Fungal infection by Paracoccidioides brasiliensis mimicking bone tumor

Paracoccidioides brasiliensis infection causes a systemic mycosis originally described in Latin America but with Current reports of worldwide distribution. The clinical presentation of paracoccidiodomycosis as an isolated long-bone lesion in children is quite unusual. This article describes a 10-year-old male with a lytic femoral bone lesion caused by P. brasiliensis infection that was first suspected of being of neoplasic etiology. The text also emphasizes the importance of including endemic fungal infections in the differential diagnosis of bone lesions.

Pitfalls in the Differential Diagnosis of Renal Tumor in an Adolescent

The differential diagnosis of renal tumors, particularly in adolescents, may be challenging. We describe an 11-year-old female with a primary intra-renal mass. Initial differential diagnoses included primitive neuroectodermal tumor (PNET), desmoplastic small round cell tumor (DSRCT), and Wilms Turner (WT). Extensive pathologic and molecular analysis on initial and relapsed tumor samples confirmed WT. The EWS-WTI and EWS-FL11 rearrange-merits, distinctive of DSRCT and PNET were negative. The differential diagnosis on monophasic blastemal WT may be complex. Primary renal DSRCT and MET have been rarely described. Nevertheless, molecular confirmation for these rare conditions may be necessary in selected cases. Pediatr Blood Cancer 2010;54:3 19-321. (C) 2009 Wiley-Liss, Inc.

Tumor necrosis factor region polymorphisms are associated with AIDS and with cytomegalovirus retinitis

Background: The tumor necrosis factor (TNF) gene is located within the highly polymorphic major histocompatibility complex region, exhibiting the -308 CA promoter region polymorphism and six microsatellites (TNFa-f) spanning the region nearby the TNF locus. Objective: In the present Study, we evaluated the frequency of -308 CA and TNFa-e polymorphisms and respective haplotypes (in chromosomal sequence: TNFd-TNFe-308GA-TNFc-TNFa-TNFb), in 222 patients with AIDS, 52 of whom exhibited cytomegalovirus retinitis, and in 202 healthy HIV-negative individuals. Method: TNF microsatellite and single nucleotide polymorphism typings were performed by PCR followed by polyacrylamide gel electrophoresis. Results: The TNF-308A allele and the 4-3-C-2-7-1 haplotype were associated with susceptibility to AIDS, whereas the TNFb4 allele and the 3-3-C-1-11-4 haplotype were associated with protection against AIDS development. The TNFc2 allele and the 4-1-G-2-2-1 haplotype, which contains the TNFc2 allele, were associated with cytomegalovirus retinitis. Conclusion: This study highlights that polymorphic sites spanning the region nearby the TNF locus are associated with AIDS per se and with cytomegalovirus retinitis in AIDS patients. (C) 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins

Distinct tumor suppressor mechanisms evolve in rodent species that differ in size and lifespan

Large, long-lived species experience more lifetime cell divisions and hence a greater risk of spontaneous tumor formation than smaller, short-lived species. Large, long-lived species are thus expected to evolve more elaborate tumor suppressor systems. In previous work, we showed that telomerase activity coevolves with body mass, but not lifespan, in rodents: telomerase activity is repressed in the somatic tissues of large rodent species but remains active in small ones. Without telomerase activity, the telomeres of replicating cells become progressively shorter until, at some critical length, cells stop dividing. Our findings therefore suggested that repression of telomerase activity mitigates the increased risk of cancer in larger-bodied species but not necessarily longer-lived ones. These findings imply that other tumor suppressor mechanisms must mitigate increased cancer risk in long-lived species. Here, we examined the proliferation of fibroblasts from 15 rodent species with diverse body sizes and lifespans. We show that, consistent with repressed telomerase activity, fibroblasts from large rodents undergo replicative senescence accompanied by telomere shortening and overexpression of p16(Ink4a) and p21(Cip1/Waf1) cycline-dependent kinase inhibitors. Interestingly, small rodents with different lifespans show a striking difference: cells from small shorter-lived species display continuous rapid proliferation, whereas cells from small long-lived species display continuous slow proliferation. We hypothesize that cells of small long-lived rodents, lacking replicative senescence, have evolved alternative tumor-suppressor mechanisms that prevent inappropriate cell division in vivo and slow cell growth in vitro. Thus, large-bodied species and small but long-lived species have evolved distinct tumor suppressor mechanisms.

