Jeanne Arno

Sinus histiocytosis with massive lymphadenopathy: virological, immunological and morphological studies.

Summary The histiocytes from a patient with sinus histiocytosis were tested for the presence of Epstein‐Barr viral nuclear antigen (EBNA) before and after in vitro growth. On both occasions the histiocytes as well as the lymphocytes were EBNA negative. Likewise the profile of EBV viral capsid antibody (VCA) suggests that this virus is unlikely to be directly involved in the development of the disease. The maintenance of an unusually high level of antibodies to EBV and measles, both viruses which produce persistent infections, indicates that the humoral immune response is active. That a normal humoral response occurred in response to mumps virus during the same period suggests that a deficiency in the cell mediated immune response to the persistent viruses might be the reason for the abnormally high antibody levels. The fresh as well as the cultured histiocytes had only Fc receptors. The affected lymph node lymphocytes developed unusual large inclusion bodies following in vitro culture.

Sinus histiocytosis with massive lymphadenopathy—Properties of cultured histiocytes

Abstract This paper describes the properties of cultured histiocytes derived from lymph node material of a patient with sinus histiocytosis. Before culture the cytoplasm of the histiocytes contained numerous leucocytes, residual bodies and large spherical membrane-bound inclusions of moderate electron density. After prolonged culture, these features disappeared from the cytoplasm. However, when buffy coat cells from a normal individual were brought in contact with the cultured histiocytes, they were phagocytozed and the residual bodies and the large spherical electron dense bodies then reappeared in the cytoplasm of the histiocytes.

Structure and Function

Unlike most other tissues, the generally held concept of a lymph node does not represent the inevitable result of spontaneous maturation of lymphoid tissue. Rather, at any given stage, it reflects the response to those stimuli affecting it.

Non-Hodgkin’s Lymphoma

This negative form of nomenclature is one of convenience. Of the total number of lymphomas, approximately 40% can be separated under the general heading of Hodgkin’s disease, leaving the remainder, a conglomerate of very different conditions. Some at least are readily distinguishable from the rest, but new entities are still in the process of recognition and description. There is at present no universally accepted method of classification and whichever system is adopted, a certain number of tumours defy classification altogether.

‘Active’ Paracortical Expansion

The ‘active’ response may be dominated by changes in the lymphocyte population, with recruitment mitotic activity and transformation. This is particularly seen in response to certain virus infections in the early stages, and also in lymph nodes draining the area of a homograft, or of skin exhibiting contact hypersensitivity.

Follicular Centre Cell Lymphomas (Follicular Lymphomas)

The majority of non-Hodgkin’s lymphomas are follicular in pattern and are thought to arise from the cells of the follicular or germinal centres. Initially this view was based upon cytological correlations which exist between neoplastic and reactive follicular structures but in addition, the cells of follicular lymphomas have been demonstrated to have the surface marker characteristics of B lymphocytes. Further, at ultrastructural level, the presence of dendritic reticular cells can be demonstated within neoplastic follicles, just as in reactive centres.

Reactive Changes Versus Neoplasia

The interpretation of the changes which occur in lymph nodes can be extremely difficult. The difficulties however are perhaps not so great as dogma inherited from the past suggests, since that dogma was based upon the fact that lymph node function was incompletely understood. However, still there occurs a steady trickle of really intriguing cases which defy a wholly confident assessment.

Some Problems in Diagnosis

Reference to problems in diagnosis has already been made, but in this section a few further difficult areas are mentioned, particularly those where different conditions show some overlap in their histological appearances.

Disordered Immunological Function

Quite apart from the normal reactive responses and frankly neoplastic conditions, there are disorders associated with abnormality in immunological function. They are important from the clinical aspect and because they predispose to the development of neoplasia; but in the present context their importance lies in their unusual histological appearances, probably often misinterpreted in the past.

Hodgkin’s Disease (Hodgkin’s Lymphoma)

Previous controversy as to the nature of this condition is still reflected in its name, but nowadays, it is widely accepted as a neoplastic disorder. However, the underlying nature of the peculiar, proliferating cells, the classical Reed-Sternberg cells and their variants, remains uncertain.