Comparison of lymphoid neoplasm classification. A blinded study between a community and an academic setting.

The revised European-American classification of lymphoid neoplasms has been reported as reproducible among expert pathologists and feasible in a community setting. We evaluated the reproducibility of lymphoid neoplasm diagnoses between a community and an academic center. We subtyped 188 lymphoid neoplasms using revised European-American classification criteria. Clinical findings, histologic or cytologic preparations, paraffin-section immunostains, and flow cytometry data were reviewed as appropriate. Diagnoses were compared only after completion of the study. Lymphoma subtype was concordant for 167 (88.8%) of 188 cases. Discordant cases included 15 B-cell, 2 T-cell, and 4 Hodgkin lymphomas. For B-cell neoplasms, discordance was most often due to classifying diffuse large cell lymphoma as another aggressive subtype of lymphoma (n = 6), marginal zone lymphoma as another subtype (n = 4), or follicle center lymphoma grade II as grade III (n = 3). For Hodgkin disease, discordance was most often due to classifying nodular sclerosis as mixed cellularity type (n = 3). Comparison of community and academic center diagnoses demonstrated high concordance for most revised European-American classification subtypes. Some sources of discordance have been addressed in the new World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues.

Utility of flow cytometry immunophenotyping for the diagnosis and classification of lymphoma in community hospital clinical needle aspiration/biopsies.

CONTEXT: Flow cytometry immunophenotyping (FC) of needle aspiration/biopsy (NAB) samples has been reported to be useful for the diagnosis and classification of lymphoma in university and cancer center-based settings. Nevertheless, there is no agreement on the utility of these methods. OBJECTIVE: To further define the utility of adjunctive FC of clinical NAB for the diagnosis and classification of lymphoma, and to determine if this approach is practicable in a routine clinical practice setting. SETTING: A community-based hospital. METHODS: Clinical NABs were submitted for adjunctive FC between June 1996 and September 1999 if initial smears were suspicious for lymphoma. Smears and cell block or needle core tissues were routinely processed and paraffin-section immunostains were performed if indicated. The final diagnosis was determined by correlating clinical and pathologic data, and the revised European-American classification criteria were used to subtype lymphomas. RESULTS: Needle aspiration/biopsies from 60 different patients were submitted for FC. Final diagnoses were lymphoma (n = 38), other neoplasm (n = 15), benign (n = 6), or insufficient (n = 1). For 38 lymphomas (20 primary, 18 recurrent), patients ranged in age from 32 to 86 years (mean, 62 years); samples were obtained from the retroperitoneum (n = 11), lymph node (n = 9), abdomen (n = 8), mediastinum (n = 6), or other site (n = 4); and lymphoma subtypes were indolent B-cell (n = 20; 2 small lymphocytic, 14 follicle center, 4 not subtyped), aggressive B-cell (n = 14; 3 mantle cell, 10 large cell, 1 not subtyped), B-cell not further specified (n = 2), or Hodgkin disease (n = 2). For the diagnosis of these lymphomas, FC was necessary in 20 cases, useful in 14 cases, not useful in 2 cases, and misleading in 2 cases. Thirty-two of 36 lymphoma patients with follow-up data received antitumor therapy based on the results of NAB plus FC. CONCLUSIONS: Adjunctive FC of NABs is potentially practicable in a community hospital, is necessary or useful for the diagnosis and subtyping of most B-cell lymphomas, and can help direct lymphoma therapy. Repeated NAB or surgical biopsy is necessary for diagnosis or treatment in some cases.

Utility of flow cytometry in subtyping composite and sequential lymphoma.

