Pólipo y/o granuloma aural en niños. Estudio prospectivo en 75 casos / Aural polyp and/or granuloma in children. A prospective study of 75 cases

En otorrinolaringología (ORL) infantil es habitual el hallazgo de pólipos y granulomas de oído en niños que consultan especialmente por otorrea de evolución prolongada. El pólipo y/o granuloma aural es una masa de carácter inflamatorio, que ocupa parte de la luz del conducto auditivo externo, generalmente pediculado, de aspecto congestivo, a veces friable y fácilmente sangrante, cuyo origen generalmente es a nivel de la mucosa del oído medio. Con el objetivo de describir las características clínicas, otológicas, bacteriológicas e histopatológicas de los pólipos y granulomas de oído diagnosticados en un servicio de ORL pediátrico se realizó un estudio prospectivo, descriptivo, observacional y longitudinal. Se estudió a la población pediátrica con diagnóstico de pólipo y/o granuloma aural en su primera consulta en el servicio de ORL del Hospital de Pediatría "Prof. Dr. Juan P. Garrahan". Se incluyeron 75 pacientes en el estudio, evaluados consecutivamente desde el 02 de diciembre 2013 y hasta 30 enero del 2015, con una edad media: 93 meses (rango 2­180). Se realizó otomicroscopía y, en los casos de granulomas y pólipos accesibles, se realizó toma de muestra para estudio bacteriológico e histopatológico y evaluaciones audiológicas y radiológicas con tomografía computarizada (TC) en los casos necesarios. Se indicó el tratamiento médico o quirúrgico adecuado a cada patología. El motivo de consulta principal fue la otorrea como único síntoma en el 81,33% de los casos y, en menor porcentaje, asociada a otros síntomas. Tiempo medio de evolución de los síntomas: 13,5 meses (rango 1-96). No se pudo extraer material en el 20% de los pacientes. Se tomaron muestras para estudio de 60/75 granulomas óticos accesibles. El informe anatomo-patológico fue: granuloma o pólipo inflamatorio en el 50%, tejido epidermoide compatible con colesteatoma en el 41,7%, tuberculosis (TBC) en 3,3%, granuloma por cuerpo extraño en 1,7%, histiocitosis de células de Langerhans (HCL) en 3,3% muestras de pólipos. Se realizó estudio bacteriológico en 57/75 casos. Se desarrollaron gérmenes en 52/57 cultivos. El 32,7% (17/52) fueron cultivos polimicrobianos. Dos casos desarrollaron Mycobacterium tuberculosis. Se observó velamiento de caja, ático o mastoides con erosión ósea en el 46,2% (24/52) de los casos evaluados con TC. Diagnóstico final: colesteatoma 39 pacientes, OMA con pólipo de Scheibe o complicada con mastoiditis 16, OMC simple granulomatosa 13, TBC 2, HCL 2, otitis externa y celulitis en conducto auditivo externo 2 y granuloma a cuerpo extraño 1. Conclusiones: es importante obtener el diagnóstico histológico y microbiológico de los pólipos aurales en niños precozmente para excluir neoplasia u otras enfermedades granulomatosas específicas y evitar cirugías que pueden provocar secuelas al no estar indicadas en el tratamiento adecuado de ciertos tumores e infecciones (AU)