Odor cues from tumor-bearing mice induces neuroimmune changes

Cohabitation for 14 days with an Ehrlich tumor-bearing mice was shown, among others, to increase locomotor activity, and hypothalamic noradrenaline levels and turnover, to decrease the innate immune responses and animal resistance to tumor growth. The present experiment was designed to access the relevance of tactile, olfactory, and visual communication to the neuroimmune changes induced by cohabitation with a tumor-bearing partner. Mice that were not allowed to perceive odor cues from their sick partners presented no alterations in neutrophil activity, a fact not observed after visual deprivation and physical isolation. Mice use scents for intraspecies communication in many social contexts. Tumors produce volatile organic compounds released into the atmosphere through breath, sweat, and urine. The present results strongly suggest that volatile compounds released by Ehrlich tumor-injected mice are perceived by their conspecifics, inducing the neuroimmune changes reported for cohabitation with a sick companion. (C) 2010 Published by Elsevier B.V.

Effects of individual housing on behavior and resistance to Ehrlich tumor growth in mice

This study analyzed in Balb/C mice the effects of individual housing on behavior, serum corticosterone and resistance to Ehrlich tumor growth. Mice (60 days old) were individually (IH) or grouped housed (G) (10-12 animals/cage) for 14-21 days. The 1st day of the housing condition was considered experimental day 1 (ED1). Results showed that on ED21, IH mice, when compared to G mice, presented no differences on corticosterone serum levels when kept undisturbed; however, an increased level of this hormone was observed in IH mice after an immobilization stress challenge. An increased time spent in the plus-maze closed arms and a decreased time in the open arms were also observed in IH mice. When compared to G animals, after inoculation with 105 Ehrlich tumor cells on ED1, IH mice presented an increase in volume of ascitic fluid and number of tumor cells. The survival time of IH mice was also shorter than that measured in G animals. Furthermore, IH mice injected with a different number of tumor cells on ED1 always presented increased Ehrlich tumor cells than G group. Interestingly. these effects were not observed when the tumor cells injection was done on ED4. These results suggest that individual-housing conditions induce an altered immune-endocrine response and, at the same time, decrease animals` resistance to Ehrlich tumor growth. It is proposed that the neural link between the behavioral and immunological changes observed after the stress of individual housing might involve the activation of the HPA axis. (C) 2008 Elsevier Inc. All rights reserved.

Cohabitation with a sick cage mate: Effects on ascitic form of Ehrlich tumor growth and macrophage activity

The present study was designed to evaluate the effects of mice cohabitation with a sick conspecific cage mate on peritoneal macrophage activity and on resistance to Ehrlich tumor growth. Female mice housed in pairs were divided into control and experimental groups. One mouse of each control pair was inoculated with NaCl (0.1 ml/10 g) intraperitoneally and the other, called `companion of healthy partner` (CHP), was kept undisturbed. One animal of each experimental pair of mice was inoculated with 5.0 x 10(6) Ehrlich tumor cells intraperitoneally and the other, the subject of this study, was called `companion of sick partner` (CSP). Peritoneal macrophages were removed from CSP and CHP mice to analyze resident macrophage activity (experiment 1), macrophage activity after Mycobacterium bovis (experiment 2) or Ehrlich tumor cells (experiment 3) in vivo inoculations. The resistance of CSP and CHP mice to Ehrlich tumor growth was also analyzed (experiment 4). Differences between groups were not found on resident macrophage activity. However, Onco-BCG- and Ehrlich tumor-activated macrophages from CSP mice presented a decreased intensity and percentage of phagocytosis and an increased respiratory burst in the presence of Staphylococcus aureus stimulation in vitro. CSP animals at the same time displayed a decreased resistance to Ehrlich tumor growth. These data were discussed in light of a possible psychological stress effect imposed by the housing condition on mice`s peritoneal macrophage activity and, as a consequence, on their resistance to Ehrlich tumor growth. Copyright (c) 2008 S. Karger AG, Basel.

Immunoprofile of Kuttner tumor (chronic sclerosing sialadenitis)

In the present study, the immunoprofile of chronic sclerosing sialadenitis, also known as Kuttner tumor, was analyzed. Two,cases that occurred in the submandibular gland of male patients were submitted to immunohistochemical reactions to different antibodies. Histological examinations showed a submandibular gland exhibiting various degrees of atrophy with destruction of acini, infiltration by inflammatory cells, and periductal fibrosis. Reactions to cytokeratins (CKs) showed acini and duct remnants positive to CKs 7, 8, 19, and 13. CK14 stained myoepithelial cells around preserved acini and intercalated duct, and also basal cell of excretory ducts, but was negative in proliferating and branching ducts. Smooth muscle actin (SMA) was expressed by myofibroblasts in periductal fibrosis, and an intense expression of extracellular components was also seen. Lymphocyte markers showed, besides mature follicles, a higher presence of CD45RO positive cells. Thus, the immunoprofile of Kuttner is much more in keeping with an inflammatory-induced degenerative disease than with a preneoplastic lesion.

