Presence Of Giant Cells Research Articles

Fine-Needle Aspiration Biopsy of Chondromyxoid Fibroma

We describe the cytologic features of chondromyxoid fibroma in fine-needle aspiration biopsy specimens in 4 patients. We analyzed rapid Romanowsky- and Papanicolaou-stained slides with a respect to overall cellularity, the presence of hypercellular chondromyxoid fragments (HCFs), nuclear atypia, cytoplasmic features, and the presence of giant cells. The most consistent and diagnostically useful feature was the presence of HCFs, which were present in all 4 cases. Mild to moderate nuclear atypia was additionally present in all 4 cases. Most cases were hypocellular (3/4). Giant cells were present in 2 cases, with 1 case exhibiting a hypercellular smear with numerous giant cells. All 4 cases were confirmed in subsequent histologic biopsy material. Strict attention to clinical, radiographic, and cytologic features, especially the presence of HCFs, can aid in the specific diagnosis of chondromyxoid fibroma on FNAB.

Tumeurs et pseudotumeurs des maxillaires riches en cellules géantes

Giant cell tumors and pseudogiant cell tumors of the jaws are divided into cherubism, central giant cell granuloma (CGCG), aneurysmal cyst, giant cell tumor, and hyperparathyroidism-jaw tumor. These tumors have variable clinical characteristics, such as bilateral tumors in cherubism, disseminated tumors in hyperparathyroidism, or focal tumors in other types. Their radiological presentation is quite similar with presence of well-delimitated uni- or multilocular radiolucency. The primary surgical treatment must be conservative. Anatomopathology gives the histologic diagnosis, with presence of giant cells. Some tumors are locally aggressive leading to larger bone exeresis. The nosology of these giant-cell tumors remains unclear, especially for giant cell central granuloma and giant cell tumors.

Induction of porcine post-weaning multisystemic wasting syndrome (PMWS) in pigs from PMWS unaffected herds following mingling with pigs from PMWS-affected herds

In this paper we present the results from two experimental studies (I and II) investigating whether post-weaning multisystemic wasting syndrome (PMWS) can be induced in pigs from PMWS unaffected herds by mingling with pigs from PMWS-affected herds and to observe whether transportation and/or mingling of healthy pigs from unaffected herds could induce PMWS. The studies comprised pigs from 12 different herds. Eight herds had PMWS while four were unaffected. All 12 herds were found to be infected with PCV2. Pigs from PMWS-affected herds were mingled with pigs from unaffected herds in four separate compartments in both study I and study II. In addition, in study II, four groups of pigs from unaffected herds were included. Two groups with pigs transported and mingled from unaffected herds and two groups with pigs which were only transported. The PMWS diagnoses on the individual pigs were based on lymphoid depletion, histiocytic proliferation and the presence of giant cells or inclusion bodies together with the demonstration of PCV2 in lymphoid tissue. Healthy pigs, in both studies, developed PMWS 4–5 weeks after mingling with pigs clinically affected with PMWS. None of the pigs from unaffected herds which had no contact with pigs from PMWS-affected herds developed clinical signs of PMWS. Transportation and mingling of pigs from PMWS unaffected herds in combination or alone was insufficient to provoke PMWS.

Imagerie de l’artérite de Takayasu

Takayasu's arteritis is the most frequent inflammatory arteritis in young patients. It is characterized by the presence of giant cells and typically involves specific vascular sites : aorta and its main branches and pulmonary arteries. Inflammatory arterial involvements leads to stenosis, aneurysm, occlusion and arterial wall thickening. Diagnosis relies mainly on imaging, namely Doppler US, CT, and MRI. The imaging features of this disease are reviewed based on a retrospective review of 36 patients imaged over a 13 year period.

