Splenic masses in dogs - Part 1: Epidemiologic, clinical characteristics as well as histopathologic diagnosis in 249 cases (2000-2011)
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Original Article © Schattauer 2012 1 Splenic masses in dogs Part 1: Epidemiologic, clinical characteristics as well as histopathologic diagnosis in 249 cases (2000–2011) N. Eberle1; V. von Babo1; I. Nolte1; W. Baumgärtner2; D. Betz1 1Small Animal Hospital, University of Veterinary Medicine Hannover, Foundation; 2Department for Pathology, University of Veterinary Medicine Hannover, Foundation Key words Schlüsselwörter Canine, splenic mass, staging, hemoperitoneum Hund, Umfangsvermehrung Milz, Staging, Hämaskos Summary Zusammenfassung Objective: Splenic masses have a high prevalence and are more com- Gegenstand: Umfangsvermehrungen der Milz haben beim Hund eine mon than diffuse splenic enlargement in dogs. It was the aim of the hohe Prävalenz und kommen häufiger vor als eine diffuse Vergrößerung present study to retrospectively describe clinical aspects and histopa- des Organs. Ziel der Studie war die retrospektive Beschreibung der kli- thologic characteristics of dogs with splenic masses. Material and nischen Aspekte und die histopathologische Charakteristika von Um- methods: Records of patients with a histologically diagnosed splenic fangsvermehrungen der Milz beim Hund. Material und Methoden: mass between January 2000 and March 2011 were reviewed. Results: Die Auswertung erfasste die Daten von Hunden mit der histopathologi- 249 dogs met the inclusion criteria and could be included in the study. schen Diagnose einer Umfangsvermehrung der Milz zwischen Januar Splenic masses were diagnosed histologically as non-malignant dis- 2000 und März 2011. Ergebnisse: 249 Hunde erfüllten die Einschluss- ease (n = 117; 47%) and malignant splenic disease (n = 132; 53%). kriterien und gingen in die Studie ein. Die Umfangsvermehrungen wur- Hemangiosarcoma was the most common histological diagnosis den histologisch als nichtmaligne Erkrankung (n = 117; 47%) und ma- (n = 97; 73.5%). Other malignant tumors included sarcoma (n = 14), fi- ligne Milzerkrankung (n = 132; 53%) klassifiziert. Das Hämangiosar- brohistiocytic nodules (n = 9) as well as lymphoma, blastoma and ade- kom war der häufigste maligne Tumor (n = 97; 73.5%). Als weitere ma- nocarcinoma. The non-malignant masses consisted of nodular hyper- ligne Tumoren wurden Sarkome (n = 14), fibrohistiozytäre Umfangs- plasia (n = 60), splenic hematoma (n = 41), and splenitis (n = 6). Dogs vermehrungen (n = 9), Lymphome, Blastome und Adenokarzinome dia- with hemoperitoneum had a higher frequency of splenic neoplasia. gnostiziert. Die nichtmalignen Umfangsvermehrungen umfassten no- Conclusion: The results corroborate previous findings that hemangio- duläre Hyperplasien (n = 60), Milzhämatome (n = 41) und Splenitiden sarcoma is the most frequent neoplasm of the canine spleen. However, (n = 6). Bei Hunden mit Hämoabdomen bestand eine höhere Wahr- in approximately half of the cases benign lesions were histologically scheinlichkeit für eine Milzneoplasie. Schlussfolgerung: Die Ergebnis- diagnosed. Clinical relevance: It is essential that a frank discussion is se der Studie bestätigen bisherige Resultate, dass das Hämangiosar- held with owners regarding the prognosis associated with the treat- kom beim Hund den häufigsten Milztumor darstellt. Allerdings wurden ment of dogs with a splenic mass associated with hemoperitoneum. bei annähernd der Hälfte der histologisch untersuchen Milzen nichtma- ligne Veränderungen diagnostiziert. Klinische Relevanz: Eine ausführ- liche Information der Besitzer hinsichtlich der Prognose und Therapie von Hunden mit einer Umfangsvermehrung der Milz in Verbindung mit einem Hämoabdomen ist bedeutsam. Correspondence to Umfangsvermehrungen der Milz beim Hund. Teil 1: Epidemiologische Aspek- Nina Eberle, Dr. med. vet., Diplomate ECVIM-CA (Oncology) te, klinische Charakteristika sowie histopathologische Befunde von 249 Fäl- Small Animal Hospital len (2000–2011) University of Veterinary Medicine Hannover, Foundation (English version of) Tierärztl Prax 2012; 40 (K): 250–260 Bünteweg 9, D-30559 Hannover Received: December 23, 2011 Germany Accepted after revision: June 5, 2012 Email: Nina.Eberle@tiho-hannover.de Introduction evidence against this (10). According to this study, non-malignant masses, such as hematoma and nodular hyperplasia even account The high prevalence of splenic masses in dogs, along with the sur- for the majority of focal canine splenic masses (10). gical accessibility of the spleen results in a relatively large number Hemangiosarcoma is a malignant tumor of vascular endothe- of splenectomies performed in veterinary medicine (1, 13). Splenic lial origin (2). In dogs, the most common site of hemangiosarcoma nodular masses are widely considered to be indicative of hem- is the spleen. Because of the high potential of splenic hemangiosar- angiosarcoma (5, 17, 26). Recent publications, however, provide coma to develop metastasis, the prognosis is poor (2, 29). Com- Tierärztliche Praxis Kleintiere 4/2012; 40(K): 250–260
