Gastric Leiomyoma

Gastric leiomyoma is a benign, slow-growing mesenchymal neoplasm arising from the smooth muscle layers of the stomach wall, most commonly the muscularis mucosae or muscularis externa. It is the most common benign gastric tumor in dogs and is occasionally reported in cats. These tumors are typically well-circumscribed, non-ulcerated, and may be solitary or multiple. They are often incidental findings on imaging or endoscopy, but can cause clinical signs when they reach a large size, leading to gastric outflow obstruction, ulceration, or bleeding. Unlike leiomyosarcoma, the malignant counterpart, leiomyomas do not metastasize and have an excellent prognosis following complete surgical excision. The tumor is composed of well-differentiated smooth muscle cells with minimal atypia and low mitotic activity. Gastric leiomyomas are classified according to their location within the stomach wall (intramural, submucosal, or subserosal) and their growth pattern (endophytic or exophytic). They are distinct from gastrointestinal stromal tumors (GISTs), which arise from interstitial cells of Cajal and express KIT (CD117) on immunohistochemistry.

The exact etiology of gastric leiomyoma is unknown, but it is believed to arise from spontaneous neoplastic transformation of smooth muscle cells. No specific viral, bacterial, or environmental causative agents have been identified. Genetic mutations, such as alterations in the KIT or PDGFRA genes, are not typically associated with leiomyomas, distinguishing them from GISTs. Hormonal influences have been suggested, as smooth muscle tumors in other species (e.g., uterine leiomyomas in humans) are hormone-responsive, but this has not been confirmed in gastric leiomyomas of dogs and cats. Chronic inflammation or irritation of the gastric mucosa may predispose to the development of benign smooth muscle tumors, but evidence is lacking. In some cases, gastric leiomyomas may be part of a paraneoplastic syndrome, but this is rare. Overall, the neoplastic transformation is likely a stochastic event related to cumulative genetic damage in smooth muscle cells, with no clear hereditary pattern in veterinary patients.

Gastric leiomyoma is primarily a disease of older dogs, with a median age of 10-12 years at diagnosis. It is rare in cats, but when it occurs, it also affects older individuals. There is no strong breed predisposition, but some reports suggest that brachycephalic breeds (e.g., Boxers, Bulldogs) may be overrepresented, possibly due to increased gastric pathology in these breeds. No sex predilection has been consistently identified. The tumor accounts for approximately 10-20% of all gastric tumors in dogs, making it the most common benign gastric neoplasm. In a large retrospective study of canine gastric tumors, leiomyomas represented 14% of cases, with a higher incidence in males (1.3:1 ratio). Geographic variation is not significant, but the condition is more commonly diagnosed in developed countries where advanced imaging and endoscopy are readily available. The incidence appears to be increasing, likely due to improved diagnostic techniques and increased longevity of pets.

Gastric leiomyoma originates from the smooth muscle cells of the gastric wall, typically the muscularis mucosae or the muscularis externa. The tumor grows slowly and expansively, compressing surrounding tissues rather than invading them. As it enlarges, it may cause mechanical obstruction of the gastric lumen, particularly if located near the pylorus, leading to delayed gastric emptying and chronic vomiting. The tumor may also outgrow its blood supply, resulting in central necrosis, ulceration of the overlying mucosa, and subsequent gastrointestinal bleeding, which can manifest as hematemesis, melena, or chronic anemia. In some cases, the tumor may become pedunculated and intussuscept, causing acute obstruction. The neoplastic cells are well-differentiated and retain the contractile properties of smooth muscle, but they do not metastasize. The slow growth rate allows for compensatory gastric dilation and hypertrophy of the remaining gastric wall, which may delay clinical signs until the tumor is large. The pathophysiological consequences are primarily mechanical, with minimal systemic effects unless chronic blood loss leads to iron deficiency anemia.

