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Role of guided FNA in gallbladder cancer: A retrospective 3-year study

1 Department of Pathology, GIPMER, New Delhi, India
2 Department of Gastromedicine, GIPMER, New Delhi, India
3 Department of Gastrointestinal Surgery, GIPMER, New Delhi, India

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Date of Submission16-Dec-2021
Date of Decision14-Oct-2022
Date of Acceptance15-Dec-2022
Date of Web Publication15-Feb-2023


Background: A majority of the patients with gall bladder cancer (GBCa) present at an advanced stage and have poor survival. The aim is to retrospectively study the role of guided FNA in the diagnosis of GBCa in a superspecialty institute and to describe the cytomorphologic spectrum of gall bladder (GB) lesions in the North Indian population. Materials and Methods: All suspected cases of GBCa who underwent guided FNA from the primary GB mass or metastatic liver space-occupying lesion from 2017 to 2019 were included. The aspirate smears were retrieved and analyzed for cytomorphological features independently by two cytopathologists. The neoplastic lesions were classified according to the WHO 2019 classification. Results: Of 489 cases, fine needle aspiration cytology (FNAC) was diagnostic in 463 cases (94.6%), of which 417 (90.1%) were positive for malignancy, 35 (7.5%) were inflammatory, and 11 (2.4%) were inconclusive for malignancy. Adenocarcinoma not otherwise specified (NOS) was the most common type seen in 330 cases (79.1%) and 87 (20.9%) were unusual variants. These included papillary adenocarcinoma (22, 5.2%), mucinous adenocarcinoma (12, 2.8%), signet ring carcinoma (2,0.4%), adenosquamous carcinoma (8, 1.9%), squamous cell carcinoma (10, 2.4%), neuroendocrine neoplasms (7, 1.7%), undifferentiated carcinoma (24, 5.7%) and non-Hodgkin lymphoma (2,0.4%), respectively. Immunohistochemistry on the cell block confirmed the diagnosis wherever possible. Histopathology was discordant in 5 out of 33 cases. Conclusion: Guided FNAC is a sensitive investigation that plays a crucial role in confirming the diagnosis and deciding the further treatment options in advanced-stage GBCa patients. The uncommon variants of GBCa can be reliably categorized on cytology.

Keywords: Adenocarcinoma, cytomorphology, fine needle aspirate cytology, gall bladder cancer

How to cite this URL:
Goyal S, Prasad G, Chaudhary D, Sakhuja P, Srivastava S, Aggarwal AK. Role of guided FNA in gallbladder cancer: A retrospective 3-year study. J Cytol [Epub ahead of print] [cited 2023 Mar 27]. Available from:

   Introduction Top

Gallbladder carcinoma (GBCa) is the most frequent neoplasm of the biliary tract, with marked gender, ethnic and geographical variation worldwide.[1] The incidence of GBCa in North India ranges from 1.01/100,000 for males to 10.1/100,000 for females.[2] The preoperative diagnosis of GBCa is often delayed owing to vague symptoms mimicking benign diseases and the relative inaccessibility of the gallbladder (GB) to biopsy. A majority of the patients present at an advanced and inoperable stage.[3]

Apart from imaging, various invasive procedures are being used to confirm the clinical diagnosis of GBCa, including bile cytology, fine needle aspiration, and biopsy.[4] A biopsy is often not preferred due to the deep-seated nature of the organ and the risk of needle-track seeding. Ultrasound (USG)-guided percutaneous fine needle aspiration cytology (FNAC) is a safe, quick, and minimally invasive diagnostic procedure that can be routinely used for the diagnosis and management of GBCa.[5] Only a few large sample studies on the cytological spectrum of GB lesions are documented in the literature. In this study, we intend to study the role of guided FNA in the diagnosis of GBCa and its implications on patient management over a span of 3 years in a dedicated tertiary care institute. We aim to describe the cytomorphological spectrum of GB lesions in the North Indian population and the problems encountered during reporting if any.

   Materials and Methods Top

This is a retrospective observational study performed over a 3-year period from January 2017 to December 2019. The study was approved by the Institute Ethics Committee, and the need for informed consent was waived. All cases with a clinico-radiological suspicion of GBCa who underwent guided FNA from the primary GB mass or the metastatic liver space-occupying lesions (SOLs) were included in the study.

