David H. Buss

Diagnosis and subclassification of primary and recurrent lymphoma. The usefulness and limitations of combined fine-needle aspiration cytomorphology and flow cytometry.

The primary diagnosis of non-Hodgkin lymphoma/leukemia by fine-needle aspiration (FNA) is still controversial and relatively underused. We evaluated our FNA experience with lymphomas using the revised European-American classification of lymphoid neoplasms to determine the reliability of FNA when combined with flow cytometry in the diagnosis of lymphoma, the types of diagnoses made, and the limitations of this technique. Slides and reports from all lymph node and extranodal FNAs performed during the period January 1, 1993, to December 31, 1998, with a diagnosis of lymphoma or benign lymphoid process were reviewed. There were 290 aspirates from 275 patients. These included 158 cases of lymphoma, of which 86 (54.4%) were primary and 72 (45.6%) were recurrent. There were 44 aspirates suggestive of lymphoma and 81 benign/reactive diagnoses. With diagnoses suggestive of lymphoma considered as positive for lymphoma, levels of diagnostic sensitivity and specificity were 95% and 85%, respectively. Specificity was 100% when only definitive diagnoses of lymphoma were considered. Clearly, FNA and immunophenotyping by flow cytometry are complementary and obviate a more invasive open biopsy for many patients with lymphadenopathy.

Occurence, etiology, and clinical significance of extreme thrombocytosis: A study of 280 cases

PURPOSE To determine the etiology and to evaluate the clinical consequences of an extremely elevated platelet count. PATIENTS AND METHODS A review of the medical records was performed on all patients encountered during a 5 1/2-year period who had at least one platelet count of 1,000 x 10(9)/L or greater. RESULTS Of the total of 280 patients with extreme thrombocytosis (EXT), 231 (82%) had reactive thrombocytosis (RT), 38 (14%) had a myeloproliferative disorder (MPD), and 11 (4%) had cases of uncertain etiology. RT was more common than MPD in all age groups except those in the eighth decade and older. Symptoms of bleeding and/or vaso-occlusive phenomena were noted in association with EXT in 21 (56%) of the MPD patients but in only 10 (4%) of the RT patients. Treatment to lower the platelet count and/or inhibit platelet function was employed in 36 MPD patients and 23 RT patients. Eight patients with MPD and 34 with RT are known to have died, but no patient in either group is known to have died of a thrombotic or bleeding event when the platelet count was greater than or equal to 1,000 x 10(9)/L. CONCLUSIONS Platelet counts greater than or equal to 1,000 x 10(9)/L should not be considered rare events in the general, acute-care hospital population, and usually represent a reactive phenomenon.

Herpesvirus infection of the esophagus and other visceral organs in adults. Incidence and clinical significance.

Abstract An autopsy review covering a 10 year period revealed 56 adult patients with histocytologic evidence of herpesvirus (herpes simplex or varicella-zoster) infection involving nongenital viscera. Review of the clinical records of these patients disclosed that herpesvirus infections were clinically suspected in only seven of them: three patients with cutaneous herpes zoster, two patients with herpetic keratitis and two patients with gingivostomatitis. Nine additional patients also had ulcerative gingivostomatitis, but this was attributed to either fungal organisms or chemotherapy. Forty patients showed no apparent clinical signs or symptoms of herpetic infection. Visceral involvement was not suspected clinically in any of the 56 patients. The most common underlying disease process afflicting these patients was a malignant neoplasm, usually involving the hematopoietic or lymphoreticular systems, but almost one-third had a variety of nonmalignant diseases. The presence of an associated infectious process involving bacterial, fungal or protozoal organisms, or additional viral agents, was confirmed by culture studies or autopsy microscopic findings in all but two patients. The viscus most commonly involved by herpetic infection was the esophagus. Herpetic esophageal ulcers were found in 50 cases, and in 41 cases no other organs appeared involved. Because esophageal ulcers are usually asymptomatic, antemortem diagnosis is extremely difficult. The data derived from this and previous studies indicate that herpetic ulcers frequently become secondarily infected with bacteria and/or fungi and that the greatest clinical significance of these ulcers is as a site of secondary infection, particularly in patients who have undergone immunosuppression (immunosuppressed patients). The advent of effective antiherpesvirus drugs and greater clinical awareness of the disease should serve as a stimulus to establish a clinical diagnosis of visceral herpesvirus infection more frequently.

Hematologic malignancies and Klinefelter syndrome: a chance association?

Klinefelter syndrome was first described in 1942 as an endocrine disorder characterized by gynecomastia, hypogonadism, small testes, and elevated levels of follicle-stimulating hormone. An extra X chromosome (i.e., 47,XXY) was subsequently demonstrated in these patients and an increased incidence of leukemia and lymphoma has been described. We report a retrospective study of a series of unselected patients with Klinefelter syndrome diagnosed by cytogenetic studies and the occurrence of hematologic malignancies. The literature is also reviewed.

Paraganglioma of the thyroid gland.