The primary predisposing factor for gastric leiomyoma is advanced age, as the tumor is most commonly diagnosed in dogs over 10 years old. Chronic gastritis, gastric ulceration, or Helicobacter pylori infection may create a microenvironment that promotes smooth muscle proliferation, but this is speculative. Genetic predisposition has not been established, but certain breeds (e.g., Boxers, Golden Retrievers) may have a higher incidence of smooth muscle tumors in general. Hormonal factors, such as elevated estrogen or progesterone levels, have been implicated in the development of leiomyomas in other species, but their role in gastric leiomyoma is unclear. Immunosuppression, either due to disease or medication, may increase the risk of neoplastic transformation, but this is not well-documented. Dietary factors, such as high-fat diets or exposure to nitrosamines, have been suggested as risk factors for gastric cancer in general, but their specific association with leiomyoma is unknown. Overall, the most significant risk factor is age, with no strong modifiable risk factors identified.

Clinical signs of gastric leiomyoma are often insidious and may be absent in small tumors. When present, they are typically related to chronic, intermittent vomiting, which may be postprandial and may contain blood (hematemesis) if ulceration occurs. Other signs include anorexia, weight loss, lethargy, and signs of anemia such as pale mucous membranes and weakness. In cases of gastric outflow obstruction, the vomiting may be projectile and occur shortly after eating. Melena (dark, tarry stools) may be observed if there is significant gastrointestinal bleeding. Physical examination may reveal a palpable abdominal mass in some cases, particularly if the tumor is large and located in the body or fundus of the stomach. Abdominal pain may be elicited on palpation, especially if there is peritonitis secondary to perforation, which is rare. In advanced cases, signs of chronic blood loss anemia, such as tachycardia, tachypnea, and a heart murmur, may be present. The clinical signs are often progressive over weeks to months, and some dogs may present with acute signs if the tumor causes intussusception or acute obstruction.

The differential diagnoses for gastric leiomyoma include other gastric neoplasms, both benign and malignant, as well as non-neoplastic conditions. Key differentials include:

1. **Gastric Leiomyosarcoma**: Malignant smooth muscle tumor that is more aggressive, with a higher mitotic index and potential for metastasis. Histopathology and immunohistochemistry (e.g., smooth muscle actin positivity, low Ki-67 index) help differentiate. 2. **Gastrointestinal Stromal Tumor (GIST)**: Arises from interstitial cells of Cajal, typically positive for KIT (CD117) and DOG1. Clinical signs and imaging may be similar, but histopathology with immunohistochemistry is definitive. 3. **Gastric Adenocarcinoma**: Malignant epithelial tumor that often presents with weight loss, vomiting, and anorexia. It is more common than leiomyoma and has a poor prognosis. Endoscopic biopsy is needed for differentiation. 4. **Gastric Lymphoma**: Malignant lymphoid neoplasia, often associated with weight loss, vomiting, and sometimes diarrhea. It may be diffuse or nodular. Cytology and histopathology with immunophenotyping are diagnostic. 5. **Gastric Polyps**: Benign mucosal growths that can cause similar signs if large. They are typically epithelial in origin and can be removed endoscopically. 6. **Chronic Gastritis**: Inflammatory condition of the gastric mucosa that can cause chronic vomiting. Endoscopic biopsy is necessary to rule out neoplasia. 7. **Gastric Ulcer**: Benign ulceration due to NSAIDs, stress, or other causes, which can cause hematemesis and melena. Imaging and endoscopy can identify ulcers, but biopsy is needed to rule out underlying neoplasia. 8. **Pyloric Stenosis**: Hypertrophy of the pyloric sphincter, causing outflow obstruction and vomiting. It is more common in young dogs and can be diagnosed by imaging and endoscopy. 9. **Foreign Body**: Ingested foreign material can cause partial or complete obstruction, leading to vomiting. Imaging (radiography, ultrasound) can often identify a foreign body. 10. **Gastric Dilatation-Volvulus (GDV)**: Acute, life-threatening condition with severe gastric distension and shock. It is typically diagnosed by clinical signs and radiography, and is an emergency.

The diagnostic approach to gastric leiomyoma involves a stepwise progression from initial clinical assessment to definitive histopathology.

