylori- keksa yoki zaif bemorlarda ijobiy va-salbiy EZML holatlari. Tizimli (ya'ni Ann Arbor bosqichi III va IV) birlamchi oshqozon EMZL kasalligi bo'lmagan bemorlar davolangan hushyor kutish yoki simptomatik davolash immunoterapiya dori, rituximab (4 hafta davomida berilgan) bilan birlashtirilgan xlorambusil 6-12 oyga beriladi; Ushbu bemorlarning 58% 5 yil davomida 58% progressiyasiz omon qolish darajasiga erishadilar. III / IV zaif bosqich bemorlar rituximab yoki bilan muvaffaqiyatli davolangan siklofosfamid yolg'iz.^[1] Davolash paytida Helicobactor heilmanni sensu lato bu juda kam miqdordagi tadqiqotlarga bog'liq bo'lib, odatda davolash uchun ishlatiladigan tavsiyalarga amal qiladi Helicobactor pylori.^[16]

Birlamchi ingichka ichak

Birlamchi ingichka ichak MZL, shuningdek, birlamchi ingichka ichak MALT lenfoma deb nomlanadi, odatda u bilan birga keladi jirkanch qorin og'rig'i, diareya va rivojlangan kasallik belgilari va alomatlari malabsorbtsiya (masalan, vazn yo'qotish, to'yib ovqatlanmaslikva anemiya), kichik ichak tutilishi, astsitlar (ya'ni qorin bo'shlig'idagi suyuqlik) va / yoki limfa tugunlari, taloq va / yoki jigar kattalashishi.^[26] Dastlabki bosqichda boshlang'ich ingichka ichak MZL bilan kasallangan bemorlar odatda progressiv kasallik bo'lib, o'z-o'zidan va to'liq remissiyaga ega bo'lishi mumkin.^[7] Immunoproliferativ ingichka ichak kasalligi, ilgari O'rta er dengizi limfomasi deb nomlangan yoki bir turi deb hisoblangan alfa og'ir zanjirli kasallik (IgA / aHCD),^[27] bu ingichka ichakning MZL varianti va eng keng tarqalgan shakli.^[26] Ushbu variant endemik mamlakatlarida O'rta er dengizi havzasi, ayniqsa Yaqin Sharq garchi ushbu kasallikka chalingan holatlar butun dunyoda uchragan bo'lsa-da, lekin har doim ham Yaqin Sharqdan kelgan muhojirlarda emas.^[26] Uning endemik mintaqalarida immunoproliferativ ingichka ichak kasalligi barcha GI taktik lenfomalarining ~ 30% ni tashkil qiladi, asosan 20-30 yoshgacha bo'lgan ijtimoiy-iqtisodiy holati past bo'lgan odamlarni azoblaydi va oziq-ovqat bilan yuqadigan bakteriya infektsiyasiga chalinadi, Campylobacter jejuni. Campylobacter jejuni-sozlik kasalligi ekspres bildiradigan odamlarda ko'proq uchraydi inson leykotsitlari antijeni AI19, B12 yoki A9 yoki mavjud qon guruhi B. Ushbu shaxslar kasallik rivojlanishiga genetik moyil bo'lishlari tavsiya etiladi.^[18] Immunostaining bu holatlarda ingichka ichak lezyonlari odatda mavjudligini aniqlaydi Campylobacter jejuni va kasallik antibiotiklarga javob berishini taxmin qiladi. Ammo bu bakteriya immunoproliferativ ingichka ichak kasalligining haqiqiy sababi ekanligi aniq emas:^[26] u faqat kasallikka chalingan odamlarning ichagini kolonizatsiya qilishi mumkin, boshqa aniqlanmagan antibiotiklarga sezgir bakteriyalar yoki bakterial bo'lmaganlar patogenlar, masalan. parazitlar, kasallikning rivojlanishi asosida yotadi.^[26]

Birlamchi ingichka ichakdagi EMZL holatlarida, ikki balonli enteroskopiya va kapsula endoskopiyasi shilliq qavatning keng eroziyasi va / yoki kamroq, poliplar, tugunlar, massalar va / yoki chandiqlar mavjudligini aniqlash.^[22] Ushbu yaralar o'n ikki barmoqli ichak, jejunum yoki iliumga tegishli ravishda taxminan 63, 17 va 8% hollarda joylashadi yoki ~ 17% hollarda bir nechta ingichka ichak joylarini o'z ichiga oladi.^[26] Shikastlanishlar atipik, limfotsitlardan iborat plazma hujayralari va kamroq, sentrosit-simon hujayralar ichakka kirib boradi lamina propria^[18] limfotsitlar va EMZL uchun xos bo'lgan marker oqsillarini (masalan, CD20 va CD79a) ifodalovchi sentrositlarga o'xshash hujayralar bilan.^[26] Campylobacter jejuni tomonidan ushbu lezyonlarda aniqlanadi immunostaining. Ushbu kasallikka chalingan bemorlarda odatda a monoklonal gammopatiya mavjudligi bilan dalil sifatida monoklonal antikor dan iborat bo'lak kristallanadigan mintaqa ning IgA og'ir zanjir ularning qonida, jejunum sharbati va / yoki kamdan-kam siydikda. Anormal IgA oqsillari bemorlarning qon zardobida aniqlanadi immunofiksatsiya IgA ning og'ir zanjir qismiga qarshi antikor yordamida.^[26]

Boshlang'ich ingichka ichakni davolash EMZL ovqatlanishni qo'llab-quvvatlash va simptomlarni nazorat qilishga, shu jumladan, ichak tutilishi va yuqori darajada lokalizatsiya qilingan kasalliklarni davolash uchun jarrohlik va / yoki radioterapiyani davolashga qaratilgan. Ammo, tadqiqotlar shuni ko'rsatadiki, kasallikka chalingan shaxslar, xususan, immunoproliferativ ingichka ichak kasalligi bo'lganlar, davolanishdan keyin umumiy javob darajasi ~ 90% ni tashkil qiladi. keng spektrli antibiotiklar tetratsiklin, metronidazol yoki tetratsiklin + ampitsillin kabi.^[3] Ushbu javoblar ko'p hollarda bardoshlidir. Shunga ko'ra, kasallikning dastlabki bosqichini davolash uchun antibiotik terapiyasi tavsiya etiladi. Antibiotik terapiyasiga chidamli bemorlar kimyoviy terapiya bilan davolangan (ya'ni.) CHOP yoki CHOPga o'xshash rejimlar), keyin tetratsiklin bilan uzoq muddatli parvarish. Ushbu davolash rejimi 5 yillik umr ko'rish darajasi 70% ga erishdi. Jarrohlik va radioterapiya kasallik uchun davolovchi bo'lmaganligi sababli, yuqori dozali kimyoviy terapiya sxemalari va autolog ildiz hujayrasini transplantatsiyasi refrakter va / yoki relapsli kasallik uchun tavsiya etilgan.^[2]

Kolorektal EMZLlar

Yo'g'on ichak yoki rektum bilan bog'liq bo'lgan ENZLlar juda kam uchraydi. 2019 yilda 73 ta holatni ko'rib chiqishda ushbu ENZL subtiplaridan biriga tashxis qo'yilgan shaxslarning o'rtacha yoshi 62 yoshda (26-72 oralig'ida), asosan ayollar (66%) va ularning asosiy o'smalari rektumda joylashgan (74%). holatlar), o'ng yo'g'on ichak (13,6%), ko'ndalang yo'g'on ichak (4,1%) yoki sigmasimon ichak (8,2%). Ushbu odamlarning o'ttiz foizida ko'payadigan o'smalar bor edi, ularning ~ 40% yo'g'on ichak va to'g'ri ichak tashqarisidagi oshqozon-ichak traktida joylashgan. Ushbu shaxslar dastlab davolangan va 19 ta holatning 18 tasida mahalliy jarrohlik rezektsiyasi, 19 holatning 18 tasida kengroq jarrohlik rezektsiyasi, 13 ta holatning 12 tasida kimyoviy terapiya, radiatsiya terapiyasi (5 ta holatning 4 tasida yoki antibiotik terapiyasi bilan) to'liq remissiyaga erishgan. Helicobacter pylori 15 holatdan 12 tasida yo'q qilish. Ikkala odam spontan remissiya bilan bittasi bilan davolanmagan. To'liq remissiyaga erisha olmagan 8 holat ikkinchi darajali davolanishni talab qildi; 3 holat remissiya etishmovchiligi edi.^[28] Keyingi bo'limlarda ushbu ikkita EMZL subtipi tasvirlangan.

