Pierwotny skórny chłoniak z komórek b
Patofizjologia i mechanizm

Pierwotne skórne chłoniaki z komórek B (PCBCL) to heterogenna grupa nowotworów limfoproliferacyjnych, stanowiąca 20-25% chłoniaków skórnych, wywodzących się z dojrzałych komórek B skóry. Patogeneza PCBCL jest wieloczynnikowa, z kluczową rolą przewlekłej stymulacji antygenowej prowadzącej do rozwoju skóry związanej tkanki limfoidalnej (SALT) i klonalnej proliferacji komórek B. Wyróżnia się podtypy, takie jak pierwotny skórny chłoniak z komórek strefy brzeżnej (PCMZL) z podkategoriami non-class switched i heavy chain class switched, pierwotny skórny chłoniak z ośrodków rozmnażania (PCFCL) oraz pierwotny skórny chłoniak rozlany z dużych komórek B typu kończynowego (PCDLBCL, LT). Mutacje genowe, m.in. CREBBP (40%), STAT6 (40%), TNFRSF14 (30%) w PCFCL oraz MYD88 L265P (60-70%) i inne zmiany w szlaku NFκB w PCDLBCL, LT, odgrywają istotną rolę w patogenezie i rokowaniu. Zakażenia Borrelia burgdorferi, EBV, HHV8 i HCV są potencjalnymi czynnikami etiologicznymi, choć dowody są ograniczone.

  1. Patogeneza pierwotnego skórnego chłoniaka z komórek B
    1. Wieloczynnikowa etiologia
    2. Rola przewlekłej stymulacji antygenowej
    3. Czynniki infekcyjne
    4. Czynniki genetyczne i molekularne
    5. Zaburzenia mechanizmów dojrzewania komórek B
    6. Profil ekspresji czynników transkrypcyjnych
    7. Mikrośrodowisko nowotworu
    8. Immunofenotyp
  2. Komórkowe mechanizmy patogenetyczne
    1. Rola czynników farmakologicznych
  3. Mechanizmy molekularne w podtypach PCBCL
    1. Pierwotny skórny chłoniak strefy brzeżnej (PCMZL)
    2. Pierwotny skórny chłoniak z ośrodków rozmnażania (PCFCL)
    3. Pierwotny skórny chłoniak rozlany z dużych komórek B typu kończynowego (PCDLBCL, LT)
  4. Implikacje terapeutyczne
    1. Kolejne rozdziały

Patogeneza pierwotnego skórnego chłoniaka z komórek B

Pierwotne skórne chłoniaki z komórek B (PCBCL – Primary Cutaneous B-cell Lymphomas) stanowią heterogeniczną grupę dojrzałych nowotworów limfoproliferacyjnych wywodzących się z komórek B, które pierwotnie zajmują skórę. Stanowią one około 20-25% wszystkich chłoniaków skórnych i rozwijają się z komórek B zlokalizowanych w skórze.12 Patogeneza i biologia PCBCL nie została jednoznacznie wyjaśniona, co stwarza potrzebę kompleksowych badań w tym zakresie.3

Wieloczynnikowa etiologia

Etiologia pierwotnych skórnych chłoniaków z komórek B wydaje się być wieloczynnikowa, a ich powstawanie prawdopodobnie wiąże się z przewlekłą stymulacją antygenową.4 Uważa się, że PCBCL rozpoczynają się jako reaktywne zapalne procesy limfoproliferacyjne, a limfomageneza zachodzi stopniowo. Przejście ze stanu przednowotworowego do nowotworowego wydaje się być determinowane przez:5

  • Zaburzenie równowagi między proliferacją komórek a apoptozą
  • Deregulację głównych szlaków biochemicznych odpowiedzialnych za przekazywanie sygnałów wewnątrzkomórkowych
  • Zaburzenia adhezji i migracji komórek
  • Ekspresję onkogenów i/lub zahamowanie genów supresorowych nowotworów

1

Rola przewlekłej stymulacji antygenowej

Przewlekła stymulacja antygenowa odgrywa kluczową rolę w patogenezie PCBCL. Skóra normalnie nie posiada związanej z nią populacji limfocytów B, jednak przewlekła stymulacja antygenowa przez antygen podany śródskórnie może prowadzić do rozwoju tkanki limfoidalnej związanej ze skórą (SALT – skin associated lymphoid tissue), a ostatecznie do pojawienia się klonu komórek B.6 Ten mechanizm jest analogiczny do roli przewlekłego zakażenia Helicobacter pylori w patogenezie chłoniaka żołądka typu MALT.7

W pierwotnym skórnym chłoniaku z komórek strefy brzeżnej (PCMZL) wyróżnia się dwie odrębne podkategorie:8

  • Nieprzełączony (non-class switched) – bardziej przypomina pozaskórny chłoniak strefy brzeżnej (MZL), powstaje w środowisku przewlekłego zapalenia typu Th1 ze zwiększoną produkcją cytokin związanych z Th1, w tym IFNγ i IL2
  • Przełączony (heavy chain class switched) – stanowi większość przypadków PCMZL, histologicznie różni się od pozaskórnego MZL i powstaje w środowisku przewlekłego zapalenia typu Th2

1

Czynniki infekcyjne

Zakażenia wirusowe i bakteryjne są uważane za czynniki predysponujące do rozwoju PCBCL, chociaż badania potwierdzające te założenia są nieliczne, a w większości przypadków czynnik etiologiczny pozostaje nieznany.9

Spośród czynników infekcyjnych najczęściej wymienia się:1011

  • Borrelia burgdorferi – związek z pierwotnym skórnym chłoniakiem strefy brzeżnej (PCMZL) jest przedmiotem dyskusji. Sekwencje DNA tego organizmu zostały znalezione w zmianach skórnych u niektórych pacjentów z PCMZL. Niektóre przypadki ustąpiły po antybiotykoterapii.121314
  • Wirusy z rodziny Herpes – szczególnie wirus Epsteina-Barr (EBV) i ludzki wirus Herpes typu 8 (HHV8) mogą odgrywać rolę w genezie niektórych chłoniaków, zwłaszcza tych występujących u osób z obniżoną odpornością.15
  • Wirus zapalenia wątroby typu C (HCV) – potencjalny związek z PCBCL.16

Czynniki genetyczne i molekularne

Badania molekularne wykazały odrębne aberracje chromosomalne i genomowe w różnych podtypach PCBCL, co dostarcza dalszych dowodów na ich kategoryzację w klasyfikacji WHO-EORTC jako oddzielnych jednostek.17

W przypadku pierwotnego skórnego chłoniaka z ośrodków rozmnażania (PCFCL) badania sekwencjonowania panel obejmujący 40 genów związanych z rozwojem komórek B i T oraz limfomagenezą wykazały najczęstsze zmiany w genach:18

  • CREBBP (40%)
  • STAT6 (40%)
  • TNFRSF14 (30%)
  • TP53 i PIM1 (po 20%)
  • Pojedyncze mutacje w siedmiu innych genach (TNFAIP3, BCL2, EP300, JAK3, KIT, KMT2D i TET2)

1

W pierwotnym skórnym chłoniaku rozlanym z dużych komórek B typu kończynowego (PCDLBCL, LT) występują mutacje w szlaku aktywowanych komórek B, podobnie jak w chłoniaku rozlanym z dużych komórek B ośrodkowego układu nerwowego. Zidentyfikowano liczne zmiany genetyczne:1920

  • Mutacje MYD88 L265P (60-70% przypadków)
  • Dodatkowe markery szlaku NFκB: CD79B, PIM1, TNFAIP3/A20 i CARD11

1

Mutacje w receptorze komórek B są związane z niższą odpowiedzią na R-polichemioterapię.21

Zaburzenia mechanizmów dojrzewania komórek B

Zmiany w mechanizmach nieodłącznie związanych z dojrzewaniem komórek B mogą być kluczowe w patogenezie PCMZL. Patogeneza większości chłoniaków nieziarniczych z komórek B jest w pewien sposób związana z błędami genetycznymi, takimi jak translokacje chromosomowe lub aberracyjna hipermutacja somatyczna (ASHM), które występują podczas procesu selekcji.22

Analiza tego zjawiska w tkankach pacjentów z PCMZL wykazała ASHM w regionach regulatorowych i kodujących w wielu proto-onkogenach w prawie wszystkich badanych próbkach PCMZL. Sugeruje to, że aberracyjne zdarzenia mutacyjne w połączeniu z załamaniem się ochronnych mechanizmów naprawczych w komórkach B ośrodków rozmnażania mogą również leżeć u podstaw powstawania bardziej indolentnych chłoniaków, takich jak PCMZL.23

Profil ekspresji czynników transkrypcyjnych

Badania wzorów ekspresji czynników transkrypcyjnych zaangażowanych w różne etapy rozwoju komórek B wykazały istotne różnice między podtypami PCBCL:24

  • W PCFCL i PCMZL obserwowano wzory ekspresji podobne do ich przypuszczalnych łagodnych odpowiedników – komórek B ośrodków rozmnażania i komórek B po ośrodkach rozmnażania – co może odzwierciedlać ich indolentny przebieg kliniczny i doskonałe rokowanie.
  • PCDLBCL, LT wykazuje aberracyjny wzór ekspresji czynników transkrypcyjnych z koekspresją Bcl-6 i Mum1/IRF4, markerów, które podczas normalnego rozwoju komórek B wzajemnie się wykluczają. Dodatkowo charakteryzuje się silną ekspresją FOXP1.

1

Ekspresja Mum1/IRF4 i FOXP1 silnie sugeruje, że nowotworowe komórki B w PCDLBCL, LT mają pochodzenie z aktywowanych komórek B (ABC), co jest zgodne z wynikami wcześniejszych badań mikromacierzy.25 Ten wzór ekspresji ABC prawdopodobnie przyczynia się do patogenezy i złego rokowania tego podtypu PCBCL.26

Mikrośrodowisko nowotworu

Mikrośrodowisko nowotworu w PCDLBCL, LT składa się z dwóch odrębnych populacji komórek:27

  • Komórki supresyjne pochodzenia szpikowego CD33+
  • Makrofagi M2 CD163+ z różną ekspresją związanego z błoną PD-L1 w obu populacjach komórek

W mikrośrodowisku chłoniaków wysokiego stopnia złośliwości obserwuje się również regulację w górę PD-L1/PD-L2, czego nie stwierdza się w chłoniakach o niskim stopniu złośliwości. Sugeruje to mechanizm ucieczki przed nadzorem immunologicznym, przyczyniający się do złego rokowania w PCDLBCL, LT.28

Immunofenotyp

Immunofenotyp komórek B strefy brzeżnej w PCMZL charakteryzuje się obecnością CD20, CD79a i Bcl-2 oraz brakiem CD5 i CD10.29 Natomiast w PCDLBCL, LT komórki wykazują ekspresję CD20 z rozlanym barwieniem BCL2 i MUM1. Ekspresja BCL6 jest zmienna, podczas gdy CD10 jest negatywny.30