Composite lymphoma (CL) is defined as more than one distinct lymphoma variant occurring in the same anatomic site, and sequential lymphoma (SL) is defined as different lymphoma variants occurring at different sites or at different times in the same patient. The utility of flow cytometry immunophenotyping in evaluating CL and SL has only been investigated in a few single-case studies. To further define the utility of flow cytometry in evaluating these tumors, records were searched at two institutions. Cases representing high-grade progression of low-grade lymphoma were excluded. For each CL/SL, clinical data was obtained and morphology was evaluated in routinely processed H&E-stained tissue sections. Tumor components were subtyped using revised European-American classification (REAL) criteria. Follicle center components were graded using modified Rappaport criteria. Immunophenotype was determined using two-color flow cytometry and paraffin-section immunostains. Four cases were identified. Case 1, nodal follicle center, follicular, grade III plus marginal zone CL, showed two discrete populations of monoclonal B-cells that differed in their expression of CD10. Case 2, cutaneous lymphoplasmacytoid lymphoma followed by mesenteric non-Hodgkin's lymphoma (lymphoplasmacytoid plus follicle center, follicular, grade III) plus Hodgkin's disease CL, showed CD5-/CD10-/CD19+/kappa+ cells by flow cytometry in both tissue samples. The Hodgkin's disease component showed CD3-/CD15-/CD20-/CD30+ Reed-Sternberg cell variants in paraffin-section immunostains. Case 3 represented nodal follicle center lymphoma, follicular, grade I (CD3-/CD5-/CD10-/CD19+/kappa+) followed by cutaneous anaplastic large T-cell lymphoma (CD2+/CD4+/CD5+/CD19- cells with partial expression of CD3 and CD7). Case 4 represented cutaneous follicle center lymphoma, follicular, grade I (CD5-/CD10+/CD19+/CD23+/lambda+) followed by bone marrow B-cell small lymphocytic lymphoma (CD5+/CD10-/CD19+/CD23+/kappa+). Results show that flow cytometry is a potentially useful adjunct in characterizing CL and SL.

Relative frequencies and sites of presentation of lymphoid neoplasms in a community hospital according to the revised European-American classification.

Relative frequencies for common subtypes in the revised European-American classification of lymphoid neoplasms (REAL classification) have been reported. We determined the relative frequencies and sites of presentation of REAL subtypes at a 700-bed community hospital in central Illinois. A database was used to identify and prospectively catalogue all newly diagnosed lymphoid neoplasms from July 1, 1995 to March 1, 1998. The approach to diagnosis and subtyping incorporated morphologic features, immunophenotype, and clinical findings according to criteria proposed in the REAL classification. Of 347 lymphoid neoplasms diagnosed, 319 were subtyped in the REAL classification. Of these, 261 were B-cell neoplasms, 21 were T-cell neoplasms, and 37 were Hodgkin disease variants. Chronic lymphocytic leukemia/small lymphocytic lymphoma/prolymphocytic leukemia, diffuse large cell, and follicle center neoplasms were the most common B-cell subtypes. Large granular lymphocyte leukemia was the most common T-cell neoplasm. Nodular sclerosis was the most common Hodgkin disease variant. The relative frequencies in a US community hospital setting are similar to those reported in other studies. Differences are attributable to patient selection criteria, study group geographic location and racial composition, and/or referral patterns. Diverse REAL classification subtypes may be expected in US community hospitals.

Myxoid liposarcoma with cartilaginous differentiation.

Common histologic variants of liposarcoma are readily recognized. Histologic classification might be difficult, however, when liposarcoma demonstrates cartilaginous differentiation. Although this phenomenon has previously been noted, it has not, to our knowledge, been reported as a specific pathologic entity. All three patients in the present study were men, ages 37, 42, and 63 years. Each presented with a solitary, enlarging mass of the thigh that was surgically excised. The tumors ranged in size from 8 to 13 cm. Microscopically, each lesion displayed characteristic features of myxoid liposarcoma; in addition, all possessed discrete, rounded foci of mature-appearing hyaline cartilage. One case displayed small foci showing chondrocyte atypia. No other patterns of mesenchymal differentiation were present. All patients received postoperative radiation therapy. No recurrences or metastases have been identified (mean duration, 39 mo). Myxoid liposarcomas with cartilaginous differentiation are of importance because they might be misdiagnosed as malignant mesenchymoma. The latter, if not qualified as to histologic grade, might be presumed to be a biologically more aggressive lesion. In addition, these lesions must be distinguished from two benign processes: chondroid lipoma and extraskeletal chondroma with lipoblast-like cells. Additional studies of this uncommon variant of liposarcoma will be necessary to document further its status as a low-grade sarcoma.

