Diagnostic Problems Involved in Detection of Metastatic Neoplasms by Bone-marrow Aspirate Compared with Needle Biopsy RICHARD A. SAVAGE, M.D., GEORGE C. HOFFMAN, M.B., B.CHIR., F.R.C.PATH., AND KAREN SHAKER, R.N.
SINCE THE FIRST large series comparing histologic sections and aspirated smears of bone marrow, 1 repeated attempts have been made to evaluate the diagnostic usefulness of smears, clot sections, and needle biopsy of bone marrow for detection of metastatic neoplasms. Some investigators8 report a very high rate of correlation between aspirate smear and needle biopsy, and feel that the two procedures have essentially the same diagnostic usefulness, while others 5 - 7 feel that many metastatic neoplasms detected by histologic examination (either clot section or needle biopsy) will be missed when aspirates alone are examined. Occasional reports 7 suggest the diagnostic criteria for evaluation of suspected malignant cells in bone marrow are unreliable and will lead to an unacceptably high rate of false-positive reports—marrow aspirates called positive for neoplasms in patients who do not have a Received August 15, 1977; accepted for publication September 15, 1977. Address reprint requests to Dr. Savage: Department of Laboratory Hematology, The Cleveland Clinic Foundation, Cleveland, Ohio 44106.
From the Division of Laboratory Medicine, The Cleveland Clinic Foundation, Cleveland, Ohio
primary tumor and remain without evidence of one for prolonged follow-up periods. After review of simultaneous marrow aspirates and needle biopsies performed in our institution, we feel that both of these positions are extreme. We contend that in approximately 75% of cases called positive for metastatic neoplasms on the basis of needle biopsy a simultaneous marrow aspirate will also be called positive, and that the 25% discrepancy rate (aspirate negative-biopsy positive) is due to unavoidable physical changes induced in the marrow spaces by the presence of the neoplasm itself. Moreover, when the cytologic criteria detailed below are employed, falsepositive aspirate smears will be rare. The compromise position outlined is supported by results of other studies. 4,6 Materials and Methods Simultaneous marrow aspiration and biopsy procedures were performed through the same skin incision using the Jamshidi needle (Regular/Adult, 11-gauge). The site evaluated was primarily the posterior superior iliac spine, but occasionally, particularly in pediatric patients, other sites such as the anterior iliac crest were evaluated. Air-dried coverslip preparations were immediately made from the marrow particles and stained with Wright's stain. Biopsy specimens were fixed overnight in high-acid (decalcifying) Zenker's solution and stained with hematoxylin and eosin. Touch preparations were routinely made
Table 1. Correlation of Results of Bone Marrow A spiration vs. Biopsy Aspirate
1973-1975 1976
Biopsy Positive
Not Done
Positive
Suspect
Hypocellular
Negative
Correlation
88 38
43 7
33 22
1 1
5 2
6 6
73% 71%
0002-9173/78/1000/0623 $00.75 © American Society of Clinical Pathologists
623
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 6, 2016
Savage, Richard A., Hoffman, George C , and Shaker, Karen: Diagnostic problems involved in detection of metastatic neoplasms by bone-marrow aspirate compared with needle biopsy. Am J Clin Pathol 70: 623-627, 1978. Comparison of a large series of bone marrow aspirations with simultaneously performed Jamshidi needle biopsies showed 75% correlation between the two procedures for detection of metastatic neoplasms. In cases where the two methods disagreed, false-negative aspirations resulting from perineoplasty desmoplasia was the usual reason for the discrepancy. Cytologic criteria for the evaluation of suspected neoplastic cells in aspirate preparations are discussed. (Key words: Bone marrow aspirate; Bone marrow biopsy; Metastatic neoplasm.)