In pediatric otolaryngology (ENT) ear polyps and granulomas are a common finding in children who consult especially for prolonged otorrhea. The aural polyp and/or granuloma is an inflammatory mass occupying part of the lumen of the external auditory canal. It is usually pedunculated, congestive, sometimes friable, and may bleed easily. Its origin is usually at the level of the mucosa of the middle ear. With the aim to describe the clinical, otological, bacteriological, and histopathological features of ear polyps and granulomas diagnosed in a Department of pediatric ENT, a longitudinal, prospective, descriptive, observational study was conducted. Pediatric patients diagnosed with an aural polyp and/or granuloma at the first visit at the Department of ENT of Hospital de Pediatría "Prof. Dr. Juan P. Garrahan" were studied. Seventy-five patients were included in the study, evaluated consecutively from December 2, 2013 to January 30, 2015; Mean age was 93 months (range 2 ­ 180). Otomicroscopy was performed and, in cases of accessible granulomas and polyps, a sample was taken for bacteriological and histopathological study. Audiological and radiological evaluations with computed tomography (CT scan) were performed when necessary. Appropriate medical or surgical treatment was indicated accordingly. The main reason for the consultation was otorrhea as the only symptom in 81.33% of cases and, in a lesser percentage, associated with other symptoms. Mean time from symptom onset to diagnosis: 13.5 months (range 1-96). No sample could be harvested in 20% of patients. Samples were taken for study of 60/75 accessible ear granulomas. Pathology report was: Inflammatory granuloma or polyp in 50%, epidermoid tissue compatible with cholesteatoma in 41.7%, tuberculosis (TBC) in 3.3%, granuloma due to a foreign body in 1.7%, and Langerhans cell histiocytosis (LHC) in 3.3% of the samples of polyps. Bacterial cultures, performed in 57/75 cases, were positive in 52/57. Polymicrobial microorganisms were found in 32.7% (17/52). Mycobacterium tuberculosis was found in two cases. Opacification of the antrum, attic, and mastoid cavities with bone erosion was observed in 46.2% (24/52) of the cases evaluated with CT. Final diagnosis: Cholesteatoma in 39 patients, OMA with a Scheibe polyp or complicated with mastoiditis in 16, simple granulomatous OMC in 13, TBC in 2, LHC in 2, external otitis and cellulitis in the external ear canal in 2, and granuloma due to a foreign body in 1. Conclusions: Histological and microbiological diagnosis of aural polyps in children should be obtained early to rule out neoplasia other granulomatous diseases to avoid surgery that may cause sequelae and is not the adequate management of certain tumors and infections (AU)

Tiña incógnita y granuloma de Majocchi adquirido de un erizo. Un caso mexicano / Mexican case of tinea incognito and granuloma de Majocchi acquired from a hedgehog

Resumen Las mascotas exóticas, como el erizo de tierra, son capaces de transmitir al ser humano diferentes infecciones, como salmonelosis, micobacterias, protozoos como Cryptosporidium parvum, y dermatofitosis. Presentamos el caso de un paciente adulto masculino, que recientemente había adquirido un erizo de tierra, que presentó en la mano una lesión de tiña incógnita y un granuloma de Majocchi. Se identificó el agente etiológico como Trichophyton erinacei, por cultivo micológico y biología molecular. El paciente se trató con terbinafina por vía oral, por seis meses, con excelente respuesta.

Exotic pets, such as the ground hedgehog, are capable of transmitting to the human being different zoonoses, such as salmonellosis, mycobacteria, protozoa such as Cryptosporidium parvum, and dermatophytosis. We present the case report of a male adult patient, who had recently acquired a ground hedgehog, who presented in his hand a ringworm lesion incognito and a Majocchi granuloma. The etiological agent was identified as Trichophyton erinacei by mycological culture and molecular biology. The patient was treated with terbinafine oral, with excellent response.

Microarray analysis of the in vitro granulomatous response to Mycobacterium tuberculosis H37Ra / Análisis con Micromatrices de la respuesta granulomatosa in vitro a Mycobacterium tuberculosis H37Ra

Background: The hallmark of tuberculosis is the granuloma, an organized cellular accumulation playing a key role in host defense against Mycobacterium tuberculosis. These structures sequester and contain mycobacterial cells preventing active disease, while long term maintenance of granulomas leads to latent disease. Clear understanding on mechanisms involved in granuloma formation and maintenance is lacking. Objective: To monitor granuloma formation and to determine gene expression profiles induced during the granulomatous response to M. tuberculosis (H37Ra). Methods: We used a previously characterized in vitro human model. Cellular aggregation was followed daily with microscopy and Wright staining for 5 days. Granulomas were collected at 24h, RNA extracted and hybridized to Affymetrix human microarrays. Results: Daily microscopic examination revealed gradual formation of granulomas in response to mycobacterial infection. Granulomatous structures persisted for 96 h, and then began to disappear. Conclusions: Microarray analysis identified genes in the innate immune response and antigen presentation pathways activated during the in vitro granulomatous response to live mycobacterial cells, revealing very early changes in gene expression of the human granulomatous response.

