Acid phosphatase and alpha-naphthyl acetate esterase in neoplastic and non-neoplastic lymphocytes. A statistical analysis.

Acid phosphatase and alpha-naphthyl acetate esterase reaction patterns were evaluated in lymphocytes from patients with a variety of neoplastic and non-neoplastic conditions: leukemia, 59; NHL, 53; and reactive follicular hyperplasia, 23. Fifteen individuals with normal peripheral blood were also studied. For both enzymes, statistical analysis showed a strong correlation between a globular reaction pattern and T lymphocytic origin in both non-neoplastic lymph nodes and normal peripheral blood specimens (P less than 0.0001). A similarly strong correlation was found between a granular acid phosphatase pattern and T lymphocytic origin in cell isolated from non-neoplastic lymph nodes (P less than 0.0001) but not in those obtained from normal peripheral blood where this pattern was observed with equal frequency in B, T, and "null" lymphocytes (P = 0.415). A granular alpha-naphthyl acetate esterase pattern was correlated with non-T lymphocytes from normal peripheral blood (P less than 0.0001), but was observed with equal frequency in B, T, and "null" lymphocytes fron non-neoplastic lymph nodes (P = 0.76). In the eight T cell neoplasias studied, a globular pattern was evident in the majority of cells for both enzymes. In the majority of the B cell neoplasias, however, a granular pattern was observed for both enzymes.

Reversal of acute ("malignant") myelosclerosis by allogeneic bone marrow transplantation.

A 28-yr-old woman with acute malignant myelosclerosis received, as primary treatment, ablative chemotherapy and total body radiation therapy followed by bone marrow transplantation from her histocompatible brother. The patient is now well more than 15 mo after bone marrow transplantation, with normal peripheral blood counts, a normal bone marrow, no evidence of graft-versus-host disease, and is on no therapy. In light of the poor results obtained with conventional chemotherapy in this disease, bone marrow transplantation may represent the treatment of choice for patients who have an appropriate donor.

Lymphoblastic lymphoma: a clinicopathologic study of 95 patients.

A retrospective clinicopathologic study of lymphoblastic lymphoma was based on 95 patients from the files of the Repository Center for Lymphoma Clinical Studies. All patients were treated according to different protocols of Cooperative Oncology groups sponsored by the National Cancer Institute. The patients ranged in age from 4 to 84 years, with a median of 30 years. Sixty-eight patients were male and 27 female, with respective median ages of 27 and 50 years. The male-to-female ratio was 2.5:1. Forty patients had mediastinal masses; 30 (75%) of whom were male. The median survival of all patients was 17 months (range 1-100 months). To ascertain the influence of various clinical and morphologic parameters of survival, univariate and multivariate statistical analyses were performed. Patients older than 30 years of age had significantly lower incidences of mediastinal involvement (P = 0.01), number of mitotic figures (P = 0.04), and development of leukemia (P = 0.02) than patients younger than 30. Whereas lymphoblastic lymphoma is generally considered to be a disease of children and young adults, this study indicates that lymphoblastic lymphoma occurs in all age groups. These findings further suggest that lymphoblastic lymphoma may have a different biologic behavior in older patients.

Follicular (nodular) lymphoma during the first two decades of life: a clinicopathologic study of 12 patients.

Twelve patients who developed non-Hodgkin's lymphoma with a follicular pattern during the first two decades of life were studied. Eight had the poorly differentiated lymphocytic type; the remaining four had the "histiocytic" type. Eleven of the 12 patients were male. Nine were asymptomatic, and eight had lymphadenopathy in the head and neck region. Comparison of ages revealed the extent of disease tended to be localized (Stages I and II) in the pediatric (less than 16 years old) patients (83%) and generalized in the adolescent-young adult (16-19 years old) patients (83%). Of ten patients treated with chemotherapy and/or radiotherapy, eight achieved complete remissions that lasted 3-58 months (median, 17.5 months). Five are still in remission; three have relapsed. Seven are alive 12-120 months from diagnosis (median, 48 months); six have no clinical evidence of disease. The remaining five patients died two to 164 months after diagnosis (median, 13 months). Three of the four patients who died with lymphoma had diffuse "histiocytic" lymphoma demonstrated at autopsy examination. Poor prognostic factors included 1) failure to achieve a complete remission following initial therapy; 2) extranodal disease (with the exception of the poorly differentiated lymphocytic type involving the spleen and liver); 3) development of diffuse "histiocytic" lymphoma. Follicular lymphoma occurring in the second decade of life has a biologic behavior similar to follicular lymphoma in adults.