The neural histogenetic origin of the oral granular cell tumor: An immunohistochemical evidence

Aims: Granular cell tumor (GCT) is a rare neoplasm that can appear in any site of the body, but most are located intraorally. Its histogenetic origin remains unclear. This report analyzes the immunoprofile of 15 cases of granular cell tumors, occurring in 13 women and 2 men and the lesions were located on the tongue or upper lip. Patient age ranged from 7 to 52. Methods: The patients demographic data and the cytological and architectural features of the lesions were analyzed in oral GCTs (n = 15). The lesions were also submitted to a panel of immunohistochemical stains with antibodies against S-100, p75, NSE, CD-68, Ki-67, Synaptofisin, HHF-35, SMA, EMA, Chromogranin, Progesterone, Androgen and Estrogen. Results: Among the fifteen cases analyzed, the most common location was the tongue (84.6%). Histologically, the tumors exhibited cellular proliferation composed mainly by polygonal cells presenting an abundant granular eosinophilic cytoplasm. The nuclei were central, and the cell membranes were moderately clear. No mitotic figures were observed. The immunohistochemical analysis showed positivity in all cases for S-100, p75, NSE and CD-68, and no immunoreactivity for Ki-67, Synaptofisin, HHF-35, SMA, EMA, Chromogranin, Progesterone, Androgen and Estrogen. Conclusion: The immunoprofile of granular cell tumors showed nerve sheath differentiation - lending support to their neural origin - and helping to establish a differential diagnosis between this lesion and other oral granular cell tumors, whether benign or malignant.

Importance of cone beam computed tomography for diagnosis of calcifying cystic odontogenic tumor associated to odontoma. Report of a case

The calcifying cystic odontogenic tumour (CCOT) is a rare benign cystic neoplasm not infrequently associated with odontoma. This report documents a case of CCOT associated with compound odontoma arising in the anterior maxilla in a 25-year-old woman. Conventional radiographs showed a large calcified mass with poorly visualized radiolucent margins. The extent and condition of the internal structure of the CCOT associated with odontoma was able to be determined based on radiographic findings from cone beam computed tomography. This advanced image technique proved to be extremely useful in the radiographic assessment of this particular neoplasm of the jawbones.

Expression of extracellular matrix proteins in adenomatoid odontogenic tumor

Altered expression of extracellular matrix (ECM) components has been reported in several pathologies; however, few ECM proteins have been evaluated in adenomatoid odontogenic tumor (AOT). The aim of this study was to analyze the expression and distribution of the ECM proteoglycans: biglycan and decorin; and glycoproteins: osteonectin, osteopontin, bone sialoprotein and osteocalcin in the AOT. Three-micrometer sections from paraffin-embedded specimens were evaluated employing a streptavidin-biotin immunohistochemical method with the antibodies against the proteins previously cited. Only the osteonectin was expressed in the epithelial cells. The eosinophilic amorphous material and the connective tissue showed expression of all components studied. The calcification foci expressed only osteopontin. In conclusion, the low expression of the components studied in neoplastic epithelial cells suggests that the epithelial cells act probably as stimulators of the expression by the stroma, which in turn can act as agonist or antagonist of the tumor growth. These results suggest that the components studied probably have a key role in the biological behavior of the AOT.

Fibronectin as an adjuvant in the diagnosis of oral inflammatory myofibroblastic tumor

Inflammatory myofibroblastic tumor is a distinctive lesion composed of myofibroblastic spindle shaped cells accompanied by inflammatory infiltrate that may arise in various organs. It is believed to be a noneoplastic inflammatory condition, although this is still controversial. The recognition of inflammatory myofibroblastic tumor as an entity is important especially to avoid unnecessary surgery. A few cases have been reported in the oral cavity. This report primarily presents a case of inflammatory myofibroblastic tumor that arose in the floor of mouth of a 23-year-old woman. The proliferating spindle cells were immunoreactive for vimentin, smooth muscle actin, and muscle specific actin and negative for desmin, AE1/AE3, S-100, CD68, MyoD1 and caldesmon. In an attempt to assess the potential neoplastic nature of this lesion, immunohistochemical expression of ALK protein was performed, although no immunoreactivity was detected. Also, the presence of well differentiated myofibroblasts identified by fibronectin is discussed, as well as the importance in establishing an immunoprofile to better consolidate the diagnosis. We conclude that the study of fibronectin in case series may aid the diagnosis as well as the prediction of the tumor course.

