Oral soft tissue manifestation of multiple myeloma after kidney transplantation: a case report.

This report presents a case in which oral soft tissue lesions were the first signs of multiple myeloma (MM) following a solid-organ transplantation. A 75-year-old man presented with bilateral primary oral gingival masses in the posterior mandible approximately 2 months after tooth extractions. A panoramic radiograph appeared normal and did not reveal "punched-out" lytic lesions of the bone, a classic sign of MM. A biopsy of the gingival masses was performed, and the resulting diagnosis was a plasma cell neoplasm. After a hematologic screening, positron emission tomography/computed tomography, and bone marrow biopsy, the diagnosis of MM with extensive disease was confirmed. Oral manifestations of MM are common, making the patient's oral health history an integral part of diagnosis. Although the isolated gingival hypertrophy observed in the present case is an atypical oral presentation, an understanding of the maxillofacial manifestations of MM is important to ensure diagnosis in the early stages of disease.

Carcinocythemia: A rare entity becoming more common? A 3-year, single institution series of seven cases and literature review.

INTRODUCTION: Carcinocythemia is a rare phenomenon defined as morphologically identifiable, circulating tumor cells in the peripheral blood. No modern case series of carcinocythemia exists in the literature. METHODS: Blood smears from carcinocythemia patients were reviewed and associated clinicopathologic findings described and compared to the literature. When available, bone marrows were examined. RESULTS: We identified 7 carcinocythemia cases over 3 years at our institution in 5 females and 2 males with a median age of 57 and compare them to 26 case reports in the literature (19 females, 10 males; median age 57). The primary neoplasms were carcinomas of breast (3 cases), lung, non-small cell (2 cases), prostate (1), and 1 case of unknown primary. Circulating tumor cells were associated with fragmentation hemolysis (2 cases), asplenic RBC changes (3 cases), and myeloid antigen expression by flow cytometry (2 cases) and were most commonly found at the feathered edge of the slide (6 cases) as single cells or in clusters. CONCLUSIONS: This represents the largest series of carcinocythemia reported. The identification of 7 cases at one institution over a 3-year period suggests carcinocythemia may becoming more common. Raising awareness of this entity and its associated clinicopathologic findings may help avoid diagnostic pitfalls in blood smear examinations and may guide timely clinical management.

CD30 Expression in Monomorphic Posttransplant Lymphoproliferative Disorder, Diffuse Large B-Cell Lymphoma Correlates With Greater Regulatory T-Cell Infiltration.

OBJECTIVES: CD30 is a protein thought to promote cell proliferation/survival and downregulate the immune response. Twenty percent to 40% of de novo diffuse large B-cell lymphomas (DLBCLs) express CD30, and some patients have been treated with the anti-CD30 agent brentuximab. In the solid organ transplant setting, allograft regulatory T cells (Tregs) have been shown to be modulated via CD30 signaling. METHODS: Posttransplant lymphoproliferative disorders (PTLDs) constitute a heterogeneous group of lymphomas, and since CD30 expression has been rarely formally assessed in PTLDs, we analyzed a cohort of PTLDs. RESULTS: We found that 26 (79%) of 33 PTLDs were CD30+. Of these, 17 (77%) of 22 DLBCL monomorphic PTLDs were CD30+ compared with 56 (38%) of 148 de novo DLBCLs (P = .009). The median FoxP3+ Treg count was higher in CD30+ than in CD30- PTLDs, 3.0 vs 0 (P = .012). CONCLUSIONS: These findings suggest a pathophysiologic link between CD30 activity and Tregs and may indicate differential expression of CD30 in B-cell lymphomas arising in the setting of immune dysregulation.

Evaluation of CD43 expression in non-hematopoietic malignancies.