Birlamchi yo'g'on ichak

Birlamchi yo'g'on ichakning MALT limfomasi deb ham ataladigan birlamchi yo'g'on ichak EMZL odatda kasallikning dastlabki bosqichida pastki GI traktidan qon ketish dalillari bilan namoyon bo'ladi (masalan, qorin bo'shlig'i harakatlari va / yoki temir tanqisligi anemiyasi), kamroq qorin og'rig'i bilan, kamdan-kam hollarda ichak teshilishi yoki intussusepsiya. Endoskopik tekshiruvda ko'pincha bitta aniqlanadi polip yoki kamdan-kam hollarda ko'plab poliplar, mukozal yara yoki mukozal tugun. Tashxis EMZLga xos gistologiyani ko'rsatadigan lezyonlarning biopsiyasida o'tkaziladi, masalan. monotsitlar va / yoki plazma hujayralarining morfologik xususiyatlarini ko'rsatishi mumkin bo'lgan kichik va o'rta kattalikdagi limfotsitlardan tashkil topgan diffuz infiltratlar. Ushbu lezyonlardagi limfotsitlar EMZL lezyonlariga xos B hujayralari markerlarini (masalan, CD19 va CD79a) ifodalaydi. Ushbu lenfoma uchun eng yaxshi davolash rejimi muhokama qilinadi. Jarrohlik yo'li bilan rezektsiya qilish, endoskopik rezektsiya qilish, nurlanish va kimyoviy terapiya qo'llanildi. Jarrohlik, so'ngra kimyoviy terapiya (mitoksantron + xlorambusil + prednizon yoki siklofosfamid + vinkristin + prednizon yoki xlorambusil yoki bilan birlashtirilgan rituximab) kasallikni davolashning birinchi bosqichi sifatida qabul qilingan. Yaqinda rituximabning o'zi bitta agent sifatida ham asosiy yo'g'on ichak MALT limfomasini davolashda muvaffaqiyatli topildi. Va nihoyat, birlamchi yo'g'on ichak EMZL holatlari to'liq hal qilindi Helicobacter pylori antibiotik terapiyasi.^[9]

Birlamchi rektal

Birlamchi rektumli EMZL, ko'pincha rektumning MALT lenfomasi deb ataladi, odatda kasallikning dastlabki bosqichida anal qon ketishi va / yoki namoyon bo'ladi najasdagi qon. Endoskopik tekshiruvda rektal polip, rektal massa yoki kamroq tarqalganida rektal oshqozon yarasi aniqlanadi.^[9] Ushbu limfomaning ayrim holatlari o'z-o'zidan orqaga qaytishi haqida xabar berilgan.^[29] Tekshiruvda> 90% hollarda lokalizatsiya qilingan (ya'ni I yoki II bosqich) kasallik mavjud. Limfomalarning shikastlanishlari sentrotsitga o'xshash yoki monotsitga o'xshash B hujayralari bilan singdirilgan reaktiv lenfoid follikulalar bilan tavsiflanadi (oxirgi hujayralar plazma hujayralari). Ushbu lezyonlardagi zararli hujayralar t (11; 18) translokatsiyasini o'z ichiga olishi mumkin va shuning uchun API2-MALT1 ximerik oqsilni (11% holatlarda) ifodalaydi. Ba'zi holatlarning 22-45% bilan bog'liq Helicobactor pylori GI traktining infektsiyasi.^[30] Kasallikni davolash usullariga radioterapiya, jarrohlik yo'li bilan rezektsiya qilish, shilliq qavatni endoskopik rezektsiya qilish, turli xil kimyoviy terapiya va antibiotiklar asosida yo'q qilish kiradi. Helicobactor pylori. Eradikatsiya terapiyasi Helicobactor pylori- hozirda tavsiya etilgan standart antibiotiklar sxemasidan foydalangan holda ijobiy holatlar 19 holatning 12 tasida to'liq javob berdi va shuning uchun bunday holatlar uchun to'g'ri davolash deb hisoblanadi. Mahalliy kasallik uchun jarrohlik rezektsiya alohida holatlarda uzoq muddatli omon qolishga erishdi.^[30] Shu bilan birga, lokalizatsiya qilingan kasallik uchun radioterapiya 5 yillik kasalliksiz va umumiy tirik qolish darajasini 76 va 96 foizni tashkil etdi, 19 ko'rib chiqilgan holatlarning 16 tasida.^[30] va azob chekayotgan bemorlar uchun eng maqbul davolash usuli sifatida tavsiya etiladi Helicobactor pylori- ijobiy birlamchi rektal EMZL.^[9]

Birlamchi qizilo'ngach

Qizilo'ngachning birlamchi EMZL-si, shuningdek MALT limfomasi deb ataladi qizilo'ngach, juda kam uchraydi, chunki aksariyat holatlar Yaponiyadan xabar qilingan. Bu qizilo'ngach sohasidagi begona jismni qiyin yutish va / yoki his qilish alomatlari bilan namoyon bo'ladi. Endoskopiya, endosonografiya va ko'krak qafasi KT tekshiruvi turli o'lchamdagi yolg'iz qizilo'ngach massasini aniqlang^[31] yoki, odatda, qizilo'ngachdagi chiziqli markaziy chuqurlik yoki tizma.^[32] 2017 yilgi tekshiruvda, qizilo'ngachning EMZL bilan kasallangan 18 kasalidan 6tasida bir vaqtning o'zida dalillar mavjud edi Helicobacter pylori infektsiya. Qizilo'ngachning EMZL-dagi shikastlanishlar gistopatologiyasi EMZLga xos bo'lib, CD20 ni ifodalaydigan, ammo CD10 ni ifodalaydigan santrotsitlarga o'xshash hujayralar, monotsitlarga o'xshash hujayralar va kichik limfotsitlar mavjudligini ko'rsatadi.^[31] Qizilo'ngachning EMZL-ni davolash endoskopik rezektsiya, jarrohlik rezektsiya, radioterapiya, endoskopik rezektsiya va radioterapiya yoki kimyoviy terapiyadan iborat. Ko'pgina bemorlar ushbu aralashuvlarga to'liq javob berishadi. Shu bilan birga, ushbu javoblarning uzoq muddatli samaradorligi ma'lum emas, chunki davolanishni kuzatish vaqtlari qisqa (6-35 oy). Davolash uchun muntazam ravishda antibiotiklarga asoslangan eradikatsiya terapiyasi Helicobactor pylori- qizilo'ngachning biriktirilgan EMZLi haqida xabar berilmagan^[31] yaqinda kasallik bilan kasallangan davolanishga qadar vonoprazan + amoksitsillin + klaritromitsin 1 hafta davomida. Bemorda karbamid nafas olish testi asosida bakteriyalarni yo'q qilishga oid dalillar mavjud, ammo keyinchalik limfomaning rivojlanishini tasdiqladi.^[33]

Birlamchi okulyar adneksiya

Birlamchi okulyar adnexa EZML (shuningdek, ko'z adneksiyasining birlamchi EMZL, asosiy ko'z adneksiyasi MALT limfomasi yoki okulyar adneksaning asosiy MALT limfomasi deb ataladi) asosan keksa yoshdagi bemorlarda (o'rtacha 65 yosh) uchraydi. Jismoniy shaxslar kasallikka moyil bo'lishi mumkin, ular uzoq vaqtdan beri chorva mollari, asosan qoramol va cho'chqalarga ta'sir qilishlari yoki bu hayvonlarning go'shti bilan ishlashlari mumkin; otoimmun kasalliklar, xususan, otoimmun tiroid kasalligi; va infektsiyalar, ayniqsa Clamydophelia psittaci, yuqumli hujayra ichidagi bakteriya yovvoyi qushlarni, qishloq xo'jaligi hayvonlarini va odamlarni yuqtiradi. Odamlarda bu nafasni keltirib chiqaradi psittakoz va ko'z infektsiyalari, ayniqsa surunkali kon'yunktivit.^[34] Clammydophelia psittaci Italiyada, Avstriyada, Germaniyada va Koreyada sodir bo'lgan ushbu ko'zning asosiy adneksasi bo'lgan EMZL bilan kasallangan bemorlarning 47-80% zararlanishida aniqlandi. Birlashgan Qirollik va Janubiy Xitoyda aniqlashning ancha past ko'rsatkichlari qayd etilgan, ammo Qo'shma Shtatlar va Yaponiyadagi holatlarda ushbu organizm haqida kam ma'lumot mavjud yoki umuman yo'q.^[14] Oshqozon Helicobactor pylori infektsiya yoki Gepatit C virusi infektsiya birlamchi okulyar adneks EZZML bilan ~ 33% va 2-36% hollarda bog'liqligi haqida xabar berilgan; kamdan-kam hollarda kasallik ham bog'liq bo'lgan Herpes simplex virusi 1, Herpes simplex 2, adenovirus 8, adenovirus 19, Chlamydia trachomatis, yoki Chlamydophila abortus infektsiya. Ushbu infektsiyalarning birlamchi okulyar adneks EZML rivojlanishi va / yoki rivojlanishi bilan aloqasi aniq emas.^[34]

