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Combining morphology and flow cytometric immunophenotyping to evaluate bone marrow specimens for B-cell malignant neoplasms.

For this study, 188 bone marrow core biopsy specimens and aspirates analyzed morphologically and by flow cytometric immunophenotyping (FCI) in patients with a previous or new diagnosis of B-cell non-Hodgkin's lymphoma or mature B-cell leukemia were retrospectively reviewed to evaluate patterns of involvement and the usefulness of FCI. The morphologic and FCI results were categorized as follows: positive by morphologic examination and by FCI (39.9%); negative by morphologic examination and by FCI (41.5%); positive by morphologic examination and negative by FCI (11.7%); negative by morphologic examination and positive by FCI (2.6%); suggestive of malignant neoplasm by morphologic examination and positive by FCI (2.1%); and suggestive of malignant neoplasm by morphologic examination and negative by FCI (2.1%). Thus, in 81.4% of cases the morphologic and FCI findings were completely concordant. In 11.7% of cases, the morphologic examination alone detected involvement, and in 4.7% of cases, the FCI data detected involvement in a morphologically negative or "suggestive" bone marrow core. Combining these modalities is essential to evaluate bone marrow specimens for involvement by B-cell non-Hodgkin's lymphoma or B-cell leukemia.

Antibodies, Monoclonal↗

A monoclonal antibody cocktail for detection of micrometastatic tumor cells in the bone marrow of breast cancer patients.

We investigated whether monoclonal antibodies (MoAbs) reactive against both acidic and basic cytokeratins alone were sufficient to detect minimal numbers of contaminating epithelial tumor cells in the bone marrow of breast cancer patients. Monoclonal anti-cytokeratin antibodies (AE1 and AE3) were used to stain 14 breast carcinomas by the avidin-biotin-peroxidase technique. Nine tumors (64.3%) showed high reactivity and five (35.7%) showed low or moderate reactivity. Nine MoAbs that proved to be unreactive to light density bone marrow cells by immunoalkaline phosphatase histochemistry were screened for reactivity to breast carcinomas having only low or moderate positivity to cytokeratin antibodies. Three of nine MoAbs showed high percentages of positivity and were selected to supplement the anti-cytokeratin antibodies for immunohistochemical detection of minimal marrow disease in breast cancer patients. A MoAb cocktail was prepared, further tested for reactivity to another five breast carcinomas, and compared with cytokeratin staining alone. The cocktail labeled 100% of carcinoma cells in all the examined specimens. To determine the sensitivity of this panel for detecting minimal numbers of contaminating tumor cells in bone marrow, in vitro mixing experiments were performed. T47D breast carcinoma cells were mixed with bone marrow mononuclear cells at ratios from one tumor cell per 10 bone marrow cells up to one tumor cell per 1 x 10(6) marrow cells, and cytospin preparations were subsequently stained with the MoAb cocktail by the immunoalkaline phosphatase method. Our approach could detect one tumor cell in 1 x 10(5) hematopoietic cells.

Antibodies, Monoclonal↗

Medulloblastoma simulating acute myeloid leukemia: case report with a review of "myeloid antigen" expression in nonhematopoietic tissues and tumors.

Medulloblastoma is a primitive neuroectodermal tumor arising in the posterior fossa usually in the first decade of life. Systemic metastases are infrequent at diagnosis and usually occur after surgical resection or shunt placement. We report a rare case of medulloblastoma in an 18-year-old woman who presented with headache, leukopenia, and anemia. Neurologic examination was normal. Bone marrow evaluation revealed primitive cells morphologically resembling blasts. By flow cytometry, these cells lacked CD45 and expressed CD13/33, CD15, CD34, HLA-DR, and strong CD56. The presence of myeloid antigens and CD34 suggested acute myeloid leukemia; however, the bone marrow core biopsy architecture and tumor cells in cerebrospinal fluid were more compatible with a nonhematopoietic tumor. Further workup revealed a cerebellar mass, and a diagnosis of desmoplastic medulloblastoma was made. To our knowledge, this is the first reported case of a nonhematopoietic small round blue-cell tumor expressing multiple myeloid antigens and CD34 by flow cytometry.

Adolescent↗

[Clinical thinking and decision making in practice. A patient with anal cancer and hypercalcemia].

A 57-year-old male patient, recently known with an anal carcinoma with inguinal lymph node involvement, was admitted because of anorexia, nausea, vomiting and constipation. On physical examination the patient was dehydrated, and a systolic murmur, grade III/VI, punctum maximum apex cordis, was heard. Serum calcium was raised (4.50 mmol/l), as was the serum creatinine (328 mumol/l). Both values had been normal 14 days before admission. Serum parathormone was suppressed. A bone scan did not reveal evident lesions in the skeleton. FDG-PET scan showed uptake of the tracer into the bone marrow. A bone biopsy showed metastasis of a squamous cell carcinoma. Shortly after that the patient died. Hypercalcaemia is associated with cancer. Colorectal/anal carcinomas have a low incidence of hypercalcaemia. The prognosis of patients with cancer associated with hypercalcaemia is poor.

Anus Neoplasms↗

Phase II radioimmunotherapy trial with 131I-CC49 in colorectal cancer.

