|Year : 2014 | Volume
| Issue : 2 | Page : 90-95
Impact of image guided fine needle aspiration cytology in diagnosis of pediatric hepatic mass and cytohistologic concordance
Chhanda Das1, Madhumita Mukhopadhyay1, Moumita Sengupta1, Ashis Kumar Saha2, Biswanath Mukhopadhyay3
1 Department of Pathology, Institute of Post-Graduate Medical Education and Research, Kolkata, West Bengal, India
2 Department of Surgery, Bankura Sammilani Medical College, Bankura, West Bengal, India
3 Department of Pediatric Surgery, Nil Ratan Sircar Medical College, Kolkata, West Bengal, India
|Date of Web Publication||29-Mar-2014|
31 Eastern Park, First Road, Santoshpur, Kolkata - 700 075, West Bengal
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Background: Pediatric hepatic mass is a heterogeneous group of benign and malignant lesions. Percutaneous fine needle aspiration cytology (FNAC) can be utilized as a diagnostic modality to assess the nature of radiologically demonstrated hepatic lesions and thus facilitate individualized treatment. Aims and Objective: The objective of the present study was to determine the diagnostic accuracy of percutaneous FNAC of pediatric liver masses, a procedure that is less invasive than open biopsy. Materials and Methods: A prospective, observational study was carried out in the Department of Pathology in collaboration with Department of Pediatric surgery and Radio-diagnosis including 31 pediatric patients presenting over last two years (June 2011 to May 2013) with focal hepatic lesion on ultrasound and computed tomography (CT) scan. FNAC was carried out under image guidance and cytodiagnosis was reached after appropriate staining. By comparing with histopathology reports, diagnostic accuracy of cytology was evaluated. Result: Among 31 cases included in the study, 51.6% cases were cytologically benign and hemangioma was the most common benign lesion. Hepatoblastoma was the most accounted malignant tumour (12.9%). FNAC provided 94% sensitivity and 92% specificity in diagnosing benign and malignant tumours. Overall diagnostic accuracy was 93.10%. No significant complication was noted. Conclusion: Percutaneous FNAC under image guidance is an effective diagnostic tool for diagnosis of primary and metastatic tumours of liver in pediatric patients.
Keywords: Histopathology, pediatric hepatic mass, percutaneous fine needle aspiration cytology
|How to cite this article:|
Das C, Mukhopadhyay M, Sengupta M, Saha AK, Mukhopadhyay B. Impact of image guided fine needle aspiration cytology in diagnosis of pediatric hepatic mass and cytohistologic concordance. J Indian Assoc Pediatr Surg 2014;19:90-5
|How to cite this URL:|
Das C, Mukhopadhyay M, Sengupta M, Saha AK, Mukhopadhyay B. Impact of image guided fine needle aspiration cytology in diagnosis of pediatric hepatic mass and cytohistologic concordance. J Indian Assoc Pediatr Surg [serial online] 2014 [cited 2019 Jul 20];19:90-5. Available from: http://www.jiaps.com/text.asp?2014/19/2/90/129602
| Introduction|| |
Diseases of liver can be broadly categorized into diffuse parenchymal disorders and focal discrete hepatic masses such as cysts, abscesses, and benign or malignant tumours. Two-thirds of primary liver tumors in the pediatric age group are malignant, and they account for 1-2% of all childhood cancers.  Rest are benign lesions and are the most common vascular in origin (e.g., hemangiomas). 
Proper diagnosis of focal hepatic masses can guide the pediatric surgeons to initiate individualized management. Image guided minimally invasive fine needle aspiration cytology (FNAC) can be used as an initial diagnostic procedure for patients with focal hepatic lesions. Either percutaneous or endoscopy guided approach can be used. In percutaneous approach radiological guidance is practically always needed to ensure a representative sample, to avoid areas of necrosis and hemorrhage and to show the relation to major vessels and other structures. To avoid radiation exposure especially in pediatric patients, ultrasound and magnetic resonance (MR) imaging as guidance for FNAC should be preferred over computed tomography (CT). Presence of on-site cytopathologist along with interventional radiologist increases diagnostic accuracy. 
