D. S. Ridley

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

&NA; 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.

Histochemical demonstration of mycobacterial antigen, specific antibody and complement in the lesions of tuberculosis

SummaryLesions were studied histochemically for mycobacterial antigen, its specific antibody and complement in 31 patients with recently-diagnosed tuberculosis. The results were related to a histological spectrum that correlated with bacterial load. The form, localization and persistence of antigen were found to be as significant as the amount. In high-resistant cases, the antigen was mainly soluble, a form which was non-toxic when ingested by macrophages but associated with tissue damage when bound to connective tissue. There was no close contact between plasma cells and antigen. However, in cases with moderate resistance, where plasma cells and antigen intermingled freely, necrosis with karyorrhexis and polymorph infiltration was associated with deposition of antigen, antibody and complement at the same sites, indicating the probability of immune complex formation in these lesions. In low-resistant cases, extensive necrosis was attributed partly to high levels of extracellular antigen.The correlation between immunological circumstances and the manifold forms of necrosis validated these forms as the basis for a histological spectrum in tuberculosis.

Stain techniques and the morphology of Mycobacterium leprae.

A comparative study of acid-fast stain techniques has shown that some methods in common use give divergent values for the MI , and smaller but significant discrepancies in the BI . The methods used by Rees and Valent ine and by Shepard to equate solid staining with viability are in fairly good agreement. The heating of carbol-fuchsin stain is the factor which causes the most variation in the MI , but fixation, time of staining, and method of differentiation all have some bearing on the results. I t is thought that all the effective staining procedures produce some alteration of bacterial morphology. The need for standardization and the suitability of certain methods for routine application are discussed.