Immunophenotypic analysis of acute leukemia.
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Antigens, CD↗
Biomedical subjects
S T Traweek
Publications and source records attributed to S T Traweek.
Extramedullary myeloid cell tumors. An immunohistochemical and morphologic study of 28 cases.
In an attempt to correlate the morphologic and immunophenotypic findings in extramedullary myeloid cell tumors (EMT), we studied 28 cases with a large panel of antibodies using paraffin section immunohistochemistry. A previous or concurrent diagnosis of acute myelogenous leukemia or chronic myelogenous leukemia was made in 25 cases. Six EMT were morphologically classified as well differentiated (WD-EMT), 17 as poorly differentiated (PD-EMT), and five as blastic EMT. The WD-EMT were easily recognized morphologically and displayed a relatively mature myeloid phenotype, with elastase, CD15, and CD68 positivity in all cases. On the other hand, the five blastic-EMT displayed no morphologic evidence of myeloid derivation, were completely negative for CD15, and were weakly positive for elastase in only one case. The PD-EMT, with a morphologic appearance that resembles large cell non-Hodgkin's lymphoma, variably expressed CD15 and elastase. CD68 and lysozyme were present in the majority of PD-EMT, with some variability, but were negative in most blastic-EMT. CD45 (LCA) was detected in 75% of all EMT and CD34 was positive in 36%; neither antigen was significantly associated with a specific morphology. CD30 reactivity was not evident in any case, but slight positive staining was seen with CD20 (L26) in one WD-EMT. CD43 (Leu 22) was the only antibody that was positive in 100% of cases; staining was always intense and widespread. Antimyeloperoxidase (MPO) was positive in all cases but two, both with a blastic morphology. We conclude that (a) an immunohistochemical panel including CD20, CD43, CD68, and MPO can successfully identify the vast majority (96%) of EMT in paraffin sections, and (b) there is an association between morphology and phenotype in these lesions.
Antigens, Differentiation↗
Keratin gene expression in non-epithelial tissues. Detection with polymerase chain reaction.
Keratin filament are characteristically present in epithelial cells and tumors, but have also been detected in many normal and neoplastic non-epithelial cell types using immunohistochemical techniques. To investigate the validity of this seemingly aberrant protein expression, we applied the highly sensitive polymerase chain reaction (PCR) technique to study keratin gene expression in a variety of non-epithelial tissues. Total RNA was extracted from nine samples of leiomyosarcoma, four non-Hodgkin's lymphoma, seven normal bone marrows, normal lymph node, normal peripheral blood cells, freshly isolated and cultured endothelial cells, cultured skin fibroblasts, and the myeloid leukemia cell line HL-60. Amplification primers and probes for the three most primitive keratin types (8, 18, and 19) were synthesized using published gene sequences. RNA from the breast carcinoma cell line MCF-7, known to be rich in all three keratins, was used as positive control. Concurrently run actin primers were used to confirm RNA integrity. After an initial cycle with reverse transcriptase, PCR amplification was performed for 30 cycles. Southern blots of the PCR products showed variably intense bands corresponding to keratin 8 and 18 gene products in all samples, offering conclusive evidence of keratin gene expression in cells of both stromal and hematopoietic derivation. However, keratin 19 gene transcription was not nearly so ubiquitous, being detected in normal fibroblasts and endothelial cells, two of four non-Hodgkin's lymphoma and four of nine leiomyosarcoma, but not in normal lymph node, peripheral blood cells, HL-60 cells, or any of the seven normal bone marrows examined. Dilutional experiments showed PCR to be highly sensitive in the detection of keratin 19 gene expression, capable of registering one MCF-7 cell in 10(6) HL-60 cells. These studies show that variable levels of keratin 8 and 18 gene expression may be detected by PCR in a wide variety of non-epithelial tissues, supporting previous immunohistochemical and phylogenetic studies. However, keratin 19 gene expression appears to be more restricted and was not evident in any hematopoietic cells devoid of contaminating stromal elements. These findings suggest a role for PCR in the detection of epithelial micrometastasis in certain sites, particularly bone marrow.
Base Sequence↗
Rearrangement of the BCL-2 gene in follicular lymphoma. Detection by PCR in both fresh and fixed tissue samples.
