SA MEDIESE TYDSKRIF DEEL 64 20 AUGUSTUS 1983 271

Review Article

Trephine biopsy of the bone marrowA. R. BIRb, P. JACOBS

Summary

We present areview of trephine biopsy of the bonemarrow based on an experience of approximately10000 examinations. It is our view that, in adults,examination of material obtained by aspirationcombined with a trephine biopsy allows for the mostthorough morphological assessment of the marrow.Morbidity is limited to transient discomfort to thepatient, and· even bilateral procedures are conve­niently performed on outpatients. There is no abso­lute contraindication to combining aspiration andtrephine biopsy, but in severe bleeding disordersdue to acquired or congenital coagulation factordeficiencies replacement therapy is indicated andthe patient should be observed in hospital for 24hours following the procedure. Thrombocytopeniais not associated with significant bleeding from thebiopsy site in our experience. l"he advantages of thetrephine biopsy are that it allows better overallassessment of ceUularity and morphology and isindispensable in cases where aspiration has failedor where infiltration due to the myeloproliferativesyndrome or to haematological and non-haemato­logical malignancies has occurred. With marrowhypoplasia and granulomatous disorC:ters involvingthe marrow, the trephine biopsy is indispensable fordiagnosis.

S Atr Med J 1963; 64: 271-276.

Examination of the bone marrow is one of the diagnostic corner­stones of haematological practice. Aspiration techniques arelimited in that they do not provide positive diagnostic informa­tion in patients with granulomatous disease, myelofibrosis andinfiltrative conditions ofthe marrow, H although some investiga­tors favour examination of sections prepared from concentratedparticles obtained by aspiration.7

•s However, up to 10 ml of

aspirated marrow is required to obtain material equivalent tothat of a trephine biopsy.9

We review the various techniques ofobtaining a core biopsy ofthe marrow and its processing and preparation for microscopicstudy. The indications and the advantages of marrow biopsy areoutlined and the diagnostic pitfalls in the interpretation of mar­row sections are emphasized.

University of Cape Town Leukaemia Centre and Depart­ment of Haematology, Groote Schuur Hospital, Cape TownA. R. BIRD, F.F.PATH. (SA), M.MED.PATH. (HAEM.l, Regisrrar (Presentappointment: Specialist Pathologist, Red Cross War MemorialChildren's Hospital)P. JACOBS, M.D., PH. D., Professor and Head

Date received: 5 August 1982.Reprint requests [0; Professor P. Jacobs, DepI of Haematology Research Cemre. University ofCape Town Medical School, ObservatOry, 7925 RSA.

Techniques of trephine biopsy

Many methods of trephining the bone marrow have been des­cribed. The Vim-Silverman needle was the first device to be usedregularly. 10 This was followed by the introduction of theWesterman-Jensen needle, 11 a modification of the Vim-Silvermanneedk, which is still used in many centres. The technique isexcellently illustrated by Ellis er al. 11 More recently, the Jam­shidi needle l2 was introduced and is now probably the mostwidely used device. Other coring techniques using the Bordiertrephine,13 Gidlund's instrument,14 the Radner needle,15 theGardner and the Sacker-Nordin needle l6 have been described.Larger specimens may be obtained with Burkhardt and Notter­Labhart needles2 or by open surgical biopsy. These proceduresare, however, time-consuming and therefore unsuitable if serialbiopsies are required.

Our preference is to use the Jamshidi needle. The'technique ofcoring is outlined by Jamshidi and Swaim l2 and is well known tomost haematologists. We have also had extensive experiencewith the Westerman-Jensen needle but now prefer the Jamshidineedle for the following reasons: (a) there is little disturbance inthe architecture of the core obtained by the Jamshidi needle; (b)it requires less maintenance than the Westerman-Jensen needlesince sharpening and replacement of cuning blades are avoided;(c) larger cores are obtained; and (d) it is our experience thatpatients tolerate trephining with the Jamshidi needle better thanthat with the Westerman-Jensen needle.

