PubMed Health⌕ Search

Biomedical subjects

William G Finn

Publications and source records attributed to William G Finn.

15 recordsLinked to original sources
PubMed2006

Unsupervised immunophenotypic profiling of chronic lymphocytic leukemia.

BACKGROUND: Proteomics and functional genomics have revolutionized approaches to disease classification. Like proteomics, flow cytometry (FCM) assesses concurrent expression of many proteins, with the advantage of using intact cells that may be differentially selected during analysis. However, FCM has generally been used for incremental marker validation or construction of predictive models based on known patterns, rather than as a tool for unsupervised class discovery. We undertook a retrospective analysis of clinical FCM data to assess the feasibility of a cell-based proteomic approach to FCM by unsupervised cluster analysis. METHODS: Multicolor FCM data on peripheral blood (PB) and bone marrow (BM) lymphocytes from 140 consecutive patients with B-cell chronic lymphoproliferative disorders (LPDs), including 81 chronic lymphocytic leukemia (CLLs), were studied. Expression was normalized for CD19 totals, and recorded for 10 additional B-cell markers. Data were subjected to hierarchical cluster analysis using complete linkage by Pearson's correlation. Analysis of CLL in PB samples (n = 63) discovered three major clusters. One cluster (14 patients) was skewed toward "atypical" CLL and was characterized by high CD20, CD22, FMC7, and light chain, and low CD23. The remaining two clusters consisted almost entirely (48/49) of cases recorded as typical BCLL. The smaller "typical" BCLL cluster differed from the larger cluster by high CD38 (P = 0.001), low CD20 (P = 0.001), and low CD23 (P = 0.016). These two typical BCLL clusters showed a trend toward a difference in survival (P = 0.1090). Statistically significant cluster stability was demonstrated by expanding the dataset to include BM samples, and by using a method of random sampling with replacement. CONCLUSIONS: This study supports the concept that unsupervised immunophenotypic profiling of FCM data can yield reproducible subtypes of lymphoma/chronic leukemia. Expanded studies are warranted in the use of FCM as an unsupervised class discovery tool, akin to other proteomic methods, rather than as a validation tool.

ADP-ribosyl Cyclase 1↗
PubMed2006

Trisomy 12-associated, t(11;14)-negative mature B-cell leukemia with gene expression profile resembling mantle cell lymphoma.

Trisomy 12 can be seen in many different lymphoid neoplasms. However, many or most mature B-cell leukemias associated with isolated trisomy 12 are reported in the literature as chronic lymphocytic leukemia (CLL) or 'atypical CLL'. This study reports a case of a mature B-cell leukemia, morphologically and immunophenotypically similar to cases previously published as atypical CLL, in which cytogenetic evaluation revealed an isolated clonal trisomy 12 but no evidence of the mantle cell lymphoma-associated t(11;14)(q13;q32). Further analysis confirmed absence of cyclin-D1 expression. Subsequent lymph node biopsy revealed evidence of large cell transformation of the underlying chronic lymphoproliferative disorder. Gene expression profiling of the initial peripheral blood sample using a cDNA micro-array of approximately 10,000 expressed genes revealed a close resemblance between the reported case and 2 cases of known mantle cell lymphoma. When further compared to 7 known 'typical' CLL cases, the reported case was classified as mantle cell lymphoma by hierarchical cluster analysis. The case reported here raises interesting questions regarding the nature of cases reported previously as trisomy 12-associated CLL and reinforces the fact that other leukemic lymphoproliferative disorders should be included in the differential diagnosis of such cases. Further study is indicated to elucidate the nature and diversity of disorders previously reported as trisomy 12-associated chronic lymphocytic leukemia.

Aged↗
PubMed2006

ALK-positive anaplastic large cell lymphoma with primary bone involvement in children.