Biocompatibility of resin composites subcutaneously implanted in rats with experimentally induced arthritis

Objective To evaluate the biocompatibility of resin composite specimens with different curing efficiency, subcutaneously implanted in rats with experimentally induced arthritis. Methods The amount of remaining C C bonds (%RDB) of hybrid resin composite specimens photopolymerized for 10 s and 40 s exposure time ( n = 3) was measured by micro-attenuated total reflectance Fourier transform infrared spectroscopy. Male Wistar rats ( n = 36) were classified in two groups ( n = 18) of healthy animals and of animals with experimentally induced arthritis. Resin composite specimens irradiated for 10 s and 40 s and calcium hydroxide control specimens were implanted subcutaneously in each animals’ dorsum. Following 2-, 4- and 9-week periods the animals were sacrificed. The development of arthritis was defined by biochemical analysis and the changes in the relative weight of animals’ organs (spleen, thymus, adrenals). Tissue reactions were examined histologically. Results %RDB per site and exposure time showed statistically significant differences. Lowest %RDB values were recorded on 40 s exposed specimens. Biochemical indices and relative organ weights demonstrated statistically significant differences between healthy animals and animals with arthritis. The health status of the animals and the materials used did not influence tissue response. First and second periods of sacrifice showed reduced propensity of connective tissue development in comparison to the third period. The same applied for the second period regarding the presence of giant cells. Significance The materials tested and the animals’ health status did not result in altered tissue response compared to control group. The period of sacrifice was associated with different tissue responses.

Microscopic colitis with giant cells: a clinico-pathological review of 11 cases and comparison with microscopic colitis without giant cells

To document clinical and pathological features of microscopic colitis with giant cells (MCGC) which is one of a number of atypical variants of microscopic colitis. Cases of microscopic colitis were assessed for giant cells during routine reporting and retrieved from the slide file at a private laboratory. The histological features and clinical data were assessed. Histochemistry (trichome and haematoxylin van Gieson) and immunohistochemistry (CD68) was performed to characterise the nature of the giant cells. Giant cells were identified in 11 cases of microscopic colitis. The histological features of MCGC are not significantly different from usual MC except for the presence of multinucleated giant cells in the superficial lamina propria. Apart from the common but not unexpected association with autoimmune disease, no unique clinical features of the MCGC group were identified versus those described in the literature for ordinary MC. Immune disorders included gluten-sensitive enteropathy, systemic lupus erythematosus and raised titres of antinuclear antibodies. The giant cells have the same immunohistochemical characteristics as histiocytes and appear to form through histiocyte fusion. The presence of giant cells does not appear to confer any further clinical significance and remains a histological curiosity.

Subcutaneous inflammation (panniculitis) in tibio-tarsal joint of rats inoculated with complete Freund’s adjuvant

Complete Freund's adjuvant (CFA)-induced arthritis in rats, which presents similar features to rheumatoid arthritis, is a model widely used in aetiopathogenetic and investigational drug studies. In this model, arthritis is induced by intradermal injection of Mycobacterium tuberculosis suspended in mineral oil in the hind footpad. Although the histopathology findings in the joint are well described, the marked subcutaneous features of panniculitis that concomitantly occur in this model have received no attention. The objective of this paper is to describe the subcutaneous histopathological features in 8 Wistar rats after intraplantar injection of CFA. We studied the subcutaneous histopathological features in 8 Wistar rats after intraplantar injection of CFA in the left hind paw. The levels of subcutaneous inflammation of the animals in this study were evaluated for the histological characteristics present in the tissue and scored with 4 parameters (acute inflammation, chronic inflammation with fibrosis, subcutaneous and profound soft tissue necrosis, and the presence of giant cells, neutrophils, macrophages and lymphocytes) on days 4, 7, 11 and 15 after induction. All animals developed intense subcutaneous inflammation characteristic of panniculitis, with predominance of acute changes in the initial period, with progression to a self-perpetuating chronic fibrotic process on day 15. These observations precede the joint changes. Besides being an interesting model for better studying diseases with panniculitis, our observations bring up issues concerning the possible relations between subcutaneous and joint inflammatory changes.