Chronic monocytic leukemia in adults.

Clinical, hematologic, and histologic material from five patients with chronic monocytic leukemia is analyzed, and the literature is reviewed on 28 patients either reported as having this disease or referenced as such in subsequent publications. Patients with chronic monocytic leukemia have a characteristic clinical course. All have splenomegaly of uncertain etiology, and initial hematologic evaluation usually shows anemia with normal leukocyte and differential counts. One of the authors' patients had slight monocytosis at presentation. In the four patients for whom presplenectomy bone marrow smears were available for review, there was no detectable increase in the number of monocytes. The patients developed monocytosis, usually with accompanying leukocytosis, at intervals ranging from 3.5 to 24 months after splenectomy. In all patients, there was a corresponding increase in the numbers of mature monocytes in the bone marrow. Survival times from the detection of monocytosis ranged from five to eight months. Of the 28 cases reported in the literature, only two were considered by the authors of this study to have the characteristics of chronic monocytic leukemia, and of these, only one had features identical to those reported in the present series. The remainder represent a variety of hematologic disorders including chronic myelomonocytic leukemia, acute leukemia, histiomonocytic proliferations that cannot be sub-classified, and cases in which the data are insufficient for analysis. The differential diagnosis includes chronic myelomonocytic leukemia, chronic malignant histiocytosis, and hairy cell leukemia. In chronic monocytic leukemia, in contrast to hairy cell leukemia, splenectomy does not appear to be beneficial. Although chronic monocytic leukemia is an extremely rare disease, it is a distinct hematologic entity that appears to have a characteristic clinical course.

Morphologic criteria for the differentiation of follicular lymphoma from florid reactive follicular hyperplasia: a study of 80 cases.

A study was made of 80 patients whose lymph nodes were characterized by the presence of follicles throughout the lymph node. The patients were divided into two groups on the basis of the clinical follow-up information. The first group consisted of 20 patients who were alive and disease-free at the end of five years without therapy. The patients in this group were classified as having florid reactive follicular hyperplasia (FRFH). The second group of 60 patients had progressive, recurrent, clinically active disease and were classified as having follicular lymphoma (FL). Forty-six were dead of active disease, and 14 were alive with disease. Various morphologic parameters were evaluated at low and high magnification, and statistical comparisons were made between FRFH and FL. Although several criteria were helpful in distinguishing FRFH from FL, the single most valuable criterion was the type of pattern encountered. Follicles of variable size and shape lying adjacent to each other throughout the lymph node without or with very little intervening tissue are diagnostic of FL. This pattern was evident in 85% of the FL cases, but was not observed in any of the cases of FRFH.

Terminal deoxynucleotidyl transferase activity in neoplastic and nonneoplastic hematopoietic cells.

Terminal deoxynucleotidyl transferase activity was investigated by enzyme assay and (or) an indirect immunofluorescence method with specimens from 151 patients who had a variety of neoplastic and nonneoplastic conditions: leukemia, 62; non-Hodgkin's lymphoma, 36; Hodgkin's disease, seven; lymph nodes without neoplasms, 21; normal peripheral blood, 15; normal bone marrow, ten. Immunologic studies were done on samples from 82 of these patients. Increased terminal deoxynucleotidyl transferase activity was found by both methods in patients who had acute lymphoblastic leukemia and the lymphoid blast crisis of chronic myelocytic leukemia and by the immunofluorescence method in patients who had lymphoblastic lymphoma. A single patient with acute monoblastic leukemia was found by both technics to have increased enzyme activity. Three B-cell proliferations were positive by the enzyme assay; none was positive with the immunofluorescence method. In the remaining 42 B-cell proliferations, the levels of terminal deoxynucleotidyl transferase activity were found to be normal by both the enzyme assay and the immunofluorescence method. Cytoplasmic positivity was observed in as much as 10% of the cells in 13 specimens that were otherwise negative and in eight samples in association with nuclear positivity. A comparison of terminal deoxynucleotidyl transferase activity in microunits/mg protein (enzyme assay) with the percentage of positive cells (immunofluorescence method) yielded a correlation coefficient of 0.62 (P less than 0.01).

Terminal deoxynucleotidyl transferase-positive lymphadenopathy in acute-phase chronic granulocytic leukemia.