SAVAGE, HOFFMAN AND SHAKER
624
1. (left). Intense desmoplasia and new bone formation elicited by metastatic carcinoma from the breast. No tumor was seen in the aspirate. Hematoxylin and eosin. x 150. FIG. 2 (right). Metastatic mammary carcinoma with desmoplasia coexisting with normal marrow foci, at top of picture. Normal marrow particles were present in the aspirate with no evidence of tumor. Hematoxylin and eosin. xl50.
from biopsies when the aspirate failed to show acceptable numbers of marrow particles by visual inspection of the unstained smear. Routine interpretations of the preparations were made by staff members of the Department of Anatomic Pathology for the biopsies and the Department of Laboratory Hematology and Blood Banking for the aspirate smears. Following issue of Table 2. Factors Responsible for Lack of Correlation of Biopsy and Aspirate 1973-1975
1976
Biopsy positive-aspirate negative Severe desmoplasia with preserved normal marrow foci Mild-moderate desmoplasia Scattered microfoci on biopsy Misinterpretation of aspirate
3 2 1 1
3 1 1 1
Biopsy negative-aspirate positive Misinterpretation of biopsy Misinterpretation of aspirate True aspirate (+)-biopsy (-)
2 3 1
* * *
* 1976 figures not included.
the final reports for each preparation, these separate evaluations were routinely collected, and the written reports were correlated by a member of the Laboratory Hematology staff. Slides were re-examined when a discrepancy between the results of the two evaluations was found by the reviewer. The aspirate smears examined were divided into three groups. Those called positive contained cytologically malignant cells, those called suspect contained clumps of distorted cells suggestive of neoplasm but not cytologically acceptable for diagnosis, and those labeled hypocellular contained no malignant foci and had differential distributions similar to that simultaneously present in the peripheral blood. Biopsy preparations were not referred to as hypocellular, but were instead evaluated descriptively for adequacy by evaluation of the cellular and histologic elements actually contained within each needle biopsy. Biopsy specimens were deemed suspect when foci of distorted cells or areas of crushed chromatin that could not be properly evaluated histologically due to crush artifact or other distortion were present. An
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 6, 2016
FIG
A.J.C.P. . October 1978
Vol. 70 • No. 4
METASTASES IN MARROW ASPIRATE AND BIOPSY
625
FIG. 3. Left: A typical cluster of neoplastic cells in the marrow aspirate. Wright's stain, x 160. Right: Higher magnification of the cells illustrated at left, showing features of malignancy described in the text. Wright's stain. x640.
attempt was made to minimize the numbers of specimens deemed hypocellular and suspect by examination of multiple recuts and multiple additional smears when the original material evaluated was deemed inadequate for exact diagnosis according to the criteria outlined above. All available material was re-examined without knowledge of the original evaluations, save for the fact that the reviewers were aware that a discrepancy existed between the results of the biopsy and the aspirate. The aspirates were reviewed by both the senior authors independently, and the biopsies were reviewed by one (RAS). No disagreement between the reviewers was found for any individual preparation. A special problem was encountered in evaluating pediatric patients' smears. In the majority of pediatric cases, simultaneous aspirate smear and biopsy combination evaluation was not done until mid-1976. However, in the period 1973-1975, three cases of aspirate-positive-biopsy-negative paired evaluations were discovered, and in each case, review showed that the aspirate had been called positive erroneously
on the basis of overinterpretation of cytologically equivocal cells. These cases are included in the second half of Table 1 but not counted for calculation of percentages of discrepancy, as the majority of the evaluations in the pediatric group were not combination aspirate-biopsy evaluations. Pediatric cases from 1976 represented a mixture of paired and unpaired evaluations and were not included in the study. Results Aspirate-negative-biopsy-positive cases formed the vast majority of discrepancies in the study. A detailed breakdown of these evaluations is shown in Table 2. Occasional cases of misinterpretation of biopsy or aspirate smear were encountered; the reasons for discrepancies in both aspirate-positivebiopsy-negative and aspirate-negative-biopsy-positive evaluations are summarized in Table 2. Reclassification of misinterpretations resulted in only slight changes. Two aspirates initially interpreted as negative were reclassified positive; two biopsy-negativeaspirate-positive evaluations were reclassified biopsy-
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 6, 2016
kx.