Pneumatosis Intestinalis

Pneumatosis intestinalis is characterized by the accumulation of gas in the gastrointestinal wall. The histopathologic diagnosis is easily made on resection specimens in which the presence of submucosal or subserosal empty spaces lined by histiocytes and giant cells presents little diagnostic dilemma. In biopsy material, though, the diagnosis is more challenging, as giant cells and histiocytes can be interpreted as granulomatous inflammation indicative of other conditions such as infection or Crohn disease. Nine gastrointestinal biopsies diagnosed as pneumatosis intestinalis from 7 patients were reviewed. Clinical history, radiologic features, and endoscopic findings were obtained from patient records. Five patients presented with blood in the stool (one also with diarrhea) and 2 patients were diagnosed after screening colonoscopies. The endoscopist frequently described polyps or raised mucosal folds (6 cases). In all biopsies submucosal cystic spaces lined by giant cells could be observed. The cysts were intact (2 biopsies), partially intact (5 biopsies), or collapsed (5 biopsies), with 3 biopsies showing 2 cyst architectural conformations. The arrangement of the giant cells lining a rounded or cleft-like space was the most helpful feature in distinguishing pneumatosis intestinalis from granulomatous colitis. Additional useful features included the recognition of "pseudolipomatosis" (n=4) and the presence of round empty spaces in the submucosa resembling fat (n=3). Nonspecific findings included variable inflammation, eosinophilia, mild gland disarray, vascular ectasia and edema, and mild melanosis coli. Two cases were initially given a diagnosis of granulomatous inflammation. One patient with acquired immunodeficiency syndrome and positive cytomegalovirus antigenemia assay had ischemic colitis on the biopsy and another had a subsequent resection with ischemic colitis. A third patient was treated for cytomegalovirus colitis. None had a history of or developed Crohn disease. Pneumatosis intestinalis remains a challenging diagnosis on biopsy material, particularly because endoscopy usually does not suggest that diagnosis. The presence of giant cells in the submucosa, variable inflammation, and crypt disarray can be easily confused with Crohn disease. Attention to the arrangement of the giant cells lining intact, partial, or collapsed cysts is crucial to making the correct diagnosis. Although nonspecific by itself, pseudolipomatosis may also indicate the presence of gas within the tissue and suggest the diagnosis.

Equine Herpesvirus 2-Associated Granulomatous Dermatitis in a Horse

Granulomatous dermatitis in horses has been linked to many etiologies, including various parasites, fungi, and bacteria. Idiopathic forms of granulomatous inflammation-producing diseases, some of which are localized to the skin, also have been reported in horses. Herein we describe a case of recurrent equine granulomatous skin disease characterized by intranuclear viral inclusions within macrophages and giant cells. The histologic changes were primarily noted in the deep dermis and included multifocal to coalescing areas of necrosis marked by histiocytic cell infiltration and presence of giant cells. Electron microscopic examination revealed intranuclear and intracytoplasmic viral particles consistent with herpesvirus. Sequence results of the polymerase chain reaction product were consistent with equine herpesvirus 2, adding another possible etiology to the list of differentials in cases of equine granulomatous skin disease.

Isolated (localized) idiopathic granulomatous (giant cell) vasculitis in an intramuscular lipoma

Isolated (localized) idiopathic granulomatous vasculitis (IGV) is an uncommon, heterogeneous, and poorly defined group of disorders characterized by infiltration of the arterial wall caused by compactly grouped mononuclear phagocytes, with or without giant cells, in segmental distribution. We report on a 55-year-old woman with IGV limited to an intramuscular lipoma of the left thigh. The vasculitis was identified incidentally upon microscopic examination of the removed tumor. The IGV was centered on two medium-sized arteries, accompanied by narrowing of the lumens, and not associated with secondary changes such as infart or postinfart fibrosis. The inflammatory infiltrate was rich in T-lymphocytes and macrophages, with the presence of giant cells. The patient was asymptomatic and well in a follow-up period of 2 months, during which she was not treated. To our knowledge, this is the first report of lipoma involvement in localized IGV. It is important to distinguish cases of isolated intratumorous IGV from systemic disease, because the latter implies a poor prognosis and requires an aggressive treatment.

