reticular cells ", the reticular (supporting) cells and endothelial cells, and it is ... lymphoreticular tissues (Table I) are ... the production of connective tissue fibres.
Br. J. Cancer (1975) 31,
Suppl. II, 73
ELECTRON MICROSCOPY IN THE NON-HODGKIN'S LYMPHOMATA K. HENRY* From the Department of Histopathology, Royal Postgraduate Medical School, London W.12
Summary.-The component cells of peripheral lymphoid tissue have been divided into the lymphocyte and plasma cell lines, mononuclear phagocytic cells, dendritic " reticular cells ", the reticular (supporting) cells and endothelial cells, and it is suggested that this system of cells should collectively be referred to as the lymphoreticular mononuclear phagocyte system or LRMPS. Seventeen tumours of the LRMPS (excluding Hodgkin's disease) have been studied at ultrastructural level. Of these 17 non-Hodgkin lymphomata 5 were follicular lymphomata and 12 diffuse. It is concluded that electron microscopy plays a valuable role in the diagnosis of this group of tumours. Not only does it allow rejection of a diagnosis of lymphoma in certain anaplastic tumours, but it also enables a more precise identification of the cellular components of a lymphoma as well as indicating the degree of differentiation of the cell line involved. Additional advantages are the visualization of subcellular structures useful as markers, and by means of specialized immunoelectron microscopic techniques the identification of antigens and antibody formation within a given tumour. Two other results of this ultrastructural study are the indication that the dendritic cells of lymphoid follicles are derived from capillary endothelium, and the identification of certain anomalous formations derived from rough endoplasmic reticulum in the case of tumours showing plasmacytoid differentiation. BEFORE discussing the role of electron (MPS). Evidence was provided and acmicroscopy in the diagnosis of the lym- cepted at the Symposium that within the phomata, it is useful to consider briefly bone marrow there is a stem cell which some aspects of current concepts and terminology of the lymphoreticular tissue and mononuclear phagocyte cell svstem (LRMPS), and the ultrastructural ap-
pearances of the component cells. The component cells of peripheral lymphoreticular tissues (Table I) are lymphocytes and plasma cells (T and B cell lines) (Roitt et al., 1969), mononuclear phagocytic cells, the dendritic " reticular " cells of the lymphoid follicles, the supportive reticular (fibre associated) cells and endothelial cells (Henry, 1972). The usage of the term " reticuloendothelium " has been avoided, the reason being that at a recent Symposium on mononuclear phagocytes Aschoff's original concept of the reticuloendothelial system was abandoned (Van Furth, 1970) and replaced by the mononuclear phagocyte system *
6
develops into an avidly phagocytic cellthe macrophage. Macrophages are widely distributed throughout the body and terminology differs according to the site in which they are found. The only phagocytic cells where proof of a monocytic origin still remains to be established are the fixed macrophages, including the sinusoidal lining cells of peripheral lymphoreticular tissue. However, since these cells are markedly phlagocytic and share morphological features in common with cells of the MPS, they are included within this system. In lymphoreticular tissue macrophages have a characteristic appearance at electron microscopic level. They possess a ruffled plasma membrane due to the presence of numerous finger-like projections from the cell surface, a prominent Golgi apparatus and numerous
Present address: Dept. of Histopathology, Westminster Medical School, London
SWIP 2PP.
74
K. HENRY
TABLE I.-Component Cells of the Periph- is evidence at electron microscopic level eral Lymphoreticular Tissue and Mono- that the follicular dendritic cells are nuclear Phagocyte System (LRMPS) derived from capillary endothelial cells, for it is possible to demonstrate continuity Lymphocyte and plasma cell series (T and B between endothelial cells and dendritic lymphocyte cell lines) Mononuclear phagocytic cells cell processes (Fig. 3), (Henry, 1973, Dendritic " reticular " cells unpublished). Also, endothelial cells, like Endothelial cells Reticular fibre associated cells (fibroblasts) dendritic cells, possess desmosomal attachments. It is particularly interesting in mitochondria, and contain many electron this context that Soderstrom, following a dense residual bodies of lysosomal nature. light