history of malignant lymphoma
DESCRIPTION
History of Malignant Lymphoma. ---- What ’s kind of road we have traced ?. By Jie Wei. Three stages of lymphoma cognition. Morphology before 70’, 21 st century. . Cell protein expression level during 70’~80’ , 21 st century. . DNA/mRNA molecular level after 80’ 21 st century. . - PowerPoint PPT PresentationTRANSCRIPT
![Page 1: History of Malignant Lymphoma](https://reader035.vdocuments.mx/reader035/viewer/2022062519/56814e58550346895dbbf238/html5/thumbnails/1.jpg)
History of Malignant Lymphoma
---- What ’s kind of road we have traced?
By Jie Wei
![Page 2: History of Malignant Lymphoma](https://reader035.vdocuments.mx/reader035/viewer/2022062519/56814e58550346895dbbf238/html5/thumbnails/2.jpg)
Three stages of lymphoma cognition
Morphology before 70’, 21st century
Cell protein expression level during 70’~80’, 21st century
DNA/mRNA molecular level after 80’ 21st century
![Page 3: History of Malignant Lymphoma](https://reader035.vdocuments.mx/reader035/viewer/2022062519/56814e58550346895dbbf238/html5/thumbnails/3.jpg)
Thomas Hodgkin published his
paper,On some Morbid appearance
of the Absorbent gland and the
spleen, in 1832.
Description of Hodgkin lymphoma
![Page 4: History of Malignant Lymphoma](https://reader035.vdocuments.mx/reader035/viewer/2022062519/56814e58550346895dbbf238/html5/thumbnails/4.jpg)
7 cases were mentioned, of which 3 / 7
were proved to be Hodgkin lymphoma l
ater.
![Page 5: History of Malignant Lymphoma](https://reader035.vdocuments.mx/reader035/viewer/2022062519/56814e58550346895dbbf238/html5/thumbnails/5.jpg)
Fig 2: A 7-year-old boy (W.D.M.,) in Dorothy Reed's classic paper, showing similar presentation to Ellenborough King. Johns Hopkins Hospital Reports with permission
![Page 6: History of Malignant Lymphoma](https://reader035.vdocuments.mx/reader035/viewer/2022062519/56814e58550346895dbbf238/html5/thumbnails/6.jpg)
Fig 1. Thomas Hodgkin (1798-1866), 'a man distinguished alike for scientific attainments, medical skill, and self-sacrificing philanthropy.' Epitaph inscribed on his tomb in Jaffa.
![Page 7: History of Malignant Lymphoma](https://reader035.vdocuments.mx/reader035/viewer/2022062519/56814e58550346895dbbf238/html5/thumbnails/7.jpg)
Sir Samuel Wilks (1865), provided a more detailed and critical clinical and pathological description of the some disorder and acknowledged Hodgkin's earlier contribution. The term “Hodgkin’s disease” was estabished.
![Page 8: History of Malignant Lymphoma](https://reader035.vdocuments.mx/reader035/viewer/2022062519/56814e58550346895dbbf238/html5/thumbnails/8.jpg)
Greenfield (1878), among others, de
scribed characteristic giant cells in p
atients with HD primarily.
A full description of the diagnostic cells
was published by Sternberg (1898) and
Dorothy Reed (1902) (Fig 3). This diagno
stic cell was termed “R-S cell” later.
![Page 9: History of Malignant Lymphoma](https://reader035.vdocuments.mx/reader035/viewer/2022062519/56814e58550346895dbbf238/html5/thumbnails/9.jpg)
Fig 3. Reed-Sternberg cells drawn by Dorothy Reed's own hand. The mirror-image cell at the lower left is diagnostic. (From Reed (1902) .John Hopkins Hosipltal Reports With permission.
