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Diagnosis of iron deficiency anemia in the elderly by transferrin receptor-ferritin index.

BACKGROUND: The diagnosis of iron deficiency anemia (IDA) in the elderly is difficult because of the prevalence of chronic diseases, which can cause anemia with high ferritin levels, even in the presence of iron deficiency. Therefore, we studied the sensitivity and specificity of a serum transferrin receptor assay, which is not affected by chronic diseases, in the diagnosis of IDA in elderly patients. METHODS: We performed a prospective controlled study of 49 consecutive male and female patients older than 80 years who were admitted to an acute geriatric department. Bone marrow aspirate confirmed IDA in all 49 patients. Fourteen additional patients, also older than 80 years, with anemia but without evidence of iron deficiency on results of bone marrow examination, served as a control group. All patients underwent evaluation by means of a detailed medical history and results of complete physical examination, routine blood tests, and specific tests for diagnosis and evaluation of anemia. Examination of bone marrow aspirate was performed for all patients. Levels of transferrin receptor in serum were determined by means of a specific enzyme-linked immunosorbent assay. The transferrin receptor-ferritin index (TR-F index) was defined as the ratio of serum transferrin receptor level to log ferritin level. RESULTS: Only 8 patients could be diagnosed as having IDA by means of routine blood test results (serum iron, ferritin, and transferrin saturation levels). In contrast, the TR-F index disclosed IDA in 43 of the 49 patients, thus increasing the sensitivity from 16% to 88%. CONCLUSIONS: The diagnosis of IDA in the elderly by means of routine blood tests has a very low sensitivity. The TR-F index is much more sensitive, and when results are positive, the TR-F index can eliminate the need for bone marrow examination.

Aged↗

False-negative rates of tumor metastases in the histologic examination of bone marrow.

Recent reports have claimed that bone marrow histology is less sensitive for detecting metastatic tumor than are other methods of marrow examination. These reports, however, did not specify methodologic information, such as the number of slides or tissue sections reviewed. To demonstrate the importance of specifying such information, we reviewed archival, tumor-positive marrow biopsy specimens from our laboratory. By means of a statistical model, we calculated the false-negative rates that would have occurred had random histologic review entailed fewer than 10 slides. Our model demonstrates a progressive increase in the percentage of false-negative diagnoses with the review of fewer slides, e.g., from 1% with review of nine slides to as high as 24% with review of only two slides. We conclude that the number of histologic slides and tissue sections reviewed should be specified when comparing bone marrow histologic examination with other techniques of marrow assessment.

Biopsy↗

Examination of bone marrow biopsy specimens and staging of small cell lung cancer.

Bone marrow biopsy specimens were evaluated retrospectively in 63 of 88 (72%) patients with small cell lung cancer (SCLC). Significant differences were not found between extensive disease (ED) patients with or without bone marrow metastases in survival nor in nadirs of leucocytes or platelets subsequent to chemotherapy. A panel of antibodies was used to investigate whether immunohistochemical analysis on routinely processed bone marrow biopsy specimens could detect marrow metastases more effectively than conventional microscopy. In histologically proven marrow metastases and in control SCLC sections a combination of an antibody against cytokeratin 8, 18 and 19 (NCL5D3) and an antibody against neurone specific enolase was validated for detection of metastases. In histologically negative marrow biopsy samples, however, this combination did not yield any additional tumour positive cases. Therefore, histological evaluation of a bone marrow biopsy specimen, even when analysed by immunohistochemistry, does not contribute information relevant for staging, therapy evaluation or prognosis in SCLC.

Aged↗

[Histomorphologic examinations of bone marrow of patients with gynecologic malignoma before, during, and after radiotherapy (author's transl)].

The histomorphological changes in the bone marrow were investigated in 9 patients treated by primary irradiation for cervical cancer. Bone marrow specimens were obtained by the Yamshidi puncture technique from the spina iliaca posterior superior after radiotherapy with different radiation dosages, as well as four months after termination of radiotherapy. All patients showed disappearance of almost all the haematopoietic cells in the irradiated area and, with the exception of one patient, no repopularization of the bone marrow or fibrosis. The possible mechanisms leading to these results are discussed and comparisons with the international literature are drawn.

Aged↗

Histologic examination of bone marrow core biopsy specimens has limited value in the diagnosis of mycobacterial and fungal infections in patients with the acquired immunodeficiency syndrome.