A case of a paraganglioma located within the thyroid gland is reported, and the light- and electron-microscopic features are described. Review of the literature reveals only one other case of intrathyroidal paraganglioma, which was associated with bilateral carotid body tumors. Regarding the present case, no similar tumors have been noted elsewhere. The findings support the view that the thyroid gland should be included among the unusual sites at which primary paragangliomas may occur.

The Use of Flow Cytometry for the Prognosis of Stage II Adjuvant Treated Breast Cancer Patients

Characterization of breast cancer cells by histology, flow cytometry, and steroid receptors was performed on 197 Stage II breast node positive cancer patients given adjuvant chemotherapy, plus tamoxifen for patients with positive hormone receptors. Histologic and steroid receptor assays were performed using standard techniques; flow cytometric analysis was performed from paraffin‐embedded blocks obtained from the primary tumor. Quality control studies on reproducibility, tissue heterogeneity, and analysis procedures have been included. Of the 197 patients studied, aneuploidy was found in 102 (52%); the median %S value was 8% with a range of 0.4% to 38%. Our results demonstrated that number of positive nodes, receptor status, and grade were of prognostic value. Cell cycle kinetic data were not of independent prognostic value in this series. However, ploidy could differentiate in prognosis in the receptor‐negative subgroup. Patients with receptor‐negative tumors had a significantly better overall survival if the tumor was diploid in nature. Cell kinetics was not significantly prognostic for either receptor subgroup, although patients with higher %S tended to have better relapse‐free and overall survival. This is in disagreement with other studies and may demonstrate that treatment has confounded our results and diminished the ability of flow cytometry data to help predict outcome.

Bone Marrow Cytogenetic Abnormalities of Aplastic Anemia

Cytogenetic abnormalities in association with aplastic anemia have been reported fairly infrequently. Clonal cytogenetic abnormalities at initial diagnosis are uncommon. A retrospective study was performed of the cytogenetic findings in patients with typical morphological and clinical features of severe aplastic anemia from a single institution for the years 1988 through 1998. A total of 30 cases of aplastic anemia, 16 men and 14 women, were identified. The median age was 60 with females being significantly older (67.5 years) in comparison to males (44 years). Bone marrow specimens failed to yield metaphases in 16 cases and normal karyotypes were detected in 11 cases. Cytogenetic abnormalities were detected in 3 cases. Clonal abnormalities, as defined, occurred in only 2 cases (6.7%). A review of the literature identified a total of 24 cases of aplastic anemia with abnormal cytogenetic findings. Overall, the most common chromosome abnormalities are trisomies of 6 and 8 and loss of chromosome 7. Trisomy 6 is more common at diagnosis while loss of chromosome 7 is more common after therapy. Am. J. Hematol. 66:167–171, 2001.

Progression of a myelodysplastic syndrome to pre-B acute lymphoblastic leukemia: a case report and cell lineage study

Abstract The evolution of acute lymphoblastic leukemia from a myelodysplastic syndrome is a very uncommon event. We describe a 46-year-old man in whom refractory anemia with excess blasts (RAEB) evolved to a pre-B acute lymphocytic leukemia. Trisomy 8 was one of the cytogenetic abnormalities in the dysplastic clone and was detected in both peripheral blood and bone marrow smears of interphase cells by the fluorescence in situ hybridization (FISH) technique. Using a chromosome 8 centromeric specific DNA probe we identified the trisomy 8 to be present in lymphoblasts, erythroid precursors, myeloblasts, promyelocytes, myelocytes, metamyelocytes, granulocytes, and monocytes. Our case supports the hypothesis that in MDS the pluripotent precursor cell is affected, and we examine the potential role of FISH for the study and follow-up of some hematological diseases.

Central diabetes insipidus and inv(3)(q21q26) and monosomy 7 in acute myeloid leukemia

Chromosomal anomalies involving region 3q21q26 have been reported associated with thrombocytosis in various hematological malignancies, such as chronic myeloid leukemia, myelodysplastic syndrome, and acute myeloid leukemia (AML). Recent reports described the association of central diabetes insipidus with AML and chromosomal anomalies involving region 3q21q26. We review the database in our institution and report five cases of inv(3)(q21q26) in consecutive cytogenetic studies of AML and myelodysplastic syndromes from 1992 to 2000, two cases presented as sole abnormalities and three cases were associated with monosomy 7. Only one case was associated with central diabetes insipidus. The literature of 3q21q26 syndrome and central diabetes insipidus in myeloid leukemia is reviewed.

Study of clonality in myelodysplastic syndromes: Detection of trisomy 8 in bone marrow cell smears by fluorescence in situ hybridization

The lineage involvement in myelodysplastic syndromes (MDS) is still unclear. To determine the clonality and the evolution of the disorder, a retrospective study on bone marrow smears from seven MDS patients with trisomy 8 was performed using fluorescence in situ hybridization (FISH). We observed that the trisomy of chromosome 8 was selectively expressed in the myeloid-derived cells. No mature lymphocytes or plasma cells expressed three signals. Our studies demonstrate here the value of FISH for identifying the affected cell lineage. Furthermore, the easy quantification of the abnormal cells can help in assessing the progression of the disease.