![Page 10: History of Malignant Lymphoma](https://reader035.vdocuments.mx/reader035/viewer/2022062519/56814e58550346895dbbf238/html5/thumbnails/10.jpg)
![Page 11: History of Malignant Lymphoma](https://reader035.vdocuments.mx/reader035/viewer/2022062519/56814e58550346895dbbf238/html5/thumbnails/11.jpg)
Jackson & Parker (1947) introduced The first histological classification of Hodgkin's lymphoma (paragranuloma, granuloma and sarcoma).
Lukes & Butler (1966) added the nodular sclerosis category and further refined the Jackson & Parker’s earlier system.
![Page 12: History of Malignant Lymphoma](https://reader035.vdocuments.mx/reader035/viewer/2022062519/56814e58550346895dbbf238/html5/thumbnails/12.jpg)
Conference held in Rye, New York in 19
66 simplified the Lukes and Butler sche
me into a four-part classification and exp
anded into its present version at confere
nces held in Ann Arbor, Michigan (1971),
which further remodified by Costwolds i
n 1989.
![Page 13: History of Malignant Lymphoma](https://reader035.vdocuments.mx/reader035/viewer/2022062519/56814e58550346895dbbf238/html5/thumbnails/13.jpg)
After further modified the Ann Arbor c
lassification in the REAL (Revised Eur
opean-American Lymphoma) classific
ation (Harris et al, 1994), WHO, In 1997,
estabished a new Hodgkin’s lympho
ma classification scheme.
![Page 14: History of Malignant Lymphoma](https://reader035.vdocuments.mx/reader035/viewer/2022062519/56814e58550346895dbbf238/html5/thumbnails/14.jpg)
View of main classification of Hodgkin’s lymphoma
Rye Lukes & ButterJackson & Parker
Lymphocyte predominant
Lymphocyte/lymph tissue predominant
Paragranuloma
Nodular sclerosis
Nodular sclerosis
Mixed cellularity type
Mixed type Granuloma
Lymphocyte depletion
Diffuse fibrosis type
Sarcoma
Reticulum cell type
![Page 15: History of Malignant Lymphoma](https://reader035.vdocuments.mx/reader035/viewer/2022062519/56814e58550346895dbbf238/html5/thumbnails/15.jpg)
WHO classification of Hodgkin’s lymphoma
Nodular lymphocyte predominance
Classic Hodgkin’s lymphoma
Mixed cellularity type
Nodular sclerosis type
Lymphocyte predominance type
Anaplasia larger cell type*
* Remain Altercation for adding anaplasia larger cell type HD and omiting Lymphocyte depletion type HD
![Page 16: History of Malignant Lymphoma](https://reader035.vdocuments.mx/reader035/viewer/2022062519/56814e58550346895dbbf238/html5/thumbnails/16.jpg)
The delineation of the Non-Hodgkin's lymphomas
Virchow (1845) and Bennett (1845) described the first cases of leukaemia.
Virchow (1864-1865) divided leukaemia into the leukaemic and 'aleukaemic' types, employing the designation 'lymphosarcoma' for a subdivision of the latter.
![Page 17: History of Malignant Lymphoma](https://reader035.vdocuments.mx/reader035/viewer/2022062519/56814e58550346895dbbf238/html5/thumbnails/17.jpg)
A probable case of acute leukaemia was published by Cohnheim (1865) under the descriptive term ‘pseudoleukaemia’.
Kundrat (1893) and colleagues again employed the term lymphosarcoma in the modern sense used by Virchow a generation earlier .
![Page 18: History of Malignant Lymphoma](https://reader035.vdocuments.mx/reader035/viewer/2022062519/56814e58550346895dbbf238/html5/thumbnails/18.jpg)
The follicular or nodular lymphomas were first clearly described by Brill et al (1925).
The term reticulum cell sarcoma was ap
plied to lymph node neoplasms by Roul
et (1930), another designation which gen
erated considerable confusion in lymph
oma classification.
![Page 19: History of Malignant Lymphoma](https://reader035.vdocuments.mx/reader035/viewer/2022062519/56814e58550346895dbbf238/html5/thumbnails/19.jpg)
Gall and Mallory (1942) introduced a lym
phoma classification based on clinicopat
hologic criteria, which, for all its shortco
mings, was the first systematic attempt t
o make order out of the chaotic NHL situ
ation.