OBJECTIVES: CD43 is normally expressed only on the surface of leukocytes, and is considered a sensitive and specific marker for hematologic malignancies. As such, it may have diagnostic utility in confirming hematolymphoid lineage in cases that are negative for CD45. Aberrant CD43 expression has been described in non-hematopoietic tumors, although literature data on this topic is variable and sometimes contradictory. To clarify and expand on existing literature findings, we evaluated CD43 expression by immunohistochemistry (IHC) in a large cohort (307) of non-hematopoietic neoplasms, including poorly differentiated malignancies. METHODS: 17 tissue microarrays and sections from 19 individual cases were stained with CD43 (clone DF-T1) monoclonal antibody. The proportion of positive cells, stain localization (nuclear, cytoplasmic or membranous), and intensity (compared to internal leukocyte controls) were recorded in all cases. RESULTS: There were 98/307 (32%) positive cases, that showed focal weak nuclear staining in 1-25% of cells, including 23/25 (92%) pancreatic ductal adenocarcinomas; 31/34 (91%) breast invasive ductal carcinomas; 13/15 (87%) papillary thyroid carcinomas; 3/4 (75%) follicular thyroid carcinomas; 6/15 (40%) renal cell carcinomas; 9/28 (32%) lung adenocarcinomas; 1/13 (8%) lung squamous cell carcinomas (SCCs); 2/8 (25%) prostate adenocarcinomas; 8/62 (13%) colon adenocarcinomas; and 2/21 (10%) neuroendocrine neoplasms. None of the positive cases demonstrated strong, membranous CD43 expression comparable to that seen in background mature lymphocytes or segmented neutrophils. Negative cases included 11 cervical SCCs, 12 cervical adenocarcinomas, 19 urothelial carcinomas, 10 lung small cell carcinomas, 11 sarcomas, and 19 poorly differentiated carcinomas from various tissue sites. CONCLUSIONS: In our cohort, most non-hematopoietic neoplasms are negative for CD43 expression, with a subset showing focal, weak nuclear positivity. This data indicates that uniform and strong membranous staining appears to be specific to hematopoietic neoplasms.

Local Disease Control in Ocular Adnexal Lymphoproliferative Disorders: Comparative Outcomes of MALT Versus Non-MALT Histologies.

INTRODUCTION: Ocular adnexal lymphoproliferative disorders (OALDs) are almost exclusively of B-cell origin, with the majority being extra-nodal marginal zone lymphomas of mucosa-associated lymphoid tissue (MALT). The comparative efficacy of involved field radiation therapy (IFRT) in MALT vs. non-MALT OALDs is not known. MATERIALS AND METHODS: We present a single-center, large cohort, retrospective study of the efficacy of IFRT in OALDs. Failure-free survival (FFS), complete remission, and local, regional, and distant failure were determined for 112 patients with MALT OALDs (n = 71) and non-MALT OALDs (n = 41) cohorts. RESULTS: Fifty-six patients with MALT OALD and 26 patients with non-MALT OALD received IFRT only (without any planned concurrent or sequential systemic chemothereapy or chemo-immunotherapies). Among the OALD cohorts treated with only IFRT, complete remission was achieved in 49 (87.5%) patients in the MALT cohort and 23 (88.4%) in the non-MALT cohort (P = .99). Clinically, resolution of symptoms occurred in 83.3% and 93.3% of the patients in the MALT and non-MALT cohorts, respectively. Local failure occurred in 4 (7.1%) patients in the MALT cohort, compared with 4 (15.3%) patients in the non-MALT cohort (P = .24). Regional failure (or extra-orbital failure) occurred in 5 (8.9%) patients in the MALT cohort and in 3 (11.5%) patients in the non-MALT cohort (P = .71). Distant failure was reported in 1 (1.7%) and 2 patients (7.6%) in the MALT and non-MALT cohorts, respectively (P = .18). The median follow-up of survivors was 5.1 years (range, 0.1-22.5 years) in the MALT cohort and 3.9 years (range, 0.1-22.9 years) in the non-MALT cohort. The 5-year and 10-year FFS was 95% (95% confidence interval [CI], 88%-100%) and 83% (95% CI, 70%-98%) for the ocular MALT and 67% (95% CI, 48%-94%) and 56% (95% CI, 34%-91%) for the non-MALT cohorts, respectively (log rank for P = .025). On multivariate analyses, age (hazard ratio [HR], 1.06; 95% CI, 1.10-1.12; P = .03), presence of non-MALT histology (HR, 13.9; 95% CI, 2.05-94.4; P = .007), and radiation dose < 30.6 Gy (HR, 5.27; 95% CI, 1.14-24.3; P = .03) were associated with worse FFS. The 5-year and 10-year overall survival was 92% (95%, CI 83%-100%) and 80% (95% CI, 66%-96%) for the MALT and 78% (95% CI, 61%-100%) and 62% (95% CI, 38%-100%) for the non-MALT cohorts, respectively (P = .80). CONCLUSION: Our results reveal that IFRT provided excellent disease control with superior FFS in the MALT cohort when compared with the non-MALT group.

