Treatment of hairy cell leukemia by leukapheresis: when, how, and why.
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Biomedical subjects
Publications and source records attributed to L T Yam.
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The clinical application of an immunohistochemical technique for prostatic acid phosphatase allowed the accurate diagnosis of metastatic prostatic carcinoma in 17 patients whose condition was not recognized by either clinical or histologic observations. The cardinal manifestations in these 17 patients included supraclavicular lymphadenopathy in 7, hilar lymphadenopathy in 1, pulmonary infiltration in 2, simulating carcinoma of the rectum in 4, fracture of femur in 1, orbital tumor in 1, and brain tumor in 1. A retrospective analysis of the radiologic features of these patients showed that the unusual manifestations were due to the route of metastasis, that is, direct invasion, lymphatic, and hematogenous. Radiologic studies, even in these unusual cases, are both useful in establishing the diagnosis and helpful in delineating the mode of metastasis of prostatic carcinoma.
A practical immunocytochemical method of demonstrating surface antigens of human blood cells on air-dried smears or other cytologic preparations has been developed. This method uses monoclonal antibodies as the primary antibodies and calf intestinal alkaline phosphatase as the enzymatic indicator. Combined staining with cytochemical stains for myeloperoxidase or nonspecific esterase on the same slide is also possible when needed. These methods are very useful for accurate identification of human blood cells on the commonly available clinical specimens and are very helpful in the diagnosis and classification of various hematologic neoplasms, including chronic lymphocytic leukemias, acute leukemias, and related diseases.
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Tartrate-resistant acid phosphatase activity determined by enzyme immunoassay was higher in the serum of cancer patients than that in normal blood donors. The highest activity was found among patients having malignancy metastatic to bone. The classic colorimetric method showed a broad range of values among normal blood donors, and the contrast between normal and cancer patients was less obvious. Most of the cancer patients had normal to low alkaline phosphatase activities.
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Nineteen patients with hairy cell leukemia were studied in order to define the hepatic changes in this disease and to correlate the morphologic changes in the liver with the clinical and biochemical findings. Although only eight of the patients had hepatomegaly, all 19 had microscopic mononuclear cell infiltration in the sinusoids or the portal areas or both. The severity of mononuclear infiltration in the liver correlated poorly with the size of the liver or spleen, the biochemical changes, or number of hairy cells in the blood. Abnormal serum biochemical values were present occasionally and were usually due to associated diseases or to complications of this disease. Elevated serum alkaline phosphatase activity was noted in four patients; three of them had granulomatous lesions in the liver. Unless the characteristic "clear cell" pattern is seen, the hepatic mononuclear cell infiltration may not be diagnostic of hairy cell leukemia and, in many instances, may not even be suggestive of neoplasia. A new technique for demonstrating tartrate-resistant acid phosphatase activity in methacrylate-embedded sections was developed, which allowed identification of hairy cells in the liver biopsy specimens of all five patients so studied. The authors concluded that liver involvement is common in this disease.
Adenocarcinoma of the prostate may occasionally present as distant metastatic disease. This tumor, if accurately identified, is amendable to effective treatment with hormonal manipulations. We have seen nine patients with prostatic cancer presenting as metastatic adenocarcinoma of undetermined origin: two presented with involvement in the lung and the mediastinum, five with left supraclavicular lymphadenopathy and two with known prostatic cancer with stable disease presented with supraclavicular lymphadenopathy. By employing an immunoperoxidase technique using prostatic acid phosphatase as the marker for the prostatic cells, we demonstrated the presence of the prostatic enzyme antigen in the paraffin embedded tissues from the metastatic tumor. This finding directed further investigation of the prostate gland leading to the discovery of the primary tumor in all nine patients. It may be beneficial to use this technique in all male patients with adenocarcinoma of undetermined primary site.
Hairy cell populations of greater than 90 purity were prepared from six samples obtained from four patients with leukemic reticuloendotheliosis (LRE). These then were analyzed for surface immunoglobulin (SIg) and antigens specified by a panel of monoclonal antibodies. The hairy cells from all patients displayed SIg and antigens reactive with OKIa-1 and OKM-1 antibodies; these markers often were expressed simultaneously. T-cell-specific antigens were not displayed on the surface of hairy cells. The simultaneous expression of SIg and OKM-1 which ordinarily are unique for B cells or myeloid cells, respectively, suggests that hairy cells may represent an aberrant form of either cell type with defective regulation of antigen expression. It alternatively suggests the possibility that B cells and myeloid elements develop along a common pathway and that the hairy cell is a component of such a pathway.
Two patients with systemic angioendotheliomatosis had prominent constitutional symptoms such as fever, loss of weight, and general weakness, and had multiple organ dysfunctions, including bizarre neurologic findings and dementia. Severe anemia that required frequent blood transfusions also was present. One patient developed severe hemolysis and hypersplenism that required splenectomy for relief; the other patient had intravascular hemolysis and autoimmune hemolytic anemia, which were treated unsuccessfully with conservative measures. In both cases, postmortem examination showed many large, noncohesive malignant cells within the lumen of the blood vessels in many of the organs. There was no infiltration or replacement of the normal tissues by the tumor cells. Histochemical studies showed that the tumor cells were pyroninophilic but did not have cytoplasmic immunoglobulins or activity of chloroacetate esterase and muramidase. The cells showed factor VIII antigen in their cytoplasm. Systemic angioendotheliomatosis may represent a true neoplastic process of the vascular endothelial cells.