![Page 20: History of Malignant Lymphoma](https://reader035.vdocuments.mx/reader035/viewer/2022062519/56814e58550346895dbbf238/html5/thumbnails/20.jpg)
Rappaport et al (1956) presented medici
ne with a lymphoma classification that c
ould be applied easily and was prognosti
cally useful. Two criteria were employed
to differentiate lymphoma subtypes: the
presence or absence of nodularity, and c
ell size (small, intermediate and large ly
mphoid cells).
![Page 21: History of Malignant Lymphoma](https://reader035.vdocuments.mx/reader035/viewer/2022062519/56814e58550346895dbbf238/html5/thumbnails/21.jpg)
Burkitt (1958) described a new type of l
ymphoma in African children restricted
to regions of high temperature and high
rainfall.
![Page 22: History of Malignant Lymphoma](https://reader035.vdocuments.mx/reader035/viewer/2022062519/56814e58550346895dbbf238/html5/thumbnails/22.jpg)
In 1972, it became possible to immunoph
enotype B and T lymphocytes, initially by
the presence of clonal immunoglobulin a
nd/or sheep cell receptor on the cell surf
ace, and later with a host of B- and T-sub
set-specific monoclonal antibodies.
![Page 23: History of Malignant Lymphoma](https://reader035.vdocuments.mx/reader035/viewer/2022062519/56814e58550346895dbbf238/html5/thumbnails/23.jpg)
Lukes & Collins (1974) established a new
immnuological classification based on th
eir knowledge about B-cell transformatio
n after antigen stimulation.
![Page 24: History of Malignant Lymphoma](https://reader035.vdocuments.mx/reader035/viewer/2022062519/56814e58550346895dbbf238/html5/thumbnails/24.jpg)
![Page 25: History of Malignant Lymphoma](https://reader035.vdocuments.mx/reader035/viewer/2022062519/56814e58550346895dbbf238/html5/thumbnails/25.jpg)
The follicle centre cell was recognized
by Lennert et al (1978) and became th
e basis of alternate classifications: Le
nnert's Kiel system (Lennert et al, 197
8; Lennert & Feller, 1992).
![Page 26: History of Malignant Lymphoma](https://reader035.vdocuments.mx/reader035/viewer/2022062519/56814e58550346895dbbf238/html5/thumbnails/26.jpg)
Ag
Ag
/ 中心细胞
中心母细胞
干细胞
前 T 细胞 T1 细胞
T 免母细胞T2 细胞
前 B 细胞
B 免母细胞
B2 细胞
浆细胞
淋浆
![Page 27: History of Malignant Lymphoma](https://reader035.vdocuments.mx/reader035/viewer/2022062519/56814e58550346895dbbf238/html5/thumbnails/27.jpg)
The recent National Cancer Institute sponsored Working Formulation for Clinical Usage (Rosenberg et al, 1985) provided an unsatisfactory solution to the vexing search for a clinically-relevant system that could be reproducibly applied by working pathologists.
![Page 28: History of Malignant Lymphoma](https://reader035.vdocuments.mx/reader035/viewer/2022062519/56814e58550346895dbbf238/html5/thumbnails/28.jpg)
The REAL classification (Harris et al, 1994) repres
ents a radical, if tentative, consensus redo of ly
mphoma classification, based on prior classific
ations and, for the first time, defining lymphom
a subtypes by immunophenotype and molecula
r genotype, as well as by morphology and clini
cal characteristics.
![Page 29: History of Malignant Lymphoma](https://reader035.vdocuments.mx/reader035/viewer/2022062519/56814e58550346895dbbf238/html5/thumbnails/29.jpg)
WHO classification of ML
First edition (1976)
1997 edition based on REAL classification
Remain alternation
Published in 2000 Finally
![Page 30: History of Malignant Lymphoma](https://reader035.vdocuments.mx/reader035/viewer/2022062519/56814e58550346895dbbf238/html5/thumbnails/30.jpg)
In 1981 B-cell lineage could be confirmed by the presence of clonally rearranged immunoglobulin heavy and light chain genes (Korsmeyer et al).
