Editors: Olga Pozdnyakova, MD, PhD, Geoffrey Wool, MD, PhD, David Bernard, MD, PhD & Raul S. Gonzalez, MD
Submit your pathology-related question for reply by appropriate medical consultants. CAP TODAY will make every effort to answer all relevant questions. However, those questions that are not of general interest may not receive a reply. For your question to be considered, you must include your name and address; this information will be omitted if your question is published in CAP TODAY. Submit a question.
Q. Are laboratories sticking to the established standard of spinning whole blood coagulation test tubes within four hours of specimen collection or are most changing to a 24-hour window (with some exceptions) per Clinical and Laboratory Standards Institute guidelines?
A. August 2026—The 2024 CLSI document H21-Ed6 (chapter 4, Whole Blood Specimen Transport Before Processing) addresses the acceptable time delay before whole blood centrifugation to obtain plasma for coagulation testing.1 Earlier guidance, such as the 2008 CLSI document H21-A5, indicated that specimens for prothrombin time could be maintained in an uncentrifuged or centrifuged state with the plasma on top of the cellular component and stored in a capped tube at room temperature for up to 24 hours from specimen collection.2 The same document indicated that activated partial thromboplastin time (APTT) specimens from patients not receiving heparin could be maintained in these conditions for up to four hours from the time of collection. Most other coagulation test stabilities were treated the same as APTT. In the H21-Ed6 edition, the four-hour requirement for activity assays of labile coagulation factors protein S and factor VIII remains, but APTT stability is updated to six to eight hours for nonheparinized patients, and an extended ambient stability of 24 hours or longer is cited for some specialized assays, which is based on published literature.
Expanded ambient stability prior to centrifugation is of interest to laboratories since there are often delays in transporting samples from the collection site to the laboratory. However, there are several factors laboratories should consider before implementing extended ambient stability for applicable coagulation assays. For instance, manufacturer instructions for use (IFU) for coagulation reagents and collection tubes may conflict with published literature showing extended stability. In addition, as mentioned in H21-Ed6, published data may not be translatable to every test system and abnormal sample a lab receives. It would also be difficult to maintain varying ambient stabilities, which are based on specific coagulation analytes, given that multiple tests are often ordered on the same sample and more complex processing instructions are required.
Local validation can determine how local data compare to published literature. A practical approach could be to maintain shorter ambient stabilities and use extended time limits for exceptions involving delayed transportation, as mentioned in H21-Ed6. Ultimately, the laboratory medical director should define the acceptable ambient stability for coagulation samples based on information relevant to the specific laboratory.
- Clinical and Laboratory Standards Institute. H21: Collection, Transport, and Processing of Blood Specimens for Testing Plasma-Based Coagulation Assays; Approved Guideline, 6th ed.; 2024.
- Clinical and Laboratory Standards Institute. H21-A5: Collection, Transport, and Processing of Blood Specimens for Testing Plasma-Based Coagulation Assays and Molecular Hemostasis Assays; Approved Guideline, 5th ed.; 2008.
Kristi J. Smock, MD
Professor of Pathology
University of Utah School of Medicine
Medical Director
ARUP Hemostasis/Thrombosis Laboratory
Salt Lake City, Utah
Chair, CAP Hemostasis and Thrombosis Committee
Q. I am evaluating a large, well-circumscribed necrotic pelvic peritoneal implant in a case of serous borderline tumor (SBT) of the ovary. The implant shows nonviable necrotic tissue displaying only residual ghost papillary outlines with calcification. My initial interpretation is the peritoneal nodule is an invasive implant because it is large. I am assuming the necrosis represents infiltrative, destructive, and expansile neoplastic cells that form the large nodule (17 mm). I considered upgrading the SBT to low-grade serous carcinoma (LGSC) because of the presence of this implant. However, since the implant is necrotic, I cannot reliably evaluate for tumor cells. In addition, it is rare to have an invasive implant without an invasive component at the primary site. What is your opinion regarding this implant?
A. Several factors should be considered when evaluating an entirely necrotic tissue sample. In general, making a definitive diagnosis based on a tissue sample that is necrotic is not advisable due to such factors as loss of architecture and cytomorphologic detail, as well as superimposed secondary changes, such as the presence of debris, calcification, or inflammation. One cannot reliably apply validated standard diagnostic criteria to a necrotic tissue fragment.
