Serum and cystic fluid CA 19–9 determinations as a diagnostic help in liver cysts of uncertain nature

Abstract: The distinction between hepatobiliary cystadenoma or cystadenocarcinoma and simple hepatic cyst complicated by intracystic hemorrhage may prove difficult to determine on the sole basis of clinical and radiological features because of the presence of intracystic structures and septations well-demonstrated by ultrasound examination in both situations. We investigated four patients with various types of hepatic cysts, in whom diagnostic difficulties led to further investigations. In this small group, CA 19–9 serum levels were abnormal only in the two patients with cystadenoma or cystadenocarcinoma. Cystic fluid CA 19–9 values were also five times higher in cystadenoma and cystadenocarcinoma than in other benign lesions. Our data thus suggest that the determination of serum and cyst fluid CA 19–9 may be of help in distinguishing between hemorrhagic simple cyst and cystadenoma or cystadenocarcinoma.     

Cystadenoma of the liver with high levels of ACE and CA 19-9 in the cyst

The development of a cystadenocarcinoma from previously benign cystadenoma is controversial. Neither clinical nor biological factors have been described to explain this transformation. High levels of serum and cystic CEA and CA 19-9 seem to help in the diagnosis of cystadenoma but not cystadenocarcinoma. Definitive histological evaluation is the only means to discriminate malignant from benign cysts. We report a case of cystadenoma of the liver with very high cystic levels and normal serum levels of CEA and CA 19-9.     

Role of cystic fluid in diagnosis of the pancreatic cystadenoma and cystadenocarcinoma

BACKGROUND/AIMS: Early and accurate diagnosis of cystic neoplasm of the pancreas is difficult especially for the differentiation of benign or malignancy. In this study, we try to compare EUS-guided fine needle aspiration biopsy combined with measurement of the cyst fluid and serum levels of CEA, and CA19-9 for the preoperative diagnosis of pancreatic cystadenoma or cystadenocarcinoma. METHODOLOGY: Retrospective analysis was made on the clinical data of 37 patients with pancreatic cystadenoma and 48 patients with cystadenocarcinoma from 1998 to 2005. RESULTS: Carcinoembryonic antigen (CEA), and CA19-9 of the cyst fluid and serum combined with EUS-guided fine needle aspiration biopsy was made. Examination of serum CEA, and CA19-9 resulted in 21.0+/-18.0, 2.7+/-1.7 U/L and 18.7+/-17.5, 269.0+/-182.0 U/L for cystadenoma and cystadenocarcinoma respectively (P<0.05). The sensitivity of cyst fluid combined with biopsy was higher than that of a single marker. However, the sensitivity and specificity of tumor markers of cystic fluid were much higher than that of the serum (P<0.05). CONCLUSIONS: EUS-guided fine needle aspiration biopsy combined with examination of cyst fluid level of CEA and CA19-9 will be a credible means for early diagnosis of pancreatic cystadenoma and cystadenocarcinoma.     

Surgical management of cystic hepatic neoplasms

Background. The clinicopathologic features of cystic neoplasms of the liver, such as cystadenoma and cystadenocarcinoma, are poorly defined because these lesions are extremely rare. Methods. Clinicopathologic findings in six patients who underwent surgery for a cystic hepatic neoplasm were reviewed retrospectively to determine the best surgical strategy to treat this condition. Results. Five patients had a multilocular cyst or elevated lesions detected on preoperative imaging studies. The remaining patient had elevated serum concentrations of carcinoembryonic antigen and carbohydrate antigen 19-9, even though preoperative imaging studies of the hepatic cystic lesion revealed no imaging features of cystadenocarcinoma. Cytology failed to detect malignant cells in the cyst contents of any patient. One patient underwent palliative resection because pleural dissemination was present, and five patients underwent curative resection. Three patients had cystadenoma diagnosed in the surgical specimen. One patient with cystadenocarcinoma has survived for more than 8 years after a curative resection that was limited to the cyst wall, and another patient died of recurrence 13 months after surgery. Conclusions. When a cystic neoplasm is suspected of being cystadenocarcinoma, hepatic resection should be considered, because reliable criteria for distinguishing cystadenoma from cystadenocarcinoma clinically do not exist.     