Antecedentes: La marca histológica de la tuberculosis es el granuloma, una acumulación celular organizada que cumple funciones claves en la defensa del hospedero contra Mycobacterium tuberculosis. Estas estructuras secuestran y confinan a las micobacterias previniendo el desarrollo de enfermedad activa; el mantenimiento a largo plazo de los granulomas conlleva al establecimiento de latencia. Un mejor entendimiento de los mecanismos involucrados en la formación y mantenimiento del granuloma es necesario. Objetivo: Monitorear la formación del granuloma y determinar los patrones de expresión génica inducidos durante la respuesta granulomatosa a M. tuberculosis (H37Ra). Métodos: En este estudio se empleó un modelo in vitro humano previamente caracterizado. La agregación celular fue examinada diariamente mediante microscopia óptica y tinción de Wright por 5 días. Para analizar la expresión génica, los granulomas fueron colectados a las 24 h, se extrajo el RNA sometiéndolo a hibridación a micromatrices de Affymetrix. Resultados: Se observó la formación gradual de granulomas en respuesta a la infección. Los granulomas persistieron por 96 h, y luego se desvanecieron. Conclusiones: Se identificaron genes de la respuesta inmune innata y vías de presentación antigénica activadas durante la respuesta granulomatosa in vitro a células micobacteriales vivas, lo cual reveló alteraciones tempranas de la expresión génica en el inicio de la respuesta granulomatosa humana.

Eficacia del diagnóstico diferencial de tuberculosis mediante reacción de polimerasa en cadena en lesiones granulomatosas de tejidos fijados en formalina e incluidos en parafina / Efficacy of PCR for the differential diagnosis of tuberculosis in granulomatous lesions of paraffin-embedded formalin fixed tissues

Background: Granulomatous lesions occur in tuberculosis (TB), other infections, toxic, allergic, and autoimmune diseases among others. In absence of a an acid-fast bacilli (AFB) confirmation of TB is necessary. Objective: To assess the efficacy of PCR for TB detection and to correlate with granuloma histology and AFB staining. Methods: We analyzed 380 fixed paraffin-embedded tissues (PETs) of granulomas with and without caseous necrosis; suppurative; sarcoidal; or of chronic nonspecific nature. Nested PCR-IS6110 for Mycobacterium tuberculosis complex (MTB) and a nested pan-Mycobacterium for the hsp65 gene were used for Mycobacterium spp detection. Results: PCR was more sensitive than AFB staining for all five catageories of granulomas: G1: PCR 71%, AFB staining 28%. G2: PCR 37%, AFB 8%. G3: PCR 17%, AFB staining 7%. G4: PCR 8%, AFB staining 4%. G5: PCR 6%, AFB staining 0%. Conclusions: Molecular diagnosis of TB using PCR-based testing is a fast, efficacious and sensitive method that increased the accuracy of PET histological diagnosis associated with granulomatous lesions.

Introducción: Lesiones granulomatosas ocurren en tuberculosis (TBC), otras infecciones, condiciones tóxicas, alérgicas y autoinmunes, entre otras. Con baciloscopia negativa, es necesario confirmar el diagnóstico de TBC. Objetivo: Evaluar la eficacia de la RPC para detectar TBC comparado con baciloscopia en relación a la histología del granuloma. Métodos: Analisis de 380 tejidos fijados en formalina e incluidos en parafina (TFFP) con diferentes tipos de granulomas: con necrosis caseosa; sin necrosis caseosa; supurativo; sarcoidal; a cuerpo extraño/inespecífico. Utilizamos RPC anidada-IS6110 para detección del complejo Mycobacterium tuberculosis (MTB) y una pan-RPC anidada-hsp65 para Mycobacterium spp. Resultados: La detección de TBC mediante RPC fue significativamente superior a baciloscopia en los cinco tipos de granuloma: G1: RPC 71%, baciloscopia 28%; G2: RPC 37%, baciloscopia 8%; G3: RPC 17%, baciloscopia 7%; G4: RPC 8%, baciloscopia 4%; G5: RPC 6%, baciloscopia 0%. Conclusión: El diagnóstico de TBC por RPC es un método rápido, eficaz y de gran sensibilidad, que aumenta la precisión del diagnóstico diferencial de lesiones granulomatosas de TFFP procesados rutinariamente en histopatología.

Synovial Cyst with Fungal Granuloma.

Synovial cysts are frequently seen and are most commonly seen at the back of the knee where it is known as popliteal cyst. But synovial cyst with fungal granuloma is rather rare. This case report illustrates an occurrence of synovial cyst with fungal granuloma, in a 40 years old male at the dorsal aspect of the right ankle joint. Clinical examination revealed lesion about 4x4x4cms in size over the dorsal aspect of the right ankle joint. Simple excision of the lesion was done with the clinical diagnosis of lipoma. Microscopic examination revealed synovial lining hyperplasia and subintimal tissue showed granulomatous reaction with foreign body giant cells and black colored fungal colonies. Patients did not attend further, so follow up was not available.

