If splenectomy is performed for conditions in which blood cells are sequestered in the spleen, failure to remove accessory spleens may result in the failure of the condition to resolve. During medical imaging, accessory spleens may be confused for enlarged lymph nodes or neoplastic growth in the tail of the pancreas, gastrointestinal tract, adrenal glands or gonads.

An accessory spleen ("supernumerary spleen", "splenule", or "splenunculus") is a small nodule of splenic tissue found apart from the main body of the spleen. Accessory spleens are found in approximately 10 percent of the population and are typically around 1 centimeter in diameter. They may resemble a lymph node or a small spleen. They form either by the result of developmental anomalies or trauma. They are medically significant in that they may result in interpretation errors in diagnostic imaging or continued symptoms after therapeutic splenectomy.

The usual treatment is splenopexy, fixation of the spleen, but if there is no blood flow after unwinding the spleen through detorsion then splenectomy must be performed. Although there have been few reported cases of treatment through laparoscopic surgery due to the rarity of the disease, it has been proven to be an effective surgical technique.

Splenic rupture is usually evaluated by FAST ultrasound of the abdomen. Generally this is not specific to splenic injury; however, it is useful to determine the presence of free floating blood in the peritoneum. A diagnostic peritoneal lavage, while not ideal, may be used to evaluate the presence of internal bleeding a person who is hemodynamically unstable. The FAST exam typically serves to evaluate the need to perform a CT. Computed tomography with IV contrast is the preferred imaging study as it can provide high quality images of the full peritoneal cavity.

American Association for the Surgery of Trauma Organ Injury Scaling: Splenic Injury Grading

Because of the increased risk of infection, physicians administer oral antibiotics as a prophylaxis after a surgical splenectomy (or starting at birth, for congenital asplenia or functional asplenia).

Those with asplenia are also cautioned to start a full-dose course of antibiotics at the first onset of an upper or lower respiratory tract infection (for example, sore throat or cough), or at the onset of any fever.

Symptoms include an enlargement in the size of the spleen, or a change from the spleen's original position to another location, usually in either other parts of the abdomen or into the pelvis. This ability to move to other locations is commonly attributed to the spleen's pedicle being abnormally long.

Physical factors may cause ischuria, constipation, as well as numerous spleen-related diseases such as hypersplenism, thrombocytopenia, and lymphoma. Blocking of the arteries and torsion in the spleen can also result in abdominal pain or swelling. However, lack of visible symptoms — except in incidents of abdominal pain — makes the disease difficult for doctors to diagnose, though medical imaging techniques such as medical ultrasonography, magnetic resonance imaging, or computed tomography can be used to confirm its occurrence.

To minimise the risks associated with splenectomy, antibiotic and vaccination protocols have been established, but are often poorly adhered to by physicians and patients due to the complications resulting from antibiotic prophylaxis such as development of an overpopulation of Clostridium difficile in the intestinal tract.

Diagnosis is confirmed with CT, or bedside ultrasound for less stable patients. Exploratory laparotomy is rarely used, though it may be of benefit in patients with particularly severe hemorrhage. A set of CT scan grading criteria was created to identify the need for intervention (surgery or embolization) in patients with splenic injury. The criteria were established using 20 CT scans from a database of hemodynamically stable patients with blunt splenic injury. These criteria were then validated in 56 consecutive patients retrospectively and appear to reliably predict the need for invasive management in patients with blunt injury to the spleen (sensitivity of 100%, specificity 88%, overall accuracy was 93%).

The study suggested that the following three CT findings correlate with the need for intervention:

1. Devascularization or laceration involving 50% or more of the splenic parenchyma

2. Contrast blush greater than one centimeter in diameter (from active extravasation of IV contrast or pseudoaneurysm formation)

3. A large hemoperitoneum.

If the splenomegaly underlies hypersplenism, a splenectomy is indicated and will correct the hypersplenism. However, the underlying cause of the hypersplenism will most likely remain; consequently, a thorough diagnostic workup is still indicated, as, leukemia, lymphoma and other serious disorders can cause hypersplenism and splenomegaly. After splenectomy, however, patients have an increased risk for infectious diseases.

Patients undergoing splenectomy should be vaccinated against "Haemophilus influenzae", "Streptococcus pneumoniae", and "Meningococcus". They should also receive annual influenza vaccinations. Long-term prophylactic antibiotics may be given in certain cases.

