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Bone marrow elements in cerebrospinal fluid: Review of literature with a case study.
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PMID:  24228067     Owner:  NLM     Status:  PubMed-not-MEDLINE    
Abstract/OtherAbstract:
Presence of bone marrow elements in cerebrospinal fluid is rare. Journal publications on this topic are few and majority of them were written over a decade ago mostly as case reports in young children or the elderly. The increased cellularity and presence of myeloid precursors can be a pitfall and may be misdiagnosed as leukemia or lymphoma or central nervous system infection, when the specimen is actually not representative. With the intention to create awareness of potential pitfalls and avoid erroneous diagnoses, as well as adding on to the current photo archive of bone marrow elements in CSF, we present a recent case of bone marrow contaminants in the CSF of a 16-year-old girl.
Authors:
Anitha Ann Thomas; Felicia Tze Yee Goh
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Publication Detail:
Type:  Journal Article     Date:  2013-09-27
Journal Detail:
Title:  CytoJournal     Volume:  10     ISSN:  1742-6413     ISO Abbreviation:  Cytojournal     Publication Date:  2013  
Date Detail:
Created Date:  2013-11-14     Completed Date:  2013-11-14     Revised Date:  2014-01-24    
Medline Journal Info:
Nlm Unique ID:  101231642     Medline TA:  Cytojournal     Country:  India    
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Languages:  eng     Pagination:  20     Citation Subset:  -    
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Journal Information
Journal ID (nlm-ta): Cytojournal
Journal ID (iso-abbrev): Cytojournal
Journal ID (publisher-id): CJ
ISSN: 0974-5963
ISSN: 1742-6413
Publisher: Medknow Publications & Media Pvt Ltd, India
Article Information
This article is available from: http://www.cytojournal.com/content/10/1/20Copyright: © 2013 Thomas AA and Goh FTY; licensee Cytopathology Foundation Inc
open-access:
Received Day: 26 Month: 4 Year: 2013
Accepted Day: 16 Month: 7 Year: 2013
collection publication date: Year: 2013
Electronic publication date: Day: 27 Month: 9 Year: 2013
Volume: 10E-location ID: 20
PubMed Id: 24228067
ID: 3814656
Publisher Id: CJ-10-20
DOI: 10.4103/1742-6413.119009

Bone marrow elements in cerebrospinal fluid: Review of literature with a case study
Anitha Ann Thomas, MBBS MD FRCPA12* Email: Anitha.Thomas@health.wa.gov.au
Felicia Tze Yee Goh, MBiomedSc CT (ASC) CT (IAC)13 Email: Felicia_gty@yahoo.com
Address: 1Department of Tissue Pathology and Cytopathology, PathWest Laboratory Medicine, QEII Medical Centre, Hospital Ave, Nedlands WA 6009
2School of Pathology and Laboratory Medicine, University of Western Australia, Western Australia
3Department of Laboratory Medicine, Jurong Health Services, Alexandra Hospital, 378 Alexandra Road, Singapore
*Corresponding author

INTRODUCTION

Bone marrow elements can be seen on rare occasions as contaminants in cerebrospinal fluid (CSF). The increased cellularity and presence of myeloid precursors may result in an erroneous cytological diagnosis of central nervous system (CNS) infection or even lymphoma or leukemia. Treatment following the misdiagnoses would be unnecessary and possibly harmful for the patient. Due to its uncommon occurrence, majority of the literature on bone marrow elements found in CSF were written over a decade ago, mostly reported in young children or the elderly. Even though some textbooks do mention bone marrow elements in CSF, there are limited good photographic illustrations. With the intention to create awareness of potential pitfalls and avoid erroneous diagnoses, as well as adding on to the current photo archive of bone marrow elements in CSF, we present a recent case of bone marrow contaminants in the CSF of a 16-year-old girl.


CASE REPORT

A 16-year-old female patient presented with a sudden onset headache, photophobia, left lower leg weakness and jerking movements of upper and lower limbs. Meningitis was queried clinically. She had no past medical history and both chest X-ray and computed topography scan were normal. A lumbar puncture (LP) was performed and CSF for cytology was collected into two tubes. The first tube had 0.5 ml of clear colorless fluid and the second tube had 0.3 ml of slightly blood-tinged fluid. Two cytospin slides were prepared from each of the tubes and stained with both Papanicolaou stain and a Romanowsky-based stain for examination.