Esporotricosis granulomatosa: presentación de dos casos inusuales / Granulomatous sporotrichosis: report of two unusual cases

Sporotrichosis is a subcutaneous mycosis caused by Sporothrix complex, endemic in Abancay, Peru. Is acquired by traumatic inoculation with plant material. Common clinical presentations are lymphatic cutaneous and fixed cutaneous disease. We report 2 cases of fixed cutaneous sporotrichosis with granulomatous appearance. The first case was a patient of 65 years old with no risk factors and the second case was a 67 year old diabetic patient. Subjects underwent mycological culture with Sabouraud agar, with isolation of Sporothrix schenckii and clinical dignosis of fixed cutaneous sporotrichosis with granulomatous appearance. One patient received oral treatment with saturated solution of potassium iodide (SSKI) with a initial dose of 3 drops tid up to a maximum dose of 40 drops tid. Mycological and clinical cure was achieved after 2 months of treatment. We should consider the unusual clinical presentations of fixed cutaneous sporotrichosis with granulomatous appearance that present morphological and clinical features in diabetic and nondiabetic patients older than 60 years from endemic areas and communicate adequate response to treatment with SSKI in one case.

La esporotricosis es una micosis subcutánea ocasionada por el complejo Sporothrix, endémica en Abancay, Perú. Se adquiere por inoculación traumática con material vegetal. Las formas clínicas comúnmente descritas son la cutánea linfática y cutánea fija. Presentamos dos casos de pacientes adultos con una esporotricosis cutánea fija granulomatosa. El primer caso era una paciente de 65 años de edad, sin antecedentes de riesgo y el segundo era una paciente de 67 años, diabética. El diagnóstico se realizó por cultivo micológico aislándose Sporothrix schenckii. Un caso se trató con solución saturada de yoduro de potasio (SSKI), vía oral, alcanzando la cura micológica y clínica tras dos meses de tratamiento. La otra paciente no acudió a tratamiento. Se revisan las presentaciones clínicas inusuales de la esporotricosis cutánea fija y la forma granulomatosa que presenta características morfológicas y clínicas poco habituales en pacientes diabéticos y no diabéticos mayores de 60 años provenientes de zonas endémicas.

Revisiting the Rich's formula: an update about granulomas in human tuberculosis

The formula proposed by Rich in 1951 explained the formation in a tuberculous lesion in a period that was unknown cellular functions, cytokines and other immunological aspects involved in granuloma formation by tuberculosis; its components are assembled conceptually to explain the pathogenic mechanisms involved in the granulomatous lesion in tuberculosis. In this manuscript, we report an update of Rich's formula based on the new and old concepts about pathogenic mechanisms involved in the granulomatous lesion in tuberculosis. Current knowledge allows us to conclude that the balance between the characteristics of the bacillus and host protective response is necessary to indicate the outcome of pathogenesis, infection or active disease and the necrosis degree of the tuberculosis lesion.

Caso para diagnóstico / Case for diagnosis

Paciente do sexo masculino, branco, 43 anos, apresentava há dois anos lesão única, localizada no joelho direito, além de descamação nas regiões plantares. O exame micológico direto das lesões plantares mostrava filamentos de dermatófitos, mas foi negativo na lesão do joelho. Porém o exame histopatológico dessa área demonstrou presença de granuloma de corpo estranho com hifas de dermatófitos, confirmando o diagnóstico de granuloma de Majocchi.

Caucasian male patient, 43 years old, presented two years ago with one single lesion in the right knee, in addition to desquamation in the plantar region. Direct mycological exam of the plantar damage showed filaments of dermatophytes, but it was negative for the knee injury. However, histopathology of the area showed presence of foreign body granuloma with hyphae of dermatophytes, confirming the diagnosis of Majocchi's granuloma.

Diagnosing multibacillary leprosy: a comparative evaluation of diagnostic accuracy of slit-skin smear, bacterial index of granuloma and WHO operational classification.