We describe the clinical, radiologic, and pathologic features of primary bone anaplastic large cell lymphoma (ALCL) in 3 boys. Radiologic imaging showed lytic lesions involving sacrum, femur, or rib. Bone was the only site of disease in 2 cases; an associated partial lymph node was involved in case 3. Differential diagnoses included osteomyelitis and small round cell tumors of childhood, particularly Ewing sarcoma. Preoperatively, ALCL was not a diagnostic consideration in any case. Two cases showed classic large pleomorphic cells; 1 showed a composite pattern with a distinct small cell component and the more typical large cell type. Neoplastic cells in all cases showed strong CD30 and anaplastic lymphoma kinase expression with relatively weak epithelial membrane antigen positivity. Cytotoxic granule protein was expressed in 2 cases. All cases showed unusually strong expression of neuron-specific enolase (NSE). Two patients were disease-free at last follow-up (15 months and 11 years); 1 patient died of disseminated disease within a year of diagnosis. ALCL should be considered a diagnostic possibility when evaluating neoplastic bone lesions in children. Although expression of NSE in ALCL has not been emphasized in the literature, it is worth noting because it may pose a diagnostic pitfall.

Adolescent↗
PubMed2003

Lymphocytic mastitis and diabetic mastopathy: a molecular, immunophenotypic, and clinicopathologic evaluation of 11 cases.

Lymphocytic mastitis and diabetic mastopathy are uncommon fibroinflammatory breast diseases. The lesions seen in these entities are unique in that the associated lymphoid infiltrates are composed of predominantly B cells. In addition, B-cell lymphoepithelial lesions, a finding commonly associated with extranodal marginal zone B-cell/mucosa-associated lymphoid tissue (MALT) lymphomas, are also often present in lymphocytic mastitis and diabetic mastopathy. Although the clinical and immunomorphologic features are well characterized, the clonality of the B-cell infiltrate and the lymphomatous potential of lymphocytic mastitis and diabetic mastopathy have not been emphasized in the literature. We evaluated 11 cases of lymphocytic mastitis/diabetic mastopathy for immunoglobulin heavy chain gene rearrangement and correlated the findings with all available clinical data. A longstanding history of Type I diabetes mellitus was present in seven patients. One nondiabetic patient had Sjogren's syndrome, and two patients had no history of diabetes mellitus or other autoimmune disease. Clinical data were unavailable for one patient. B-cell-predominant lymphoid infiltrates were seen in all cases, and B-cell lymphoepithelial lesions were found in five. No evidence of a B-cell clone was found in any of the 11 cases by appropriately controlled immunoglobulin heavy chain gene rearrangement studies, and none of the patients developed lymphoma during follow-up intervals ranging from 2-126 months. These findings suggest that despite the presence of B-cell-predominant lymphoid infiltrates and lymphoepithelial lesions, lymphocytic mastitis and diabetic mastopathy do not appear to be associated with an increased risk for lymphoma.

Adult↗
PubMed2003

Nodular lymphocyte predominant Hodgkin lymphoma. An immunophenotypic reappraisal based on a single-institution experience.

In our experience, certain commonly cited immunophenotypic features of nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) are not encountered in day-to-day practice. We reviewed 60 cases of NLPHL (18 women, 42 men; median age, 34 years) to discern immunophenotypic features from a large, single-institution cohort. All cases contained lymphocytic and histiocytic (L&H) cells. These cells expressed CD20 in 98% (59/60), CD79a (usually faint) in 87% (27/31), CD30 in 7% (4/59), epithelial membrane antigen in 21% (12/56), bcl-2 in 5% (2/41), and bcl-6 in 83% (30/36) of cases. CD10 was negative in all 36 cases studied; 100% of cases (55/55) demonstrated CD3+ rosettes. Although CD57+ T cells were common within the background infiltrate, CD57+ rosettes were seen in only 48% of cases (15/31) and were rare when encountered. Based on these patterns, we conclude that bcl-2 and bcl-6 may be useful additions to the immunophenotypic analysis of NLPHL, but that the diagnostic usefulness of epithelial membrane antigen and CD57 rosettes may have been overemphasized in previous reports.

Adolescent↗
PubMed2003

Histopathologic features of splenic small B-cell lymphomas. A study of 42 cases with a definitive diagnosis by the World Health Organization classification.

