Search PubMed⌕ Search

Biomedical subjects

S H Kroft

Publications and source records attributed to S H Kroft.

29 records · Page 2Linked to original sources

Follicular large cell lymphoma with immunoblastic features in a child with Wiskott-Aldrich syndrome: an unusual immunodeficiency-related neoplasm not associated with Epstein-Barr virus.

Patients with Wiskott-Aldrich syndrome, a severe inherited immunodeficiency disorder, have a markedly increased risk of developing non-Hodgkin's lymphoma compared with the general population. These are uniformly diffuse aggressive B-cell neoplasms that resemble those seen in AIDS and the posttransplantation setting and also may be associated with Epstein-Barr virus. We report what to our knowledge is the first case of follicular lymphoma in a 14-year-old child with Wiskott-Aldrich syndrome. The neoplasm was composed predominantly of large cells with immunoblastic features, and it possessed light chain-restricted surface immunoglobulin, clonal immunoglobulin gene rearrangements, and a t(14;18). The tumor lacked Epstein-Barr virus sequences by in situ hybridization and Southern blot terminal repeat analysis. Interestingly, however, the tumor contained c-myc gene rearrangement.

Blotting, Southern↗

Evaluation of CD23 expression in paraffin-embedded gastric lymphomas of mucosa-associated lymphoid tissue.

The CD23 antigen is expressed in a normal subset of B lymphocytes and in some non-Hodgkin's lymphomas. Reactivity for anti-CD23 (BU38) is present in paraffin-embedded tissue in the large majority of nodal small lymphocytic lymphomas, as well as in follicular center cell lymphomas. Most studies of gastric lymphomas of mucosa-associated lymphoid tissue (MALT) reported a lack of CD23, but these studies were performed on frozen tissue. We evaluated CD23 staining in paraffin-embedded tissue in a large series of gastric MALT lymphomas, as well as in cases of chronic gastritis. We assayed 49 well-characterized gastric lymphomas (9 high-grade non-MALT and 40 MALT [20 low grade, 13 mixed low and high grade, and 7 high grade]). High-grade MALT lymphomas without a low-grade component were distinguished from high-grade non-MALT lymphomas by the presence of lymphoepithelial lesions composed of large cells. In addition, we studies nine cases of chronic gastritis containing B-cell aggregates. We used anti-CD23 (BU38) in formalin-fixed, paraffin-embedded tissue. All of our low-grade gastric MALT lymphomas lacked CD23 immunoreactivity. One of the 13 mixed low-grade and high-grade lesions showed CD23 expression in the high-grade component. All of the high-grade MALT and high-grade non-MALT lesions lacked CD23. All of the nine cases of chronic gastritis lacked CD23. CD23 highlighted residual follicular dendritic cells and gastric epithelium. We concluded that gastric MALT lymphomas lacked CD23 (BU38) in paraffin-embedded tissue, with rare exceptions. This lack of CD23 expression might represent a useful feature in small or partially crushed biopsy specimens, particularly in the differential diagnosis with follicular small cleaved cell lymphoma presenting in the gastrointestinal tract.

Chronic Disease↗

Isolated 13q14 abnormalities and normal karyotypes are associated with typical lymphocyte morphology in B-cell chronic lymphocytic leukemia.

Peripheral blood lymphocyte morphology and karyotype were correlated across the spectrum of cytogenetic abnormalities in 78 previously karyotyped cases of B-cell chronic lymphocytic leukemia (CLL). Cases were classified according to French-American-British morphologic criteria as typical CLL or CLL, mixed-cell type; the latter category was divided into CLL with a mixture of small and large cells and CLL with increased prolymphocytes (CLL/PL). Other leukemic lymphoproliferative disorders were excluded from this analysis. CLL cases with normal karyotypes were more likely to demonstrate typical morphology than those with clonal abnormalities (P = .042). In addition, all six cases containing isolated 13q14 abnormalities had typical morphology, compared with six of 16 other isolated abnormalities (P = .009), including one of seven cases of isolated trisomy 12. In contrast with the cases of isolated 13q14 changes, only seven of 17 cases with 13q14 as part of complex abnormalities had typical morphology (P = .012). Trisomy 12 was associated with mixed-cell morphology, particularly CLL/PL, consistent with previous reports. We conclude that isolated 13q14 abnormalities and normal karyotype are associated with typical CLL morphology, while other clonal abnormalities, including trisomy 12, are associated with mixed-cell morphology. These results further support the concept of distinct CLL subgroups based on karyotype. Furthermore, the association of trisomy 12 and complex abnormalities with mixed-cell morphology may have implications for clonal evolution in CLL.