Identify clonal T-cell proliferations by the presence of clonally rearranged T-cell receptor genes (Aisenberg; Minden; Waldmann et al, 1985)
![Page 31: History of Malignant Lymphoma](https://reader035.vdocuments.mx/reader035/viewer/2022062519/56814e58550346895dbbf238/html5/thumbnails/31.jpg)
Lymphoblastic lymphoma (Barcos & Lukes,
Lennert) was a separate clinicopathologi
c entity.
Adult T-cell leukaemia/lymphoma reported
in 1977 from Japan, concentrated in the
South-western islands.
![Page 32: History of Malignant Lymphoma](https://reader035.vdocuments.mx/reader035/viewer/2022062519/56814e58550346895dbbf238/html5/thumbnails/32.jpg)
MALT (mucosa-associated lymphoid tiss
ue) lymphomas (Isaacson & Wright, 197
8),
Mantle cell lymphoma (Banks, 1992).
![Page 33: History of Malignant Lymphoma](https://reader035.vdocuments.mx/reader035/viewer/2022062519/56814e58550346895dbbf238/html5/thumbnails/33.jpg)
large cell lymphomas of the mediastinum
derived from B cells of the thymic medull
a (Aisenberg, 1999).
![Page 34: History of Malignant Lymphoma](https://reader035.vdocuments.mx/reader035/viewer/2022062519/56814e58550346895dbbf238/html5/thumbnails/34.jpg)
Aetiology and pathogenesis
The nature of Hodgkin's lymphoma
The malignant nature of Hodgkin's lym
phoma was disputed. The majority of i
nvestigators, Virchow, Wilks, and most
modern students of the disorder, consi
dered it a neoplasm of the lymphoid sy
stem.
![Page 35: History of Malignant Lymphoma](https://reader035.vdocuments.mx/reader035/viewer/2022062519/56814e58550346895dbbf238/html5/thumbnails/35.jpg)
but some distinguished observers, including both Reed and Sternberg, held a contrary opinion. Indeed, until recently, the R-S cell resisted attempts to define its lineage because of its sparsity. Its immunophenotypic characteristics were not those of garden-variety B lymphocytes, T lymphocytes, macrophage/monocytes, or dendritic cells.
![Page 36: History of Malignant Lymphoma](https://reader035.vdocuments.mx/reader035/viewer/2022062519/56814e58550346895dbbf238/html5/thumbnails/36.jpg)
Recent evidence of clonally rearranged I
g genes obtained from PCR study of sing
le R-S cell, and from immunophenotype s
tudy, strongly supports their neoplastic a
nd aberrant ('crippled') B-cell lineage in n
odular sclerosis, mixed cellularity and ly
mphocyte-depletion HD (Kuppers & Raje
wsky, 1998; Kuppers et al, 1999).
![Page 37: History of Malignant Lymphoma](https://reader035.vdocuments.mx/reader035/viewer/2022062519/56814e58550346895dbbf238/html5/thumbnails/37.jpg)
The regular isolation of Epstein-Barr vir
us (EBV) from African Burkitt's lympho
ma in 1964 and since that time (Epstein
et al, 1964), together with extensive epid
emiologic (serologic) evidence, establis
hed an aetiologic role of this DNA herpe
s-type virus in the endemic disorder.
Viruses and the aetiology of lymphoma
![Page 38: History of Malignant Lymphoma](https://reader035.vdocuments.mx/reader035/viewer/2022062519/56814e58550346895dbbf238/html5/thumbnails/38.jpg)
EBV has been identified in
lymphomas which complicate a
variety of acquired and inherited
immune deficiency states.