A patient who had Philadelphia chromosome-positive chronic granulocytic leukemia had generalized lymphadenopathy. The lymph node biopsy revealed blast cells with small numbers of eosinophilic myelocytes indicative of granulocytic differentiation. In addition, the blast cells were found to have Philadelphia (Ph1) chromosome and extremely high levels of terminal deoxynucleotidyl transferase (TdT). The patient's peripheral blood and bone marrow reverted to the chronic phase, and the lymphadenopathy disappeared on two occasions with vincristine and prednisone therapy. The extramedullary proliferation of blastic chronic granulocytic leukemia, therefore, seems to share the histologic, cytogenetic biochemical, and chemotherapeutic sensitivity features of the basic disease process. TdT assay of enlarged lymph nodes in acute-phase chronic granulocytic leukemia might be used to identify the patients responsive to vincristine and prednisone despite the granulocytic histologic features of their lymph nodes.

Malignant lymphoma with primary manifestation in the gonad: a clinicopathologic study of 38 patients.

This study is based on 38 patients, each of whom had a malignant lymphoma in which the gonad was the site of the main tumor mass at the time of diagnosis. Histiocytic lymphoma was the predominant type in the 27 male patients; in the 11 female patients, poorly differentiated lymphocytic lymphoma was the most frequent type (36%). All of the neoplasms in the males were diffuse, whereas two of the females had neoplasms that were nodular and diffuse. A striking feature was the high frequency of vascular invasion (41%) in the testicular lymphomas, which was reflected in a high incidence (86%) of noncontiguous lung involvement at autopsy, suggesting hematogenous spread. Clinically occult disease is probably responsible for the short interval between the discovery of a gonadal mass and the appearance of generalized disease. A poor prognosis may be expected if there is evidence of generalized disease within one year after diagnosis. Only 2 patients had disseminated disease after a year, whereas all those who died of disseminated disease manifested it within six months after diagnosis. Disease-freee survival times in excess of 60 months in 3 patients who were treated only by orchiectomy or oophorectomy indicate that the gonads may be the primary site of a malignant lymphoma.

Prolymphocytic leukemia. An ultrastructural study.

The ultrastructural features of the leukemic cells from three patients with prolymphocytic leukemia were examined. In all patients, the prolymphocytes were characterized by a single prominent nucleolus and a chromatin structure intermediate between that of a mature lymphocyte and a lymphoblast. The cytoplasm contained a few short segments of rough endoplasmic reticulum and a poorly-developed Golgi apparatus. Polyribosomes and lysosomes were scarce. These ultrastructural features help in distinguishing prolymphocytic leukemia from other malignant lymphoproliferative disorders. A unique feature of the leukemic cells from one patient was the presence of intracytoplasmic inclusions. These were concentrated in the region of the Golgi zone, were surrounded by a smooth, trilaminar membrane, and had a substructure of parallel lines with a periodicity of approximately 60 A. To the authors' knowledge, similar inclusions have not been previously described in prolymphocytic leukemia.

Prolymphocytic leukemia: flow microfluorometric, immunologic, and cytogenetic observations.

Cells isolated from four patients with prolymphocytic leukemia were evaluated by surface markers, cytogenetics, and flow microfluorometric analysis of cell size and DNA content. All four patients had B-cell markers with a high density of IgM, kappa type, and Ia-like antigen. Less intense staining for surface IgD was also observed. In each patient studied, chromosomal modes were in the hypodiploid or near-diploid range. Despite the karyotypic abnormalities, the cellular DNA content, as determined by flow microfluorometry, was within the normal limits in all cases. This suggests that the variability in chromosome numbers seen in these patients may reflect an abnormality in DNA package rather than differences in total DNA content. The modal electronic cell size of the prolymphocytes, determined by light scatter, was readily distinguishable from that of normal peripheral blood lymphocytes and the lymphocytes of chronic lymphocytic leukemia. Fewer than 4% of the peripheral prolymphocytes had S-phase DNA content, a finding consistent with the chronic nature of this leukemia.

Acute ("malignant") myelosclerosis.

This study is based upon an analysis of the hematologic and pathologic material from seven patients with acute myelosclerosis, as well as a review of the literature of 49 cases reported under this designation, or one of its synonyms. Patients with this disease characteristically present with pancytopenia, minimal or absent anisocytosis and poikilocytosis, and a fibrotic bone marrow showing hyperplasia and immaturity of all three cell lines, with particular prominence of megakaryocytes and their precursors. In addition, clinical splenomegaly is almost always absent, and the disease has a rapidly fatal course. We consider only one-fourth of the cases reported in the literature to have the clinical and hematologic features consistent with the diagnosis of acute myelosclerosis; the remainder represent a variety of myeloproliferative disorders, including chronic myelosclerosis with an accelerated terminal phase, acute myeloblastic leukemia with bone marrow fibrosis, myeloproliferative diseases that cannot be subclassified, and cases in which the data are insufficient for analysis. Using strict clinical and hematological criteria, acute myelosclerosis can be separated from other myeloproliferative disorders as a distinct clinicopathologic entity.