2 N. Eberle et al.: Characteristics of canine splenic masses mon sites for metastasis via hematogenous or transabdominal nal effusion. The size of a mass (largest dimension) was evaluated routes are the liver, the omentum, the lung and the heart (2). The and recorded. All images were viewed by use of a standard com- two thirds rule has been applied to canine splenic masses. Appro- puter workstation with Digital Imaging and Communications in ximately two thirds of all splenic masses will have a malignant Medicine (DICOM) viewing softwarea and 3-megapixel grayscale tumor, and two thirds of these malignancies will have a hem- monitorsb. For the determination of the dimension the largest dia- angiosarcoma of the spleen (4, 16, 24). meter was measured in DICOM. Presenting complaints vary and can range from vague, non- With abdominal ultrasonography the appearance of the splenic specific illness, asymptomatic swelling of the abdomen to acute and hepatic lesions was evaluated. The splenic mass was categor- death secondary to hypotensive shock (1, 12). Clinical signs com- ized as being cavernous, inhomogeneous, or homogenous. Mass monly associated in dogs with ruptured splenic masses are related size (largest dimension) was evaluated and recorded. The appear- to severe anemia (12). ance of the liver parenchyma was categorized as homogenous, in- Abdominal radiographs and ultrasonography are used to evalu- homogeneous or containing a cavernous mass. The abdominal ate the spleen. The ultrasonographic appearance of splenic hema- cavity was also reviewed for the presence of effusion. Cardiac ultra- tomas and hemangiosarcomas has been described, but both tend sound was performed in order to evaluate for the evidence of to vary in echogenicity and appearance (30, 31). Based on radio- lesions compatible with metastasis. The echocardiographic exam- graphic findings, ultrasonographic findings and gross inspection, ination and the abdominal ultrasound were performed by clini- malignant and non-malignant splenic masses have non-specific cians with long-standing academic experience in cardiac and ab- characteristics (1, 8, 13, 30). dominal ultrasound. It was the aim of the present study to retrospectively describe clinical aspects and histopathological characteristics of dogs with Tissue sampling and histopathologic examination splenic masses and, based on this, to verify previously described histopathologic distributions for the own hospital population. The entire spleen was surgically removed. An open liver biopsy was obtained with suture fracture on the periphery of the liver lobe and fixed in 10% buffered formalin. In case of focal lesions or other Material and methods changes of the liver parenchyma an additional wedge biopsy was performed. Patients Following splenectomy or euthanasia, each spleen was fixed in 10% buffered formalin. Tissue samples from at least two represen- Dogs with a histopathologically confirmed splenic mass were in- tative areas of the margin between the splenic masses and adjacent cluded in the retrospective study. Exclusion criteria were splenic spleen and one sample of the centre of the mass plus a minimum of enlargement without a splenic mass, sole medical management two grossly appearing normal sections of the spleen were sampled. and lack of histopathologic examination. In case of multiple splenic masses, every nodule was examined. The The routine diagnostic workup included general examination, samples were dehydrated and embedded in paraffin, and 5-μm complete blood count, serum biochemistry, thoracic and abdo- sections were prepared and stained with hematoxylin and eosin. A minal radiographs, transabdominal ultrasound to describe the specific histopathologic diagnosis was made for each mass and the splenic mass and the liver and to evaluate for abdominal effu- presumed normal section of spleen. Each mass was classified as sion, as well as an echocardiographic examination. Information re- malignant or nonmalignant by a board-certified pathologist of trieved from medical records included signalment and presenting the Department for Pathology. The examination of the spleen was complaint (weakness, lethargy, collapse, unspecific symptoms, fe- a routine diagnostic work-up so that different board-certified pa- ver, abdominal distension, weight loss). thologists were involved in the diagnosis. Immunhistochemical Clinical staging in dogs with hemangiosarcoma was performed staining procedures were conducted in cases of indifferent find- according to the WHO clinical staging system for canine hem- ings in the hematoxylin and eosin stained sections. The antibodies angiosarcoma (24). Dogs that are classified as stage I have a pri- used in immunhistochemistry included CD 117, CD 3, CD 79a, mary tumor only, whereas dogs classified as stage II have a primary MAC 387, lysozym, vimentin, desmin, smooth muscle actin, factor tumor with splenic rupture or lymph node involvement, and dogs VII-antigen, MHC-II, melan-A, S-100 protein and cytokeratin. classified as stage III have a primary tumor with splenic rupture or lymph node involvement and evidence of distant metastasis. Diagnostic imaging a Digital Imaging and Communications in Medicine (DICOM) viewing soft- Abdominal radiographs were evaluated by one board-certified ware dicom PACS Version 5; Oehm & Rehbein GmbH, Rostock, Germany oncologist (NE) for the presence of a mass in the mid or cranial b EIZO RadiForce RX 211 grayscale monitor; EIZO NANAO corporation, Is- abdomen, and generalized loss of detail associated with abdomi- hikawa, Japan Tierärztliche Praxis Kleintiere 4/2012; 40(K): 250–260 © Schattauer 2012
