Cytologic mimics of non-Hodgkin lymphoma in the head and neck.

Non-lymphoid small round blue cell tumors of the head and neck are particularly difficult to diagnose when metastatic to a lymph node. The cytopathologist or surgical pathologist evaluating these lesions has to be aware of the various non-hematopoetic neoplasms that present in the head and neck area that can mimic non-Hodgkin lymphoma. Presented here are the various lesions commonly seen which needs to be entertained depending on where in the head and neck the lesion is located. More recently, a plethora of HPV related head and neck tumors has been described and these lesions add to the mix in this challenging milieu of cases.

Complete response to induction therapy in patients with Myc-positive and double-hit non-Hodgkin lymphoma is associated with prolonged progression-free survival.

BACKGROUND: Myc-positive B-cell non-Hodgkin lymphoma (NHL) with or without a B-cell chronic lymphocytic leukemia/lymphoma 2 (BCL2) rearrangement is associated with inferior progression-free survival (PFS) and overall survival (OS). In this study, the authors reviewed the outcomes of patients with myc-positive and double-hit NHL at The Ohio State University. METHODS: All patients who had non-Burkitt, aggressive B-cell NHL from 2008 to 2011 were assessed for the t(14;18) translocation and for v-myc avian myelocytomatosis viral oncogene homolog (CMYC) rearrangements at diagnosis, and all myc-positive patients were included in the current analysis. Associations with clinical characteristics were described, and univariable and multivariable models were used to assess correlations between clinical variables and outcomes. RESULTS: Of 49 myc-positive patients, 29 patients also had BCL2 rearrangements (double-hit NHL). No patients underwent autologous stem cell transplantation in first remission. For all myc-positive patients, the median PFS was 16.6 months, and the median OS was 37.7 months. For patients who had double-hit NHL, the median PFS was 8 months, and the median OS was 12.5 months; whereas the median PFS and OS were not reached for myc-positive patients. A complete response (CR) after front-line therapy, the presence of t(14;18), International Prognostic Index (IPI) group, and age were associated with PFS; whereas only the achievement of a CR and age >60 years were associated with OS in the multivariable setting. The median PFS was 3.3 months, and the median and OS was 7.0 months for patients who did not attain a CR; and the medians were not reached for patients who achieved a CR (P < .00001). CONCLUSIONS: The achievement of a CR with front-line therapy is associated with a prolonged PFS and OS in patients with myc-positive NHL, even after adjusting for type of initial therapy, histology, age, IPI, or the presence of a concurrent BCL2 translocation.

Comparison of three reference methods for the measurement of intracellular pH using 31P MRS in healthy volunteers and patients with lymphoma.

31P magnetic resonance spectroscopy (31P MRS) can measure intracellular pH (pHi) using the chemical shift difference between pH-dependent inorganic phosphate (Pi) and a pH-independent reference peak. This study compared three different frequency reference peaks [phosphocreatine (PCr), α resonance of adenosine triphosphate (αATP) and water (using 1H MRS)] in a cohort of 10 volunteers and eight patients with non-Hodgkin's lymphoma (NHL). Well-resolved chemical shift imaging (CSI) spectra were acquired on a 1.5T scanner for muscle, liver and tumour. The pH was calculated for all volunteers and patients using the available methods. The consistency of the resulting pH was evaluated. The direct Pi­PCr method was best for those spectra with a very well-defined PCr, such as muscle (pH=7.05 ± 0.02). In liver, the Pi­αATP method gave more consistent results (pH=7.30 ± 0.06) than the calibrated water-based method (pH=7.27 ± 0.11). In NHL nodes, the measured pH using the Pi­αATP method was 7.25 ± 0.12. Given that the measured range includes some biological variation in individual patients, treatment-related changes of the order of 0.1 pH units should be detectable.

Simultaneous quantification of pirarubicin, doxorubicin, cyclophosphamide, and vincristine in human plasma of patients with non-Hodgkin's lymphoma by LC-MS/MS method.