Nephrogenic Fibrosing Dermopathy: A Review of the Massachusetts General Hospital Experience

We have undertaken a review of the Massachusetts General Hospital experience of nephrogenic fibrosing dermopathy (NFD). Twelve cases were identified, and the dermatopathologic features of lesional skin biopsies were examined. We looked systematically at nine parameters and graded each on a scale of 0 (minimal or none) to 3 (highest or most): 1) extent of fibrocytic proliferation, 2) extent of collagen thickening, 3) extent of vascularity, 4) extent of pannicular involvement, 5) extent of elastolysis, 6) presence of mucin, 7) presence of calcification, 8) presence of giant cells, and 9) presence of inflammation. Results demonstrate that fibrocytic proliferation, collagen thickening, inflammation, and vascularity most commonly were classified as grade 1–2; mucin deposition and elastolysis varied from 0–2; pannicular involvement ranged from 1–3; nearly all had calcification grade of 0, and there were no giant cells detected in any of the twelve cases. Comparing our results to published reports suggests that there are some interesting observations. Our cases tended to be less fibrocellular, have less mucin, and have more vascularity than the initial 14 cases described by Cowper et al (2001). The implications of the dermatopathologic findings for clinical course and prognosis are currently being evaluated.

The influence of sex and the presence of giant cells on postoperative long-term survival in adult patients with supratentorial glioblastoma multiforme.

Glioblastoma multiforme (GBM) remains incurable by conventional treatments, although some patients experience long-term survival. A younger age, a higher Karnofsky Performance Scale (KPS) score, more aggressive treatment, and long progression-free intervals have been reported to be positively associated with long-term postoperative patient survival. The aim of this retrospective study was the identification of additional favorable prognostic factors affecting long-term survival in surgically treated adult patients with supratentorial GBM. Of 113 adult patients newly diagnosed with histologically verified supratentorial GBM who were enrolled in Phase III trials during the period between 1987 and 1998, six (5.3%) who survived for longer than 5 years were defined as long-term survivors, whereas the remaining 107 patients served as controls. All six were women and were compared with the controls; they were younger (mean age 44.2 years, range 31-60 years), and their preoperative KPS scores were higher (mean 85, range 60-100). Four of the six patients underwent gross-total resection. In five patients (83.3%) the progression-free interval was longer than 5 years and in three a histopathological diagnosis of giant cell GBM was made. This diagnosis was not made in the other 107 patients. Among adult patients with supratentorial GBM, female sex and histopathological characteristics consistent with giant cell GBM may be predictive of a better survival rate, as may traditional factors (that is, younger age, good KPS score, more aggressive resection, and a long progression-free interval).

Diagnostic relevance of multinucleated giant cells in papillary thyroid cancer. A cytological and histological study

Cytological smears of 17 papillary carcinomas (PC) of the thyroid as well as histological slides of 58 PC and 50 follicular adenomas (FA) and 50 follicular carcinomas (FC) were reviewed to assess the presence of intrafollicularly located multinucleated giant cells. In accordance with the data published, such giant cells were found in 70% of PC but in only 8% of FA and FC. The presence of giant cells, which probably represents a foreign body reaction to, in case of PC, physicochemically altered colloid, is a useful additional criteria for the cytological and histological diagnosis of PC.

Inducible nitric oxide synthase deficiency in mice increases resistance to chronic infection with Echinococcus multilocularis.