In cases of infectious mononucleosis splenomegaly is a common symptom and health care providers may consider using abdominal ultrasonography to get insight into a person's condition. However, because spleen size varies greatly, ultrasonography is not a valid technique for assessing spleen enlargement and should not be used in typical circumstances or to make routine decisions about fitness for playing sports.

Symptoms may include abdominal pain, chest pain, chest pain similar to pleuritic pain when stomach, bladder or bowels are full, back pain, early satiety due to splenic encroachment, or the symptoms of anemia due to accompanying cytopenia.

Signs of splenomegaly may include a palpable left upper quadrant abdominal mass or splenic rub. It can be detected on physical examination by using Castell's sign, Traube's space percussion or Nixon's sign, but an ultrasound can be used to confirm diagnosis. In patients where the likelihood of splenomegaly is high, the physical exam is not sufficiently sensitive to detect it; abdominal imaging is indicated in such patients.

Littoral cell angiomas show in CT scans. They are diagnosed by pathologists by taking a sample of the tumour via Fine Needle Aspiration or Core Needle Aspiration or from a splenectomy. Histologically, they have anastoming small vascular channels and cystic spaces with papillary projections.

Treatment of accessory pancreas depends on the location and extent of the injured tissue. Surgery may be an option, or some physicians order prophylactic antibiotics.

Erythrocytes with membrane pits can be indicative of splenic dysfunction as a healthy spleen clears blood of pitted erythrocytes. Pitted erythrocytes can be counted using Normarsky optics. Humans with healthy spleens have less than two percent of their red blood cells contain pits. In comparison, a person with asplenia may have up to 50% of their red blood cells contain pits.

Pancreatic disorders are often accompanied by weakness and fatigue. The past Medical history may reveal previous disorders of the biliary tract or duodenum, abdominal trauma or surgery, and metabolic disorders such as diabetes mellitus. The medication history should be detailed and specifically include the use of thiazides, furosemide, estrogens, corticosteroids, sulfonamides, and opiates. Note a family history of pancreatic disorders. In the review of systems, obtain a complete description of any pain in the upper abdomen or epigastric area. Symptoms that may be important in relation to pancreatic disorders are pruritus, abdominal pain, dyspnea, nausea, and vomiting. The functional assessment includes data about the patient’s dietary habits and use of alcohol.

Note any restlessness, flushing, or diaphoresis during the examination. Vital signs may disclose low-grade fever, tachypnea, tachycardia, and hypotension. Inspect the skin for jaundice. Assess the abdomen for distention, tenderness, discoloration, and diminished bowel sounds.

Tests and procedures used to diagnose pancreatic disorders include laboratory analyses of blood, urine, stool, and pancreatic fluid, and imaging studies. Specific blood studies used to assess pancreatic function include measurements of serum amylase, lipase, glucose, calcium, and triglyceride levels. Urine amylase and renal amylase clearance tests may also be ordered. Stool specimens may be analyzed for fat content. The secretin stimulation test measures the bicarbonate concentration of pancreatic fluid after secretin is given intravenously to stimulate the production of pancreatic fluid.

Asplenia is the absence of normal spleen function. It predisposes to some septicemia infections. Therefore, vaccination and antibiotic measures are essential in such cases. There are multiple causes:

- Some people congenitally completely lack a spleen, although this is rare.

- Sickle-cell disease can cause a functional asplenia (or autosplenectomy) by causing infarctions of the spleen during repeated sickle-cell crises.

- It may be removed surgically (known as a splenectomy), but this is rarely performed, as it carries a high risk of infection and other adverse effects. Indications include following abdominal injuries with rupture and hemorrhage of the spleen, or in the treatment of certain blood diseases (Idiopathic thrombocytopenic purpura, hereditary spherocytosis, etc.), certain forms of lymphoma or for the removal of splenic tumors or cysts.

Treatment has traditionally been splenectomy. However, splenectomy is avoided if possible, particularly in children, to avoid the resulting permanent susceptibility to bacterial infections. Most small, and some moderate-sized lacerations in stable patients (particularly children) are managed with hospital observation and sometimes transfusion rather than surgery. Embolization, blocking off of the hemorrhaging vessels, is a newer and less invasive treatment. When surgery is needed, the spleen can be surgically repaired in a few cases, but splenectomy is still the primary surgical treatment, and has the highest success rate of all treatments.