Pirarubicin (THP), doxorubicin (DOX), cyclophosphamide (CTX), and vincristine (VCR) are widely used in the treatment of patients with non-Hodgkin's Lymphoma. Herein, a precise and sensitive method was developed for the determination of THP, DOX, CTX and VCR in human plasma by high-performance liquid-chromatography-tandem mass spectrometry (LC-MS/MS). Liquid-liquid extraction was applied to extract THP, DOX, CTX, VCR, and the internal standard (IS, Pioglitazone) in plasma. Agilent Eclipse XDB-C18 (3.0 mm × 100 mm) was utilized and chromatographic separation was obtained in eight minutes. Mobile phases were composed of methanol and buffer (10 mM ammonium formate containing 0.1% formic acid). The method was linear within the concentration range of 1-500 ng/mL for THP, 2-1000 ng/mL for DOX, 2.5-1250 ng/mL for CTX, and 3-1500 ng/mL for VCR. The intra- and inter-day precisions of QC samples were found to be below 9.31 and 13.66%, and accuracy ranged from -0.2 to 9.07%, respectively. THP, DOX, CTX, VCR and the internal standard were stable in several conditions. Finally, this method was successfully utilized to simultaneously determine THP, DOX, CTX and VCR in human plasma of 15 patients with non-Hodgkin's Lymphoma after intravenous administration. Finally, the method was successfully employed in the clinical determination of THP, DOX, CTX, and VCR in patients with non-Hodgkin lymphoma after administration of RCHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) regimens.

Identification of potential surrogate end points in randomized clinical trials of aggressive and indolent non-Hodgkin's lymphoma: correlation of complete response, time-to-event and overall survival end points.

BACKGROUND: The correlation between efficacy end points in randomized controlled trials (RCTs) of systemic therapy for non-Hodgkin's lymphoma (NHL) was investigated to identify an appropriate surrogate end point for overall survival (OS). METHODS: RCTs of previously untreated NHL published from 1990 to 2009 were identified. Associations between absolute differences in efficacy end points were determined using nonparametric Spearman's rank correlation coefficients (r(s)). RESULTS: Thirty-eight RCTs representing 85 treatment arms for aggressive NHL and 20 RCTs representing 42 arms for indolent NHL were included. For aggressive NHL, differences in 3-year progression-free survival (PFS)/event-free survival (EFS) were high correlated with differences in 5-year OS {r(s) of 0.90 [95% confidence interval (CI) 0.73-0.96]} and linear regression determined that a 10% improvement in 3-year EFS or PFS would predict for a 7% ± 1% improvement in 5-year OS. For indolent histology disease, differences in complete response were strongly correlated with differences in 3-year EFS [r(s) 0.86 (95% CI 0.35-0.97)], but there was no correlation between 3-year time-to-event end points and 5-year OS. CONCLUSIONS: Improvements in 3-year EFS/PFS are highly correlated with improvements in 5-year OS in aggressive NHL and should be explored as a candidate surrogate end point. Definition of these relationships may inform future clinical trial design and interpretation of interim trial data.

Flow cytometry as an accurate tool to complement fine needle aspiration cytology in the diagnosis of low grade malignant lymphomas.