Bemorlarda konjunktiva (25% holatlar) yoki intra-orbital (75% holatlar) shikastlanishlar mavjud bo'lib, ular odatda bitta ko'zni qamrab oladilar, ammo 10-15% hollarda, ayniqsa kon'yunktiva holatlarida ikkala ko'zni ham qamrab oladilar. Konyunktiva shikastlanishlari, odatda, ko'z olmasining tashqi qatlamini qoplaydigan qizil ikra qizil patch shaklida namoyon bo'ladi; intra-orbital lezyonlar odatda mavjud ekzoftalm (ya'ni ko'zning shishishi) (27% hollarda), a sezgir ko'z massasi (19%), ptozis (ya'ni ko'z qovoqlari tushishi) (6%) va / yoki, kamroq, diplopiya (ya'ni ikki tomonlama ko'rish), orbital harakatchanlikning buzilishi, ortiqcha yirtilish va / yoki orbital tugunlar.^[34] Konyunktiva kasalligi bo'lgan bemorlar asemptomatik bo'lishi mumkin.^[35] Birlamchi ko'z adneksasi MZL bo'lgan bemorlarning o'zgaruvchan foizlari bir vaqtning o'zida zararlanishi mumkin Hashimoto tiroiditi, Syogren sindromi, yoki IgG4 bilan bog'liq kasallik. Ba'zi tadqiqotlar, shuningdek, kasallik bilan bog'liqligini aniqladi Helicobactor pylori oshqozon infektsiyasi (45% hollarda) yoki boshqa to'qimalarda EMZL (25% hollarda). Birlamchi okulyar adneksadagi shikastlanishlar EMZLga xosdir: ular tarkibida sentrositB-hujayralar singari, monotsitga o'xshash B-hujayralar va / yoki kichik lenfositalar, ularning ko'pchiligi CD20, CD791, PAZ5 va BCL2 ni ifodalaydi, ammo CD10 yoki siklin D1 oqsillarini ifoda etmaydi.^[36] T (1:14) (p22: q320 xromosoma translokatsiyasi, bu esa haddan tashqari ifodalanishiga olib keladi MALT1 gen, trisomiya 3, trisomiya 18 va xromosomaning 6 uzun qo'lidagi 23-pozitsiyadagi o'chirishlar ko'pincha asosiy ko'z adneksasi EMZLda uchraydi.^[34]

Kasallikni davolash qo'shimcha o'rganishni talab qiladi. Mahalliy kasallikka chalingan bemorlarda: 1) radioterapiya 52-93% hollarda to'liq javoblarga erishdi va 5 yillik tizimli (ammo mahalliy bo'lmagan) relaps darajasi> 90% ni tashkil etdi; 2) a bilan kimyoviy terapiya CHOP 15 bemordagi rejim 9 oyda relapssiz remissiyaga, 5 yilda mahalliy relaps va 55 oylik kuzatuvdan so'ng 2 bemorda tizimli relapssiz erishildi; 3) bilan kimyoviy davolash xlorambusil 33 bemorda 24 oylik kuzatuvdan so'ng 26 bemorda to'liq javoblarga erishildi; 4) bilan immunoterapiya rituximab qisqa muddatli davrda o'zgaruvchan natijalarga erishdi va uzoqroq kuzatuv davomida qo'shimcha o'rganishni talab qiladi^[36] kon'yunktiva kasalligi bo'lgan bemorlarda biroz yaxshiroq natijalar paydo bo'lishi bilan;^[34] va 5) bilan antibiotik terapiyasi doksisiklin 2 yillik va 5 yillik muvaffaqiyatsizlikka uchragan holda, mos ravishda 67% va 55% va 5 yillik progressiyasiz 61% ga erishdi.^[36] Tizimli ishtirok etgan bemorlarni tanlagan umumiy tan olingan davolashda ko'pincha rituximab bilan birlashtirilgan turli xil kimyoviy terapiya sxemalari qo'llaniladi. Xlorambusil, CHOP rejimlari yoki rituximab bilan davolangan bemorlarning ko'pchiligida to'liq javoblar kuzatilgan, ammo takrorlanish darajasi yuqori (masalan, ~ 33%).^[34]

Birlamchi teri

Birlamchi teri EMZL yoki birlamchi teri MALT lenfoma (shuningdek, ular deb ataladi) teri bilan bog'langan limfoid to'qima lenfoma) odatda bitta yoki bir nechta kichik sifatida taqdim etiladi papules yoki plakatlar odatda qo'l va / yoki magistralda joylashgan. Gistologik jihatdan bu shikastlanishlar a ga ega bo'lgan kichik B hujayralari aralashmasini o'z ichiga olgan reaktiv germinal markazlardan iborat plazma hujayrasikabi yoki monotsito'xshash morfologiya ko'p sonli interlaced T xujayrasi limfotsitlar.^[37] Ushbu jarohatlardagi B-hujayralar odatda EMZLda ko'rilgan B-hujayra belgilarini ifodalaydi.^[38] The DNK ning Borrelia burgdorferi, ning qo'zg'atuvchisi Lyme kasalligi, bemorlarning 10% -42% lezyonlarida aniqlangan^[39] Germaniya, Italiya, Yaponiya va Turkiyada, ammo Ispaniya, Finlyandiya, Gollandiya yoki AQShdan kelgan bemorlar emas.^[40] Kasallik deyarli har doim o'ta beparvolik kursiga ega bo'lsa-da, odatda terida cheklangan takroriy relapslarga duchor bo'ladi. Kamdan kam hollarda birlamchi teri EMZL boshqa to'qimalarga tarqaladi va tizimli kasallikka aylanadi.^[40] Birlamchi teri EMZLni davolash konservativ usul bo'lib, kasalliklarga moyillik xatti-harakatlarini hisobga olgan holda. Yilda Borrelia burdorferi- ijobiy kasallik, antibiotik terapiyasi (a kurslari sefalosporin yoki tetratsiklin birinchi darajali antibiotiklarni tanlash deb hisoblanadi) e'tiborga olinishi kerak^[7] garchi bu chora AQSh kabi joylarda, bakteriya kasallik bilan bog'liq bo'lmagan joylarda kamroq qo'llaniladi.^[38] Davolash Borrelia burdorferi- antibiotikli terapiya imkoniyati bo'lmagan yoki muvaffaqiyatsiz tugagan salbiy kasallik yoki kasallik shikastlanish darajasiga bog'liq. Yagona lezyonni davolash usullari jarrohlik yo'li bilan rezektsiya qilish, to'g'ridan-to'g'ri in'ektsiya qilish interferon-alfa yoki rituximab jarohatlarga va lokalizatsiya qilingan tashqi nurli radioterapiya. Ushbu muolajalardan 5 va 10 yil o'tgach aniqlangan kasalliksiz stavkalar mos ravishda 57% va 43% ni tashkil qiladi. Tarqoq kasallikda, hushyor kutish, tomir ichiga rituximab va kimyoviy terapiya qo'llanilgan. Vena ichiga yuborilgan rituximab ximioterapiya olmagan bemorlarda remissiya darajasi 85% ni tashkil qiladi; xlorambusil Rituksimab bilan yoki tomir orqali yuborilgan kimyoviy terapiya hodisalarsiz yashash vaqtini sezilarli darajada yaxshiladi; va CHOP bemorlarga kimyoviy terapiya tavsiya etiladi B belgilari (masalan, isitma, tunda terlash, vazn yo'qotish va boshqalar), sarum darajasining ko'tarilishi sut kislotasi dehidrogenaza, yoki kasallik yanada tajovuzkor bosqichga o'tdi.^[7]