BACKGROUND: Radiolabeled CC49, a second generation high affinity monoclonal antibody (MoAb) reactive with tumor-associated glycoprotein 72 (TAG72) has undergone previous Phase I testing in patients with colon cancer. Based on this report, the authors treated 15 refractory metastatic colon cancer patients with 131I-CC49 to determine its overall toxicity and the response to therapy of patients treated with it. METHODS: Patients received 75 mCi/m2 131I-CC49 (20 mg MoAb) intravenously for a period of 30-60 minutes. Whole body retention was derived from the measured dose-rate of I-131 monitored daily at 1 m using an ion chamber. Two whole-body and static-gamma camera images were taken of patients on days 4 and 7 after the infusion. RESULTS: Nonhematologic toxicity (Grade 1-2) consisted of nausea (two patients), arthralgias (three patients), transient fever and chills (two patients), and transient blood pressure changes (two patients). At 4-5 weeks posttreatment, reversible Grade 3-4 thrombocytopenia was observed in 7 of 15 patients, and reversible Grade 3-4 granulocytopenia was observed in 6 of 15 patients. Twelve of 13 patients tested developed human anti-mouse antibody (range, 161 to > 20,000 ng/ml) at 6-8 weeks postinfusion. Mean +/- SD whole-body half-life (whole-body retention) of 131I-CC49 was 57.3 +/- 13.4 hours. Tumors were seen in all patients. In two of three patients treated a second time, an increased whole body clearance rate correlated with elevated human anti-mouse antibody, reduced uptake in tumor, and enhanced uptake in the thyroid. Estimated tumor doses ranged from 19-667 rads. Red marrow dose estimated from whole body retention ranged from 60 to 117 rads and correlated with decreases in platelet count. No objective tumor responses (i.e., partial or complete) were observed. CONCLUSIONS: Despite minimal toxicity and favorable tumor uptake, efficacy has been limited at this dose and schedule.

Animals↗

131I-meta-iodobenzylguanidine scintigraphy in patients with neuroblastoma.

Twenty-six studies by meta-(131I)-iodobenzylguanidine scintigraphy (131I-MIBG), 26 studies by 67Ga-citrate and 33 99mTc-hydorxymethylene diphosphate (99mTc-HMDP) scintigraphic studies were performed for 10 patients with abdominal neuroblastoma. Comparing the 131I-MIBG images obtained at 24, 48 and 72 h, the 48-h image was the most distinctive for the tumor. Intrabdominal primary lesions, which ranged from bean to fist-size, were visualized in 7/7 cases (100%) by 131I-MIBG, 4/7 cases (57%) by 67Ga-citrate and 4/8 cases (50%) by 99mTc-HMDP before surgery and at diagnosis. In serial follow-up of these patients after starting chemotherapy, 131I-MIGB detected 100% of regressing primary tumors. Studies of 5 postoperative patients showed negative images for the primary tumor in all 3 scintigraphies except one in whom 131I-MIBG was positive, but not 67Ga-citrate or 99mTc-HMDP, for an unresectable residual tumor. 131I-MIBG also detected metastatic lesions not predicted by 67Ga-citrate or 99mTc-HMDP and reflected tumor progression more sensitively than known tumor markers such as urinary vanillylmandelic acid (VMA), homovanillic acid (HVA), serum neuron-specific enolase (NSE) and ferritin. These findings indicate that the 48 hr 131I-MIBG scintigraphy is superior to 67Ga-citrate or 99mTc-HMDP images and to other biochemical markers in monitoring the effect of treatment on neuroblastoma.

3-Iodobenzylguanidine↗

Radionuclides in oncology.

Radionuclides already have a major role in the daily practice of oncology and will, undoubtedly, be of even greater importance in the future. The variety of current and potential applications is shown in tab. 1. Their major use at this time is, in the broadest sense, for 'tumour scanning', which includes the evaluation of specific organs for the presence of tumour (usually with different radiopharmaceuticals for each organ) and the entire body (generalized tumour searches with radiopharmaceuticals like 67Ga-citrate or 111In-labeled bleomycin). The clinician uses these agents in the initial evaluation of extent of tumour (staging) and in the subsequent management of the patient with cancer to assess response to treatment, to reveal early relapse, and to assist in making decisions concerning treatment. The other potential roles for radionuclides are also briefly considered in this review.

Abdominal Neoplasms↗

Human breast cancer cells share antigens with the myeloid monocyte lineage.

We have examined the expression of several myeloid cell associated antigens, some of which are involved in myelomonocyte adhesion, in seven well characterized human breast cancer cell lines, since common properties of adhesiveness and migration are found in haemopoietic cells and epithelial cancer cells. Five of these cell lines were of metastatic origin and two were derived from primary breast carcinoma. Antigenic expression was evaluated by immunofluorescence (IF), flow cytometry (FCM), radioimmunoassay on live cells (RIA) and immunoperoxidase staining. None of these cell lines expressed T or B lymphoid specific antigens. Myeloid antigens My4, MO1, and MOF11 (derived from the hybridization of mouse X63 - Ag8 cells with spleen cells from Balb/c mice immunized with purified human monocytes) were expressed in the 7 cell lines. Leu M1, Leu M3, My9, and MO2 antigens were expressed in some of the cell lines. Leu M2 and My7 antigens were not expressed or at very low levels. The expression of these myeloid antigens was also tested by immunoperoxidase staining, and found on frozen sections of normal mammary gland, fibroadenoma of the breast, primary breast cancer, and lymph node and skin metastases of breast tumours. This common expression in epithelial breast cells and in myeloid cells might be related to common biological functions such as interaction with extracellular matrix which precedes cell migration, a normal function of macrophages and an abnormal function expressed or amplified in human cancer epithelial cells.

Antibodies, Monoclonal↗

[Myelomatosis].

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Bone Marrow↗