Clonal evolution in diffuse large B-cell lymphoma with central nervous system recurrence.

BACKGROUND: The prognosis of patients with secondary central nervous system lymphoma (SCNSL) is poor and despite massive advances in understanding the mutational landscape of primary diffuse large B-cell lymphoma (DLBCL), the genetic comparison to SCNSL is still lacking. We therefore collected paired samples from six patients with DLBCL with available biopsies from a lymph node (LN) at primary diagnosis and the central nervous system (CNS) at recurrence. PATIENTS AND METHODS: A targeted, massively parallel sequencing approach was used to analyze 216 genes recurrently mutated in DLBCL. Healthy tissue from each patient was also sequenced in order to exclude germline mutations. The results of the primary biopsies were compared with those of the CNS recurrences to depict the genetic background of SCNSL and evaluate clonal evolution. RESULTS: Sequencing was successful in five patients, all of whom had at least one discordant mutation that was not detected in one of their samples. Four patients had mutations that were found in the CNS but not in the primary LN. Discordant mutations were found in genes known to be important in lymphoma biology such as MYC, CARD11, EP300 and CCND3. Two patients had a Jaccard similarity coefficient below 0.5 indicating substantial genetic differences between the primary LN and the CNS recurrence. CONCLUSIONS: This analysis gives an insight into the genetic landscape of SCNSL and confirms the results of our previous study on patients with systemic recurrence of DLBCL with evidence of substantial clonal diversification at relapse in some patients, which might be one of the mechanisms of treatment resistance.

Correction: The influence of FCGR2A and FCGR3A polymorphisms on the survival of patients with recurrent or metastatic squamous cell head and neck cancer treated with cetuximab.

In the abstract and in other parts of the manuscript the authors wrote that the mutation rs396991 causes a valine (V) to phenylalanine (F) substitution at position 157. However, the correct codon number is 158. These errors have not been fixed in the original Article.

Consensus molecular subgroups (CMS) of colorectal cancer (CRC) and first-line efficacy of FOLFIRI plus cetuximab or bevacizumab in the FIRE3 (AIO KRK-0306) trial.

BACKGROUND: FIRE-3 compared first-line therapy with FOLFIRI plus either cetuximab or bevacizumab in 592 KRAS exon 2 wild-type metastatic colorectal cancer (mCRC) patients. The consensus molecular subgroups (CMS) are grouping CRC samples according to their gene-signature in four different subtypes. Relevance of CMS for the treatment of mCRC has yet to be defined. PATIENTS AND METHODS: In this exploratory analysis, patients were grouped according to the previously published tumor CRC-CMSs. Objective response rates (ORR) were compared using chi-square test. Overall survival (OS) and progression-free survival (PFS) times were compared using Kaplan-Meier estimation, log-rank tests. Hazard ratios (HR) were estimated according to the Cox proportional hazard method. RESULTS: CMS classification could be determined in 438 out of 514 specimens available from the intent-to-treat (ITT) population (n = 592). Frequencies for the remaining 438 samples were as follows: CMS1 (14%), CMS2 (37%), CMS3 (15%), CMS4 (34%). For the 315 RAS wild-type tumors, frequencies were as follows: CMS1 (12%), CMS2 (41%), CMS3 (11%), CMS4 (34%). CMS distribution in right- versus (vs) left-sided primary tumors was as follows: CMS1 (27% versus 11%), CMS2 (28% versus 45%), CMS3 (10% versus 12%), CMS4 (35% versus 32%). Independent of the treatment, CMS was a strong prognostic factor for ORR (P = 0.051), PFS (P < 0.001), and OS (P < 0.001). Within the RAS wild-type population, OS observed in CMS4 significantly favored FOLFIRI cetuximab over FOLFIRI bevacizumab. In CMS3, OS showed a trend in favor of the cetuximab arm, while OS was comparable in CMS1 and CMS2, independent of targeted therapy. CONCLUSIONS: CMS classification is prognostic for mCRC. Prolonged OS induced by FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab in the FIRE-3 study appears to be driven by CMS3 and CMS4. CMS classification provides deeper insights into the biology to CRC, but at present time has no direct impact on clinical decision-making.The FIRE-3 (AIO KRK-0306) study had been registered at ClinicalTrials.gov: NCT00433927.

In-situ analysis of mast cells and dendritic cells in coronary atherosclerosis in chronic kidney disease (CKD).