Prolymphocytic leukemia: clinical, histopathological, and cytochemical observations.

The clinical, histopathological, and cytochemical features of eight patients with prolymphocytic leukemia, a rare variant of chronic lymphocytic leukemia, were reviewed. Six of the patients had clinical evidence of "massive" splenomegaly at the time of diagnosis, and in four of these this clinical impression was confirmed by splenic weights in excess of 2000 g. No patient had significant lymph node enlargement. The initial leukocyte count was elevated in seven patients and was greater than 100 X 10(9)/1 in four of them. The absolute prolymphocyte count ranged from 16.3 to 378.1 X 10(9)/1 and was greater than 100 X 10(9)/1 in four patients. Splenectomy in four patients had no lasting effect on the peripheral leukocyte count. In the four patients in whom the disease was shown by surface marker or immunocytochemical studies to be of B-cell origin, the histopathologic features were distinctive and were characterized by a pattern of infiltration which was nodular and diffuse in both the splenic red pulp and the bone marrow, whereas involvement of the lymph nodes was pseudonodular. In one patient in whom the prolymphocytes had cytochemical characteristics suggestive of T-cells, the distribution of the abnormal cellular proliferation in the lymph nodes was paracortical and the infiltrations of the spleen and the bone marrow were diffuse.

The ultrastructure of the normal human thymus: a study of 36 cases.

Electron microscopy of the normal human thymus demonstrates a supporting framework of epithelial-reticular cells with long branchticular cell processes lie lymphocytes, macrophages, and rare myoid cells. Both small and large lymphocytes are evident. No desmosomes are observed between the lymphocytes and the epithelial-reticular cells. Macrophages are most numerous in the cort(x were they often contain phagocytized nuclear debris. The possible functional significance of the above-described fine structural features is discussed.

The normal human thymic vasculature: an ultrastructural study.

Electron microscopy of the normal human thymus demonstrates a characteristic vascular-parenchymal relationship. The vascular lumen is always separated from the thymic parenchyma by: the endothelial cell cytoplasm, a muscular coat in arterioles and veins, the vascular basal lamina, a perivascular space containing collagen fibers and cells, the epithelial-reticular cell basal lamina and the epithelial-reticular cell cytoplasm. The width of this perivascular space is proportional to the size of the vessel it surrounds; it is wide around the vessels in the septa and at the cortical-medullary junction, but narrow around capillaries. While many cells are present in this space around larger vessels, only collagen is observed around the capillaries. Lymphocytes are the predominant cell type in the space; however, plasma cells, eosinophils, histiocytes, polymorphonuclear leukocytes, mast cells and unidentified granulated cells are also seen. The vascular complex described above may function as a blood-thymus barrier, as the initial site of exposure of the lymphocytes to circulating antigen and as the route of lymphocytes from the thymus.

The fine structure of thymoma, with emphasis on its differential diagnosis. A study of ten cases.

In this study, thymoma is defined as a neoplasm of the epithelial-reticular framework cells of the thymus. As in the normal thymus, these cells regularly displayed branching tonofilaments, macuale adherens, elongated processes, and basal lamina. These characteristics proved useful in the differential diagnosis of thymoma from a variety of anterior mediastinal tumors including thymic carcinoid, lymphoma, germinoma (seminoma type), and fibrous mesothelioma. Lymphocytes in the thymomas often showed mitotic activity and a moderate degree of transformation. The significance of this and the gland-like spaces, vacuolated epithelial cells, starry-sky appearance, emperipolesis, and perivascular spaces is discussed.

Clear cell sarcoma with melanin pigment.

A patient with a clear cell sarcoma of tendons and aponeuroses arising in the left sacral area is reported. The tumor grossly contained two black foci that had pigment with the staining characteristics of melanin on light microscopy. Electron microscopy of these areas showed the pigment to be within melanosomes. This is the second report of a neoplasm diagnosed as clear cell sarcoma in which melanin was demonstrated; the possibility that the tumor represents a soft tissue variant of malignant melanoma is discussed. It is suggested that clear cell sarcoma is a heterogeneous entity, and that a number of different soft tissue neoplasms may present with a clear cell pattern, making diagnosis and classification difficult.