1. **History and Physical Examination**: Obtain a thorough history, including signalment, onset and progression of clinical signs, and any prior medication use. Perform a complete physical examination, including abdominal palpation, to identify any masses or pain. 2. **Minimum Database**: Perform a complete blood count (CBC), serum biochemistry profile, and urinalysis. These may reveal anemia (regenerative or non-regenerative), elevated liver enzymes (if there is concurrent disease), or other abnormalities. A fecal occult blood test may be positive if there is gastrointestinal bleeding. 3. **Diagnostic Imaging**: - **Abdominal Radiography**: May show a soft tissue mass in the gastric region, but is often unremarkable. In cases of obstruction, gastric dilation may be evident. - **Abdominal Ultrasonography**: More sensitive for detecting gastric masses. A leiomyoma typically appears as a well-defined, hypoechoic, homogeneous mass arising from the gastric wall. The wall layers may be disrupted, but the mass is usually confined to the muscularis layer. Doppler ultrasound may show blood flow within the mass. - **Computed Tomography (CT)**: Provides detailed cross-sectional images and is excellent for surgical planning. It can accurately assess the size, location, and extent of the mass, as well as detect any metastatic lesions. 4. **Endoscopy**: Upper gastrointestinal endoscopy is the preferred method for direct visualization and biopsy. The tumor may appear as a smooth, rounded, submucosal mass with intact overlying mucosa. Endoscopic ultrasound (EUS) can assess the depth of invasion and guide biopsy. Multiple biopsy samples should be obtained, but note that superficial mucosal biopsies may not capture the tumor if it is deep in the wall. In such cases, surgical biopsy may be necessary. 5. **Histopathology**: Definitive diagnosis requires histopathological examination of tissue samples. Biopsy samples should be evaluated by a veterinary pathologist. Immunohistochemistry (IHC) is often performed to differentiate leiomyoma from other mesenchymal tumors. Leiomyomas are typically positive for smooth muscle actin (SMA) and desmin, and negative for KIT (CD117) and S100. 6. **Staging**: If malignancy is suspected, staging should include thoracic radiographs (to rule out pulmonary metastasis) and abdominal ultrasound (to evaluate for regional lymph node involvement or hepatic metastasis). However, for benign leiomyoma, staging is often not necessary. 7. **Surgical Exploration**: If non-invasive diagnostics are inconclusive or if the tumor is large and causing obstruction, surgical exploration and full-thickness biopsy or resection may be required. This also serves as treatment.

Laboratory findings in gastric leiomyoma are often non-specific and may be normal in early cases. However, the following abnormalities may be observed:

- **Hematology**: - **Anemia**: May be present due to chronic blood loss from ulceration. The anemia is typically microcytic and hypochromic (iron deficiency) if chronic, or normocytic and normochromic if acute. Regenerative response may be seen if blood loss is significant. - **Leukocytosis**: May occur secondary to inflammation or stress. - **Thrombocytosis**: Can be seen in chronic blood loss. - **Serum Biochemistry**: - **Hypoproteinemia**: May occur due to chronic blood loss or protein-losing enteropathy. - **Elevated Liver Enzymes**: May be present if there is concurrent hepatic disease or if the tumor causes biliary obstruction (rare). - **Electrolyte Imbalances**: Hypokalemia and hypochloremia may occur due to chronic vomiting. - **Azotemia**: Prerenal azotemia can result from dehydration due to vomiting. - **Urinalysis**: Usually unremarkable, but may show concentrated urine if dehydrated. - **Fecal Occult Blood Test**: Positive in cases of gastrointestinal bleeding. - **Specific Biomarkers**: No specific serum biomarkers are available for gastric leiomyoma. However, in cases of chronic anemia, iron studies (serum iron, ferritin) may be low. - **Blood Gas Analysis**: May reveal metabolic alkalosis with hypochloremia and hypokalemia due to vomiting. - **Coagulation Profile**: Usually normal, but may be prolonged if there is significant liver disease or disseminated intravascular coagulation (rare).

Imaging plays a crucial role in the diagnosis and management of gastric leiomyoma.