Rearrangement of the BCL-2 gene is the molecular consequence of the t(14;18) chromosomal translocation, which is found in approximately 60-90% of follicular lymphomas. To investigate the ability of the polymerase chain reaction (PCR) to detect this rearrangement in fixed-tissue samples, we studied 48 cases of follicular lymphoma using DNA extracted from paired samples of fresh-frozen tissue and formalin-fixed, paraffin-embedded tissue. A standard phenol-chloroform DNA extraction method was used for both types of tissue. Rearrangements of the major breakpoint region (MBR) and minor cluster sequence (MCS) were examined. Three segments of the human beta-globin gene were also amplified to estimate the degree of DNA degradation in the fixed-tissue samples. PCR of fresh-tissue (intact) DNA revealed amplifiable products in 29 of the 48 follicular lymphomas (60%), whereas the fixed-tissue (degraded) DNA studies were positive in 24 (50%). MBR products were detected in 24 fresh-tissue samples, and varied from 80 bp to > 1.5 kb. Twenty of these cases yielded MBR products in the corresponding fixed-tissue DNA, ranging from 80 to 276 bp. Five fresh-tissue and four fixed-tissue samples produced MCS segments that ranged from 340 bp to 1.2 kb. Four of the five samples with no detectable MBR or MCS translocations using degraded DNA had products greater than 1.0 kb in the fresh-tissue studies. A 175-bp segment of the beta-globin gene was amplified in all 29 fixed-tissue samples; a 324 bp fragment was produced in 20 samples (69%), and a 676 bp segment was detected in 13 (45%).(ABSTRACT TRUNCATED AT 250 WORDS)
Base Sequence↗
Cytokeratin expression in adrenocortical neoplasia: an immunohistochemical and biochemical study with implications for the differential diagnosis of adrenocortical, hepatocellular, and renal cell carcinoma.
The immunostaining patterns of adrenocortical tumors are not clearly defined, primarily due to their inconsistent expression of cytokeratins (CK). To address this issue and to investigate whether adrenocortical tumors can be immunohistochemically differentiated from histologically similar tumors arising from the kidney and liver, we studied four normal adrenal glands, two adrenocortical adenomas (ACAs), 31 adrenocortical carcinomas (ACCs), 37 renal cell carcinomas (RCCs), and 33 hepatocellular carcinomas (HCCs) with anti-CK antibodies AE1, CAM 5.2, UCD/PR10.11, 35BH11, PKK1, and Ks19.1, as well as antibodies to vimentin (VIM), epithelial membrane antigen (EMA), and HMFG-2. Normal adrenal cortical cells showed variable staining with all anti-CK antibodies on fixed and frozen sections. In contrast, only one of two fixed ACAs stained with a single anti-CK, although both neoplasms reacted with multiple anti-CK antibodies on frozen sections. Similarly, 20 of 31 fixed ACCs contained VIM, but only one tumor stained for CK; frozen sections of this and another, previously negative tumor, however, stained with most of the anti-CK antibodies tested. One-dimensional Western immunoblot analysis confirmed the presence of CKs 18 and 19 in two examples of normal adrenal cortex, one ACA, and the ACC immunohistochemically positive on fixed and frozen sections, with CK 19 identified in the ACC that was positive on frozen section alone. All fixed HCCs and most RCCs stained with multiple anti-CK antibodies (33 and 34 cases, respectively), with a proportion of tumors positive for VIM (six and 22 cases, respectively), EMA (seven and 30 cases, respectively), and HMFG-2 (15 and 28 cases, respectively). The results suggest that CK expression is diminished in most adrenocortical tumors to levels too low to be recognized following the deleterious effects of fixation. While the immunohistochemical absence of CK, EMA, and HMFG-2 in fixed sections in the majority of ACCs is distinctive, sufficient phenotypic overlap exists such that differentiation between RCC and HCC may not be possible in an individual case.
Adrenal Cortex Neoplasms↗
Monocytoid B-cell lymphoma. The biologic and clinical implications of peripheral blood involvement.