![Page 39: History of Malignant Lymphoma](https://reader035.vdocuments.mx/reader035/viewer/2022062519/56814e58550346895dbbf238/html5/thumbnails/39.jpg)
Gallo and Wong-Staal (1982) isolated a novel retr
ovirus (HTLV-I) from a patient with an atypical cut
aneous T-cell lymphoma. Subsequently, the sam
e virus was regularly recovered from the tumour
cells of Japanese and Caribbean patients with ad
ult T-cell leukaemia/lymphoma (ATL), and antibo
dy to the virus was demonstrated in almost all in
dividuals with that disorder.
![Page 40: History of Malignant Lymphoma](https://reader035.vdocuments.mx/reader035/viewer/2022062519/56814e58550346895dbbf238/html5/thumbnails/40.jpg)
Recently, the relation between H. pylori
and MALToma of Gastrointestinal tract, H
CV and regional B-cell lymphomas was el
evation.
![Page 41: History of Malignant Lymphoma](https://reader035.vdocuments.mx/reader035/viewer/2022062519/56814e58550346895dbbf238/html5/thumbnails/41.jpg)
Molecular genetics and oncogenes.
The chromosomal localization of the hum
an immunoglobulin genes between 1979
and 1981 provided the basis for breathta
king insight into the pathogenesis of Bur
kitt's lymphoma
![Page 42: History of Malignant Lymphoma](https://reader035.vdocuments.mx/reader035/viewer/2022062519/56814e58550346895dbbf238/html5/thumbnails/42.jpg)
In 1982, both the Leder and the Croc
e laboratories cloned the translocati
on breakpoint, and identified the c-m
yc oncogene on the chromosome 8 f
ragment (8q24).
![Page 43: History of Malignant Lymphoma](https://reader035.vdocuments.mx/reader035/viewer/2022062519/56814e58550346895dbbf238/html5/thumbnails/43.jpg)
Tsujimoto et al (1984) cloned the breakpo
int of the 14;18 translocation of follicular
lymphoma. This breakpoint involved the j
unction of a joining region segment of th
e IgM gene at chromosome 14q32, and th
e bcl-2 oncogene (at 18q21), whose prote
in product suspends apoptosis or progra
mmed cell death.
![Page 44: History of Malignant Lymphoma](https://reader035.vdocuments.mx/reader035/viewer/2022062519/56814e58550346895dbbf238/html5/thumbnails/44.jpg)
The 11;14 translocation of mantle cell
lymphoma juxtaposed the bcl-1 gene
(cyclinD) on chromosome 11q13 to th
e same IgM gene (Rosenberg et al, 19
91) .
![Page 45: History of Malignant Lymphoma](https://reader035.vdocuments.mx/reader035/viewer/2022062519/56814e58550346895dbbf238/html5/thumbnails/45.jpg)
Bcl-3, an oncogene at 19q13 whose p
roduct regulates gene transcription, i
s similarly joined in a small fraction o
f cases of CLL (Wulczyn et al, 1992).
![Page 46: History of Malignant Lymphoma](https://reader035.vdocuments.mx/reader035/viewer/2022062519/56814e58550346895dbbf238/html5/thumbnails/46.jpg)
Putative oncogene Bcl-6 involved in
chromosome 3q27 translocated to a
variety of chromosomal sites in a fra
ction of large cell lymphomas (Offit,
1994).
![Page 47: History of Malignant Lymphoma](https://reader035.vdocuments.mx/reader035/viewer/2022062519/56814e58550346895dbbf238/html5/thumbnails/47.jpg)
BCL-8 involved in DLBC with t(14;15) (q32; q11-13).
BCL-9 gene cloned in precusror B lymphoblastic leukemia with t(1;14) (q21;q32).
![Page 48: History of Malignant Lymphoma](https://reader035.vdocuments.mx/reader035/viewer/2022062519/56814e58550346895dbbf238/html5/thumbnails/48.jpg)
BCL-10 gene cloned in MALToma, whic
h may contribute to the occurrence of su
ch kind of low grade lymphoma.
