Pancreatic cystic tumors include a set of rare and heterogeneous neoplasms, characterized by a highly variable degree of evolution. Some of them present benign aspects, others transform into malignant forms, still others present borderline aspects (precancerous forms or "borderline").
Patients with von Hippel Lindau syndrome, a genetic syndrome of the central nervous system, develop a cystic tumor in 15-30% of cases. In general, they can be classified as follows:
- Serous cystic tumors
- serous cystadenoma
- serous cystadenocarcinoma
- Mucinous cystic tumors
- Mucinous cystadenoma
- Mucinous cystadenoma with moderate dysplasia (borderline)
- Mucinous cystadenocarcinoma
- non-invasive
- invader
- Mucosecretory intraductal papillary adenoma
- Mucus-secreting intraductal papillary neoplasm with moderate dysplasia
- Mucosecretory intraductal papillary carcinoma
- non-invasive
- invader
- Solid pseudopapillary tumor
The correct diagnostic classification of these neoplasms is essential to establish a correct management from the therapeutic point of view.
SEROUS CYSTIC TUMOR
It represents about 30% of pancreatic cystic tumors, predominates in females (65%) with a mean age of 62 years (range 35-84 years). Their dimensions are highly variable, but at the time of diagnosis they usually have a diameter of about 6-8 cm, and they affect the head of the pancreas in 50% of cases.
They appear as a well-defined mass of the surrounding pancreatic tissue, ovoid in shape, with cysts inside. The cystic growth does not communicate with the pancreatic ducts.
The microcystic variant, characterized by the presence of multiple cysts < 2 cm, is the most common and produces a neoformation with a "honeycomb" appearance, often also presenting a characteristic central fibrous scar.
The macrocystic variant, on the other hand, has fewer and larger cysts, without a fibrous scar inside.
Often, the distinction between these two forms is not clear, and so exist cases of mixed forms, in which both variants are common.
Serous cystadenocarcinoma is the malignant form and is extremely rare. Given the small number of cases observed, it is not clear if this already develops as a malignancy initially or if it is the degeneration of the serous cystic tumor.
Clinical presentation
Serous cystic tumors are generally asymptomatic and are diagnosed incidentally during complementary examinations performed for other pathologies. When present, the most common symptom is widespread abdominal pain. The presence of other symptoms, such as jaundice, vomiting, weight loss, and dyspepsia, are more rare and secondary to the large size of the tumor, sometimes palpable, which causes compression of nearby structures.
Diagnosis
Ultrasound is the initial examination, which initiates the clinical suspicion of the pathology, highlighting numerous small cysts delimited by partitions, with a "honeycomb" appearance. CT (Computerized Tomography) is the second level radiological examination, which generally allows confirming the diagnosis, especially after evidence of a polycystic appearance following injection of contrast medium. As an alternative or in addition to CT, magnetic resonance imaging (MRI) may also be helpful.
In the face of strong diagnostic doubts and especially in elderly patients with high surgical risk, a fine needle aspiration may be useful to allow a cytological and biochemical study (amylase, lipase, neoplastic markers, mucin dosage).
The differential diagnosis, often difficult if it is based exclusively on images, must be made mainly with pseudocysts, mucinous cystic tumor and the most common, ductal adenocarcinoma.
Treatment
Serous cystic tumors are considered benign and have a very low tendency to malignant degeneration, so the therapeutic strategy adopted by some surgeons is careful clinical monitoring, especially in asymptomatic forms. Sometimes, however, in young patients with low surgical risk, a more aggressive attitude is preferred when performing a pancreatic resection, especially when the diagnosis is uncertain. Intervention is certainly indicated in symptomatic cases. Surgery: when a tumor involves the body-tail of the pancreas, resection (central pancreatectomy or left pancreatectomy with preservation of the spleen) is the treatment of choice. Serous cystic tumors are generally easily separable from surrounding tissue; however, even when it seems technically feasible to remove the tumor alone (an operation known as "enucleation"), this is not routinely done because it carries a higher risk of injury. Postoperative pancreatic disorders such as fistula, that is, loss of pancreatic fluid and its discharge into the abdominal cavity, Other surgical techniques, such as cystoenterostomy or external drainage, are contraindicated.
MUCINOUS CYSTIC TUMOR
Mucinous cystic tumors represent almost 50% of pancreatic cystic neoplasms, predominantly affecting women, with the highest incidence between 50 and 60 years of age. They are most frequently located at the level of the body-tail of the pancreas (75%) and do not usually communicate with the other pancreatic cells, although they can still cause narrowing due to compression, considering that they measure more than 5 cm on average. With a smooth surface and being easily separable from pancreatic tissue, they are predominantly macrocystic (>80%) and may have small daughter cysts or calcified nodular areas within the wall (more common in malignant forms). The cysts contain slimy mucoid material within them.
Clinical presentation
The symptoms and signs, often absent or non-specific, are generally secondary to the compressive effect on nearby organs: presence of a palpable mass; abdominal pain sometimes radiating to the dorsal-lumbar region; sensation of weight after meals; jaundice (present more often when the location of the tumor is the head of the pancreas); bleeding from gastric erosion; or varices due to portal hypertension. A careful differential diagnosis of pancreatic pseudocysts is necessary. The presence of symptoms greatly increases the likelihood that the cystic tumor has aspects of malignancy.