Measuring implant size from necrotic tissue is also inadvisable since one cannot accurately assess the volume of tumor within this necrotic tissue fragment. Papillary formations may represent florid mesothelial hyperplasia, while clusters of ghost cells may represent aggregates of macrophages and inflammatory cells.1
The limited information points to a noninvasive process—either a benign, inflammatory-reactive or noninvasive serous borderline ovarian tumor (SBOT) implant. Circumscription, easy stripping from underlying tissue, and the absence of an evaluable tumor-tissue interface are criteria for noninvasive implants.2,3 The description of ghost papillary outlines with calcifications also suggests a noninvasive SBOT implant.
LGSC/invasive implants are epithelial predominant and composed of complex glandular-cribriform arrangements, micropapillae with fine tissue cores, or solid epithelial nests surrounded by clefts in a fibrotic-desmoplastic stroma.4 (The 2020 World Health Organization classification of female genital tumors considers LGSC synonymous with invasive implants, while the European Society for Medical Oncology and European Society of Gynecological Oncology working group does not support using these labels synonymously.5,6) The inability to evaluate the cytology of the necrotic cells precludes a diagnosis of LGSC. Low-grade serous carcinoma shows a relatively monomorphic population of small cells lining micropapillae, while SBOT shows a more varied population of cells.3,4
Since the majority of peritoneal LGSC/invasive implants are associated with a similar tumor in the ovary or an SBOT with micropapillary architecture, it would be prudent to ensure good sampling of the primary tumor and other peritoneal sites to ensure that an LGSC/invasive implant is not overlooked elsewhere. If the primary tumor shows areas of microinvasion, extended sampling with two sections per centimeter may be warranted, as a subset of tumors with microinvasion will meet criteria for overt carcinoma on extended sampling.7
In keeping with standard practices, collaborative decision-making with the clinician and discussion at a multidisciplinary tumor board would ensure optimal patient management.
- Clement PB, Young RH. Florid mesothelial hyperplasia associated with ovarian tumors: a potential source of error in tumor diagnosis and staging. Int J Gynecol Pathol. 1993;12(1):51–58.
- Bell DA, Weinstock MA, Scully RE. Peritoneal implants of ovarian serous borderline tumors: histologic features and prognosis. Cancer. 1988;62(10):2212–2222.
- McKenney JK, Gilks CB, Kalloger S, Longacre TA. Classification of extraovarian implants in patients with ovarian serous borderline tumors (tumors of low malignant potential) based on clinical outcome. Am J Surg Pathol. 2016;40(9):1155–1164.
- Bell KA, Smith Sehdev AE, Kurman RJ. Refined diagnostic criteria for implants associated with ovarian atypical proliferative serous tumors (borderline) and micropapillary serous carcinomas. Am J Surg Pathol. 2001;25(4):419–432.
- Colombo N, Sessa C, du Bois A, et al.; ESMO–ESGO Ovarian Cancer Consensus Conference Working Group. ESMO–ESGO consensus conference recommendations on ovarian cancer: pathology and molecular biology, early and advanced stages, borderline tumours and recurrent disease. Int J Gynecol Cancer. 2019;29(4):728–760.
- Renz M, Friedlander M, Berek JS. Cancer of the ovary, fallopian tube, and peritoneum: 2025 update. Int J Gynecol Obstet. 2025;171(suppl 1):6–35.
- Seidman JD, Savage J, Krishnan J, Vang R, Kurman RJ. Intratumoral heterogeneity accounts for apparent progression of noninvasive serous tumors to invasive low-grade serous carcinoma: a study of 30 low-grade serous tumors of the ovary in 18 patients with peritoneal carcinomatosis. Int J Gynecol Pathol. 2020;39(1):43–54.
Vinita Parkash, MBBS, MPH
Associate Clinical Professor of Pathology
Yale School of Medicine
Senior Research Scientist in Health Policy
Yale School of Public Health
New Haven, Conn.
Ekene Okoye, MD
Associate Professor
Department of Pathology and Genomic Medicine
Houston Methodist Hospital
Houston, Tex.
Member, CAP Surgical Pathology Committee