OBJECTIVE: Diagnosis of low grade non-Hodgkin B-cell lymphomas on cytological material may be problematic and in the past frequently required lymph node excision. We analysed our experience of the value of flow cytometry (FC) as an additional tool for the diagnosis of lymphoproliferative processes in the setting of a university cytology division with a busy fine needle cytology service. METHODS: Consecutive cytological specimens with FC over a period of 3 years were retrospectively analysed and correlated with histology and follow-up if available. FC was performed with the following antibodies: CD3, CD4, CD8, CD2, CD7, CD19, CD5, CD10, CD23, lambda and kappa chains. RESULTS: Of 299 probes (273 fine needle aspirations and 26 fluids from 285 patients), 179 cases (60%) were diagnosed as reactive, 91 cases (30%) as malignant or suspicious and 29 cases (10%) as inconclusive. The results of histological examination of the lymph nodes were available in 41 of 91 (45%) malignant or suspicious cases and in 13 of 179 (7%) reactive cytological diagnoses. Cytologically diagnosed malignancy was confirmed in all histologically examined cases. In 12 of 13 reactive cytological cases (92%), a benign process was diagnosed histologically. In 34 of 299 cases (11%) additional molecular investigations of B-cell clonality or specific translocations were performed. The lymphomas most frequently diagnosed were follicular lymphoma and lymphocytic lymphoma, followed by mantle cell and marginal zone lymphomas. Correlation with histology showed a sensitivity of 98% and a specificity of 100% for cytology in our series. CONCLUSIONS: FC is an important additional tool in the cytological diagnosis of lymphoproliferative disorders. The combined approach has a high diagnostic value that allows a reliable subclassification of low grade B-cell non-Hodgkin lymphomas.

Primary central nervous system lymphoma: immunohistochemical profile and prognostic significance.

Primary central nervous system lymphoma (PCNSL) is a rare subtype of non-Hodgkin lymphoma (NHL) with extranodal location affecting only the CNS, meninges and eye, without visceral or lymph node involvement. Its incidence has increased sharply over the past three decades, especially in immunocompetent subjects. Most PCNSL cases are diffuse large B-cell lymphomas (DLBCLs). However, it differs from nodal DLBCL in that it has a worse prognosis. DLBCLs are a heterogeneous entity and according to new genomic discoveries, classifications into prognostic subgroups have been embarked upon. Two prognostic algorithms were then prepared using a panel of immunohistochemical markers (CD10, Bcl6, MUM1/IRF-4, and Bcl2), thus categorizing DLBCL into two subgroups, GCB (germinal centre B-cell-like) or non-GCB, and into Group 1 or Group 2. Our goal is to apply both of these two sub-classifications to 39 PCNSLs, in order to assess their usefulness and prognostic relevance. 74.3% of our PCNSLs were of a non-GCB phenotype, corresponding to an activated postgerminal origin. They were evenly distributed across G1 and G2. Two- and 5-year overall survival rates were 34.8% and 19.6%, respectively. Younger age (<65) and a therapeutic combination of chemotherapy and radiotherapy significantly improved our patients' survival rates. The other clinical or biological markers tested had no prognostic impact. The two classifications did not reveal any significant survival difference. The recent discovery of a specific "transcriptional signature" of PCNSL, marking them out of DLBCL could account for the irrelevance of such prognostic classifications to PCNSL.

TCL1A expression delineates biological and clinical variability in B-cell lymphoma.

The assembly of a collection of gene-expression signatures of the major types of B-cell non-Hodgkin's lymphoma has identified increased T-cell leukemia/lymphoma 1A (TCL1) expression in multiple lymphoma types and cases, and has enabled the investigation of the functional and clinical importance of TCL1 expression. Specifically, Burkitt's lymphoma cases show a homogeneously strong expression of TCL1, whereas diffuse large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma, chronic lymphocytic leukemia, nodal marginal zone lymphoma, and splenic marginal zone lymphoma display a striking variability in the intensity of TCL1 staining. This was validated in two independent series. A Gene-Set Enrichment Analysis of the genes correlated with TCL1A expression found that variation in the level of expression of TCL1A was significantly associated with some of the most important gene signatures recognizing B-cell lymphoma pathogenesis and heterogeneity, such as germinal center, B-cell receptor, NF-kappaB (and its target genes), death, MAP kinases, TNFR1, TOLL, and IL1R. Additionally, TCL1 expression was correlated with shorter time to treatment in chronic lymphocytic leukemia cases and shorter lymphoma-specific survival in mantle cell lymphoma series, thus indicating the clinical and biological significance of TCL1 expression, and suggesting TCL1A as a potential therapeutic target.