Birlamchi o'pka

Birlamchi o'pka EMZL (yoki birlamchi o'pka MALT limfomasi) kamdan-kam uchraydigan kasallikdir, ammo shunga qaramay o'pkadan kelib chiqqan barcha limfomalarning 80% gacha. Ushbu lenfoma rivojlanishining sababi aniq emas. Kasallik bilan kasallangan odamlarning taxminan 16 foizi otoimmun buzilish xususiyatlariga ega bo'lib, bitta tadqiqotga ko'ra, ushbu kasallikka chalingan 124 bemorning 57 tasi dalolat beradi Axromobakteri ksilosoksidanlar DNK ularning o'pka lezyonlarida.^[41] Axromobakteri ksilosoksidanlar a betaproteobakteriyalar ning o'pkasidan muntazam ravishda ajratib olinadi kistik fibroz bemorlar; u past zaharlanish ammo antibiotiklarga juda chidamli.^[7] Birlamchi o'pka EMZL odatda 50-60 yoshli bemorlarni azoblaydi; deyarli 50% hollarda kasallik anormal ko'krak rentgenogrammasi yoki simptomsiz odamlarda aniqlanadi KTni tekshirish bog'liq bo'lmagan sabablarga ko'ra o'tkazilgan.^[41] Semptomlari bo'lgan bemorlarda odatda ko'krak qafasi og'rig'i, nafas qisilishi va / yoki takroriy nafas olish yo'llari infektsiyalari mavjud.^[14] Ko'krak qafasi rentgenografiyasi va tomografiya odatda ikki tomonlama ko'rinishga ega alveolyar xiraliklar <5 sm. O'pkaning jiddiy shikastlanishi (masalan, atelektaz, plevra effuziyasi, yoki mediastinal limfadenopatiya) <10% hollarda uchraydi. Keyinchalik rivojlangan kasallikka chalingan bemorlar murojaat qilishlari mumkin ilik tutilish (13-30% holatlar), oshqozon yoki ko'z, quloq, burun va / yoki tomoq singari o'pkadan tashqarida bo'lgan joylar (25-35%) yoki kamdan-kam hollarda, ayniqsa agressiv kasallik, tizimli B belgilari isitma kabi, tungi terlarva / yoki vazn yo'qotish. A monoklonal gammopatiya (ya'ni haddan tashqari a monoklonal gamma globulin ichida qon) 20-60% hollarda uchraydi, xususan plazma hujayrasi ko'rinishidagi limfotsitlarni o'z ichiga olgan to'qima lezyonlari bo'lgan odamlarda. Birlamchi o'pka limfomasidagi shikastlanishlar shilliq qavatda bo'ladi bronxial nafas yo'llari va igna biopsiyasi, bronxial biopsiya, trans-bronxial biopsiya va / yoki tashxis qo'yilgan bronxoalveolyar lavaj. Findings consistent with the diagnosis include biopsy specimens revealing mucosa infiltrates of small B-cells bearing the typical B cell markers found in EMZL; occasional specimens consist of B lymphocytes with a plasma cell appearance. Bronxoalveolyar lavaj fluid may contain >10% of cells which bear these markers. B-cells in the pulmonary lesions have the t(11;18)(q21;q21) translocation and therefore express the API2-MALT1 chimeric protein in ~40% of cases. Other, less frequently occurring genomic abnormalities in these cells include t(1;14)(p22;q32), t(14;18)(q32;q21), and t(3;14)(p14.1;q32) translocations and trisomiya of chromosomes 3 and/or 18.^[41]

Treatment of primary pulmonary EMZL varies. Antibiotic therapy has not been studied and cannot be recommended. Recommended treatments which have afforded overall 5 year survival rates of 89-100%^[42] include surgery, radiotherapy, chemotherapy, immunoterapiyava hushyor kutish.^[41] Surgical resection or radiotherapy may be considered for localized disease. In more extensive disease, rituximab immunotherapy has achieved a 70% response rate but with a high rate of recurrence (~36%). Bilan davolash fludarabin, CHOP, xlorambusil, or chlorambucil + rituximab have been used to treat extensive disease with each treatment giving approximately similar overall median survival times of >10 years.^[41]

Primary salivary gland

Primary salivary gland EMZL (also termed MALT lymphoma of the tuprik bezlari) or, in cases primarily involving the ko'z yoshi bezlari, primary lacrimal gland EMZL (also termed MALT lymphoma of the lacrimal gland) is a complication of Syogren sindromi, an otoimmun kasallik characterized by chronic inflammation of the salivary and/or lacrimal glands.^[17] This autoimmune disease is thought to be caused by a combination of genetik va atrof-muhit factors including yuqumli moddalar. This lymphoma afflicts ~3% of patients with Sjögren syndrome^[8] and involves one or more of the afflicted salivary or, less commonly, lacrimal glands.^[17] The median time between diagnosis of the autoimmune disease and EMZL varies between 7.5^[17] and 11 years.^[19] Afflicted individuals typically are 55–60 years old and present with localized hardening and/or enlargement of the parotid bezi or, less commonly, other salivary or lacrimal gland. Some 20% of cases present with or progress to involve local lymph nodes or the spleen to cause limfadenopatiya yoki splenomegali while ~10% of cases present with or progress to a high-grade lymphoma, primarily diffuse large B-cell lymphoma.^[17] Histologically, the involved glands show lymphocyte-based lesions that are typical of EMZL with the infiltrating lymphocytes in some cases having morphological features resembling plazma hujayralari. In individuals with more advanced disease, these lesions develop in the mucosal linings of the ko'z teshigi, nasal cavity, tomoq, airways of the lower nafas olish yo'llari, stomach, and/or thyroid gland.^[8]

Treatment of primary salivary/lacrimal gland EMZL has not been standardized. A minority of patients have been treated by hushyor kutish but most patients have been subjected to surgery, radiotherapy, chemotherapy (i.e. xlorambusil), immunotherapy (i.e. rituximab, or a combination (e.g. chlorambucil + rituximab or fludarabin + rituximab or bendamustin + rituximab) immunotherapy plus chemotherapy regimen. In general, overall survival rates after 5, 10, and 15 years of treatment have been 95%, 85%, and 78% respectively. While the response to these therapeutic regimens has been very good, ~33% of treated patients have experience a recurrence of their lymphoma in the salivary/lacrimal glands, lymph nodes, or other sites.^[19]

Lymphoepithelial sialadenitis

Lymphoepithelial sialadenitis, also termed chronic sialadenitis, is a benign infiltration of salivary glands by B-cells with morphological features of marginal zone B-cells, centrocytes, and monocytes. Histologically, this disorder is associated with atrofiya ning ustunli epiteliy in salivary gland ducts as well as the proliferation of epithelial cells and lymphoepithelial lesions in these glands. While usually a component of Sjorgen syndrome, these histological finding can also occur in patients without evidence of this syndrome. Very rarely, lymphoepitheleial sialadenitis progressed to salivary gland EMZL.^[14]

Primary thyroid

Primary thyroid EMZL, also termed MALT lymphoma of the qalqonsimon bez, is extremely rare. It occurs almost exclusively in thyroid glands afflicted by Hashimoto tiroiditi, an autoimmune disease characterized by the accumulation of lymphocytes, including B-cells, in the thyroid gland and the subsequent destruction of thyroid tissue by these cells.^[43] Patients with this syndorme have a 40- to 80-fold increased risk of developing a thyroid lymphoma, 25% of which are primary thyroid EMZLs. Hashimoto's thyroiditis patients who develop this lymphoma are typically women (median age 70 years) who have had the thyroiditis for 20–30 years and present with a rapid increase in the thyroid gland's size and, in association with this, have developed ovozning balandligi, high-pitched nafas tovushlari, and/or difficulty in swallowing and/or breathing.^[17] Histologically, the lesions in this lymphoma generally consist of reactive limfoid follikulalar va lymphoepithelial lesions which are populated by intermediate-sized B-cells, tsentrotsitlar, plazma hujayralari, and, in ~1/3 of cases, sheets of large lymphocytic cells similar to those seen in diffuz katta B hujayrali lenfomalar. The malignant cells in these lesions express B-cell markers that are typical for EMZL, e.g. CD20 and BCL-6 but not CD10 proteins.^[44] Patients with primary thyroid EMZL are at an increased risk of developing a more disseminated lymphoma, particularly diffuse large B-cell lymphoma or, alternatively, nodal MZL, or splenic MZL.^[17]

Treatment of primary thyroid EMZL is generally conservative since up to 90% of patients are diagnosed with early stage disease.^[17] Although the optimal treatment for this disease is uncertain, the majority of patients with localized disease are treated with surgery, radiotherapy, or a combination of both modalities and attain overall response rates of up to 100%^[19] and an estimated 5 year disease-free survival of 95%.^[17] Surgery plus radiotherapy does not appear to give better results that radiotherapy alone.^[44] Patients with extensive disease or disease that has progressed to a higher grade lymphoma (principally diffuse B-cell lymphoma) have been treated with kimyoviy terapiya (odatda CHOP^[44][45]) va / yoki immunoterapiya (ya'ni rituximab^[44]). However, the 5 year survival rates in chemotherapy-treated patients with disseminated primary thyroid EMZL^[46] or disease that has progressed to a more malignant lymphoma^[17] are only 35% and 44%, respectively.