We studied 42 cases of splenic small B-cell lymphoma (SBL) (21 women, 21 men; aged 32-82 years; median, 65 years) with a definitive diagnosis by the World Health Organization classification: chronic lymphocytic leukemia (CLL), 8; mantle cell lymphoma (MCL), 9; follicular lymphoma (FL), 12; marginal zone lymphoma, 13 (splenic [SMZL], 12; extranodal [EMZL], 1). Splenectomy was performed for diagnosis or therapy; splenic weights were 0.2 to 3.8 kg (median, 1.4 kg). In general, splenic SBLs showed white pulp (WP) expansion; morphologic features of the nodules recapitulated the corresponding lymph node histopathologic features. "Marginal zones" were observed commonly in SMZL and FL, may be present in MCL involving the spleen, and may be seen in hilar lymph nodes (HLNs) in SBLs other than SMZL. FL may simulate SMZL and can be distinguished by the presence of neoplastic follicles and HLN morphologic features. Extracellular hyaline deposits (EH) are common in FL and SMZL. MCL typically shows WP expansion by a monotonous small lymphocytic infiltrate, without diffuse red pulp (RP) infiltration or EH; leukemic MCL may show RP infiltration. Splenic morphologic features in CLL vary in WP or RP dominance; marginal zones usually are not observed in CLL.

Adult↗
PubMed2003

Elimination of instrument-driven reflex manual differential leukocyte counts. Optimization of manual blood smear review criteria in a high-volume automated hematology laboratory.

Automated peripheral blood leukocyte differential counts (LDCs) are widely accepted in routine practice. However, many laboratories still reflexively perform manual LDCs based solely on abnormal automated results or instrument "flags," before any manual triage step. We describe our transition to a procedure that uses manual methods to validate, rather than to replace, automated LDCs (an approach recommended early in the development of automated methods, but still not used in many clinical laboratories). Manual microscopic scans were performed in lieu of manual LDCs. Each scan that revealed cell types not quantifiable by the instrument triggered a manual LDC. However, if the manual scan simply confirmed the cell types seen on automated LDC, then the automated result was released, even if clinically significant quantitative abnormalities were present. This policy reduced manual LDCs by more than 70% and was validated by a manual retrospective audit. Patient care and laboratory operations can be optimized by using manual microscopic examination as a validation procedure rather than as a reflexive substitute for automated methods. There is no clinical rationale for reflex performance of manual LDCs based solely on instrument warnings.

Automation↗
PubMed2002

Peripheral T-cell lymphoma mimicking marginal zone B-cell lymphoma.

Peripheral T-cell lymphoma (PTCL) may assume a variety of histologic and cytologic appearances. We describe eight cases of PTCL morphologically simulating marginal zone B-cell lymphoma. We reviewed PTCL cases diagnosed in our institution between 1990 and 2000 and selected eight cases for study based on the following criteria: small-cell morphology with abundant, clear cytoplasm and either marginal zone involvement by the neoplastic infiltrate in lymph node biopsies or lymphoepithelial lesions in extranodal biopsies. Histologic features and ancillary studies were reviewed. Patients included six women and two men with a median age of 53 years (range, 35 to 74 years). Six patients were diagnosed with primary nodal PTCL, and two presented with primary extranodal disease. The original diagnosis was PTCL in only four cases; three cases were diagnosed as atypical lymphoid infiltrate, and one case as benign lymphoepithelial lesion. Lymph node biopsies revealed partial effacement of the architecture with residual follicles surrounded by the neoplastic small cells. Extranodal sites included hard palate, tongue, tonsil, and submandibular glands; all but one case demonstrated lymphoepithelial lesions. Monoclonality was demonstrated in six of eight cases (rearrangement of T-cell receptor gene), and three of eight had an aberrant T-cell population by flow cytometry. The differential diagnosis of atypical lymphoid infiltrates with morphologic features of marginal zone B-cell lymphoma should include PTCL. This uncommon morphological mimicry should be recognized, because PTCL is an aggressive disease regardless of morphology and should be treated accordingly.

Adult↗
PubMed2002

Composite germ cell tumor and B-cell non-Hodgkin's lymphoma arising in the sella turcica.

We report the case of a composite malignant neoplasm consisting of germ cell tumor and B-cell non-Hodgkin's lymphoma occurring in the sella turcica of a young girl who presented with hypopituitarism. Routine hematoxylin and eosin-stained sections of a resected suprasellar tumor demonstrated a neoplasm composed of 2 distinct morphologies. A panel of immunohistochemical markers was used to confirm the morphologic impression of germinoma (cytokeratin AE1/AE3-CAM 5.2, cytokeratin 7, neuron-specific enolase, and focally placental alkaline phosphatase positive) and mature B-cell lymphoma (CD20 positive; pancytokeratin, placental alkaline phosphatase, and terminal deoxynucleotidyl transferase negative). To the best of our knowledge, this is the first reported case of such a composite tumor in the central nervous system.