626
SAVAGE, HOFFMAN AND SHAKER
^
* *
FIG. 4. A solitary focus of neoplasm identified in the aspirate preparation. The biopsy showed numerous areas of prostatic carcinoma with dense perineoplastic fibroplasia. Wright's stain. xl60.
positive-aspirate-positive, and one biopsy-positive aspirate-negative evaluation became biopsy-negative aspirate-negative on review. These changes largely cancelled one another out, so that the correlation rate changed only slightly. The results were divided into two time periods. Correlation between biopsy and aspirate was determined for 1973-1975, and a separate correlation was determined for 1976. The correlation rate changed only slightly, from 73% in 1973-1975 to 71% in 1976. This correlation rate agrees with those in other published series.3-4 Analysis for the reasons of this lack of correlation indicated that most of the discrepancies (five of seven in 1973-1975; four of six in 1976) were due to the coexistence in the bone marrow of normal marrow and metastatic foci that produced perineoplastic fibroplasia and sometimes, new bone formation (Fig. 1). Such marrows need not appear hypocellular on aspirate, as islands of fibrosis may be interspersed with residual normal marrow (Fig. 2). Such normoblastic foci were aspirated readily, giving the
impression of an uninvolved marrow on the aspirate smear preparation. Only when the desmoplasia was severe would the aspirate smear produce a dry tap or be hypocellular. Minute foci of neoplasm on biopsy were occasionally encountered, and not surprisingly the simultaneous aspirate smears for these cases were negative. However, surprisingly small amounts of neoplasm could be detected by painstaking screening of the entire aspirate preparation and careful cytologic evaluation of the suspect foci detected by the screening procedures. Careful cytologic evaluation of the abnormal cells detected is of utmost importance in the correct classification of suspect cells found in the bone marrow aspirate smears. Very high false-positive rates were found by some investigators 7 ; analysis of published illustrations in this work suggests that atypical megakaryocytes or histiocytes were incorrectly interpreted by these investigators. 6 Cytologic evaluation should be based on clusters and masses of suspect cells, as evaluation of isolated cells has been proved to be misleading. 711 " 13 Useful cytologic criteria 11-14 include nuclear pleomorphism within the clump of suspect cells, irregular hyperchromatic condensations within the nucleus, prominent bluish nucleoli, a syncyntial appearance of the cells within the mass, and indistinct cytoplasmic borders with smudging (Fig. 3). Even with severely hypocellular specimens, isolated clumps of malignant cells could be readily detected (Fig. 4). Six aspirate-positive-biopsy-negative simultaneous evaluations were found in this study (Table 2). In two instances misinterpretations of the biopsies had resulted in false-negative initial evaluations; in the other three, misinterpretations of distorted osteoblasts or histiocytes on the aspirate resulted in discrepancies. No false-positive evaluation due to misinterpretation of megakaryocytes was encountered. The sixth case, on review, was confirmed to be a true aspirate-positive-biopsy-negative evaluation, with both specimens considered adequate by the criteria outlined above. The value of careful screening under intermediate power is illustrated by this series and by that of Garrett and associates, 8 in which screening technics doubled the rate of detection of metastatic neoplasms in aspirate smears compared with a previous study of patients at the same institution. 5 The sensitivity of either aspiration or biopsy for detection of neoplaspis metastatic to the marrow was not evaluated in the study. Published rates of detection vary widely, from 1.2% in an unselected series of aspirate preparations 11 to approximately 10-20% in series in which the members of the population evaluated were known to have primary neoplasms.2-5-8-13 A study 15 comparing ability to detect neoplasms in bone
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 6, 2016
.
A.J.C.P. • October 1978
Vol. 7 0 . No. 4
METASTASES IN MARROW ASPIRATE AND BIOPSY
References 1. Agress H: Comparative study of spreads and sections of bone marrow. Am J Clin Pathol 27:282-299, 1957 2. Anner RM, Drewinko B: Frequency and significance of bone marrow involvement by metastatic solid tumors. Cancer 37:1337-1344, 1977
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 6, 2016
marrow aspirates performed on cadavers with the detection ability of subsequent dissection and routine gross and microscopic autopsy examination showed that 10% of the cadavers had metastases demonstrated on aspiration smear, compared with 34.5% by dissection and histologic autopsy evaluation. Thus, bone marrow aspiration appears to be able to detect about 28% of the cases with actual osseous metastases. Limitations of bone-marrow aspirate smears for detection of metastatic neoplasms are obvious from this study. Although aspirate smears should be considered complementary to biopsy for detection of metastases, good aspirates can yield useful information regarding morphology and maturation of hematopoietic cells. Additionally, most series5,8-912 suggest a higher rate of detection of neoplasms when the two procedures are performed simultaneously. Our practice at present is to perform aspiration plus biopsy or biopsy alone, when hematologic indices of peripheral blood appear adequate, for detection of metastatic neoplasms involving bone marrow.
