Pathology of post primary tuberculosis of the lung: An illustrated critical review

Abstract

Post primary tuberculosis occurs in immunocompetent adults, is restricted to the lungs and accounts for 80% of all clinical cases and nearly 100% of transmission of infection. The supply of human tissues with post primary tuberculosis plummeted with the introduction of antibiotics decades before the flowering of research using molecular methods in animal models. Unfortunately, the paucity of human tissues prevented validation of the models. As a result, it is a paradigm of contemporary research that caseating granulomas are the characteristic lesion of all tuberculosis and that cavities form when they erode into bronchi. This differs from descriptions of the preantibiotic era when many investigators had access to thousands of cases. They reported that post primary tuberculosis begins as an exudative reaction: a tuberculous lipid pneumonia of foamy alveolar macrophages that undergoes caseation necrosis and fragmentation to produce cavities. Granulomas in post primary disease arise only in response to old caseous pneumonia and produce fibrosis, not cavities. We confirmed and extended these observations with study of 104 cases of untreated tuberculosis. In addition, studies of the lungs of infants and immunosuppressed adults revealed a second type of tuberculous pneumonia that seldom produces cavities. Since the concept that cavities arise from caseating granulomas was supported by studies of animals infected with Mycobacterium bovis, we investigated its pathology. We found that M. bovis does not produce post primary tuberculosis in any species. It only produces an aggressive primary tuberculosis that can develop small cavities by erosion of caseating granulomas. Consequently, a key unresolved question in the pathogenesis of tuberculosis is identification of the mechanisms by which Mycobacterium tuberculosis establish a localized safe haven in alveolar macrophages in an otherwise solidly immune host where it can develop conditions for formation of cavities and transmission to new hosts.

Diagnóstico genotípico y fenotípico de tuberculosis ósea y miliar en un paciente VIH positivo en Bogotá, Colombia

“…El análisis macroscópico del órgano afectado suele revelar lesiones redondeadas, pequeñas, de color rojo pálido a gris, y en la histología se evidencia el típico hallazgo de granulomas con centro caseificante. En la infección avanzada por HIV las características cambian notablemente, pues es común encontrar granulomas poco formados, con mínima reacción celular, necrosis seria y bacilos abundantes (21,22). No obstante, en el presente caso el patólogo reportó que el patrón histológico observado tenía las características habituales, aunque sí se detectó la presencia de abundantes bacilos tanto en el tejido pulmonar como en el óseo.…”

“…Los casos extrapulmonares y óseos, en particular, suelen ser paucibacilares, lo que aumenta la dificultad del diagnóstico, incluso cuando la tuberculosis es el diagnóstico diferencial (21,25,26).…”

“…Aunque la prueba de referencia para el diagnóstico de la tuberculosis es el aislamiento del agente etiológico, recientemente se ha reportado que las pruebas más efectivas para el diagnóstico rápido de la tuberculosis osteoarticular son la PCR y el análisis histopatológico del tejido afectado (21,22,25).…”

Mycobacterial TDM: A Coat to Modulate Post Primary Pathogenesis?

“…Reports by Hunter suggest that the rapid necrosis of tuberculous pneumonia might be due to both the activation of toxic and adaptive immunogenic properties of cord factor after contact with host lipids [4,5,7,49]. This hypothesis diverges from classical interpretation of expanding granulomas as the basis of necrotizing lesions [1,50].…”

“…The abundant surface glycolipid antigens, mycolic acid and trehalose 6,6'-dimycolate, dictate much of the primary pathological response [3], with known granulomatous-inducing properties. In contrast, post primary tuberculosis (also referred to as secondary or adult tuberculosis) was recently redefined as a caseating pathology arising in immune competent individuals whereby organisms evade strong and effective systemic specific immunity [4][5][6]. In modern day cases, post primary tuberculosis is often associated with a lipid pneumonia, challenging long held beliefs that cavities arise from expansion of caseating granulomas [7].…”