Biomarkers, Tumor↗
PubMed2002

Cerebrospinal fluid involvement in mantle cell lymphoma.

Mantle cell lymphoma (MCL) is an aggressive neoplasm that is incurable by standard therapy. Patients often present with high-stage disease (Stages III-IV) and frequently have involvement at multiple extranodal sites. Although the gastrointestinal tract, spleen, lung, pleura, bone marrow, and peripheral blood are among the most commonly involved tissues, MCL may also disseminate to so-called sanctuary sites including the central nervous system. Despite this, current clinical evaluations do not routinely include assessment of the cerebrospinal fluid (CSF) for lymphomatous infiltrates at presentation, and moreover, only few authors have specifically examined CSF involvement in MCL. In this study, we reviewed the medical records of 108 patients with MCL seen at three centers over a 5-year period to determine the rate of CSF sampling and the frequency of CSF involvement by MCL. The clinical and cytologic characteristics associated with CSF involvement were also studied. Central nervous system (CNS) signs and/or symptoms prompted CSF sampling in 25/108 patients (23%). Specific radiographic abnormalities were present in 9/25 patients (36%). CSF involvement by MCL was identified in 10 of the 25 CSF-sampled patients (40%) by morphology (3 patients), flow cytometry alone (1 patients), or both (6 patients). The CSF-positive cases included two blastoid variants. The CSF cytology of the nine morphologically positive cases was pleomorphic, and prominent cytoplasmic granules were observed in two cases. The overall rate of CSF involvement by MCL among the cohort was 9%, which is comparable to that reported in other selected studies examining this issue.

Adult↗
PubMed2002

Follicular hodgkin lymphoma: a histopathologic study.

Follicular Hodgkin lymphoma (FHL) is a form of classic Hodgkin lymphoma with morphologic similarity to nodular lymphocyte predominant Hodgkin lymphoma (NLPHL). We present the clinicopathologic features of 13 FHL cases and compare their morphologic features with 40 cases of NLPHL. Seven males and 6 females had FHL in the lymph nodes of the neck (6 patients), axilla (3 patients), groin (2 patients), and mediastinum (1 patient) and in the nasopharynx (1 patient). All FHLs had follicles with small, eccentric germinal centers (GCs) and expanded mantle zones containing classic Reed-Sternberg (RS) cells; reactive GCs also were seen in 6 of 13 cases. The RS cells were CD30+, fascin+ in 13 cases; CD15+ in 11 cases; CD20+ in 4 cases; CD79alpha+CD20- in 1 case; and negative for epithelial membrane antigen in 12 cases; they were surrounded by CD3epsilon+ and CD57+ rosettes in 13 and 2 cases, respectively. Morphologically, FHL may closely simulate NLPHL, and, thus, immunohistochemical analysis is essential to confirm the diagnosis. Clues helpful in diagnosing FHL include the presence offollicles with GCs, classic RS cells, and a relative absence of histiocytes.

Adolescent↗
PubMed2002

Usefulness of anti-CD117 in the flow cytometric analysis of acute leukemia.

We assessed the diagnostic usefulness of adding anti-CD117 to our existing flow cytometric profile in the analysis of 150 consecutive cases of acute leukemia (de novo or relapsed acute myelogenous leukemia [AML], AML arising in myelodysplastic syndrome, blast crisis of chronic myelogenous leukemia [CML], acute lymphoblastic leukemia, acute unclassifiable leukemia, and biphenotypic leukemia). CD117 was expressed on more than 10% of blasts in 64% of de novo AMLs (42/66), 95% of relapsed AMLs (19/20), 75% of AMLs arising from a myelodysplastic syndrome (6/8), and 25% of myeloid blast crisis in CMLs (1/4). CD117 was not expressed in acute lymphoblastic, acute biphenotypic, or unclassified leukemia or lymphoid blast crisis of CML. The specificity, positive predictive value, sensitivity, and negative predictive value of CD117 for AML were 100%, 100%, 69%, and 62%, respectively. CD117 is a specific marker for myeloblastic leukemias. Sensitivity is greatest in French-American-British M2 and relapsed AML. Intensity of CD117 expression is dim. Despite the high specificity and positive predictive value, the addition of anti-CD117 to our panel did not prove essential for the assignment of blast lineage.

Acute Disease↗