Immunophenotypes of Chronic Myelomonocytic Leukemia (CMML) Subtypes by Flow Cytometry: A Comparison of CMML-1 vs CMML-2, Myeloproliferative vs Dysplastic, De Novo vs Therapy-Related, and CMML-Specific Cytogenetic Risk Subtypes.

OBJECTIVES: We sought to immunophenotype blasts, monocytes, and granulocytes in chronic myelomonocytic leukemias (CMMLs) and compare CMML subtypes, to identify if significant antigen expression differences existed. METHODS: Bone marrow blasts, monocytes, and granulocytes from CMML subgroups (n = 30; World Health Organization types 1/2, proliferative/dysplastic, therapy related/de novo, and low/intermediate/high cytogenetic risk) were immunophenotypically compared by flow cytometry with 10 nonneoplastic control marrows. RESULTS: Aberrancies were present in blasts of 26 (87%) of 30 CMMLs (26 diagnostic; four follow-up) and six (60%) of 10 controls (P = .089), monocytes of 28 (93%) of 30 CMMLs and six (60%) of 10 controls (P = .026), and granulocytes of eight (28%) of 29 CMMLs and zero of 10 controls (P = .166). Underexpression of CD14 and CD15 on monocytes was more common in CMMLs compared with controls (P = .008 and P = .043). Statistical analysis showed no significant difference in antigen expression between the CMML subgroups on blasts or monocytes; granulocytes demonstrated more common HLA-DR expression in CMML-2 vs CMML-1. CONCLUSIONS: These findings confirm heterogeneity within CMML subgroups and find no specific qualitative or quantitative findings characteristic of a subgroup.

Pure Erythroid Leukemia and Erythroblastic Sarcoma Evolving From Chronic Myeloid Neoplasms.

OBJECTIVES: Pure erythroid leukemia (PEL) is an extremely rare entity that may, even more rarely, evolve from a preexisting chronic myeloid neoplasm (CMN); there is minimal literature regarding this latter phenomenon. METHODS: We describe 14 patients with PEL that represented progression from a preexisting myelodysplastic syndrome (MDS, n = 8) or myeloproliferative neoplasm (MPN, n = 6), three of which manifested as erythroblastic sarcoma (EBS), a rare entity. These patients had a highly complex karyotype with prominent clonal evolution and a very aggressive clinical course. RESULTS: Patients with PEL from MDS showed a more rapid progression time to PEL and had lower platelet counts compared with PEL from MPN. No other significant differences were found between the two groups. CONCLUSIONS: These data represent the largest cohort of patients with PEL and an antecedent CMN, as well as the largest series of EBS reported to date, and underscore the unique morphologic, cytogenetic, immunophenotypic, and clinical features of this uncommon entity.

ATP synthase is responsible for maintaining mitochondrial membrane potential in bloodstream form Trypanosoma brucei.

The mitochondrion of Trypanosoma brucei bloodstream form maintains a membrane potential, although it lacks cytochromes and several Krebs cycle enzymes. At this stage, the ATP synthase is present at reduced, although significant, levels. To test whether the ATP synthase at this stage is important for maintaining the mitochondrial membrane potential, we used RNA interference (RNAi) to knock down the levels of the ATP synthase by targeting the F1-ATPase alpha and beta subunits. RNAi-induced cells grew significantly slower than uninduced cells but were not morphologically altered. RNAi of the beta subunit decreased the mRNA and protein levels for the beta subunit, as well as the mRNA and protein levels of the alpha subunit. Similarly, RNAi of alpha subunit decreased the alpha subunit transcript and protein levels, as well as the beta-subunit transcript and protein levels. In contrast, alpha and beta RNAi knockdown resulted in a 60% increase in the F0 complex subunit 9 protein levels without a significant change in the steady-state transcript levels of this subunit. The F0-32-kDa subunit protein expression, however, remained stable throughout induction of RNAi for alpha or beta subunits. Oligomycin-sensitive ATP hydrolytic and synthetic activities were decreased by 43 and 44%, respectively. Significantly, the mitochondrial membrane potential of alpha and beta RNAi cells was decreased compared to wild-type cells, as detected by MitoTracker Red CMXRos fluorescence microscopy and flow cytometry. These results support the role of the ATP synthase in the maintenance of the mitochondrial membrane potential in bloodstream form T. brucei.