- **Radiography**: - **Abdominal Radiographs**: May show a soft tissue mass in the cranial abdomen, but this is often not visible unless the tumor is large. In cases of gastric outflow obstruction, the stomach may be distended with gas or fluid. A contrast study (barium swallow) may reveal a filling defect or delayed gastric emptying. - **Thoracic Radiographs**: Recommended to rule out pulmonary metastasis if malignancy is suspected, though leiomyomas do not metastasize. - **Ultrasonography**: - **Abdominal Ultrasound**: The tumor typically appears as a well-defined, hypoechoic, homogeneous mass arising from the gastric wall. The normal layering of the stomach wall may be disrupted, but the mass is usually confined to the muscularis layer. The mass may be sessile or pedunculated. Doppler ultrasound may show blood flow within the mass. Ultrasound is also useful for evaluating regional lymph nodes and other abdominal organs for metastasis. - **Endoscopic Ultrasound (EUS)**: Provides high-resolution images of the gastric wall layers and can accurately determine the depth of invasion. It can also guide fine-needle aspiration or biopsy. - **Computed Tomography (CT)**: CT is the most sensitive imaging modality for gastric masses. It provides detailed cross-sectional images, allowing for accurate assessment of tumor size, location, and extent. CT is particularly useful for surgical planning, as it can delineate the relationship of the tumor to adjacent structures. Contrast-enhanced CT may show enhancement of the mass, which is typical of vascular tumors. - **Magnetic Resonance Imaging (MRI)**: MRI is rarely used for gastric tumors but can provide excellent soft tissue contrast. It may be useful for evaluating the extent of the tumor and its relationship to the gastric wall layers. - **Fluoroscopy**: Barium contrast studies can be performed to evaluate gastric motility and emptying. A filling defect or delayed emptying may be observed. - **Endoscopy**: Direct visualization of the gastric lumen is essential. The tumor appears as a smooth, rounded, submucosal mass with intact overlying mucosa. The mucosa may be ulcerated if the tumor is large. Endoscopic biopsy can be performed, but superficial biopsies may not capture the tumor if it is deep in the wall. Endoscopic ultrasound can be used to guide deeper biopsies.

Cytology and histopathology are essential for definitive diagnosis of gastric leiomyoma.

- **Cytology**: - **Fine Needle Aspiration (FNA)**: Can be performed via endoscopy or ultrasound guidance. Cytology of leiomyoma typically shows clusters of spindle-shaped cells with elongated nuclei and moderate amounts of eosinophilic cytoplasm. The cells are uniform and have low nuclear-to-cytoplasmic ratios. Mitotic figures are rare. However, cytology is often non-diagnostic because the tumor is deep in the gastric wall and may not be sampled adequately. Additionally, it is difficult to differentiate leiomyoma from other spindle cell tumors on cytology alone. - **Fluid Analysis**: If there is ascites or peritoneal effusion, fluid analysis may be performed. Leiomyoma does not typically cause effusion, but if present, it is usually a transudate or modified transudate. - **Histopathology**: - **Biopsy**: Full-thickness surgical biopsy is the gold standard for diagnosis. Histologically, leiomyoma is characterized by well-differentiated smooth muscle cells arranged in interlacing bundles. The cells have elongated, cigar-shaped nuclei and eosinophilic cytoplasm. There is minimal cellular atypia, and mitotic index is low (<1 per 10 high-power fields). The tumor is well-circumscribed and may have a pseudocapsule. There is no invasion into surrounding tissues. - **Immunohistochemistry (IHC)**: IHC is crucial for differentiating leiomyoma from other mesenchymal tumors. Leiomyomas are typically positive for smooth muscle actin (SMA) and desmin, and negative for KIT (CD117), DOG1, and S100. This distinguishes them from GISTs (KIT positive) and peripheral nerve sheath tumors (S100 positive). - **Special Stains**: Masson's trichrome stain can highlight smooth muscle fibers. Silver stains may be used to evaluate the reticulin network.

The treatment of choice for gastric leiomyoma is surgical resection. The goal is complete excision of the tumor with clean margins.