Aged↗

Optimal procedures for detecting analytic bias using patient samples.

We recently described the performance characteristics of the exponentially adjusted moving mean (EAMM), a patient-data, moving block mean procedure, which is a generalized algorithm that unifies Bull's algorithm and the classic average of normals (AON) procedure. Herein we describe the trend EAMM (TEAMM), a continuous signal analog of the EAMM procedure related to classic trend analysis. Using computer simulation, we have compared EAMM and TEAMM over a range of biases for various sample sizes (N or equivalent smoothing factor alpha) and exponential parameters (P) under conditions of equivalent false rejection (fixed on a per patient sample basis). We found optimal pairs of N and P for each level of bias by determination of minimum mean patient samples to rejection. Overall optimal algorithms were determined through calculation of undetected lost medical utility (ULMU), a novel function that quantifies the medical damage due to analytic bias. The ULMU function was calculated based on lost test specificity in a normal population. We found that optimized TEAMM was superior to optimized EAMM for all levels of analytic bias. If these observations hold true for non-Gaussian populations, TEAMM procedures are the method of choice for detecting bias using patient samples or as an event gauge to trigger use of known-value control materials.

Algorithms↗

Ruptured spleens with expanded marginal zones do not reveal occult B-cell clones.

An indolent variant of splenic marginal zone lymphoma (SMZL) lacking massive splenomegaly has been described as an incidental finding in spleens removed for rupture or hypersplenism. We studied traumatically ruptured spleens with expanded marginal zones (MZs) to assess the incidence of occult monoclonal B-cell populations in this setting. Ninety-one ruptured or lacerated spleens removed from 1984 to 1995 were classified as to whether they had expanded MZs (> 12 cell layers thick). When available, paraffin-embedded, formalin-fixed tissue from cases with expanded MZs was examined for immunoglobulin heavy chain gene rearrangement by polymerase chain reaction (PCR) and stained for CD20, CD43, and kappa and lambda light chains. Splenectomies were performed for blunt (70 patients) and penetrating (7 patients) trauma, surgical misadventure (13 patients), or spontaneous rupture (1 patient). There were 58 men and 33 women in our study, ranging in age from 17 to 87 years (mean, 40 yr). Average spleen weight was 183 g (range, 44-505 g). Twenty-seven (30%) of 91 patients had expanded MZs. There were no significant differences in age, sex, spleen weight, or reason for excision between those cases with and without MZ expansion. Germinal centers varied from absent to inactive to floridly reactive. Paraffin blocks were available in 24 cases; the 20 with amplifiable DNA were polyclonal by PCR. Follow-up was available for 25 of the 27 patients with expanded MZs (range, 1-85 mo; median, 6 mo); lymphoma did not develop in anyone, although one patient's spleen was morphologically suspicious for lymphoma, showing involvement of red pulp by MZ-type B-cells; PCR revealed a polyclonal pattern. This patient's 3-year follow-up revealed no evidence of lymphoma. Traumatically ruptured spleens with expanded MZs do not seem to harbor occult B-cell clones, as detected by PCR. Although a few cases of incidentally removed spleens have been reported to contain low-stage SMZL, this seems to be an infrequent event.

Adolescent↗

Exponentially adjusted moving mean procedure for quality control. An optimized patient sample control procedure.