AIMS: Mast cells (MC) and dendritic cells (DC) have immune modulatory function and can influence T-cell activity. Both cell types have been found in atherosclerotic plaques and are thought to play an important role for plaque stability. Compared to matched segments of the non-renal population, patients with chronic kidney disease (CKD) show a more pronounced and more aggressive course of atherosclerosis with higher plaque calcification and significantly higher complications rates. It was the aim of this study to analyze the number and localization of MCs and DCs, macrophages, T- and B-cells as well as the expression of markers of inflammation such as CRP and NFκB in calcified and non-calcified atherosclerotic plaques of patients with CKD and control patients. METHODS: Fifty coronary atherosclerotic plaques from patients with endstage CKD (CKD, n=25) and control (n=25) patients were categorized according to the Stary classification and investigated using immunohistochemistry (markers for MC, DC, T, B, macrophage and NFκB). Expression was analyzed separately for the complete plaque area as well as for the different plaque subregions and correlations were analyzed. RESULTS: We found only very few DCs and MCs per lesion area with slightly increased numbers in calcified plaques. MCs per plaque area were significantly more frequent in CKD than in control patients and this was independent of plaque calcification. MCs were most frequently found in the shoulder and basis of the plaque. DCs per plaque area were significantly less in calcified plaques of CKD compared to control patients. In control, but not in CKD patients, DCs were significantly more frequent in calcified than in non-calcified plaques. Within the plaques DCs were similarly distributed between all 4 subregions. CONCLUSIONS: Coronary atherosclerotic plaques of CKD patients showed a significantly higher number of MCs whereas DCs were less frequent compared to control patients particularly if plaques were calcified. These findings might indicate a potential proinflammatory role of MCs, but not of DCs in atherosclerotic lesions of CKD patients, adding another characteristic of advanced atherosclerosis in these patients.

The influence of FCGR2A and FCGR3A polymorphisms on the survival of patients with recurrent or metastatic squamous cell head and neck cancer treated with cetuximab.

FCGR2A-H131R and FCGR3A-V157F are single-nucleotide polymorphisms known to influence the outcome of patients treated with rituximab, cetuximab and trastuzumab. We investigated the impact of these polymorphisms on the clinical outcome of 103 patients with recurrent or metastatic squamous cell carcinoma of the head and neck treated with a platinum compound, fluorouracil and cetuximab as palliative first-line therapy. The survival of patients with FCGR2A-131H/H and/or FCGR3A-157V/V genotypes was significantly longer compared with patients carrying 131R and 157F alleles (median progression-free survival (PFS): 5.5 vs 4.1 months, P=0.02; median overall survival: 10.2 vs 7.2 months, P=0.04). In multivariate analysis, the FCGR2A and 3A genotypes as well as the time between initial diagnosis and relapse of disease not amenable to curative therapy remained the only independent prognostic factors for PFS. The results are in line with previous reports in colorectal cancer patients and confirm the possible value of genetic polymorphisms of immunocompetent cells for the success of cetuximab treatment.

[Impact of anastomotic leakage on long-term survival in mid-to-low rectal cancer]. / Einfluss der Anastomoseninsuffizienz auf das Langzeitüberleben beim tiefen Rektumkarzinom.

BACKGROUND: The occurrence of anastomotic leakage (AL) after sphincter preserving anterior rectal resection in patients with rectal cancer is associated with increased morbidity and mortality. The impact of AL on long-term survival has, however, still not been sufficiently investigated and is currently the subject of controversial discussion. OBJECTIVES: The aim of this study was to investigate the impact of AL on long-term survival in patients with Union of International Cancer Control (UICC) (y)0-III stage mid-to-low rectal cancer who underwent sphincter preserving rectal resection. MATERIAL AND METHODS: A total of 108 patients with a mid-to-low rectal cancer (UICC stage (y)0-III) who underwent sphincter preserving surgery between January 2003 and October 2010 were identified within the institutional prospective colorectal cancer database. The impact of AL on 5-year overall (OS), cancer specific (CSS) and relapse-free survival (RFS) was investigated. RESULTS: The overall leakage rate was 17.6 % (grade A 4.6 %, grade B 4.6 % and grade C 8.3 %). After a median follow-up of 70 months (range 24-123 months), patients with an anastomotic leakage had a significantly decreased 5-year OS (63.6 % versus 87.8 %, p = 0.02), CSS (72.2 % versus 93.5 %, p = 0.02) and RFS rate (61.1 % versus 84.2 %, p = 0.01). In univariable Cox regression analysis AL was associated with an unfavorable OS (hazard ratio HR 3.05, 95 % CI: 1.11-8.39, p = 0.03), CSS (HR 4.21, 95 % CI: 1.13-15.70, p = 0.03) and RFS (HR 3.02, 95 % CI: 1.20-7.58, p = 0.02). CONCLUSION: In the study cohort anastomotic leakage after sphincter preserving anterior resection in patients with mid-to-low rectal cancer was associated with a significantly unfavorable impact on overall and oncological survival.