Howell–Jolly bodies are found on red blood cells and contain chromatin remnants from basophilic cells. Under normal conditions, these nuclear remnants are removed from the blood by the spleen by the spleen's filtering capabilities. Howell-Jolly bodies can be identified and quantified using a blood smear or by flow cytometry. A high number of Howell-Jolly bodies is indicative of splenic hypofunction and potentially autosplenectomy.

A complete blood count (CBC) can be done to diagnose anemia (normochromic, normocytic), thrombocytopenia, and neutropenia. Abnormal liver function tests are commonly used to help in diagnosis as the spleen and liver are strongly affected by one another.

If rheumatoid arthritis is present and other symptoms occur that are not commonly found within RA itself, such as a palpable spleen, further testing should be done. A palpable spleen is not always a clinical significance, therefore CT scan, MRI, or ultrasound can be administered in order to help diagnose the condition. According to Poulin et al, dimensional guidelines for diagnosing splenomegaly are as follows:

- Moderate if the largest dimension is 11-20 cm

- Severe if the largest dimension is greater than 20 cm

Enlargement of the spleen is known as splenomegaly. It may be caused by sickle cell anemia, sarcoidosis, malaria, bacterial endocarditis, leukemia, pernicious anemia, Gaucher's disease, leishmaniasis, Hodgkin's disease, Banti's disease, hereditary spherocytosis, cysts, glandular fever (mononucleosis or 'Mono' caused by the Epstein-Barr Virus), and tumours. Primary tumors of the spleen include hemangiomas and hemangiosarcomas. Marked splenomegaly may result in the spleen occupying a large portion of the left side of the abdomen.

The spleen is the largest collection of lymphoid tissue in the body. It is normally palpable in preterm infants, in 30% of normal, full-term neonates, and in 5% to 10% of infants and toddlers. A spleen easily palpable below the costal margin in any child over the age of 3–4 years should be considered abnormal until proven otherwise.

Splenomegaly can result from antigenic stimulation (e.g., infection), obstruction of blood flow (e.g., portal vein obstruction), underlying functional abnormality (e.g., hemolytic anemia), or infiltration (e.g., leukemia or storage disease, such as Gaucher's disease). The most common cause of acute splenomegaly in children is viral infection, which is transient and usually moderate. Basic work-up for acute splenomegaly includes a complete blood count with differential, platelet count, and reticulocyte and atypical lymphocyte counts to exclude hemolytic anemia and leukemia. Assessment of IgM antibodies to viral capsid antigen (a rising titer) is indicated to confirm Epstein-Barr virus or cytomegalovirus. Other infections should be excluded if these tests are negative.

LCAs most often are not clinically detectable. On occasion, their first presentation may be with splenic rupture.

Most patients show no symptoms and the tumours are found incidentally.

Banti's syndrome (also known as Banti's disease), named for is Guido Banti., is a chronic congestive enlargement of the spleen resulting in premature destruction of the red blood cells by the spleen.

Enlargement of spleen, ascites, jaundice, and the result of destruction of various blood cells by spleen – anemia, leukopenia, thrombocytopenia, gastrointestinal bleeding – may constitute the presenting symptoms.

Splenogonadal fusion is a rare congenital malformation that results from an abnormal connection between the primitive spleen and gonad during gestation. A portion of the splenic tissue then descends with the gonad. Splenogonadal fusion has been classified into two types: continuous, where there remains a connection between the main spleen and gonad; and discontinuous, where ectopic splenic tissue is attached to the gonad, but there is no connection to the orthotopic spleen. Patients with continuous splenogonadal fusion frequently have additional congenital abnormalities, most commonly cryptorchidism.

The anomaly was first described in 1883 by Bostroem. Since then more than 150 cases of splenogonadal fusion have been documented. The condition is considered benign. A few cases of testicular neoplasm have been reported in association with splenogonadal fusion. The reported cases have occurred in patients with a history of cryptorchidism, which is associated with an elevated risk of neoplasm.

Splenogonadal fusion occurs with a male-to-female ratio of 16:1, and is seen nearly exclusively on the left side. The condition remains a diagnostic challenge, but preoperative consideration of the diagnosis may help avoid unnecessary orchiectomy. On scrotal ultrasound, ectopic splenic tissue may appear as an encapsulated homogeneous extratesticular mass, isoechoic with the normal testis. Subtle hypoechoic nodules may be present in the mass. The presence of splenic tissue may be confirmed with a technetium-99m sulfur colloid scan.