Komórkowe mechanizmy patogenetyczne

DNA komórek zawiera instrukcje mówiące komórce, co ma robić. W zdrowych komórkach DNA daje instrukcje wzrostu i namnażania się w określonym tempie oraz instrukcje dotyczące czasu śmierci komórki. W komórkach nowotworowych zmiany w DNA dają inne instrukcje. Zmiany nakazują komórkom nowotworowym szybki wzrost i namnażanie się. Komórki nowotworowe mogą żyć, gdy zdrowe komórki powinny obumrzeć. Powoduje to powstanie zbyt wielu komórek.31

W pierwotnym skórnym chłoniaku z komórek B komórki nowotworowe gromadzą się w skórze. Komórki nowotworowe rzadko rozprzestrzeniają się na inne obszary ciała.32 Mechanizmy molekularne prowadzące do rozwoju chłoniaka obejmują:

  • Konstytutywną aktywację szlaków sygnałowych – podobnie jak w przypadku skórnych chłoniaków T-komórkowych, gdzie obserwuje się konstytutywną fosforylację Stat333
  • Zaburzenia apoptozy – niedawno zidentyfikowano nawracające mutacje dotyczące FAS, które wpływały na domenę śmierci białka regulującego apoptozę FAS/CD95 w 24 z 38 przypadków34
  • Zaburzenia immunologiczne – podobnie jak w zaawansowanych chłoniakach T-komórkowych, gdzie klon złośliwy prawdopodobnie odpowiada za wiele zaburzeń immunologicznych35

Rola czynników farmakologicznych

Chłoniaki skórne z komórek B były również opisywane u pacjentów leczonych metotreksatem, szczególnie z powodu reumatoidalnego zapalenia stawów.36 W wielu z tych przypadków udokumentowano obecność EBV w komórkach chłoniaka B, a regresja zmian nastąpiła po odstawieniu leku, co sugeruje, że immunosupresja indukowana metotreksatem odegrała decydującą rolę w wywołaniu limfoproliferacji.37

Niektóre przypadki PCMZL są związane z przyjmowaniem leków, w tym:38

  • Metotreksatu
  • Cyklosporyny
  • Leków przeciwdepresyjnych
  • Leków przeciwhistaminowych

1

Mechanizmy molekularne w podtypach PCBCL

Pierwotny skórny chłoniak strefy brzeżnej (PCMZL)

PCMZL jest chłoniakiem z komórek B wywodzącym się z dojrzałych, głównie po-germinalnych komórek B.39 Mechanizm spontanicznej regresji chłoniaków skórnych jest niejasny. Czynniki związane ze spontaniczną regresją obejmują przede wszystkim apoptozę, odpowiedź immunologiczną gospodarza i szczególne warunki mikrośrodowiska guza, takie jak obecność inhibitorów metaloproteinaz i angiogenezy oraz brak lub niedobór określonych białek.40

Niedawno Fujii i wsp. donieśli, że liczba komórek pozytywnych dla forkhead box P3 i komórek pozytywnych dla programowanej śmierci komórki 1 może być związana ze spontaniczną regresją. Innym prawdopodobnym czynnikiem jest nieadekwatna odpowiedź immunologiczna komórek T. Najnowsze doniesienia ujawniły, że niektóre mikroRNA mogą być stosowane jako markery prognostyczne.41

Pierwotny skórny chłoniak z ośrodków rozmnażania (PCFCL)

Etiologia PCFCL jest nieznana, ponieważ nie zidentyfikowano specyficznych mutacji genetycznych (w przeciwieństwie do systemowego chłoniaka grudkowego). Zaproponowano rolę lektyn pochodzących z bakterii komensalnych skóry w patogenezie tego rzadkiego dojrzałego chłoniaka z komórek B.42 Zaburzenia regulacji proliferacji komórek B ośrodków rozmnażania może odgrywać rolę w PCFCL.43

Dane molekularne potwierdzają, że PCFCL wykazuje odrębne mutacje somatyczne, które mogą pomóc w różnicowaniu PCFCL od pseudochłoniaka, a także od innych indolentnych i agresywnych skórnych chłoniaków z komórek B.44 Nakładające się zmiany molekularne i cechy immunofenotypowe w systemowym FBCL i PCFCL sugerują wspólne mechanizmy patogenezy.45

Pierwotny skórny chłoniak rozlany z dużych komórek B typu kończynowego (PCDLBCL, LT)

Etiologia PCDLBCL, LT jest słabo poznana, choć ciągłe postępy w badaniach genetycznych przyczyniły się do lepszego zrozumienia mechanizmów molekularnych zaangażowanych w patogenezę.46 Profil genetyczny PCDLBCL, LT jest podobny do chłoniaka rozlanego z dużych komórek B typu aktywowanych komórek B (ABC DLBCL) i chłoniaka rozlanego z dużych komórek B ośrodkowego układu nerwowego.47

PCDLBCL, LT wykazuje wysoce nawracające mutacje MYD88 (wariant p.L265P), PIM1 i CD79B, które są zaangażowane w szlaki sygnałowe NF-κB i receptora komórek B, podobnie jak w pierwotnym chłoniaku ośrodkowego układu nerwowego (PCNSL).48 Przypadki PCDLBCL, LT wykazują profil mutacyjny przypominający PCNSL, z wysokim odsetkiem (80%) mutacji w szlaku TLR MYD88 i/lub CD79B i TNFAIP3/A20.49

W PCDLBCL, LT obserwuje się specyficzny wzór ekspresji czynników transkrypcyjnych z koekspresją Bcl-6 i Mum1/IRF4 oraz silną ekspresją FOXP1, co sugeruje pochodzenie z aktywowanych komórek B.50 Marker Bcl-2 jest nadekspresjonowany w 85% PCDLBCL, LT i jest uważany za jeden z czynników związanych z gorszym rokowaniem.51

Implikacje terapeutyczne

Zrozumienie mechanizmów patogenetycznych PCBCL ma istotne implikacje terapeutyczne. W leczeniu PCBCL stosuje się m.in. rituksymab – chimeryczne przeciwciało mysio-ludzkie, które celuje w antygen CD20 występujący zarówno w normalnych, jak i nowotworowych komórkach B.52

Badania in vitro wykazały, że rituksymab indukuje lizę komórek B chłoniaka poprzez cytotoksyczność komórkową zależną od przeciwciał, aktywację dopełniacza i bezpośrednią indukcję apoptozy. Ten mechanizm nie zależy od układu immunologicznego i zachodzi, ponieważ region zmienny pochodzenia mysiego wiąże się z wysokim powinowactwem z antygenem CD20 ekspresjonowanym na złośliwych limfocytach B, zatrzymując ich proliferację i indukując apoptozę, prawdopodobnie poprzez transbłonowe kanały wapniowe.53

Wykazano również, że rituksymab indukuje odpowiedź antygenowo-specyficzną w komórkach T poprzez mechanizm immunizacji.54 Wiadomo również, że rituksymab działa poprzez białko bcl-2, które jest nadekspresjonowane w 85% PCDLBCL, LT.55

Mutacje w receptorze komórek B są związane z niższą odpowiedzią na R-polichemioterapię w PCDLBCL, LT.56 Wytyczne EORTC dotyczące postępowania w CBCL zalecają leczenie PCDLBCL, LT polichemioterapią z lub bez rituksymabu (schematy CHOP-like lub R-CHOP).57 Rola rituksymabu w monoterapii w PCDLBCL, LT nie jest dobrze zdefiniowana; wyniki przedstawione w literaturze sugerują, że istnieje wyraźna początkowa odpowiedź, ale nawroty i progresja choroby są częste.58

W przypadku indolentnych chłoniaków B-komórkowych, tj. PCFCL i PCMZL, uzyskuje się dobre wskaźniki odpowiedzi zarówno przy dożylnym, jak i wewnątrzzmianowym podawaniu rituksymabu, chociaż nawroty są częste.59 Zastosowanie wewnątrzzmianowe stało się powszechne w ostatnich latach, z podobnymi wynikami jak przy zastosowaniu dożylnym, ale z mniejszą liczbą działań niepożądanych i niższym kosztem.60

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  1. 09.04.2026
  2. www.leksykon.com.pl