Certain points, however, should be noted. Firstly, the cuttingtip of the Jamshidi needle should be sharpened regularly and thetip should be kept acutely angled to reduce the incidence of 'lostcores'. Secondly, we have experien<;:ed difficulty in obtainingspecimens from very osteoporotic patients using large-gaugeJamshidi needles. In these circumstances, the Westerman­Jensen needle is often preferable. Thirdly, the anatomy of thepelvis must obviously be considered when performing a trephinebiopsy. The posterior iliac crest (the most convenient and proba­bly the safest site for marrow biopsy) is usually easily palpablewith the patient lying prone. The sacro-iliac joint lies perpen­dicularly below the posterior crest. The wing of the ilium slopeslaterally and it is in this direction that the biopsy needle shouldbe aimed.

We routinely perform marrow aspiration just prior to biopsy.We do not aspirate with the same needle but prefer to use theKlima l6 or similar needle. As long as the needle is directed awayfrom the site ofthe proposed biopsy, there is no distortion on thesubsequent trephine sections. .

It is well known that aspiration of marrow can cause sharppain. Trephining of the marrow, with few exceptions, seems tocause less discomfort. Unallayed anxiety, inadequate local anaes­thesia and poor technique are factors which may make the proce­dure unacceptable. Physicians inexperienced in the technique oftrephine biopsy usually provide inadequate specimens andtherefore the procedure has to be repeated. In our hospital,therefore, all patients requiring bone marrow examination arereferred to the Haematology Department. The marrow aspiratesand trephine biopsies are then performed by the residents.

272 SA MEDICAL JOURNAL VOLUME 64 20 AUGUST 1983

Preparation of the specimen for examination

FixationOnce an adequate core (> 2,0 cm) has been obtained, it is fixed

for a minimum of 4 hours in Zenker's fixative, with constantagitation. It is washed overnight to remove the dichromate andthe following morning is placed in Formol/Decal solution for 4hours to decalcify the bone using a roller mixed to ensure evenexposure of the core to solution. After washing for IS minutes, itis then processed and embedded in Paraplast according to stan­dard methods.

Poor-quality sections are often the result of one or more ofthree problems involving fixation: (i) inadequate time allowedfor proper fixation - we have run a number of trials to assessoptimum fixation time, and 4 hours is the absolute minimumusing Zenker's fixative; (ii) using a Zenker's stock solution olderthan 2 weeks; (iii) fixative prepared too far in advance of thebiopsy procedure; it should be prepared just prior to biopsy.

Preparation of sectionsThe preparation of good sections ensures accurate identifica­

tion of the haematopoietic cells. Ideally, serial sections should beexamined. We recommend that at least three sections taken atdifferent levels should be studied. If properly decalcified andfixed, sections can be cut at 4 ).Lm. By using a methacrylateembedding process, sections as thin as I ).Lm can be prepared. 17

This allows for very accurate identification of haematopoieticcells. The major disadvantage of this technique is the time re­quired for preparation of the blocks, usually a minimum of 4days.

Staining proceduresAt least three sections from each core biopsy specimen should

be stained with haematoxylin and eosin, and one section forreticulin. Romanowsky stains have been recommended2 but inour experience add little diagnostic information. Iron stores arebest evaluated on the aspirate smears using Perls's reaction, butif smears are not obtainable, sections may also be stained forassessment of iron stores. Loss of iron from the section, however,may occur during fixation and we do not recommend core biop­sies for the assessment of iron stores. Special stains for fungi ortubercle bacilli may be indicated in the presence of granulomas,although these stains, too, may be affected during the fixationprocesses.

Indications for trephine biopsy

In the following section we outline what we consider to beabsolute indications. In these situations, failure to do a trephinebiopsy may result in a missed or delayed diagnosis.

Failure to aspirate marrowThree failed aspirations from different puncture sites should

be regarded as a 'dry tap'. In these cases, material for cytologicalassessment may still be obtained by performing a touch prepara­tion with the trephine biopsy.