FNAC is preferred as a preoperative diagnostic modality due its easy accessibility, low cost and lesser complications than biopsy. The incidence of minor and major complications are 0.5% and 0.05%, respectively.  Hemorrhage is the most common accounted complication.
| Materials and Methods|| |
This prospective, observational study was a collaborative effort of the Department of Pathology, Paediatric surgery and Radio-diagnosis including 31 pediatric patients presenting over last two years (June 2011 to May 2013) with focal hepatic lesion based on ultrasound and CT scan. Inclusions criteria were 1) patients presented with clinically symptomatic hepatic mass and 2) incidentally diagnosed hepatic mass on imaging. Patients with ascites, suspected bacterial cholangitis and extrahepatic biliary obstruction, platelet count less than 50000/cumm, INR >1.5 and aPTT >50 seconds were excluded from the study population.
Proper approval from the institutional ethical committee and informed consent from the parents for procedure and anesthesia were taken. History of pre-existing liver disease along with biochemical, serological and radiological data was documented. Laboratory investigation was carried out for assessing platelet count and coagulation profile. Intervention was performed in supine position with leaning to the left. Premedication with midazolam was given to majority of the patients. Selection of the entry site depends on the shortest distance of the lesion and skin surface. Under ultrasound or CT guidance, 21-23 gauge lumber puncture needle was introduced aseptically and materials were aspirated using 10 ml disposable syringe after 4-5 rapid excursion. Special care was taken to avoid injury of the costophrenic angle and major vessels. Monitoring of the patient's vital signs was done at 15 minutes interval during the first two hours.
The aspirate was spread on four slides. Two air-dried smears were stained with May-Grünwald-Giemsa stain and rest alcohol-fixed smears were stained with conventional papanicolaou (Pap) stain. Special cytochemical staining like Periodic acid Schiff (PAS) and Ziehl-Neelsen (Z-N) were performed whenever necessary.
Depending on the cytological findings, smears were broadly categorized into benign, suspicious of malignancy, malignant and unsatisfactory. Report of histopathology was obtained either from post-operative specimen or from core needle biopsy sample. Cytodiagnoses were compared taking histopathology reports as gold standard.
Histopathological diagnosis of the tumor was taken as the 'gold standard' and the reports of FNAC were statistically analyzed using chi square test, Mathews correlation test, sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy etc. Software used in statistical analysis of our study was MedCalc version 11.6 [Mariakerke, Belgium: MedCalc Software 2011].
| Results|| |
A total of 31 patients with hepatic masses were aspirated under ultrasonography guided (USG)-guidance during the two-year study period. Most of the patients in our study presented with abdominal lump and/or dull aching pain in upper abdomen. A few patients presented with non-specific symptoms and weight loss. Total of 16 (51.6%) patients were male and 15 (48.4%) patients were female [Table 1].
Cytological diagnosis were broadly classified into four major categories - unsatisfactory (6.5%), benign (51.6%), suspicious of malignancy (3.2%), and malignancy (38.7%) [Table 2].
|Table 2: Distribution of all cases according to cytological diagnostic category (N = 31)|
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Benign hepatic lesions
In present study, 16 cases (51.6%) were grouped under this category. Haemangioma was the commonest benign lesion.
Constituting four cases of infantile hemangioma, it was the most frequently accounting benign lesion in present study. Presenting symptom was asymptomatic abdominal mass.
Smears prepared from aspirated samples in three cases showed fragments of fibro-vascular tissue against a hemorrhagic background. One case had unsatisfactory aspiration showing only blood elements. Four cases were diagnosed as hemangioma on histological examination.
Four cases of mesenchymal hamartoma aged below 1½ year presented with palpable nontender abdominal mass. Reports of liver function test and serum tumor markers level were unremarkable.
Stained smears showed clusters of benign looking spindle cells against a myxoid background. Resected specimens were available for histopathological examination and final reports were in concordance with cytological findings in all cases [Figure 1]a and b.
|Figure 1: (a) Mesenchymal hamartoma cytology 400 × MGG. (b) Mesenchymal hamartoma histology 100 ×|
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Benign cystic lesions
One case of hepatic foregut cyst was grouped under this category which was diagnosed by ultrasound.