Materiały źródłowe

  • #1 Cutaneous B-cell lymphomas – pathogenesis, diagnostic workup, and therapy – PubMed
    https://pubmed.ncbi.nlm.nih.gov/27992127/
    Cutaneous B-cell lymphomas (CBCLs) comprise a group of mature lymphoproliferative B-cell disorders that primarily affect the skin. […] Given that the pathogenesis and biology of CBCLs has not been conclusively elucidated, and given the limited therapeutic armamentarium available, there is great need for comprehensive research, especially with respect to DLBCL-LT.
  • #1
    https://pmc.ncbi.nlm.nih.gov/articles/PMC4631235/
    Primary cutaneous B-cell lymphomas are a heterogeneous group of mature B-cells neoplasms with tropism for the skin, whose biology and clinical course differ significantly from the equivalent nodal lymphomas. […] Although its physiopathology is still poorly understood, the origin appears to be multifactorial and its genesis probably involves chronic antigen stimulation, such as that associated with bacterial and viral infections. […] The physiopathology of PCBCL is only partially understood. It is believed that they begin as reactive inflammatory lymphoproliferative processes and that lymphomagenesis occurs in successive steps. Hence there are „borderline cases” in which it is difficult to distinguish between pseudolymphomas (reactive lymphoid hyperplasias) and real lymphomas. The transition from a pre-neoplastic to a neoplastic condition seems to be determined by imbalance between cell proliferation and apoptosis, deregulation of major biochemical pathways for intracellular signal transmission, cell adhesion and migration, as well as expression of oncogenes and/or inhibition of tumor suppressor genes.
  • #1 Pathology Outlines – Primary cutaneous marginal zone lymphoma / lymphoproliferative disorder
    https://www.pathologyoutlines.com/topic/skintumornonmelanocyticMALT.html
    B cell lymphoma derived from mature, predominantly postgerminal center B cells […] Etiology is poorly understood, although thought to evolve in the setting of cutaneous lymphoid hyperplasia resulting from a variety of antigenic triggers […] Chronic antigenic stimulation may lead to immune dysregulation (analogous to the role of chronic Helicobacter pylori infection in the pathogenesis of gastric MALT lymphoma) […] Two distinct subcategories […] Nonclass switched […] More closely resembles extracutaneous MZL in that it arises in the setting of chronic Th1 type inflammation with increased production of Th1 associated cytokines including IFNγ and IL2 […] Heavy chain class switched […] Majority of cutaneous MZL, is histologically distinct from extracutaneous MZL and arises in the setting of chronic Th2 type inflammation
  • #1 Panel Sequencing of Primary Cutaneous B-Cell Lymphoma
    https://www.mdpi.com/2072-6694/14/21/5274
    Recurrent somatic mutations are present in PCFBCL. Our panel included 40 genes, which are associated with B- and T-cell development, as well as lymphomagenesis. In 10 out of 12 analyzed cases, we identified genetic alterations within 15 of the selected 40 target genes. Within the clear-cut PCFBCL cases (n = 10), the most frequently detected alterations affected the CREBBP (40%), STAT6 (40%) and TNFRSF14 (30%) genes. Moreover, TP53 and PIM1 were each affected in two patients (20%). In single cases, mutations in seven further genes, affecting different cellular processes, were detected (TNFAIP3, BCL2, EP300, JAK3, KIT, KMT2D and TET2). […] To conclude, our molecular data support that PCFBCL shows distinct somatic mutations which may aid to differentiate PCFBCL from pseudo-lymphoma as well as from other indolent and aggressive cutaneous B-cell lymphomas. While the detected genetic alterations of PCFBCL did not turn out to harbor any prognostic value in our cohort, our molecular data may add adjunctive discriminatory features for diagnostic purposes on a molecular level.
  • #1
    https://link.springer.com/article/10.1007/s40257-022-00704-0
    Several genetic abnormalities have been identified and serve as diagnostic and prognostic markers. […] The genetic landscape of PCDLBCL, LT is similar to that of activated B-cell type diffuse large B-cell lymphoma and diffuse large B-cell lymphoma of the central nervous system with mutations in the activated B-cell pathway elicited with massive parallel sequencing. […] Mutations in MYD88 L265P (60-70% of cases) and additional NFB pathway markers CD79B, PIM1, TNFAIP3/A20, and CARD11 are also observed. […] These B-cell receptor mutations are associated with a lower response rate to R-polychemotherapy. […] The tumor microenvironment of PCDCBL, LT comprises two distinct cell populations: CD33+ myeloid-derived suppressor cells and CD163+ M2 macrophages with differential expressions of membrane-bound PD-L1 in both cell populations. […] Upregulation of PD-L1/PD-L2 is also observed within the microenvironment of high-grade lymphomas, and is not seen in low-grade lymphomas. […] The culmination of these findings suggests a mechanism of immune surveillance escape contributing to the poor prognosis in PCDLBCL, LT.
  • #1 Expression of B-cell transcription factors in primary cutaneous B-cell lymphoma | Modern Pathology
    https://www.nature.com/articles/3800650
    Expression patterns of eight transcription factors involved in different stages of B-cell development were investigated in a large group of primary cutaneous B-cell lymphomas and compared with expression patterns during normal B-cell development. […] Primary cutaneous large B-cell lymphomas, leg type showed aberrant coexpression of Bcl-6 and Mum1/IRF4 and in addition strong expression of FOXP1. Expression of FOXP1 and Mum1/IRF4 strongly suggests an activated B-cell type of origin. […] In conclusion, in primary cutaneous follicle center lymphoma and primary cutaneous marginal zone B-cell lymphoma expression patterns were observed similar to their supposed benign counterparts, germinal center B-cells and postgerminal center B-cells, respectively, which might reflect their indolent clinical behaviour and excellent prognosis. In contrast, the activated B-cell expression pattern in the group of primary cutaneous large B-cell lymphoma, leg type may contribute to its poor prognosis and Mum1/IRF4 and FOXP1 may serve as additional diagnostic markers for this type of primary cutaneous B-cell lymphoma.
  • #1 Pathology Outlines – Primary cutaneous marginal zone lymphoma / lymphoproliferative disorder
    https://www.pathologyoutlines.com/topic/skintumornonmelanocyticMALT.html
    Some cases associated with medications including methotrexate, cyclosporine, antidepressants and antihistamines […] Infectious disease associations have also included Helicobacter pylori, Hepatitis C and Epstein Barr virus […] Autoimmune disease associations include polyarteritis nodosa, Sjögren syndrome, rheumatoid arthritis, Hashimoto thyroiditis and ulcerative colitis […] Recurrent mutations involving FAS that affected the death domain of the apoptosis regulating FAS / CD95 protein were recently identified in 24 of 38 cases.
  • #2 About Cutaneous Lymphoma | Cutaneous Lymphoma Foundation
    https://www.clfoundation.org/
    Cutaneous B-cell lymphomas (CBCL) make up about 20-25% of all cutaneous lymphomas, and are cancers that develop from skin-based B-cells. There are 3 main types of CBCL; primary cutaneous follicle center (follicular) lymphoma, primary cutaneous marginal zone (MALT) lymphoma, and primary cutaneous diffuse large B-cell (DLBCL, leg type) lymphoma. Primary cutaneous follicle center and primary cutaneous marginal zone lymphomas are the most common forms of CBCL, and are slow growing or indolent types that respond well to mild treatments. […] Systemic or nodal B-cell lymphomas can secondarily involve the skin, and when a skin biopsy shows B-cell lymphoma it is very important to make sure that the lymphoma is truly coming from the skin and not from a systemic lymphoma that has spread to the skin. […] Primary cutaneous B-cell lymphomas (CBCLs) are a cutaneous lymphoma (a cancer of white blood cells) that affects B-cells in the skin.
  • #3 Cutaneous B-cell lymphomas – pathogenesis, diagnostic workup, and therapy – PubMed
    https://pubmed.ncbi.nlm.nih.gov/27992127/
    Cutaneous B-cell lymphomas (CBCLs) comprise a group of mature lymphoproliferative B-cell disorders that primarily affect the skin. […] Given that the pathogenesis and biology of CBCLs has not been conclusively elucidated, and given the limited therapeutic armamentarium available, there is great need for comprehensive research, especially with respect to DLBCL-LT.
  • #4
    https://pmc.ncbi.nlm.nih.gov/articles/PMC4631235/
    Primary cutaneous B-cell lymphomas are a heterogeneous group of mature B-cells neoplasms with tropism for the skin, whose biology and clinical course differ significantly from the equivalent nodal lymphomas. […] Although its physiopathology is still poorly understood, the origin appears to be multifactorial and its genesis probably involves chronic antigen stimulation, such as that associated with bacterial and viral infections. […] The physiopathology of PCBCL is only partially understood. It is believed that they begin as reactive inflammatory lymphoproliferative processes and that lymphomagenesis occurs in successive steps. Hence there are „borderline cases” in which it is difficult to distinguish between pseudolymphomas (reactive lymphoid hyperplasias) and real lymphomas. The transition from a pre-neoplastic to a neoplastic condition seems to be determined by imbalance between cell proliferation and apoptosis, deregulation of major biochemical pathways for intracellular signal transmission, cell adhesion and migration, as well as expression of oncogenes and/or inhibition of tumor suppressor genes.
  • #5
    https://pmc.ncbi.nlm.nih.gov/articles/PMC4631235/
    Primary cutaneous B-cell lymphomas are a heterogeneous group of mature B-cells neoplasms with tropism for the skin, whose biology and clinical course differ significantly from the equivalent nodal lymphomas. […] Although its physiopathology is still poorly understood, the origin appears to be multifactorial and its genesis probably involves chronic antigen stimulation, such as that associated with bacterial and viral infections. […] The physiopathology of PCBCL is only partially understood. It is believed that they begin as reactive inflammatory lymphoproliferative processes and that lymphomagenesis occurs in successive steps. Hence there are „borderline cases” in which it is difficult to distinguish between pseudolymphomas (reactive lymphoid hyperplasias) and real lymphomas. The transition from a pre-neoplastic to a neoplastic condition seems to be determined by imbalance between cell proliferation and apoptosis, deregulation of major biochemical pathways for intracellular signal transmission, cell adhesion and migration, as well as expression of oncogenes and/or inhibition of tumor suppressor genes.
  • #6 Cutaneous Marginal Zone Lymphoma : Pathogenesis
    https://www.webpathology.com/images/hematopathology/mature-b-cell-neoplasms—part-i/extranodal-marginal-zone-lymphoma/37509
    Cutaneous Marginal Zone Lymphoma (CMZL) – Pathogenesis: Skin normally does not have an associated B-cell lymphocyte population. Chronic antigenic stimulation from an intradermally-applied antigen can lead to the development of skin associated lymphoid tissue and eventually to the emergence of a B-cell clone. An association has been reported between a proportion of primary CMZL and infection by Borrelia burgdorferi. Some cases have resolved following antibiotic therapy. Rare cases of primary CMZL have occurred following tattoos, tick bites and vaccinations. […] The translocations reported in EMZL at other sites, including t(11;18), t(14;18), t(1;14), and t(3;14), are only rarely seen in primary CMZL.
  • #7 Pathology Outlines – Primary cutaneous marginal zone lymphoma / lymphoproliferative disorder
    https://www.pathologyoutlines.com/topic/skintumornonmelanocyticMALT.html
    B cell lymphoma derived from mature, predominantly postgerminal center B cells […] Etiology is poorly understood, although thought to evolve in the setting of cutaneous lymphoid hyperplasia resulting from a variety of antigenic triggers […] Chronic antigenic stimulation may lead to immune dysregulation (analogous to the role of chronic Helicobacter pylori infection in the pathogenesis of gastric MALT lymphoma) […] Two distinct subcategories […] Nonclass switched […] More closely resembles extracutaneous MZL in that it arises in the setting of chronic Th1 type inflammation with increased production of Th1 associated cytokines including IFNγ and IL2 […] Heavy chain class switched […] Majority of cutaneous MZL, is histologically distinct from extracutaneous MZL and arises in the setting of chronic Th2 type inflammation