627
3. Bearden JD, Ratkin GA. Coltman CA: Comparison of the diagnostic value of bone marrow biopsy and bone marrow aspiration in neoplastic disease. J Clin Pathol 27:738-740, 1974 4. Brunning RD, Bloomfield CD, McKenna RW, et al: Bilateral trephine biopsies in lymphoma and other neoplastic disease. Ann Intern Med 82:365-366, 1975 5. Conteras E, Ellis LD, Lee RE: Value of the bone marrow biopsy in the diagnosis of metastatic carcinoma. Cancer 29:778-783, 1972 6. Ellman L: Bone marrow biopsy in the evaluation of lymphoma, carcinoma and granulomatous disorders. Am J Med 60: 1-7, 1976 7. Emerson CP, Finkel HF: Problems of tumor cell identification in the bone marrow. Cancer 17:1527-1532, 1966 8. Garrett TJ, Gee TS, Lieberman PH, et al: The role of bone marrow aspiration and biopsy in detecting marrow involvement by nonhematologic malignancies. Cancer 38:2401-2403, 1976 9. Grann V, Pool JL, Mayer K: Comparative study of bone marrow aspiration and biopsy in patients with neoplastic disease. Cancer 19:1878-1900, 1966 10. McFarland W, Dameshek W: Biopsy of bone marrow with the Vim-Silverman needle. JAMA 166:1464, 1958 11. Pittman G, Tung KSK, Hoffman GC: Metastatic cells in bone marrow. Cleve Clin Q 38:55-64. 1971 12. Roeckel I: Diagnosis of metastatic carcinoma of bone marrow biopsy vs bone marrow aspiration. Ann Clin Lab Sci 4: 193-197, 1974 13. Slager WT, Reilly EG: Value of examining bone marrow in diagnosing malignancy. Cancer 20:1215-1220. 1967 14. Stonier PF, Evans PV: Carcinoma cells in bone marrow aspirates. Am J Clin Pathol 45:722-727, 1966 15. Suprun H, Rwylin AM: Metastatic carcinoma in histiologic sections of aspirated bone marrow; A comparative autopsy study. South Med J 69:438-439, 1976
SINCE THE FIRST large series comparing histologic sections and aspirated smears of bone marrow, 1 repeated attempts have been made to evaluate the diagnostic usefulness of smears, clot sections, and needle biopsy of bone marrow for detection of metastatic neoplasms. Some investigators8 report a very high rate of correlation between aspirate smear and needle biopsy, and feel that the two procedures have essentially the same diagnostic usefulness, while others 5 - 7 feel that many metastatic neoplasms detected by histologic examination (either clot section or needle biopsy) will be missed when aspirates alone are examined. Occasional reports 7 suggest the diagnostic criteria for evaluation of suspected malignant cells in bone marrow are unreliable and will lead to an unacceptably high rate of false-positive reports—marrow aspirates called positive for neoplasms in patients who do not have a Received August 15, 1977; accepted for publication September 15, 1977. Address reprint requests to Dr. Savage: Department of Laboratory Hematology, The Cleveland Clinic Foundation, Cleveland, Ohio 44106.
