Fred R. Dick

Comparison of a virtual microscope laboratory to a regular microscope laboratory for teaching histology.

Emerging technology now exists to digitize a gigabyte of information from a glass slide, save it in a highly compressed file format, and deliver it over the web. By accessing these images with a standard web browser and viewer plug‐in, a computer can emulate a real microscope and glass slide. Using this new technology, the immediate aims of our project were to digitize the glass slides from urinary tract, male genital, and endocrine units and implement them in the Spring 2000 Histology course at the University of Iowa, and to carry out a formative evaluation of the virtual slides of these three units in a side‐by‐side comparison with the regular microscope laboratory. The methods and results of this paper will describe the technology employed to create the virtual slides, and the formative evaluation carried out in the course. Anat Rec (New Anat) 265:10–14, 2001.

Predicting therapeutic outcome in patients with diffuse histiocytic lymphoma treated with cyclophosphamide, adriamycin, vincristine and prednisone (CHOP)

Seventy‐five patients with diffuse histiocytic lymphoma (DHL) ranging in age from 33 to 94 years were treated with cyclophosphamide, Adriamycin, vincristine and prednisone (CHOP). Thirty‐eight patients (51%) achieved complete remission, but nine of these patients relapsed after remission lasting one to 23 months (median time to relapse, four months). We used multivariate analysis to identify those characteristics that significantly affected treatment outcome. The chances for complete remission were adversely affected by DHL appearing after histologic conversion from another lymphoma (P = 0.006), the presence of systemic symptoms (P = 0.024), and not having the large noncleaved (LNC) histologic subtype (P = 0.040). The chance for relapse from complete remission was increased only by the presence of systemic symptoms (P = 0.042). Overall survival was adversely affected by the presence of bone marrow involvement (P = 0.002), having other than LNC histologic subtype (P = .010), and the presence of systemic symptoms (P = 0.043). It appears that patients whose DHL appears de novo and who also are symptom status A (70% long‐term disease‐free survival) or have the LNC histologic subtype (67% long‐term disease‐free survival) have an excellent outlook when treated with CHOP at the doses used in this study. However, patients with B symptoms (16% long‐term disease‐free survival), histologic conversion to DHL (8% long‐term disease‐free survival), previous chemotherapy (8% long‐term disease‐free survival), and bone marrow involvement (8% long‐term disease‐free survival) respond poorly and for these patients other treatments need to be identified. In addition, patients with B symptoms who achieve complete remission with CHOP are at high risk to relapse (59% relapse rate) and should be considered for “intensification” therapy after complete remission is documented. Cancer 50:1695‐1702, 1982.

Familial cancers associated with subtypes of leukemia and non-Hodgkin's lymphoma.

To investigate whether a history of hematolymphoproliferative cancers (HLP) and other cancers among a parent or sibling is a risk factor for specific subtypes of leukemia and non-Hodgkins lymphoma (NHL), data from a population-based case-control study, in Iowa and Minnesota, of 578 leukemia cases, 622 NHL cases and 1245 controls were evaluated. Having at least one sibling with HLP significantly increased the risk for all leukemias combined (odds ratio (OR) = 2.3) and for NHL (OR = 2.7). In particular, chronic lymphocytic leukemia (CLL) was significantly increased among those reporting a sibling with leukemia (OR = 3.0) or lymphoma (OR = 4.3). Elevated risks of small lymphocytic NHL (SML) (OR = 7.3) and diffuse NHL (DIF) (OR = 5.4) were also observed among subjects who had a sibling with lymphoma (primarily Hodgkins disease). A significantly increased risk of follicular NHL was noted among those with a sibling history of pancreatic cancer (OR = 4.8) and colorectal cancer (OR = 2.7). Parental history of HLP was not associated with any type of leukemia or NHL. A history of stomach cancer among parents was associated with a 2-fold elevation of CLL and DIF compared to controls. Increased risks of CLL and DIF were also linked to breast cancer among sisters and mothers, respectively. Prostate cancer among fathers increased the risk 2-fold for CLL and 3-fold for SML. This study confirms some familial cancer associations previously reported for leukemia and NHL, and provides new information regarding the various subtypes of leukemia and NHL.