  • #8 Pathology Outlines – Primary cutaneous marginal zone lymphoma / lymphoproliferative disorder
    https://www.pathologyoutlines.com/topic/skintumornonmelanocyticMALT.html
    B cell lymphoma derived from mature, predominantly postgerminal center B cells […] Etiology is poorly understood, although thought to evolve in the setting of cutaneous lymphoid hyperplasia resulting from a variety of antigenic triggers […] Chronic antigenic stimulation may lead to immune dysregulation (analogous to the role of chronic Helicobacter pylori infection in the pathogenesis of gastric MALT lymphoma) […] Two distinct subcategories […] Nonclass switched […] More closely resembles extracutaneous MZL in that it arises in the setting of chronic Th1 type inflammation with increased production of Th1 associated cytokines including IFNγ and IL2 […] Heavy chain class switched […] Majority of cutaneous MZL, is histologically distinct from extracutaneous MZL and arises in the setting of chronic Th2 type inflammation
  • #9
    https://pmc.ncbi.nlm.nih.gov/articles/PMC4631235/
    Chronic antigenic stimulation and viral and bacterial infections appear to be predisposing factors, but studies to support these assumptions are scarce and, in most cases, the etiologic agent is not known. […] Regarding viral infections, an important role of the herpes viruses, such as Epstein Barr virus (EBV) and Human Herpes Virus type 8 (HHV8), was noted in the genesis of some lymphomas, particularly in those occurring in immunocompromised individuals, such as in patients infected with human immunodeficiency virus (HIV) and in transplant recipients. […] Also noteworthy is the possible association between Hepatitis C Virus (HCV) infection and PCBCL. […] Concerning bacteria, PCMZL have been associated with Borrelia burgdorferi infection, although the subject is still controversy. […] Cutaneous B-cell lymphomas have also been described in patients treated with methotrexate, in particular for rheumatoid arthritis. […] In many of these cases, EBV has been documented in B-cells lymphoma and regression of lesions has occurred after discontinuation of the drug, suggesting that methotrexate induced immunosuppression have had a decisive role in triggering the lymphoproliferation.
  • #10
    https://pmc.ncbi.nlm.nih.gov/articles/PMC4631235/
    Chronic antigenic stimulation and viral and bacterial infections appear to be predisposing factors, but studies to support these assumptions are scarce and, in most cases, the etiologic agent is not known. […] Regarding viral infections, an important role of the herpes viruses, such as Epstein Barr virus (EBV) and Human Herpes Virus type 8 (HHV8), was noted in the genesis of some lymphomas, particularly in those occurring in immunocompromised individuals, such as in patients infected with human immunodeficiency virus (HIV) and in transplant recipients. […] Also noteworthy is the possible association between Hepatitis C Virus (HCV) infection and PCBCL. […] Concerning bacteria, PCMZL have been associated with Borrelia burgdorferi infection, although the subject is still controversy. […] Cutaneous B-cell lymphomas have also been described in patients treated with methotrexate, in particular for rheumatoid arthritis. […] In many of these cases, EBV has been documented in B-cells lymphoma and regression of lesions has occurred after discontinuation of the drug, suggesting that methotrexate induced immunosuppression have had a decisive role in triggering the lymphoproliferation.
  • #11 Pathology Outlines – Primary cutaneous marginal zone lymphoma / lymphoproliferative disorder
    https://www.pathologyoutlines.com/topic/skintumornonmelanocyticMALT.html
    Some cases associated with medications including methotrexate, cyclosporine, antidepressants and antihistamines […] Infectious disease associations have also included Helicobacter pylori, Hepatitis C and Epstein Barr virus […] Autoimmune disease associations include polyarteritis nodosa, Sjögren syndrome, rheumatoid arthritis, Hashimoto thyroiditis and ulcerative colitis […] Recurrent mutations involving FAS that affected the death domain of the apoptosis regulating FAS / CD95 protein were recently identified in 24 of 38 cases.
  • #12 Primary Cutaneous B-Cell Lymphomas
    https://atlasgeneticsoncology.org/haematological/1851/primary-cutaneous-b-cell-lymphomas?cookies_accepted=1
    Primary cutaneous B-cell lymphomas (PCBCL) are a heterogeneous group of mature B-cells neoplasms that present in the skin without evidence of nodal or systemic involvement. […] The exact etiology and pathogenesis of CBCL is poorly understood. However, dysregulation of an antigen-driven response and infectious etiologies have been proposed in some cases. Dysregulation of germinal center B-cell proliferation might play a role in PCFCL. Infection by Borrelia burgdorferi has been implicated as etiological factor in PCMZL since DNA sequences of this organism were found in skin lesions of some PCMZL cases. […] Molecular study of immunoglobulin genes rearrangement is detected in all subtypes that are valuable to document clonality and differentiate PCBCL from pseudolymphomas. […] These studies clearly demonstrate distinct chromosomal and genomic aberrations in PCFCL and PCDLBCL, LT which provides further support for their categorization in the WHO-EORTC classification as separate entities.
  • #13 Skin (cutaneous) B-cell lymphoma | Lymphoma Action
    https://lymphoma-action.org.uk/types-lymphoma-skin-lymphoma/skin-cutaneous-b-cell-lymphoma
    B-cell skin lymphomas are skin lymphomas that develop from B cells. […] Scientists dont know exactly what causes skin lymphoma but there are some factors that might increase your risk of developing it. […] There is a link between B-cell skin lymphoma and an infection called Borrelia burgdorferi. […] Most types of B-cell skin lymphomas are slow-growing (low-grade). […] Primary cutaneous follicle centre lymphoma is the most common type of B-cell skin lymphoma. […] Primary cutaneous marginal zone lymphoma is also a low-grade lymphoma. […] Primary cutaneous diffuse large B-cell lymphoma, leg-type, is a very rare, high-grade lymphoma. […] Primary cutaneous diffuse large B-cell lymphoma, leg type, is a high-grade skin lymphoma.
  • #14 Primary cutaneous B-cell lymphomas – Altmeyers Encyclopedia – Department Dermatology
    https://www.altmeyers.org/en/dermatology/primary-cutaneous-b-cell-lymphomas-121812
    Primary cutaneous B-cell lymphomas are neoplasms of the lymphatic system that exhibit a tissue-specific homing pattern with primary infiltration and manifestation in the skin. They exhibit a characteristic B-cell phenotype. […] The decisive factor for therapy and prognosis is whether it is a primary cutaneous B-cell lymphoma or a secondary skin involvement in the presence of nodal B-cell lymphoma! […] The association of primary cutaneous lymphomas (especially primary cutaneous B-cell lymphomas) with Borrelia antigens is remarkable. This applies to both B-cell lymphomas (prevalence is calculated at 7.3% for marginal zone lymphoma, 8.1% for follicular lymphoma, 7.5% for diffuse large B-cell lymphoma and 7.5% for follicular lymphoma) and T-cell lymphomas (prevalence for mycosis fungoides: 8%). Molecular tests for Borrelia are therefore justified in collectives from endemic areas (Travaligno A et al. 2020).
  • #15
    https://pmc.ncbi.nlm.nih.gov/articles/PMC4631235/
    Chronic antigenic stimulation and viral and bacterial infections appear to be predisposing factors, but studies to support these assumptions are scarce and, in most cases, the etiologic agent is not known. […] Regarding viral infections, an important role of the herpes viruses, such as Epstein Barr virus (EBV) and Human Herpes Virus type 8 (HHV8), was noted in the genesis of some lymphomas, particularly in those occurring in immunocompromised individuals, such as in patients infected with human immunodeficiency virus (HIV) and in transplant recipients. […] Also noteworthy is the possible association between Hepatitis C Virus (HCV) infection and PCBCL. […] Concerning bacteria, PCMZL have been associated with Borrelia burgdorferi infection, although the subject is still controversy. […] Cutaneous B-cell lymphomas have also been described in patients treated with methotrexate, in particular for rheumatoid arthritis. […] In many of these cases, EBV has been documented in B-cells lymphoma and regression of lesions has occurred after discontinuation of the drug, suggesting that methotrexate induced immunosuppression have had a decisive role in triggering the lymphoproliferation.
  • #16
    https://pmc.ncbi.nlm.nih.gov/articles/PMC4631235/
    Chronic antigenic stimulation and viral and bacterial infections appear to be predisposing factors, but studies to support these assumptions are scarce and, in most cases, the etiologic agent is not known. […] Regarding viral infections, an important role of the herpes viruses, such as Epstein Barr virus (EBV) and Human Herpes Virus type 8 (HHV8), was noted in the genesis of some lymphomas, particularly in those occurring in immunocompromised individuals, such as in patients infected with human immunodeficiency virus (HIV) and in transplant recipients. […] Also noteworthy is the possible association between Hepatitis C Virus (HCV) infection and PCBCL. […] Concerning bacteria, PCMZL have been associated with Borrelia burgdorferi infection, although the subject is still controversy. […] Cutaneous B-cell lymphomas have also been described in patients treated with methotrexate, in particular for rheumatoid arthritis. […] In many of these cases, EBV has been documented in B-cells lymphoma and regression of lesions has occurred after discontinuation of the drug, suggesting that methotrexate induced immunosuppression have had a decisive role in triggering the lymphoproliferation.
  • #17 Primary Cutaneous B-Cell Lymphomas
    https://atlasgeneticsoncology.org/haematological/1851/primary-cutaneous-b-cell-lymphomas?cookies_accepted=1
    Primary cutaneous B-cell lymphomas (PCBCL) are a heterogeneous group of mature B-cells neoplasms that present in the skin without evidence of nodal or systemic involvement. […] The exact etiology and pathogenesis of CBCL is poorly understood. However, dysregulation of an antigen-driven response and infectious etiologies have been proposed in some cases. Dysregulation of germinal center B-cell proliferation might play a role in PCFCL. Infection by Borrelia burgdorferi has been implicated as etiological factor in PCMZL since DNA sequences of this organism were found in skin lesions of some PCMZL cases. […] Molecular study of immunoglobulin genes rearrangement is detected in all subtypes that are valuable to document clonality and differentiate PCBCL from pseudolymphomas. […] These studies clearly demonstrate distinct chromosomal and genomic aberrations in PCFCL and PCDLBCL, LT which provides further support for their categorization in the WHO-EORTC classification as separate entities.
  • #18 Panel Sequencing of Primary Cutaneous B-Cell Lymphoma
    https://www.mdpi.com/2072-6694/14/21/5274
    Recurrent somatic mutations are present in PCFBCL. Our panel included 40 genes, which are associated with B- and T-cell development, as well as lymphomagenesis. In 10 out of 12 analyzed cases, we identified genetic alterations within 15 of the selected 40 target genes. Within the clear-cut PCFBCL cases (n = 10), the most frequently detected alterations affected the CREBBP (40%), STAT6 (40%) and TNFRSF14 (30%) genes. Moreover, TP53 and PIM1 were each affected in two patients (20%). In single cases, mutations in seven further genes, affecting different cellular processes, were detected (TNFAIP3, BCL2, EP300, JAK3, KIT, KMT2D and TET2). […] To conclude, our molecular data support that PCFBCL shows distinct somatic mutations which may aid to differentiate PCFBCL from pseudo-lymphoma as well as from other indolent and aggressive cutaneous B-cell lymphomas. While the detected genetic alterations of PCFBCL did not turn out to harbor any prognostic value in our cohort, our molecular data may add adjunctive discriminatory features for diagnostic purposes on a molecular level.
