This study has provided information on the spectrum of changes which can occur in different PID. Using a pattern-based approach for the analysis of the lymph node parenchyma, it is obvious that there are no morphological features specifically associated with a single disease. This indicates that the lymph node biopsy is per se insufficient to identify any specific form of PID. There are, however, a few exceptions: with the advantage of immunohistochemistry we found severe abnormalities of FDC in X-linked hyper-IgM, which can be used for diagnostic purposes. Other morphological phenotypical features of lymph nodes, when correlated with clinical and hematological data, can be relevant for the correct attribution to a specific disease: a lymph node with preserved cellularity is never found in T⁻B⁻ SCID, unless associated with engraftment of maternal/donor lymphocytes. On the other hand, lymph node changes that have been considered characteristic of OS, can also be observed in other conditions, and may sometimes derive from associated skin diseases. This indicates that the distinction between these PID might not be absolute, not only in terms of morphology, but also in terms of cell defects and pathogenesis.

The heterogeneity of lymph node histology observed within the same disease can be explained by the complex of interactions regulating the ontogeny and development of lymphoid organs. In addition, it may reflect the phenomenon of identical genetic anomalies that give different phenotypes [72]. In certain conditions, such as the WAS, this morphological variability can be correlated with clinical variations of the disease, and can be helpful in the study of the biological mechanisms associated with gene mutations and protein expression defects.

Knowledge of the spectrum of changes which can be found in lymph nodes in different forms of PID may be helpful not only in better defining the clinical diagnosis, but also in the evaluation of biopsy/autopsy material from patients who died without a precise diagnosis being made, and in genetic counselling. With the help of advanced techniques, such as in situ hybridization for mRNA encoding specific immune-related gene products, the study of lymph node biopsy samples will provide greater insight into the processes regulating the immune response, in normal and pathological conditions.