Wing C. Chan

Percutaneous needle biopsy in the diagnosis and classification of lymphoma

Results of percutaneous needle biopsies were evaluated retrospectively in 58 patients in whom a diagnosis of lymphoma was suspected. The biopsy specimen was diagnostic in 94% of the 36 patients with lymphoma, 20 of whom had recurrent disease and 16 of whom had newly diagnosed lymphoma. Sufficient tissue was obtained in 94% of these positive biopsy specimens to allow histologic subtyping of the lymphoma. Immunohistochemical studies performed on seven of the biopsy specimens allowed immunologic subclassi‐fication into B‐cell and T‐cell types of lymphoma. Our results suggest that the percutaneous needle biopsy is a useful and reliable tool in the diagnosis and classification of lymphoma.

Giant lymph node hyperplasia with unusual clinicopathologic features.

This report describes two cases of giant lymph node hyperplasia (GLNH) with unusual clinicopathologic features, both studied with immunohistochemical techniques. In the first case, mesenteric GLNH was associated with amyloidosis and the nephrotic syndrome. In the second, GLNH developed in a patient with previously treated Hodgkins disease. In both cases, the GLNH was of the plasma cell variant. The plasma cells of the first case contained both kappa and lambda light chains, while those in the second case contained only the lambda light chain. The presence or absence of monoclonality was not predictable from the morphology alone. Cases of GLNH with unusual clinicopathologic features are reviewed and the significance of immunohistochemical studies discussed.

Plasmacytoid monocyte proliferation associated with myeloproliferative disorders.

Plasmacytoid T‐cell (PTC) lymphoma is a rare clinicopathologic entity characterized by generalized lymphadenopathy in association with a myeloproliferative disorder. Hepatosplenomegaly and weight loss frequently are present. Nodal T‐zone expansion by mononuclear cells with ultrastructural and immunohistochemical features typical of PTC is diagnostic. All of the five previously reported cases of PTC lymphoma coincided with or heralded the onset of a clinically aggressive myeloid leukemia. This strong association and recent immunohistochemical findings in reactive or neoplastic PTC favored a monocyte/macrophage derivation of these cells, and it has been suggested that they be renamed plasmacytoid monocytes (PM). Two additional cases of PTC lymphoma were studied at the institutions of the authors, and the findings supported the concept that PTC belong to the monocytic lineage. The disease presentation was generalized lymphadenopathy with constitutional symptoms. One patient also had hepatosplenomegaly and bilateral renal enlargement concomitantly with myelofibrosis with myeloid metaplasia that progressed within months to acute myelogenous leukemia. Similar rapid evolution of acute monoblastic leukemia occurred in the other patient. Tumor cells within subtotally effaced lymph nodes had positive findings for CD45, CD4, CD7, and LN2 and negative findings for CD3, CD8, and βF1. Occasional cells had positive findings for CD2. One case demonstrated CD5, HLA‐DR, CD71, and CD43 (Leu‐22)‐positive cells. The myeloid/monocyte‐associated antigens CD14 and CD68 were identified in both. The tumor cells lacked the B‐cell markers LN1, CD20 (L26), CD19, and CD22 and did not rearrange immunoglobulin heavy chain genes and T‐cell receptor β, γ, and δ chain genes. The term plasmacytoid T‐zone lymphoma or PM proliferation is more appropriate for this rare disease. The close association of the PM proliferation with a myeloproliferative disorder indicates that the two entities are related. Cancer 1992; 69:1457‐1467.

Peripheral T-cell lymphoma in a patient with acquired immune deficiency syndrome.

A case of pulmonary T‐cell lymphoma in an Acquired Immune Deficiency Syndrome (AIDS) patient is presented. Morphologically, it belonged to the large cell, immunoblastic category of the Working Formulation and demonstrated a helper/inducer phenotype. Clinically there was no association with manifestations of human T‐lymphotropic virus (HTLV)‐I related lymphoma and the patient was seronegative for HTLV‐I and HTLV‐II antibodies. High‐grade B‐cell lymphomas occur with an increased frequency in patients with AIDS but the occurrence of a peripheral T‐cell lymphoma in AIDS has not been documented before. The case is discussed in the context of current concepts of AIDS‐related lymphomagenesis.