The production of nitric oxide (NO) by intraperitoneal macrophages of mice during secondary infection with Echinococcus multilocularis mediates immunosuppression at early and late stages of infection. We addressed the role of NO in host resistance against this extracellular metazoan parasite by infecting inducible nitric oxide synthase knockout ((iNOS-KO) mice (of the C57BL/6 background) with 100 metacestode vesicles. The parasite weight was significantly lower in iNOS-KO mice when compared with wild-type (WT) mice at 4 months postinfection (late stage), thus demonstrating that iNOS deficiency confers a certain degree of resistance against persistent chronic infection. However, histological analysis of periparasitic tissue showed no differences between WT and iNOS-KO mice, as both exhibited granuloma formation and the presence of giant cells. Together with histology, the production of a high level of interferon-gamma (IFN-gamma) in infected iNOS-KO mice upon stimulation with concanavalin A (Con A) and VF-antigen indicated normal T-cell signalling in these animals. As expected, peritoneal exudate cells (PEC) from infected iNOS-KO mice produced no detectable NO, while the PEC from infected WT mice produced high levels of NO after stimulation with lipopolysaccharide (LPS) and parasite protein or carbohydrate antigen, or even without in vitro stimulation. Consequently, the high level of NO production observed during chronic infection in WT mice appears to contribute more to immunosuppression than to limitation of parasite growth. This is also reflected by the fact that splenocyte proliferation was significantly higher and parasite masses lower in iNOS-KO mice (at 1 and 4 months postinfection) than in WT mice.

HIV and drug misuse in the Edinburgh cohort.

The Edinburgh cohort of intravenous drug users (IVDUs) became infected with HIV between 1983 and 1984. Before the era of effective therapy, many of these infected IVDUs displayed cognitive impairments on progressing to AIDS and were found to have HIV encephalitis (HIVE). Full autopsies were conducted on these patients, providing an opportunity to study the intersecting pathology of pure HIVE and drug use. High proviral load in the brain correlated well with the presence of giant cells and HIV p24 positivity. In presymptomatic HIV infection, IVDUs were found to have a lymphocytic infiltrate in the central nervous system (CNS). Apart from the expected microglial activation in the presence of HIV infection of the CNS, drug use in its own right was found to be associated with microglial activation. Examination of HIV-negative IVDUs revealed a number of neuropathologic features, including microglial activation, which may underpin HIV-related pathology in the CNS. HIV isolated from different regions of the brain was exclusively of R5-tropic type throughout the course of infection. Detailed studies of p17 and V3 sequences suggest that viral sequestration occurs in the CNS before the onset of AIDS and that increasing diversity of HIV variants within the brain is associated with increasing severity of HIVE. Because brain isolates have proved to be different from those in lymphoid tissue (and blood), it is likely that selective neuroadaptive pressures operate before HIVE supervenes. Drug abuse may be synergistic in this process through activation of microglia, breakdown of the blood-brain barrier, and direct neurotoxicity. Collections of clinically well-characterized HIV-infected tissues such as those in the Edinburgh Brain Bank are a vital resource to support ongoing studies of viral pathogenesis in the CNS and interactions with drug abuse.

Alumina–alumina artificial hip joints. Part I: a histological analysis and characterisation of wear debris by laser capture microdissection of tissues retrieved at revision