Protein profiling of B-cell lymphomas using tissue biopsies: A potential tool for small samples in pathology.

Non-Hodgkin's lymphoma comprises many related but distinct diseases and diagnosis and classification is complex. Protein profiling of lymphoma biopsies may be of potential value for use in this lymphoma classification and the discovery of novel markers. In this study, we have optimized a method for SELDI-TOF MS based protein profiling of frozen tissue sections, without dissection of tumour cells. First we have compared chip surfaces and lysis buffers. Also, we have determined the minimal input using laser dissection microscopy. Subsequently, we have analyzed and compared protein profiles of diffuse large B-cell lymphoma (n=8), follicular lymphoma (n=8) and mantle cell lymphoma (n=8). Benign, reactive lymph nodes (n=14) were used as a reference group.CM10 chip surface in combination with urea lysis buffer and an input of approximately 50,000 lymphocytes allowed the detection of many differential peaks. Identification of the diffuse large B-cell lymphoma cases was reliably made in the supervised classification. Unsupervised clustering showed segregation into a benign/indolent cluster predominantly formed by benign, reactive lymph nodes and follicular lymphoma cases and into a more aggressive cluster formed by diffuse large B-cell lymphoma and mantle cell lymphoma cases. In conclusion, our protocol enables protein profiling of protein lysates derived from small histological samples and the subsequent detection of many differentially expressed proteins, without the need of tumour cell dissection. These results support further evaluation of protein profiling of small lymphoma biopsies as an additional tool in pathology.

Expression of Foxo3a in non-Hodgkin's lymphomas is correlated with cell cycle inhibitor p27.

OBJECTIVE: Cell cycle arrest by FOXO transcription factors involves in transcriptional activation of p27(kip1), although the exact mechanism remains unclear. And it has been evidenced that reduced level of p27(kip1) which is frequently occurred in human cancers has been associated with poor prognosis. In this study, our purpose is to investigate the clinical relevance of altered patterns of Foxo3a and p27(kip1) expression in Chinese patients with localized non-Hodgkin's lymphomas (NHL). METHODS: We analyzed the Foxo3a and p27(kip1) expression of Chinese NHL patients by immunohistochemistry and protein levels using Western Blot. RESULTS: There was a direct relationship between the low level of Foxo3a and the rapid proliferation in immunohistochemical analyses. We also found a positive correlation between Foxo3a and p27(kip1) in immunohistochemical analyses and cell culture. Additionally we revealed that activation of Foxo3a could induce the accumulation of p27(kip1) at protein levels when cell cycle was arrested. CONCLUSIONS: The expression of Foxo3a may be correlated with patients' survival.

Difficulties in diagnosing small round cell tumours of childhood from fine needle aspiration cytology samples.

There are four basic reasons for the difficulties in diagnosing small round cell tumours (SRCT) in childhood from fine needle aspiration cytology (FNAC) samples. First, SRCTs are rare and it is difficult for cytopathologists to obtain enough experience for rendering reliable diagnoses. Second, SRCTs are morphologically very similar. Third, many SRCTs do not have specific antigens which could be demonstrated with immunocytochemistry (ICC) or they lose them when poorly differentiated. In addition, cross reactivity exists between some SRCTs. Unstandardized performance of ICC also contributes to the difficulties due to unreliable results. Fourth, suboptimal FNAC samples add additional pitfalls. The latter may be due to partly degenerate samples or to unrepresentative ones in cases where a SRCT is a heterologous component of another nosological entity. Lymphoma, neuroblastoma, nephroblastoma, Ewing's tumour/primitive neuroendocrine tumours and rhabdomyosarcoma are discussed in detail, while other less common SRCTs are mentioned as differential diagnoses when appropriate. The use of cytogenetic and molecular techniques for differentiating between certain SRCTs is helpful in some doubtful cases. However, there are still problems in the use of these techniques, especially their cost which may delay their being introduced in every cytopathology laboratory.

