Introduction: Due to the increasing trend in gall bladder (GB) carcinoma in India, early diagnosis of GB lesion has become essential. Aim: It is to determine the accuracy of Ultrasonography (USG)-guided fine needle aspiration cytology (FNAC) and an attempt to classify the cytological material according to World Health Organization classification. Materials and Methods: This retrospective study for a span of 3 years was done in the Departments of Radiology and Pathology in Tertiary Teaching Hospital. US-guided FNAC of GB lesion and their histopathological finding were compared. Results: Sensitivity of US-guided FNAC was 98.6% and specificity 97.3%.
Keywords: Chronic cholecystitis, gall bladder carcinoma, histopathology, mucinous, papillary
Carcinoma gall bladder (CaGB) was first described by De Stoll in 1777. CaGB is the most frequent neoplasm of the biliary tract., CaGB predominates in the female population with variable prevalence in different parts of the world. India has an increasing trend of CaGB especially in the Indo-gangetic plain of the eastern Uttar Pradesh and western Bihar regions. North India has 10 times more incidence than South India., In North India, it is one of the most common causes of cancer mortality., Incidence rate is 2.3/1 00 000 female and 1.03/1 00 000 male.
CaGB has a rapid course with high mortality. The preoperative diagnosis of CaGB is difficult owing to vague symptoms and the relative inaccessibility of the gall bladder (GB) to biopsy. CaGB clinically mimics benign GB diseases and usually escapes detection until late in its course.
GB has a wide spectrum of disease ranging from congenital anomalies, cholelithiasis, inflammation, and noninflammatory disease to noninvasive and invasive neoplastic diseases. This study aims to see the sensitivity of ultrasound (US)-guided fine needle aspiration cytology (FNAC) in GB lesions and also attempt to classify the cytological material according to World Health Organization, classification.
Extensive resection is the best available therapeutic option for long-term survival, but majority of patients present in an advanced stage are inoperable. The prognosis depends mainly on the extent of the disease and histological type. US-guided FNAC is a safe, quick, and precise diagnostic procedure for early diagnosis and management of GB cancer in developing countries.
This is a retrospective study held between Feb’13 to Jan’15, a span of 3 years. US-guided FNAC had been done in the Department of Radiology in Tertiary Teaching Hospital by pathologist under aseptic condition. FNAC was done by 18/20 gauge lumber puncture needle with 10 ml syringe. In case of inadequate material, repeat FNAC had been done. Smears were stained by May–Grunwald–Giemsa stain and Papanicolaou stain and studied and reported.
Most of the patients whose FNAC was done had cholecystectomy later and the biopsy was sent to the Department of Pathology. The H and E sections were viewed by the pathologist and the final diagnosis made. In case of doubt more than one pathologist’s opinion was taken and then reported.
Retrospective cytomorphological analysis was done in all cases of CaGB diagnosed by USG guided FNAC with histopathological correlation were included in the study over a period of 3 years. Tumour sub-typing based on WHO classification on cytological aspirate was done.
A total of 84 cases of US-guided FNAC were reported between the year 2013 and 2015. Out of these three had inadequate material so were not considered in this study. Out of the 84 cases only 77 had histological follow-up.
In total 77 cases were considered in this study.
One adenocarcinoma in FNAC was later diagnosed as empyema and another adenocarcinoma was diagnosed as metastasis from liver.[Table 1]
One chronic cholecystitis was diagnosed as adenocarcinoma later on histology.
False positive = 2
False negative = 1
Sensitivity = 98.6%
Specificity = 97.3%
Male: female ratio in our study was 1:4.2
Mean age was 52 years
A total of 61 cases which were diagnosed as adenocarcinoma were further subclassified according to World Health Organization (WHO) classification. And two cases which were false positive were discarded.
59 cases were categorized according to following [Table 2]:
Adenocarcinoma NOS showed cells in sheets, cohesive fragments, and acini. Papillary adenocarcinoma showed papillae with vascular core [Figure 1],[Figure 2] &[Figure 3]. Mucinous adenocarcinoma had single cells and clusters of cells with pools of extracellular mucin [Figure 4] &[Figure 5]. One case of signet ring adenocarcinoma was reported with typical signet ring cells showing pushed nucleus at the periphery [Figure 6]. Adenosquamous carcinoma showed glandular and squamous component. The adenocarcinoma cases (61) were also categorized into well, moderate, and poorly differentiated subtypes, which constituted 3/59 (5.0%), 51/59 (86.5%), and 5/59 (8.5%) of all adenocarcinoma.