  • #19
    https://link.springer.com/article/10.1007/s40257-022-00704-0
    Several genetic abnormalities have been identified and serve as diagnostic and prognostic markers. […] The genetic landscape of PCDLBCL, LT is similar to that of activated B-cell type diffuse large B-cell lymphoma and diffuse large B-cell lymphoma of the central nervous system with mutations in the activated B-cell pathway elicited with massive parallel sequencing. […] Mutations in MYD88 L265P (60-70% of cases) and additional NFB pathway markers CD79B, PIM1, TNFAIP3/A20, and CARD11 are also observed. […] These B-cell receptor mutations are associated with a lower response rate to R-polychemotherapy. […] The tumor microenvironment of PCDCBL, LT comprises two distinct cell populations: CD33+ myeloid-derived suppressor cells and CD163+ M2 macrophages with differential expressions of membrane-bound PD-L1 in both cell populations. […] Upregulation of PD-L1/PD-L2 is also observed within the microenvironment of high-grade lymphomas, and is not seen in low-grade lymphomas. […] The culmination of these findings suggests a mechanism of immune surveillance escape contributing to the poor prognosis in PCDLBCL, LT.
  • #20 Integrative diagnosis of primary cutaneous large B-cell lymphomas supports the relevance of cell of origin profiling | PLOS One
    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0266978
    Primary cutaneous large B-cell lymphomas (PCLBCL) represent a diagnostic challenge because they are classified as PCLBCL, leg type (PCLBCL, LT) or primary cutaneous follicle centre lymphoma, large cell (PCFCL, LC), which differ by prognosis and therapeutic requirement. […] A cell-of-origin classification of PCLBCL by genomic profiling of a restricted set of frozen material indicated that PCFCL, LC exhibits a germinal centre (GC) signature, whereas PCLBCL, LT has a non-GC signature. […] PCLBCL, LT showed highly recurrent mutations of MYD88 (p.L265P variant), PIM1, and CD79B, which are involved in the NF-B and B-cell receptor signaling pathways, similar to primary central nervous system lymphoma (PCNSL). […] The data confirm our findings from Hans algorithm analysis of typical cases, and suggest that PCFCL, LC is of GC origin whereas PCLBCL, LT is of non-GC origin. […] Our PCLBCL, LT cases exhibited a mutational profile resembling that of PCNSL, with a high rate (80%) of mutations in the TLR MYD88 pathway and/or CD79B and TNFAIP3/A20.
  • #21
    https://link.springer.com/article/10.1007/s40257-022-00704-0
    Several genetic abnormalities have been identified and serve as diagnostic and prognostic markers. […] The genetic landscape of PCDLBCL, LT is similar to that of activated B-cell type diffuse large B-cell lymphoma and diffuse large B-cell lymphoma of the central nervous system with mutations in the activated B-cell pathway elicited with massive parallel sequencing. […] Mutations in MYD88 L265P (60-70% of cases) and additional NFB pathway markers CD79B, PIM1, TNFAIP3/A20, and CARD11 are also observed. […] These B-cell receptor mutations are associated with a lower response rate to R-polychemotherapy. […] The tumor microenvironment of PCDCBL, LT comprises two distinct cell populations: CD33+ myeloid-derived suppressor cells and CD163+ M2 macrophages with differential expressions of membrane-bound PD-L1 in both cell populations. […] Upregulation of PD-L1/PD-L2 is also observed within the microenvironment of high-grade lymphomas, and is not seen in low-grade lymphomas. […] The culmination of these findings suggests a mechanism of immune surveillance escape contributing to the poor prognosis in PCDLBCL, LT.
  • #22 Recurrent localized primary cutaneous marginal-zone B-cell lymphoma
    https://escholarship.org/uc/item/3c78x4gz
    Primary cutaneous B cell lymphomas are comprised of a heterogeneous group of diseases with various clinical, histopathologic, and immunophenotypic properties. […] The immunophenotype of the marginal-zone B lymphocytes in PCMZL is distinguished by the presence of CD20, CD79a, and Bcl-2 and the absence of CD5 and CD10. […] Although the pathogenesis of PCMZL remains unclear, an infectious agent that leads to chronic antigenic stimulation has been purported as potentially causative. […] Alterations in mechanisms inherent to B cell maturation may be central to the pathogenesis of PCMZL. […] The pathogenesis of most non-Hodgkin B cell lymphomas has been thought to be in some way associated with genetic errors, such as chromosomal translocations or aberrant somatic hypermutation (ASHM), which occur during this selection process.
  • #23 Recurrent localized primary cutaneous marginal-zone B-cell lymphoma
    https://escholarship.org/uc/item/3c78x4gz
    An analysis of this phenomena in tissue from PCMZL patients found ASHM in the regulatory and coding regions in a number of proto-oncogenes in nearly all of the PCMZL samples that were evaluated. […] This observation suggests that aberrant mutation events coupled with a breakdown in the protective repair mechanisms in germinal center B cells also may underlie the genesis of more indolent lymphomas such as PCMZL. […] It is as yet unclear as to why this type of lymphoma remains largely confined to the skin.
  • #24 Expression of B-cell transcription factors in primary cutaneous B-cell lymphoma | Modern Pathology
    https://www.nature.com/articles/3800650
    Expression patterns of eight transcription factors involved in different stages of B-cell development were investigated in a large group of primary cutaneous B-cell lymphomas and compared with expression patterns during normal B-cell development. […] Primary cutaneous large B-cell lymphomas, leg type showed aberrant coexpression of Bcl-6 and Mum1/IRF4 and in addition strong expression of FOXP1. Expression of FOXP1 and Mum1/IRF4 strongly suggests an activated B-cell type of origin. […] In conclusion, in primary cutaneous follicle center lymphoma and primary cutaneous marginal zone B-cell lymphoma expression patterns were observed similar to their supposed benign counterparts, germinal center B-cells and postgerminal center B-cells, respectively, which might reflect their indolent clinical behaviour and excellent prognosis. In contrast, the activated B-cell expression pattern in the group of primary cutaneous large B-cell lymphoma, leg type may contribute to its poor prognosis and Mum1/IRF4 and FOXP1 may serve as additional diagnostic markers for this type of primary cutaneous B-cell lymphoma.
  • #25 Expression of B-cell transcription factors in primary cutaneous B-cell lymphoma | Modern Pathology
    https://www.nature.com/articles/3800650
    Recent studies have also established the significance of B-cell transcription factors in the diagnosis and pathogenesis of primary cutaneous B-cell lymphomas. […] The main finding of the study was that primary cutaneous large B-cell lymphoma, leg type showed an aberrant expression pattern of B-cell transcription factors with coexpression of Bcl-6 and Mum1/IRF4, markers which appear mutually exclusive during normal B-cell development. […] Expression of Mum1/IRF4 and FOXP1 strongly suggests that the neoplastic B-cells in primary cutaneous large B-cell lymphoma, leg type have an activated B-cell origin, which is consistent with the results of our previous microarray study. […] The strong expression of Mum1/IRF4 and FOXP1 in all primary cutaneous large B-cell lymphoma, leg type, and the almost absent expression of these markers in the group of primary cutaneous follicle center lymphoma suggest that Mum1/IRF4 and FOXP1 may serve as useful diagnostic markers for primary cutaneous large B-cell lymphoma, leg type. […] In contrast, an ABC-type expression pattern was observed in primary cutaneous large B-cell lymphoma, leg type, which is likely to contribute to the pathogenesis and poor prognosis of this primary cutaneous B-cell lymphoma subtype.
  • #26 Expression of B-cell transcription factors in primary cutaneous B-cell lymphoma | Modern Pathology
    https://www.nature.com/articles/3800650
    Recent studies have also established the significance of B-cell transcription factors in the diagnosis and pathogenesis of primary cutaneous B-cell lymphomas. […] The main finding of the study was that primary cutaneous large B-cell lymphoma, leg type showed an aberrant expression pattern of B-cell transcription factors with coexpression of Bcl-6 and Mum1/IRF4, markers which appear mutually exclusive during normal B-cell development. […] Expression of Mum1/IRF4 and FOXP1 strongly suggests that the neoplastic B-cells in primary cutaneous large B-cell lymphoma, leg type have an activated B-cell origin, which is consistent with the results of our previous microarray study. […] The strong expression of Mum1/IRF4 and FOXP1 in all primary cutaneous large B-cell lymphoma, leg type, and the almost absent expression of these markers in the group of primary cutaneous follicle center lymphoma suggest that Mum1/IRF4 and FOXP1 may serve as useful diagnostic markers for primary cutaneous large B-cell lymphoma, leg type. […] In contrast, an ABC-type expression pattern was observed in primary cutaneous large B-cell lymphoma, leg type, which is likely to contribute to the pathogenesis and poor prognosis of this primary cutaneous B-cell lymphoma subtype.
  • #27
    https://link.springer.com/article/10.1007/s40257-022-00704-0
    Several genetic abnormalities have been identified and serve as diagnostic and prognostic markers. […] The genetic landscape of PCDLBCL, LT is similar to that of activated B-cell type diffuse large B-cell lymphoma and diffuse large B-cell lymphoma of the central nervous system with mutations in the activated B-cell pathway elicited with massive parallel sequencing. […] Mutations in MYD88 L265P (60-70% of cases) and additional NFB pathway markers CD79B, PIM1, TNFAIP3/A20, and CARD11 are also observed. […] These B-cell receptor mutations are associated with a lower response rate to R-polychemotherapy. […] The tumor microenvironment of PCDCBL, LT comprises two distinct cell populations: CD33+ myeloid-derived suppressor cells and CD163+ M2 macrophages with differential expressions of membrane-bound PD-L1 in both cell populations. […] Upregulation of PD-L1/PD-L2 is also observed within the microenvironment of high-grade lymphomas, and is not seen in low-grade lymphomas. […] The culmination of these findings suggests a mechanism of immune surveillance escape contributing to the poor prognosis in PCDLBCL, LT.
  • #28
    https://link.springer.com/article/10.1007/s40257-022-00704-0
    Several genetic abnormalities have been identified and serve as diagnostic and prognostic markers. […] The genetic landscape of PCDLBCL, LT is similar to that of activated B-cell type diffuse large B-cell lymphoma and diffuse large B-cell lymphoma of the central nervous system with mutations in the activated B-cell pathway elicited with massive parallel sequencing. […] Mutations in MYD88 L265P (60-70% of cases) and additional NFB pathway markers CD79B, PIM1, TNFAIP3/A20, and CARD11 are also observed. […] These B-cell receptor mutations are associated with a lower response rate to R-polychemotherapy. […] The tumor microenvironment of PCDCBL, LT comprises two distinct cell populations: CD33+ myeloid-derived suppressor cells and CD163+ M2 macrophages with differential expressions of membrane-bound PD-L1 in both cell populations. […] Upregulation of PD-L1/PD-L2 is also observed within the microenvironment of high-grade lymphomas, and is not seen in low-grade lymphomas. […] The culmination of these findings suggests a mechanism of immune surveillance escape contributing to the poor prognosis in PCDLBCL, LT.
  • #29 Recurrent localized primary cutaneous marginal-zone B-cell lymphoma
    https://escholarship.org/uc/item/3c78x4gz
    Primary cutaneous B cell lymphomas are comprised of a heterogeneous group of diseases with various clinical, histopathologic, and immunophenotypic properties. […] The immunophenotype of the marginal-zone B lymphocytes in PCMZL is distinguished by the presence of CD20, CD79a, and Bcl-2 and the absence of CD5 and CD10. […] Although the pathogenesis of PCMZL remains unclear, an infectious agent that leads to chronic antigenic stimulation has been purported as potentially causative. […] Alterations in mechanisms inherent to B cell maturation may be central to the pathogenesis of PCMZL. […] The pathogenesis of most non-Hodgkin B cell lymphomas has been thought to be in some way associated with genetic errors, such as chromosomal translocations or aberrant somatic hypermutation (ASHM), which occur during this selection process.