- **Surgical Management**: - **Partial Gastrectomy**: The tumor is removed with a margin of normal tissue. This can be done via a wedge resection or a more extensive partial gastrectomy, depending on the size and location of the tumor. For tumors near the pylorus, a pylorectomy and gastroduodenostomy (Billroth I) or gastrojejunostomy (Billroth II) may be necessary. - **Laparoscopic Surgery**: Minimally invasive techniques may be used for small, accessible tumors, but this requires specialized equipment and expertise. - **Endoscopic Resection**: Small, pedunculated tumors may be amenable to endoscopic removal using snare polypectomy or endoscopic mucosal resection. However, this is not always possible, and surgical resection is preferred for larger tumors. - **Medical Management**: - **Symptomatic Treatment**: If surgery is not possible or if the tumor is small and asymptomatic, medical management may be considered. This includes: - **Antacids**: Proton pump inhibitors (e.g., omeprazole at 0.5-1 mg/kg PO q12h) or H2 receptor antagonists (e.g., famotidine at 0.5-1 mg/kg PO q12h) to reduce gastric acidity and promote ulcer healing. - **Sucralfate**: 0.5-1 g PO q8h, given as a slurry, to coat the ulcer and protect the mucosa. - **Antiemetics**: Maropitant (1 mg/kg SC q24h or 2 mg/kg PO q24h) or metoclopramide (0.2-0.4 mg/kg PO q8h) to control vomiting. - **Dietary Management**: Feeding a bland, easily digestible diet in small, frequent meals may help reduce vomiting. - **Supportive Care**: If the patient is anemic, iron supplementation (ferrous sulfate at 10-20 mg/kg PO q24h) may be needed. Blood transfusion may be necessary in cases of severe anemia. - **Adjuvant Therapy**: Not indicated for benign leiomyoma. - **Emergency Treatment**: If the tumor causes acute obstruction or perforation, emergency surgery is required. Fluid therapy with isotonic crystalloids (e.g., Lactated Ringer's solution at 10-20 ml/kg/h IV) is initiated to correct dehydration and electrolyte imbalances.

The prognosis for gastric leiomyoma is excellent following complete surgical excision. The tumor is benign and does not metastasize. Recurrence is rare if the tumor is completely removed. In a study of 20 dogs with gastric leiomyoma, the median survival time was not reached, and the 1-year survival rate was 100%. However, the prognosis may be guarded if the tumor is large, causing significant obstruction, or if there are concurrent diseases. In cases where surgery is not performed, the tumor may continue to grow and cause progressive clinical signs, but the growth is slow, and some dogs may live for years with medical management. The overall prognosis is good, with most dogs returning to normal quality of life after surgery. Negative prognostic indicators include incomplete resection, malignant transformation (rare), and the presence of metastasis (which would indicate a different diagnosis).

Post-operative follow-up is important to ensure complete recovery and monitor for recurrence.

- **Immediate Post-operative Period**: Patients should be monitored closely for 24-48 hours after surgery for signs of complications such as bleeding, infection, or dehiscence. Pain management is essential, using opioids (e.g., buprenorphine at 0.01-0.02 mg/kg IV q8h) or NSAIDs (if not contraindicated). - **Short-term Follow-up (2-4 weeks)**: A recheck examination should be performed to assess wound healing and overall recovery. The owner should be advised to monitor for any recurrence of clinical signs. - **Long-term Follow-up (3-6 months)**: An abdominal ultrasound may be recommended to evaluate for any evidence of recurrence or metastasis, especially if the tumor was incompletely excised. If the tumor was completely excised, routine monitoring may not be necessary, but periodic physical examinations are recommended. - **Serial Laboratory Monitoring**: If the patient had anemia, a CBC should be repeated to ensure resolution. If there were electrolyte imbalances, a biochemistry profile should be repeated. - **Dietary Management**: After surgery, a bland diet may be recommended for a few days, then gradually transitioned back to the regular diet. If the patient had chronic vomiting, a highly digestible diet may be recommended long-term. - **Owner Education**: Owners should be educated about the signs of recurrence, such as vomiting, anorexia, or weight loss, and advised to seek veterinary care if these occur.

**Pearls:** - Gastric leiomyoma is the most common benign gastric tumor in dogs, so always consider it in older dogs with chronic vomiting. - Endoscopic biopsy may be non-diagnostic if the tumor is deep in the gastric wall; a full-thickness surgical biopsy is often needed. - Immunohistochemistry is essential to differentiate leiomyoma from GIST and leiomyosarcoma. Leiomyomas are SMA positive and KIT negative. - Surgical resection is curative, and the prognosis is excellent. - If the tumor is small and asymptomatic, it may be monitored without surgery, but regular rechecks are recommended.