Cytological findings

Both specimens show similar findings, with the second specimen more cellular than the first specimen. The specimen contains myeloid and erythroid precursors at various stages of maturation together with occasional lymphocytes and monocytes [Figure 1]. Myeloid precursors such as promyelocyte, myelocyte and metamyelocyte are seen in Figure 1. No megakaryocytes are seen. On review by the cytopathologist, the diagnosis of bone marrow elements as contaminants in the CSF was suggested.

The CSF was reported as non-diagnostic as it contains predominantly bone marrow elements, which are indicative of sampling error and as such, an unsuitable specimen for accurate assessment. Correlation with microbiology and hematology studies was recommended. Subsequent microbiology studies showed decreased leucocyte count (<1 × 106/l) and no growth in blood culture. Hematology studies were within normal limits despite the slight increase in neutrophils and a slight decrease in lymphocytes, red blood cell count and hemoglobin and hematocrit value. Patient was discharged subsequently.

Most CSF specimens are obtained from the subarachnoid space by LP.[1] The cutting Quincke needle remains the most commonly used needle for LP despite the introduction of the non-cutting atraumatic needle that decreases the incidences of post LP headache.[2, 3, 4] Wright et al.,[1] details the stepwise procedure for CSF collection, from the preferable lateral recumbent position that the patient assumes, the use of the L4 vertebra to locate the L3-L4 or L4-L5 intervertebral spaces,[5] insertion of an LP needle, indication of successful needle entry into the subarachnoid space and assessment of CSF flow. Needle repositioning is indicated if the attempt is unsuccessful such as when the needle strikes bone or when the patient experiences a shooting leg pain, which indicates overly lateral needle placement touching the lateral nerve root. The needle is withdrawn slightly, re-angled and advanced gently until a gap is found.[1] Multiple attempts at different sites during the procedure are discouraged, but when needed, the use of muscle relaxants such as a low dose benzodiazepine may aid in minimizing risk of muscle spasms.[1] CSF collected from a traumatic LP will be tinged with blood, which should disappear with serial collections.[1]

Normal CSF, collected from an adult who does not have a neurologic disorder, seizures or undergoing myelography, has low cellularity containing less than 5 cells/mm3.[5, 6] These cells consist of small numbers of mature lymphocytes, monocytes and occasional neutrophils. Other non-neoplastic cellular elements that may be seen in CSF include squamous cells, chondrocytes, meningothelial cells, brain fragments, choroidal cells, ependymal cells and hemopoietic elements from bone marrow or peripheral blood.[5, 6] Germinal matrix cells and notochord remnants may also be seen in newborns.[6] Most of the above mentioned cells are easily recognizable. Bone marrow and peripheral blood elements however require discernment when deciding if a specimen is representative of the area sampled. Bone marrow contamination in particular is rare and may be misinterpreted or overlooked due to inexperience.

The sole cytological diagnostic criterion for bone marrow elements in CSF is the presence of erthyroid precursors, for example a normoblast, together with myeloid precursors.[7, 8, 9] Megakaryocytes may be helpful and have been seen in some cases.[6] When unnoticed, bone marrow elements may become a pitfall for CNS infection such as bacterial or viral meningitis or hematological malignancies including acute leukemia or lymphoma.[10]

Increased cellularity of CSF due to bone marrow elements presents an abnormal CSF picture and has many differential diagnoses. It is important to identify these cases and not over diagnose them as lymphomas or leukemia. Bone marrow elements in CSF should not be misdiagnosed as inflammatory infection caused by CNS infection to prevent the unnecessary antibiotic administration. A cytological picture of predominantly polymorphonuclear leukocytes may indicate non-specific mixed inflammation [Figure 2], bacterial meningitis [Figure 3], cerebral abscess and empyema, CNS hemorrhage and infarction or occasionally the early stages of viral and fungal infection.[5, 8] Immune response caused by malignant processes may present a similar picture [Figure 4].[11] Other infective differential diagnoses include mycobacterial tuberculosis and viral meningoencephalitis in which the CSF contains predominantly lymphocytes and monocytes [Figure 5].[5] The presence of myeloid and lymphoid precursors may suggest CNS involvement by acute leukemia [Figure 6], lymphoma [Figure 7] or contamination by peripheral blood with abnormal blasts [Figure 8].[11] Increased numbers of red blood cells may also result in misdiagnosis of a traumatic tap [Figure 9].