ALK-NPM (p80) involved in anaplasia
large cell lymphoma.
![Page 49: History of Malignant Lymphoma](https://reader035.vdocuments.mx/reader035/viewer/2022062519/56814e58550346895dbbf238/html5/thumbnails/49.jpg)
In T-cell lymphomas, one breakpoint
site is at chromosome 14;q11, the
site where the gene for the delta
chain of the T-cell receptor is
embedded in the T-cell receptor
alpha chain gene (Reis, 1989).
![Page 50: History of Malignant Lymphoma](https://reader035.vdocuments.mx/reader035/viewer/2022062519/56814e58550346895dbbf238/html5/thumbnails/50.jpg)
Thus, the generation of antigen receptor genes, immunogloblin genes and T-cell receptor genes is a major cause of human lymphoma. Available evidence suggests that more than a single genetic misadventure is required for tumour induction. The remarkable progress in understanding the molecular events in lymphomagenesis achieved in the past several years suggests that comprehensive understanding of the process is not far off.
![Page 51: History of Malignant Lymphoma](https://reader035.vdocuments.mx/reader035/viewer/2022062519/56814e58550346895dbbf238/html5/thumbnails/51.jpg)
Year Reference Advance in cognition of lymphoma
1832 Hodgkin The primary malignant tumor of lymph nodes subsequently termed Hodgkin’s disease described
1845 Virchow The nature of leukemia defined
1856
1965
Wilks Hodgkin’s cases rediscovered
1864 Viechow The concept of lymphoma is defined and placed under the rubric ‘aleukemic leukemia’
1865 Cohnheim The term ‘pesudoleukaemia’ prpposed for Virchow’s ‘aleukaemic leukaemia’
1892 Dreschfeld Lymphosarcoma separated from pseudoleukaemia and Hodgkin’s disease
1893 Kundrat Lymphosarcoma separated from pseudoleukaemia and Hodgkin’s disease
![Page 52: History of Malignant Lymphoma](https://reader035.vdocuments.mx/reader035/viewer/2022062519/56814e58550346895dbbf238/html5/thumbnails/52.jpg)
Year Reference Advance in cognition of lymphoma
1898 Sternberg The histological picture of Hodgkin’s disease characterized including the diagnostic giant cell
1902 Reed The histological picture of Hodgkin’s disease characterized including the diagnostic giant cell
1925 Brill et al Follicular (nodular ) lymphoma descrbed
1927 Symmers Follicular (nodular ) lymphoma descrbed
1930 RouletReticulum- cell sarcoma distinguished from lymphosarcoma
1947 Jachson & Packer
Hodgkin’s disease divided into paragranuloma, granuloma and sarcoma
1956 Rappaport The first modern classification of non-Hodgkin’s lymphoma based on cytology and the presence orabsebce of follicular structure introduced
![Page 53: History of Malignant Lymphoma](https://reader035.vdocuments.mx/reader035/viewer/2022062519/56814e58550346895dbbf238/html5/thumbnails/53.jpg)
Year Reference Advance in cognition of lymphoma
1958 Burkitt Endemic (African) Burkitt’s lymphoma described
1966Lukes & Bu
tler
Nodular sclerosis Hodgkin’s disease described
1966 Lukes et alThe modern four-part classification of Hodgkin’s disease developed
1972 Aisenberg Preud’homme
Surface markers employed to establish B- and T- cell lineage of lymphoid neoplasms
1973 Barcos & Lukes
Lymphoblastic lymphoma defined
1973Lennert et al
The concept of the follicle centre cell developed and employed to the Kiel classification of non-Hodgkin’s lymphoma
1974Lukes & Collins
An immunological classification of non-Hodgkin’s lymphoma based on perceived B- and T-cell lineage proposed