FNA was performed using a 22-gauge lumbar puncture needle under continuous sonographic guidance through the percutaneous trans-hepatic route by an interventional radiologist (Philips Affiniti 70, Netherlands). For endoscopic guided FNA (EUS), a linear echo-endoscope (Olympus TJF 180, Japan) with a longitudinal convex ultrasound transducer was used. FNA was obtained under sonographic guidance through an endoscope using a 24-25 gauge needle (Boston Scientific). Prior informed patient consent was taken in all patients.

Rapid on-site microscopic evaluation of the aspirate slides with toluidine blue was performed in most cases to reduce the rate of inadequacy.

The remaining slides were air-dried for May–Grunwald–Giemsa stain or were fixed in 95% ethanol for hematoxylin and eosin (H&E) and Papanicolaou staining. Cell blocks (CBs) were prepared in all cases where sufficient material was left in the syringe after making adequate smears. The material was rinsed into an Eppendorf tube containing 1 mL of CB fluid comprising 10% neutral buffered formalin and isopropanol and left for overnight fixation. The next day the material was transferred on a filter paper and was processed routinely. Special stains such as periodic acid Schiff's (PAS), Zeihl–Neelsen stain, and mucicarmine were used whenever required.

All cytology smears were reviewed by two pathologists (SG and GP) for the cytomorphological features. In neoplastic cases, the smears were evaluated for cellularity, architecture, or arrangement of tumor cells as cohesive clusters, glands, acini, papillae, rosettes, trabeculae, or discohesive and singly scattered. The shape of the tumor cells (round/cuboidal or columnar/polygonal) and the degree of pleomorphism in cell shape and size were noted. Specific features like extracellular or intracellular mucin, signet ring cells, atypical squamoid cells, spindle cells, or giant cells were noted. Among nuclear features, nuclear size, overlapping/crowding, nature of chromatin, presence of irregular nuclear membranes, prominent or inconspicuous nucleoli, and nuclear pleomorphism were observed. The presence of any background necrosis, the predominant type of inflammation, and granulomas or histiocytic response were carefully looked for.

On the basis of the abovementioned cytomorphological features, the neoplastic lesions were classified according to the WHO 2019 classification of tumors of the digestive system into adenocarcinoma not otherwise specified (NOS), mucinous adenocarcinoma (>50% of extracellular mucin), colloid carcinoma (>90% of extracellular mucin), poorly cohesive carcinoma with or without signet ring cells, squamous cell carcinoma, adenosquamous carcinoma, poorly differentiated carcinoma, and neuroendocrine neoplasms (NENs). Papillary adenocarcinoma was diagnosed when papillary features were predominant. NENs were further categorized into well-differentiated neuroendocrine tumors and poorly differentiated neuroendocrine carcinoma (PDNEC) including small-cell neuroendocrine carcinoma (NEC) and large-cell NEC (LCNEC). The categorization was carried out on the basis of various architectural and cytological features such as nucleocytoplasmic ratio, mitoses, apoptosis, nuclear molding, and necrosis. Further grading of NENs based on the Ki67 labeling index was performed wherever possible on CBs. A histopathologic correlation was carried out wherever available.

   Results Top

A total of 6997 cytological specimens including fluid cytology were received in the cytopathology section of the pathology department between January 1, 2017, and December 31, 2019. Of these, 489 (6.9% of cytology samples) FNAs from GB mass/thickening and liver SOL in suspected cases of GBCa were included in the study. Of 489 cases, FNAC was diagnostic in 463 cases (94.6%) comprising 154 and 263 guided aspirates from gallbladder mass and liver SOL, respectively. Of the 463 diagnostic cases, 417 (90.1%) were positive for malignancy, 35 (7.5%) were inflammatory, and 11 (2.4%) were inconclusive of malignancy. Overall, the mean patient age was 51.2 years (range = 17–85 years) with a female: male ratio of 2:1 (330:165).

Most of the patients presented with variable and nonspecific clinical features such as right upper quadrant/abdominal pain, jaundice, pruritus, weight loss, and anorexia. Ultrasound revealed obvious mass lesions in the GB with/without liver infiltration and hypoechoic single or multiple SOLs in the liver in most cases. A histopathologic correlation was available in 33 cases [Table 1].
Table 1: Cytologic histologic correlation in 33 cases

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Aspirates from 26 cases were nondiagnostic or labeled inadequate either due to low cellularity (n = 19), necrosis only (n = 4), or obscured morphology by a blood clot or drying artifact (n = 3). Two patients underwent surgery despite repeated inadequate aspirates in view of strong radiological suspicion of malignancy and were diagnosed as malignant on resection.