Bone marrow-contaminated CSF submitted for hematological review may result in abnormal white cell counts, unusual differential counts and occasional erroneous diagnosis.[9] Therefore, correlation with microbiological, biochemical and cytological results is important for the assessment of CSF. Negative cultures for virus, fungal, tuberculosis and bacteria exclude the possibility of an infection. The lack of malignant cells together with a combination of low total protein (<45 mg/dl), high glucose (above 45 mg/dl) and normal total cell count has a high negative predictive value, eliminating the possibility of a malignant process.[11] The presence of bone marrow elements cytologically highlights the possibility that the abnormal white blood cell population could be benign hemopoietic elements.

The common explanation for having bone marrow elements in a CSF is when the LP needle is pushed too far anteriorly into the marrow cavity of a vertebral body sampling bone marrow elements. The cells adhere to the needle barrel and are subsequently flushed out together with the flow of CSF after the needle is successfully repositioned.[9] McIntyre[12] suggested an alternate situation where the tip of the needle gets embedded in the bone marrow and cells are aspirated into the needle by very high vacuum forces generated when the stylet is withdrawn rapidly. CSF specimen containing bone marrow elements previously reported were most often from elderly or infant and young patients whereby decreased bone density resulting from geriatric conditions, metastatic diseases or developing bones may have allowed easier penetration of vertebral bone by the LP needle.[7, 8, 9, 10]

It is rare to see bone marrow elements in CSF because the vertebral body is avoided during the LP to reduce patient discomfort and ensure good CSF collection flow.[1] Experienced neurologists and imaging aids play a great role in improving accuracy and efficiency of CSF collection.[1, 13] Improved knowledge of nutrition and ideal dietary habits aid in prevention and treatment of bone conditions such as osteoporosis, reducing the likelihood of needle penetration of the vertebral body. There may also be cases that have been overlooked or misinterpreted by cytotechnologists and pathologists.


SUMMARY

In summary, there are three take home messages from this case. Firstly, bone marrow elements should always be considered when assessing cellular CSF containing erythroid precursors presenting together with myeloid precursors. Secondly, a polymorphous picture should not be automatically assumed to be a proliferative lymphoid disease or inflammatory changes due to infections; instead it should initiate a search for erythroid precursors and metastatic malignant cells. Lastly, correlations between cytological findings, hematology, biochemistry and microbiology results are important as these aid to avoid pitfalls like immune response in a CNS infection or leukemia and lymphoma.


Notes

Available FREE in open access from: http://www.cytojournal.com/text.asp?2013/10/1/20/119009

ACKNOWLEDGMENT

The authors would like to thank Dr. Felicity Frost (PathWest Laboratory Medicine, QEII Medical centre) for her contribution in the diagnosis of the case.

COMPETING INTERESTS STATEMENT BY ALL AUTHORS

The authors declare that they have no competing interests.

AUTHORSHIP STATEMENT BY ALL AUTHORS

All authors of this article declare that they qualify for authorship as defined by ICMJE http://www.icmje.org/#author. Each author has participated sufficiently in the study and takes public responsibility for appropriate portions of the content of this article. Each author acknowledges that this final version has been read and approved by them.

ETHICS STATEMENT BY ALL AUTHORS

As this is case report without identifiers, our institution does not require approval from Institutional Review Board (IRB) (or its equivalent). Authors take responsibility to maintain relevant documentation in this respect.

EDITORIAL/PEER-REVIEW STATEMENT

To ensure the integrity and highest quality of CytoJournal publications, the review process of this manuscript was conducted under a double blind model (authors are blinded for reviewers and vice versa) through automatic online system.