Monocytoid B-cell lymphoma (MBCL) is a newly recognized malignant lymphoma that shares clinical and pathologic features with other low-grade B-cell neoplasms, especially small lymphocytic lymphoma and hairy cell leukemia. However, although circulating malignant cells and bone marrow involvement are relatively common in small lymphocytic lymphoma and are characteristic features of hairy cell leukemia, MBCL in the peripheral blood and bone marrow rarely have been described. From 124 patients entered in the MBCL registry, three cases with peripheral blood involvement are described and the clinical and pathologic features in these patients are compared with those of other low-grade B-cell neoplasms. Monocytoid B-cell lymphoma was confirmed by lymph node biopsy in each case. Two patients had lymphocytosis at the time of presentation; the remaining patient presented with pancytopenia. For each patient, phenotypic studies of lymph node and peripheral blood revealed identical monoclonal surface immunoglobulin expression. The morphologic appearance of the circulating MBCL cells was different in each case, varying from a relatively homogeneous population of small lymphocytes to a heterogeneous collection of large and small lymphoid cells. The two patients with lymphocytosis also had extensive replacement of the bone marrow by MBCL; the third patient had diffuse infiltration by MBCL in a normocellular marrow. All three patients had advanced-stage (Stages III or IV) disease, and all required systemic chemotherapy for disease control. The two patients with lymphocytosis had relentless, progressive infirmity despite relatively aggressive treatment regimens. These patients ultimately died of lymphoma 13 and 18 months after initial diagnosis. The third patient is alive and well with stable disease 30 months after coming to the authors' institution. The clinical and pathologic features of the patients reported here reaffirms the placement of MBCL in the spectrum of low-grade B-cell neoplasms. However, unlike small lymphocytic lymphoma and hairy cell leukemia, MBCL only rarely undergoes leukemic conversion. Furthermore, it appears that peripheralization of MBCL occurs primarily in patients with advanced-stage disease and may be indicative of a relentless course and progressive disease despite aggressive chemotherapeutic intervention.
Adult↗
Acute monoblastic leukemia (FAB-M5b) with t(8;14)(p11;q11.1).
A case of acute monocytic leukemia (FAB-M5b) expressing natural killer cell-associated antigens containing a t(8;14)(p11;q11.1) is presented. We interpret this translocation to represent a variant of the t(8;16) previously reported in FAB-M5b. These findings support the contention that the 8p11 breakpoint site is the critical junction in the oncogenesis of acute monoblastic leukemia with differentiation.
Aged↗
The human hematopoietic progenitor cell antigen (CD34) in vascular neoplasia.
The human hematopoietic progenitor cell antigen CD34 is synthesized and expressed by early normal hematopoietic progenitor cells and by many acute leukemias. Anti-CD34 antibodies also have been reported to stain blood vessels in tissue sections, and, more recently, CD34 mRNA has been detected in vascular endothelial cells. Therefore, the authors studied the diagnostic utility of immunohistochemical CD34 antigen detection in tumors of endothelial cell derivation and compared the results with stains for von Willebrand (vW) factor. A wide variety of epithelial and mesenchymal neoplasms also were examined to assess the specificity of CD34 for vascular neoplasia. Seven cases of angiosarcoma (seven of seven), five cases of Kaposi's sarcoma (five of five), and eight cases of epithelioid hemangioendothelioma (eight of eight) were moderately to strongly positive for CD34. This reactivity was equally intense in frozen sections, alcohol-fixed tissue, and formalin-fixed specimens. In many cases, the malignant endothelial cells stained more strongly than adjacent benign endothelium. Moreover, in most cases CD34 positivity was quantitatively and qualitatively stronger than staining for vW factor. Two cases of hemangiopericytoma (two of two) were CD34 positive but stained less intensely than the angiosarcomas, Kaposi's sarcomas, or hemangioendotheliomas. Five of six cases of hemangioma also stained positively for CD34; the nonreactive tumor in this group was the only one among 28 vascular neoplasms studied that was not reactive for CD34. In comparison, 9 of the 28 vascular tumors did not stain for vW factor. Three hundred fifty-seven tumors of nonvascular derivation also were examined for CD34 antigen expression. Focal light staining was seen in one pulmonary squamous cell carcinoma; moderate to intense staining was observed in half of the epithelioid sarcomas studied (8 of 16) and in a minority of leiomyosarcomas (3 of 22). These findings indicate that CD34 is a sensitive and relatively specific marker for neoplasms of vascular origin.