C-reactive protein level is a prognostic indicator for survival and improves the predictive ability of the R-IPI score in diffuse large B-cell lymphoma patients.

BACKGROUND: High levels of C-reactive protein (CRP), an acute phase protein, proofed being associated with decreased clinical outcome in small-scale studies in diffuse large B-cell lymphoma (DLBCL). The aim of this study was to evaluate the prognostic impact of pretreatment CRP levels on overall survival (OS) and disease-free survival (DFS) in a large bicentre study of DLBCL patients. METHODS: Data from 477 DLBCL patients, diagnosed and treated between 2004 and 2013 at two Austrian centres, were evaluated retrospectively. The prognostic influence of CRP and other factors, including age, tumour stage, and revised International Prognostic Index (R-IPI) on 5-year OS and 5-year DFS, were studied by Kaplan-Meier curves as well as univariate and multivariate Cox regression models. Influence of CRP on the predictive accuracy of the R-IPI score was determined by the Harrell concordance index. RESULTS: Kaplan-Meier curves revealed elevated CRP as a factor for decreased 5-year OS and DFS in DLBCL patients (P<0.001, log-rank test). An independent significant association between high CRP levels and poor clinical outcome in multivariate analysis for 5-year OS (HR=1.51, CI 95%=1.04-2.20, P=0.031) and for DFS (HR=1.91, CI 95%=1.28-2.85, P=0.002) was found. The estimated concordance index was 0.75 using the original R-IPI score and 0.79 when CRP was added. CONCLUSIONS: In the present study, we demonstrated high CRP levels at diagnosis of DLBCL as an independent poor prognostic factor for clinical outcome. Adding CRP to the well-established prognostic models such as the R-IPI score might improve their predictive ability.

Increased body mass index is associated with improved overall survival in diffuse large B-cell lymphoma.

BACKGROUND: Obesity is a well-known risk factor for the development of several types of cancer including lymphomas, but its influence on the course of disease is fairly unknown. Recently, a retrospective cancer registry analysis demonstrated significantly prolonged survival for overweight and obese patients with diffuse large B-cell lymphoma (DLBCL). The study population almost exclusively consisted of male US American patients of lower socioeconomic status and one-fifth of patients received cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) chemotherapy without rituximab. Therefore, it remains unclear if these results can be extrapolated to the general DLBCL population. PATIENTS AND METHODS: This retrospective single-center analysis included 183 unselected DLBCL patients who were treated with rituximab and standard-dosed anthracycline-based chemoimmunotherapy as first-line therapy between January 2004 and December 2012. Patients were stratified by body mass index (BMI) into 'low BMI' (<25.0 kg/m(2)) and 'high BMI' (≥25.0 kg/m(2)). RESULTS: The two groups were well balanced regarding age, performance score, international prognostic index, B-symptoms and extranodal involvement. However, there was a trend for male sex (P = 0.053) and higher-stage disease (P = 0.066) in the high-BMI group. Patients with higher BMI had significantly longer overall survival (OS; hazard ratio [HR] 0.546; P = 0.035) with 80.9% of patients alive at 3 years versus 64.2% in the low-BMI group. BMI was also an independent prognostic factor for OS in multivariate analysis (HR 0.557; P = 0.043). CONCLUSION: We could show a significant association between overweight/obesity and improved OS in an unselected DLBCL cohort.

Inhibition of GLI, but not Smoothened, induces apoptosis in chronic lymphocytic leukemia cells.