N. Eberle et al.: Characteristics of canine splenic masses 3 Table 1 Patient characteristics (weight, sex distribution, age) in dogs with Tab. 1 Patientendaten (Gewicht, Geschlecht, Alter) bei Hunden mit Um- splenic mass with versus without hemoperitoneum (HP) and with malignant fangsvermehrung der Milz mit versus ohne Hämoperitoneum (HP) sowie mit (MT) versus non-malignant tumor (NMT) (p < 0.05 indicates a significant dif- malignem (MT) versus nichtmalignem Tumor (NMT) (p < 0,05 bezeichnet ei- ference). nen signifikanten Unterschied) Dogs with HP Dogs without HP p Dogs with MT Dogs with NMT p n = 145 (58%) n = 104 (42%) n = 134 n = 115 Median body weight (kg) 31 26 0.002 30.5 28 0.008 Range body weight (kg) 6–60 2–85 # 6–85 2–55 # Male 63 (43%) 41 (39%) 0.602 55 (42%) 49 (43%) 1.000 Male castrated 28 (19%) 12 (12%) 0.117 23 (17%) 17 (15%) 0.605 Female 18 (13%) 33 (32%) 0.000 20 (15%) 31 (26%) 0.029 Female spayed 36 (25%) 18 (17%) 0.164 34 (26%) 20 (16%) 0.123 Median age (years) 10 10 0.334 10 11 0.758 Range age (years) 2–16 5–18 # 2–18 5–11 # Statistics dy weight than those with no evidence of abdominal effusion (n = 104) (p = 0.002). Furthermore, there was a higher frequency Descriptive statistics (median, minimum, maximum) of the con- of female dogs in the non-hemoperitoneum group. There was no tinuous variables were calculated separately for the nonmalig- other difference in population characteristics between dogs with nant and malignant splenic masses. The data were not normally and without hemoperitoneum (씰Table 1). distributed, so parametric methods were used to analyze for statis- tical significance. In order to verify the similarity or difference be- 3. Comparison of dogs with malignant and non-malignant tween groups with malignant versus non-malignant masses as tumor well as those with hemoperitoneum and without hemoperito- Dogs with malignant tumor (n = 134) had a higher median body neum, a Mann Whitney U-test was performed for continuous vari- weight than those without malignant tumor (n = 115) (p = 0.008). ables and Fischer’s exact test for categorical variables. A p-value of There was a higher frequency of female dogs in the non-malignant < 0.05 was considered significant. All statistical analyses were per- group (p < 0.029). No other difference in population characteris- formed using SPSS 19.0 statistics Software.c tics between dogs with malignant and non-malignant tumor was found (씰Table 1). Results Presenting complaint Patient characteristics 1. Complete patient population The dogs were presented with clinical signs of apathy/listlessness 1. Complete patient population (n = 114; 46%), collapse (n = 26; 10%), abdominal distension A total of 249 with a splenic mass were included into the study be- (n = 15; 6%), no appetite (n = 16; 7%), fever (n = 6; 2%), and un- tween January 2000 and March 2011. Eighty-five dogs were mixed- specific symptoms (n = 22; 9%). In 50 dogs (20%), the diagnosis breed, with the remaining 164 dogs belonging to 57 breeds. Breeds was an incidental finding. The general condition was assessed by represented by more than five dogs included the German Shepherd the veterinarian as unremarkable (n = 49; 20%), slightly reduced (n = 25), Golden Retriever (n = 13), Labrador Retriever (n = 12), (n = 34; 14%), moderately reduced (n = 96; 39%), and profoundly Dachshund (n = 8) and Boxer (n = 5). The median body weight reduced (n = 70; 28%). was 30 kg (range 2–85 kg). Gender distribution was as follows: 104 male dogs (40 male castrated), 51 female dogs (54 female spayed) 2. Comparison of dogs with and without hemoperitoneum amounting to a male : female ratio of 2 : 1. Median age at the time of Apathy/listlessness and collapse were significantly (p < 0.000; diagnosis was 10 years (range 2–18 years). p = 0.005) more common in the hemoperitoneum group (씰Table 2). Also, the general condition in dogs with hemoperito- 2. Comparison of dogs with and without hemoperitoneum neum was more frequently profoundly reduced (n = 56; p < 0.000). Dogs with hemoperitoneum (n = 145) had a higher median bo- In the dogs with a splenic mass without hemoperitoneum, it was c SPSS 19.0; SPSS Inc., Chicago, IL, USA Tierärztliche Praxis Kleintiere 4/2012; 40(K): 250–260