EMZL and other autoimmune diseases

Patients suffering an otoimmun kasallik other then Hashimoto's thyroiditis also have an increased risk of developing an EZML in one or more tissue sites. For example, patients with systemic lupus erythematosus have a 7.5-fold increased risk of developing an EMZL compared to the general population and at diagnosis of this development have a median age of 50 years and been diagnosed with systemic lupus erthyematosis for 6.7 to 17.8 years.^[17] Bemorlar romatoid artrit,^[17] immun trombotsitopenik purpura,^[47] va otoimmun gemolitik anemiya^[48] are similarly susceptible to developing an EZML. While the exact reasons for these associations are unclear, it is generally considered that the chronic inflammation involved in each disease promotes the malignant behavior of B-cells and thereby the development of EZML.^[17] Treatment of patients with an autoimmune disease complicated by EMZL has usually involved the standard measures used to treat both the autoimmune disease and EMZL.^[48]

Primary central nervous system

Primary EMZL of the markaziy asab tizimi is an extremely rare disorder. Compared to other central nervous system lymphomas which are highly aggressive, primary EMZL of the central nervous system is a non-aggressive, low-grade lymphoma. In a review of 70 published cases, the disease involved the proliferation of malignant marginal zone B-cells within the dura mater, i.e. thick membrane surrounding the brain and spinal cord, (56 cases), the brain or spinal parenxima (6 cases), the brain's cavernous sinusn (4 cases), the brains choroid pleksus (3 cases), inside brain [[Ventricular system[ventricle]] (1 case), the cerebellopontine angle (2 cases), and the optik asab (2 ta holat). Patients (77% female; median age 55 years, ranging from 18 to 78 years) presented with various neurological signs and symptoms depending on the site of involvement. The most common presenting symptoms were bosh og'rig'i (30 cases); soqchilik (22 cases); and visual changes (19 cases). Less commonly, patients presented with paresteziyalar (i.e. abnormal skin sensations), motor deficits, and ataksiyalar, memory failures, and dizziness. At the time of diagnosis, there was no evidence of EMZL outside of the central nervous system. Malignant cells were detected in the miya omurilik suyuqligi in 5 of the 19 cases tested for this.^[49] Histologically, lesions in the disorder were typical of EMZL in that they consisted of small to medium-sized B-cells that express CD19, CD20, and CD79a) but not CD10, CD23, or cyclin D1 marker proteins along with some plasma cells and a variable number of reactive T-cells.^[49][50] Fifty percent of cases tested for trisomy of chromosome 3 were positive.^[49]

Treatment of localized disease consisted of surgery, radiotherapy, or a combination of both modalities whereas treatment of extensive central nervous system disease consisted of chemotherapy, including intratekal kimyoviy davolash, with or without surgery and/or radiotherapy. Regardless of treatment regimen, primary central nervous system EZML has a good prognosis with complete response (CR) occurring in 77% of patients and 22% of patients alive with evidence of disease after 1–86 months of follow-up times. The values of systemic and intrathecal chemotherapy in treating the disease are unclear and require further study.^[49]

Primary breast

Primary EMZL of the breast (also termed primary MALT lymphoma of the breast) is an exceedingly rare disease. It usually presents as a palpable breast mass in an otherwise symptom-free patient.^[51] Histopathological findings are typical for EMZL: lesions consist of small- to medium-sized B cells, centrocyte-like B-cells, small lymphoid cells with some features of plazma hujayralari yoki monotsitlar, and mature plasma cells with the lymphoid cells in these lesions expressing CD20 and CD79a but usually not CD10, CD43 or BCL6 marker proteins.^[52] Moderate doses of local radiation therapy are recommended to treated localized EMZL of the breast. This treatment has achieved overall survival rates of >90%. Given these results and the high sensitivity of EMZL to radiation therapy, mastektomiya is not recommended and wide excision is not usually necessary to treat localized disease. For patients with disseminated disease, treatment options include hushyor kutish and chemotherapy (typically employing a CHOP or CHOP-like regimen) with or without radiation therapy and/or excision. These approaches have attained complete disease remissions in 9 of 9 patients followed for 6–74 months and one death due to progressive disease in a patient followed for 107 months. Other drugs used to treat the disease include rituximab, tamoksifenva oksaliplatin.^[51]

Primary urinary tract

Birlamchi siydik yo'llari EMZLs of the siydik pufagi and kidney are extremely rare but the most common forms of lymphoma that are found in these organs. They occur most commonly in middle aged females who have a history of chronic sistit, i.e. inflammation of the bladder due to siydik yo'li infektsiyasi yoki boshqa sabablar.^[19]

Primary bladder

Presenting symptoms of primary bladder lymphoma include weight loss, fatigue, gematuriya, dizuriya, nikturiya, urinary frequency, and pain in the abdomen and/or suprapubic maydon.^[53] However, this lymphoma commonly occurs as a disseminated disease involving other organs and tissues.^[54] Radiological and cystoscopy examinations reveal one or more mucosal masses in, or diffuse thickening of, the bladder wall.^[19] The histopathology of these lesions is typical of EMZL; they contain small lymphocytes some or many of which have plasma cell features with the malignant cells in these lesions typically expressing CD20 and PAX-5 but not CD5 or CD10 marker proteins.^[53] The cells may also contain the t(11;18)(q21:q 21) translocation typical of EZML.^[54] Treatment of primary bladder EMZL depends on the extent of disease. Localized disease should be confirmed using, e.g. Positron emission tomography–computed tomography (i.e. PET/CT), Magnit-rezonans tomografiya (i.e. MRI) of the tos suyagi maydon va Suyak iligi tekshiruvi. Confirmed localized disease has been treated by surgery and radiotherapy with radiotherapy being the clearly preferred and most appropriate modality given this lymphoma's high sensitivity to radiation. However, surgical resection with resection of bladder tumor (i.e. TURBT) may be the best treatment where fertility is of concern. Disseminated and recurrent primary bladder EMZL have been treated with systemic chemotherapy (usually a CHOP or CHOP + rituximab rejim.^[53] Prognoses for treated localized and disseminated disease are good^[19] with long-term (e.g. up to 40 years) remissions reported for most patients with localized disease and (up to 10 years) for patients with disseminated disease.^[53]

Buyrak

Kidney EMZL (i.e. kidney MALT lymphoma, renal EMZL, or renal MALT lymphoma) occurs primarily in individuals >50 years old but has been reported in individuals as young as 9 years. In slightly more than half of the reported cases, this lymphoma was localized to the kidney or detected in the kidney plus lymph nodes around the kidney, elsewhere in the retroperitonium, yoki bo'ylab qorin aortasi. These cases could therefore be regarded as primary kidney EMZLs. The remaining cases had widespread disease some of which appear related to primary salivary gland EMZL, primary orbital EMZL, Helicobactor pylori- aloqador gastrit, systemic lupus erythematosus, or possibly an Epstein–Barr virus-associated lymphoproliferative disease, i.e. a lymphocyte-proliferating disease related to and thought to be caused by infection with this virus.^[55] Patients may present with signs and symptoms of a kidney mass (e.g. low pack pain and/or abnormal kidney function as determined by elevation in serum kreatinin). The best treatment for kidney EMZL is unclear. Reported cases have been subjected to nefrektomiya and/or chemotherapy.^[56]

Primary gallbladder

Birlamchi o't pufagi EMZL (i.e. extranodal marginal zone lymphoma of the gallbladder,^[57] primary MALT lymphoma of the gall bladder^[58]) is an extremely rare disease with only 17 cases being reported in the literature as of 2017.^[58] Presenting features in individuals (aged 31–84 years, median age 74, >60% females) with the disease are similar to those seen in other lymphomas and non-lymphomatous cancers of the gallbladder;^[57] these include pain in the upper right-side of the abdomen, nausea, vomiting, and in about two-thirds of cases, gallstoness.^[58] Given these similarities as well as similarities in the laboratory, tibbiy ultratovush, and X-ray findings of primary gallbladder EMZL compared to other gallbladder cancers which account for >99% of bladder cancers, the diagnosis of primary gallbladder EMZL has not yet been made pre-operatively. Rather, its diagnosis has rested exclusively on examination of surgically-removed gallbladders.^[58] The lesions in these gallbladders show infiltrates in the gland's submukoza that consist of small lymphocytes interspersed with lymphoepithelial lesions. The lymphocytes have marker protein profiles (e.g. CD20 and Bcl-2 positive; CD5, cyclin D1^[58] and CD10^[57] negative) that are typical for EMXL. Xoletsistektomiya, i.e. surgical removal of the gallbladder, has produced remissions in all patients with only one recurrence over observation periods of 2 to 96 months.^[58]

