College of American Pathologists
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  Q & A





July 2010

Fredrick L. Kiechle, MD, PhD

Question Q. Our cytology laboratory has received a request to process and report gynecologic cytology specimens from endocervical brushings that do not include a squamous ectocervical or T-zone component. Is there a place for this version of an endocervical curettage in gynecologic cytology? If so, how should it be reported? Do Bethesda System adequacy requirements regarding a squamous component (5,000 squamous cells) apply?

A. Cytology specimens submitted separately as “endocervical brushings” clearly are gynecologic cytology specimens but are not Pap tests (Pap smears). Thus, the Bethesda System adequacy and reporting criteria do not apply. Although these specimens are generally liquid-based, they may also be prepared as conventional direct smears similar to bronchial brushings. There are no approved limits on cellularity, and the significance of the presence or absence of any squamous component in this specimen is unknown. Similar limitations also apply to endocervical curettage specimens, for which these brushings are often used as a substitute. As with any other cytology specimen, individual laboratories must establish their own adequacy standards through the use of standard reporting formats such as the Bethesda System; by consulting the literature; or, for those specimens for which these resources are not available, by analyzing the specimen in terms of what the intent of the sampling is and how sample characteristics might relate to the presence of a target lesion.

The reporting format is also the choice of the individual laboratory and may be similar to a Pap test report. The information on the report should contain all of the elements discussed in the CAP “Guidelines for the reporting of non-gynecologic cytopathology specimens” (Arch Pathol Lab Med. 2009;133:1743–1756., and an educational note explaining the goals and limitations of the specimen would be helpful. These specimens would not be appropriate for any of the existing imaging technologies (SurePath Focal-Point Guided Screening or ThinPrep Imager). For billing purposes, it is important to remember that although the specimen is gynecologic in terms of its source, as indicated above, it is not a Pap test and does not meet the CPT definition of “cytopathology, cervical or vaginal.” If the sample is prepared as a direct smear, the most analogous code is the nongynecologic code 88104 (Cytopathology, fluids, washings or brushings, except cervical or vaginal; smears with inter-pretation). If it is prepared from a liquid-based sample (ThinPrep or SurePath), 88112 is the most appropriate code. Remembering to count the resulting slide(s) in the daily workload limits is important, and since the prep-aration is not a Pap test (cervical or vaginal sample), a physician must review the case and sign it out just like all nongynecologic specimens.

William D. Tench, MD
Associate Director, Laboratory Services
Chief, Cytology Services
Palomar Medical Center
Escondido, Calif.

Question Q. When a patient’s pretransfusion temperature is less than 98.6°F but then rises above 98.6°F (upper limit of normal range), when is it considered a febrile trans-fusion reaction? In our institution, we consider a 2°F increase over 98.6°F a febrile reaction. However, if the pretransfusion temperature is less than 98.6°F, and the temperature during or one hour after transfusion exceeds 98.6°F but is less than 100.6°F, when is it a febrile reaction requiring workup?

A. There is no standard definition or set of criteria used uniformly throughout the country or in various textbooks for the evaluation and diagnosis of febrile transfusion reaction. Thus, each institution must define its own criteria.

First, when is it necessary to perform a febrile reaction evaluation?

Neither the College of American Pathologists nor the AABB cite specific signs and symptoms requiring a transfusion workup. Both organizations say there must be criteria, processes, and procedures (CAP TRM.41650 and AABB Standards for Blood Banks and Transfusion Services, 26th ed. Standard 7.4.1. AABB;2009). The CAP checklist reference says febrile nonhemolytic transfusion reaction (FNHTR) is “characterized by fever (defined as an increase in temperature by ≥1ºC above pretransfusion baseline)....” This article did not define fever for acute hemolytic reactions.1

AABB’s Technical Manual, 16th ed., lists the signs and symptoms that may be indicators of a transfusion reaction as fever (generally defined as ≥1ºC rise in temperature above 37ºC); chills with or without rigors; respiratory distress (wheezing, coughing, and dyspnea); hyper- or hypo-tension; abdominal, chest, flank, or back pain; pain at the infusion site; skin manifestations (urticaria, rash, flushing, pruritus, and localized edema); nausea/vomiting; abnormal bleeding; and oliguria/anuria.2

One textbook recommends laboratory evaluation for transfusion reaction if the temperature increases by ≥1ºC.3

Second, what is the definition of febrile transfusion reaction?