4 N. Eberle et al.: Characteristics of canine splenic masses more often an incidental finding (n = 40; p < 0.000) than in dogs Ultrasound findings with hemoperitoneum (n = 10). 1. Complete patient population 3. Comparison of dogs with malignant and non-malignant The appearance of the splenic mass was characterized with ab- tumor dominal ultrasonography in 158 dogs (63%). The mass appeared Dogs presented with clinical signs of apathy/listlessness more fre- inhomogeneous in 91 dogs (58%) and cavernous in 67 cases quently had a malignant splenic mass (p < 0.000). In cases in which (42%). The median largest dimension of the splenic mass was 6 cm the splenic mass was an incidental finding, 32% had a non-malig- (range 2–15 cm). The appearance of the liver parenchyma was nant splenic lesion and 10% had a malignant tumor (씰Table 2) characterized in 167 dogs (67%), presenting as homogenous in 124 (p < 0.000). dogs (74%), inhomogeneous in 37 dogs (22%), or cavitated in six cases (4%). Diagnostic imaging In 151 dogs (61%) echocardiography was performed. A right atrial mass could be seen in four cases (3%). Radiographic appearance 2. Comparison of dogs with and without hemoperitoneum Abdominal radiographs were performed in 223 dogs and revealed The splenic mass in dogs without hemoperitoneum was more a mid or cranial abdominal mass in 137 cases (56.4%). The medi- commonly inhomogeneous (p = 0.002) than in dogs with hemo- an largest dimension of the mass was 11 cm (range 3–28 cm). A peritoneum. The liver was more commonly homogenous in dogs generalized loss of detail associated with abdominal effusion was without hemoperiteoneum (p = 0.012; 씰Table 4). obvious in 37 dogs (15.2%). Abdominal radiographs of 19 dogs (8%) showed no intraabdominal mass or signs of hemoabdomen. 3. Comparison of dogs with malignant and non-malignant In six dogs, no radiographs were performed. Because of gastric di- tumor latation (n = 5), pyometra (n = 1) and a large intraabdominal lipo- Dogs with a malignant tumor more commonly had a cavitated ma (n = 1) the radiographic evaluation of the spleen was not pos- mass than dogs with a non-malignant tumor (p = 0.003). A cavi- sible in some patients. There was a significant difference between tated appearance of the liver was associated with a malignant the size of non-malignant splenic masses (median 12 cm; range tumor in all cases (p = 0.031) (씰Table 4). 4–28 cm) and malignant splenic masses (median 10 cm; range 3–24 cm) (p = 0.001) (씰Table 3). Furthermore, loss of detail was Laboratory findings significantly more common in dogs with a malignant tumor (p < 0.000). 1. Complete patient population The median hematocrit was 34% (range 9–70%; reference range Table 2 Presenting complaint in dogs with splenic mass with verus with- Tab. 2 Symptomatik bei Hunden mit Umfangsvermehrung der Milz mit out hemoperitoneum (HP) and with malignant (MT) versus non-malignant versus ohne Hämoperitoneum (HP) sowie mit malignem (MT) versus nicht- tumor (NMT) (p < 0.05 indicates a significant difference). malignem Tumor (NMT) (p < 0,05 bezeichnet einen signifikanten Unter- schied) Dogs with HP Dogs without HP p Dogs with MT Dogs with NMT p n = 145 n = 104 n = 134 n = 115 Apathy/listlessness 86 (59%) 28 (27%) 0.000 76 (59%) 38 (33%) 0.000 Collapse 22 (15%) 4 (4%) 0.005 16 (12%) 10 (9%) 0.421 Abdominal distension 10 (7%) 5 (5%) 0.496 6 (4%) 9 (8%) 0.424 No appetite 7 (5%) 9 (9%) 0.421 11 (8%) 5 (4%) 0.606 Fever 2 (1%) 4 (4%) 0.239 2 (1%) 4 (3%) 0.424 Unspecific symptoms 8 (6%) 14 (13%) 0.040 10 (7%) 12 (10%) 0.507 Incidental finding 10 (7%) 40 (38%) 0.000 13 (10%) 37 (32%) 0.000 Unremarkable 12 (8%) 37 (36%) 0.000 17 (13%) 32 (28%) 0.006 Slightly reduced 12 (8%) 22 (21%) 0.008 17 (13%) 17 (15%) 0.357 Moderately reduced 65 (45%) 31 (30%) 0.018 58 (43%) 38 (33%) 0.069 Profoundly reduced 56 (39%) 14 (13%) 0.000 42 (31%) 28 (24%) 0.323 Tierärztliche Praxis Kleintiere 4/2012; 40(K): 250–260 © Schattauer 2012
N. Eberle et al.: Characteristics of canine splenic masses 5 40–55%); the median platelet count was 199,500/μL (range count (p = 0.000), white blood count (p = 0.046) and the PTT 700–1,007,000/μL; reference range 150.000–500.000/μL); and (p = 0.012) (씰Fig. 1). the median white blood count (WBC) was 15 × 103/μL (range 1–127 ×103/μL; reference range 6.0–12.0 ×103/μL). The prothrom- 3. Comparison of dogs with malignant and non-malignant bin time (PT) was recorded in 148 dogs, and the activated partial tumor thromboplastin time (aPTT) was documented in 149 dogs. The In the group of patients with malignant tumor, the prothrombin median PT was 85% (range 12–150%; reference range 75–130%), time (PT) was recorded in 85 dogs, and the activated partial and the median aPTT was 14 s (range 5–130 s; reference range thromboplastin time (aPTT) was recorded in 86 dogs. In dogs with 10.0–13.1 s). non-malignant tumor the prothrombin time (PT) was recorded in 63 dogs, and the activated partial thromboplastin time (aPTT) was 2. Comparison of dogs with and without hemoperitoneum recorded in 63 dogs. There was a significant difference in the he- The prothrombin time (PT) was recorded in 92 dogs with hemo- matocrit (p = 0.000), platelet count (p = 0.002), white blood count peritoneum and in 56 dogs without hemoperitoneum. The acti- (p = 0.009), and activated PTT (p = 0.001) between the dogs with vated partial thromboplastin time (aPTT) was recorded in 93 dogs malignant and