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Article of the Week


We will be posting commentaries on articles relating to internal medicine and endocrinology that we think are of interest.


Dec 22nd, 2022


Evaluation of the validity of the double two-thirds rule for diagnosing hemangiosarcoma in dogs with nontraumatic hemoperitoneum due to a ruptured splenic mass: a systematic review

Splenic masses are common in dogs and can be of malignant or benign etiologies. The most common malignant diagnoses include hemangiosarcoma, lymphoma, and other sarcomas, while the most common benign diagnoses include hematoma, hyperplasia, and hemangioma. Diagnosis of the etiology of a canine splenic mass lesion prior to surgical excision via splenectomy and pathologic evaluation is currently not possible, as benign lesions are grossly indistinguishable from malignant lesions and no preoperative factors have been found to be sufficiently accurate for diagnosis. Although many clinical variables on their own are nonspecific for a diagnosis, 2 groups have reported on a combination of clinical variables that may be more specific for a diagnosis. The hemangiosarcoma likelihood score was developed for dogs with spontaneous hemoperitoneum by using patient body weight, total protein, platelet count, and thoracic radiographic findings to determine a patient’s risk of having a diagnosis of hemangiosarcoma.  A second group developed a prediction tool for malignant or benign splenic masses by using information on serum total protein, nucleated RBC count, amount of abdominal effusion, number of splenic nodules, inhomogeneity of the splenic mass, diameter of the splenic mass, number of liver nodules, and whether mesenteric, omental, or peritoneal nodules were present. Although these models can be used to help owners understand the risk of a diagnosis of a malignant lesion, they are not definitive for any particular diagnosis.

Although blood tests such as flow cytometry for endothelial precursor cells and measurement of plasma vascular endothelial growth factor and thymidine kinase have been evaluated for ability to diagnose hemangiosarcoma, none of these tests are both sensitive and specific enough for a diagnosis of hemangiosarcoma. Other groups have evaluated circulating microRNAs for the diagnosis of hemangiosarcoma in dogs, but more work is needed in this area before this is useful clinically. Splenic aspirates may be unrewarding in attempts to achieve a diagnosis, as focal sampling may miss an area of interest, tissue architecture cannot be assessed with cytology, and blood contamination is common. Accuracy of cytology compared to histopathology for splenic lesions is 60% to 61%, although accuracy may be improved when evaluating nonneoplastic lesions. Mass rupture with subsequent hemorrhage and tumor seeding is a concern when aspirating splenic masses, although this complication was not reported in 1 study of splenic aspiration. Diagnostics such as contrast harmonic ultrasound, CT, and MRI may show characteristics that can differentiate malignant from benign lesions, but the availability of these techniques is limited and cost can be prohibitive in some cases. Another group found that smaller masses compared to splenic volume were more likely to be hemangiosarcoma than benign lesions, but numerous factors can alter the size of the spleen, which could affect these measurements, and no optimal cutoffs for size were determined. 

In the absence of more definitive diagnostics prior to surgery, veterinarians frequently rely on the double two-thirds rule to guide owners on the probability of a malignant versus benign lesion and a diagnosis of hemangiosarcoma. This rule states that two-thirds of splenic masses will be malignant, and of those malignancies, two-thirds will be hemangiosarcoma. Although this rule seems to have originated for all splenic masses independent of the presence of hemoperitoneum, the double two-thirds rule more closely applies to dogs with hemoperitoneum due to their splenic mass based on the literature. Previous groups have identified that approximately 62.5% to 84.3% of dogs with hemoperitoneum due to a ruptured splenic mass have a malignancy, and of those, 85.1% to 100.0% have hemangiosarcoma. A more favorable prognosis has been found for dogs with incidentally identified, nonruptured splenic masses, with 70.5% of dogs with nonruptured masses having benign lesions and only 17.1% having splenic hemangiosarcoma in 1 study. The objective of the current study was to systematically examine the peer-reviewed veterinary literature to assess the validity of the double two-thirds rule for dogs with hemoperitoneum due to a splenic mass. The hypothesis was that the double two-thirds rule would be accurate, with two-thirds of dogs with hemoperitoneum due to a splenic mass having a malignant lesion and two-thirds of those dogs having splenic hemangiosarcoma.


To evaluate the validity of the double two-thirds rule for a diagnosis of splenic hemangiosarcoma in dogs with nontraumatic hemoperitoneum due to a ruptured splenic mass.


Systematic literature review.


3 databases (PubMed, CAB abstracts, and World of Science) were searched in November 2020. Articles were included if data on dogs with nontraumatic hemoperitoneum due to a splenic mass were included and subsequent pathologic diagnosis could be determined.


In total, 2,390 unique articles were identified, with 66 articles meeting the criteria for full-text review and 14 articles included for analysis. A total of 1,150 dogs were evaluated, with 73.0% (840/1,150) of dogs being diagnosed with a malignant splenic lesion and 27.0% (310/1,150) being diagnosed with a benign splenic lesion. Of the malignancies, 87.3% (733/840) were hemangiosarcoma. Levels of evidence were low, and bias was high as most included studies were retrospective case series.


The double two-thirds rule should be refined when evaluating dogs with nontraumatic hemoperitoneum from a ruptured splenic mass, with more dogs being diagnosed with a malignancy and hemangiosarcoma specifically than the double two-thirds rule indicates. These findings may be useful in an emergency setting to guide owners on potential diagnoses for dogs with nontraumatic hemoperitoneum due to a ruptured splenic mass. However, there remains a portion of these dogs with benign conditions and nonhemangiosarcoma malignancies that may have a good long-term prognosis compared to dogs with hemangiosarcoma. Studies with higher levels of evidence, lower risks of bias, and large case numbers are needed in the literature.

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