Primary hepatic

Primary hepatic EMZL (i.e. primary hepatic extranodal marginal zone B-cell lymphoma, primary hepatic mucosa-associated lymphoid tissue lymphoma, primary hepatic mucosa-associated lymphoma) is an extremely rare malignancy representing <3% of all primary lymphomas of the liver.^[59] Only 47 cases of primary hepatic EMZL were reported in the English literature as evaluated by a 2019 review.^[60] Based on this review, individuals with primary hepatic EMZL had concomitant liver disease ( principally hepatitis B viral hepatitis yoki hepatitis C viral hepatitis, less commonly, birlamchi biliar sirroz yoki jigar hujayralari karsinomasi, and, rarely, other liver diseases^[60] kabi hepatitis A viral hepatitis. Patients (median age 63 years, range 30–85 years) presented with no symptoms (~64% of cases) or symptoms (which may have been related to their other liver diseases) such as abdominal pain, generalized weakness, cough, elevations in their blood levels of jigar fermentlari, and/or evidence of one or more liver masses as detected by magnit-rezonans tomografiya, computed tomography scans, yoki pozitron emissiya tomografiyasi.^[60] These presentations are virtually identical to those seen in other forms of liver cancer. Accordingly, the diagnosis of primary hepatic EMZL has been extremely hard to make without obtaining tissue by surgical methods.^[59] Histological examination of involved liver tissues commonly showed diffuse infiltrations of small- to medium-sized atypical lymphocytes. These infiltrations, which may involve the liver's bile ducts, often contained lymphoepithelial lesions. Immunohistokimyo testing of these tissues revealed lymphocytes that expressed CD20 and BCL-2 but not CD10 or cyclin D1. While optimal therapeutic strategies for this disease have not been established, primary hepatic EMZL appears to be an indolent cancer. Patients who underwent surgical resection with or without chemotherapy or rituximab treatment regimens and were observed over a median period of 31 months had mostly positive outcomes: 92% survived, 8% died of causes unrelated or only indirectly related to their cancer, and 11% suffered relapses.^[60]

EMZL associated with hepatitis C

EMZL occurs more frequently (~2.5-fold increased risk) in individuals who have gepatit C virusi- tushuntirilgan gepatit. The lymphoma typically occurs 15–25 years (median times) after the viral infection and involves the skin (35% of cases), salivary glands (25%), orbital adnexa (15%) or, uncommonly, the stomach or other tissues. Bu bilan bog'liq type II cryoglobulinemia, i.e. the circulation of an immune complex consisting of poliklonal IgG, monoklonal IgM, and hepatitis C viral RNK. This immune complex causes signs and symptoms of vasculitis in 10% of cases. Other signs and symptoms of the disorder include those associated with surunkali gepatit and the specific subtype of EMZL.^[61] Rarely EMZL associated with hepatitis C virus infection presents as single or multiple soft, mobile sub-cutaneous nodules.^[27] This presentation occurs mainly in female (83% of cases) and elderly patients.^[61] Patients with this disorder may have detectable levels of circulating hepatitis C virus.^[39] The histology of the lesions in EMZL associated with hepatitis C virus infection is typical of EMZL^[39] although the genomic abnormalities in the disorders malignant cells has not been well-defined beyond their expression of the t(14;18) chromosome translocation in a significant number of cases.^[62] Treatment of this disease had relied on eradicating the virus using peginterferon-alfas, interferon-alpha-like drugs to mobilize the hosts' immune systems. This treatment cured the viral infection in ~50% and produced lymphoma remissions in <50% of cases. More recently, drugs (e.g. simeprevir, daklatasvir, sofosbuvirva dasabuvir) that directly inhibit the virus's reproduction have cured the infection and achieved lymphoma responses in up to 100 and 73%, respectively, of patients with one year overall and progression-free survival rates of 98 and 75%, respectively. For patients who's lymphoma fails to respond to this therapy (~25% of cases), recommended treatments include rituximab or rituximab + a peginterferon-alfa. Beri kimyoviy terapiya regimens are highly toxic in patients with liver disease, they should be avoided, where possible, in treating EMZL associated with hepatitis C virus infection.^[61]

Dalakning marginal zonasi lenfoma

Splenic marginal zone lymphoma (SMZL) is a low grade lymphoma in which malignant B-cells accumulate in the spleen, bone marrow, and, less commonly, the circulation. While generally an indolent disease, about 5-10% of cases transform into a far more aggressive malignancy, diffuz katta B-hujayrali limfoma.^[63] In a variable percentage of cases, SMZL has been observed to occur with an increased incidence in individuals who are chronically infected with Gepatit C virusi^[62] or have any one of various chronic autoimmune diseases or abnormalities.^[64]

Belgilari va alomatlari

At presentation, patients (median age 65 years; range 30–90 years) generally exhibit enlargement of their spleens (75% of cases).^[65] They typically do not have enlargements of their limfa tugunlari tashqari lymph nodes around the hilum of their spleens.^[66] Most patients have no systemic symptoms such as fever, tungi terlar, weight loss, or fatigue.^[65] Blood tests reveal reductions in the levels of red blood cells, trombotsitlar, and/or white blood cells in 25% of cases;^[65] an abnormal circulating IgM miyeloma oqsili in <33% of cases; and in ~20% of cases evidence of otoimmunitet abnormalities such as circulating otoantikorlar (ya'ni antikorlar directed against the patients' own antigens), autoimmune hemolytic anemia, immune thrombocytopenic purpura,^[65] sovuq aglutininlar, and/or anticoagulant antibodies.^[64] Individuals with SMZL also commonly exhibit increased levels of circulating blood limfotsitlar which in some cases can be identified as malignant B-cells; these malignant cells may have hair-like projections similar to the malignant B-cells found in the circulation of patients with tukli hujayra leykemiyasi.^[66] Patients with SMZL may also present with signs and symptoms of acquired von Willebrand disease, angioedema due to C1-esterase inhibitor deficiency,^[64] or hepatitis C virus infection (e.g. clinical hepatitis, circulating hepatitis C virus). The association of hepatitis C virus infection with SMZL varies with location and may be as high as 10% in some areas.^[62] Finally, careful examination of patient bone marrows almost always finds pockets or more extensive accumulations of malignant B-cells.^[65]

Patofiziologiya

The malignant cells involved in SMZL are tentatively identified as antigen-experienced B-cells. The disease appears to be initiated in at least some cases by chronic antigen stimulation of the precursor B-cells that thereby become antigen-experienced. Evidence for this derivation comes from studies showing that the antigen-experienced B-cells inn SMZL express structurally restricted immunoglobulinlar va B-cell receptors (qarang klonli tanlov) that likely bind specific but generally unidentified antigens.^[67] Furthermore, patients with SMZL are often found to have autoimmune abnormalities such as circulating otoantikorlar (ya'ni antikorlar directed against patients' own antigens), otoimmun gemolitik anemiya, immun trombotsitopenik purpura,^[65] sovuq aglutinin kasalligi, circulating anticoagulant antibodies, acquired fon Willebrand kasalligiva angeoedema due to C1-esterase inhibitor deficiency.^[64] It is thought that the B-cell receptor binding of unidentified antigens including those involved in the cited autoimmune abnormalities stimulate the B-cells' proliferation, long-term survival, and thereby the step-wise acquisition of genomic abnormalities which ultimately cause the antigen-experienced B-cells to become malignant.^[63][67][65] The genomic abnormalities thought to contribute to this malignant transformation include:

• Chromosome abnormalities such as: 1) deletions in the long (i.e. "q") arm of chromosome 7 (annotated as del7q) in 30-40% of cases (this deletion is rare in other lymphomas and therefore used as a marker for SMZL);^[63] 2) deletion of a region on the short (i.e. "p") arm of chromosome 17 in 3-17% of cases to result in a loose of one of the two p53 genes that encode a tumor suppressor that acts to regulate cellular survival; and 3) gains in the q arm of chromosome 3 in 10-20% of cases.^[65]
• Mutatsiyalar in genes such as: 1 KLF2 (21% of cases),^[63] a transkripsiya omili that indirectly regulates the NF-DB signaling pathway of cellular survival, proliferation, and the production of cell-stimulating sitokinlar;^[68] 2) NOTCH2 (20% of cases),^[63] a membrane protein that regulates the development of marginal zone B-cells from their precursor cells and has tumor suppressor activity to thereby promote cellular survival;^[69] 3) TP53 (14% of cases), a transcription factor that indirectly regulates cell proliferation and dasturlashtirilgan hujayralar o'limi to thereby promote cellular survival;^[63] 4) IGLL5 (14% of cases) with unclear functions;^[63] 5) TNFAIP3 (13% of cases), which acts indirectly to inhibit NF-κB activation and programmed cell death;^[63] and 6) in <10% of cases at least 16 other genes.^[63]