The idea of using patient samples as the basis for control procedures elicits a continuing fascination among laboratorians, particularly in the current environment of cost restriction. Average of normals (AON) procedures, although little used, have been carefully investigated at the theoretical level. The performance characteristics of Bull's algorithm have not been thoroughly delineated, however, despite its widespread use. The authors have generalized Bull's algorithm to use variably sized batches of patient samples and a range of exponential factors. For any given batch size, there is an optimal exponential factor to maximize the overall power of error detection. The optimized exponentially adjusted moving mean (EAMM) procedure, a variant of AON and Bull's algorithm, outperforms both parent procedures. As with any AON procedure, EAMM is most useful when the ratio of population variability to analytical variability (standard deviation ratio, SDR) is low.

Algorithms↗

Inflammatory pseudotumor of the pancreas.

We describe a rare example of inflammatory pseudotumor of the pancreas in a 42-yr-old woman, which developed following chemotherapy for lymphoma of the uterine cervix. The patient had developed fatigue, weight loss, abdominal pain, and anemia; abdominal CT scan showed a large mass in the pancreas. Examination of the resected specimen revealed a fleshy, well-circumscribed, 7-cm mass. Histologically, there was a hypocellular to moderately hypercellular, bland spindle-cell proliferation admixed with a prominent infiltrate of lymphocytes, histiocytes, and plasma cells. The spindle cells were vimentin positive but negative for muscle markers; electron microscopy revealed only fibroblastic cells. DNA analysis revealed a diploid population with low S-phase fraction. The patient was well at 6-mo follow-up. It is important for the pathologist to be aware of the existence of this entity in unusual locations such as the pancreas so as to avoid a mistaken diagnosis of malignancy.

Adult↗

The pathology of the chronic lymphoid leukaemias.

The chronic lymphoid leukaemias, though they all possess relatively mature lymphoid phenotypes, are a diverse group of diseases at the clinical, morphological, immunophenotypical, and biological levels. Generally accepted entities within this category include B-cell chronic lymphocytic leukaemia of classical and mixed-cell types, B-cell and T-cell prolymphocytic leukaemia, hairy-cell leukaemia and hairy-cell variant, splenic lymphoma with circulating villous lymphocytes, large granular lymphocytic leukaemia, adult T-cell leukaemia/lymphoma syndrome, and leukaemic phases of malignant lymphomas of both B-cell and T-cell types. Recent advances have helped to differentiate these diseases, allowing the development of more specific therapy and more accurate prognostication. In this article, we review the pathological aspects of these diseases.

Humans↗

Appendiceal involvement as a skip lesion in ulcerative colitis.

Despite the frequency of ulcerative colitis (UC), and numerous studies related to this disease, controversy remains regarding its distribution patterns. It is generally believed that UC starts in the rectum and progresses proximally in continuity to involve cecum along with appendix in 50% of all cases. However, recent endoscopic and histological studies suggest that UC can occur as a discontinuous process. Furthermore, the few existing studies specifically addressing appendiceal histology in UC are divided over whether ulcerative appendicitis (UA) may be seen without cecal involvement (i.e., as a "skip lesion"). To study the appendiceal pathology in UC, and in particular the frequency of UA as a "skip lesion," we retrospectively evaluated 39 proctocolectomy specimens containing appendices removed for UC. Six cases (17%) had obliterated appendices; appendiceal and cecal histologies of the remaining 33 cases were divided into (a) active disease, (b) quiescent disease, or (c) nonspecific or normal histology. Twenty of 39 appendices (51%) showed active disease, four (10%) had quiescent disease, and nine (23%) were either normal or nonspecifically inflamed. After exclusion of one case for inadequate cecal sampling, comparison of cecal and appendiceal histologies showed concordance in 16 cases and discordance in the remaining 16. Of these discordant cases, six had greater disease activity in the cecum and 10 had greater activity in the appendix. Of these latter 10 cases, six showed normal or nonspecific cecal histology associated with active UA. Thus, "skip lesions" of the appendix were detected in 15% of the UC specimens examined.

Adolescent↗