J Clin Pathol: first published as 10.1136/jcp.26.5.317 on 1 May 1973. Downloaded from J. clin. Path., 1973, 26, 317-331 A proposal for a standardized system of reporting human lymph node morphology in relation to immunological function' H. COTTIER, J. TURK, AND L. SOBIN2 From the Department of Pathology, University of Berne, Switzerland, the Department of Pathology, Royal College ofSurgeons, London, and the World Health Organization, Geneva SYNOPSIS This memorandum proposes a standardized system of reporting the histology of human lymph nodes based on commonly used simple staining techniques. The purpose is to provide a uniform, internationally acceptable system by which the histological structure of lymph nodes can be correlated with other parameters of immunological status. The proposed protocols are intended to provide information that is not available in conventional written reports that use such terms as 'hyperplasia' or 'nonspecific lymphadenitis'. The increasing use of immunological tests in of reporting. Correlation between lymph node copyright. clinical medicine has demonstrated a need for morphology and other parameters of immunological standardized reporting of the appearance of lymph response, associated with humoral antibody pro- node sections. Although there have been many duction and cell-mediated immunity, could assist advances in the knowledge of lymph node structure the physician in his final assessment and treatment in the past 10 years as a result of correlation be- of the patient. This approach may be of special tween lymph node changes and immunological value in the management of patients with disorders function, these have not been reflected in the reports such as neoplastic and infectious diseases. http://jcp.bmj.com/ generally issued from histopathology laboratories. In the present proposals care has been taken to Such changes are now well recognized by immuno- use terms that are descriptive rather than those logists but have not yet been adopted by histo- based on as yet debatable functional interpretations. pathologists, since until now emphasis has been Thus the term 'paracortical area' has been used in given almost exclusively to major pathological preference to 'thymus-dependent area' and the lesions rather, than to changes associated with term 'large lymphoid cell' in preference to 'immuno- variations in the immune response. The present blast', 'plasmablast', etc. on September 25, 2021 by guest. Protected proposals have been prepared in the hope that pathologists will also comment in their reports on Recommendations for Handling and Processing of structural variations associated with immunological the Tissue function. This could add a further dimension to the physician's analysis of the immunological Unusual care should be exerted during excision status of the patient analogous to information on of the lymph node. It is important that the node the endocrine state as determined by endometrial itself should not be handled with forceps as com- biopsies. Since the lymph node is one of the tissues pression of the tissue during the procedure can result most frequently examined by histopathologists, in distortion and prolonged manipulation during a considerable amount of information is currently surgery can produce acute inflammatory changes. being lost because of the lack of a consistent system Forceps should be applied only to the surrounding tissue and not to the node. It is strongly recommend- "Reprinted in slightly modified form, and with the addition of a bibliography, from Bulletin of the World Health Organization (1972), ed that the whole node should be removed rather 47, 375-406. than fragments of the tissue. 'Requests for reprints should be addressed to Dr L. Sobin, WHO, Once removed the node should be cut trans- 1211 Geneva, 27 Switzerland. versely through its short axis in order to permit 317 J Clin Pathol: first published as 10.1136/jcp.26.5.317 on 1 May 1973. Downloaded from 318 H. Cottier, J. Turk, and L. Sobini penetration of the fixative. For a comparable result of fixation, dehydration, and embedding assessment of immunological function it is neces- and an absolute assessment of size is omitted from sary to examine a transverse section cut along the the following description. short axis from the middle portion of the node; Recent developments in cell kinetics have shown this will contain representative areas of the cortex that the non-proliferating precursors of all immuno- and the medulla. logically active cells have the morphological ap- It is understood that as a routine procedure it pearance of small lymphocytes. These cells when may be difficult to use fixatives other than neutral proliferating and differentiating acquire a common formalin. However, Carnoy's solution