Myeloproliferative syndrome (Fig. 1)This is probably the commonest condition leading to failed

aspiration. The appearance of the marrow is pathognomonic, 18

although in the early cellular phase of polycythaemia vera thediagnosis may not be obvious. A stain for reticulin is mandatory,

Fig. 1. Silver stain showing dense parallel strands of reticulin in apatient who presented with pancytopenia and splenic enlarge­ment. Myelofibrosis was diagnosed.

however, as even in polycythaemia vera the typical pattern ofincreased marrow reticulin is seen.

Metastatic neoplasia (Fig. 2)'Dry taps' in patients with cancer metastatic to the marrow are

not infrequent. A review of 74 marrow aspirates and trephinespecimens obtained over a 2-year period (January 1973 ­December 1974) from patients with non-haematologicalmalignant disease showed the presence of metastatic tumour in18 (24%). In 7 of these tumour was found in both the aspirate andthe trephine specimen, while 5 were 'dry taps'. In only I, a childwith metastatic retinoblastoma, was the aspirate positive in theface of a negative trephine specimen (A. R. Bird and P. ]acobs-unpublished observations).

Fig. 2. Metastatic carcinoma with intense desmoplastic reactionand blood vessel invasion in a patient with fever and weight losswho was eventually found to have a 0,5 cm primary carcinoma ofthe proximal colon.

In a study by Savage et al. 6 utilizing~a Jamshidi needle forbiopsy and aspiration, a correlation between biopsy and aspira­tion results was shown in 75% of cases positive for metastaticcancer. In only I" instance was the aspirate positive and thetrephine biopsy negative. The remaining discrepancies were alldue to biopsy-positive, aspirate-negative specimens. Other stu­dies also attest to the efficacy of the trephine biopsy in increasingthe yield of positive specimens. 1

,ll,19 Performing bilateral tre

phine biopsies further increases the yield ofpositive specimens.20Garrett et al.,21 however, reviewed 291 patients with non­haematological malignancies and found 39 positive for metasta­tic rumour. The biopsy was positive in 3 patients witha negativeaspirate, and in 3 others the aspirate was positive with a negativebiopsy. They attributed their high rate of tumour detection inthe aspirate to a thorough initial screening by technologists; thisprocess, however, sometimes occupied several hours in scanningmany smears.

The yield of positive marrow specimens may be increased ifbiopsies are performed at sites of local tenderness or in asuspicious area as depicted on the radiograph or bone scan.However, needle biopsies can be performed safely only from theanterior or posterior iliac crests, or occasionally from the verte­bral spines. Negative radiographic studies or bone scans do notmilitate against the performance of a marrow biopsy, as positivemarrow specimens may be obtained in the case of a negativeskeletal surveyor scan. 22

Concurrent aspiration and trephine biopsy from the posterioriliac crest, bilaterally if possible and aided by radiographic stu­dies and a bone scan, should therefore ensure the best possibleyield of positive specimens from the marrow in the diagnosis ofmetastatic rumours.

Acute leukaemiaAlthough aspirate smears are indicated for the cytological

diagnosis of acute leukaemia, the marked increase in reticulinsometimes seen in both acute lymphoblastic and acute myelo­blastic variants may lead to a 'dry tap'. A recent srudy has shownthat the presence of this reticulin does not appear to be related tothe prognosis,23 although there has been a report to the con­trary.24 Induction of remission in patients with increased mar­row reticulin results in a distinct reduction in the reticulin.Recurrence of increased reticulin may herald the onset of arelapse of the leukaemia.23,24

In the follow-up of patients with acute leukaemia, and particu­larly in the post-induction period of hypoplasia, marrow biopsyallows for a more comprehensive assessment of marrow reservethan the scanty particles obtained on aspiration alone.

Leukaemic reticulo-endotheliosisThis rare but well-described condition mainly affects adults,

and patients with pancytopenia and splenomegaly. The diag­nosis is usually made from the peripheral blood smear where thediagnostic 'hairy' cells are seen. 25 These cells show a characteris­tic positive acid phosphatase reaction which is resistant to tart­rate pretreatment. 26 Attempted marrow aspiration is invariablynon-productive and a marrow biopsy is required. Sections showthe'characteristic infiltrate with a dense reticulin pattern.