Ocular adnexal lymphoma in the Northeast Indian population.

We present the clinical profile of biopsy and immunohistochemistry-proven ocular adnexal lymphomas in the Northeast Indian population. Nineteen patients between October 2004 and June 2006 with ocular adnexal lymphoma were analyzed retrospectively. Histopathological classification was done according to international working formulation. Twelve patients were male and seven were female. All were diagnosed as non-Hodgkin's lymphoma and the majority were B cell type (89%). Most of the cases (42%)were treated with radiotherapy followed by chemotherapy.

Serum organochlorines and non-Hodgkin lymphoma: A case-control study in Israeli Jews and Palestinians.

Associations of organochlorine (OC) pesticides and polychlorinated biphenyls (PCBs) with non-Hodgkin lymphoma are controversial. We compared serum levels of 6 OC pesticides and 38 PCBs in Israeli Jews (IJ) and Palestinian Arabs (PA) and assessed possible associations with B-cell non-Hodgkin lymphoma (B-NHL). Ninety B-NHL cases (50 IJ and 40 PA) and 120 controls (65 IJ and 55 PA) were included. Median concentrations of analytes in controls were compared across ethnic groups using quantile regression, adjusting for age and sex. We used logistic regression to derive odds ratios (OR) and 95% confidence intervals (CI) for detectable analytes and B-NHL, adjusting for age, ethnic group, faming and body mass index. Median values of PCBs and dichlorodiphenyldichloroethylene (DDE) were higher in IJ vs PA controls (P = 0.0007), as were several PCBs (74, 99, 118, 138, 146, 153, 156, 163, 170, and 180). Overall, OC pesticide and PCB exposures were comparable with reports from high-income countries. B-NHL was associated with PCB 146 (OR 1.70, 95% CI: 1.02, 2.83), PCB 156 (OR 1.75, 95% CI: 1.06, 2.89), and high-chlorinated PCBs (OR 1.55, 95% CI: 1.00, 2.40) in all study subjects. These associations were robust in quantile as well as sensitivity analyses. An association of DDE with B-NHL was noted in PA (OR 1.72, 95% CI: 1.07, 2.77), but not in IJ (OR 0.87, 95% CI: 0.59, 1.27). Although high-chlorinated PCB concentrations did not indicate high exposure levels, our findings indicate that B-NHL may be associated with this exposure.

Composite splenic marginal zone lymphoma and mantle cell lymphoma arising from 2 independent B-cell clones.

We report the first case of composite lymphoma involving both mantle cell lymphoma (MCL) and splenic marginal zone lymphoma (SMZL) with circulating villous lymphocytes. Morphological, immunohistochemical, immunophenotyping, as well as detailed genetic studies (fluorescence in situ hybridization, IGVH gene sequencing), were performed and confirmed the existence of 2 independent, unrelated tumor clones. The MCL component expressed IgMD lambda, was CD5+, harbored a t(11;14)(q13;q32) involving CCND1, and showed an unmutated VH1-18 gene rearrangement. The SMZL component expressed IgMD kappa, was CD5-, showed a t(10;14)(q24;q32) and an unmutated VH3-7 gene rearrangement. Interestingly, this t(10;14) targeted the NFKB2 gene. Only a single other case of SMZL with t(10;14)/NFKB2 has been reported. Taken together, these data indicate that the MCL and SMZL arose as a consequence of independent malignant transformation events within an antigen-naive B-cell population. This case highlights the importance of a multidisciplinary approach and tissue diagnosis in these complex situations.

The expression of the peripheral cannabinoid receptor on cells of the immune system and non-Hodgkin's lymphomas.