Overall, mutations in the NOTCH, NF-κB, and KLF2 signaling pathways appear particularly important in the pathogenesis of SMZL.^[64]

Tashxis

The clearest evidence for the diagnosis of SMZL is obtained by examination of patients' spleens obtained by splenektomiya. These spleens characteristically show lymphoid infiltrates in the oq pulpa and, to a lesser and more variable extent, the qizil pulpa. These infiltrates consist of small lymphocytes, marginal zone B-cells, sentroblast-like B-cells, monotsit-like B-cells, and plazma hujayralari. Epiteliyoido'xshash histiositlar may be found in the red pulp. Splenic hilar lymph nodes may show nodular infiltrates of small lymphocytes. Careful and thorough examination of patients' bone marrow commonly shows aggregates of lymphoid cells between the organs trabekulalar and within its sinuslar. Neoplastic B-cells may also circulate in patient's blood. The neoplastic cells in all of these tissues, similar the neoplastic cells in extranodal and nodal MZL, express CD20, CD27va BCL2 lekin emas CD10, CD23, CD5, CD43, CD38, BCL6, velosiped D1, yoki annexin A1 marker oqsillari. These cells may also express the del7q deletion (i.e. deletions in the q arm of chromosome 7) in 30-40% of cases^[65] and in lower percentages of cases the mutated genes listed in the Pathophysiology section. While the diagnosis of SMZL was initially based on the examination of splenic tissue, currently the diagnosis is made in most cases on clinical findings plus examinations of patients' bone marrow and/or blood that detect neoplastic B-cells that express some of the proteins and/or genomic abnormalities cited above;^[65] however, cases difficult to diagnose based on bone marrow and blood findings require examination of the spleen to obtain a definitive diagnosis of SMZL.^[66]

Davolash

Given its rarity, there have been no systematic and controlled studies on the treatment of SMZL. Current recommendations for this include the following. Ehtiyotkorlik bilan kutish, which is the withholding of specific treatments while performing follow-up examinations every 3 to 6 months to detect disease progression. This course is recommended for the ~33% of SMZL patients who present with asymptomatic, non-progressive, or slowly progressive disease. These patients may not require therapeutic interventions for long periods. Historically, the initial therapy for patients with rapidly progressing disease was splenektomiya. Some 90% of these patients show reductions in their symptoms and improvements in their low red blood cell, platelet, and white blood cell counts; they had median progression-free, 5 year overall, and 10 year overall survival rates of 8.2 years, 84%, and 67%, respectively. However, these patients show no alteration in the neoplastic B-cells levels in their blood, were subject to serious complications from their splenectomy (e.g. tromboz, infections), and did not show alter overall survival rates better than those obtained with other treatment strategies. Accordingly, splenectomy for SMZL has been limited to cases of significantly symptomatic enlarged spleens in patients with mild-to-moderate bone marrow involvement and no bulky lymph node enlargements.^[66]

Current treatment recommendations for patients with symptomatic or rapidly progressive SMZL rely on drugs. Rituximab, a commercial preparation of a monoklonal antikor directed at the CD20 protein on B-cells, is significantly active in SMZL, with short-term treatments (e.g. ~4 weeks) achieving overall response rates of 90-100%, complete remission rates of >50%, and a 7-year progression-free survival rate of 69%. Long-term maintenance therapy with rituximab appears to improve these results and patients who relapse after rituximab therapy commonly respond to a second course of the drug. Prior to rituximab availability, single drug kimyoviy terapiya (masalan, xlorambusil, siklofosfamid, fludarabin, pentostatin, 2CDA, yoki bendamustin) and multiple drug regimens (i.e. the CVP regimen of siklofosfamid, vinkristinva prednizonyoki CHOP regimen of CVP plus doksorubitsin) were used to treat the disease. However, current studies indicate that these chemotherapeutic agents are not superior to single agent rituximab therapy in terms of response rate as well as the quality and duration of these responses.^[66] A phase II clinical trial has found that the treatment of SMZL with a combination of rituximab plus bemdamustine achieves overall response and complete response rates of 91% and 73%, respectively, with percentage responses enduring for >3 years, progression-free survival rate, and overall survival rate of 93%, 90%, and 96%, respectively. The results of this trial, while requiring confirmation, strongly suggest that this two-drug regimen be used in place of rituximab alone, the cited chemotherapy regimens, or rituximab plus the cited chemotherapy regimens for patients with symptomatic/progressive SMZL.^[70]

Experts recommend that SMZL patients who also have hepatitis C virus infection should be treated with drugs that act to eliminate the virus as their first line approach. Before the development of directly acting anti-viral agents, several studies reported that IFN-a davolash of these patients produced improvements not only in the viral infection but also remissions (~65% of cases) in their lymphomas.^[66] Several newer, directly acting anti-viral agents, e.g. grazoprevir, daklatasvir, sofosbuvirva dasabuvir, are more effective in treating hepatitis C viral infection^[61] and in s small number of patients have been or are expected to be more effective in producing lymphoma remissions in patients with SMZL plus hepatitis C virus infection.^[61][66]

Prognoz

SMZL generally follows an indolent course with 10 year survival rates of 42-95%.^[65] About one-third of these deaths are unrelated to SMZL and ~5-10 of these deaths are due to the transformation of their SMZL disease to diffuse large C-cell lymphoma.^[66]

Tugunli marginal zonadagi limfoma

Nodal marginal zone lymphoma (NMZL), previously termed monocytoid B-cell lymphoma, nodal monocytoid B-cell lymphoma, and nodal marginal zone lymphoma with or without monocytoid B-cells, is an infiltration of tissues with malignant lymphoid cells that have the morfologik va fenotipik features of all marginal zone lymphomas.^[71] NMZL differs from the other subtypes of marginal zone lymphomas by its primary involvement of limfa tugunlari rather than other tissues and organs.^[72] NMZL is the least common subtype of the three marginal zone lymphomas.^[73]

Belgilari va alomatlari

Almost all patients with NMZL present (median age 50–64 years;^[71] male to female ration 1.5 to 1^[73]) with non-bulky enlargement of their lymph nodes in the neck, groin, abdomen, and thoracic regions;^[71] some cases may also exhibit this involvement in their Voldeyerning bodomsimon halqasi.^[74] Patients at presentation are generally fully functional but in 10-20% of cases complain of B belgilari isitma kabi, tungi terlar, weight loss, and/or fatigue.^[74] Laboratory studies show malignant B[cells infiltrating the ilik in ~33% of patients and an abnormal IgM miyeloma oqsili in ~20% of cases. Rarely, patients may present with circulating malignant marginal zone B cells and/or reductions in one or more types of circulating normal qon hujayralari.^[71] Biopsy of involved tissues various patterns (e.g. diffuse throughout lymph node, centered between the follicles of lymph nodes, and/or a nodules spread throughout the lymph node) lymphocyte infiltration.^[74] These patterns are similar to those seen in EMZL MALT lymphomas.^[73] The cells in these infiltrations ore, in varying proportions, small lymphocytes, marginal zone-like B-cells, centrocyte-like cells, monotsit-like cells, plazma hujayrasi-like cells, and in >20% of cases large blastic B-cells. The malignant B-cells in these infiltrations are, like those in other marginal zone lymphomas, Marginal zone B-cells that typically express CD20, CD19, CD79va Bcl2 lekin emas CD10, CD5, CD23, yoki velosiped D1.

Patofiziologiya

Some 6-19% of NMZL cases have been reported to be associated with otoimmun kasalliklar kabi romatoid artrit, Syogren sindromi, otoimmun gemolitik anemiyava surunkali tiroidit. However, there is little evidence that these diseases contribute to the development of NMZL.^[74] Furthermore, the association of NMZL with gepatit C virusi infections found in earlier studies has not been confirmed in more recent studies.^[73] It therefore appears that the postulated role of chronic immune stimulation in promoting extranodal and splenic marginal zone lymphomas has not been clearly demonstrated in and may not apply to NMZL: the underlying initiating cause for developing this disease is currently unclear. Nonetheless, instigating B-cells in NMZL acquire genomic abnormalities that are thought to contribute to their malignant transformation. These genomic abnormalities include the following.