The aims of this study were to investigate the tissues from uncemented Mittelmeier alumina ceramic-on-ceramic total hip replacements using histological methods and to isolate and characterise the ceramic wear debris using laser capture microdissection and electron microscopy. Tissues from around 10 non-cemented Mittelmeier alumina ceramic on ceramic THRs were obtained from patients undergoing revision surgery. Tissues were also obtained from six patients who were undergoing revisions for aseptic loosening of Charnley, metal-on-polyethylene prostheses. Tissue sections were analysed using light microscopy to determine histological reactions and also the location and content of alumina ceramic wear debris. Tissue samples were extracted from sections using laser capture microdissection and the characteristics of the particles subsequently analysed by TEM and SEM.The tissues from around the ceramic-on-ceramic prostheses all demonstrated the presence of particles, which could be seen as agglomerates inside cells or in distinct channels in the tissues. The tissues from the ceramic-on-ceramic retrievals had a mixed pathology with areas that had no obvious pathology, areas that were relatively rich in macrophages and over half of the tissues had in the region of 60% necrosis/necrobiosis. In comparison, the Charnley tissues showed a granulomatous cellular reaction involving a dense macrophage infiltrate and the presence of giant cells and <30% necrosis/necrobiosis. The tissues from the ceramic prostheses also showed the presence of neutrophils and lymphocytes, which were not evident in the tissues from the Charnley retrievals. There were significantly more macrophages (p<0.05), and giant cells (p<0.01) in the Charnley tissues and significantly more neutrophils (p<0.01) in the ceramic-on-ceramic tissues.TEM of the laser captured tissue revealed the presence of very small alumina wear debris in the size range 5–90nm, mean size±SD of 24±19nm whereas SEM (lower resolution) revealed particles in the 0.05–3.2μm size range. This is the first description of nanometre sized ceramic wear particles in retrieval tissues. The bi-modal size range of alumina ceramic wear debris overlapped with the size ranges commonly observed with metal particles (10–30nm) and particles of ultra-high molecular weight polyethylene (0.1–1000μm). It is possible that the two size ranges of contributed to the mixed tissue pathology observed. It is speculated that the two types of ceramic wear debris are generated by two different wear mechanisms in vivo; under normal articulating conditions, relief polishing wear and very small wear debris is produced, while under conditions of microseparation of the head and cup and rim contact, intergranular and intragranular fracture and larger wear particles are generated.

Suture-Line Reinforcement With Glutaraldehyde-Preserved Bovine Pericardium for Nonanatomic Resection of Lung Tissue

In this study we assessed the usefulness of glutaraldehyde-preserved bovine pericardium (GPBP), preparated in our laboratory, in nonanatomic resection of lung tissue in dogs. A 30% resection of the right cranial lobe of the lung was performed in 18 mongrel dogs. The suture line was reinforced with GPBP strips. For group I (n = 6), the GPBP strips were fixed on the lung with nonabsorbable suture by thoracotomy. In Group II (n = 6), the resection and fixation of the GPBP strips were performed with an endoscopic linear stapler by thoracotomy. In Group III (n = 6), the resection and fixation of the GPBP strips were performed with a linear stapler by thoracoscopy. The animals were evaluated each day during the first week after surgery and every other day during the study time. At the end of the study all animals were euthanized with an overdose of pentobarbital. Macroscopic and microscopic examinations of the bioprosthesis and lung were evaluated. All animals survived the surgical procedure and study time (8 weeks). In the three groups, macroscopic examination of the bioprosthesis showed good adaptation to the lung tissue. Microscopically, all groups of animals presented good healing, with the presence of fibrotic tissue layer on the GPBP and its periphery as well as in the lung. However, in group I we observed the presence of giant cells in the suture line. GPBP proved to be a useful material for reinforcement of the nonanatomic resection suture line of lung tissue in dogs.

Effect of heparin-surface-modified intraocular lenses on postoperative inflammation after phacoemulsification: A randomized trial in a United States patient population

