College of American Pathologists
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  Q & A





February 2011

Fredrick L. Kiechle, MD, PhD

Question Q. What is the best way to report the color of cerebrospinal fluid? When I was in school we were taught to report colored CSF as xanthochromic, but, as you know, this covers all colors from pale pink to yellow to green. Should we report colored CSF as xanthochromic, or, because reporting a color seems to provide the physician with more information about the cause of the color, should we report the color?

A. Xanthochromia is a term that means “other color,” and therefore can describe a spectrum of colors ranging from pale pink to yellow to green, etc., as noted in the question. In most circumstances, xanthochromia is due to the presence of blood in the CSF. To examine for xanthochromia, the tube of CSF is spun down and examined over a white background. Any color change, including pale pink or yellow, is indicative of xanthochromia.

As I noted in a 1994 discussion on this topic for a Surveys specimen (see 1994 CM-A, slides CM-07, 08, 09),1xanthochromia is one of the earliest changes that is seen, and can be useful in distinguishing path-ologic hemorrhage from the peripheral blood contamination of a traumatic lumbar tap. Xanthochromia is a pale orange pink color that appears in the normally clear cerebrospinal fluid” as early as two to four hours after hemorrhage and “is due to the breakdown of red blood cells and release of oxyhemoglobin into the CSF. This process peaks in 24 to 36 hours and gradually disappears in four to eight days. A pale yellow color appears at approximately 12 hours due to the presence of bilirubin in the CSF, peaking in two to four days, and disappearing after two to four weeks.”1,2

However, as I also noted at that time, “there are a few causes of xanthochromia which are not related to hemorrhage, including elevated serum levels of direct bilirubin, CSF protein greater than 150 mg/dL, carotenoids in CSF due to systemic hypercarotenemia, melanin in CSF due to meningeal melanoma, or contamination of CSF by merthiolate used to disinfect the skin. Premature newborns can be expected to have mild xanthochromia normally.”1-3 If only “xanthochromia present” is reported instead of the actual color observed, the erroneous impression of intracerebral hemorrhage could be implied or misunderstood by the clinician, or both, and the search for a more obscure cause of xanthochromia may not be undertaken in a timely manner.

Another helpful clue for distinguishing true intracerebral hemorrhage from a traumatic tap or other cause of xanthochromia is the presence of erythrophages or siderophages in the CSF. As I also noted in the 1994 discussion: “Macrophages begin scavenging the extravasated blood almost immediately, and intact red blood cells can be identified within their cytoplasm within one to two days.” If the sample is allowed to sit for any length of time, one can observe erythrophagocytosis in a traumatic tap, but examination of CSF is usually fairly rapid and this potentially confounding finding should be avoided. “The red blood cells are broken down, losing their color and appearing as pale vacuoles in the cytoplasm. After approximately two to four days, hemosiderin appears within the cytoplasm as bluish-black or yellow to brown granules (siderophage). The granules can be further demonstrated with an iron stain. Siderophages may persist for several months after hemorrhage. Hematoidin pigment may also be seen as brown yellow to red granules in the cytoplasm of macrophages.”1-3

Therefore, I would agree with the questioner that it is better to report the actual color of the CSF rather than use the term “xanthochromia.” However, you will want to communicate this decision to your clinical colleagues clearly and carefully. I recently had a physician ask that a CSF be sent out for “xanthochromia testing” because we were not using that term, but rather reporting the color observed. It is also important to report the presence of erythrophages or siderophages in CSF, as it implies hemorrhage into the fluid before collection of the sample. One should also take care to examine cerebrospinal fluid samples as soon as possible after collection.


1. Galagan KA. CAP Proficiency Testing Surveys. CM-A; 1994.

2. Smith GP, Kjeldsberg CR. Cerebrospinal, Synovial and Serous Body Fluids. In: Henry JB, ed. Clinical Diagnosis and Management by Laboratory Methods. 20th ed. Philadelphia, Pa.: WB Saunders Co.;1991:404–405.

3. Galagan KA, Blomberg D, Cornbleet PJ, et al., eds. Color Atlas of Body Fluids: An Illustrated Field Guide Based on Proficiency Testing. Northfield, Ill.: College of American Pathologists; 2006:50–51, 148–151, 158–159, 272–275.

Katherine A. Galagan, MD
Director of Clinical Laboratories
Virginia Mason Medical Center

Question Q. Is it acceptable to reflex a pathologist review of a peripheral blood smear from a CBC with differential order? Or is a separate physician’s order needed? Currently, we do this as a reflex test (approved by our medical executive committee) from the results of the CBC/diff, and we automatically include the review without a separate physician’s order if the results meet the criteria for review. Whether we can charge for the review without a separate physician’s order has come into question. Do you know how other labs handle this situation?

A. A reflex order for a peripheral smear should func-tion in the same way as other reflex lab testing, such as “progressive” thyroid tests. All reflex testing protocols should be approved by the medical executive committee or the entire medical staff in small settings. Ours are reviewed and reapproved annually. We do not require a separate physician’s order. The order is initiated in the information system as part of a reflex protocol and the charges cross over accordingly.

That being said, there may be unaccountable differences based on specific payers. Regions of the country vary, especially for Medicare and Medicaid.

Roberta L. Zimmerman, MD
Grand Itasca Clinic and Hospital
Grand Rapids, Minn.
Member, CAP Hematology/Clinical Microscopy Resource Committee

Question Q. Can hypersegmented polymorphs be a manifestation of myelodysplasia? An elderly patient had slightly enlarged hypersegmented polymorphs, some with as many as 10 lobes. Serum folate and vitamin B12 levels were normal. A normochromic normocytic anemia was present, manifestation of anemia of chronic disease (decreased iron, decreased total iron-binding capacity, and normal ferritin), with some response to erythropoietin (procrit). Also present were hypersegmented eosinophils (three lobed), basophils with lighter staining granules, mild thrombocytopenia (100,000), and a decreased mean platelet volume. A bone marrow biopsy was not performed.

A. Hypersegmentation of cells of myeloid lineage can be observed in the peripheral blood of patients with myelodysplastic syndromes, or MDS. Hypersegmented polymorphonuclear leukocytes may be seen in addition to the hypo- and unsegmented nuclei of the pseudo-Pelger-Huët anomaly and ring-shaped nuclei. This finding in a patient with normal serum folate and vitamin B12 levels with anemia and thrombocytopenia raises the possibility of MDS. Other dysplastic findings in the myeloid cells include Auer rods, nuclear sticks, and hypogranular cytoplasm. Dysplastic erythroid maturation may be represented in oval macrocytes, elliptocytes, acanthocytes, stomatocytes, teardrops, nucleated red blood cells, basophilic stippling, and Howell-Jolly bodies. Dysplastic features of giant, hypogranular, or agranular platelets may be observed.

Diagnosis of MDS does require examination of the bone marrow, especially a bone marrow aspirate. Cytogenetics are usually obtained at the time of bone marrow aspirate and biopsy. In addition to nutritional deficiencies, other entities that should be excluded in diagnosing MDS include viral infections; toxic or drug exposures, including arsenic and lead exposure; recovery from chemotherapy; and growth factor administration.


Kjeldsberg CR, Perkins SL, eds. Practical Diagnosis of Hematologic Disorders. 5th ed. Chicago: ASCP Press;2010:547–582.

Martha R. Clarke, MD
St. Clair Hospital
Member, CAP Hematology/Clinical
Microscopy Resource Committee

Dr. Kiechle is medical director of clinical pathology, Memorial Healthcare, Hollywood, Fla.