Mucinous biliary cystadenoma with mesenchymal stroma: Expressions of CA 19-9 and carcinoembryonic antigen in serum and cystic fluid

a case of mucinous biliary cystadenoma with mesenchymal stroma (CMS tumor) in a 64-year-old woman is reported. The patient presented with acute abdominal pain and a palpable mass in the upper abdomen. Computed tomography and abdominal sonography showed characteristic multilocular cysts in the left lobe of the liver. Serum CA 19-9 was elevated to 108 U/ml with normal carcinoembryonic antigen (CEA) and alpha-fetoprotein (AFP) levels. The levels of CA 19-9 and CEA in the cystic fluid were high at 7430 U/ml and 576ng/ml, respectively. The serum CA 19-9 returned to 35 U/ml 4 weeks after tumor resection. These corresponding findings of both tumor markers in the serum and cystic fluid imply that (1) CA 19-9 and CEA both exist in the epithelial component of CMS tumors as evidenced by immunohistochemical stain, (2) serum CA 19-9 is a valuable marker in the diagnosis and monitoring of CMS, and (3) in cystic fluid, there are more significantly high levels of CA 19-9 in CMS compared with levels in simple cyst and polycystic liver disease. Therefore, measurement of CA 19-9 in cystic fluid and serum may be helpful in the differential diagnosis of hepatic cystic lesions.     

Thirteen cases of intrahepatic biliary cystadenoma and cystadenocarcinoma: a single center experience]

BACKGROUND/AIMS: Biliary cystadenoma (BCA) and biliary cystadenocarcinoma (BCACa) are rare cystic neoplasms that usually arise from the liver. We reviewed the clinicopathologic and radiologic findings of 13 cases of intrahepatic biliary cystic neoplasms. METHODS: Seven patients with BCA and 6 patients with BCACa which were pathologically proven within past 10 years were included in this retrospective study. RESULTS: BCA (7 of 7) was more common in female compared to BCACa (4 of 6). Mean age at diagnosis was 53.4 years (BCA) and 58.5 years (BCACa). Abdominal pain (54%) was the most common presenting symptom. Eleven patients (61.5%) exhibited normal liver function profiles and 5 patients (38%) showed elevated levels of serum CA19-9 levels (mean 894.2 U/mL, range: 78.7-2,080). Mean size of tumor was 11.7 cm (range: 5-15). Most frequent radiologic finding was a single cystic mass with septation. BCACa tended to have intracystic solid portion. The cut surface revealed a unilocular or multilocular cystic mass with mucinous contents. Complete surgical excision was done in 12 patients. After the complete resection, recurrence was observed in 1 case of BCACa. CONCLUSIONS: The possibility of biliary cystic neoplasm should be suspected when an intrahepatic cystic lesion with multiseptation or solid portion is noted on imaging study. In addition, complete excision for definite diagnosis and treatment need to be performed.     

Two cases of pancreatic cystadenocarcinoma with elevated CA 19-9 levels in the cystic fluid in comparison with two cases of pancreatic cystadenoma

A 39-year-old woman was hospitalized with left hypochondralgia. Ultrasonography and abdominal computed tomography showed a cystic mass in the tail of the pancreas. Echo-guided aspiration of the cyst was performed, and a markedly elevated CA 19-9 level in the cystic fluid was found. A surgical operation was performed, and the tumor was radically resected. The pathologic diagnosis was papillary adenocarcinoma of the pancreas. Another case of pancreatic cystadenocarcinoma also had an extremely high cystic CA 19-9 level, whereas two cases with benign pancreatic cysts had very low cystic CA 19-9 levels. Moreover, positive localization of CA 19-9 in the cancerous tissue was clearly demonstrated by an immunohistochemical technique, indicating active secretion of CA 19-9 into the cyst, while CA 19-9 in the tissue of pancreatic cystadenoma was almost non-existent. Measurement of the CA 19-9 level in the cystic fluid might therefore be a valuable additional aid in the diagnosis of cystadenocarcinoma of the pancreas.     

