College of American Pathologists
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  PAP/NGC Q and A





January 2009

Question Q. In cytology specimens, diathesis is often cited as a feature of malignant processes. What causes diathesis, and how reliable is it for the diagnosis of malignancy?

A. Diathesis is the acellular material that can be present in the background of both gynecologic and nongynecologic cytology specimens in patients who have some type of tissue breakdown or destruction. The material that makes up diathesis is typically finely or coarsely granular, consisting of proteinaceous debris or cells. It can also consist of broken down red blood cells or red cell ghosts, or fibrinous debris. Diathesis is associated with any process that leads to tissue necrosis. Such processes can be of either neoplastic or infectious/inflammatory origin, so a diathesis pattern is not specific for invasive tumors. Examples of benign conditions that can present in cytologic specimens with a diathesis pattern include ulcerating processes, such as active herpes simplex infections in Pap tests, or lesions having prominent necrosis, such as cavitary lung lesions caused by Aspergillus. Diathesis is also commonly seen with specimens from invasive carcinomas. In these cases, the diathesis material is derived from the necrotic material and bleeding caused by either tumor cell or normal parenchymal destruction.

The pattern of the background is entirely dependent on the type and location of tissue destruction and the method of preparing the sample. If the degenerated material is sampled directly by the procedure, the diathesis material tends to be more abundant, the granularity of the material is coarse, and it may contain recognizable cell fragments. If the degenerated material is traveling to the sampling device from a remote location, the material tends to be less abundant and more finely granular. The distribution of diathesis across the slide surface is dependent on whether the specimen was conventionally smeared or prepared from a liquid-based specimen. Conventionally prepared slides show a diffuse background of diathesis debris, whereas specimens prepared by the liquid-based method show a clumped or coagulated pattern with the diathesis material present in aggregates and adherent to the surface of intact cells and cell groupings (so-called clinging diathesis).1

Because diathesis patterns can be present in both neoplastic and nonneoplastic conditions, the presence of such background patterns is not specific for the presence of malignancy. However, the presence of diathesis is noted in many invasive carcinomas and, as such, its identification should prompt a thorough review of the slide for malignant cells. In addition, some slides associated with invasive carcinomas having significant components of necrosis can be composed almost entirely of diathesis material—this is most commonly noted in liquid-based specimens but can be present also in conventionally prepared smears. Such a circumstance can prompt an erroneous unsatisfactory interpretation. When one encounters such a specimen, a thorough examination must take place to look for the often rare clues of carcinoma that can be found in some of these cases.

For additional illustrations and discussion about diathesis and other topics of interest, please refer to the CAP’s new gynecologic cytopathology monograph.2


  1. Wilbur DC, Dubeshter B, Angel C, Atkison KM. Use of thin-layer preparation for gynecologic smears with emphasis on the cytomorphology of high-grade intraepithelial lesions and carcinomas. Diagn Cytopathol. 1996;14:201–211.
  2. Henry MR, Clayton A, Cobb C. Look-alikes and morphologic spectrums of change. In: Wilbur DC, Henry MR, eds. College of American Pathologists Practical Guide to Gynecologic Cytopathology. Morphology, Management, and Molecular Methods. Northfield, Ill.: College of American Pathologists; 2008:145–176.

David C. Wilbur, MD
Director, Cytopathology
Massachusetts General Hospital
Chair, CAP Cytopathology Committee