Bone marrow cultures and biopsy specimens are commonly obtained to rule out disseminated infections, especially in persons with the acquired immunodeficiency syndrome (AIDS) and cytopenias. Using culture as the gold standard, we reviewed 130 consecutive bone marrow cores obtained from 114 AIDS patients along with results of concurrent blood and/or bone marrow aspirate cultures to determine the usefulness of histologic examination for diagnosis of mycobacterial and fungal infections. We also compared the ability of Ziehl-Neelsen, auramine-rhodamine (AR), polyclonal antibody to Mycobacterium bovis (Ab), and Gomori's methenamine silver staining to detect infections. Twenty-seven patients had mycobacterial infection (25 Mycobacterium avium-intracellulare complex cases and two Mycobacterium tuberculosis cases) detected by blood and/or bone marrow cultures. The maximum sensitivity of histology was 50% when the auramine-rhodamine stain and the polyclonal antibody to M bovis were used in combination. The single best stain was auramine-rhodamine, with a sensitivity of 44%, followed by the polyclonal antibody to M bovis (35%). Granulomas were observed in nine cases of mycobacterial infection and did not correlate with the presence of stainable organisms. Of seven patients with positive fungal cultures of bone marrow, four had granulomas and a positive Gomori's methenamine silver stain, one had only a positive stain, and two had neither granulomas nor a diagnostic stain. Overall, granulomas were not sensitive for the detection of infections when culture-proven mycobacterial and fungal cases were evaluated together. We conclude that bone marrow examination has a limited value in the routine evaluation of common opportunistic infections in AIDS patients and recommend that less-invasive tests, such as blood cultures, be obtained initially in most circumstances.

AIDS-Related Opportunistic Infections↗

How reliable is histologic examination of bone marrow trephine biopsy specimens for the staging of non-Hodgkin lymphoma? A study of hairy cell leukemia and mantle cell lymphoma involvement of the bone marrow trephine specimen by histologic, immunohistochemical, and polymerase chain reaction techniques.

Analysis of non-Hodgkin lymphoma (NHL) involvement of bone marrow trephine biopsy specimens by morphologic features and immunohistochemistry is often difficult, and the criteria for involvement are ill defined. We compared the morphologic and immunohistochemical analysis of B-cell NHL involvement with immunoglobulin heavy chain gene (IgH) rearrangement analysis by polymerase chain reaction (PCR) amplification of the complementarity determining region 3 (CDR3) in bone marrow biopsy specimens from patients with mantle cell lymphoma (n = 53) or hairy cell leukemia (n = 71). By combing morphologic features and phenotype, 54 specimens were considered positive, 62 negative, and 8 inconclusive. PCR analysis showed clonal IgH rearrangements in 46 positive and 6 inconclusive specimens. No clonal IgH rearrangements were present in 61 negative specimens. The 1 false-positive and most false-negative PCR results were likely due to sampling error or DNA degradation of the fixed tissues. In most cases, bone marrow involvement by NHL can be identified by histologic and immunohistochemical examination. Furthermore, clonality of the B-cell population can be detected by amplification of the IgH CDR3 on DNA extracted from bone marrow trephine biopsy sections, which can be helpful in cases diagnosed as inconclusive.

Bone Marrow Examination↗

Megaloblastic marrow in macrocytic anaemias at Kenyatta National and M P Shah Hospitals, Nairobi.

OBJECTIVE: To determine the diagnostic value of megaloblastic marrow in patients with possible vitamin B12 and/or folate deficiency and to look for criteria that could be used in diagnosis of vitamin B12 deficiency. DESIGN: Prospective study. SETTING: Kenyatta National Hospital and M P Shah Hospital, Nairobi. SUBJECTS: Patients of all age groups and both sexes presenting with clinical and blood picture of macrocytic anaemia. MAIN OUTCOME MEASURES: Response to vitamin B12 injections. Vitamin B12 deficiency diagnosed by the following methods: Vitamin B12 serum level assays alone, bone marrow examination alone and both vitamin B12 assays and bone marrow examination. Response was measured clinically and by increase in haemoglobin level after three weeks of treatment. RESULTS: Three hundred and forty-three patients were evaluated; 156 (45.5%) were males, and 187 (54.5%) females. Age range was 13-80 years and a mean of 37.7 years. Initial investigations were as follows: 21.9% had vitamin B12 assays only, 59.2% bone marrow examination only and 19.9% both vitamin B12 assayed and bone marrow evaluated. Haemoglobin increase after a total of 6,000 mcg of vitamin B12 was between 2.6-4.6 g/dl in three weeks. Reticulocytes measured on day ten ranged between 12% and 17%. Uniform improvement in all patients was observed for white blood cells (WBC) and platelet counts. Other significant results and observations included clinical improvement in the signs and symptoms of anaemia after the 6,000 mcg injection of vitamin B12 given over three weeks. Serum folic acid level was determined in 21% of cases and in all these it was normal. CONCLUSION: The important practical points were response to vitamin B12 in all cases and the importance of re-assessing patients after a total of 6,000 mcg of vitamin B12. Folic acid deficiency was not detected. Patients in these two institutions with megaloblastic anaemia had vitamin B12 deficiency. It is proposed that a model consisting of oval macrocytosis on blood film and megablastic bone marrow be treated with vitamin B12 injections in settings where vitamin B12 serum level assays are not easily available.