A simple immunocytochemical method using calf intestinal alkaline phosphatase as the enzymatic indicator to demonstrate surface antigens on human blood cells has been developed. The blood cells were labeled with cell specific monoclonal antibodies followed by linkage with an antiimmunoglobulin alkaline phosphatase conjugate. Cytochemical demonstration of alkaline phosphatase activity on the blood cells reflects the presence of surface antigens on these cells. The effects on the cytochemical reaction of fixation, substrates, couplers, activators and inhibitors, and storage of cytologic materials have been examined systematically. The best staining conditions are to incubate labeled smears in a 0.04 M barbital buffer at pH 7.6 containing 30 mg% naphthol AS-TR phosphate, 40 mg% fast red ITR, and 1 mM levamisole. This method is both sensitive and specific and appears most practical for objective identification of the human blood cells.
The human cytotoxic/suppressor T-cell subpopulation has characteristic cytoplasmic granules and unique surface antigens that are recognized by OKT8 monoclonal antibody. Using immunocytochemical techniques, we identified three patients with an indolent T-cell lymphoproliferative disorder having morphologic and immunocytochemical characteristics of a cytotoxic/suppressor T-cell phenotype. Review of the literature revealed 22 similar cases, which were frequently associated with neutropenia and anemia. These cases may represent a distinct clinicopathologic entity with an apparently indolent clinical course that differs from other T-cell lymphoproliferative disorders, which are generally considered to be more aggressive diseases.
Systemic mast cells disease (SMCD) is an uncommon disorder that constitutes approximately 10% of all mastocytoses. Diagnosis requires a substantial degree of clinical suspicion, which may not be present if characteristic skin lesions of urticaria pigmentosa are not observed. Lack of well-defined histopathologic features for the disease have delayed or prevented the diagnosis of SMCD. An initial diagnosis of "myeloproliferative disorder," chronic granulocytic leukemia, or myelofibrosis is frequently made. Study of the clinical and pathologic features of 26 cases of SMCD indicated that affected patients are generally middle aged and may have had urticaria pigmentosa for many years. Gastrointestinal symptoms are common, and splenomegaly and hepatomegaly along with radiographic evidence of generalized bone disease are usually noted. Hematologic factors are highly variable. Characteristic histopathologic features of SMCD are described for bone marrow, lymph nodes, liver, and spleen. The authors consider tissue fixation and staining methods to help identify mast cell lesions.
A patient had chronic neutrophilic leukemia. The characteristic clinical features of this disease include long-standing neutrophilia in the absence of an underlying disease, marked granulocytic hyperplasia in the bone marrow, increased leukocyte alkaline phosphatase activity, and absence of Philadelphia chromosome in the marrow cells. The patient survived for six years but eventually died of acute erythroleukemia. Neutrophilic leukemia although rare, possesses characteristic features sufficient to be considered a distinct clinical and hematologic entity.
Examination of the blood of 40 patients with leukaemic reticuloendotheliosis (LRE) revealed a drastic reduction in monocyte numbers (mean 74/microliter) when compared to a normal group of 33 (mean 442/microliter). Repeated blood studies in 8 LRE patients were made over periods of 2 months to 5 years and monocytopenia was observed to be a persistent phenomenon. Similarly, tissues from 29 patients showed an overall decrease in numbers of monocytes/ histiocytes when compared with those of 73 control subjects. Skin window examinations in all 11 patients so studied showed marked reduction or absence of monocyte response to inflammation. 2 exceptional cases to this trend are noted. In one, circulating monocyte levels remained normal over a 14-month period while examinations of blood and marrow in this case showed few hairy cells. In another case, severe and persistent monocyte deficiency was noted during a 2-year period of unsuccessful treatment. When he eventually responded to low dose chlorambucil and his Hb rose from 40-140 g/l and WBC became normal, the number of circulating monocytes also became normal.
Electrophoresis and ion-exchange column chromatography were used to separate the wide varieties of acid phosphatases with different biological and clinical significance. Band 0 was very strong in ascitic cells with many autophagic vacuoles, indicating a role in autophagic function. Band 1 was a membrane-bound acid phosphatase, seen mainly in the microsomal fraction. Band 3 was the major lysosomal acid phosphatase of all nonprostatic tissues. Bands 2 and 4 were antigenically identical to each other, and were observed in unusually high amounts in the prostate. The different electrophoretic mobility between bands 2 and 4 was due to their carbohydrate content. Band 5 was a characteristic enzyme of the osteoclast. The tartrate-sensitive enzymes included bands 0 through 4. Only band 5 was tartrate resistant. The tartrate-resistant acid phosphatase of erythrocytes was not detected by the electrophoresis method. Clinical applications were seen for both bands 2 and 5. Band 2 was a secretory enzyme, normally secreted into the seminal plasma. Band 2 was absorbed into the blood circulation in some prostatic cancer patients. A small amount of bands 2 and 4 was observed in nonprostatic tissues. The diagnostic value of band 2 resulted from its extremely high concentration in the prostate. Band 5 was not observed in the normal prostate. A high concentration of band 5 was observed in hairy cells, Gaucher cells, and osteoclasts. The serum level of band 5b was an indicator of osteoclastic activity in the bone. Elevation of band 5b in serum was observed in normal children during physiological bone growth, in Gaucher's disease, and in malignancies metastasized to bone.
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