is better appearance and are referred to here as 'large for the assessment of cellular morphology and is lymphoid cells'. During the cell-mediated immune especially useful for subsequent staining with response these cells will divide into elements that are methyl green and pyronin. Although for most pur- usually morphologically indistinguishable in tissue poses haematoxylin-eosin staining is adequate for sections from the precursor small lymphocyte. the examination of the tissue, Giemsa stain or Similar cells when proliferating and differentiating methyl green and pyronin allow very rapid assess- into plasma cells start off with the same appearance ment at low-power magnification of the immunolo- and, therefore, should also be called 'large lymphoid gically important cells and structures such as plasma cells'. It is recognized that in tissue sections there are cells and germinal centres. cells that appear identical under the light microscope with small lymphocytes but examination under the Recommended Nomenclature for Cell Types in the electron microscope and the use of immuno- Lymph Nodes as Seen in Histological Sections histological techniques indicate that they are involved in immunoglobulin synthesis. However, Ideally, the nomenclature of tissue structures and they cannot be recognized as such without the use cells of the lymphoid and plasma cell systems of these methods. should be based on functional as well as morpholo- gical criteria. Although one may say definitely LARGE LYMPHOID CELLS (figs 1, 3, 14) copyright. that a mature or immature plasma cell is producing These cells have large vesicular nuclei with prominent immunoglobulin, one cannot ascribe a function to nucleoli and moderate amounts of basophilic and a given large lymphoid cell or a small lymphocyte pyroninophilic cytoplasm. They are frequently seen purely on morphological appearance. For example, in mitosis. Cells with these characteristics occur small lymphocytes morphologically identical in during the proliferation of lymphocytes during a tissue sections can be the precursors of plasma cell-mediated immune response as well as in relation http://jcp.bmj.com/ cells involved in immunoglobulin synthesis or of to plasma cell proliferation and in germinal centres the effector cells of cell-mediated immunity. The in humoral antibody responses, when they may latter also have the morphological appearance of contain immunoglobulin. small lymphocytes. Similarly, it may be difficult to distinguish the large proliferating precursor cells of elements involved in cell-mediated immunity from MEDIUM-SIZED LYNMPHOCYTES (figs 1, 3) those involved in immunoglobulin synthesis. Even There is a range of nuclear and cytoplasmic size the precursors of other blood cell lines resemble between large lymphoid cells and small lymphocytes. on September 25, 2021 by guest. Protected may This large lymphoid cells or small lymphocytes. may reflect transition between a proliferating and Terms such as immunoblast, plasmablast, or resting state as well as some degree of functional haemocytoblast indicate a function that cannot be differentiation. The term 'medium-sized lymphocyte' directly determined from the histological examination is used to describe cells with any appearance in of lymphoid tissue alone. The use of these terms between that of large lymphoid cells and small is often based on circumstantial evidence and they lymphocytes. should be applied only to describe large lymphoid cells in certain controlled immunological situations. SMALL LYMPHOCYTES (figs 2, 3, 4) For practical reasons, the following nomenclature These are defined according to conventional has been based essentially on the morphological nomenclature. and staining characteristics of cells that are easily recognizable with the aid of simple staining methods MATURE PLASMA CELLS (fig 4) and the light microscope. In this way, it should This term is restricted to cells with a typical eccentric be possible to obtain agreement between patholo- cart-wheel nucleus of similar size to that of a small gists and immunologists on their microscopic lymphocyte, abundant basophilic and pyronino- findings. The sizes of cells are subject to change as a philic cytoplasm, and a pale paranuclear area. J Clin Pathol: first published as 10.1136/jcp.26.5.317 on 1 May 1973. Downloaded from copyright. Fig 2 Fig 1 Corticomedullary junction ofa lymph node. LL, large lymphoid cell; RE, reticulum cell or endothelial http://jcp.bmj.com/ cell (endothelial cells may resemble reticulum cells in tangential sections); NG, neutrophilic granulocyte. Note that in sections only a few micrometres in thickness, and without special staining, it is often difficult to distinguish between medium-sized lymphocytes and a cross-sectioned reticulum