Mitchell A. Bitter

Association of an inversion of chromosome 16 with abnormal marrow eosinophils in acute myelomonocytic leukemia. A unique cytogenetic-clinicopathological association.

We identified 18 patients with an inversion of chromosome 16, inv(16)(p13q22), among 308 patients with newly diagnosed acute nonlymphocytic leukemia. Each of these 18 patients had acute myelomonocytic leukemia (M4 subtype) and eosinophils with distinctly abnormal morphology, cytochemical staining, and ultrastructure. These eosinophils constituted from 1 to 33 per cent of the nucleated marrow cells. In our series, every patient with acute myelomonocytic leukemia and abnormal eosinophils also had an abnormal chromosome 16. This subgroup of M4 patients had a good response to intensive therapy designed to induce remission; 13 of 17 treated patients entered a complete remission, and 10 remain in first remission. Thus, patients with an inversion of chromosome 16 appear to represent a unique cytogenetic-clinicopathological subtype of acute nonlymphocytic leukemia with a favorable prognosis.

Morphology in Ki-1(CD30)-positive non-Hodgkin's lymphoma is correlated with clinical features and the presence of a unique chromosomal abnormality, t(2;5)(p23;q35).

Ten patients with strongly Ki-1(CD30)-positive non-Hodgkins lymphoma (NHL) were identified at our institution during the past 5 years. Based on morphology, the lymphomas of five of these patients were classified as anaplastic large-cell lymphoma (ALCL); the lymphomas of four patients lacked the morphologic features of ALCL (non-ALCL); and the lymphoma of one patient was unclassifiable. Significant clinical and cytogenetic differences were observed between patients with ALCL and those with non-ALCL. The patients with ALCL tended to be young at the time of diagnosis. They presented with peripheral lymphadenopathy, and two of the five patients had skin involvement. An identical reciprocal translocation involving chromosomes 2 and 5 [t(2;5)(p23;q35)] was observed in lymph nodes from each of the two ALCL patients whose chromosomes were studied. Four of the five patients with ALCL are alive and in complete remission 10–27 months after receiving systemic chemotherapy. In contrast, the patients with non-ALCL were heterogeneous with respect to clinical findings. All of the non-ALCLs were histologically aggressive; however, their morphology varied. The t(2;5) was absent in the lymphoma specimens from each of three non-ALCL patients studied. Three of the four patients died within 17 months after receiving systemic chemotherapy. Thus, differences in morphology are correlated with differences in the clinical findings, karyotype, and outcome in Ki-1-positive NHL.

Relapse after interferon alfa-2b therapy for hairy-cell leukemia: analysis of prognostic variables.

Sixty-nine patients with hairy-cell leukemia (HCL) were treated with interferon alfa-2b (IFN) in a single-institution study. The dose used was 2 x 10(6) U/m2 self-administered subcutaneously three times weekly, for a planned treatment duration of 12 to 18 months. Of the 68 evaluable patients, the major response rate was 75%, with 13% complete responses (CRs) and 62% partial responses (PRs). An additional eleven patients (16%) had minor responses (MRs). Duration of response was denoted as failure-free survival (FFS), defined as the time from the end of IFN therapy to a need for further antileukemic therapy. Of the 60 responding patients followed after discontinuation of IFN, 27 have relapsed, requiring further therapy. The median actuarial FFS for these 60 patients is 25.4 months. All but five patients are alive, and the actuarial overall survival for the 69 patients is 91% +/- 4% at 4 years from the start of IFN. The best indicators of relapse were the neutrophil alkaline phosphatase (NAP) score and degree of residual bone marrow hairy cells (%HCL) at the completion of therapy. Patients with NAP less than 30 (n = 21) had the best prognosis (median FFS, 30.4 months), while those with NAP greater than or equal to 30 and %HCL less than or equal to 30 (n = 21) or %HCL greater than 30 (n = 16) had intermediate and poor prognoses, respectively (median FFS, 23.5 and 12.4 months) (P = .0005). Fourteen of the relapsing patients are evaluable for response to a second course of IFN, with seven PRs and four MRs. Stratified randomized trials are indicated to determine the role of maintenance therapy for responding patients.

Giant lymph node hyperplasia with osteoblastic bone lesions and the POEMS (takatsuki's) syndrome

A 38‐year‐old black man with giant lymph node hyperplasia (GLH), osteoblastic lesions, and the POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M protein, skin changes) was treated at the University of Chicago Hospitals. The patient had hepatosplenomegaly and generalized peripheral lymphadenopathy. Endocrinologic abnormalities included decreased testosterone with elevated luteinizing hormone and follicle‐stimulating hormone, as well as hyperprolactinemia and possible hypothyroidism. Biopsy of a right femoral lymph node revealed GLH, and an osteoblastic pelvic lesion showed a marked lymphoplasmacytic infiltrate. By immunohistochemical techniques, plasma cells in the lymph node and osteoblastic lesion were polyclonal. A polyclonal hypergammaglobulinemia was present. The lymph node T‐lymphocyte population showed a decreased helper‐to‐suppressor cell ratio. Other findings included thickening of the skin, finger clubbing, and anasarca. A severe sensory‐motor polyneuropathy was the major factor contributing to the patients death. The association of GLH, osteoblastic bone lesions, and the POEMS syndrome has been noted previously in Japan; however, the authors are unaware of reports on Western patients who had this combination of clinical and laboratory findings.