The Hedgehog (Hh) pathway regulates cell proliferation and survival and contributes to tumorigenesis. We investigated the expression and function of this pathway in B-cell chronic lymphocytic leukemia (CLL) cells and in healthy B lymphocytes. Profiling of cognate Hh pathway members revealed reduced expression of two key Hh signaling effectors, Smoothened (SMOH) and GLI, in CLL cells, whereas transcription levels of other investigated members resembled normal B-lymphocyte levels. Examining the functional role of SMOH and GLI in cell survival, we found that CLL cells were hardly sensitive toward specific SMOH inhibition, but showed an unspecific decline in cell viability in response to high concentrations of the SMOH antagonist cyclopamine. In contrast, treatment with the novel GLI antagonist GANT61 reduced expression of the target gene Patched and preferentially decreased the viability of malignant cells. Specific RNA interference knockdown experiments in a CLL-derived cell line confirmed the autonomous role of GLI in malignant cell survival. GANT61-induced apoptosis in primary leukemic cells was partly attenuated by protective stromal cells, but not soluble sonic hedgehog ligand. In summary, our data show a downregulation of the classical Hh pathway in CLL and suggest an intrinsic SMOH-independent role of GLI in the ex vivo survival of CLL cells.

[A comparative study of the hepatic transit time (HTT) of different ultrasound contrast agents in patients with liver metastases and healthy controls]. / Vergleich der hepatischen Transitzeit (HTT) verschiedener Ultraschallkontrastmittel (USKM) bei Patienten mit Lebermetastasen und gesunden Probanden.

PURPOSE: Liver metastases lead to a shortening of the HTT of an echo enhancer. Studies using SonoVue™ also showed a shortening of the HTT in healthy controls. Hence the HTT depends on the applied contrast agent. We examined whether the HTT of SonoVue™, Luminity™ und Levovist™ is useful to discriminate between patients with and without liver metastases. MATERIALS AND METHODS: We compared the arteriovenous HTT of Levovist™, Sonovue™ und Luminity™ in 20 patients with liver metastases and in 15 controls. An Acuson Sequoia™ ultrasound system was used. The HTT results from the difference of the arrival time of the microbubbles in the hepatic artery and a hepatic vein. RESULTS: Using Levovist™ six patients and three controls had to be excluded from further analysis. The arrival time was undetectable. The mean HTT values in healthy controls were: Levovsit™ 14.75 sec (SD ± 2.53 sec), SonoVue™ 9.27 sec (SD ± 2.41 sec) and Luminity™ 9.2 sec (SD ± 2.34 sec). In patients the mean HTT values were: Levovist™ 9.89 sec (SD ± 1.04 sec), SonoVue™ 6.28 sec (SD ± 2.41 sec) and Luminity™ 6.33 sec (SD ± 1.37 sec). Using a cut off of 8 sec for SonoVue™ and Luminity™, the sensitivity to exclude liver metastases was 75% and 80%. CONCLUSION: The mean HTT values of all contrast agents were shorter in patients. Levovist™ showed a longer HTT in patients and controls than Luminity™ and SonoVue™. Levovist™ showed the best separation between patients and controls but some patients and controls had to be excluded. The HTT could still be a useful tool to exclude liver metastases but the HTT depends on the contrast agent and the applied contrast technique.

Lack of complex I is associated with oncocytic thyroid tumours.

Oncocytic tumours are characterised by hyperproliferation of mitochondria. We immunohistochemically analysed all enzymes of the oxidative phosphorylation system in 19 oncocytic thyroid tumours. A specific lack of complex I was detected, which was expressed at <5% of the level determined in surrounding non-cancerous tissue.

Comparison of histological parameters for the diagnosis of eosinophilic oesophagitis versus gastro-oesophageal reflux disease on oesophageal biopsy material.

AIMS: Eosinophil infiltration of the oesophageal epithelium is the cardinal pathomorphological finding in eosinophilic oesophagitis (EO), but gastro-oesophageal reflux disease (GORD) is also associated with increased eosinophils. The aim was to compare histological parameters for the diagnosis of EO versus GORD on routinely taken biopsy specimens. METHODS AND RESULTS: One hundred and five routine biopsy specimens with EO (n = 62), GORD (n = 24) and probable EO (n = 19) from 74 patients (52 men, 22 women; mean age 43.7 years) were analysed for numbers of eosinophils, mast cells, degranulation and qualitative changes of oesophageal epithelium using immunohistochemistry with monoclonal antibodies against eosinophil peroxidase and eosinophil major basic protein and mast cell tryptase. Eosinophil infiltration was significantly higher in EO than in GORD both on haematoxylin and eosin staining (54.8 versus 9.1; P < 0.05) and immunohistochemistry (77.5 versus 24.7; P < 0.05). Eosinophil degranulation was significantly more intense in EO than in GORD (1.16 versus 0.41; P < 0.05). Furthermore, eosinophilia-codependent secondary qualitative changes of squamous epithelium in EO were generally more extensive than those in GORD. CONCLUSIONS: Histological differential diagnosis of EO and GORD should be based on eosinophil counts, secondary morphological changes of eosinophils and oesophageal squamous epithelium, especially in cases suspicious of EO.