Human immunodeficiency virus-associated Hodgkin's disease contains latent, not replicative, Epstein-Barr virus.

Severe immunodeficiency is associated with reactivation of latent Epstein-Barr virus (EBV) that is manifested by virus replication. It is unknown whether EBV replication also occurs in the Hodgkin's disease (HD) tissue of patients infected with the human immunodeficiency virus (HIV). Therefore, we studied paraffin-embedded lymph nodes from 13 cases of HIV-associated HD to determine the latent or replicative state of EBV infection. All patients were seropositive HIV-infected men; additional clinical information was available for 12 patients. The risk factor(s) for HIV infection were homosexuality (n = 7), intravenous drug abuse (n = 2), homosexuality and intravenous drug abuse (n = 1), sexual promiscuity (n = 1), or hemophilia (n = 1). Advanced clinical stage and B symptoms were common at the time of initial diagnosis of HD. The histological subtype of Hodgkin's disease was universally mixed cellularity, except for a single case classified as nodular sclerosis. Seven cases exhibited foci of relative lymphoid depletion. Five cases contained foci of necrosis. Reed-Sternberg (RS) cells and RS cell variants were positive for CD30/BerH2 and negative for CD45/LCA, CD45RO/UCHL1, and CD20/L26 in all cases. Tumor cells were positive for CD15/LeuM1 in seven cases. In all 13 cases, RS cells and RS cell variants were infected by latent EBV as shown by in situ hybridization to EBV-encoded ribonucleic acid (EBER1). In 12 of 13 cases neoplastic cells coexpressed EBV latent membrane protein 1 (LMP1). EBV replication was examined by two different methods: immunohistochemistry to identify EBV-encoded BZLF1 protein and in situ hybridization to detect EBV BHLF1 transcripts. No positivity in RS or RS cell variants was detected with either assay of EBV replication (95% confidence interval [CI] = 0% to 23%). The findings confirm that EBV is detected more frequently in HIV-associated HD when compared with immunocompetent patients with HD. The findings also suggest that EBV is tightly latent within RS and RS cell variants of HIV-associated HD. It appears that factors other than host immune status are important in maintaining EBV latency in HIV-associated HD.

Hodgkin's disease, mixed cellularity type, with a B-cell immunophenotype. Report of a case and literature review.

The origin of the Reed-Sternberg cell, the neoplastic cell of Hodgkin's disease, has not been defined. We evaluated a case of Hodgkin's disease, mixed cellularity type, which presented in the retroperitoneum of a 45-year-old woman. Reed-Sternberg cells and Hodgkin's cells expressed the characteristic markers CD15 and CD30. In addition, they expressed the B-cell antigens CD19 and CD20, as well as CD45/leukocyte common antigen. Clonal rearrangement of the immunoglobulin heavy chain gene was detected by Southern blot analysis. These results suggest that some cases of Hodgkin's disease are derived from an activated cell of lymphoid origin. This case documents a close relationship between Hodgkin's disease and non-Hodgkin's lymphoma, and it demonstrates that even when newer ancillary techniques are employed these two entities can have overlapping features.

Extranodal lymphocyte predominance Hodgkin's disease. Clinical and pathologic features.