Objective To compare postoperative inflammation occurring with heparin-surface-modified (HSM) versus non-HSM polymethyl methacrylate intraocular lenses (IOLs) after phacoemulsification. Design Randomized, double-masked, multicenter, parallel trial. Participants A total of 367 patients, consisting of routine (n = 220), glaucoma (n = 58), and diabetes (n = 89) patients, from eight US medical centers. Methods Patients were observed for 1 year after phacoemulsification and lens implantation (week 1, months 1, 3, 6, 12). Main outcome measures Primary measures of postoperative inflammation defined as the presence of giant cells on the lens surface via specular micrography and cellular deposits via slit-lamp examination. Results The cross-sectional analyses showed that consistently fewer routine patients with HSM lens implants had giant cells on the IOL than those with non-HSM lens implants across all follow-up visits. The statistical significance ( P < 0.05) was observed at all visits except month 12 for routine patients. The diabetes patients also demonstrated the same giant cell difference, and the statistical significance was observed at all visits including month 12. A similar trend was also observed in the glaucoma patients, with statistical significance only at the 3-month visit. For cell deposits, significant differences in favor of the HSM lens ( P < 0.05) were observed at 3 months among routine and diabetes patients, and at 3 and 6 months among glaucoma patients. A longitudinal data analysis using the generalized estimating equation approach indicated statistically significant treatment effect of HSM lenses in reducing inflammation in all patients except for cellular deposits in diabetes patients. In all patient groups, sight-threatening complications were not reported either more frequently or with more severity than normally expected for patients who have undergone cataract extraction and IOL implantation. Conclusions The present study, the only one to have used phacoemulsification in virtually all patients (211/220 [96%] routine, 57/58 [98%] glaucoma, and 84/89 [94%] diabetes) is the largest to evaluate and compare concurrently routine, glaucoma, and diabetes patients. It is also the first US patient population study to document that heparin surface modification reduces postoperative inflammatory responses, as measured by specular micrography and slit-lamp examination, especially in the early postoperative period.

Cytologic demonstration of ?dysplastic? follicular dendritic cells in a case of hyaline-vascular Castleman's disease

Large atypical follicular dendritic cells, considered dysplastic by some authors, were first described in association with Castleman's disease in 1991, but until now there has been no cytologic account regarding these cells. We report the cytologic and histologic findings of a case of hyaline-vascular Castleman's disease associated with "dysplastic "follicular dendritic cells which presented as a mediastinal mass in a young man. The presence of giant cells within the preoperative fine-needle aspirate specimen caused initial diagnostic uncertainty and their true nature was only confirmed retrospectively following application of an immunostain for CD21 to direct smears. Awareness of "dysplastic" follicular dendritic cells within aspirates of Castleman's disease will result in less cytological confusion in the future and may help to avoid the possibility of misdiagnosing Hodgkin's lymphoma which has certain cytologic similarities.

Correlation among immune response, morphogenesis of the granulomatous reaction and spleen lymphoid structure in murine experimental paracoccidioidomycosis.

We studied the correlation among cellular immune response, the pattern of lung granulomatous lesions and alterations in spleen lymphoid structure in Swiss mice inoculated intravenously with Paracoccidioides brasiliensis strain 18. The animals were evaluated at 24, 48 and 96 h after infection and further studied weekly for 18 weeks by: (i) the macrophage migration inhibition test with phytohemagglutinin (PHA) and P. brasiliensis antigen (PbAg); and (ii) histopathology of the lung and spleen lesions. One group of animals was gamma-irradiated (8 Gy), infected under the same conditions and evaluated for the pattern of lung granulomatous lesions and spleen lymphoid structure at 24, 48 and 96 h after infection. During the first week of infection, the non-irradiated animals presented a positive response to PHA and PbAg, compact granulomas in the lungs and a typical hyperplasia of the spleen white pulp. However, from weeks 2 to 5, a depression of the cell-mediated immunity (CMI) response to PHA and PbAg was observed in association with granulomas presenting only large mononuclear cells and lacking both giant cells and a peripheral halo of small mononuclear cells. This pattern of granuloma formation was similar to that seen in gamma-irradiated animals, whose cells involved in CMI were absent. After week 7, the non-irradiated animals showed granulomas characterized by the presence of giant cells and a peripheral halo of small mononuclear cells. This type of granuloma was formed concomitantly with recovery of the CMI and of the lymphoid structure of the spleen. The results showed a correlation among granulomas composed of large mononuclear cells, hypoplasia of the splenic tissue and impaired CMI. This correlation indicated that although granuloma morphogenesis per se does not depend on the activation of CMI, this response is important at later stages during modulation of the cellular composition of the granulomas.