Inflammatory lesions

[Table 2] shows the distribution of 35 cytologically negative cases. The common entities encountered in the GB were xanthogranulomatous cholecystitis (XGC, n = 8) and acute inflammatory lesion (n = 7). There were two cases of granulomatous cholecystitis with caseous necrosis. Acid-fast bacilli on Ziehl–Neelsen stain were confirmatory for tuberculosis in both these cases. Cytological smears in XGC showed numerous histiocytes and foamy macrophages with focal clustering around capillaries in a background of mixed inflammatory cells [Figure 1]. Histopathology was available in three cases of XGC and was concordant.
Figure 1: Smear from xanthogranulomatous cholecystitis showing loose collections of histiocytes, polymorphs, and foam cells in a hemorrhagic background (MGG). (a) 200×; (b) 400× MGG stain

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Table 2: Spectrum of negative cases diagnosed on cytology

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Among the inflammatory lesions, the most common diagnosis was a hepatic abscess (n = 14, 2.24%), followed by xanthogranulomatous inflammation (n = 3, 0.61%) in aspirates from liver SOLs. Smears from liver abscess revealed numerous viable and degenerated polymorphs in a dirty background, without any evidence of malignancy. In 3 out of 14 cases, epithelioid granulomas were seen; however, special stains for fungus, Entamoeba, and acid-fast bacilli were negative. So, in view of granulomatous inflammation, the possibility of a tubercular abscess was suggested in these three cases. Histopathology confirmed the diagnosis of resolving hepatic abscess and tubercular abscess in two and one cases, respectively.

Suspicious/Inconclusive for malignancy

In this category, the aspirates showed mild cytologic atypia and nuclear pleomorphism, enlargement, and hyperchromasia in the absence of a significant inflammatory background, but these equivocal atypical nuclear features were qualitatively short of definite malignancy (n = 8). Also, aspirates revealing only an occasional or single cluster of unequivocal atypical cells after extensive screening were categorized as suspicious but inconclusive for malignancy (n = 3). Three of these cases underwent resection and were confirmed as adenocarcinoma.

Malignant lesions

Of the positive cases, adenocarcinoma NOS was diagnosed in 330 cases (79.1%), whereas 87 (20.9%) cases were of unusual types as described in [Table 3].
Table 3: Spectrum of positive cases diagnosed on cytology

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The detailed cytomorphologic spectrum of the positive cases (n = 417) is discussed below:


Adenocarcinoma NOS was the most common cytologic diagnosis in the positive category (n = 330,79.1%). It was characterized by cuboidal to columnar tumor cells arranged in cohesive clusters, sheets, and vague glandular or acinar configuration [Figure 2]a. The cells showed nuclear crowding with enlarged and hyperchromatic nuclei and prominent 1–3 nucleoli. In focal areas, cells showed intracellular mucin vacuoles. Biliary, gastric, and intestinal subtypes could not be accurately identified on cytology. Around 38 cases (9.06%) had focal areas of extracellular mucin, accounting for less than 50% of the tumor. [Figure 2]b Aspirates from 275 cases (83.3%) were labeled as moderately differentiated in view of their architectural arrangement in the form of cohesive clusters, vague glandular or acinar configuration, and moderate cytologic atypia. Aspirates from 29 cases (8.7%) comprising of predominant discohesive cell pattern, high-grade cytological atypia along with pleomorphic, bizarre cells qualified for poorly differentiated adenocarcinoma. Histopathology was available in 12 cases and was concordant; however, it revealed additional focal squamous differentiation in 2 cases.
Figure 2: (a) Aspirate smear from GB adenocarcinoma showing tumor cells arranged in tight cohesive clusters and vague glandular pattern (HandE 200×). (b) Higher magnification showed focal intracytoplasmic mucin within the tumor cells (MGG ×400). (c) Tumor cells floating in abundant extracellular mucin (>50%) suggestive of mucinous adenocarcinoma (Papanicolaou ×100) (d) signet ring cell carcinoma with abundant intracytoplasmic mucin and eccentrically placed hyperchromatic nuclei (MGG ×600)

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Mucinous carcinoma

Mucinous carcinoma constituted 2.8% of the total positive cases (n = 12). Cytologically, it was characterized by predominantly single and small clusters of tumor cells floating in pools of abundant metachromatic mucinous material [Figure 2]c. Some of these cells had intracytoplasmic mucin with signet ring cell morphology (<50%). The diagnosis was confirmed in one case on histopathology.