The National Healthcare Safety Network: Biovigilance Component defines a FNHTR as fever or chills, or both, without hemolysis occurring in the patient up to four hours after transfusion. A fever is defined as ≥38ºC (100.4ºF) oral or equivalent and a change of ≥1ºC (1.8ºF) from pre-transfusion value.4

In AABB’s Technical Manual, 16th ed., FNHTR is “defined as the occurrence of ≥1°C rise in temperature above 37ºC (98.6ºF) associated with transfusion for which no other cause is identifiable.”2

Other references use a temperature rise of 1ºC or more, without requiring the patient to have a “fever.”3,5,6,7 In these resources, fever in acute hemolytic transfusion reactions is not defined.


  1. Sazama K, DeChristopher PJ, Dodd R, et al. Practice parameter for the recognition, management, and prevention of adverse consequences of blood transfusion. College of American Pathologists. Arch Pathol Lab Med. 2000;124:61–70.
  2. Roback JD, ed. Technical Manual, 16th ed. Bethesda, Md.: AABB;2008.
  3. McPherson RA, Pincus MR. Henry’s Clinical Diagnosis and Management by Laboratory Methods, 21st ed. China: WB Saunders Elsevier;2007.
  5. Uhlmann EJ, Isgriggs E, Wallhermfechtel M, et al. Prestorage universal WBC reduction of RBC units does not affect the incidence of transfusion reactions. Transfusion. 2001;41:997–1000.
  6. sec11-ch146-ch146d-1093.
  7. Hoffman R, Benz EJ, Shattil SJ, et al., eds. Hematology: Basic Principles and Practice, 4th ed. Philadelphia, Pa.: Churchill Livingston;2005.

Beth H. Shaz, MD
Associate Professor of Pathology
and Laboratory Medicine
Emory University School of Medicine
Liaison, CAP Transfusion
Medicine Resource Committee

Question Q. Does chromosomal analysis contribute in decisions for therapy, staging, or prognosis for patients with myeloma?

A. Several clinical parameters have been used as prognostic factors for survival in patients with multiple myeloma (MM), including serum beta-2 microglobulin, age, performance status, serum albumin, serum creatinine, platelet count, plasma cell labeling index, serum calcium, and hemoglobin.1

Chromosome analysis by cytogenetics and fluorescent in situ hybridization (FISH) has an important role in determining the prognosis and choice of therapeutic interventions in patients with MM.2 Though nearly all MM patients have chromosomal abnormalities at the time of diagnosis, only about one-third of patients have detectable chromosomal abnormalities by conventional cytogenetic analysis because of the low proliferation activity of plasma cells. MM patients with hyperdiploidy due to nonrandom gains of chromosomes 3, 5, 7, 9, 11, 15, 19, and 21 have better overall survival. In contrast, hypodiploid patients show more resistant disease and shorter survival.3

Since FISH is performed on interphase cells, it overcomes the low proliferation activity of plasma cells. The IgH (heavy chain) locus (14q32) is most commonly involved in translocations in MM patients. FISH for t(11;14) (IgH, cyclin D1), t(4;14) (IgH, FGFR3), del(17p) (p53), del(13q) (Rb-1), and t(14;16) are commonly used targets for prognostication.2 The presence of del(17p), t(4;14), and t(14;16) and del(13q) predicts shorter overall survival, while t(11;14) is associated with improved survival. The amplification of the 1q or deletion of 1p, or both, may predict poor outcome.3

Cytogenetics and FISH should be performed at the time of diagnosis and time of relapse.2 The impact of clinical and molecular factors on a patient’s prognosis/survival depends not only on other genetic and microenvironmental factors but also on the type of therapeutic interventions.2, 3


  1. Kyle RA, Gertz MA, Witzig TE, et al. Review of 1027 patients with newly diagnosed multiple myeloma. Mayo Clin Proc. 2003;78:21–33.
  2. Munshi NC. Investigative tools for diagnosis and management. Hematology Am Soc Hematol Edu Program. 2008:298–305.
  3. Avet-Loiseau H. Role of genetics in prognostication in myeloma. Best Pract Res Clin Haematol. 2007;20:625–635.

M. Ali Ansari-Lari, MD, PhD
Pathology Consultants of South Broward
Memorial Healthcare System
Hollywood, Fla.

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