Staging and follow-up of patients withlymphoma

Hodgkin's disease (HD) (Fig. 3)Marrow specimens positive for HD show disruption of the

normal marrow architecrure by fibrosis, necrosis, and a cellularinfiltrate of lymphocytes, plasma cells, eosinophils and histio­cytes, even in the absence of Reed-Sternberg cells. The patternof infiltration may be diffuse or focal. 27 Marrow aspiration aloneis of limited value in the detection of marrow involvement byHD. This is not unexpected, in view of the often focal nature ofthe infiltrate and the high incidence ofaccompanying fibrosis. Areview of 53 trephine biopsies and aspirate smears from patientswith HD during a 2-year period from January 1973 to December1974 revealed 19 positive specimens. Of these 4 were 'dry taps',

SA MEDIESE TYDSKRIF DEEL 64 20 AUGUSTUS 1983 273

Fig. 3. High-power view of marrow involved by Hodgkin'sdisease. Typical Reed-Sternberg cells were not found. Characte­ristic Hodgkin's mononuclear cells with giant nucleoli are seen.The diagnosis was subsequently established on examination of apara-aortic lymph node specimen obtained at laparotomy.

while the remainder were all biopsy-positive and aspirate­negative (authors' unpublished data).

Positive bone marrow biopsy specimens from untreatedpatients have not been reported in patients iJ;litially clinicallyclassified as stage I and HA. However, up to 25% of patientsthought to have stage III disease may be reclassified as stage IVas a result of a positive core biopsy.28,29 Occasionally, marrowinfiltration may be the only evidence of stage IV disease. Bilat­eral biopsies have been shown to increase the yield of positivespecimens.2o

The diagnosis of HD on the basis of marrow infiltration alonein patients without peripheral lymphadenopathy presents manydifficulties. Neiman et al. 30 described a group of 13 patients withlymphocyte-depleted HD. The patients had fever, pancytopenia.and abnormal liver function, but there was no striking peripherallymphadenopathy. The outcome was consistently fatal, usuallywithin a short period. In 5 patients the marrow sections werediagnostic, and in 3 of these were the sole criterion for thediagnosis.

The occurrence of granulomatous lesions in tissues involvedby HD is well recognized.3! The significance of isolated non­caseating granulomas in otherwise uninvolved tissues, however,is less clear. Kadin eT al. 32 reviewed tissue obtained from 185patients with HD prior to treatment and noted isolated granulo­mas in the liver and spleen. Further extensive sectioning ofthesetissues failed in many instances to reveal a diagnostic infiltrate ofHD. In some, however, the granulomas were intimately associa­ted with an HD infutrate. It was concluded that the discovery ofisolated epithelioid cell granulomas in HD should not influencethe staging criteria.

Another phenomenon occasionally encountered is the pre­sence of extensive lymphoid aggregates in otherwise normalbiopsy specimens from patients with HD. The significance ofthis remains uncertain.

Non-Hodgkin's lymphomaProper histopathological classification and clinicopathological

staging are now regularly employed in the non-Hodgkin's lym­phomas: (1) to define patterns of disease better; (il) to correlatethese patterns with the clinical course and response to treatment;and (iil) for selection of the appropriate therapy.

Although aspiration smears or sections of aspirated particleshave been used in the detection of marrow involvement bylymphoma, several reviews testify to the trephine biopsy as the

274 SA MEDICAL JOURNAL VOLUME 64 20 AUGUST 1983

best method for detection of marrow lymphoma.3.33-35 By per­

forming bilateral posterior iliac crest biopsies the yield of posi­tive specimens is increased by 10 _ 20%.2 ,36

Marrow biopsy often influences the staging of patients withnon-Hodgkin's lymphoma. It has been shown that 50 - 65% ofpatients thought to be in stage I - III m~ be reclassified as stageIV as a result of a marrow biopsy.20,2, ,35 A normal full bloodcount does not exclude infiltration of the marrow.33

