Rationale for the histological spectrum of tuberculosis. A basis for classification.

There is need to re-appraise the cellular response to Mycobacterium tuberculosis. Histological analysis of 54 untreated patients with established disease demonstrated a continuous spectrum of tissue responses in which six groups correlated with evidence of resistance to bacterial multiplication. A predominance of cases in the two middle groups (82%) signified an immunological equilibrium in middle grade resistant patients that is absent in related diseases such as leprosy and cutaneous leishmaniasis. The dominant feature was necrosis, which increased progressively across the spectrum. Its form varied from minimal fibrinoid change, through fine eosinophilic necrosis, to basophilic necrosis characterized by neutrophil karyorrhexis, and finally to an almost acellular lesion with many bacilli. Cytological differentiation of the granuloma was of subsidiary significance, mature epithelioid cells being found only in high resistant cases. No correlation was found for the number of lymphocytes. This classification is thought to be an accurate reflection of the immune state in relation to antigenic load. It raises a hitherto unconsidered possibility that "caseation", a loosely applied macroscopic term, may embrace immunologically distinct states. The classification of multiple lesions was consistent. Histology offers a promising basis for further immunopathological investigation.