Although B-cell nodular lymphocyte predominance Hodgkin's disease (nodular paragranuloma, LPHD) typically presents at low stage, reported series have identified a minor population of patients with advanced disease. Clinicopathologic findings in 13 cases of LPHD are described that had extranodal manifestations. The B-cell immunophenotype was confirmed in all cases with paraffin-section immunostains. Nine patients presented with extranodal disease; distribution was in Waldeyer's ring (n = 2), spleen (n = 3), spleen and liver (n = 3), or bone marrow (n = 1). Three cases, clinically stage III/IV at presentation, had involvement of bone marrow (n = 2) or bone marrow, liver and spleen (n = 1) at relapse. One patient presented with clinical stage IIe disease and had involvement of spleen at relapse. Follow-up was available for 11 patients (range 4 months to 11 years; mean, 5 years). One patient died of disease and one died with disease because of therapeutic complications. Six patients were disease-free and three had persistent or recurrent LPHD. Microscopically, LPHD was difficult to recognize in extranodal sites and could easily be mistaken for low-grade non-Hodgkin's lymphoma or conventional Hodgkin's disease. Certain morphologic and immunophenotypic findings were effective in avoiding such diagnostic confusion. Thorough staging evaluation appears warranted for LPHD because it may be responsive to therapy, even in advanced stage or after relapse. Although LPHD is unexpected in extranodal samplings, the wary pathologist can suspect its presence on the basis of characteristic histopathologic features. Confirmation of the diagnosis may require paraffinsection immunostains.

Emergence of antimicrobial resistance in gram-negative bacilli causing bacteremia during therapy.

Treatment of serious infections caused by gram-negative bacilli with beta-lactam antimicrobial agents can induce Class I beta-lactamase production. This phenomenon can result in resistant microorganisms, and has been postulated to be a cause of therapeutic failure. The charts of patients bacteremic with Pseudomonas aeruginosa, Serratia marcescens, Enterobacter cloacae, Citrobacter freundii, Proteus vulgaris, and Providencia species (n = 120) during a 3-year period were reviewed to determine how common the emergence of resistance was, and to determine if in vitro susceptibility testing was a reliable therapeutic guide. Emergence of resistance was believed to occur when a subsequent bacteremic isolate showed at least a fourfold increase in minimum inhibitory concentration accompanied by a change of interpretive susceptibility category. In the group of patients who survived at least 48 hours that received beta-lactam therapy (n = 76), one case of emergence of resistance was identified (1.3%). Emergence of resistance to beta-lactam antimicrobial agents did not commonly cause therapeutic failure at our institution, and susceptibility testing of gram-negative bacilli by usual methods was a reliable guide to antimicrobial therapy.

Pharmacologic modulation of intimal hyperplasia in canine vein interposition grafts.

PURPOSE: The purpose of this study was to evaluate the efficacy of three drugs (cilazapril, cyclosporine, and aspirin) in modulating the progression of intimal hyperplasia during short postoperative times in short-segment, autogenous vein bypass grafts in a canine model. The relative effects of the drugs on the progression of intimal hyperplasia were compared with the Gilman parameter, a measure used extensively as a wound healing descriptor. To our knowledge this is the first use of the Gilman parameter in assessing vascular disease. METHODS: Seventy-two conditioned mongrel dogs were randomly and equally divided according to a three-factor analysis of variance. The factors included (1) drug treatments (cilazapril [10 mg/kg/day], cyclosporine [4 mg/kg/day], aspirin [325 mg/day], and control [nonmedicated]), (2) implantation sites (femoral and carotid arteries), and (3) postoperative times of graft harvest (1, 3, and 6 weeks). Each dog had 2 cm segments of autogenous jugular vein interpositioned bilaterally into each of the paired carotid and femoral arteries. Quantitative data on luminal narrowing over time from intimal hyperplasia were compared from calculated Gilman parameters after image analysis of retrieved, histologically processed graft sections. RESULTS: The observed variability in the data was attributed to drug treatments and time. At 1 week after operation the mean Gilman parameters did not differ significantly among the treatment groups in either midgraft or distal graft segments. At 3 weeks the mean Gilman parameters of midgraft and distal graft sections of cyclosporine-treated dogs differed significantly (p < 0.05) from those of the control group and the cilazapril and aspirin-treated groups, which did not differ from each other. At 6 weeks after operation, mean Gilman parameters from aspirin- and cyclosporine-treated dogs differed statistically from control and cilazapril-medicated dogs and from each other (p < 0.001). CONCLUSIONS: These data support the efficacy of aspirin and cyclosporine in reducing intimal hyperplasia in short-segment arterialized vein grafts during short postoperative periods. Additional studies are required to ascertain whether the beneficial effects of aspirin and cyclosporine persist long-term.