,35

One of the major problems in the diagnosis of marrow lym­phoma is the distinction between benign lymphoid aggregatesand lymphoma. Studies of the prevalence of benign lymphoidfollicles in marrow biopsies and clot sections obtained in virroshow a wide variation. Although most biopsy srudies (includingour unpublished data) report an incidence of 1 - 9%,37 muchhigher fi?ures, up to 47%, are reported when clot sections areused.37-3 These benign lymphoid nodules are commoner inolder patients and in many cases constitute a normal findingwithout any known clinical significance. Not infre.quently, how­ever, we have found it difficult to decide whether the marrow wasinvolved by a Iymphoproliferative disorder, both in patients withknown lymphoma and in those without evidence of lymphomaelsewhere. The following features have been described as sugges­tive of early lymphomatous infiltration: (i) size of aggregate-any aggregate covering more than 25% ofa 40 high-power fieldis suspect;36 (ii) cytological atypicality; (iil) multiplicity ofaggre­gates; (iv) infiltration into surrounding normal marrow; and ('v)paratrabecular location.

These criteria must be viewed critically, however, as we haveseen several marrow specimens with many of the above fearuresin patients in whom subsequent follow-up revealed no evidenceof lympho.ma. Moreover, nodular lymphoid hyperplasia of themarrow is a well-described entity. 31 Recent reports of this syn­drome have emphasized that caution must be exercised before adefinitive diagnosis of lymphoma is made.37

.40 In a study byRywlin er al.J7 10 patients with lymphoid hyperplasia of themarrow were noted. In 5 of these, follow-up was possible.During a 2 - 21/ 2-year period, none of these patients developedsigns or symptoms suggestive of a lymphoproliferative disorder.Careful follow-up of patients in whom the isolated finding oflymphoid hyperplasia ofrhe marrow is made is therefore prefer­able to treating them as cases of early lymphoma.

Diagnosis of the hypoplastic anaemiasMarrow trephine biopsy, preferably from more than one site,

is an essential procedure in the diagnosis ofhypoplasia. Althoughthis is important diagnostically, no correlation between estima­tions of cellularity and prognosis has been shown.41 ,42

Granulomatous disorders (Figs 4 and 5)Granulomas represent a host inflammatory response which

may be the result of a wide variety of stimuli. In an extensivestudy by Pease43 of 150 patients with granulomatous lesions insections of aspirated marrow particles, the commonest underly­ing disorders were tuberculosis, histoplasmosis, infectiousmononucleosis, sarcoidosis, brucellosis, and Hodgkin's and non­Hodgkin's lymphoma. Marrow granulomas were also found in awide variety ofother disorders, some of which are not ordinarilyassociated ~ith granulomatous change. Okun er al. 44 have des­cribed the presence of marrow granulomas in a patient with Qfever. Unless a specific organism can be identified by specialstains or bacteriological culture, there are no diagnostic featuresof a granuloma characteristic of a definite etisorder, althoughprominent caseous necrosis favours the diagnosis of tuberculosis.

Granulomas may very occasionally be seen in aspirate smears,but the yield is considerably increased by sectioning particles ofmaterial. Although no adequately controlled studies are avail-

Fig, 4. Granuloma containing Langhans giant cell and epithelioidhystiocytes in a patient with fever of undetermined origin. Tuber­culosis was subsequently diagnosed on examination of a sputumspecimen.

Fig. 5. High-power view showing numerous Gaucher cells in a5-year-old black girl with massive splenomegaly.

able, biopsy will presumably further increase the yield owing toits ability to reach more deep-seated tissue.