From the Division of Laboratory Medicine, The Cleveland Clinic Foundation, Cleveland, Ohio
primary tumor and remain without evidence of one for prolonged follow-up periods. After review of simultaneous marrow aspirates and needle biopsies performed in our institution, we feel that both of these positions are extreme. We contend that in approximately 75% of cases called positive for metastatic neoplasms on the basis of needle biopsy a simultaneous marrow aspirate will also be called positive, and that the 25% discrepancy rate (aspirate negative-biopsy positive) is due to unavoidable physical changes induced in the marrow spaces by the presence of the neoplasm itself. Moreover, when the cytologic criteria detailed below are employed, falsepositive aspirate smears will be rare. The compromise position outlined is supported by results of other studies. 4,6 Materials and Methods Simultaneous marrow aspiration and biopsy procedures were performed through the same skin incision using the Jamshidi needle (Regular/Adult, 11-gauge). The site evaluated was primarily the posterior superior iliac spine, but occasionally, particularly in pediatric patients, other sites such as the anterior iliac crest were evaluated. Air-dried coverslip preparations were immediately made from the marrow particles and stained with Wright's stain. Biopsy specimens were fixed overnight in high-acid (decalcifying) Zenker's solution and stained with hematoxylin and eosin. Touch preparations were routinely made
Table 1. Correlation of Results of Bone Marrow A spiration vs. Biopsy Aspirate
1973-1975 1976
Biopsy Positive
Not Done
Positive
Suspect
Hypocellular
Negative
Correlation
88 38
43 7
33 22
1 1
5 2
6 6
73% 71%
0002-9173/78/1000/0623 $00.75 © American Society of Clinical Pathologists
623
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 6, 2016
Savage, Richard A., Hoffman, George C , and Shaker, Karen: Diagnostic problems involved in detection of metastatic neoplasms by bone-marrow aspirate compared with needle biopsy. Am J Clin Pathol 70: 623-627, 1978. Comparison of a large series of bone marrow aspirations with simultaneously performed Jamshidi needle biopsies showed 75% correlation between the two procedures for detection of metastatic neoplasms. In cases where the two methods disagreed, false-negative aspirations resulting from perineoplasty desmoplasia was the usual reason for the discrepancy. Cytologic criteria for the evaluation of suspected neoplastic cells in aspirate preparations are discussed. (Key words: Bone marrow aspirate; Bone marrow biopsy; Metastatic neoplasm.)
SAVAGE, HOFFMAN AND SHAKER
624
1. (left). Intense desmoplasia and new bone formation elicited by metastatic carcinoma from the breast. No tumor was seen in the aspirate. Hematoxylin and eosin. x 150. FIG. 2 (right). Metastatic mammary carcinoma with desmoplasia coexisting with normal marrow foci, at top of picture. Normal marrow particles were present in the aspirate with no evidence of tumor. Hematoxylin and eosin. xl50.
from biopsies when the aspirate failed to show acceptable numbers of marrow particles by visual inspection of the unstained smear. Routine interpretations of the preparations were made by staff members of the Department of Anatomic Pathology for the biopsies and the Department of Laboratory Hematology and Blood Banking for the aspirate smears. Following issue of Table 2. Factors Responsible for Lack of Correlation of Biopsy and Aspirate 1973-1975
1976
Biopsy positive-aspirate negative Severe desmoplasia with preserved normal marrow foci Mild-moderate desmoplasia Scattered microfoci on biopsy Misinterpretation of aspirate
3 2 1 1
3 1 1 1
Biopsy negative-aspirate positive Misinterpretation of biopsy Misinterpretation of aspirate True aspirate (+)-biopsy (-)
2 3 1
* * *
* 1976 figures not included.
the final reports for each preparation, these separate evaluations were routinely collected, and the written reports were correlated by a member of the Laboratory Hematology staff. Slides were re-examined when a discrepancy between the results of the two evaluations was found by the reviewer. The aspirate smears examined were divided into three groups. Those called positive contained cytologically malignant cells, those called suspect contained clumps of distorted cells suggestive of neoplasm but not cytologically acceptable for diagnosis, and those labeled hypocellular contained no malignant foci and had differential distributions similar to that simultaneously present in the peripheral blood. Biopsy preparations were not referred to as hypocellular, but were instead evaluated descriptively for adequacy by evaluation of the cellular and histologic elements actually contained within each needle biopsy. Biopsy specimens were deemed suspect when foci of distorted cells or areas of crushed chromatin that could not be properly evaluated histologically due to crush artifact or other distortion were present. An
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 6, 2016
FIG
A.J.C.P. . October 1978
Vol. 70 • No. 4
METASTASES IN MARROW ASPIRATE AND BIOPSY
625
FIG. 3. Left: A typical cluster of neoplastic cells in the marrow aspirate. Wright's stain, x 160. Right: Higher magnification of the cells illustrated at left, showing features of malignancy described in the text. Wright's stain. x640.