Serous cystic neoplasm of the pancreas-indications for surgery

BACKGROUND/AIMS: Serous cystic neoplasm is a rare pancreatic tumor. Almost all of these tumors are benign and only 9 cases of serous cystadenocarcinoma have been reported. Although serous cystic neoplasm is typically a microcystic lesion, there is a wide range of cyst sizes from micro to macro and even unilocular cysts have been reported. Thus, the diagnosis is difficult and indications for surgery are controversial. We aimed to elucidate the clinicopathological and imaging features of serous cystic neoplasm of the pancreas. METHODOLOGY: We investigated 15 cases of resected and 6 cases of nonresected cases of serous cystic neoplasm, evaluating the symptoms, imaging findings, preoperative diagnosis, macroscopic morphology, microscopic findings, and results of follow-up. RESULTS: Imaging diagnosis of serous cystic neoplasm was not easy, because not so many tumors had the typical microcystic pattern. Most of the resected serous cystic neoplasms were non-microcystic or were small tumors, which could not be precisely evaluated. CONCLUSIONS: Small serous cystic neoplasms, which can be diagnosed by imaging, do not need to be resected because serous cystadenocarcinoma is rare. Tumors of the pancreas that cannot be confirmed to be serous cystic neoplasm should be resected because of the possibility of pancreatic cancer, mucinous cystadenocarcinoma, or mucinous cystadenoma with malignant potential.     

Macrocystic serous cystadenoma of the pancreas: clinicopathologic features in seven cases.

BACKGROUND: Serous cystic neoplasms of the pancreas are uncommon tumors classified as microcystic adenomas. In this article, the authors report clinico-pathologic features of seven cases of macrocystic variant of the serous cystadenoma. METHODS: Seven patients (5 females and 2 males) with a diagnosis of cystic lesion of the pancreas were observed after 1995. Clinical, radiological, and pathologic features, including immunohistochemistry, were reported. Enzymes and tumor markers CEA, CA 19-9, CA 125, CA 15-3, CA 72-4, and mucin-like carcinoma-associated antigen (MCA) were investigated in the serum and cyst fluid of the patients. Cytology was also performed. RESULTS: Six patients were symptomatic complaining abdominal pain. All cases had radiologic evidence of unilocular cyst of the pancreas. The suspected diagnosis was consistent with mucinous cystic neoplasm. Serum tumor markers were all in the normal range. After surgery, pathology showed in all cases a cyst lined with cuboidal, periodic acid-Schiff (PAS)-positive epithelium, without mucin content or atypia. Minute microcysts were found surrounding the main cavity. Immunohistochemical stains were positive for cytokeratin, CA19-9, CA15-3, CA 72-4, and MCA. CEA was unexpressed. CA 125 in the cyst fluid were found elevated in three cases and CA 19-9 in three cases. Cytology was negative in all cases. CONCLUSION: When a unilocular pancreatic cyst is found, without history of pancreatitis and gallstones, having low serum tumor markers levels and negativity of CA 72-4 and MCA in the cyst fluid, the diagnosis of the macrocystic variant of the serous cystadenoma may be suggested. At present, the diagnosis is still based on pathological examination after cyst removal.     

DIC-CT findings of biliary cystadenocarcinoma communicating with the bile duct: a case report

Among the intrahepatic cystic diseases except Caroli's disease, only biliary cystadenoma/cystadenocarcinoma may communicate with the bile duct. We present a case of biliary cystadenocarcinoma in which drip infusion cholangiographic-computed tomography demonstrated communication between an intrahepatic cyst and the biliary system preoperatively. Drip infusion cholangiographic-computed tomography, a simple and noninvasive examination, is useful for differentiating biliary cystadenoma/cystadenocarcinoma from other intrahepatic cystic lesions.     

Hemorrhagic hepatic cysts mimicking biliary cystadenoma

The hemorrhagic simple hepatic cyst is extremely rare and can sometimes be confused with biliary cystadenoma or cystadenocarcinoma. Here we present two cases of huge hemorrhagic simple hepatic cysts. Case 1 was a 43-year-old man with a cystic lesion measuring 13 cm× 12 cm in the right hepatic lobe. Ultrasound and computed tomography showed several mural nodules on the irregularly thickened wall and high-density straps inside the cyst. Case 2 was a 60-year-old woman with a huge cyst measuring 15 cm × 14 cm in the central liver. Ultrasound and magnetic resonance imaging showed the cystic wall was unevenly thickened and there were some flame-like prominences on the wall. The iconographic representations of the two cases mimicked biliary cystadenoma. Cystectomy and left hepatectomy were performed for the two patients, respectively. Both patients recovered quickly after their operations and showed no recurrence.     