Although marrow aspiration and biopsy are complementary toother investigations, marrow examination and culture maysometimes succeed in establishing the diagnosis ofa granuloma­tous disorder when orher tests have failed to do SO.40-47

Chronic lymphocytic leukaemia (CLL)Bone marrow histological patterns and rheir relationship to

prognosis in chronic lymphocytic leukaemia have been evaluatedby some authors. Gray er al. 48 studied 115 patients and showedthat those wirh diffuse marrow infiltration had a poorer prog­nosis than those presenting with a nodular or mixed (nodular anddiffuse) pattern. Rozman er al. 49 studied 63 patients with eLLand described 4 different histological patterns: (i) interstitial(lymphoid infiltration without displacement of fat cells); (ii)nodular (abnormal lymphoid nodules without interstitial infil­tration); (iii) mixed (combination of the first two patterns); and(iv) diffuse (replacement of both haematopoietic and fat cells bylymphoid infiltration). Statistical analysis of actuarial curvesshowed a significant difference ofsurvival probability accordingto the marrow infiltration patterns. In patients with interstitial ornodular patterns life expectancy is significantly less than in thosewith mixed or diffuse patterns. They also noted a significantdegree of correlation between bone marrow infiltration patternsand the various methods of clinical staging.

--

MiscellaneousBone disease. Bone trabeculae can easily be studied in mar­

row trephine sections and thus provide a simple method for thediagnosis of bone disease, such as may accompany chronic renalfailure, intestinal malabsorption, and other disorders. 50

Lead poi.soning. Bone is a primary site of lead storage andcore biopsies may therefore be used to estimate stored lead levels.A recent study of skeletal lead concentrations in Americans hasdocumented the presence of plumbism in polluted environmentsand underlines the value of this investigation in such epidemio­logical studies.51

Contraindications to marrow trephinebiopsy

These are all associated with a tendency to increased bleeding.Thrombocytopenic bleeding (Fig. 6) has never been a problem inour experience, provided adequate compression has been appliedto the biopsy site on completion of the procedure. In the face ofdisseminated intravascular coagulation, haemorrhage followinga trephine can be catastrophic, and marrow biopsy is thereforecontraindicated in the presence of this disorder. In patients withhereditary coagulation factor deficiencies, marrow biopsy shouldbe performed only with adequate cover by the approximatecomponent. For patients on anticoagulant therapy, cessation oftherapy is indicated until adequate haemostatic status has beenregained.

Fig. 6. Megakaryocytic hyperplasia in an otherwise normal bonemarrow specimen from a patient who presented with purpuricbleeding and a platelet count of 5 x 109/1. Auto-immune thrombo­cytopenic purpura was diagnosed.

ComplicationsThe problem of post-biopsy bleeding has been discussed

above. The only other complication we have experienced isinfection. Our incidence of infection is less than 1%. Infectionhas occurred only in immunocompromised patients on cytotoxicdtugs. We therefore use a strict aseptic technique and wearsurgical masks and gloves when biopsying these patients.

Diagnostic pitfalls

Besides some of the diagnostic problems that have already beenmentioned, we should like to emphasize a few other problems ofinterpretation occasionally encountered.

SA MEOIESE TYOSKRIF OEEL 64 20 AUGUSTUS 1983 275

Megaloblastic anaemiaThe cellular and apparently blastic appearance of the marrow

tissue on sections stained with haematoxylin and eosin may leadto an erroneous diagnosis of leukaemia or lymphoma. The mar­row aspirate should obviously lead to the correct diagnosis, butthe trephine biopsy may still be misinterpreted by the inexpe­rienced, especially if examined in isolation.

Angio-immunoblastic lymphadenopathyThis unusual hyperimmune disorder ofB-lymphocyte origin52

may involve the marrow. 53 The characteristic morphologicalfeatures ofimmunoblastic and plasma cell infiltrates, amorphousacidophilic interstitial material and vascular proliferation mayclosely resemble HD. The diagnosis is usually made on clinicalgrounds in conjunction with a lymph node biopsy.

Eosinophilic fibrohistiocytic lesionsThese lesions were described by Rywlin el al. 54 in 1972. They

consist ofspindle cells, numerous eosinophils, some plasma cellsand occasional mast cells. In Rywlin el al.'s series, some of thepatients were anaemic and all of them were raking numerousmedications. Withdrawal of the drugs led to an improvement inthe anaemia and disappearance of the eosinophilic lesions. Wehave noted a similar lesion in a patient with urticaria pigmentosa.

