splenic tumors

BACKGROUND

Splenic tumors are relatively common in dogs, accouinting for up to 2% of all tumors, but is rare in cats. German Shepherd Dogs, Golden Retrievers, and Labrador Retrievers are over-represented. Overall, in dogs, approximately 50% of splenic tumors are benign and 50% are malignant; however, if there is evidence of rupture of the splenic tumor and hemoperitoneum, then 30% of these splenic tumors are benign and 70% are malignant. Hemangiosarcoma (HSA) is the most common malignant splenic tumor, but others include lymphoma, non-angiomatous/non-lymphomatous sarcomas (such as histiocytic sarcoma, leiomyosarcoma, fibrosarcoma, and osteosarcoma), and mast cell tumors. Splenic HSA is a highly malignant tumor with a high metastatic risk. Splenic HSA is divied into three stages: non-ruptured and non-metastatic splenic HSA (stage I), ruptured but non-metastatic HSA (stage II), and metastatic HSA regardless of whether there is evidence of rupture or not (stage III). Splenic HSA can metastasize to any site, but liver, omentum, lungs, and heart are the most common sites of metastasis.

The majority of splenic tumors in cats are malignant and mast cell tumors are the most common feline splenic malignancy.

DIAGNOSIS

Abdominal ultrasound or CT scan is recommended for the detection of a splenic mass. Fine-needle aspirates can be performed, but they are rarely diagnostic because of blood contamnination, and risks of aspiration include tumor rupture, hemorrhage, and seeding the abdominal cavity with tumor cells. Furthermore, knowledge of the tumor type does not change the recommended treatment of abdominal exploration and splenectomy.

CLINICAL STAGING

Both the abdominal and thoracic cavities should be imaged to assess intra-abdominal organs (especially the liver), lungs, and heart (8.7%-18.5%) for evidence of metastatic disease. Abdominal imaging techniques include ultrasonography, contrast harmonic ultrasonography, CT scan, and MRI. Thoracic imaging options include three-view thoracic radiographs, echocardiography, and CT scan.

Liver Metastasis

Omentum Metastasis

Falciform Ligament Metastasis

Body Wall Metastasis

Diaphragm Metastasis

Kidney Metastasis

TREATMENT

Blood tests are done to check for anemia (low red blood cells), thrombocytopenia (low platelets), and other common hematologic abnormalities. An ECG is recommended as cardiac arrhythmias are common, particularly postoperatively.

Splenectomy is the recommended treatment for all non-metastatic (stage I and II) splenic tumors. Biopsy of grossly abnormal lesions should be performed if present to determine if these represent metastatic lesions. However, biopsy of grossly normal organs is not required as detection of microscopic metastatic disease is rare (0% of 21 dogs in one study). Palliative splenectomy can also be performed in dogs with metastasis (stage III) to prevent tumor rupture and hemorrhage.

Postoperative chemotherapy is recommended for dogs with malignant splenic tumors, especially HSA and non-angiomatous/non-lymphomatous splenic sarcomas. Doxorubicin-based protocols are preferred, either alone or in combination with other agents such as cyclophosphamide, vincristine, ifofsamide, dacarbazine, and/or non-steroidal anti-inflammatory drugs. Low-dose oral chemotherapy protocols (or metronomic chemotherapy) may also be effective, but there is minimal information on the outcome with this approach with only published study of 9 dogs with stage II splenic HSA.

PROGNOSIS

Hemangiosarcoma - Dogs

The median survival time for dogs with splenic HSA, regardless of clinical stage, treated with surgery alone is 19-86 days with a 1- and 2-year survival rates of 6%-12% and 3%-4%, respectively. The median survival times and 1- and 2-year survival rates for dogs with stage I disease following splenectomy alone are 151-238 days and 35% and 12%, respectively. The median survival times and 1- and 2-year survival rates for dogs with stage II disease following splenectomy alone are 61-143 days and 13% and 5%, respectively. The median survival times and 1-year survival rates for dogs with stage III disease following splenectomy alone are 27-65 days and 0% The The most common cause of deterioration is rupture of a metastatic lesion, usualy in the liver, with subsequent intra-abdominal bleeding. These dogs typically have a very good quality of life up until the point of rupture of the metastatic lesion, and their deterioration is usually quick and non-painful.

Metronomic chemotherapy is low-dose oral chemotherapy and is associated with minimal risk of adverse effects. Metronomic chemotherapy is intended to be anti-angiogenic rather than cytotoxic. In one small study of 9 dogs with stage II HSA, the median survival time for dogs treated with splenectomy and metronomic chemotherapy was 178 days and not significantly different to the median survival time of 133 days for the control group of dogs treated with splenectomy and full-course doxorubicin chemotherapy. In another study (2015) of 13 dogs with various stages of splenic HSA treated with splenectomy and metronomic chemotherapy, the median survival time was 103 days with 1- and 2-year survival rates of 8% and 0%, respectively. In this same study, when full-course chemotherapy was combined with metronomic chemotherapy, the median survival time was 131 days with 1- and 2-year survival rates of 8% and 0%, respectively.