  • #30 Primary cutaneous diffuse large B cell lymphoma pathology
    https://dermnetnz.org/topics/primary-cutaneous-diffuse-large-b-cell-lymphoma-pathology
    Within the group of cutaneous B cell lymphomas, further categorisation includes primary cutaneous diffuse large B cell lymphoma, leg type; primary cutaneous diffuse large B cell lymphoma, other; plasmablastic lymphoma and T cell-rich large B cell lymphoma. […] The primary cutaneous B cell lymphoma leg type indicates a poor prognostic group typically seen on the lower legs of the elderly and is illustrated in the figures below. […] Scanning power view of the histology of primary cutaneous diffuse large B cell lymphoma is of a dense superficial and deep cellular infiltrate. Higher power identifies a dense atypical lymphocytic proliferation, which frequently extends into the subcutaneous tissue. […] The lymphocytes are large centroblast-like and immunoblast-like cells with non-cleaved nuclei and prominent nucleoli. […] Immunostaining reveals a CD20 positive B cell population with diffuse BCL2 and MUM1 staining. BCL6 expression is variable while CD10 is negative.
  • #31 Cutaneous B-cell lymphoma – Symptoms and causes – Mayo Clinic
    https://www.mayoclinic.org/diseases-conditions/cutaneous-b-cell-lymphoma/symptoms-causes/syc-20577439
    Cutaneous B-cell lymphoma is a cancer that starts in the white blood cells and attacks the skin. It often causes a lump or group of lumps on the skin. […] Cutaneous B-cell lymphoma happens when B lymphocytes develop changes in their DNA. A cell’s DNA holds the instructions that tell the cell what to do. In healthy cells, the DNA gives instructions to grow and multiply at a set rate. The instructions tell the cells to die at a set time. In cancer cells, the DNA changes give different instructions. The changes tell the cancer cells to grow and multiply quickly. Cancer cells can keep living when healthy cells would die. This causes too many cells. […] In cutaneous B-cell lymphoma, the cancer cells build up in the skin. The cancer cells rarely spread to other areas of the body.
  • #32 Cutaneous B-cell lymphoma – Symptoms and causes – Mayo Clinic
    https://www.mayoclinic.org/diseases-conditions/cutaneous-b-cell-lymphoma/symptoms-causes/syc-20577439
    Cutaneous B-cell lymphoma is a cancer that starts in the white blood cells and attacks the skin. It often causes a lump or group of lumps on the skin. […] Cutaneous B-cell lymphoma happens when B lymphocytes develop changes in their DNA. A cell’s DNA holds the instructions that tell the cell what to do. In healthy cells, the DNA gives instructions to grow and multiply at a set rate. The instructions tell the cells to die at a set time. In cancer cells, the DNA changes give different instructions. The changes tell the cancer cells to grow and multiply quickly. Cancer cells can keep living when healthy cells would die. This causes too many cells. […] In cutaneous B-cell lymphoma, the cancer cells build up in the skin. The cancer cells rarely spread to other areas of the body.
  • #33
    https://www.jci.org/articles/view/24826
    The state of activation of the malignant T cell in MF/SS is evidenced by the constitutive phosphorylation of Stat3 that is observed. […] Although it is unknown what precisely triggers the constitutive activation of a population of skin-homing, mature CD4+ T cells in MF/SS, this may result in a skewed Th2-cytokine expression profile and subsequent inflammatory disease and immune dysregulation. […] The malignant CD4+ T cells observed in most cases of MF/SS appear to exhibit a Th2 phenotype. […] The end results of alterations in cytokine expression pathways during progressive MF/SS are multiple abnormalities in cellular immunity. […] Even in advanced disease, the host response, although effete, may play a role, albeit small, in containment of disease progression. […] The malignant clone is probably responsible for much of the immune dysregulation that occurs in SS.
  • #34 Pathology Outlines – Primary cutaneous marginal zone lymphoma / lymphoproliferative disorder
    https://www.pathologyoutlines.com/topic/skintumornonmelanocyticMALT.html
    Some cases associated with medications including methotrexate, cyclosporine, antidepressants and antihistamines […] Infectious disease associations have also included Helicobacter pylori, Hepatitis C and Epstein Barr virus […] Autoimmune disease associations include polyarteritis nodosa, Sjögren syndrome, rheumatoid arthritis, Hashimoto thyroiditis and ulcerative colitis […] Recurrent mutations involving FAS that affected the death domain of the apoptosis regulating FAS / CD95 protein were recently identified in 24 of 38 cases.
  • #35
    https://www.jci.org/articles/view/24826
    The state of activation of the malignant T cell in MF/SS is evidenced by the constitutive phosphorylation of Stat3 that is observed. […] Although it is unknown what precisely triggers the constitutive activation of a population of skin-homing, mature CD4+ T cells in MF/SS, this may result in a skewed Th2-cytokine expression profile and subsequent inflammatory disease and immune dysregulation. […] The malignant CD4+ T cells observed in most cases of MF/SS appear to exhibit a Th2 phenotype. […] The end results of alterations in cytokine expression pathways during progressive MF/SS are multiple abnormalities in cellular immunity. […] Even in advanced disease, the host response, although effete, may play a role, albeit small, in containment of disease progression. […] The malignant clone is probably responsible for much of the immune dysregulation that occurs in SS.
  • #36
    https://pmc.ncbi.nlm.nih.gov/articles/PMC4631235/
    Chronic antigenic stimulation and viral and bacterial infections appear to be predisposing factors, but studies to support these assumptions are scarce and, in most cases, the etiologic agent is not known. […] Regarding viral infections, an important role of the herpes viruses, such as Epstein Barr virus (EBV) and Human Herpes Virus type 8 (HHV8), was noted in the genesis of some lymphomas, particularly in those occurring in immunocompromised individuals, such as in patients infected with human immunodeficiency virus (HIV) and in transplant recipients. […] Also noteworthy is the possible association between Hepatitis C Virus (HCV) infection and PCBCL. […] Concerning bacteria, PCMZL have been associated with Borrelia burgdorferi infection, although the subject is still controversy. […] Cutaneous B-cell lymphomas have also been described in patients treated with methotrexate, in particular for rheumatoid arthritis. […] In many of these cases, EBV has been documented in B-cells lymphoma and regression of lesions has occurred after discontinuation of the drug, suggesting that methotrexate induced immunosuppression have had a decisive role in triggering the lymphoproliferation.
  • #37
    https://pmc.ncbi.nlm.nih.gov/articles/PMC4631235/
    Chronic antigenic stimulation and viral and bacterial infections appear to be predisposing factors, but studies to support these assumptions are scarce and, in most cases, the etiologic agent is not known. […] Regarding viral infections, an important role of the herpes viruses, such as Epstein Barr virus (EBV) and Human Herpes Virus type 8 (HHV8), was noted in the genesis of some lymphomas, particularly in those occurring in immunocompromised individuals, such as in patients infected with human immunodeficiency virus (HIV) and in transplant recipients. […] Also noteworthy is the possible association between Hepatitis C Virus (HCV) infection and PCBCL. […] Concerning bacteria, PCMZL have been associated with Borrelia burgdorferi infection, although the subject is still controversy. […] Cutaneous B-cell lymphomas have also been described in patients treated with methotrexate, in particular for rheumatoid arthritis. […] In many of these cases, EBV has been documented in B-cells lymphoma and regression of lesions has occurred after discontinuation of the drug, suggesting that methotrexate induced immunosuppression have had a decisive role in triggering the lymphoproliferation.
  • #38 Pathology Outlines – Primary cutaneous marginal zone lymphoma / lymphoproliferative disorder
    https://www.pathologyoutlines.com/topic/skintumornonmelanocyticMALT.html
    Some cases associated with medications including methotrexate, cyclosporine, antidepressants and antihistamines […] Infectious disease associations have also included Helicobacter pylori, Hepatitis C and Epstein Barr virus […] Autoimmune disease associations include polyarteritis nodosa, Sjögren syndrome, rheumatoid arthritis, Hashimoto thyroiditis and ulcerative colitis […] Recurrent mutations involving FAS that affected the death domain of the apoptosis regulating FAS / CD95 protein were recently identified in 24 of 38 cases.
  • #39 Pathology Outlines – Primary cutaneous marginal zone lymphoma / lymphoproliferative disorder
    https://www.pathologyoutlines.com/topic/skintumornonmelanocyticMALT.html
    B cell lymphoma derived from mature, predominantly postgerminal center B cells […] Etiology is poorly understood, although thought to evolve in the setting of cutaneous lymphoid hyperplasia resulting from a variety of antigenic triggers […] Chronic antigenic stimulation may lead to immune dysregulation (analogous to the role of chronic Helicobacter pylori infection in the pathogenesis of gastric MALT lymphoma) […] Two distinct subcategories […] Nonclass switched […] More closely resembles extracutaneous MZL in that it arises in the setting of chronic Th1 type inflammation with increased production of Th1 associated cytokines including IFNγ and IL2 […] Heavy chain class switched […] Majority of cutaneous MZL, is histologically distinct from extracutaneous MZL and arises in the setting of chronic Th2 type inflammation
  • #40 Primary cutaneous marginal zone B-cell lymphoma with unusual manifestation and spontaneous regression – Indian Journal of Dermatology, Venereology and Leprology
    https://ijdvl.com/primary-cutaneous-marginal-zone-b-cell-lymphoma-with-unusual-manifestation-and-spontaneous-regression/
    Primary cutaneous marginal zone B-cell lymphoma is a low-grade B-cell lymphoma and runs an indolent course. The histological examination usually reveals dermal confluent nodular or diffuse lymphocytic infiltrates composed of small lymphocytes, lymphoplasmacytoid cells, mature plasma cells and reactive germinal centers with tingible body macrophages. The marginal zone B cells express CD20, CD79a and Bcl-2, and are negative for CD5, CD10 and Bcl-6, which may be useful in differentiating it from primary cutaneous follicle center lymphoma. Immunoglobulin heavy chain genes are clonally rearranged. […] The mechanism of spontaneous resolution of cutaneous lymphoma is unclear. Factors associated with spontaneous regression primarily include apoptosis, the host’s immune response and particular conditions of the tumor microenvironment, such as the presence of inhibitors of metalloproteinases and angiogenesis and the absence or scarcity of specific proteins. Recently, Fujii et al. reported that numbers of forkhead box P3-positive cells and programmed cell death 1-positive cells may be associated with spontaneous regression. Other probable factor includes an inadequate T-cell immune response. Recent reports revealed that some microRNAs can be used as prognostic markers.
  • #41 Primary cutaneous marginal zone B-cell lymphoma with unusual manifestation and spontaneous regression – Indian Journal of Dermatology, Venereology and Leprology
    https://ijdvl.com/primary-cutaneous-marginal-zone-b-cell-lymphoma-with-unusual-manifestation-and-spontaneous-regression/