microscopic study of the development Their nucleus usually is eccentrically loca- of lymph nodes in mice, suggested that the ted and contains a well defined nucleolus. secondary follicles (germinal centres) The true reticular cells or supporting cells might develop from post-capillary venules have a very different appearance. They due to a massive proliferation of the tall tend to be elongated, show a dense endothelial cells (Soderstrom, 1967). fibrillary or felt-like material along their The lymphoid cells found within cytoplasmic borders and desmosomal germinal centres are lymphocytes with attachments between these cells can also distinctive irregularly shaped nuclei, often be demonstrated. In some instances they with nuclear protrusions or blebs (Fig. 2). are indistinguishable from fibroblasts and, They are the germinocytes described by indeed, they are the cells responsible for Mori and Lennert (1969) and the cleaved the production of connective tissue fibres cells originally described as haematogones with the same periodicity of collagen by Rosenthal (1954). Compared with (reticulin). They are found in close paraffin embedded material or imprint relationship to mononuclear phagocytic preparations, the nuclei do not appear so cells. The dendritic reticular cells first clearly notched and there is also more described by Maruyama and Masuda cytoplasm. Other lymphoid cells present (1964) are not included in the mono- in germinal centres are larger, also contain nuclear phagocyte cell system since they an irregular nucleus with a prominent are not avidly phagocytic. They are the nucleolus, and contain an appreciable RNTA cells especially associated with lymphoid content with formation of polyribosomes. follicles. However, they are found else- These correspond to the germinoblasts where in peripheral lymphoid tissue and (Mori and Lennart, 1969). Both types of are thought to function by virtue of lymphocytes inter-digitate with processes trapping antigens on to their surface of the dendritic reticular cells. As one (Nossall et al., 1968). Dendritic cells also proceeds out of the germinal centre, have a very distinctive appearance, with communications between the cells become long cytoplasmic processes forming com- less prominent and one also encounters plex inter-digitations with neighbouring large rounded lymphoid cells or immunodendritic cells and lymphocytes (Fig. 1). blasts (Fig. 4). These cells are rich in A special feature, to which attention has polyribosomes and also show profiles of been drawn only comparatively recently rough endoplasmic reticulum. They cor(Swarzendruber, 1965) is the presence of respond to the pyroninophilic blast cells desmosomal attachments between one and are aiso found outside the lymphoid dendritic cell and another (Fig. 1, inset). follicles. Other common findings are fine filaments One of the main (lisadvantages of within the cytoplasmic processes and electron microscopy in the lymphomata is electron dense material lving between the that of sampling and this applies particucytoplasmic extensions (Fig. 2). Their larly to the follicular lymphomata. Beorigin has niot been established but there cause the tissue is cut into small pieces for
75
ELECTRON MICROSCOPY IN THE NON-HODGKIN'S LYMPHOMATA
4* 0 .O.
00
Ox C)
4a, 0
CO oX
0
4D
C)
0
0-
C)
x
76
K. HENRY
00
;Zo "o
4D
0 4D
(D o
*^ 0D
>4o
;b0
s B 000
0 4.
k!"ll
'w .7
'l.
41. 11
iN 1-
.
If.,
at
ELECTRON MICROSCOPY IN THE NON-HODGKIN'S LYMPHOMATA
77
0
0
0 4a) 00
0
z,
0D -4-
0 C) *C Q
V1,
CD
.O
00 ._
tiC) ._0
00
02C
,-
'D
Q-
0
C)
78
K. HENRY
00
bOw
0-
soQ 4-C
w _0o
B
a;
00
_-i
0X
0
N
.4
79
ELECTRON MICROSCOPY IN THE NON-HODGKIN S LYMPHOMATA
0
00
c4Q
0
4a,
-4/*~j
I00
0
.;
wt.A
.V. 4U2
10 -7
...
-:a
I, 11I..,
I
4.
.-
.Ii-.
.if
'.
.
... .''.
.16, P.,P
I
^', ;,
*;fit,+ 80
K. HENRY
0-
~o C1) 0
040 U's
0 .0 00
04c;
a.4
O
54z O 4) -0
b*¢WR
E
0 4b0
.Po o z
gD
.,.
a)
*4-
.1 14
i
84
K. HENRY
C)
._ ._
o
g)
_D 0 Jim
I
I I
o o Ca
1, ; -4a 4)
4)
2.;
I. o e
0-
o
O
ELECTRON MICROSCOPY IN THE NON-HODGKIN S LYMPHOMATA
85
CD
ci)
Z-4 C) >'
,o m
0
o o" o
dbCo
eo
0" C)g oP,C)^ E--
-Y ci) 0
0 -C) ci) 4-Z
86
K. HENRY
e. 4.-t
C)
0
c
0 eD 0
hoo~ 0
XD
0-
2D I
rU 0 9 rQ
B r° .;
im
;V--.., ,4
0'.-
ELECTRON MICROSCOPY IN THE NON-HODGKIN S LYMPHOMATA
w %;.-% ,
V.7
C)
.
I
Co
7
f
.n.
4,
*
..
ovX
,.1.4
., --r:
..i
.1
x
U2
-WI,
;X.c
87
i.
"'
PO-
A
0-
4zC)
C)
OC 0
4Z
4CC) 4z
Co Ezo
4..-
C0
*1 t 4.iiir*4.
.A"
C) _D
&t.
-I.
e r
bR.1 t1 .t
hO" -o
Ae.
'su W.77k ,%0:s ;,
t'':
__56 tS '
>'':t
t
46'^
r i.t i
>;
S; 't * t f ;'S a
.
i.
,