Diffuse histiocytic lymphoma complicating chronic lymphocytic leukemia.

Nine patients with chronic lymphocytic leukemia (CLL) who also developed diffuse histiocytic lymphoma (DH) are described. The incidence of patients with CLL developing DH was at least 3.3%. CLL existed for a median of 2 years before the diagnosis of DH. DH presented in 8 patients with abdominal symptoms and/or enlarging lymph nodes, spleen and liver. There were no consistent laboratory abnormalities associated with the onset of DH. In 4 of the patients the DH appeared to be localized. Eight of the 9 patients have died with a median survival of 2 months from the diagnosis of DH. Whether DH occurs as a result of „blastic transformation”︁ of pre‐existing CLL or is a second, unrelated malignancy is not certain. It is hypothesized that utilizing current therapies for DH might favorably influence survival.

The lymph node in chronic lymphocytic leukemia

Lymph nodes were examined from 41 cases of typical chronic lymphocytic leukemia (CLL). Degree of immaturity was graded as absent to minimal (Grade I), moderate (Grade II) and marked (Grade III). A moderate degree of immaturity was found in the lymph node in 14 of 41 cases even though the cells seen on the initial bone marrow and peripheral blood smears obtained from these patients were essentially all mature. The morphology of these nodes could be confused with poorly differentiated lymphocytic or mixed lymphocytic‐his‐tiocytic lymphoma in terms of the degree of immaturity present. A marked degree of immaturity was found in 5 cases; the morphology of these cases resembled histiocytic lymphoma. In the remaining 22 cases immaturity was essentially absent. The morphology of these cases was similar to that of diffuse well differentiated lymphocytic lymphoma. Our studies suggest that a moderate degree of immaturity in the lymph node of patients with CLL does not indicate that these patients will have a marked shortening of their survivial.

Cutaneous and nasal allergic responses in ragweed hay fever: Lack of clinical and histopathologic correlations with late phase reactions

The present study was designed to test the hypotheses that late cutaneous and nasal responses to allergen in patients with ragweed hay fever were human correlates of cutaneous basophil hypersensitivity, and that late responses in the nose and skin reflect similar pathogenesis. Forty-seven patients with ragweed hay fever were studied during a ragweed season for peripheral basophilia and clinical patterns reflecting late responses. Provocative nasal challenge, skin testing, and biopsy were carried out subsequently in 21 of the same patients during the winter months. Conclusions were as follows: (1) no histologic features distinguish positive from negative late skin reactions at 24 hr in patients with immediate wheal-and-flare responses; (2) cutaneous basophil hypersensitivity, i.e., tissue basophilia, is not a distinguishing feature of late skin responses in ragweed pollenosis; (3) seasonal peripheral basophilia was not found; (4) late responses in the nose were difficult to document objectively and did not correlate with late skin reactions; and (5) lymphocyte responses to antigen failed to correlate with late responses in either the nose or the skin.

Immunoblastic lymphadenopathy with pulmonary infiltrates, hypocomplementemia and vasculitis: A hyperimmune syndrome

A detailed description of the clinical and morphologic characteristics of four patients with immunoblastic lymphadenopathy, pulmonary infiltrates, hypocomplementemia and vasculitis is presented. Noteworthy in the patients described here is the clinical similarity to patients with collagen-vascular diseases and systemic drug reactions. The frequent occurrence of pulmonary symptoms, bilateral interstitial infiltrates and pleural effusions is emphasized. The morphology suggests stimulation of the immune system by antigenic agents, and the low complement levels and the presence of vasculitis suggest that circulating immune complexes may be present. Immunoblastic lymphadenopathy may represent a syndrome in which the adenopathy is but a nonspecific part of a systemic hyperimmune response to unknown antigens. The clinical course of the patients reviewed suggests that supportive treatment and corticosteroids constitute the safest therapeutic approach.