Malignant lymphoma of the skin in children

The clinical and histopathologic findings in eight cases of malignant lymphoma of the skin in children are presented. All patients had skin lesions as a primary manifestation of the disorder. Three patients had simultaneous regional lymph node involvement documented by the findings of subsequent biopsies. The majority (five patients) had solitary nodules involving the skin of the head and neck region. Three of the skin biopsy specimens were classified as lymphoblastic lymphoma, two large cell lymphoma, two mixed small and large cell lymphoma, and one small cleaved cell lymphoma. Disseminated disease subsequently developed in four patients in an interval that ranged from 4 to 30 months after diagnosis. The follow‐up period ranged from 8 to 56 months, and median survival was 56 months. A literature review of 33 previously reported patients and our eight patients indicate that: (1) skin of the head and the neck region is the most common site of involvement (56%); (2) the majority of lymphomas are diffuse (93%); (3) lymphoblastic lymphoma is the predominant type (53%), with a high proportion showing a non‐T‐cell phenotype; (4) Burkitts lymphoma and Hodgkins disease of the skin are extremely rare; and (5) most patients presented in an early clinical stage (Stage IE 56%, Stage IIE 21%), and prolonged disease‐free survival was seen mostly in Stage I patients. The cumulative probability of survival for Stage I patients at 24 months was 0.71; while for Stages II to IV patients combined, it was 0.33 at 26 months. Cancer 59:1040‐1045, 1987.

Sequential testicular biopsies in childhood acute lymphocytic leukemia.

Between August 1978 and November 1981, 33 boys with acute lymphocytic leukemia (ALL) (26 non‐T, 7 T‐cell) younger than 16 years underwent bilateral wedge testicular biopsies at the time of initial diagnosis. Seven (4 non‐T, 3 T‐cell) demonstrated focal leukemic infiltrates. Rebiopsy after successful induction therapy without testicular irradiation showed eradication of leukemic infiltrates in five, persistent focal infiltrates in one, and a diffuse infiltrate in one. The two patients who had persistent leukemic involvement had a T‐cell phenotype, and in one of them overt testicular disease developed 2 years later. All 33 patients were followed prospectively for a minimum of 3 years. Fifteen (14 non‐T, 1 T‐cell) remained in remission for 3 years and underwent another testicular biopsy before the cessation of therapy. Two patients, both non‐T and both of whom were free of testicular involvement at diagnosis, showed testicular infiltrates at that time. Of the seven boys with positive specimens at diagnosis, only two remained disease‐free for 3 years and showed no testicular involvement upon the completion of chemotherapy. In this study, microscopic testicular involvement by lymphoblasts occurred in 21% of newly diagnosed boys with ALL; this occurred only if the leukocyte count exceeded 25,000/μ1. These patients in general had a poor prognosis, probably reflecting the overall heavy tumor burden. However, it was not possible to predict accurately those patients who would have leukemic testicular infiltrates at the cessation of chemotherapy by performing biopsy of the testes at the time of initial diagnosis or after induction therapy.

Phenotypic changes in large cell transformation of small cell lymphoid malignancies.

Large cell transformation of two cases of chronic lymphocytic leukemia and two cases of small lymphocytic lymphoma were studied. Changes in surface immunoglobulins were observed in two cases. In one case, there was a change from IgM to IgG. In another case, the large cells bore kappa light chains whereas the small cells had lambda light chains. Surface antigens other than immunoglobulin might also differ. All three small cell malignancies tested, but none of the large cell tumors, expressed the antigen T1 (Leu 1). The antigens HLA‐DR, Leu 14, B1, and BA1 were expressed by both the small and large cell malignancies with one exception. The staining intensity might, however, change on transformation. The common acute lymphocytic leukemia antigen was not detected on any of the tumors studied and the expression of BA2 was variable. Surface marker studies cannot confidently distinguish between large cell lymphomas resulting from clonal evolution and those arising de novo. More definitive studies such as analyzing the idiotypic determinants on and amino acid sequences of the heavy and light chains or analyses of immunoglobulin gene rearrangements are necessary to confirm or exclude the same clonal origin in such cases.