with non-malignant tumor of the spleen (씰Fig. 1). with hemoperitoneum and 56 dogs without. There was significant difference in the laboratory findings between the dogs with and without hemoperitoneum in the hematocrit (p = 0.000), platelet Table 3 Radiographic findings of dogs with splenic mass with versus Tab. 3 Röntgenologische Befunde bei Hunden mit Umfangsvermehrung without hemoperitoneum (HP) and with malignant (MT) versus non-malig- der Milz mit versus ohne Hämoperitoneum (HP) sowie mit malignem (MT) nant tumor (NMT) (p < 0.05 indicates a significant difference). versus nichtmalignem Tumor (NMT) (p < 0,05 bezeichnet einen signifikanten Unterschied) Dogs with HP Dogs without HP p Dogs with MT Dogs with NMT p n = 130 n = 93 n = 123 n = 100 Abdominal mass 75 62 0.246 64 73 0.031 Diameter (cm) 11 10,5 0.536 10 12 0.001 Range (cm) 3–23 3–28 # 3–24 4–24 # Loss of detail 35 2 0.000 32 5 0.000 Splenomegaly 14 16 0.236 21 9 0.122 Unremarkable 6 13 0.027 6 13 0.059 Table 4 Ultrasound findings of spleen and liver in dogs with splenic mass Tab. 4 Sonographische Befunde von Milz und Leber bei Hunden mit Um- with versus without hemoperitoneum (HP) and with malignant (MT) versus fangsvermehrung der Milz mit versus ohne Hämoperitoneum (HP) sowie mit non-malignant tumor (NMT) (p < 0.05 indicates a significant difference). malignem (MT) versus nichtmalignem Tumor (NMT) (p < 0,05 bezeichnet ei- nen signifikanten Unterschied) Dogs with HP Dogs without HP p Dogs with MT Dogs with NMT p n = 82 n = 76 n = 90 n = 68 Spleen Inhomogeneous 41 (50)% 50 (66%) 0.002 44 (49%) 47 (69%) 0.293 Cavitated 41 (50%) 26 (34%) 0.664 46 (51%) 21 (31%) 0.003 Diameter (cm) 7 5 0.575 6 5 0.574 Range (cm) 2–15 1–15 # 1–12 2–15 # Liver n = 92 n = 75 n = 91 n = 76 Inhomogeneous 24 (26%) 13 (18%) 0.471 23 (25%) 14 (19%) 0.285 Homogeneous 63 (69%) 61 (81%) 0.012 62 (68%) 62 (81%) 0.339 Cavitated 5 (5%) 1 (1%) 0.405 6 (7%) 0 0.031 Tierärztliche Praxis Kleintiere 4/2012; 40(K): 250–260
6 N. Eberle et al.: Characteristics of canine splenic masses a) b) c) d) Fig. 1 Hematocrit (a), white blood count (b), platelet count (c), pro- thrombin time (d), and activated partial thromboplastin time (e) in dogs with splenic mass with versus without hemoperitoneum (HP) and with malignant (MT) versus non-malignant tumor (NMT) (asterisks indicate significant differences between the groups [p < 0.05]; º outliers). Abb. 1 Hämatokrit (a), Leukozytenzahl (b), Thrombozytenzahl (c), Pro- thrombinzeit (d) und aktivierte partielle Thromboplastinzeit (e) bei Hunden mit Umfangsvermehrung der Milz mit versus ohne Hämoperito- neum (HP) sowie mit malignem (MT) versus nichtmalignem Tumor (NMT) (Stern bezeichnet signifikante Unterschiede zwischen den Gruppen e) [p < 0,05]; º Ausreißer). Tierärztliche Praxis Kleintiere 4/2012; 40(K): 250–260 © Schattauer 2012
N. Eberle et al.: Characteristics of canine splenic masses 7 Histopathologic diagnoses of splenic masses Other non-malignant findings in the spleen were a myelolipoma, a fibrosis of the splenic parenchyma and one spleen with fibrous 1. Complete patient population granulation tissue (씰Table 5). The entire spleen was submitted to the Department of Pathology so that multiple tissue specimens could be selected to ensure an ac- 2. Comparison of dogs with and without hemoperitoneum curate diagnosis. In 44 dogs, a necropsy was performed because the In patients with hemoperitoneum, a malignant tumor within owner elected euthanasia at the time of diagnosis. the spleen was found in 67%, and a non-malignant tumor in Based upon histopathologic examination, 132 of 249 (53%) 33%. The most common malignant tumor in dogs with hemo- dogs had a malignant neoplasm diagnosed within the spleen. Of peritoneum was hemangiosarcoma with 82 cases (56%). In the these, 97 (39%) were diagnosed with hemangiosarcoma and 14 group without hemoperitoneum, 14% (n = 15) had a hemangio- (5%) were diagnosed with sarcoma. Two of the sarcomas were a sarcoma (p < 0.000). Splenic lymphoma was detected in three pa- fibrosarcoma and one was a leiomyosarcoma. Other malignant tients with a hemoperitoneum. Nodular hyperplasia was more diagnoses comprised fibrohistiocytic nodules (n = 9; 3%), malig- common in the group of patients without hemoperitoneum nant lymphoma (n = 3), blastoma (n = 7), myeloproliferative dis- (p = 0.000). The incidence of hematoma was nearly equally dis- ease suspected myeloid leukemia (n = 1), and adenocarcinoma tributed (씰Table 6). (n = 1) (씰Table 5). Immunohistochemistry was performed in nine tissue samples of splenic masses. These further investigations led to WHO clinical staging the diagnosis of four fibrohistiocytic nodules, two sarcomas, one hematoma, and one lymphoma. One mass was inconclusive even Dogs with splenic hemangiosarcoma were classified as stage I in with immunohistochemistry. 