Multicystic biliary hamartoma with extremely elevated CA19-9: a case report

Multicystic biliary hamartoma (MCBH) is a rare cystic disease of the liver. We herein report a case of MCBH associated with extremely elevated levels of serum carbohydrate antigen (CA) 19-9. A 53-year-old man was referred to our hospital because of extremely elevated CA19-9 levels (more than 12,000?U/mL). Enhanced abdominal computed tomography and magnetic resonance imaging (MRI) revealed a multicystic tumor with a calcified wall in the left lobe of the liver, although no apparent intracystic nodule was detected. Because of the possibility of a malignant tumor, such as intraductal papillary neoplasm of the bile duct or cystadenocarcinoma, the patient underwent left hepatectomy. Based on the postoperative pathological findings, the lesion was diagnosed as MCBH. The serum CA19-9 level drastically decreased after surgery. We encountered a rare case of MCBH with extremely elevated CA19-9 levels.     

Biliary cystadenoma of the liver

Hepatobiliary cystadenoma is an uncommon lesion that is difficult to diagnose preoperatively. Here we report a 34-year-old woman who presented with enlargement of a cyst that had been observed for the previous 6 months. Diagnostic imaging revealed a 7-cm diameter cystic mass with irregular multiple septation in her liver. All laboratory test results were normal except for serum carbohydrate antigen (CA) 19–9 (62.5 U/ml). Because of the malignant potential and the history of enlargement, a complete surgical excision was performed. The patient was discharged after a good recovery; 2 months after surgery her serum CA19-9 level had returned to normal (32.9 U/ml). Regardless of the diagnostic modalities used, cystadenoma and cystadenocarcinoma cannot be differentiated with accuracy. Therefore complete surgical resection is the recommended therapy.     

Macrocystic serous cystadenoma of the pancreas

Summary Background. Serous cystic neoplasms of the pancreas are uncommon tumors classified as microcystic adenomas. In this article, the authors report clinico-pathologic features of seven cases of macrocystic variant of the serous cystadenoma. Methods. Seven patients (5 females and 2 males) with a diagnosis of cystic lesion of the pancreas were observed after 1995. Clinical, radiological, and pathologic features, including immunohistochemistry, were reported. Enzymes and tumor markers CEA, CA 19-9, CA 125, CA 15-3, CA 72-4, and mucin-like carcinoma-associated antigen (MCA) were investigated in the serum and cyst fluid of the patients. Cytology was also performed. Results. Six patients were symptomatic complaining abdominal pain. All cases had radiologic evidence of unilocular cyst of the pancreas. The suspected diagnosis was consistent with mucinous cystic neoplasm. Serum tumor markers were all in the normal range. After surgery, pathology showed in all cases a cyst lined with cuboidal, periodic acid-Schiff (PAS)-positive epithelium, without mucin content or atypia. Minute microcysts were found surrounding the main cavity. Immunohistochemical stains were positive for cytokeratin, CA19-9, CA15-3, CA 72-4, and MCA. CEA was unexpressed. CA 125 in the cyst fluid were found elevated in three cases and CA 19-9 in three cases. Cytology was negative in all cases. Conclusion. When a unilocular pancreatic cyst is found, without history of pancreatitis and gallstones, having low serum tumor markers levels and negativity of CA 72-4 and MCA in the cyst fluid, the diagnosis of the macrocystic variant of the serous cystadenoma may be suggested. At present, the diagnosis is still based on pathological examination after cyst removal.     

Spontaneous rupture of a nonparasitic liver cyst complicated by intracystic hemorrhage

A case of spontaneous rupture of simple liver cyst complicated by intracystic hemorrhage is described. This rare condition was detected in a 61-year-old man who underwent left trisegmentectomy of liver under a suspected diagnosis of cystadenocarcinoma because of elevated serum levels of carbohydrate antigen (CA) 19-9 and DUPAN 2, and the presence of an intracystic structure. The resected specimen showed a benign liver cyst with intracystic hematoma and high levels of CA19-9 and DUPAN 2 in the cystic fluid. It is suggested that cyst rupture may increase serum levels of tumor markers whose levels are high in the cystic fluid, and that repeated observations of an intracystic structure may be the most reliable method to distinguish intracystic hemorrhage from cystic neoplasm. Received: November 30, 1998 / Accepted: February 26, 1999     