Antibodies, Monoclonal↗
Prostatic acid phosphatase in carcinoid tumors. Immunohistochemical and immunoblot studies.
The immunohistochemical demonstration of prostatic acid phosphatase (PAcP) and/or prostate-specific antigen (PSA) has been accepted as being reliable in identifying metastatic adenocarcinoma of prostate origin. However, islet cell tumors, especially hindgut-derived carcinoid tumors, have occasionally been reported to be positive for PAcP. We therefore studied a series of carcinoid tumors of the lung and gastrointestinal tract immunohistochemically for PAcP expression by using two polyclonal antibodies and one monoclonal antibody. Thirty-three carcinoid tumors were examined. All five rectal carcinoids in the series showed convincing PAcP positivity with at least two of the three anti-PAcP antibodies. No significant PAcP positivity was observed in the remaining 28 foregut- and midgut-derived carcinoid tumors, except for weak focal positivity in one lung carcinoid. PSA antibody reacted negatively in all cases. Western blots of an aqueous cell lysate from one rectal carcinoid revealed protein bands in the region of 45-55 kd that immunoreacted with anti-PAcP antibodies, confirming the validity of the immunostains. These results suggest that PAcP positivity is common in rectal carcinoid tumors and that it most likely represents true PAcP expression. This seemingly aberrant protein expression may be explained by the shared cloacal derivation of the rectum and prostate, giving rise to cells with both endocrine and partial prostatic epithelial differentiation.
Acid Phosphatase↗
The in-vitro response of CD2-positive acute myelogenous leukemia to proliferation and differentiation inducing agents.
Acute mixed lineage leukemias (MLL) are a heterogeneous group of acute leukemias that express morphologic and/or immunophenotypic features of more than one hematopoietic cell line. The ontogenetic significance of this mixed lineage expression is unclear. We therefore studied the conviction of the lineage commitment in a group of MLL by examining the in-vitro response of five CD2+ (E-rosette receptor) acute myelogenous leukemia (AML) to a panel of proliferation and differentiation-inducing agents. Three of the five CD2+ AML were TdT-positive. Antigen receptor gene studies revealed no rearrangements at either the T beta or immunoglobulin heavy chain gene loci in any case. When blast-enriched cell populations were placed in short term suspension cultures with PHA, IL-2, PHA + IL-2, GM-CSF or TPA, three of the leukemias responded in a similar fashion while the remaining two cases showed no response. In the three MLL that responded to the in-vitro culture manipulations, features indicative of differentiation along the monocytic lineage pathway were observed. This differentiation was not pronounced in the presence of the phorbol ester TPA, and was manifested by loss of CD2 and CD7 expression, continued expression of myeloid antigens, and the development by the blasts of morphologic and cytochemical characteristics of monocytic cells. None of the five MLL showed any evidence of induced maturation along the T-lymphocyte line of differentiation with any of the agents used. rGM-CSF was the only exogenously added agent to induce proliferation; the proliferative response was slight and was seen in only one of the five leukemias. Therefore, the phenotypic expression of CD2 and CD7 in blasts from MLL is not indicative of irreversible commitment to T-lymphocyte development. The in-vitro loss of T-cell antigens in concert with the development of monocytic features in three of the five CD2+ AML in this study suggests the leukemic cells were preferentially committed to a non-lymphoid lineage differentiation pathway.
Adolescent↗
Regarding the article entitled "Monocytoid B-cell lymphoma with bone marrow and peripheral blood involvement at presentation".
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B-Lymphocytes↗
Relationship between eosinophil density and T-cell activation markers in lymph nodes of patients with Hodgkin's disease.