REFERENCES
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2. Thomas SR,Jamieson DR,Muir KW. Randomised controlled trial of atraumatic versus standard needles for diagnostic lumbar punctureBMJYear: 2000Last accessed on 2012 May 1132198690 Available from: http://www.bmj.com/content/321/7267/986?view=long and pmid=11039963. 11039963
3. Tung CE,So YT,Lansberg MG. Cost comparison between the atraumatic and cutting lumbar puncture needlesNeurologyYear: 2012Last accessed on 2012 May 117810913 Available from: http://www.ncbi.nlm.nih.gov/pubmed/22205758http://www.neurology.org/content/78/2/109.long. 22205758
4. Arendt K,Demaerschalk BM,Wingerchuk DM,Camann W. Atraumatic lumbar puncture needles: After all these years, are we still missing the point?NeurologistYear: 2009Last accessed on 2012 May 11151720 Available from: http://www.ncbi.nlm.nih.gov/pubmed/19131853. 19131853
5. Bigner SH,Johnston WW. Cytopathology of the Central Nervous SystemYear: 1994LondonEdward Arnold Publishers2146
6. Cibas ES,Ducatman BS. Cytology: diagnostic Principles and Clinical CorrelatesYear: 20093rd edPhiladelphiaSaunders Elsevier17196
7. Lane PA,Githens JH. Contamination of cerebrospinal fluid with bone-marrow cells during lumbar puncture [letter to the editor]N Engl J MedYear: 1983Last accessed on 2012 May 1130974345 Available from: http://www.ncbi.nlm.nih.gov/pubmed/?term=6877306[uid]. 6877306
8. Luban NL,Alessi RM,Gold BG,Kapur S. Cerebral spinal fluid pleocytosis with bone marrow contaminationJ PediatrYear: 1984Last accessed on 2012 May 111042546 Available from: http://www.ncbi.nlm.nih.gov/pubmed/6694022. 6694022
9. Kruskall MS,Carter SR,Ritz LP. Contamination of cerebrospinal fluid by vertebral bone-marrow cells during lumbar punctureN Engl J MedYear: 1983Last accessed on 2012 May 11308697700 Available form: http://www.ncbi.nlm.nih.gov/pubmed/6828109http://www.nejm.org/doi/full/10.1056/NEJM198303243081206. 6828109
10. Craver RD,Carson TH. Hematopoietic elements in cerebrospinal fluid in childrenAm J Clin PatholYear: 1991Last accessed on 2012 May 11955325 Available from: http://www.ncbi.nlm.nih.gov/pubmed/2014779. 2014779
11. Almeida SM,Nanakanishi E,Conto AJ,Souza LP,Antonelli Filho D,Roda CD. Cerebrospinal fluid cytological and biochemical characteristics in the presence of CNS neoplasiaArq NeuropsiquiatrYear: 2007Last accessed on 2012 May 11658029 Available from: http://www.scielo.br/scielo.php?script=sci_arttext and pid=S0004-282×2007000500014 and lng=en and nrm=iso and tlng=enhttp://www.scielo.br/scielo.php?script=sci_arttext and pid=S0004-282×2007000500014 and lng=en and nrm=iso and tlng=en. 17952285
12. McIntyre HD. Contamination of cerebrospinal fluid by vertebral bone-marrow cells during lumbar puncture [letter to the editor]N Engl J MedYear: 1983Last accessed on 2012 May 1130974345 Available from: http://www.nejm.org/doi/pdf/10.1056/NEJM198308183090719. 6877306
13. Stiffler KA,Jwayyed S,Wilber ST,Robinson A. The use of ultrasound to identify pertinent landmarks for lumbar punctureAm J Emerg MedYear: 2007Last accessed on 2012 May 11253314 Available from: http://www.ncbi.nlm.nih.gov/pubmed/17349909. 17349909

Figures

[Figure ID: F1]
Figure 1 

Cerebrospinal fluid containing bone marrow elements including promyelocyte, myelocyte, metamyelocyte and nucleated red blood cells



[Figure ID: F2]
Figure 2 

Mixed inflammation showing small numbers of lymphocytes and neutrophils



[Figure ID: F3]
Figure 3 

Neutrophilia together with small numbers of normal and activated lymphocytes



[Figure ID: F4]
Figure 4 

Malignant cells of metastatic squamous cell carcinoma surrounded by polymorphous inflammation



[Figure ID: F5]
Figure 5 

Viral meningitis showing normal and activated lymphocytes with and scattered macrophages



[Figure ID: F6]
Figure 6 

Acute lymphoblastic leukemia containing numerous lymphoblasts



[Figure ID: F7]
Figure 7 

Abnormal blasts in B-cell non-Hodgkin's lymphoma



[Figure ID: F8]
Figure 8 

Contaminant peripheral blood containing abnormal blasts



[Figure ID: F9]
Figure 9 

Traumatic tap showing numerous red blood cells with scattered neutrophils and lymphocytes consistent with peripheral blood



Article Categories:
  • Case Report

Keywords: Bone marrow, cerebrospinal fluid, contaminant, pitfall.

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