BACKGROUND: In view of the relatively poor performance of skin smears WHO adopted a purely clinical operational classification, however the poor specificity of operational classification leads to overdiagnosis and unwarranted overtreatment while the poor sensitivity leads to underdiagnosis of multibacillary (MB) cases with inadequate treatment. Bacilli are more frequently and abundantly demonstrated in tissue sections. AIMS AND METHODS: We compared WHO classification, slit-skin smears (SSS) and demonstration of bacilli in biopsies (bacterial index of granuloma or BIG) with regards to their efficacy in correctly identifying multibacillary cases. The tests were done on 141 patients and were evaluated for their ability to diagnose true MB leprosy using detailed statistical analysis. RESULTS: A total of 76 patients were truly MB with either positive smears, BIG positivity or with a typical histology of BB, BL or LL. Amongst these 76 true-MB patients, WHO operational classification correctly identified multibacillary status in 56 (73.68%), and SSS in 43 (56.58%), while BIG correctly identified 65 (85.53%) true-MB cases. CONCLUSION: BIG was most sensitive and effective of the three methods especially in paucilesional patients. We suggest adding estimation of bacterial index of granuloma in the diagnostic workup of paucilesional patients.

Immunohistochemical localization of mycobacterium tuberculosis complex antigen with antibody to 38 kDa antigen versus Ziehl Neelsen staining in tissue granulomas of extrapulmonary tuberculosis.

BACKGROUND: Extra-pulmonary tuberculosis often presents a diagnostic challenge because of its diverse clinical manifestations and low yield of acid fast bacilli in tissue sections. AIM: The aim of the present study is immuno-histochemical localization of tuberculous bacilli or their components that persist in the granulomas but have lost the property of staining with acid fast stains and to assess the advantage of immuno-staining over conventional Ziehl Neelsen staining. MATERIAL AND METHODS: Immuno-histochemical staining using species-specific monoclonal anti-body to 38 kDa protein of Mycobacterium tuberculosis complex and Ziehl-Neelsen staining for acid fast bacilli (AFB) was done on 69; 36 cases of confirmed extra-pulmonary tuberculosis and 33 non-tuberculous cases, in archival formalin fixed paraffin embedded tissue sections OBERVATIONS: AFB positivity was observed in only 36.1% of tuberculous granulomas while immuno-histochemical staining was positive in 100% of tuberculous granulomata with zero false positivity and negativity. CONCLUSIONS: The immuno-hiostochemical localization of tuberculous bacilli and their components in tissue sections may be an efficient diagnostic adjunct to conventional ZN staining for the diagnosis of granulomas of extra-pulmonary tuberculosis. The technique is simple, sensitive and specific. It can be standardized and performed by trained technicians in routine laboratory. This will also help in clinical decision-making and in reducing the usual practice of prescribing empirical anti-tubercular treatment based on clinical suspicion alone in the absence of demonstrable evidence of tuberculous infection.

Aspergillus iris granuloma in a young male: a case report with review of literature.

Endogenous aspergillosis is a rare occurrence. Endogenous Aspergillus endophthalmitis is a rare but devastating infection usually associated with disseminated aspergillosis or with intravenous drug abuse. We report a case of an isolated Aspergillus iris granuloma in a young immunocompetent male patient with review of the literature.

High mast cell density associated with granulomatous formation in tuberculous lymphadenitis.

Mast cells are one of the main inflammatory cells involved in the pathogenesis of tuberculosis. Previous reports revealed that mast cells participated in both acute and chronic states of infection with Mycobacterium tuberculosis through direct contact or indirect enhancement by releasing mediators. The authors evaluated mast cell density on tissue sections of tuberculous lymphadenitis stained with 0.1% toluidine blue from 45 cases, all of which were retrieved from the surgical pathology files of King Chulalongkorn Memorial Hospital from 1999 to 2006. A number of mast cells were correlated semiquantitatively with granulomas which were formed by aggregation of epithelioid histiocytes, multinucleated giant cells, and caseous necrosis. We found that mast cell density was significantly increased in lymph nodes with greater granuloma involvement (p = 0.030) and multinucleated giant cell formation (p = 0.010). These findings indicate a significant correlation between mast cell density and the granulomatous formation responsible for M. tuberculosis.

Intracranial necrotizing granuloma caused by Cladophialophora bantiana.