[Uncommon cystic appearance of lymph nodes in malignant lymphoma]. / Aussergewöhnlich zystisches Erscheinungsbild von Lymphknoten bei malignem Lymphom.

Sonographic examination of the abdomen and of superficial lymph nodes in a patient with weight loss and rectal bleeding showed numerous lymph nodes with partially cystic areas. Biopsy and histological examination revealed mantle cell lymphoma. Additional staining with immunological markers confirmed the diagnosis of cystic transformation of the lymph node sinuses.

Eosinophil infiltration and degranulation in oesophageal mucosa from adult patients with eosinophilic oesophagitis: a retrospective and comparative study on pathological biopsy.

AIM: To examine eosinophil infiltration and degranulation in 50 oesophageal biopsy specimens from 30 patients (21 men, 9 women; mean 39 years) with eosinophilic oesophagitis, by haematoxylin and eosin staining and immunohistochemistry. METHODS: Immunohistochemistry was carried out using a monoclonal antibody for human eosinophilic major basic protein (MBP). Eosinophils were counted in three high power fields (x40) and degranulation, as quantified by extracellular MBP immunostaining, was scored on a scale of 1-4. Morphological changes (basal cell hyperplasia, elongation of papillae and dilatation of intercellular spaces) were scored on a 1-4 scale on sections stained with haematoxylin and eosin. RESULTS: Numbers of intraepithelial eosinophils were significantly higher with MBP immunostaining than with haematoxylin and eosin staining (mean 109.6 v 80.6; p<0.001), whereas numbers of eosinophils were considerably correlated (r = 0.794). Eosinophil degranulation was higher in the distal oesophagus. Additionally, basic morphological changes were markedly associated with eosinophil infiltration. Extracellular deposition of eosinophil-MBP and eosinophil infiltration in subepithelial connective tissue, present in the biopsy specimens, were detected by immunohistochemistry. CONCLUSION: Numbers of eosinophils and degranulation are underestimated by haematoxylin and eosin staining. Immunohistochemistry detected up to two times more eosinophils than routine haematoxylin and eosin staining. Moreover, eosinophil-MBP immunoreactivity in extracellular regions indicates the release of toxic eosinophil granule proteins and gives further evidence for a causative role of eosinophils with regard to structural changes in eosinophilic oesophagitis. Immunohistochemistry may serve as a useful diagnostic tool to support the morphological differential diagnosis of eosinophilic oesophagitis and gastro-oesophageal reflux disease.

[Alpha 1-proteinase inhibitor deficiency and isolated liver cirrhosis without pulmonary emphysema in a 53-year-old female patient]. / Alpha 1-Proteinaseninhibitormangel und isolierte Leberzirrhose ohne Lungenemphysem bei einer 53-jährigen Patientin.

HISTORY: A 53 year-old woman presented with an elevated serum aminotransferase and cirrhosis of the liver of unknown cause. She reported neither alcohol nor drug abuse and had no previous serious illness. She had smoked about 10 pack years of cigarettes in the past. INVESTIGATIONS: Serological markers were negative for infectious agents, hemochromatosis, Wilson's disease and autoimmune diseases. Serum electrophoresis showed a decrease of the alpha1-globulin fraction (1 %; normal: 1.5 - 4.0); serum alpha1-antitrypsin was very low at 0.25 ng/l (normal: 0.9 - 2.0). The histology revealed liver cirrhosis due to alpha1-proteinase-inhibitor deficiency. Genetic testing proved a PiZZ type of proteinase-inhibitor deficiency. The patient had normal lung functions. Because of the increased risk of hepatocellular carcinoma, future sonographic monitoring and alpha-fetoprotein measurements every 6 months were recommended. TREATMENT AND COURSE: As lung functions were normal there was no indication for administering alpha1-antitrypsin. CONCLUSION: Although proteinase-inhibitor deficiency is a rare cause of liver cirrhosis, especially without any sign of emphysema, it should be considered when other, more common causes of liver cirrhosis are excluded.

Variants of bcl-2 specific siRNA for silencing antiapoptotic bcl-2 in pancreatic cancer.