Full-course chemotherapy has been widely studied following splenectomy in dogs with splenic HSA. Full-course chemotherapy, usually with doxorubicin (alone or in combination with other agents), results in significant improvements in survival times in dogs with stage I HSA, possibly dogs with stage II splenic HSA, and rarely in dogs with stage III HSA. Overall, the median survival time for dogs treated with splenectomy alone is 19-86 days, compared to 87-166 days when splenectomy is combined with chemotherapy (with 1- and 2-year survival rates of 8%-23% and 8%, respectively). The median survival time for dogs with stage I splenic HSA treated with splenectomy and chemotherapy is 239-345 days (although one retrospective study reported a median survival time of 983 days for dogs with stage I splenic HSA treated with splenectomy and epirubicin). The median survival time for dogs with stage II splenic HSA treated with splenectomy and chemotherapy is 93-210 days, with a 1-year survival rate of 12%. Some studies have demonstrated a significantly improved survival time when surgery is combined with adjuvant chemotherapy for dogs with stage II solenic HSA, while other studies have found no difference in survival times with adjuvant chemotherapy. The median survival time for dogs with stage III splenic HSA treated with splenectomy and chemotherapy is 68-195 days, with a 1-year survival rate of 8%. Only one study has demonstrated a significantly improved survival time in dogs with stage III splenic HSA treated with surgery and chemotherapy, whereas in the vast majority of studies adjuvant chemotherapy did not result in a survival advantage for dogs with stage III splenic HSA.

Maintenance therapy following doxorubicin-based chemotherapy has been investigated in 31 dogs with stage I or II splenic HSA and was not shown to increase survival times or rates compared to dogs treated with adjuvant chemotherapy. The overall median survival time and the median survival time in dogs treated with post-chemotherapy maintenance therapy (using toceranib) were 169 days and 172 days, respectively. The overall 1-year survival rate and the 1-year survival rate in dogs treated with post-chemotherapy maintenance therapy were 21.2% and 24.4%, respectively.

Lymphoma - Dogs

Splenic lymphoma is uncommon in dogs. In one retrospective study of 29 dogs (2013) with B-cell (or marginal zone) lymphomas, the overall median survival time was 383 days following treatment with splenectomy with or without adjuvant chemotherapy. In another study (2015) of 41 dogs with splenic lymphoma, the median survival times were not reached for dogs with marginal zone lymphoma (with a 1-year survival rate of 64%) and mantle cell lymphoma (with a 1-year survival rate of 89%), but was 561 days for dogs with other B-cell lymphomas (with a 1-year survival rate of 50%). T-cell lymphomas were diagnosed in only three dogs in this latter study and the median survival time and 1-year survival rate in these dogs was 4 days and 0%. The presence of clinical signs attributable to the splenic lymphoma (such as abdominal distension, lethargy, and anorexia) was prognostic in both studies with median survival times of 1153 days and 222-309 days for dogs with incidental and symptomatic splenic lymphomas, respectively. In the latter study, hemoabdomen was also a prognostic factor with a median survival time of 120 days if dogs presented with hemoabdomen compared to a median survival time which was not reached for dogs without hemoabdomen. No other prognostic factors were identified in these studies, including the use of adjuvant chemotherapy.

Non-Angiomatous/Non-Lymphomatous Splenic Sarcoma - Dogs

The prognosis for dogs with non-angiomatous/non-lymphomatous splenic sarcomas is guarded. This group of splenic sarcomas includes tumor types such as leiomyosarcoma, chondrosarcoma, osteosarcoma, fibrosarcoma, histiocytic sarcoma, and liposarcoma. There have been two published studies specifically investigating this classification of splenic sarcomas and both were published over 20 years ago. Metastasis at the time of diagnosis and mitotic index were prognostic factors in these studies. The median survival times were 1 month and 9 months for dogs with and without metastasis at the time of diagnosis, respectively. In the other study, the 1-year survival rates were 40% for dogs with a mitotic index of 0-9 per 10 high power fields and 0% for dogs with a mitotic index > 9 per 10 high power fields. Both of these studies were for dogs treated with splenectomy alone, and no study has been published investigating whether adjuvant chemotherapy makes a significant difference to the outcome when compared to surgery alone. However, because most dogs die as a result of metastatic disease, adjuvant chemotherapy is indicated.

Two other studies have looked at non-angiomatous/non-lymphomatous splenic sarcomas through indirect means. In one study (2012), which only included eight dogs with splenic stromal sarcomas, the median survival time was 488 days with 1- and 2-year survival rates of 56% and 19%, respectively. In the second study (2019), which included 20 dogs with soft tissue (or stromal) sarcomas of the spleen, the outcome was dependent on mitotic index and histologic grade. The median survival times were 269 days and not reached for dogs with a mitotic index of ≥ 9 or < 9 per 10 high power fields, respectively. The median survival times for dogs with grade I, II, and III sarcomas was not reached, 589 days, and 158 days, respectively.

More specifically, the median survival time for 47 flat-coated retrievers with visceral histiocytic sarcoma (including spleen) was 29 days following surgery alone. In a latter study (2012) investigating 32 dogs with splenic fibrohistiocytic nodules, immunohistochemistry was used to reclassify these nodules with six of these dogs ultimately diagnosed with splenic histiocytic sarcoma. The median survival time in these six dogs was 74 days following splenectomy. In a study of 44 dogs with intra-abdominal leiomyosarcoma, which included 16 dogs with splenic leiomyosarcoma, the median survival time was 10 months following surgery with 48% of these dogs dying as a result of metastatic disease. In a study of 13 dogs with splenic liposarcoma (2015), the overall median survival time was 623 days. Prognostic factors included the presence of metastatic disease at the time of splenectomy and histologic grade. The median survival times for dogs with and without metastasis at the time of diagnosis were 45 days and 767 days, respectively. The median survival time for dogs with grade I splenic liposarcoma was 1009 days and this was significantly better than the median survival times of 206 and 74 days for dogs with grade II and III splenic liposarcomas, respectively.

Mast Cell Tumor - Cats

The prognosis is good for cats with splenic mast cell tumor with median survival times of 12-19 months with surgery alone.

Splenic Hemangioma