    Primary cutaneous marginal zone B-cell lymphoma is a low-grade B-cell lymphoma and runs an indolent course. The histological examination usually reveals dermal confluent nodular or diffuse lymphocytic infiltrates composed of small lymphocytes, lymphoplasmacytoid cells, mature plasma cells and reactive germinal centers with tingible body macrophages. The marginal zone B cells express CD20, CD79a and Bcl-2, and are negative for CD5, CD10 and Bcl-6, which may be useful in differentiating it from primary cutaneous follicle center lymphoma. Immunoglobulin heavy chain genes are clonally rearranged. […] The mechanism of spontaneous resolution of cutaneous lymphoma is unclear. Factors associated with spontaneous regression primarily include apoptosis, the host’s immune response and particular conditions of the tumor microenvironment, such as the presence of inhibitors of metalloproteinases and angiogenesis and the absence or scarcity of specific proteins. Recently, Fujii et al. reported that numbers of forkhead box P3-positive cells and programmed cell death 1-positive cells may be associated with spontaneous regression. Other probable factor includes an inadequate T-cell immune response. Recent reports revealed that some microRNAs can be used as prognostic markers.
  • #42
    https://link.springer.com/article/10.1007/s40257-022-00704-0
    Primary cutaneous B-cell lymphomas (pCBCLs) constitute a heterogeneous group of extra-nodal B-cell non-Hodgkin lymphomas (B-NHLs). […] The etiology of PCMZL remains unknown but likely occurs in the setting of chronic antigen stimulation. […] The association of PCMZL with Borrelia burgdorferi is debated, as only European cases have been described. […] The etiology of PCFCL is unknown as no specific genetic mutations have been identified (unlike in systemic follicular BCL). There is a proposed role for lectins from commensal skin bacteria in the pathogenesis of this rare mature B-cell lymphoma. […] The etiology of PCDLBCL, LT is poorly understood, though continued advancements in genetic studies have contributed to an enhanced understanding of the molecular mechanisms involved in the pathogenesis.
  • #43 Primary Cutaneous B-Cell Lymphomas
    https://atlasgeneticsoncology.org/haematological/1851/primary-cutaneous-b-cell-lymphomas?cookies_accepted=1
    Primary cutaneous B-cell lymphomas (PCBCL) are a heterogeneous group of mature B-cells neoplasms that present in the skin without evidence of nodal or systemic involvement. […] The exact etiology and pathogenesis of CBCL is poorly understood. However, dysregulation of an antigen-driven response and infectious etiologies have been proposed in some cases. Dysregulation of germinal center B-cell proliferation might play a role in PCFCL. Infection by Borrelia burgdorferi has been implicated as etiological factor in PCMZL since DNA sequences of this organism were found in skin lesions of some PCMZL cases. […] Molecular study of immunoglobulin genes rearrangement is detected in all subtypes that are valuable to document clonality and differentiate PCBCL from pseudolymphomas. […] These studies clearly demonstrate distinct chromosomal and genomic aberrations in PCFCL and PCDLBCL, LT which provides further support for their categorization in the WHO-EORTC classification as separate entities.
  • #44 Panel Sequencing of Primary Cutaneous B-Cell Lymphoma
    https://www.mdpi.com/2072-6694/14/21/5274
    Recurrent somatic mutations are present in PCFBCL. Our panel included 40 genes, which are associated with B- and T-cell development, as well as lymphomagenesis. In 10 out of 12 analyzed cases, we identified genetic alterations within 15 of the selected 40 target genes. Within the clear-cut PCFBCL cases (n = 10), the most frequently detected alterations affected the CREBBP (40%), STAT6 (40%) and TNFRSF14 (30%) genes. Moreover, TP53 and PIM1 were each affected in two patients (20%). In single cases, mutations in seven further genes, affecting different cellular processes, were detected (TNFAIP3, BCL2, EP300, JAK3, KIT, KMT2D and TET2). […] To conclude, our molecular data support that PCFBCL shows distinct somatic mutations which may aid to differentiate PCFBCL from pseudo-lymphoma as well as from other indolent and aggressive cutaneous B-cell lymphomas. While the detected genetic alterations of PCFBCL did not turn out to harbor any prognostic value in our cohort, our molecular data may add adjunctive discriminatory features for diagnostic purposes on a molecular level.
  • #45 Panel Sequencing of Primary Cutaneous B-Cell Lymphoma
    https://www.mdpi.com/2072-6694/14/21/5274
    Our findings are in line with previous data that clearly separate these lymphoma subtypes, by means of molecular profiling, as belonging to biologically distinct entities. To conclude, our deep sequencing data revealed recurrent mutations in PCFBCL, such as in TNFRSF14, CREBBP and STAT6, thus classifying this lymphoma subtype as a distinct lymphoma entity within the spectrum of cutaneous lymphomas based on molecular grounds. Beyond already known genetic alterations, we detected novel mutations in genes such as BCL2 which impact cardinal mechanisms of tumorigenesis. Overlapping molecular alterations and immuno-phenotypical features in systemic FBCL and PCFBCL imply common mechanisms of pathogenesis.
  • #46
    https://link.springer.com/article/10.1007/s40257-022-00704-0
    Primary cutaneous B-cell lymphomas (pCBCLs) constitute a heterogeneous group of extra-nodal B-cell non-Hodgkin lymphomas (B-NHLs). […] The etiology of PCMZL remains unknown but likely occurs in the setting of chronic antigen stimulation. […] The association of PCMZL with Borrelia burgdorferi is debated, as only European cases have been described. […] The etiology of PCFCL is unknown as no specific genetic mutations have been identified (unlike in systemic follicular BCL). There is a proposed role for lectins from commensal skin bacteria in the pathogenesis of this rare mature B-cell lymphoma. […] The etiology of PCDLBCL, LT is poorly understood, though continued advancements in genetic studies have contributed to an enhanced understanding of the molecular mechanisms involved in the pathogenesis.
  • #47
    https://link.springer.com/article/10.1007/s40257-022-00704-0
    Several genetic abnormalities have been identified and serve as diagnostic and prognostic markers. […] The genetic landscape of PCDLBCL, LT is similar to that of activated B-cell type diffuse large B-cell lymphoma and diffuse large B-cell lymphoma of the central nervous system with mutations in the activated B-cell pathway elicited with massive parallel sequencing. […] Mutations in MYD88 L265P (60-70% of cases) and additional NFB pathway markers CD79B, PIM1, TNFAIP3/A20, and CARD11 are also observed. […] These B-cell receptor mutations are associated with a lower response rate to R-polychemotherapy. […] The tumor microenvironment of PCDCBL, LT comprises two distinct cell populations: CD33+ myeloid-derived suppressor cells and CD163+ M2 macrophages with differential expressions of membrane-bound PD-L1 in both cell populations. […] Upregulation of PD-L1/PD-L2 is also observed within the microenvironment of high-grade lymphomas, and is not seen in low-grade lymphomas. […] The culmination of these findings suggests a mechanism of immune surveillance escape contributing to the poor prognosis in PCDLBCL, LT.
  • #48 Integrative diagnosis of primary cutaneous large B-cell lymphomas supports the relevance of cell of origin profiling | PLOS One
    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0266978
    Primary cutaneous large B-cell lymphomas (PCLBCL) represent a diagnostic challenge because they are classified as PCLBCL, leg type (PCLBCL, LT) or primary cutaneous follicle centre lymphoma, large cell (PCFCL, LC), which differ by prognosis and therapeutic requirement. […] A cell-of-origin classification of PCLBCL by genomic profiling of a restricted set of frozen material indicated that PCFCL, LC exhibits a germinal centre (GC) signature, whereas PCLBCL, LT has a non-GC signature. […] PCLBCL, LT showed highly recurrent mutations of MYD88 (p.L265P variant), PIM1, and CD79B, which are involved in the NF-B and B-cell receptor signaling pathways, similar to primary central nervous system lymphoma (PCNSL). […] The data confirm our findings from Hans algorithm analysis of typical cases, and suggest that PCFCL, LC is of GC origin whereas PCLBCL, LT is of non-GC origin. […] Our PCLBCL, LT cases exhibited a mutational profile resembling that of PCNSL, with a high rate (80%) of mutations in the TLR MYD88 pathway and/or CD79B and TNFAIP3/A20.
  • #49 Integrative diagnosis of primary cutaneous large B-cell lymphomas supports the relevance of cell of origin profiling | PLOS One
    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0266978
    Primary cutaneous large B-cell lymphomas (PCLBCL) represent a diagnostic challenge because they are classified as PCLBCL, leg type (PCLBCL, LT) or primary cutaneous follicle centre lymphoma, large cell (PCFCL, LC), which differ by prognosis and therapeutic requirement. […] A cell-of-origin classification of PCLBCL by genomic profiling of a restricted set of frozen material indicated that PCFCL, LC exhibits a germinal centre (GC) signature, whereas PCLBCL, LT has a non-GC signature. […] PCLBCL, LT showed highly recurrent mutations of MYD88 (p.L265P variant), PIM1, and CD79B, which are involved in the NF-B and B-cell receptor signaling pathways, similar to primary central nervous system lymphoma (PCNSL). […] The data confirm our findings from Hans algorithm analysis of typical cases, and suggest that PCFCL, LC is of GC origin whereas PCLBCL, LT is of non-GC origin. […] Our PCLBCL, LT cases exhibited a mutational profile resembling that of PCNSL, with a high rate (80%) of mutations in the TLR MYD88 pathway and/or CD79B and TNFAIP3/A20.
  • #50 Expression of B-cell transcription factors in primary cutaneous B-cell lymphoma | Modern Pathology
    https://www.nature.com/articles/3800650
    Expression patterns of eight transcription factors involved in different stages of B-cell development were investigated in a large group of primary cutaneous B-cell lymphomas and compared with expression patterns during normal B-cell development. […] Primary cutaneous large B-cell lymphomas, leg type showed aberrant coexpression of Bcl-6 and Mum1/IRF4 and in addition strong expression of FOXP1. Expression of FOXP1 and Mum1/IRF4 strongly suggests an activated B-cell type of origin. […] In conclusion, in primary cutaneous follicle center lymphoma and primary cutaneous marginal zone B-cell lymphoma expression patterns were observed similar to their supposed benign counterparts, germinal center B-cells and postgerminal center B-cells, respectively, which might reflect their indolent clinical behaviour and excellent prognosis. In contrast, the activated B-cell expression pattern in the group of primary cutaneous large B-cell lymphoma, leg type may contribute to its poor prognosis and Mum1/IRF4 and FOXP1 may serve as additional diagnostic markers for this type of primary cutaneous B-cell lymphoma.
  • #51 Rituximab in the Treatment of Primary Cutaneous B-Cell Lymphoma: A Review | Actas Dermo-Sifiliográficas
    https://actasdermo.org/es-rituximab-in-treatment-primary-cutaneous-articulo-S1578219014001073
    Rituximab has also been shown to induce an antigen-specific response in T cells by an immunization mechanism. […] Rituximab is also known to act via the bcl-2 protein. This marker is overexpressed in 85% of CDLBCL-LT and is considered one of the factors associated with worse prognosis. […] The guidelines for management of CBCL, issued by the EORTC, recommend treatment of CDLBCL-LT with polychemotherapy with or without rituximab (cyclophosphamide, hydroxydaunorubicin, Oncovin, prednisone [CHOP]-like or R-CHOP regimens). […] The role of rituximab as monotherapy in CDLBCL-LT is not well defined; the results reported in the literature suggest that there is a marked initial response but recurrences and disease progression are frequent. […] Rituximab is an anti-CD20 antibody that is increasingly used in the treatment of CBCL. Good response rates are obtained in indolent B-cell lymphomas, FL, and MZL, for both the intravenous and intralesional route of administration, although recurrence is frequent. […] Intralesional use has become widespread in recent years with similar outcomes to intravenous use, but with fewer side effects and a lower cost.
  • #52 Rituximab in the Treatment of Primary Cutaneous B-Cell Lymphoma: A Review | Actas Dermo-Sifiliográficas
    https://actasdermo.org/es-rituximab-in-treatment-primary-cutaneous-articulo-S1578219014001073