12 cases (12%), whereas 54 dogs were classified as stage II (56%), 117 of 249 (47%) dogs were diagnosed with non-malignant dis- and 31 dogs were classified as stage III (32%). ease. 60 dogs (24%) were diagnosed with lymphocytic nodular hy- perplasia, 41 dogs (16%) with splenic hematoma, six (3%) with splenitis, four dogs (2%) with hemangioma, and three dogs showed extramedullary hematopoiesis within the spleen (1%). Table 6 Histopathological distribution of splenic masses in dogs with or without hemoperitoneum (HP) (p < 0.05 indicates a significant difference). Tab. 6 Histopathologische Charakterisierung von Umfangsvermehrungen Table 5 Histopathological distribution of splenic masses in dogs. der Milz bei Hunden mit versus ohne Hämoperitoneum (HP) (p < 0,05 be- Tab. 5 Histopathologische Charakterisierung von Umfangsvermehrungen zeichnet einen signifikanten Unterschied) der Milz bei Hunden Dogs with HP Dogs without HP p Dogs with splenic mass n = 145 n = 104 n = 249 Malignant tumor 97 (67%) 35 (34%) 0.000 Malignant tumor 132 (53%) Hemangiosarcoma 82 (56%) 15 (14%) 0.000 Hemangiosarcoma 97 (39%) Sarcoma 5 (3%) 9 (9%) 0.242 Sarcoma 14 (5%) Fibrohistiocytic nodules 3 (2%) 6 (6%) 0.723 Fibrohistiocytic nodules 9 (3%) Lymphoma 3 (2%) 0 # Lymphoma 3 (1%) Blastoma 4 (3%) 3 (3%) # Blastoma 7 (3%) Adenocarcinoma 0 1 (1%) # Adenocarcinoma 1 (1%) Myeloid leukemia 0 1 (1%) # Myeloproliferative disease suspected 1 (1%) Non-malignant 48 (33%) 69 (66%) 0.000 myeloid leukemia tumor Non-malignant tumor 117 (47%) Hematoma 23 (16%) 18 (17%) 0.863 Nodular hyperplasia 60 (24%) Nodular hyperplasia 19 (13%) 41 (39%) 0.000 Hematoma 41 (16%) Hemangioma 3 (2%) 1 (1%) # Splenitis 6 (3%) Splenitis 2 (1%) 4 (4%) 0.239 Hemangioma 4 (2%) Extramedullary 1 (1%) 2 (2%) # Extramedullary hematopoeisis 3 (1%) hematopoeisis Other 3 (1%) Other 0 3 (3%) # Tierärztliche Praxis Kleintiere 4/2012; 40(K): 250–260
8 N. Eberle et al.: Characteristics of canine splenic masses Histopathologic examination of liver biopsies In those cases, surgical intervention could result in long-term sur- vival times. Differentiating between malignant and benign splenic A liver biopsy specimen was obtained in 173 of the 249 dogs (69%). masses before splenectomy would be helpful when treatment deci- Of the dogs with splenic hemangiosarcoma, 26 (15%) had histo- sions are being made to better advise owners on the extent of the pathologic confirmation of metastases within the liver at the time disease. of examination. In two dogs with splenic sarcoma metastases with- In contrast to the presented results, the two thirds rule has been in the liver were diagnosed (1.7%). Five dogs had metastases of applied to canine splenic masses. Approximately two thirds of all other malignant tumors within the liver (blastoma n = 3, adeno- splenic masses will have a malignant tumor, and two thirds of these carcinoma n = 1, bile duct carcinoma n = 1). No evidence of malig- malignancies will have a hemangiosarcoma of the spleen (4, 16, nant hepatic neoplasia based upon histopathologic examination 24). According to one study non-malignant masses, such as hema- was detected in 140 of 173 (81%) dogs (씰Table 7). toma and nodular hyperplasia even account for the majority of focal canine splenic masses (10). The majority of the malignant splenic masses in the present study were hemangiosarcomas Discussion (n = 97; 73.5%), which is consistent with the results of other studies (4, 21). Other malignant tumors in the present study were The goal of the study was to retrospectively describe clinical as- sarcomas of different origin, fibrohistiocytic nodules, malignant pects and histopathological characteristics of dogs with splenic lymphoma, blastoma, myeloid leukemia, and adenocarcinoma. masses. Dogs included had a splenic mass either with or without The nonmalignant splenic masses comprised of nearly similar hemoperitoneum. The distribution of malignant and non-malig- numbers of splenic nodular hyperplasia (n = 60; 24%) and splenic nant tumors was nearly equal with 53% malignant and 47% be- hematomas (n = 41; 16%). Previous studies evaluated the preva- nign masses. In this study population, patients with a splenic mass lence and histological classification of disease of the canine spleen had a chance of nearly one half of having a non-malignant tumor. (4, 24, 25). The frequency of splenic hematoma amounted to Table 7 Histopathological distribution of hepatic lesions in dogs with or Tab. 7 Histopathologische Charakterisierung von Umfangsvermehrungen without hemoperitoneum (HP) and with malignant (MT) or non-malignant der Milz bei Hunden mit versus ohne Hämoperitoneum (HP) sowie mit mali- tumor (NMT) (p < 0.05 indicates a significant difference). gnem (MT) versus nichtmalignem Tumor (NMT) (p < 0,05 bezeichnet einen signifikanten Unterschied) Dogs with HP Dogs without HP p Dogs with MT Dogs with NMT p n = 114 n = 59 n = 103 n = 70 Hemangiosarcoma 20 6 0.057 26 0 0.000 Sarcoma 0 2 0.072 2 0 0.250 Malignant, other than 3 2 0.642 5 0 0.624 sarcoma Non-malignant 91 49 0.020 70 70 0.444 a) b) Fig. 2 Macroscopic image of a spleen with a hemangiosarcoma (a) and with a nodular hyperplasia (b). Abb. 2 Makroskopisches Bild einer Milz mit einem Hämangiosarkom (a) und einer nodulären Hyperplasie Tierärztliche Praxis Kleintiere 4/2012; 40(K): 250–260 © Schattauer 2012