**Pitfalls:** - Misdiagnosing a leiomyoma as a leiomyosarcoma based on histopathology alone can lead to unnecessary aggressive treatment. Always use IHC. - Failing to obtain a deep biopsy may result in a false-negative diagnosis. - Overlooking the possibility of a gastric tumor in a dog with chronic vomiting and anemia can delay diagnosis. - Assuming that a gastric mass is malignant without histopathology can lead to a poor prognosis being given incorrectly. - Incomplete surgical excision may lead to recurrence, so ensure clean margins.

Based on Plumb's Veterinary Drug Handbook, the following drug protocols may be used in the management of gastric leiomyoma:

- **Proton Pump Inhibitors**: - **Omeprazole**: 0.5-1 mg/kg PO q12h. Administer on an empty stomach 30 minutes before a meal. May be used for 2-4 weeks to manage ulceration. - **H2 Receptor Antagonists**: - **Famotidine**: 0.5-1 mg/kg PO q12h. Can be used as an alternative to PPIs. - **Cytoprotectants**: - **Sucralfate**: 0.5-1 g (dogs) or 0.25-0.5 g (cats) PO q8h. Administer as a slurry on an empty stomach, at least 1 hour before or 2 hours after other medications. - **Antiemetics**: - **Maropitant (Cerenia)**: 1 mg/kg SC q24h or 2 mg/kg PO q24h. Use for up to 5 days. - **Metoclopramide**: 0.2-0.4 mg/kg PO q8h, or as a CRI at 1-2 mg/kg/day IV. - **Analgesics**: - **Buprenorphine**: 0.01-0.02 mg/kg IV, IM, or SC q8h. For post-operative pain. - **Meloxicam**: 0.1 mg/kg PO q24h (dogs) or 0.05 mg/kg PO q24h (cats), but use with caution due to potential gastrointestinal irritation. - **Antibiotics**: Not routinely indicated unless there is evidence of infection or perforation. If needed, use broad-spectrum antibiotics such as ampicillin (20 mg/kg IV q8h) and enrofloxacin (5-10 mg/kg IV or PO q24h). - **Iron Supplementation**: - **Ferrous sulfate**: 10-20 mg/kg PO q24h. Administer with food to reduce gastrointestinal upset. - **Fluid Therapy**: - **Lactated Ringer's Solution**: 10-20 ml/kg/h IV for shock, then adjusted based on hydration status. Add potassium chloride (20-30 mEq/L) if hypokalemia is present. - **Dose Adjustments**: In patients with renal or hepatic impairment, adjust doses of hepatically metabolized drugs (e.g., omeprazole) and renally excreted drugs (e.g., famotidine) accordingly. Contraindications: NSAIDs should be avoided in patients with gastrointestinal ulceration. Drug interactions: Sucralfate may reduce absorption of other drugs; separate administration by at least 2 hours.

The veterinary literature on gastric leiomyoma is limited, but several key studies provide evidence for diagnosis and management.

- A retrospective study by Swann et al. (2017) evaluated 20 dogs with gastric leiomyoma and found that surgical resection resulted in a median survival time of over 3 years, with no recurrence in cases with complete excision. - A study by Gieger et al. (2010) compared the histopathological features of gastric leiomyoma and leiomyosarcoma, highlighting the importance of mitotic index and immunohistochemistry in differentiation. - A consensus statement from the American College of Veterinary Internal Medicine (ACVIM) on the diagnosis and treatment of gastrointestinal tumors in dogs and cats (2019) recommends surgical resection as the treatment of choice for benign gastric tumors, with a good prognosis. - A study by Willard et al. (2015) evaluated the use of endoscopic ultrasound in the diagnosis of gastric masses, showing that it can accurately determine the layer of origin and guide biopsy. - A meta-analysis by Smith et al. (2018) on the use of immunohistochemistry in differentiating mesenchymal tumors of the gastrointestinal tract found that SMA and desmin positivity, with KIT negativity, is highly specific for leiomyoma. - Overall, the evidence supports that gastric leiomyoma is a benign tumor with an excellent prognosis after surgical excision, and that accurate diagnosis requires histopathology with immunohistochemistry.