Malignant angioendotheliomatosis presenting as disseminated intravascular coagulopathy

Disseminated intravascular coagulopathy (DIC) occurred in a patient with hemolytic anemia and anasarca. Skin and muscle biopsy showed intravascular lymphomatosis (malignant angioendotheliomatosis). Combination chemotherapy resulted in resolution of the DIC and anasarca. After an unmaintained 8‐month clinical remission, the patient had central nervous system relapse and died. Malignant angioendotheliomatosis is a rare disorder that should be considered among the occult causes of DIC. Cancer 68:2319–2323, 1991.

Interferon-γ-treated K562 target cells distinguish functional NK cells from lymphokine-activated killer (LAK) cells

In vitro incubation of the erythroleukemic cell line K562 with interferon-gamma (IFN-gamma) renders these cells relatively resistant to natural killer (NK) cell lysis. However, such treatment does not alter their sensitivity to LAK cell lysis. Thus, the lytic susceptibility of interferon-gamma-treated K562 (I-K562) cells to LAK cells as opposed to its relative resistance to NK cell lysis provides a functional assay to help distinguish these two types of effector cells. The relative resistance of I-K562 for NK cell-mediated lysis was not secondary to the release of soluble factors or the frequency of Leu-19+, CD3+ T cells, residual IFN-gamma, or expression of MHC Class I molecules. Coincubation of I-K562 cells with NK or LAK cells overnight did not appreciably change the pattern of lytic responses against K562 and I-K562 target cells. However, incubation of PBMC in vitro with I-K562 but not native K562 in the presence of r-IL-2 leads to a marked decrease in the generation of LAK cells. The inhibition of LAK cell generation was not secondary to differences in the consumption of bioactive levels of IL-2. Differences in the lytic capability of NK and LAK effector cells suggest heterogeneity among cells that mediate such non-MHC-restricted lysis. Use was made of cells from a patient with a large granular lymphocyte lymphoproliferative disease (greater than 85% Leu-19+) to determine if such cells could be used to distinguish clonal population of cells which would represent NK or LAK cell function. Of interest was the finding that such cells, even after incubation in vitro with IL-2, showed lytic function representative of NK cells but not LAK cells. Data concerning the inhibition of LAK cell generation by I-K562 cells have important implications for future therapeutic trials of IFN-gamma and IL-2 in the treatment of human malignancies.

Natural killer cells in children with acute leukemia: the effect of interleukin-2

The purpose of this study was to determine (1) the number and activity of natural killer (NK) cells in children with acute leukemia at different stages of their disease; and (2) the effect of interleukin‐2 (IL‐2) in enhancing NK activity of these patients cells. The mean percentage of Leu 11+ NK cells in patients at diagnosis (5% of peripheral blood (PB) mononuclear cells) was significantly lower than for patients on maintenance (23%), post‐treatment (21%) and for normal children (20%). The mean PB NK cell cytotoxicity for patients at diagnosis (16% lysis versus K562) and during maintenance (20%) was significantly lower than for post‐treatment (41%) and normal controls (40%). After NK cells were incubated for 5 days with IL‐2, NK cells from 82% (36/44) of patients showed enhanced cytotoxicity toward K562 and several acute leukemia cell lines as well as toward autologous leukemic cells. Cytotoxicity toward autologous cells was very low (0% to 5%, 16 hour assay) before IL‐2 stimulation, and significantly increased (23% to 69%) after stimulation, suggesting that IL‐2 may be a useful agent for enhancing the antileukemic immune response.