N. Eberle et al.: Characteristics of canine splenic masses 9 10–20% of all examined spleens, which is comparable with the re- as body weight demonstrated no difference between the dogs with sults of the present study. malignant and those with non-malignant splenic masses. Hematomas in humans are almost always the result of abdomi- In a previous retrospective study the biological behaviour of nal trauma. Splenic hematomas in dogs often occur secondary to splenic hemangiosarcoma was characterized (27). Metastatic pat- an underlying splenic disorder, such as primary nodular hyperpla- tern data of 25 dogs presented with clinical signs related to splenic sia, and are uncommonly a result of blunt trauma (24). An associ- mass that had undergone necropsy were analysed. Six of 25 dogs ation between splenic hematomas and underlying splenic nodular had right atrial hemangiosarcoma. Disease confined to the peri- hyperplasia has been proposed. It has been suggested that the pres- toneal cavity was present in 79% of dogs without right atrial in- ence of nodular hyperplasia may disrupt the normal blood supply volvement. The most common metastatic sites in these dogs were of the canine spleen with secondary regional blood accumulation liver, omentum and mesentery (27). In the present study a liver and hematoma formation (24). Nontraumatic hemoabdomen is biopsy specimen was obtained from 173 of 249 dogs. Histology re- considered to be a poor prognostic indicator, and dogs with hemo- vealed hemangiosarcoma in 26 (15%) dogs and seven dogs (4%) peritoneum have been shown to be significantly more likely to have had evidence of metastasis of other malignant neoplasias. On the hemangiosarcoma than splenic nodular hyperplasia/hematoma other hand, in 70 cases of liver biopsy with a malignant splenic complex (1, 16, 21). In the present study, a higher proportion tumor the histopathologic examination showed no evidence for (67%) of dogs with peritoneal effusion based on ultrasound or la- malignant neoplasia. Therefore, hepatic nodules identified during parotomy had a malignant splenic mass. The presence of hemo- celiotomy could represent a nonmalignant process, such as vacuo- peritoneum has been indicated as a predictor of malignancy in lar change or hyperplasia and should not automatically be inter- studies of canine splenic disease (1, 16, 21). In the study from Ham- preted as being malignant. On the other hand, biopsy sites may not mond et al. (12), the prevalence of malignant splenic neoplasia was have been representative. Incidence of malignancy in liver biopsies 76% in dogs with hemoperitoneum, whereas only 24% dogs had a therefore may have been underestimated in the present study. As benign splenic lesion. In the present study the distribution of macroscopic changes within the liver detected during surgery can- splenic masses was comparable. not be distinguished from benign lesions such as hyperplastic no- Some of the splenic masses included in this study (n = 50; 20%) dules, it is imperative not to recommend euthanasia without histo- were identified incidentally with abdominal ultrasound or celio- pathologic confirmation. tomy. These patients were presented for various clinical signs not Hemangiosarcoma and splenic hematoma have been reported directly related to the presence of a splenic mass. Of these dogs, to be macroscopically indistinguishable from each other in most 26% (n = 13) had a malignant tumor and 37 (74%) had a non-ma- cases (1, 16, 21, 24). Abdominal radiography and ultrasonography lignant tumor. This result is of interest, because the decision are traditionally used to evaluate the spleen (10). Based on radio- whether or not to perform a splenectomy in dogs without hemo- graphic findings, ultrasonographic findings and gross inspection, peritoneum must be carefully considered. Splenectomized dogs malignant and nonmalignant splenic masses have nonspecific may have some reduction of functional immune surveillance. This characteristics (10). In the present study, there was no difference may have negative consequences such as increased susceptibility to between the size (largest diameter) of nonmalignant (median microbial infection and erythrocyte parasitism (6). However, the 5 cm) and malignant splenic masses (median 6 cm) in the ultra- results of the present study pointed out a risk of one fourth to have sound examination. Even though, there was a difference between a malignant tumor in incidental splenic masses. Furthermore, the the size of nonmalignant (median 12 cm) and malignant splenic risk of a rupture of the splenic mass resulting in a life threatening masses (median 10 cm) in the radiographic estimation of the lar- condition should be taken into account in the process of decision gest diameter (p = 0.001), it was not possible to predict malignan- making. cy. Both findings are in agreement with prior studies (16, 25). An The literature shows that German Shepherd dogs, Labrador Re- additional finding of the study is the diverse median largest size of trievers, and Golden Retrievers are at higher risk for the devel- the splenic masses in the radiographic and ultrasound examina- opment of abdominal hemangiosarcoma and splenic hematoma tion. An explanation could be the difficulty to measure very large (1, 5, 19, 20, 23–25). The findings of the present study support the splenic masses appropriately. The results of the present study em- breed predisposition data from the previous reports. Because they phasizes the inability to distinguish between malignant and non- are common breeds in the general population of the hospital, it is malignant splenic masses based on size or other gross findings (16, difficult to conclude whether these breeds were overrepresented. 