The dematiaceous fungi are a group of pigmented hyphal yeasts best known as agents of chronic skin and subcutaneous infections. Extracutaneous disease is exceptional. We report herewith a case of necrotizing granuloma caused by one member of the group, Cladophialophora bantiana. This organism is fully capable of invading the nervous system of apparently immunocompetent hosts and in many cases does so in the absence of demonstrable foci of extraneural infection. It has also been reported to be the most frequently found causative organism in the central nervous system phaeohyphomycosis. C. bantiana has several older names in the literature including Clodosporium trichoides, C. bantianum and Xylohypha bantiana. Patients require treatment with a combination of medical and surgical therapy. Rarity of the case and the usefulness of a simple diagnostic method such as smear cytology, which lead us to the diagnosis, is highlighted by the report.

Mediastinal histoplasmosis: report of the first two Brazilian cases of mediastinal granuloma

São relatados os dois primeiros casos de granuloma mediastinal por histoplasmose no Brasil, apresentando aspectos selecionados sobre dignóstico. O diagnóstico tecidual de histoplasmose foi obtido por mediastinoscopia e toracotomia, respectivamente. Em um paciente a massa calcificada subcarinal erodiu na árvore brônquica com pneumonite de aspiração bilateral uma semana após a toracotomia. Embora rara, histoplasmose deve ser incluída no diagnóstico diferencial de granuloma mediastinal especialmente com calcificação maior do que 10 mm de diâmetro.

Inoculation of Lacazia loboi into the subcutaneous tissue of the hamster cheek pouch

The subcutaneous tissue of the hamster cheek pouch, a site of immunologic privilege, has been used to investigate the potential infectivity of different types of parasites. It has been demonstrated that the implantation of fragments of lesions induced by the fungus Lacazia loboi, the etiologic agent of Jorge Lobo's disease, into the subcutaneous tissue of the hamster cheek pouch resulted in parasite multiplication and dissemination to satellite lymph nodes16. Here we describe the evolution of lesions induced by the inoculation of the isolated fungus into this immunologically privileged site. The morphology of the inflammatory response and fungal viability and proliferation were evaluated. Inoculation of the fungus into the cheek pouch induced histiocytic granulomas with rare lymphocytes. Although fungal cells were detected for a period of up to 180 days in these lesions, the fungi lost viability after the first day of inoculation. In contrast, when the parasite was inoculated into the footpad, non-organized histiocytic lesions were observed. Langhan's giant cells, lymphocytes and fungal particles were observed in these lesions. Fungal viability was observed up to 60 days after inoculation and non-viable parasites were present in the persistent lesions up to 180 days post-inoculation. These data indicate that the subcutaneous tissue of the hamster cheek pouch is not a suitable site for the proliferation of Lacazia loboi when the fungus isolated from human tissues is tested.

Granuloma dermatofítico: informe de 4 casos / Dermatophytic granuloma: report of 4 cases

Se reportan cuatro mujeres con granuloma dermatofítico por Trichophyton rubrum. Tres se encontraban asociados a otras dermatofitosis con tiña de pies, uñas y cuerpo. Dos casos se asociaron a trasplante renal y dos a rasurado de piernas. La respuesta al tratamiento fue excelente en dos casos con itraconazol, dosis de 200 mg diarios por 1 mes, y en otro a ketoconazol, 200 mg diarios por el mismo tiempo

Experimental paracoccidioidomycosis of hamster inoculated in the cheek pouch

We comparaed the granuloma morphology and immune response of hamsters inoculated with Paracoccidioides brasiliensis (Pb) into the cheek pouch, which lacks lymphatic drainage, and the ffotpad, which is rich in lymphatics. Our objective was to better understand the modulation of Pb granuloma in an immunocompetent animal inoculated in an immunologically privileged site. The humoral immune response (ELISA) and cell mediated immunity (footpad test) became positive on days 7 and 14, respectively in animal inoculated into footpad and on days 35 and 60 in animals inoculated into the pouch. Typical epithelioid granulomas were observed at both sites on day 14. The number of fungi gradually decreased from the beginning of the experiment in footpad lesions, but only after day 35 in pouch granulomas, when cell mediated immunity was detectable. The results indicate that typical epithelioid paracoccidioidomycotic granulomas may develop in the absence of a detectable immune response; however, they are incapable of controlling fungal reproduction. Lack of lymphatic drainage delays the appearance of a detectable immune response, but with time fungi escape from the pouch, elicit an immune response and reach other organs. Our results further indicate the importance of the lymphatics in the pathogenesis of paracoccidioidomycosis.