LYMPHÔM NGUYÊN PHÁT Ở ĐƯỜNG TIÊU HÓA

1. LYMPHÔM NGUYÊN PHÁT Ở ĐƯỜNG TIÊU HÓA
(PRIMARY LYMPHOMAS IN THE GASTROINTESTINAL TRACT)
• Học viên: HUỲNH THỊ LIÊN
• Giảng viên hướng dẫn: TS. LÊ MINH HUY

2. Extranodal Lymphoid Tissues Including
the Waldeyer Ring
• nonencapsulated lymphoid tissues
• mostly located in mucosal sites - known as the “mucosa-associated
lymphoid tissues.”
• Waldeyer ring
• intestinal tract
• and respiratory tract
• No capsule and No sinus
• two components are found: B-cell follicles separated by a T-cell–rich
interfollicular zone
• close interaction between the lymphocytes and the overlying epithelium

3. TIẾP CẬN CHẨN ĐOÁN
1. Vị trí + loại tổn thương thường gặp
2. Tăng san/Lymphoma/ tăng san+Lymphoma
3. Kích thước tế bào U: Mô bào phản ứng/ Nội mô mạch máu
a. nhỏ, trung bình: EMZL & grade or MCL or EATL
b. lớn: DLBCL
4. HMMD

5. VỊ TRÍ – PHÂN LOẠI
• 1 vị trí thường gặp của Lymphoma ngoài hạch
• 5-10% U đường tiêu hóa
• Dạ dày: 50-60%; 30% ruột non; 10% ruột già
• Khoang miệng và thực quản: hiếm gặp
• Chủ yếu Lymphoma tb B lớn lan tỏa (DLBCL): 45%
• 17% Lymphoma vùng rìa ngoài hạch (MZL)

8. Tăng sản lympho: khu trú
• Có thể loét niêm mạc phủ gây chảy máu
• hyperplastic lymphoepithelial complexes: lymphocytes (typically small
and mature appearing), infiltrating within glandular or stratified
epithelial structures
• Tonsil: normal and “ expected” lymphoepithelial lesions (thường liên
quan MALT lymphoma) lymphocytes migrate to the surface of the
epithelial lining to expose antigen
• enlarged germinal centers with typical benign features

9. Tăng sản lympho: LAN TỎA
• Thường liên quan rối loạn khiếm khuyết
miễn dịch
• Lymphoid hyperplasia
• Ulcerative colitis can produce diffuse
lymphoid hyperplasia
with sheets of lymphocytes and plasma cells
that expand the
lamina propria
• Đôi khi gây lồng ruột, tắc nghẽn nhất là HIV

10. Diễn tiến tự nhiên lành tính
• Đáp ứng miễn dịch
• Gia tăng tb dạng lympho B & T
• Hình thành trung tâm mầm
• Tăng sinh tạo MALT
• Tự nhiên : mảng Peyer
• Mắc phải: liên quan dến HP, đáp ứng lại kích thích kháng nguyên tại chỗ
• Bệnh Celiac: tăng sinh lympho trong biểu mô nổi bật. Tạo
lymphoepithelial lesions are not pathognomonic of a neoplastic
process
• Khó phân biệt Lymphoma

11. Xâm nhập lympho nghi ngờ LYMPHOMA

12. MALT LYMPHOMA
• = Extranodal marginal zone lymphoma of MALT type
• a wide variety of extranodal sites, in particular the gastrointestinal
tract, thyroid, salivary gland, and lung and, less commonly, the ocular
adnexa, thymus, skin, soft tissue, breast, tongue, tonsil, gallbladder,
liver, urogenital tract, and dura
• Predisposing conditions are chronic inflmmation (e.g.,
Helicobacterassociated gastritis) and autoimmune diseases (e.g.,
Hashimoto thyroiditis and Sjögren syndrome
• Approximately 70% to 80% of gastric extranodal marginal zone
lymphomas
associated with Helicobacter gastritis show complete remission with
anti-Helicobacter therapy

13. • Antibiotic therapy appears to
be effective predominantly in
pure low-grade disease
confied to the mucosa and
submucosa.
• Although recent studies
suggest that even gastric large
B-cell lymphomas (early stage)
show complete remission with
antiHelicobacter therapy in a
high proportion of cases
MALT LYMPHOMA

14. • Reactive lymphoid follicles are frequently interspersed
throughout.
• The neoplastic lymphoid infitrate is diffuse, interfollicular, or
perifollicular
• The infitrate is often heterogeneous, comprising a mixture of
cell types, although rare cases can exhibit a monomorphic
population
• centrocyte-like, being small to medium sized, with slightly
folded or elongated angulated nuclei, moderately dense
chromatin, inconspicuous nucleoli, and a small amount of
pale to clear cytoplasm
• Some cells are slightly larger, with abundant clear cytoplasm,
resembling monocytoid B cells
MALT LYMPHOMA

15. centrocyte-like, with clear cytoplasm. Note
the mixture of cell types, including plasma cells
monotonous population of small cells
lymphoepithelial lesions (H) which can be highlighted by staining for pan-keratin

16. • “lymphoepithelial lesions: defied as
epithelial units expanded or distorted by
groups of more than three lymphoid cells
• destroyed epithelium may remain as
isolated or small groups of oncocytic or
signet ring cells
• lymphoma cells within and around the
epithelial structures often assume a
centrocyte-like or monocytoid B-cell–like
appearance, producing pale “collars”
around the lymphoepithelial lesions
MALT LYMPHOMA
residual epithelial cells have an
oncocytic appearance or
groundglass appearance
monocytoid B-cell–like appearance,
producing a
pale collar at low magnifiation