BACKGROUND AND AIMS: Pancreatic cancer remains a devastating diagnosis with only limited therapeutic options. Specific inhibition of expression of target genes has become possible using small interfering (si) RNAs. We therefore investigated how far siRNA specific for bcl-2 may serve as a therapeutic option for pancreatic cancer in vitro and in vivo. METHODS: siRNAs targeting two different regions in the bcl-2 gene were transfected to YAP C and DAN G pancreatic carcinoma cells and human foreskin fibroblasts. Permutations were generated by changing 3' and 5' overhangs and varying the length of the paired RNA duplex. Transfection efficacy was determined using FITC labelled siRNAs and fluorescence microscopy. Cell survival and apoptosis were quantified at 24-120 hours. Pancreatic cancer xenografts in male nude mice were treated intraperitoneally with siRNAs daily for 24 days. siRNA pharmacokinetics in vivo were assessed using radioactively labelled siRNAs. Total protein and RNA were extracted for western Blot analysis and quantitative polymerase chain reaction. RESULTS AND CONCLUSIONS: Bcl-2 specific siRNAs specifically inhibited expression of the target gene in vitro and in vivo. Antiproliferative and proapoptotic effects were observed in tumour cells but not in fibroblasts or non-malignant tissues. siRNA permutations and diverse overhangs influenced gene silencing efficacy. siRNA was quickly distributed to all organs and excreted via the kidney and liver. Bcl-2 specific siRNA is a promising adjunctive treatment for pancreatic carcinoma.

Atherosclerosis and vascular calcification in chronic renal failure.

Cardiovascular complications are a major clinical problem in patients with chronic kidney disease and end-stage renal failure; cardiac death accounts for approximately 40-50% of all deaths in these patients. Death from cardiovascular causes is up to 20 times more common in uremic patients than in the general population with the risk being even higher than in patients with diabetes mellitus. A high rate of myocardial infarction and excessive cardiac mortality have repeatedly been documented in patients with kidney disease and renal failure. Not only is the prevalence of myocardial infarction high, but also the case fatality rate is significantly higher in uremic patients with and without diabetes, respectively, compared to nonuremic patients. This is of particular interest since the prevalence of coronary atheroma in uremic patients was shown to be approximately 30% by autopsy and coronary angiography studies. Thus, coronary factors, i.e. atherosclerosis, and non-coronary factors may play an important role in the genesis of cardiac complications in the renal patient. In addition, renal failure recently has also be identified as a predictor of mortality in different stages of peripheral vascular disease. In particular, marked differences in the pathogenesis, morphology and course of atherosclerosis and arteriosclerosis under the conditions of renal failure have been documented. Among others increased plaque formation and particularly higher proportion and intensity of vascular calcification have been found in clinical and autopsy studies. In addition to the so-called classical or traditional risk factors, an important role for nonclassical risk factors such as microinflammation, hyperphosphatemia and oxidative stress has been documented in patients with renal failure and is discussed in detail.

[Central giant cell granuloma and osteitis fibrosa cystica of hyperparathyroidism. A challenge in differential diagnosis of patients with osteolytic jawbone lesions and a history of cancer]. / Riesenzellgranulom und Osteitis fibrosa cystica bei Hyperparathyreoidismus. Differenzialdiagnose bei Osteolysen der Maxilla und bekannter maligner Grunderkrankung.

BACKGROUND: Giant cell lesions of the bone present similar histological features. The differential diagnosis comprises central giant cell granuloma, giant cell tumor of bone, and osteitis fibrosa cystica (brown tumor) in combination with hyperparathyroidism. Since these lesions may mimic metastatic bone disease in patients with a history of cancer, a malignant process has to be considered. Since the treatment and prognosis of these entities-benign versus malignant osteolytic bone processes-differ greatly, definitive differential diagnosis is of utmost importance. CASE REPORT: Two patients presenting with osteolytic lesions of the maxilla are reported here. In both cases a history of cancer (breast and prostate) suggested bone spreading of these malignant tumors. The clinical and histological findings were similar in both patients. One lesion was diagnosed as central giant cell granuloma, the other was found to be brown tumour in osteitis fibrosa cystica as an initial manifestation of hyperparathyroidism. DISCUSSION: The presented cases demonstrate the difficulties in establishing the correct diagnosis of patients found to have osteolytic lesions of the jawbones which is critical for the appropriate management of these patients. The article discusses the different entities of osteolytic lesions of the jawbones and the necessary diagnostic and therapeutic approach.