Adult acute lymphoblastic leukemia: results of the Iowa HOP-L protocol.

Fifty-nine consecutive previously untreated adult patients with acute lymphoblastic leukemia (ALL) were entered onto a prospective single-arm trial of doxorubicin, vincristine, prednisone, and asparaginase (HOP-L) induction therapy followed by CNS prophylaxis and 3 years of maintenance therapy. Consolidation therapy was not administered. The study population included a large number of older (greater than 50 years) patients. Seventy-five percent of patients achieved complete remission. With a median follow-up of 6 years, the median duration of complete remission is greater than 4 years, with 53% of patients expected to remain in remission at both 3 and 5 years. Overall, median survival duration is 27.9 months, with 45% and 35% of all patients expected to survive 3 and 5 years, respectively. Multivariate analysis identified patients with T-cell disease and mediastinal masses (P less than .001) and those with low values of lactic dehydrogenase (LDH) (P = .057) as being at greatest risk of relapse. Therapy was well tolerated by patients under age 35, but older patients suffered appreciable mortality. We conclude that this treatment program is effective therapy for adult ALL, yielding a large proportion of durable remissions despite the exclusion of consolidation therapy.

Smoking and Risk of Non-Hodgkin Lymphoma Subtypes in a Cohort of Older Women

Although non-Hodgkin lymphoma (NHL) has not been considered to be a smoking-related malignancy, recent investigations suggest otherwise. We evaluated this association in a cohort of 37,336 women, aged 55-69 years, who reported in a mailed questionnaire in 1986 information regarding smoking history as well as demographic, medical history and dietary factors. Cancer and mortality experience through 1996 was determined by linkage to the Iowa Cancer Registry and other databases; there were 200 incident cases of NHL during the 380231 total person-years of follow-up. Compared to never smokers, former (age-adjusted RR = 1.0; 95% CI 0.8-1.5) and current smokers (age-adjusted RR = 1.0; 95% CI 0.7-1.5) were not at elevated risk of NHL, and there was no trend with pack-years smoked (ptrend = 0-3)- Multivariate adjustment for other NHL risk factors did not alter these findings. Age-adjusted analysis by NHL subtype revealed a suggestive positive association of smoking with follicular NHL (RRformer= 1.3; 95% CI 0.6-2.8), (RRcurrent = 1.8; 95% CI 0.8-3.8)], which strengthened after multivariate adjustment [(RRformer = 1.6; 95% CI 0.7-3.4), (RRcurrent = 2.3; 95% CI 1.0-5.0)]; there was no association for diffuse or small cleaved-cell NHL. Our study findings, which are consistent with other recent investigations, suggest that smoking may be associated with an increased risk of follicular NHL.

Analysis of the presenting features of adult acute leukemia: The French‐American‐British classification

The authors have performed a clinical and statistical analysis of the presenting features of adult acute leukemia classified according to the French‐American‐British (FAB) hematopathologic criteria. Observations were made on 70 variables of history, physical examination, and laboratory examination recorded for 195 patients seen during a recent six year interval. The incidence of each category as determined by consensus of three observers was L1, 9%; L2, 17%; L3, 3%; M1, 21%; M2, 22%; M3, 5%; M4, 21%; M5, 4%; and M6 1%. There were recurring features of each FAB category and for aggregated categories (myeloid, lymphoid). Some groups such as L1, M3, M4, and M5 were characterized by many distinctive characteristics. In contrast, the L2, M1, and M2 categories had few distinctive characteristics, although L2 shared many features with the other lymphoid groups. The distinctness of the categories was quantitated by stepwise discriminant analysis. Using only a few computer‐selected clinical variables, the authors classified patients into the correct FAB category with an accuracy of over 65% for some groups. The accuracy in discriminating between lymphoid and myeloid groups, the important therapeutic distinction, was 82%. This study demonstrates that many of the categories defined by the FAB criteria have characteristic clinical features at presentation.