Post-induction therapy for leukaemiaA trephine biopsy is indicated in the follow-up of patients with

acute leukaemia after intensive cytotoxic therapy for the induc­tion ofa remission. This applies particularly to acute myeloblas­tic leukaemia. The trephine biopsy ensures good assessment of:(i) the extent of residual disease, if present; and (ii) the extent ofhaematopoietic reserve and early signs of regeneration of normalhaematopoietic tissue.

Occasionally, diagnostic problems may be encountered in theassessment of biopsy specimens when clusters of blasts are pre­sent - is this a sign of residual disease or of regeneration? It isour experience that these sections should be interpreted withcaution. Very often these blasts are part ofa regenerative processand do not represent residual leukaemia.

\1( e have also noted some unusual regenerative phenomena inclassic myeloid leukaemias following induction therapy, e.g.megakaryocytic hyperplasia.

Comment

Needle biopsy of the bone marrow has for some time been theaccepted method for obtaining a specimen of bone marrow forexamination when aspiration has resulted in a 'dry tap'. It is onlyin the last decade, however, that it has become clear that biopsy issuperior to aspiration in the detection of Ho.dgkin's and non­Hodgkin's lymphomas and metastatic malignant tumours. Someauthors have advocated the use of sections of aspirated materialand have demonstrated their superiority to aspirate smears in thedetection of granulomas, metastatic tumours and lymphoma. Acomparative study by Dee el al. 3 indicated a distinct superiorityof the biopsy specimen when this was compared with the aspirateand sections of aspirated particles in the diagnosis of HD.In non-Hodgkin's lymphomas, biopsy was also the mostsensitive diagnostic procedure, particularly with follicular lym­phomas, although there were several positive clot sections in thepresence of negative biopsies. On the basis of a study performedon 30 cadavers, Rywlin9 concluded that aspirated marrow par-

276 SA MEDICAL JOURNAL VOLUME 64 20 AUGUST 1983

ticles which were concentrated before sectioning yielded largerareas of marrow for examination than needle biopsy sections.This may be misleading, as 10 ml of marrow was aspirated ineach case and this is not always possible in vivo. It is neverthelessclear that the various techniques are complementary. In practice,however, we have found it simpler to obtain and process biopsyspecimens as described earlier. Moreover, in contrast to Rywlin,we are able to obtain equally as good cytological detail in ourtrephine sections as in the particle sections. It is rare to obtaininadequate specimens, whereas with aspiration inadequate sec­tions for examination may be obtained in as many as 10% ofcases.7

We should like to re-emphasize the importance of properfixation and preparation of sections. We have frequently recei­ved slides which are difficult to interpret owing to poor fixationand thick sections. To obtain good trephine sections is an artwhich requires some practice and it is therefore preferable torefer patients requiring marrow trephines to centres where biop­sies are regularly performed and the specimens examined, ratherthan submit an inadequate specimen for opinion. This oftenleads to the patient having to undergo the procedure a secondtime.

Bone marrow sections should be interpreted by a pathologistor haematologist in conjunction with a thorough examination ofthe smear preparations. The practice of examining marrow sec­tions in isolation is not recommended and may lead to misdiag­nosis.

In summary, therefore, it is our experience that bone marrowbiopsy sections with concurrent marrow aspiration smears arecomplementary, and together allow for a thorough assessment ofthe bone marrow. The morbidity is minimal and the procedurecan be performed on outpatients. The few contraindications tobiopsy are those associated with a severe bleeding tendency as aresult of depletion of coagulation factors.

This study was supported by the Universiry ofCape Town Leuk­aemia Centre and Staff Research Fund, the South African MedicalResearch Council and the National Cancer Association. We thankDonald Alexander, Kathy Hunter and Johan van Wyk for excellenttechnical assistance, Jackie Davies for typing, Sheila Katcher forbibliographic assistance and the Medical Superintendent, GrooteSchuur Hospital, for permission to publish.

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