Hodgkin's disease (HD) is characterized morphologically by a variable infiltration of tissues by eosinophilic granulocytes. The lesions also contain numerous T cells, predominantly of the CD4+ immunophenotype. To investigate whether the presence or absence of tissue eosinophilia is related to the immunophenotype of the T cells, we studied 43 cases of HD (28 nodular sclerosing, ten mixed cellularity, and five unclassifiable) for the relative numbers of lymphocytes positive for CD2, CD3, CD4, CD5, CD8, CD25, CD38, T9, TQ1, HLA-DR, and beta F1, and for the number of eosinophils in tissue sections. By univariate and multivariate analysis, we determined that there was an inverse relationship between the number of eosinophils and the presence of TQ1+ (P less than .0005) and CD25+ (P less than .0005) lymphocytes. In addition, we observed that TQ1 stained the Reed-Sternberg cells in these lesions. We also determined that the T cells expressed HLA-DR more frequently in the nodular sclerosis subtype than in other subtypes of HD (P less than or equal to .0001). We therefore conclude that the degree of tissue eosinophilia in the lymph nodes of patients with HD may be explained, at least in part, by the immunophenotype of the T cells present in the affected lymph nodes.
Antibodies, Monoclonal↗
Monocytoid B-cell lymphoma: its evolution and relationship to other low-grade B-cell neoplasms.
Monocytoid B-cell lymphoma (MBCL) is a newly recognized B-cell neoplasm of uncertain histogenesis. The cytologic features of the neoplastic monocytoid B lymphocytes are virtually identical to those of hairy cell leukemia (HCL). As with HCL, progression of MBCL to a higher histologic grade is very unusual. However, whereas circulating leukemic cells are a characteristic feature of HCL, peripheral blood involvement has not been reported in MBCL. We recently studied a patient with MBCL of the spleen and axillary lymph nodes who developed peripheral blood involvement by MBCL cells. Unlike the cells of HCL, the circulating MBCL cells exhibited strong acid phosphatase activity that was tartrate sensitive. The leukemic cells had the antigenic phenotype IgM lambda, CD20+, CD11c+, CD5-, CD25(TAC)-, and PCA-1-. Immunogenetic studies of both lymph node and peripheral blood cells revealed identical immunoglobulin heavy-chain gene rearrangements. When compared with a series of HCL, the immunophenotype was similar except for the absence of PCA-1 and TAC. Progression of the MBCL to a large cell lymphoma, also expressing IgM lambda, was documented in an abdominal lymph node of this patient. Therefore, although rare, peripheral blood involvement by lymphoma cells may occur during the course of MBCL and should be distinguished from HCL with cytochemical and immunophenotypic studies. In addition, comparison of the clinical, pathologic, and immunologic features of MBCL with those of other low-grade B-cell neoplasms suggests that a close lineage relationship exists between MBCL and HCL.
Adult↗
Monocytoid B-cell lymphoma: point on a spectrum.
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Bone Marrow↗
Methylthioadenosine phosphorylase deficiency in acute leukemia: pathologic, cytogenetic, and clinical features.
Blast cells from 100 cases of acute leukemia were evaluated for the presence of methylthioadenosine phosphorylase (MTAase), an enzyme important in polyamine metabolism. Ten cases (10%) had undetectable levels of MTAase activity. Of the 10, 5 had acute lymphoblastic leukemia (ALL), 3 had acute myeloblastic leukemia (AML) and 2 expressed mixed lineage markers as determined by immunophenotyping. A relatively high frequency (38%) of MTAase deficiency was seen in ALL of T-cell origin. Nonmalignant hematopoietic cells from three patients with MTAase-deficient leukemias had readily detectable enzyme activity. Chromosomal abnormalities were detected in four of the seven MTAase-deficient cases in which karyotypic analysis was performed. No consistent karyotypic defect was apparent, and only one case displayed changes in chromosome 9, the putative location of the MTAase structural gene. The clinical findings among the enzyme-deficient cases were unremarkable except that all patients were male (P less than .01). Only one patient had "lymphomatous" features. We conclude that MTAase deficiency occurs in a wide variety of acute leukemias, that the lack of enzyme activity is specific to the malignant cells, and that an increased incidence occurs in ALL of T-cell origin. Furthermore, no specific gross chromosomal abnormality is associated with the enzyme deficiency. The marked male predominance in patients with MTAase-deficient acute leukemias suggests involvement of the X chromosome in the loss of enzyme activity. The absence of MTAase in some leukemias may be therapeutically exploitable.
Acute Disease↗
Benign oncocytic endocrine tumor of the pancreas in a patient with polyarteritis nodosa.