Since the first description of CaGB, about 2 centuries ago, the disease has evaded all attempts of early detection and a potential cure. There are only a few studies involving Indian population which has a high incidence of GB cancer. Indians are ethnically and culturally different from their western counterparts, for whom the incidence of this disease is comparatively low. Lack of specific signs and symptoms prevents early detection of CaGB. Clinical presentation of GB malignancy and benign GB disease is almost similar and most of the times it is masked by chronic cholecystitis., Establishing diagnosis in early stage of disease is difficult. Role of FNAC in diagnosis of CaGB has been documented in the literature early in late 1980s and 1990s. FNAC under image guidance has been considered superior in term of diagnostic yield and sample adequacy results into higher sensitivity. FNAC has been found to be a useful modality for the diagnosis of CaGB with sensitivity reported 74 –100% and inadequacy rate of 4–29%. In GB malignancies, false negativity of 11-41% has been documented.
Guided FNAC of the GB lesions provides an accurate diagnosis with sensitivity of 98.6%. Similar studies by Nigam et al. shows 83.3% accuracy, Pachori and Sharma 83.4% accuracy, whereas Kumar et al. showed 95.3% accuracy and Yadav et al showed 96.8%.
Male: female ratio in our study was 1:4.2. Similar studies by Ahmad et al. showed 1:3.8 ratio, Akosa et al. showed 1:3 male:female ratio.
In our study, the mean age group of the patients was 52.2 years, whereas in study by Ahmad et al. it is 44.1 years by Zargar et al., it is 44.1 years and 53 years respectively.
Our study had one case diagnosed by USG FNAC as adenocarcinoma turned out to be metastasis from liver. Another case of adenocarcinoma turned out to be empyema. Ahmad et al. and Kedar et al. also had false positive of empyema diagnosed on USG FNAC as adenocarcinoma.
Shukla et al. had 52.5% adenocarcinoma, 23.3% suspicious of malignancy, 16.6% infection, and 6.6% acellular smear.
Ahmad et al. had 37.3% adenocarcinoma, 13.3% – Infection + Suspicious of malignancy, and 3.8% acellular smear.
Kumar et al. has 79.2% adenocarcinoma, 6.9% suspicious of malignancy, 6.9% chronic cholecystitis, 4.7% xanthogranulomatous lesion, and 2.3% adenoma.
Our present study had 79.2% adenocarcinoma, 12.9% chronic cholecystitis, 1.2% tuberculosis, 5.10% metastasis from liver, and 1.2% squamous cell carcinoma.
According to Yadav et al. 86.7% of the total USG FNAC cases were adenocarcinoma. Of which 72.8% were adenocarcinoma NOS, 8.0% were papillary adenocarcinoma, 5.5% were mucinous adenocarcinoma, 4.1% were adenosquamous, and 1.1% was pure squamous.
Our study had 89.83% adenocarcinoma NOS, 3.38% were papillary, 3.38% mucinous, 1.69 of signet ring adenocarcinoma, 1.69% adenosquamous. and1.29% were only squamous.
WHO (2010) classifies CaGB into various morphological subtypes with their associated prognostic relevance. Papillary adenocarcinoma is not included, it has been considered a good prognostic subtype as described previously by Armed Forces Institute of Pathology.
Papillary adenocarcinoma shows predominantly papillary fragments and corresponds to well- differentiated category with histopathological concordance.
Mucinous adenocarcinoma is characterized by presence of more than 50% of extracellular mucin. It is important to identify mucinous variant as it possesses more aggressive behavior than ordinary CaGB.
Squamous differentiation is uncommon in CaGB. Squamous and adenosquamous constituted 7% of the cases in the study by Roa et al, whereas in present study it was 3% of malignancies.
As far as predictors of outcome of CaGB are concerned, histologic type, grade, and stage of the disease are considered useful parameters in various series., Subtyping and grading of the tumor on cytological material can be of great advantage in guiding the clinician in opting better patient management approach as it is helpful in predicting the patient outcome.
USG FNAC of GB lesion is a very accurate method to diagnose and plan surgery beforehand because of its high sensitivity and specificity. Subtyping and grading of the tumors on cytological material based on WHO classification is helpful in deciding further patient management and may prevent unnecessary burden on already stressed health set-up in a developing Country like ours.
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Conflicts of interest
Authors declare no competing financial interests.
Source of Support: None, Conflict of Interest: None
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]
[Table 1], [Table 2]