Glial fibrillary acidic protein in tumor types with cartilaginous differentiation

Glial fibrillary acidic protein (GFAP) is a member of the intermediary filament protein family. It is an important component of astrocytes and a known diagnostic marker of glial differentiation. GFAP is expressed in other neural tumors and pleomorphic adenoma and, less frequently, in cartilage tumors, chordomas, and soft tissue myoepitheliomas. The aim of this study was to evaluate the role of GFAP and its reliability in nonglial tumors as an immunohistochemical marker. We evaluated GFAP gene and protein expression using Q-PCR and immunohistochemistry, respectively, in 81 and 387 cases of soft tissue, bone tumors, and salivary pleomorphic adenomas. Immunohistochemistry staining for GFAP was observed in all osteosarcomas (8 cases), all pleomorphic adenomas (7 cases), in 5 of 6 soft tissue myoepitheliomas, and in 21 of 76 chondrosarcomas. By Q-PCR, GFAP was highly expressed in pleomorphic adenomas and, to a lesser extent, chondrosarcomas, soft tissue myoepitheliomas, and chondroblastic osteosarcomas. The results that we obtained by immunohistochemistry and Q-PCR were well correlated. GFAP is a potential marker for tumors with cartilaginous differentiation, supported by evidence that GFAP is expressed in certain cases of myoepithelial tumors by immunohistochemistry, including soft tissue myoepitheliomas, which are related to cartilaginous differentiation. These findings contribute significantly to the diagnosis of soft tissue myoepitheliomas with cartilaginous differentiation and chondroblastic osteosarcoma in mesenchymal tumors. Modern Pathology ( 2009) 22, 1321-1327; doi: 10.1038/modpathol.2009.99; published online 7 August 2009

Recurrent bilateral gingival peripheral calcifying epithelial odontogenic tumor (Pindborg tumor): A case report

Calcifying epithelial odontogenic tumor (CEOT) is an extremely rare, benign neoplasm, accounting for approximately 1% of all odontogenic tumors. Peripheral CEOTs commonly resemble oral hyperplastic or reactive lesions and are histologically similar to their intraosseous counterparts. We report an unusual case of multifocal peripheral CEOT. A 40-year-old female presented with bilateral soft, painful, erythematous, gingival swellings localized in premolar areas of the mandibular gingiva. The presumptive diagnosis was bilateral pyogenic granuloma. The masses were surgically excised under local anesthesia without bone curettage and both recurred 12 months later. Morphologic features, and histochemical and immunohistochemical tests revealed bilateral peripheral calcifying odontogenic epithelial tumor. There is no clinical or radiographic evidence of recurrence 3.5 years after excision. This multifocal phenomenon has been reported previously only for intraosseous CEOT. Gingival masses must be carefully evaluated for clinical and histologic evidence of neoplasia. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2009; 108: e66-e71)

Patients with oral squamous cell carcinoma are characterized by increased frequency of suppressive regulatory T cells in the blood and tumor microenvironment

Oral squamous cell carcinoma (OSCC) is a cancerous lesion with high incidence worldwide. The immunoregulatory events leading to OSCC persistence remain to be elucidated. Our hypothesis is that regulatory T cells (Tregs) are important to obstruct antitumor immune responses in patients with OSCC. In the present study, we investigated the frequency, phenotype, and activity of Tregs from blood and lesions of patients with OSCC. Our data showed that > 80% of CD4(+)CD25(+) T cells isolated from PBMC and tumor sites express FoxP3. Also, these cells express surface Treg markers, such as GITR, CD45RO, CD69, LAP, CTLA-4, CCR4, and IL-10. Purified CD4(+)CD25(+) T cells exhibited stronger suppressive activity inhibiting allogeneic T-cell proliferation and IFN-gamma production when compared with CD4(+)CD25(+) T cells isolated from healthy individuals. Interestingly, approximately 25% of CD4(+)CD25(-) T cells of PBMC from patients also expressed FoxP3 and, although these cells weakly suppress allogeneic T cells proliferative response, they inhibited IFN-gamma and induced IL-10 and TGF-beta secretion in these co-cultures. Thus, our data show that Treg cells are present in OSCC lesions and PBMC, and these cells appear to suppress immune responses both systemically and in the tumor microenvironment.