An 8-cm mass in the tail of the pancreas was resected from a 40-year-old man with polyarteritis nodosa. The tumor cells contained abundant, finely granular, eosinophilic cytoplasm arranged in a gyriform pattern that suggested the tumor was an oncocytoma of the endocrine pancreas. Electron microscopy confirmed that the tumor was an oncocytoma by demonstrating tumor cell cytoplasm packed with mitochondria. Ultrastructural and immunocytochemical studies confirmed the neuroendocrine nature of the tumor by demonstrating dense-core, membrane-bound structures consistent with neurosecretory granules and neuron-specific enolase immunoreactivity. No immunoreactivity for insulin, glucagon, gastrin, somatostatin, or pancreatic polypeptide was found. No human chorionic gonadotropin alpha-chain immunoreactivity was detected. The patient is well without evidence of tumor five years after operation. The apparently benign behavior of the pancreatic endocrine oncocytoma reported here is in contrast to the malignant nature of another case reported recently.
Adult↗
Isolated metastasis to small bowel from anaplastic thyroid carcinoma. With a review of extra-abdominal malignancies that spread to the bowel.
Symptomatic involvement of the small bowel by isolated metastasis from an extra-abdominal primary malignancy is rare, most commonly resulting from malignant melanoma and lung cancer. A few other extra-abdominal tumors, not including thyroid cancer, have been documented on rare occasions to present with small-bowel involvement as the first evidence of metastasis. We report a case of anaplastic thyroid carcinoma with isolated symptomatic metastasis to the small intestine. We review the literature regarding the frequency and origin of extra-abdominal malignancies developing small-bowel metastases and the spectrum of clinical manifestations resulting from this syndrome.
Aged↗
Kaposi's-sarcoma-associated herpesvirus is detected in peripheral blood mononuclear cells of HIV-infected homosexuals more often than in heterosexuals.
PURPOSE: The Kaposi's-sarcoma-associated herpesvirus is thought likely to play an important part in the pathogenesis of Kaposi's sarcoma, which is the most common tumor in AIDS patients. To determine whether peripheral blood is also infected by the virus, we prospectively tested mononuclear cells from HIV-infected individuals, both with and without Kaposi's sarcoma. PATIENTS AND METHODS: Thirty-three patients with AIDS were studied. Twenty-three were homosexuals, and 10 of these patients had Kaposi's sarcoma. All 10 nonhomosexual patients were free of Kaposi's sarcoma. PCR amplification of peripheral blood mononuclear cells was performed for a 233-base-pair segment of Kaposi's-sarcoma-associated herpesvirus on all patients. Fisher's exact test was used to compare the patient groups. RESULTS: Kaposi's-sarcoma-associated herpesvirus sequences were detected in the peripheral blood mononuclear cells of homosexual men both with (7/10) and without (5/13) Kaposi's sarcoma. However, none of the nonhomosexual patients (0/10) had detectable virus. Therefore, those with Kaposi's sarcoma are at greater risk for Kaposi's-sarcoma-associated herpesvirus infection than patients without Kaposi's sarcoma, and among HIV-positive patients without Kaposi's sarcoma, homosexuals are more likely to have detectable Kaposi's-sarcoma-associated herpesvirus than are nonhomosexuals. In the homosexual patients, the presence of virus was unrelated to total CD4+ cell counts. A comparative dilutional analysis showed that the nonhomosexual patients had a low viral load in their peripheral blood mononuclear cells relative to most homosexuals with Kaposi's sarcoma. Sequential studies on two patients revealed clearing of the virus while on therapy; one patient was treated for HIV with the protease inhibitor indinavir, and the other patient was treated for Kaposi's sarcoma with liposomal doxorubicin. CONCLUSIONS: These results indicate that Kaposi's-sarcoma-associated herpesvirus is harbored in peripheral blood mononuclear cells of HIV-infected patients, and that the rates of infection are significantly higher in homosexual men compared with their nonhomosexual counterparts. The significance of viral clearing in response to therapy is unknown but warrants further study, as prophylactic treatment for this virus might alter the occurrence of Kaposi's sarcoma in this susceptible patient population.
AIDS-Related Opportunistic Infections↗