    Rituximab is a chimeric mouse-human antibody that targets the CD20 antigen, which is found in both normal and neoplastic B cells. In recent years, it has been increasingly used to treat cutaneous B-cell lymphoma and is now considered an alternative to classic treatment (radiotherapy and surgery) of 2 types of indolent lymphoma, namely, primary cutaneous follicle center lymphoma and primary cutaneous marginal zone B-cell lymphoma. […] Rituximab is also administered as an alternative to polychemotherapy in the treatment of primary cutaneous large B-cell lymphoma, leg type. Its use as an alternative drug led to it being administered intralesionally, with beneficial effects. […] In vitro studies of rituximab have shown this agent induces lysis of lymphoma B-cells by antibody-dependent cell mediated cytotoxicity, complement activation, and direct induction of apoptosis. This mechanism does not depend on the immune system and occurs because the variable region of murine origin binds with high affinity to the CD20 antigen expressed on malignant B lymphocytes, halting their proliferation and inducing apoptosis probably through transmembrane calcium channels.
  • #53 Rituximab in the Treatment of Primary Cutaneous B-Cell Lymphoma: A Review | Actas Dermo-Sifiliográficas
    https://actasdermo.org/es-rituximab-in-treatment-primary-cutaneous-articulo-S1578219014001073
    Rituximab is a chimeric mouse-human antibody that targets the CD20 antigen, which is found in both normal and neoplastic B cells. In recent years, it has been increasingly used to treat cutaneous B-cell lymphoma and is now considered an alternative to classic treatment (radiotherapy and surgery) of 2 types of indolent lymphoma, namely, primary cutaneous follicle center lymphoma and primary cutaneous marginal zone B-cell lymphoma. […] Rituximab is also administered as an alternative to polychemotherapy in the treatment of primary cutaneous large B-cell lymphoma, leg type. Its use as an alternative drug led to it being administered intralesionally, with beneficial effects. […] In vitro studies of rituximab have shown this agent induces lysis of lymphoma B-cells by antibody-dependent cell mediated cytotoxicity, complement activation, and direct induction of apoptosis. This mechanism does not depend on the immune system and occurs because the variable region of murine origin binds with high affinity to the CD20 antigen expressed on malignant B lymphocytes, halting their proliferation and inducing apoptosis probably through transmembrane calcium channels.
  • #54 Rituximab in the Treatment of Primary Cutaneous B-Cell Lymphoma: A Review | Actas Dermo-Sifiliográficas
    https://actasdermo.org/es-rituximab-in-treatment-primary-cutaneous-articulo-S1578219014001073
    Rituximab has also been shown to induce an antigen-specific response in T cells by an immunization mechanism. […] Rituximab is also known to act via the bcl-2 protein. This marker is overexpressed in 85% of CDLBCL-LT and is considered one of the factors associated with worse prognosis. […] The guidelines for management of CBCL, issued by the EORTC, recommend treatment of CDLBCL-LT with polychemotherapy with or without rituximab (cyclophosphamide, hydroxydaunorubicin, Oncovin, prednisone [CHOP]-like or R-CHOP regimens). […] The role of rituximab as monotherapy in CDLBCL-LT is not well defined; the results reported in the literature suggest that there is a marked initial response but recurrences and disease progression are frequent. […] Rituximab is an anti-CD20 antibody that is increasingly used in the treatment of CBCL. Good response rates are obtained in indolent B-cell lymphomas, FL, and MZL, for both the intravenous and intralesional route of administration, although recurrence is frequent. […] Intralesional use has become widespread in recent years with similar outcomes to intravenous use, but with fewer side effects and a lower cost.
  • #55 Rituximab in the Treatment of Primary Cutaneous B-Cell Lymphoma: A Review | Actas Dermo-Sifiliográficas
    https://actasdermo.org/es-rituximab-in-treatment-primary-cutaneous-articulo-S1578219014001073
    Rituximab has also been shown to induce an antigen-specific response in T cells by an immunization mechanism. […] Rituximab is also known to act via the bcl-2 protein. This marker is overexpressed in 85% of CDLBCL-LT and is considered one of the factors associated with worse prognosis. […] The guidelines for management of CBCL, issued by the EORTC, recommend treatment of CDLBCL-LT with polychemotherapy with or without rituximab (cyclophosphamide, hydroxydaunorubicin, Oncovin, prednisone [CHOP]-like or R-CHOP regimens). […] The role of rituximab as monotherapy in CDLBCL-LT is not well defined; the results reported in the literature suggest that there is a marked initial response but recurrences and disease progression are frequent. […] Rituximab is an anti-CD20 antibody that is increasingly used in the treatment of CBCL. Good response rates are obtained in indolent B-cell lymphomas, FL, and MZL, for both the intravenous and intralesional route of administration, although recurrence is frequent. […] Intralesional use has become widespread in recent years with similar outcomes to intravenous use, but with fewer side effects and a lower cost.
  • #56
    https://link.springer.com/article/10.1007/s40257-022-00704-0
    Several genetic abnormalities have been identified and serve as diagnostic and prognostic markers. […] The genetic landscape of PCDLBCL, LT is similar to that of activated B-cell type diffuse large B-cell lymphoma and diffuse large B-cell lymphoma of the central nervous system with mutations in the activated B-cell pathway elicited with massive parallel sequencing. […] Mutations in MYD88 L265P (60-70% of cases) and additional NFB pathway markers CD79B, PIM1, TNFAIP3/A20, and CARD11 are also observed. […] These B-cell receptor mutations are associated with a lower response rate to R-polychemotherapy. […] The tumor microenvironment of PCDCBL, LT comprises two distinct cell populations: CD33+ myeloid-derived suppressor cells and CD163+ M2 macrophages with differential expressions of membrane-bound PD-L1 in both cell populations. […] Upregulation of PD-L1/PD-L2 is also observed within the microenvironment of high-grade lymphomas, and is not seen in low-grade lymphomas. […] The culmination of these findings suggests a mechanism of immune surveillance escape contributing to the poor prognosis in PCDLBCL, LT.
  • #57 Rituximab in the Treatment of Primary Cutaneous B-Cell Lymphoma: A Review | Actas Dermo-Sifiliográficas
    https://actasdermo.org/es-rituximab-in-treatment-primary-cutaneous-articulo-S1578219014001073
    Rituximab has also been shown to induce an antigen-specific response in T cells by an immunization mechanism. […] Rituximab is also known to act via the bcl-2 protein. This marker is overexpressed in 85% of CDLBCL-LT and is considered one of the factors associated with worse prognosis. […] The guidelines for management of CBCL, issued by the EORTC, recommend treatment of CDLBCL-LT with polychemotherapy with or without rituximab (cyclophosphamide, hydroxydaunorubicin, Oncovin, prednisone [CHOP]-like or R-CHOP regimens). […] The role of rituximab as monotherapy in CDLBCL-LT is not well defined; the results reported in the literature suggest that there is a marked initial response but recurrences and disease progression are frequent. […] Rituximab is an anti-CD20 antibody that is increasingly used in the treatment of CBCL. Good response rates are obtained in indolent B-cell lymphomas, FL, and MZL, for both the intravenous and intralesional route of administration, although recurrence is frequent. […] Intralesional use has become widespread in recent years with similar outcomes to intravenous use, but with fewer side effects and a lower cost.
  • #58 Rituximab in the Treatment of Primary Cutaneous B-Cell Lymphoma: A Review | Actas Dermo-Sifiliográficas
    https://actasdermo.org/es-rituximab-in-treatment-primary-cutaneous-articulo-S1578219014001073
    Rituximab has also been shown to induce an antigen-specific response in T cells by an immunization mechanism. […] Rituximab is also known to act via the bcl-2 protein. This marker is overexpressed in 85% of CDLBCL-LT and is considered one of the factors associated with worse prognosis. […] The guidelines for management of CBCL, issued by the EORTC, recommend treatment of CDLBCL-LT with polychemotherapy with or without rituximab (cyclophosphamide, hydroxydaunorubicin, Oncovin, prednisone [CHOP]-like or R-CHOP regimens). […] The role of rituximab as monotherapy in CDLBCL-LT is not well defined; the results reported in the literature suggest that there is a marked initial response but recurrences and disease progression are frequent. […] Rituximab is an anti-CD20 antibody that is increasingly used in the treatment of CBCL. Good response rates are obtained in indolent B-cell lymphomas, FL, and MZL, for both the intravenous and intralesional route of administration, although recurrence is frequent. […] Intralesional use has become widespread in recent years with similar outcomes to intravenous use, but with fewer side effects and a lower cost.
  • #59 Rituximab in the Treatment of Primary Cutaneous B-Cell Lymphoma: A Review | Actas Dermo-Sifiliográficas
    https://actasdermo.org/es-rituximab-in-treatment-primary-cutaneous-articulo-S1578219014001073
    Rituximab has also been shown to induce an antigen-specific response in T cells by an immunization mechanism. […] Rituximab is also known to act via the bcl-2 protein. This marker is overexpressed in 85% of CDLBCL-LT and is considered one of the factors associated with worse prognosis. […] The guidelines for management of CBCL, issued by the EORTC, recommend treatment of CDLBCL-LT with polychemotherapy with or without rituximab (cyclophosphamide, hydroxydaunorubicin, Oncovin, prednisone [CHOP]-like or R-CHOP regimens). […] The role of rituximab as monotherapy in CDLBCL-LT is not well defined; the results reported in the literature suggest that there is a marked initial response but recurrences and disease progression are frequent. […] Rituximab is an anti-CD20 antibody that is increasingly used in the treatment of CBCL. Good response rates are obtained in indolent B-cell lymphomas, FL, and MZL, for both the intravenous and intralesional route of administration, although recurrence is frequent. […] Intralesional use has become widespread in recent years with similar outcomes to intravenous use, but with fewer side effects and a lower cost.
  • #60 Rituximab in the Treatment of Primary Cutaneous B-Cell Lymphoma: A Review | Actas Dermo-Sifiliográficas
    https://actasdermo.org/es-rituximab-in-treatment-primary-cutaneous-articulo-S1578219014001073
    Rituximab has also been shown to induce an antigen-specific response in T cells by an immunization mechanism. […] Rituximab is also known to act via the bcl-2 protein. This marker is overexpressed in 85% of CDLBCL-LT and is considered one of the factors associated with worse prognosis. […] The guidelines for management of CBCL, issued by the EORTC, recommend treatment of CDLBCL-LT with polychemotherapy with or without rituximab (cyclophosphamide, hydroxydaunorubicin, Oncovin, prednisone [CHOP]-like or R-CHOP regimens). […] The role of rituximab as monotherapy in CDLBCL-LT is not well defined; the results reported in the literature suggest that there is a marked initial response but recurrences and disease progression are frequent. […] Rituximab is an anti-CD20 antibody that is increasingly used in the treatment of CBCL. Good response rates are obtained in indolent B-cell lymphomas, FL, and MZL, for both the intravenous and intralesional route of administration, although recurrence is frequent. […] Intralesional use has become widespread in recent years with similar outcomes to intravenous use, but with fewer side effects and a lower cost.

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pierwotny skórny chłoniak z komórek B reumatoidalne zapalenie stawów apoptoza wirus zapalenia wątroby typu C Borrelia burgdorferi polichemioterapia pierwotny skórny chłoniak rozlany z dużych komórek B typu kończynowego aberracja chromosomalna Helicobacter pylori nowotwór limfoproliferacyjny indukcja apoptozy pierwotny skórny chłoniak strefy brzeżnej schemat CHOP wirus Epsteina-Barr antygen CD20 pierwotny skórny chłoniak z ośrodków rozmnażania rytuksymab mutacja MYD88 immunofenotyp tkanka limfoidalna aktywacja dopełniacza metaloproteinaza ludzki wirus herpes typu 8 cytotoksyczność komórkowa chłoniak typu MALT