24). Ivancic et al. (15) showed that even contrast harmonic ultra- The results from the present study were consistent with previous sonography of splenic masses cannot distinguish between splenic reports that older and larger dogs are predisposed to splenic mass- hemangiosarcoma and hematoma. Due to the retrospective nature es (16, 20). There is not a consistent sex predilection in the litera- of the study, a more detailed description of the sonographic char- ture (16, 21). In contrast to the literature however the present study acteristics of liver and spleen was not possible. showed overrepresentation of male dogs (104 dogs [40 male cas- Analysis of a recent study suggested that anemic dogs with clini- trated] versus 51 female dogs [54 female spayed]). Furthermore, cal signs, a splenic mass, and hemoperitoneum that required a comparison of epidemiologic data and patient characteristics such transfusion without a history of trauma or coagulopathy had a Tierärztliche Praxis Kleintiere 4/2012; 40(K): 250–260
10 N. Eberle et al.: Characteristics of canine splenic masses 76% risk of having malignant neoplasia and a 70% risk of having ranted. Studies evaluating hepatic parenchyma, using helical CT hemangiosarcoma (12). In the present study, the presence of ane- while infusing contrast material (wash in/wash out) may improve mia showed a significant difference between dogs with malignant the sensitivity for detecting hepatic neoplasia (9, 26). and non-malignant tumor (p < 0.000). Cytological examination of fine-needle aspirates could be an A limitation of the present study lies in its retrospective nature aid in the diagnosis of splenic masses. In human medicine, an as- and in that not all of the above-mentioned parameters were evalu- sociation between target lesions in the liver and malignancy has ated in every case. Since the majority of dogs with splenic masses been described (28). The presence of a target lesion had a positive with hemoperitoneum in the present study were presented as predictive value for malignancy of 86% (28). emergency cases at times when an experienced radiologist was not In veterinary medicine, the finding of one or more target lesions available, ultrasonography was only performed in 158 cases. Addi- in the liver or spleen had a positive predictive value for malignan- tionally, a possible bias due to including patients with splenic cy of 74% (3). In case of multiple target lesions within one organ, masses that did not undergo surgery needs to be considered. An- the positive predictive value for malignancy was 81% (3). In one other limitation of the study is that description of gross inspection, other study, the accuracy rate of splenic cytological examination number of splenic masses and macroscopic size of the spleen was was only 38% (7). A reason for the poor accuracy rate for splenic not performed due to the retrospective nature of the study. A more masses can lie in the highly cavernous composition of some mass- detailed characterization of the macroscopic findings of the spleen es. Even when the fine-needle aspirate is obtained from a visibly could hold additional information in comparison to ultrasound solid part of the mass, the specimen can be contaminated with examination. blood and contain unrepresentative cellular material. Because of Future studies in dogs with splenic masses may involve new the inconsistent use of fine-needle aspirations in the present study, diagnostic imaging modalities such as contrast-enhanced ultra- this technique could not be evaluated any further and should be sound and computed tomography (14). The use of ultrasound, considered for future investigations of splenic masses in the dog. computed tomography, and magnetic resonance imaging of the spleen and liver for detection of mass lesions in humans has been Conflict of interest extensively described (7, 9, 22, 26). Computed tomography of ca- The authors confirm not to have any conflict of interest. nine splenic masses showed that malignant masses had lower Houndsfield values than nonmalignant masses pre- and post-con- Acknowledgments trast medium administration (10). Further investigation of pre- The authors thank members of the oncology service, as well as the operative abdominal CT evaluation of patients is therefore war- emergency and surgery staff. Conclusion for practice References Distinguishing between benign or malignant splenic masses based on 1. Aronsohn MG, Dubiel B, Roberts B, Powers BE. 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