The case of hepatic foregut cyst showed occasional ciliated columnar cells in a background composed of cyst macrophages.
Benign infective lesions
Infective lesions comprised of hepatic abscess, granulomatous inflammation and hydatid cyst.
Four cases of hepatic tuberculosis presented as focal lesion mimicking hepatic malignancy with low grade fever. Aspiration smears prepared which demonstrated presence of epithelioid cell granulomas against a background composed of chronic inflammatory cells and no acid-fast bacilli. Tissue core biopsy showed nodular collection of epithelioid histiocytes with central caseous necrosis and presence of Langhan's type of giant cells.
Two cases of hydatid cyst presented with nonspecific constitutional symptoms and diagnosed incidentally on abdominal imaging. Aspirates smears revealed well preserved protoscolices along with fragment of laminated membrane. Histological sections showed cyst wall composed of outer laminated membrane and inner germinal layer.
Aspirations from two cases of liver abscesses were performed. Former revealed inflammatory cells chiefly neutrophils and latter was unsatisfactory yielding only necrotic materials. Diagnosis of pyogenic liver abscess was made both on cytology and histology in former case. Resected specimen in latter case demonstrated trophozoites of Entamoeba histolytica in the abscess wall.
Malignant hepatic lesions
In present study, 12 cases of malignant hepatic lesions were diagnosed by FNA among 31 diagnostic smears. Histological confirmation was done in all cases either by postoperative specimen or by core needle biopsy. Nine primary lesions and three metastatic lesions belonged to this group.
Four cases of hepatoblastoma aged between 6 months to 3 years were diagnosed and all presented with palpable abdominal lump involving right lobe of liver. Male predominance was noticed with M:F ratio 3:1. Laboratory investigation revealed normal liver function test and elevated alfa-fetoprotein (AFP) level in all above cases.
Stained smears from three cases demonstrated cellular aspirates comprised of uniform population of small cells having scanty cytoplasm leading to cytological diagnosis of hepatoblastoma. Extramedullary hematopoiesis along with large cells having granular cytoplasm were found in one case. Histopathological examination of resected specimen confirmed the diagnosis of epithelial hepatoblastoma in all cases [Figure 2]a and b.
|Figure 2: (a) Hepatoblastoma cytology 400 × PAP. (b) Hepatoblasstoma histology 100 ×|
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Three out of 12 cases were hepatocellular carcinoma. All patients were aged between 10-14 years and male to female ratio was 2:1. Liver function test showed elevated serum bilirubin levels. Serological test for hepatitis B was negative in all cases. The significant finding was elevated AFP level in one case.
FNA smears displayed loosely cohesive clusters of neoplastic cells in a hemorrhagic background. Neoplastic cells are polygonal in shape having high nucleus: Cytoplasm (N:C) ratio and eosinophilic cytoplasm. Traversing spindle shaped endothelial cells and intranuclear cytoplasmic inclusions were evident. Cytological diagnosis of well differentiated hepatocellular carcinoma was reported. Histological confirmation of cytological diagnosis was performed [Figure 3].
In our study, out of the 2 cases of hepatic lymphoma, one was diagnosed on cytological examination as non-Hodgkin lymphoma (NHL) showing monotonous population of intermediate size lymphoid cells with speckled nuclear chromatin and prominent nucleoli in a background of lymphoglandular bodies. This case was diagnosed as NHL (B-cell lymphoblastic lymphoma) on consecutive histological examination. Other case was diagnosed as Burkitt lymphoma both on cytology and histology based examination. Cytology smear revealed monomorphous population of lymphoid cell having granular chromatin and dense blue cytoplasm with lipid vacuoles [Figure 4].
Considering known history of extra-hepatic malignancies at the time of aspiration, three cases represented metastatic malignancy to liver including one case of metastatic neuroblastoma, metastatic Wilms' tumor and metastatic embryonal rhadomyosarcoma each.