The peripheral cannabinoid receptor CB2 is expressed highly on normal human B-lymphocytes. C-terminal specific anti-CB2 antibody recognises a non-phosphorylated inactive receptor on naïve and resting B-lymphocytes. Another, N-terminal specific CB2 antibody, primarily recognises B-cells present in the germinal centres of secondary follicles in lymph nodes. We hypothesise that N-terminal specific CB2 antibody recognises activated CB2 receptors. In this study, we showed using these antibodies, that expression of CB2 is generally absent on T-lymphocytes in reactive, non-malignant human lymphoid tissues. Applying single and dual immunohistochemistry, CD23(+) follicular dendritic cells and a small but significant subpopulation of CD68(+) macrophages showed positive staining with the N-terminal specific CB2 antibody but not with the C-terminal specific CB2 antibody. This may indicate the presence of an active CB2 receptor on these cells with possible involvement in immunomodulation. In contrast to the low expression on normal T-cells, abundant levels of CB2 protein were present on T-non-Hodgkin's lymphomas (NHL). Moreover, in many B-NHL, high CB2 protein expression was found as well. In contrast to the distinct expression patterns in normal immune tissues using the two different CB2 antibodies, NHL specimens in general stained positively with both. We conclude that CB2 receptor expression pattern may be abnormal in NHL.

Cutaneous manifestations in non-Hodgkin's lymphoma.

OBJECTIVE: To examine and subtype cutaneous lymphoma specimens for diagnosis. STUDY DESIGN: Aspiration smears from skin lesions and lymph nodes diagnosed as non-Hodgkin's lymphoma (NHL) on cytology in 6 cases over a period of 1 year were reviewed. Two were follow-up cases of nodal lymphoma and were receiving chemotherapy, during which they developed skin lesions. In 4, the patients had cutaneous lesions as a presenting manifestation. Cytologic findings were correlated with histologic and hematologic findings and immunocytochemical markers for subtyping. RESULTS: Patients ranged from 14 to 50 years, with equal sex ratio. All presented with 0.5-5 cm multiple nodular, ulcerated and fungating skin lesions at various body sites. The aspirate was satisfactory in all cases. Cytologically, all cases were diagnosed as NHL. They were then immunocytochemistry subtyped as various lymphomas. CONCLUSION: Cutaneous lymphoma should always be considered in the presence of predominantly atypical lymphoid cells in smears from nodular and fungating skin lesions, even in the absence of a definitive clinical diagnosis.

Cancer monitoring by FTIR spectroscopy.

Evidence for balanced cell growth where protein and RNA content rise at a constant relative rate with respect to DNA content with increasing grade of cancer and with malignant transformation, is derived from analysis of infrared spectra of malignant lymphoma and transformed fibroblasts within the literature. This evidence is consistent with flow cytometry derived RNA-protein relationships, and supports the biosynthetic connection proposed here between the RNA/DNA ratio as calculated from the absorbance pulse at 1121 cm(-1), and the protein/nucleic acid ratio as measured by the absorbance ratio A1650 cm(-1)/A1084 cm(-1). The present analysis is the first to explain and show evidence for a simple unifying biomolecular content theory for interdependent changes seen within the fingerprint region (900 cm(-1)-1750 cm(-1)) of the infrared spectrum of cells. Structural changes to lipids and proteins in the wavenumber range 2800 cm(-1)-3000 cm(-1), seen as increasing CH3/CH2 ratio and decreasing symmetric CH2/asymmetric CH2 ratio, are found for the first time to occur with increasing cancer (lymphoma) grade as well. These lipid/protein structural changes (2800-3000 cm(-1)) may reflect an increasing protein/lipid content ratio with malignant grade, and are the same as those shown recently for benign to malignant transformation, further supporting their cellular metabolic basis. Rising ribose content (1121 cm(-1)) is seen to correlate with rising 996 cm(-1)/966 cm(-1) ratio (another index of RNA/DNA) with increasing malignant lymphoma grade as well, The proposed spectral connections have a high signal/noise ratio with respect to clinically meaningful information. They may potentially be applied to clinical cancer grading, or in vitro cancer treatment sensitivity testing.