Impact of chromosomal translocations on prognosis in childhood acute lymphoblastic leukemia.

The presence of a chromosomal translocation in the leukemic cells at diagnosis of acute lymphoblastic leukemia (ALL) in children is associated with a high risk for treatment failure. We have reexamined the relationship between translocations and prognosis in 146 children with ALL who received risk-based therapy such that high-risk patients were treated with intensive drug schedules. In univariate analysis, multiple factors were associated with a relatively poor event-free survival (EFS) including age less than 2 years or greater than 10 years (combined group), WBC count greater than 10 x 10(9)/L, French-American-British (FAB) morphologic classification L2, absence of common ALL antigen (CALLA, CD10) expression, absence of hyperdiploidy with a chromosome number of 50 to 60, and presence of the specific translocations t(4; 11)(q21;q23) or t(9;22)(q34;q11) (combined group). However, there was no disadvantage with respect to EFS in patients with translocations compared with those who lacked translocations (73% at 4 years in both groups). Furthermore, when patients with specific cytogenetic abnormalities for which the prognostic significance has been well established (hyperdiploid 50 to 60, t(4;11), and t(9;22] were removed from the analysis, the remaining group with other translocations had a better EFS than the remaining group lacking translocations, although this was not statistically significant (81% v 65% at 4 years, P = .24). In a multivariate analysis, a model including WBC count and FAB classification was the strongest predictor of EFS. The presence or absence of translocations was not an independent predictor of EFS and did not contribute to the ability of any model to predict EFS. In conclusion, when effective intensive therapy is used to treat childhood ALL with high-risk clinical features, categorization of patients on the basis of chromosomal translocations without attention to the specific abnormality is not useful as a prognostic factor.

Gastric adenocarcinoma after gastric lymphoma

Three men and one woman developed intestinal‐type moderately or poorly differentiated gastric adenocarcinoma 4 to 15 years after the diagnosis of gastric lymphoma. Treatment of the lymphomas had included partial gastrectomy and follow‐up radiotherapy and/or chemotherapy. Review of the literature reveals an additional 12 patients who developed adenocarcinoma 3.5 to 34 years (median, 14.5 years) after diagnosis of gastric lymphoma. In the total series of 16 patients, only four were women, who tended to be younger (median age, 36.5 years) than the men (median, 48.5 years) when lymphoma was diagnosed. Patients with gastric lymphoma seem to have an increased incidence of gastric adenocarcinoma. Carcinoma after gastric lymphoma often arises in the distal stomach and appears to occur irrespective of the type of therapy for the lymphoma.

der(5)t(5;7)(q11.2;p11.2): A new recurring abnormality in malignant myeloid disorders☆

Complete or partial monosomy for the long arm of chromosomes 5 and/or 7 is frequently observed in malignant cells from patients with a therapy-related myelodysplastic syndrome (t-MDS) or therapy-related acute nonlymphocytic leukemia (t-ANLL). Partial monosomy is usually the result of a chromosomal deletion; however, unbalanced translocations have also been observed. We have identified one such translocation in three patients who had either t-ANLL or a primary MDS. The genetic consequences of this translocation [-5,-7,+der(5)t(5;7)(q11.2;p11.2)] are partial monosomy for the long arm of chromosome 5 and complete monosomy for the long arm of chromosome 7. Thus, this rearrangement may represent a new, recurring abnormality that is associated with malignant myeloid disorders.

Variant translocations (9;11): Identification of the critical genetic rearrangement

The t(9;11)(p22;q23) is a recurring abnormality in acute nonlymphocytic leukemia. The analysis of complex 9;11 translocations will aid in the identification of the conserved chromosomal junction or the critical genetic alteration created by the rearrangement; however, variant translocations involving chromosomes #9 and #11 have not been reported. We have identified such variants in two patients who had acute myelomonocytic leukemia and acute monocytic leukemia, characterized by a t(9;11;18)(p22;q23;q12) and a t(9;11;13)(p22;q23;q34), respectively. The conserved junction resulting from these rearrangements is created by the translocation of chromosomal material from 9p to 11q.

Insertion (10;11)(p11;q23q24) in two cases of acute monocytic leukemia

An insertion (10;11)(p11;q23q24) was found in bone marrow metaphase cells from two children with acute monocytic leukemia (AMoL-M5b). This rearrangement involves a small chromosomal segment of 11q and may be misinterpreted as a deletion of 11q. Insertion (10;11) may represent a new recurring abnormality involving 11q associated with acute leukemia of the M5b type.

The Histopathologic Diagnosis and Subclassification of Hodgkin’s Disease

Although Hodgkins disease is considered a distinct clinical entity, it exhibits a wide range of histologic and cytologic features. It is important to recognize histologic subtypes and their variants for diagnostic reasons, as well as for their clinical significance. An appreciation of the histologic diversity of Hodgkins disease may also be critical for the interpretation of data regarding the origin of the RS cell.