17. Wotherspoon scoring system for scoring gastric
lymphoid infiltrates

18. WOTHERSPOON criteria for Grading EMZL
Grade 1: Gastric biopsy with
normal appearance or minimal
hyperplasias with apparent
benign features
. E, Grade 2: Lymphoid infiltrate with
features of low suspicion for
EMZLMALT.
F, Grade 3: Lymphoid infiltrate
suspicious for EMZL-MALT

19. • B-lineage markers: CD20, CD79a positive. Ig is usually of IgM,
sometimes IgG or IgA type, but not IgD. CD21 (+)
• CD5 −, CD10 −, CD23 −, cyclin D1 −, BCL6 −. has become a
“wastebasket” for unclassifible cases of low-grade B-cell lymphoma
• BCL2 is often positive and CD43 expression is
observed in approximately 50% of cases.796,797 The
Ki67 (proliferation) index is low
MALT LYMPHOMA

20. Aberrant CD43 expression is a
very useful tool for histological diagnosis of
mucosa-associated lymphoid tissue (MALT)
lymphoma. (A) Low-power view of a gastric
MALT lymphoma (H&E). (B) CD20 highlights
a diffuse infiltrate of neoplastic B cells
(immunoperoxidase). (C) CD3 is expressed
by a small number of reactive T cells
(immunoperoxidase). (D) CD43 is strongly
expressed by neoplastic B cells

21. Low grade & high grade Lymphoma
• MALT lymphomas usually host scattered large transformed
blasts; their number varies from case to case, but it does not
exceed 10% of lymphoid population.
• WHO recommends that cases showing transformation to large-cell
lymphoma should be called DLBCL instead of high grade MALT
lymphoma

22. Development of B lymphocytes and the changes in
immunophenotypic profile

23. Chẩn đoán phân biệt

24. DLBCL
• Gastric DLBCL has features similar to
other sites. However, in all cases, the
presence or absence of H. pylori, and
the presence or absence of a low-grade
component (eg, EMZL) should be
noted.
• Rare cases of gastric DLBCL have been
shown to respond to H pylori
eradication therapy, and may be
pathophysiologically related
to previous or underlying gastric EMZL
Transformed lymphocytes present (greater
than 30% of all cells), along with a
polymorphous cellular infiltrate including
small lymphocytes and plasma cells
monomorphous, with no evidence of
a low-grade component

25. follicular lymphoma (FL) of small intestine
• young or middle-aged women, and preferentially in the
proximal small bowel
• features typical of FL with typical immunophenotypic
features of follicular lymphoma (CD20+, BCL-2+, BCL-6+ and
CD10+, abnormally low proliferative rate by Ki-67)
• localized to the small intestine only,without systemic spread
of disease

26. Follicular lymphoma of small intestine. A, Low
magnification image of polypoid fragment of small
intestinal mucosa. There are many atypical-
appearing nodular aggregates of lymphocytes in
the submucosa. B, High magnification of an
atypical follicle
CD20 staining BCL-2 protein stainin
BCL-6 staining in the
abnormal follicle
Ki-67 in an abnormal
follicle

27. EATL(Enteropathy-associated T cell lymphoma)
rare T cell lymphoma that most
commonly
presents in the small intestine
association with celiac disease
CD8 CD56

28. Mantle cell Lymphoma(MCL)
• distinctive small B cell lymphoma, with a typically aggressive clinical
course
• lymphomatous polyposis
• associated with some or innumerable polypoid lesions of small intestine,
colon or other portions of the GI tract
• The neoplastic mantle cell lymphocytes have dense chromatin, irregular
nuclei and scant cytoplasm
• no large centroblastic cells
• positive for pan–B cell antigens (CD20, PAX5, CD22, CD19), with
expression of CD5 and cyclin D1.
• Cyclin D1 expression in lymphocytes is almost pathognomonic of this
disorder

29. Mantle cell lymphoma. A, Gross
image of colon with multiple
polypoid excrescences, leading
to the descriptive
diagnosis,lymphomatous
polyposis. B, Low magnification
image of colon with a polyp
dominated by an abnormal
nodule of mantle cell lymphoma.
C, High magnification of mantle
cell lymphoma
CD20 CD5
CD43
cyclin D1

30. Plasmablastic lymphoma in oral cavity
• Arises most commonly in the oral cavity (58% of cases in HIV patients; fewer in
non-HIV)
• high-grade neoplasm of immature plasmacytic/immunoblastic lymphoid cells
• Large lymphocytes with large, rounded nuclei, relatively dispersed
or open chromatin, prominent single nucleoli and small to moderate amounts of
blue cytoplasm (immunoblast-like)
• Approximately 80% of all cases are EBV positive, although nearly 100% of cases in
the oral cavity are positive, as defined by in situ hybridization
staining for EBV
• the plasmablastic cells express CD138,CD38,Vs38candMUM1. Theytypicallylack
CD20, PAX5 and CD45 staining

31. Thuật ngữ
• MALT: mucosa-associated lymphoid tissue
• DLBCL
• EMZL
• EATL
• hyperplastic lymphoepithelial complexes
• lymphoepithelial lesions