attempt was made to minimize the numbers of specimens deemed hypocellular and suspect by examination of multiple recuts and multiple additional smears when the original material evaluated was deemed inadequate for exact diagnosis according to the criteria outlined above. All available material was re-examined without knowledge of the original evaluations, save for the fact that the reviewers were aware that a discrepancy existed between the results of the biopsy and the aspirate. The aspirates were reviewed by both the senior authors independently, and the biopsies were reviewed by one (RAS). No disagreement between the reviewers was found for any individual preparation. A special problem was encountered in evaluating pediatric patients' smears. In the majority of pediatric cases, simultaneous aspirate smear and biopsy combination evaluation was not done until mid-1976. However, in the period 1973-1975, three cases of aspirate-positive-biopsy-negative paired evaluations were discovered, and in each case, review showed that the aspirate had been called positive erroneously
on the basis of overinterpretation of cytologically equivocal cells. These cases are included in the second half of Table 1 but not counted for calculation of percentages of discrepancy, as the majority of the evaluations in the pediatric group were not combination aspirate-biopsy evaluations. Pediatric cases from 1976 represented a mixture of paired and unpaired evaluations and were not included in the study. Results Aspirate-negative-biopsy-positive cases formed the vast majority of discrepancies in the study. A detailed breakdown of these evaluations is shown in Table 2. Occasional cases of misinterpretation of biopsy or aspirate smear were encountered; the reasons for discrepancies in both aspirate-positivebiopsy-negative and aspirate-negative-biopsy-positive evaluations are summarized in Table 2. Reclassification of misinterpretations resulted in only slight changes. Two aspirates initially interpreted as negative were reclassified positive; two biopsy-negativeaspirate-positive evaluations were reclassified biopsy-
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 6, 2016
kx.
626
SAVAGE, HOFFMAN AND SHAKER
^
* *
FIG. 4. A solitary focus of neoplasm identified in the aspirate preparation. The biopsy showed numerous areas of prostatic carcinoma with dense perineoplastic fibroplasia. Wright's stain. xl60.
positive-aspirate-positive, and one biopsy-positive aspirate-negative evaluation became biopsy-negative aspirate-negative on review. These changes largely cancelled one another out, so that the correlation rate changed only slightly. The results were divided into two time periods. Correlation between biopsy and aspirate was determined for 1973-1975, and a separate correlation was determined for 1976. The correlation rate changed only slightly, from 73% in 1973-1975 to 71% in 1976. This correlation rate agrees with those in other published series.3-4 Analysis for the reasons of this lack of correlation indicated that most of the discrepancies (five of seven in 1973-1975; four of six in 1976) were due to the coexistence in the bone marrow of normal marrow and metastatic foci that produced perineoplastic fibroplasia and sometimes, new bone formation (Fig. 1). Such marrows need not appear hypocellular on aspirate, as islands of fibrosis may be interspersed with residual normal marrow (Fig. 2). Such normoblastic foci were aspirated readily, giving the
impression of an uninvolved marrow on the aspirate smear preparation. Only when the desmoplasia was severe would the aspirate smear produce a dry tap or be hypocellular. Minute foci of neoplasm on biopsy were occasionally encountered, and not surprisingly the simultaneous aspirate smears for these cases were negative. However, surprisingly small amounts of neoplasm could be detected by painstaking screening of the entire aspirate preparation and careful cytologic evaluation of the suspect foci detected by the screening procedures. Careful cytologic evaluation of the abnormal cells detected is of utmost importance in the correct classification of suspect cells found in the bone marrow aspirate smears. Very high false-positive rates were found by some investigators 7 ; analysis of published illustrations in this work suggests that atypical megakaryocytes or histiocytes were incorrectly interpreted by these investigators. 6 Cytologic evaluation should be based on clusters and masses of suspect cells, as evaluation of isolated cells has been proved to be misleading. 711 " 13 Useful cytologic criteria 11-14 include nuclear pleomorphism within the clump of suspect cells, irregular hyperchromatic condensations within the nucleus, prominent bluish nucleoli, a syncyntial appearance of the cells within the mass, and indistinct cytoplasmic borders with smudging (Fig. 3). Even with severely hypocellular specimens, isolated clumps of malignant cells could be readily detected (Fig. 4). Six aspirate-positive-biopsy-negative simultaneous evaluations were found in this study (Table 2). In two instances misinterpretations of the biopsies had resulted in false-negative initial evaluations; in the other three, misinterpretations of distorted osteoblasts or histiocytes on the aspirate resulted in discrepancies. No false-positive evaluation due to misinterpretation of megakaryocytes was encountered. The sixth case, on review, was confirmed to be a true aspirate-positive-biopsy-negative evaluation, with both specimens considered adequate by the criteria outlined above. The value of careful screening under intermediate power is illustrated by this series and by that of Garrett and associates, 8 in which screening technics doubled the rate of detection of metastatic neoplasms in aspirate smears compared with a previous study of patients at the same institution. 5 The sensitivity of either aspiration or biopsy for detection of neoplaspis metastatic to the marrow was not evaluated in the study. Published rates of detection vary widely, from 1.2% in an unselected series of aspirate preparations 11 to approximately 10-20% in series in which the members of the population evaluated were known to have primary neoplasms.2-5-8-13 A study 15 comparing ability to detect neoplasms in bone
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 6, 2016
.