Diagnosis
The lesion is usually visible on ultrasound, although it is not sufficient to make a definitive diagnosis. Endoscopy can only provide additional information. On CT, the most sensitive and specific examination, the neoformation can often mimic a pancreatic pseudocyst, but the simultaneous presence of thick walls and calcifications almost certainly indicates malignancy of the lesion (mucinous cystadenocarcinoma). MRI cholangio-Wirsung allows a correct diagnosis to be made in most cases, as does ERCP (endoscopic retrograde cholangiopancreatography), which allows studying the main pancreatic duct and its possible communication with the cystic lesion, with the possibility of also performing a sample for a cytological study. Finally, the cytological and biochemical examination of the intracystic fluid can be reliable to differentiate a pseudocyst or a malignant or benign form of a mucinous cystic tumor, although the histological examination of the entire surgical specimen is still the most accurate.
Treatment
Given the possible malignancy despite the negativity of the biopsy examination, the suggested therapy is radical resection surgery to prevent the progression of the disease towards malignant forms, preventing metastasis and recurrences. For mucinous cystic tumors located in the head of the pancreas, the procedure of choice is duodenocephalopancreatectomy, while for those of the body-tail, central pancreatectomy or left pancreatectomy is performed. When there are easily surgically removable liver metastases, they can be removed at the same time as the neoplasm.
Follow-up
Cystadenomas, cystadenomas with moderate dysplasia, and noninvasive cystadenocarcinomas undergoing radical surgery have a prognosis of up to 100% at 10 years. However, it must be emphasized that cases of recurrence and metastasis after complete resection are reported in the literature even in apparently non-invasive mucinous cystic tumors. Invasive histoadenocarcinomas, on the other hand, have a worse prognosis, 15-33% at 5 years. The benefit of pre- or post-surgical radio and/or chemotherapy is still a matter of debate.
MUCINOUS PAPILLARY INTRADUCTAL NEOPLASIS (IPMN)
NPIMs account for 5% of all pancreatic cancers. They predominantly affect males (65-70%) and have a peak incidence at 60–70 years of age. In 70% of cases, they are located in the head of the pancreas. NPIMs cause cystic dilation of the Wirsung (i.e., the main pancreatic duct) and/or its secondary branches. They are classified into three subtypes:
- The "main pancreatic duct" type, characterized by diffuse or partial dilatation of the Wirsung, is the type that most commonly presents malignant features (57-92%).
- The "secondary branches" type, involving one or more Wirsung's secondary branches, has a more variable rate of malignancy (4–66%).
- "mixed" type, involving both the Wirsung and its secondary branches.
Clinical presentation
NPIM often mimics the symptoms of chronic pancreatitis. About 80% of patients complain of ongoing epigastric, lumbar, and back pain and weight loss. They may also present with jaundice, diabetes mellitus, and an increased blood amylase level.
Diagnosis
CT shows one or more pancreatic cystic dilatations (secondary branch type) or diffuse or segmental dilatation of the Wirsung (main pancreatic duct type). ERCP and MRI of the cholangiopancreatic duct, which visualize the main pancreatic duct, may also be helpful in reaching the diagnosis. Endoscopy and pancreatoscopy have recently allowed the identification and biopsy of proliferations in the Wirsung (fish egg), although they do not allow a direct view of the secondary branches, thus being not very diagnostic in the "secondary branch" form, which is suspected by the presence of mucoid material within an unaffected main pancreatic duct. The differential diagnosis must be made with chronic pancreatitis, whose symptoms simulate, and with mucinous cystic tumors (which, however, are more frequently located in the body-tail and do not communicate with the Wirsung).
Treatment
IMPNs have a high malignant potential, and surgical treatment is considered the treatment of choice. Total pancreatectomy is indicated in NPIM with global involvement of the ductal tree. In NPIM with only partial pancreatic involvement, the choice between radical surgery and partial resection with close follow-up is still debated and must be analyzed on a case-by-case basis. Intraoperative ultrasound and histological examination may be useful even if they do not allow 100% accuracy.
SOLID PSEUDOPAPILAR NEOPLASM
Solid pseudopapillary neoplasm (NSP) is a rare neoplasm that accounts for 2% of all pancreatic cancers. It almost exclusively affects young women, can be located in any region of the pancreas, and is usually large, although it does not correlate with malignancy or a worse prognosis. It is a tumor with a heterogeneous appearance due to the alternation of solid and cystic areas. It presents local aggression with invasion of surrounding structures, while distant metastases are less frequent.
Clinical presentation
The symptoms (epigastric pain, vomiting, anorexia, and weight loss) are non-specific, vague, and not always present, secondary to compression of nearby organs. Often, by virtue of its size, the tumor can be palpable.
Diagnosis
The diagnosis is made by ultrasound, CT, and MRI, which show an ovoid, capsulated, heterogeneous neoformation with possible internal septa and calcifications. Preoperative diagnosis is quite difficult, both because of its extreme rarity and because of its similar characteristics to other neoplasms. A biopsy can help, but it doesn't always give accurate results.
Treatment
The PNS is considered to be of low malignancy, and the treatment of choice is surgical resection (duodenocephalopancreatectomy, central pancreatectomy, spleen-sparing left pancreatectomy). When there are single and/or easily removable liver metastases, they can be resected at the same time as the primary neoplasia. Chemotherapy and radiotherapy, for neoadjuvant and adjuvant purposes, have also given encouraging results, but because of the rarity of this neoplasia and because of the high survival rate even in advanced forms, these therapies have limited use.
Follow-up
The prognosis is excellent, with an overall survival (with and without distant metastases) of 97% at 2 years and 95% at 5 years, reaching 100% at 5 years if the tumor is confined to the pancreas only.