![Page 54: History of Malignant Lymphoma](https://reader035.vdocuments.mx/reader035/viewer/2022062519/56814e58550346895dbbf238/html5/thumbnails/54.jpg)
Year Reference Advance in cognition of lymphoma
1977 Uchiyama et al
Adult T-cell leukaemia/lymphoma described in Japan
1978 Isaacson & Wright
Delineation of MALT-lymphoma
1981 Korsmeyer et al
Lineage and clonality of B-cell lymphomas defined by immunoglobulin gene rearrangement
1982Taub et al
Dalla-Favera et al
Cloning of the c-myc oncogene from the t(11;14) of Burkitt lymphoma
1984 Tsujimoto et al
Cloning of the bcl-2 oncogene from the t(14;18) of follicular lymphomas
1985 Aisenberg, et al
Lineage and clonality of T-cell lymphoma defined by T-cell receptor gene rearrangement
1991Rosenberg
et al Cloning of the bcl-1 oncogene from the t(11;14) of mantle cell lymphoma
![Page 55: History of Malignant Lymphoma](https://reader035.vdocuments.mx/reader035/viewer/2022062519/56814e58550346895dbbf238/html5/thumbnails/55.jpg)
Year Reference Advance in cognition of lymphoma
1993 Ye et al Cloning of the bcl-6 oncogene from diffuse large cell lymphoma
1994 Harris et al Revised European-American Classification of Lymphoid Neoplasms (REAL classification)
1997 WHO classification first edition
1998 Cloning of the bcl-10 oncogene from MALT-lymphomas
1999 Aisenberg large cell lymphomas of the mediastinum derived from B cells of the thymic medulla
2000 Later WHO classification edition
![Page 56: History of Malignant Lymphoma](https://reader035.vdocuments.mx/reader035/viewer/2022062519/56814e58550346895dbbf238/html5/thumbnails/56.jpg)
![Page 57: History of Malignant Lymphoma](https://reader035.vdocuments.mx/reader035/viewer/2022062519/56814e58550346895dbbf238/html5/thumbnails/57.jpg)
![Page 58: History of Malignant Lymphoma](https://reader035.vdocuments.mx/reader035/viewer/2022062519/56814e58550346895dbbf238/html5/thumbnails/58.jpg)
![Page 59: History of Malignant Lymphoma](https://reader035.vdocuments.mx/reader035/viewer/2022062519/56814e58550346895dbbf238/html5/thumbnails/59.jpg)
![Page 60: History of Malignant Lymphoma](https://reader035.vdocuments.mx/reader035/viewer/2022062519/56814e58550346895dbbf238/html5/thumbnails/60.jpg)
细胞性淋巴瘤
![Page 61: History of Malignant Lymphoma](https://reader035.vdocuments.mx/reader035/viewer/2022062519/56814e58550346895dbbf238/html5/thumbnails/61.jpg)
淋巴母细胞淋巴
瘤
![Page 62: History of Malignant Lymphoma](https://reader035.vdocuments.mx/reader035/viewer/2022062519/56814e58550346895dbbf238/html5/thumbnails/62.jpg)
浆细胞瘤
![Page 63: History of Malignant Lymphoma](https://reader035.vdocuments.mx/reader035/viewer/2022062519/56814e58550346895dbbf238/html5/thumbnails/63.jpg)
免疫母细胞淋巴瘤
![Page 64: History of Malignant Lymphoma](https://reader035.vdocuments.mx/reader035/viewer/2022062519/56814e58550346895dbbf238/html5/thumbnails/64.jpg)
滤泡性淋巴瘤
![Page 65: History of Malignant Lymphoma](https://reader035.vdocuments.mx/reader035/viewer/2022062519/56814e58550346895dbbf238/html5/thumbnails/65.jpg)
Burkitt
淋巴瘤
![Page 66: History of Malignant Lymphoma](https://reader035.vdocuments.mx/reader035/viewer/2022062519/56814e58550346895dbbf238/html5/thumbnails/66.jpg)
HL 之 LP 、 MC
![Page 67: History of Malignant Lymphoma](https://reader035.vdocuments.mx/reader035/viewer/2022062519/56814e58550346895dbbf238/html5/thumbnails/67.jpg)
Thank you !