• Chromosomal abnormalities such as: 1) trisomiya of chromosome 3 (24% of cases) which causes the overexpression of FOXP1, NFKBIZva BCL6 whose protein products promote cellular proliferation and survival;^[71] 2) trisomy of chromosome 18 (~50% of cases) causing the overexpression of NFATC1^[71] whose protein product may act to promote cell proliferation and survival;^[75] 3) uncommonly, trisomy of chromosomes 7 and 12 and deletion of the long arm of chromosome 6 which have as yet unknown functional effects;^[71] and 4) xromosoma translokatsiyasi between the short (i.e. "p") arm of chromosome 2 at position 24 and the long (i.e. "q") arm of chromosome 14 at position 32, a translocation of as yet unknown functional consequence but not found in the other marginal zone lymphoma forms and therefore useful as a diagnostic marker for NMZL.^[76]
• Mutations in genes such as: 1) NOTCH2 (25% of cases)^[63] a membrane protein that regulates the development of marginal zone B-cells from their precursor cells and also is a tumor suppressor which acts to regulate cellar survival;^[69] 2) TNFAIP3 (5-15% of cases) whose product is a deubikuitinatsiya qiluvchi ferment that functions to suppress the NF-DB transkripsiya omili and thereby the NF-κB signaling pathway which controls cellular activation, proliferation, and survival;^[67] 3) BIRC3, which encodes the cIAP2 protein that functions to regulate cell death caused by apoptoz;^[67] 3) MYD88 (0-10% of cases) whose protein product indirectly regulates activation of the NF-DB cell signaling pathway;^[67] 4) KLF2 whose product protein is a transcription factor which indirectly regulates the NF-DB cell signaling pathway;^[67] 5) PTPRD whose product protein is a receptor tyrosine phosphatase bor tumor suppressor activity and indirectly regulates several signaling programs that regulate cell proliferation and responses to sitokinlar;^[67] and 5) in ~40% of cases one or more of various other genes such as MLL2, SIN3A, ARID1A, EP300, CREBBPva TBL1XR1) bor xromatinni qayta qurish shu bilan boshqa genlarning keng doirasini ifodalashni tartibga solish bo'yicha faoliyat.^[67]

Tashxis

NMZL diagnostikasi limfa tugunlarida va ba'zi hollarda suyak iligida neoplastik B hujayralarini aniqlashga bog'liq, ammo hech bo'lmaganda kasallikning dastlabki bosqichida tugundan tashqari organlarda emas. Ushbu neoplastik hujayralar marginal zonadagi lenfomalarga xos bo'lgan marker oqsillarini (oldingi bo'limga qarang) va aksariyat hollarda Patofiziologiya bo'limida ko'rsatilgan bir yoki bir nechta genomik anormalliklarni ifoda etishi kerak.^[71]

Davolash

NMZL uchun tavsiya etilgan davolash usullari kasallik holatiga bog'liq. Asemptomatik NMZL ishlatilishi mumkin hushyor kutish muntazam kuzatuvlar bilan har, masalan. 3-6 oy, kasallikning rivojlanishini tekshirish uchun. Shu bilan birga, lokalizatsiya qilingan kasallik, hatto asemptomatik bemorlarda ham ketma-ket jarrohlik yo'li bilan davolandi va keyinchalik mahalliy radioterapiya o'tkazildi. Lokalizatsiya bosqichidan o'tib tarqaladigan, tez sur'atlarda rivojlanib boradigan kasallik va simptomatik kasallikka aylanadigan kasallik bitta ximioterapiya vositasida davolangan (masalan.). kladribin, fludarabin, xlorambusil, yoki bendamustin); bitta immunoterapiya giyohvand moddalar (masalan, rituximab); ko'p dori-darmonli kimyoviy terapiya rejimi (masalan. CHOP) yoki kombinatsiyalangan ko'p sonli kimyoterapiya preparati va immunoterapiya preparatlari rejimi (ya'ni CHOP + rituximab). Ushbu rejimlarning birortasi yoki bir nechtasi boshqalarnikidan ustun ekanligi aniq emas.^[73]

Prognoz

NMZL - bu davolanib bo'lmaydigan, ammo nisbatan sustkashlik kasalligi deb hisoblanadi, u asta-sekin o'sib boruvchi, qaytalanuvchi yo'lni oladi. Uning prognozi ekstranodal va taloqning marginal zonasi limfomalarida kuzatilganidan bir oz yomonroq ko'rinadi^[71] ~ 15% odamlarning ko'proq agressiv lenfomaga o'tishi bilan, diffuz katta B hujayra lenfomasi, NMZL tashxisi qo'yilganidan keyin ~ 4,5 yil davomida.^[73] Turli tadkikotlarda kasallikka chalingan odamlarning 5 yillik hayot darajasi 62-90% ni tashkil qiladi.^[73]

Bolalar

Bolalarda NMZL tasniflangan Jahon Sog'liqni saqlash tashkiloti (2016) taqdimoti asosida NMZLning alohida varianti sifatida, gistologiya jalb qilingan limfa tugunlari va klinik kurs.^[73] > 60 ta nashr etilgan holatlarning 95% Pediatrik NMZL holatlarida> 90% asemptomatik, lokalizatsiya qilingan (I / II bosqich) kasallik sifatida bosh va bo'yin mintaqalari limfa tugunlari kengayishini o'z ichiga olgan o'spirin o'g'il bolalarda uchradi. Ushbu holatlarda autoimmun yoki patogen- qo'zg'atiladigan yallig'lanish kasalliklari. Ushbu topilmalarning barchasi bolalarda uchraydigan ekstranodal marginal zonadagi lenfomalarda ko'rilganlarga ziddir. Gistologik nuqtai nazardan, ishtirok etgan limfa tugunlari germinal markazlar odatda CD20 va ifoda etuvchi limfoid hujayralar tomonidan zararlangan limfa tugunlari CD43, ko'pincha (~ 50% hollarda) Bcl2 ni ifodalaydi va odatda CD10 ni ifoda etmaydi BCL6. Ushbu infiltratsiyalardagi chekka zonadagi B hujayralari kattalardagi NMZL bilan solishtirganda nisbatan kam genomik anormalliklarga ega. 21% hollarda 18-xromosoma trisomiyasi va kamdan-kam hollarda 3-xromosoma trisomiyasi qayd etilgan. Ushbu hujayralarda takroriy gen mutatsiyalari sodir bo'lmaganligi haqida xabar berilgan.^[77] Pediatrik NMZL kursi relaps darajasi past bo'lgan va odatda juda yaxshi natijaga ega bo'lgan kasallik bilan juda befarq.^[73] 12-18 yoshgacha bo'lgan kuzatuv periondlari shuni aniqladiki, bemorlarning umumiy omon qolish darajasi 100%, relaps darajasi esa ~ 4%.^[77] Pediatrik NMZL davolashda a ishlatilgan hushyor kutish strategiya, rituximab, kimyoviy terapiya va / yoki mahalliy nurlanish terapiyasi. Ehtiyotkorlik bilan kutish strategiyasi boshqa davolanishlar singari ham o'z samarasini berdi va shuning uchun kasallik uchun tavsiya etilgan dastlabki davolash usuli hisoblanadi.^[77]

So'nggi tadqiqotlar

B hujayra retseptorlari.

Kabi turli xil yangi dorilar B hujayra retseptorlari (qo'shni rasmga qarang) signalizatsiya blokerlari va ibritumomab tiuxetan (Zevlin) MZL uchun klinik sinovlarda sinovdan o'tkazilmoqda.^[78] Ushbu sinovlar o'rganilayotgan dorilarning dozalari va xavfsizligini aniqlashda muhim ahamiyatga ega. 2017 yil 19-yanvar holatiga ko'ra FDA MZL uchun birinchi maqsadli dori-darmonni tasdiqladi, ibrutinib.^[79] Ushbu preparat inhibisyon bilan ishlaydi Bruton tirozin kinazasi (BKT), bu tirik qolish uchun yadroga signallarni yuborishga qodir. Boshqacha qilib aytganda, bu o'sishni sekinlashtiradi B hujayralari.^[79] Vaksinalar sonini sezilarli darajada kamaytiradigan ishlab chiqilgan Helicobacter pylori ilgari ushbu bakteriyalar bilan kolonizatsiya qilingan hayvonlarning oshqozonida. Ushbu vaktsinalardan biri yoki bir nechtasi nazorat qilish uchun umidvor bo'lgan nomzodlar bo'lishi mumkin Helicobacter pylori odamlarda, shuningdek qishloq xo'jaligi va uy hayvonlarida yuqtirish.^[80]

Adabiyotlar

Tashqi havolalar

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