Adolescent↗

Bone marrow necrosis diagnosed during life: clinical and laboratory features of extensive involvement.

Bone marrow necrosis occurred in two patients with non-Hodgkin's lymphoma. One had a four-year history of lymphoma for which he received combination chemotherapy. Severe bone pain, abdominal pain and fever occurred during the terminal part of his illness. The other patient presented initially with symptoms of bone pain and lymphadenopathy. At bone marrow examinations, both had anatomically extensive bone marrow necrosis with associated evidence of involvement by lymphoma. The previously recognized clinical features of bone marrow necrosis and its complications occurred in one or both of these illustrative cases, with the exception that bone tenderness was absent in both. Attempts were made to correlate the technetium-99m sulphur colloid scans with sites of disease as determined by the bone marrow examinations.

Aged↗

[Bone marrow changes in patients with thyroid carcinoma].

In 62 patients with thyroid carcinoma 79 MRI bone marrow examinations and 48 bone marrow scintigraphies were recorded before or following radioiodine therapy, to study the extent of bone marrow expansion. The results of both methods were the same. In 34/79 investigations normal findings were seen, in 18 the bone marrow expanded to the middle third and in 26 to the distal third of the femur. One patient showed bone marrow expansion to the tibia. These results were compared with the following data: histology of tumor, TNM-staging, time passed since thyroidectomy, accumulated doses of radioiodine therapy, results of 131I scintigraphy, hematological changes, thyroglobulin level, age and sex. No significant correlations were found between these and the bone marrow imaging results. Bone marrow changes in patients before radioiodine therapy were similar to those in patients treated with up to 48 GBq 131I. Blind biopsy of the posterior iliac crest in five patients showed slightly pathological reactive changes. In only 2/17 follow-up studies an increase of bone marrow expansion was seen. In 8 patients localized findings indicating malignant infiltration were observed. In 4/8 patients metastases of thyroid carcinoma were known or confirmed by pathological radioiodine uptake and in 2/8 metastatic involvement was assumed because of an increased thyroglobulin level.

Adenocarcinoma↗

[8;21 translocation acute myelocytic leukemia developing in the second trimester of pregnancy with successful delivery].

A 28 year-old woman in the 26th week of pregnancy was admitted to our hospital on February 6, 1993, because of anemia and thrombocytopenia. On admission, her hemoglobin was 8.2 g/dl, platelet count 6.3 x 10(4)/microliter, and WBC 6,300/microliter with 43% blasts. The bone marrow examination showed hyperplastic bone marrow with 38.8% blasts. She was diagnosed as having 8;21 translocation acute myelocytic leukemia (M2). In the 30th week of pregnancy, she gave birth to a 1449 g male infant by induction delivery. After DCMP therapy, complete remission was obtained. She has been in complete remission for 32 months and her child is growing healthy after overcoming an underweight condition due to premature birth, respiratory distress syndrome, circulation insufficiency and hyperbilirubinemia. This case suggests that in the event of second trimester pregnant patients with acute leukemia, we should wait for the proper time at which successful delivery can be expected, and then intensified remission induction chemotherapy should be carried out after the delivery.

Adult↗

Bone marrow metastases without cortical bone involvement in breast cancer patients.

Bone marrow involvement by breast carcinoma in the absence of demonstrable bone lesions is unusual. We report six patients with medullary tumor without demonstration of cortical bone abnormality on scan or radiographs. This represents 2.8% of 213 patients with breast cancer in which bone marrow examination was performed and 6.2% of those in which marrow involvement was demonstrated.

Adenocarcinoma↗

[Cytogenetic examination of bone marrow cells in stem cell diseases of myelodysplastic syndromes].

Cytogenetic examination of bone marrow cells was performed in 43 patients with myelodysplastic syndrome (MDS). MDS was diagnosed from bone marrow biopsies and smears according to the FAB classification. Of all 43 patients 24 (56%) had clonal karyotype changes including frequently monosomies of chromosomes #5 and #7 as well as interstitial deletions of the long arm of #5, 5 q-. Chromosome aberrations were observed in patients belonging to all FAB-subgroups, e.g. 11/15 patients with RA, 6/10 with RAEB, 5/9 with RAEB/T, and 1/9 with CMMoL. Complex chromosome aberrations involving more than 2 chromosomes occurred predominantly in patients with RAEB/T (4/9) but also in patients with RA (2/15) and RAEB (2/10), and correlated significantly (p less than 0.002) with a shorter survival. No correlation was found between chromosome aberrations and the development of ANLL in 9/43 patients (21%).

Aged↗