Cytodiagnoses were correlated taking histopathology reports as gold standard in 29 cases, as 2 cases were unsatisfactory. In 15 cases, cytological diagnoses of benign diseases were concordant with histopathology. One discordant case (cytologically diagnosed as hemangioma) was histopathologically confirmed as epithelioid hemongioendothelioma. We could accurately diagnose all malignant neoplasm cytologically. The case of nodular myeloid metaplasia was misdiagnosed as suspicious of malignancy. The sensitivity and specificity of USG-guided FNAC in the diagnosis of liver diseases was 94% and 92%, respectively, with a positive predictive value of 92% and negative predictive value of 94%, and overall diagnostic accuracy of 93.10%.[P < 0.001(significant)].
| Discussion|| |
Lindquist  introduced fine needle aspiration biopsy (FNAB) of the neoplastic and non-neoplastic lesions of liver. In present study, FNAC was incorporated as a diagnostic workup under following conditions - 1) symptomatic hepatic mass lesions, 2) image detected mass 3) workup in known cancer patient.
Aspiration was performed under USG or CT guidance. Das et al., stated that image guided aspiration helped to reach definite diagnosis in focal liver lesions.
No major complication was reported in our study. Michielsen PP et al., experienced that rate of complication depends on diameter of needle and number of passes.
Among the four cytological categories, unsatisfactory smear comprised of 6.5% of cases. In Bell et al.,  and Guo et al., studies, the incidences of unsatisfactory smear were 13% and 1%, respectively.
In the benign category, hemangioma was the most common accounted tumor. Three out of four cases were diagnosed successfully depending on the presence of fibro-vascular connective tissue. All the lesions were categorized as cystic intrahepatic lesion rather than hemangioma until the cytological diagnosis was obtained. One case was unsatisfactory that yielded only blood elements which was in concordance with the finding of Layfield LJ et al.  The diagnoses of benign cystic lesions were fairly easy and mesenchymal hamartoma was diagnosed with certain reliability. Granulomatous inflammation of tuberculous origin was the most common benign infective lesion which was similar to other study.  The case of hydatid cyst was diagnosed perfectly without any complication which was in accordance with other study.  Wee et al. emphasized on the examination of the wall of the abscess cavity. FNAC played a crucial role in differentiating pyogenic abscess from tumor with extensive necrosis. But, it failed to diagnose the case of amoebic liver abscess on cytological examination. Wee et al.,  emphasized the importance of histopathology examination of the wall of abscess cavity.
As the malignant lesions were concerned, we came across 4 patients with hepatoblastoma among which 3 were infants. Weinberg AG et al.,  stated that hepatoblastoma was mostly diagnosed during infancy. Regarding laboratory findings, high level of serum AFP was detected in both hepatoblastoma and hepatocellular carcinoma. Chhieng DC  also reported similar findings. As epithelial hepatoblastoma shows spectrum of differentiation,  two types of cytological findings were encountered by us. Based on cell morphology and additional criteria comprised of presence of endothelial cells and intranuclear inclusions,  three cases of hepatocellular carcinoma were accurately diagnosed. All cases of metastatic malignancies were small round cell tumors.
The overall sensitivity and specificity of FNAC in detecting benign and malignant hepatic lesions were 94% and 92%, respectively. There were one false positive and one false negative case. Cytological diagnosis of the epithelioid hemangioendothelioma was difficult. It was wrongly interpreted as hemangioma. We were not able to diagnose nodular myeloid metaplasia. Megakaryocytes are sometimes misinterpretated as malignant cells. 
In present study, the overall diagnostic accuracy of FNAC in focal hepatic lesions is at par with other studies. Kuo et al., Ramdas et al., Cochand-Priollet et al., Franca et al.,, and Mallikarjuna et al., had diagnostic accuracy of 86.1%, 87.5%, 82.6%, 78%, and 97.82%, respectively in their studies. With an accuracy of 93.10% for hepatic lesions, the significance of FNAC as a rapid diagnostic method was established in our study.
| Conclusion|| |
Minimally invasive image guided percutaneous FNAC helps in proper triaging of pediatric hepatic masses and thus leads to initiation of individualized management.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2]