A.J.C.P. • October 1978
Vol. 7 0 . No. 4
METASTASES IN MARROW ASPIRATE AND BIOPSY
References 1. Agress H: Comparative study of spreads and sections of bone marrow. Am J Clin Pathol 27:282-299, 1957 2. Anner RM, Drewinko B: Frequency and significance of bone marrow involvement by metastatic solid tumors. Cancer 37:1337-1344, 1977
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 6, 2016
marrow aspirates performed on cadavers with the detection ability of subsequent dissection and routine gross and microscopic autopsy examination showed that 10% of the cadavers had metastases demonstrated on aspiration smear, compared with 34.5% by dissection and histologic autopsy evaluation. Thus, bone marrow aspiration appears to be able to detect about 28% of the cases with actual osseous metastases. Limitations of bone-marrow aspirate smears for detection of metastatic neoplasms are obvious from this study. Although aspirate smears should be considered complementary to biopsy for detection of metastases, good aspirates can yield useful information regarding morphology and maturation of hematopoietic cells. Additionally, most series5,8-912 suggest a higher rate of detection of neoplasms when the two procedures are performed simultaneously. Our practice at present is to perform aspiration plus biopsy or biopsy alone, when hematologic indices of peripheral blood appear adequate, for detection of metastatic neoplasms involving bone marrow.
627
3. Bearden JD, Ratkin GA. Coltman CA: Comparison of the diagnostic value of bone marrow biopsy and bone marrow aspiration in neoplastic disease. J Clin Pathol 27:738-740, 1974 4. Brunning RD, Bloomfield CD, McKenna RW, et al: Bilateral trephine biopsies in lymphoma and other neoplastic disease. Ann Intern Med 82:365-366, 1975 5. Conteras E, Ellis LD, Lee RE: Value of the bone marrow biopsy in the diagnosis of metastatic carcinoma. Cancer 29:778-783, 1972 6. Ellman L: Bone marrow biopsy in the evaluation of lymphoma, carcinoma and granulomatous disorders. Am J Med 60: 1-7, 1976 7. Emerson CP, Finkel HF: Problems of tumor cell identification in the bone marrow. Cancer 17:1527-1532, 1966 8. Garrett TJ, Gee TS, Lieberman PH, et al: The role of bone marrow aspiration and biopsy in detecting marrow involvement by nonhematologic malignancies. Cancer 38:2401-2403, 1976 9. Grann V, Pool JL, Mayer K: Comparative study of bone marrow aspiration and biopsy in patients with neoplastic disease. Cancer 19:1878-1900, 1966 10. McFarland W, Dameshek W: Biopsy of bone marrow with the Vim-Silverman needle. JAMA 166:1464, 1958 11. Pittman G, Tung KSK, Hoffman GC: Metastatic cells in bone marrow. Cleve Clin Q 38:55-64. 1971 12. Roeckel I: Diagnosis of metastatic carcinoma of bone marrow biopsy vs bone marrow aspiration. Ann Clin Lab Sci 4: 193-197, 1974 13. Slager WT, Reilly EG: Value of examining bone marrow in diagnosing malignancy. Cancer 20:1215-1220. 1967 14. Stonier PF, Evans PV: Carcinoma cells in bone marrow aspirates. Am J Clin Pathol 45:722-727, 1966 15. Suprun H, Rwylin AM: Metastatic carcinoma in histiologic sections of aspirated bone marrow; A comparative autopsy study. South Med J 69:438-439, 1976