Giant biliary mucinous cystadenoma of the liver

Biliary mucinous cystadenomas (BMC) of the liver are rare benign cystic tumors, however an estimated 20% undergo malignant transformation. They have recently been redefined as mucinous cystic neoplasms in the 2010 WHO classification. The preferred treatment is through radical resection, as there are high recurrence rates with other treatment modalities; however this is often not possible in patients with bilobar or giant cysts, and liver transplantation may be indicated. We present a patient with a giant biliary mucinous cystadenoma of the liver and discuss the management with reference to the literature. A 47 year-old woman presented with a 6-week history of moderate epigastric discomfort on a background of 12 months of symptom-free abdominal distension. A giant cystic bilobar tumor of the liver measuring 22 × 23 × 17 cm was diagnosed and characterised by ultrasound scan and magnetic resonance imaging. Serum bilirubin, alkaline phosphatase and gamma-glutamyl transpeptidase were elevated, though other laboratory data including tumor markers (CEA, aFP, CA19-9) were within normal limits. Total excision of the cyst was not possible due to its size and position, and the patient underwent cyst drainage, a sub-total cyst excision and omentoplasty. Histology confirmed a benign biliary mucinous cystadenoma with an ovarian stroma. Though the patient remained clinically well, routine post-operative computed tomography (CT) surveillance showed an 11 cm recurrent cyst at 6 months. A partial cyst resection with close follow-up, regular CA19-9 serology and ultrasound/CT imaging, may be a reasonable alternative for bilobar or giant cysts. However should any features pathognomonic of malignancy develop, then a liver transplantation is indicated.     

Determination of tumor marker levels in cystic fluid of benign liver cysts

The levels of tumor markers in cystic fluid and serum were measured in six patients with benign biliary cyst of the liver. AFP in the cystic fluid was lower than the upper normal limit for serum in all cases, and CEA in the cystic fluid was higher than the upper normal limit for serum in one of the six cases. CA19-9, DU-PAN 2, and SPAN 1 in cystic fluid were much higher than the upper normal limit for serum in all cases (more than 100-fold for CA19-9, twofold for DU-PAN 2, and ninefold for SPAN 1). CA19-9, DU-PAN 2, and SPAN 1 in cystic fluid were significantly higher than the levels in the corresponding serum. Positive immunohistochemical staining against CA19-9, DU-PAN 2, and SPAN 1 was observed in the cytoplasm of the epithelial cells of the cyst wall. These results suggested that the high concentrations of CA19-9, DU-PAN 2, and SPAN 1 in the cystic fluid were due to secretion from the epithelial cells in the benign biliary cysts.     

Intrahepatic biliary cystadenoma: a need for radical resection

BACKGROUND: Intrahepatic biliary cystadenoma (IBC) is a rare liver tumour, which has strong tendency to recur and malignant potential as it can progress to cystadenocarcinoma (IBCa). METHODS: From June 2003 to December 2006, four patients diagnosed with hepatic cystadenoma were operated on our Liver Surgical Unit. All patients were females with median age of 51 years (range 45-63 years). Liver resections included three left and one right hepatectomies. In two patients, IBC was diagnosed by abdominal imaging and serum tumour markers but the rest of the patients were initially misdiagnosed as simple cysts, treated by laparoscopic fenestration and referred to our unit after cyst recurrence. RESULTS: In all cases, the pathology report was consistent with liver cystadenomas. The postoperative course was uneventful and the median hospital stay was 8 days (range 5-12 days). In a median 18-month follow-up (range 2-40 months), all patients are alive and free of recurrence. CONCLUSION: Liver cystadenomas can be easily misdiagnosed with other hepatic cystic lesions. An aggressive surgical approach is recommended, due to their malignant potential and high recurrence rate after fenestration.     

Clinical features and imaging diagnosis of biliary cystadenocarcinoma of the liver

Biliary cystadenocarcinoma of the liver is a relatively rare disease. Herein, we reported a case of biliary cystadenocarcinoma with a review of the literature. A 71-year-old female was admitted with the chief complaint of epigastralgia. The imaging studies revealed a biliary cystadenocarcinoma in the left hepatic lobe with suspicion of direct invasion to the left and middle hepatic veins and inferior vena cava. However, there was no direct invasion of the tumor to these veins in operation findings, and an extended left hepatic resection was performed without resection of inferior vena cava. The tumor was histologically diagnosed as biliary cystadenocarcinoma of the liver. Diagnosis of biliary cystadenocarcinoma is usually difficult preoperatively, however, a diagnosis was possible with the use of imaging studies. It was suggested that this tumor originated from a benign cystadenoma because of the existence of a transitional zone between normal cells and atypical cells in the cystic wall. Systematic hepatectomy was recommended as the initial treatment in consideration of the features of cystadenocarcinoma.