Molecular markers (PECAM-1, ICAM-3, HLA-DR) determine prognosis in primary non-Hodgkin's gastric lymphoma patients.

AIM: To investigate the prognostic significance of PECAM-1, ICAM-3 and HLA-DR antigens in patients with primary non-Hodgkin's gastric lymphoma. METHODS: We immunohistochemically studied PECAM-1, ICAM-3 and HLA-DR antigen expression in 36 B-cell MALT-type primary gastric lymphoma patients. Ten non-malignant and ten healthy gastric tissue specimens were used as controls. Clinicopathological and survival data were correlated with the staining results. RESULTS: HLA-DR antigen expression was detected in 33 gastric lymphoma patients (91.7%) and 6 non-malignant patients (54.5%). PECAM-1 stained tumor cells of 10 patients (27.8%), endothelial cells of 9 patients (25%) and inflammatory infiltrate of 4 patients (40%) with benign gastric disease. ICAM-3 expression was observed on the tumor cells of 17 patients (47.2%), while 5 non-malignant patients (50%) were stained positive as well. None of the healthy controls was stained for any of the genes studied. In the multivariate analysis, HLA-DR antigen and PECAM-1 were proved to be statistically significant independent prognostic factors associated with a favourable and an unfavourable prognosis respectively (P=0.009 and P=0.003). In the univariate analysis, PECAM-1(+)/ICAM-3(-) and HLA-DR(-)/ICAM-3(-) patients exhibited a significantly decreased overall survival compared to those with the exactly opposite gene expression patterns (P=0.0041 and P=0.0091, respectively). Those patients who were HLA-DR(+)/ICAM-3(+)/PECAM-1(-) (n=8) had a significantly higher survival rate compared to the rest of the group (n=24) (P=0.0289). CONCLUSION: PECAM-1, ICAM-3 and HLA-DR are representative markers of tumor expansion potential and host immune surveillance respectively. Their combined use may help us to identify high-risk patients who could benefit from more aggressive therapeutic protocols.

The truncated glucocorticoid receptor in the P1798 mouse lymphosarcoma is associated with resistance to glucocorticoid lysis but not to other glucocorticoid-induced functions.

Glucocorticoid receptors in lines of the P1798 mouse lymphosarcoma either sensitive or resistant to glucocorticoid-induced lysis have been characterized and their functional significance determined. The glucocorticoid receptor from the cortisol-sensitive tumor is an Mr approximately 98,000 protein with a Stokes radius of 7.4 nm in the oligomeric, non-DNA-binding state and 5.6 nm in the transformed, DNA-binding state. This receptor binds glucocorticoid and reacts with the BUGR-2 monoclonal antibody. In contrast, two abnormal receptor species were identified in the cortisol-resistant tumor. One is an Mr approximately 98,000 non-steroid-binding but immunologically reactive protein. The other is an Mr approximately 45,000 species which contains both steroid- and DNA-binding sites but exhibits little or no reactivity with BUGR-2, suggesting that its NH2 terminus is truncated in a region within or adjacent to the BUGR epitope. This species had Stokes radii of 5.8 and 3.5 nm in nontransformed and transformed states, respectively. In both tumor lines, glucocorticoids stimulated the activities of glutamine synthetase and 5'-nucleotidase and the synthesis of glucocortin. However, glucocorticoid-induced tumor regression occurred only in the cortisol-sensitive tumor. Additionally, the glucocorticoid inducibility of a specific protein in the sensitive, but not in the resistant, tumor was demonstrated, as well as the presence of a protein specific to the resistant line. Taken together, these results suggest that the truncated glucocorticoid receptor in the P1798 lymphosarcoma is functional, although possibly in a more restricted gene-specific manner, and that the lysis defect, while possibly resulting from a truncated receptor, may also result from the inability of glucocorticoids to induce a critical protein in the pathway of programmed cell death and/or from the presence of a protein which inhibits the lytic response.