Signet ring cell carcinoma

In two cases (0.4%), aspirates revealed predominantly singly scattered discohesive signet ring cells having abundant intracytoplasmic mucin and peripherally pushed hyperchromatic nuclei [Figure 2]d. A moderate degree of nuclear atypia was noted in most of these cells. The proportion of signet ring cells was far more than 50% of the tumor population, justifying the basis of this rare variant.

Papillary adenocarcinoma

Aspirates from 22 cases (5.2%) showed a predominantly papillary architecture (>90) with a well-differentiated cytomorphology. These cases showed highly cellular smears with numerous cohesive true papillary fragments having central slender fibrovascular cores. The lining tumor cells showed very minimal to mild nuclear pleomorphism and atypia with rare mitotic figures. A histopathologic correlation was available in three cases and was concordant.

Squamous cell carcinoma

A possibility of pure squamous cell carcinoma (SCC) was suggested in ten (2.4%) cases on the basis of cytological features and extensive areas of tumor diathesis. These cases showed scattered polygonal-to-elongated tumor cells with abundant dense keratinized cytoplasm (orangeophilia on Papanicolaou), angulated borders, and pyknotic hyperchromatic nuclei [Figure 3]a and [Figure 3]b. No definite glandular elements were found on extensive screening. Histopathology was available in only two cases which revealed moderately differentiated SCC.
Figure 3: (a) Smear from SCC shows a cohesive cluster of atypical round to polygonal cells having angulated margins and abundant cytoplasm. (MGG ×200). (b) Higher magnification showed malignant squamous cells having abundant dense cytoplasm and central hyperchromatic nucleus in a background of tumor diathesis, with few elongated cells also seen (Papanicolaou ×400). Small-cell carcinoma (c) loose cohesive clusters showing nuclear molding, streaking, and crush artifacts (MGG ×100). (d) Preserved areas showed small round cells with scant cytoplasm and hyperchromatic nuclei (MGG ×400)

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Adenosquamous carcinoma

A diagnosis of adenosquamous carcinoma was rendered in eight cases (1.9%) on the basis of two distinct cell populations of adenocarcinoma and SCC. The malignant squamous cells were polygonal and had well-defined cell borders, abundant dense cytoplasm, and pyknotic hyperchromatic nuclei. Other areas showed cuboidal to oval tumor cells in glandular and acinar configuration, with a moderate amount of cytoplasm, vesicular chromatin, and prominent nucleoli. One case was confirmed, and two cases showed adenocarcinoma with focal squamous differentiation (<25%) on histopathology.

Neuroendocrine neoplasm (NEN)

Neuroendocrine neoplasms were diagnosed in seven cases (1.7%) and were categorized into well-differentiated neuroendocrine tumors (WDNET) and PDNEC. Aspirate smears from four cases comprised small loosely cohesive groups and rosettes of relatively monomorphic cells with marked anisonucleosis, round nuclei, and a moderate amount of finely granular cytoplasm. The nuclei showed fine granular (salt and pepper) chromatin with inconspicuous nucleoli [Figure 4]. These were labeled as WDNET as they lacked any mitoses and necrosis. On the CB, the Ki67 labeling index varied between 2 and 20% in three cases and less than 2% in one case; therefore, they were assigned as G2 and G1, respectively [Figure 4]d.
Figure 4: Well-differentiated neuroendocrine tumor, grade 2, showing (a) loosely cohesive groups and rosettes of relatively monomorphic cells having a moderate amount of cytoplasm (MGG ×200). (b) Higher magnification showed sudden anisonucleosis, round nuclei with fine granular (salt and pepper) chromatin, and inconspicuous nucleoli (MGG ×400). (c) CB synaptophysin positive (×400) and (d) MiB index was 10% (×400)

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Two cases showed predominantly dispersed small hyperchromatic round cells with very scant cytoplasm, high N/C ratio, nuclear molding, streaking, and crushing [Figure 3]c and [Figure 3]d. Brisk mitotic activity and apoptosis with karyorrhectic debris were noted. A possibility of small cell carcinoma (G3) was suggested on cytosmears and was confirmed on the CB.

A 64-year-old woman diagnosed with mixed neuroendocrine non-neuroendocrine carcinoma in 2017 presented with recurrence after 6 months of radical cholecystectomy. FNA from GB fossa mass showed very poorly differentiated large tumor cells in loose cohesive sheets and clusters. These cells had a moderate degree of nuclear atypia and pleomorphism, coarse granular chromatin, and prominent nucleolus. On the CB, diffuse positivity for synaptophysin and chromogranin and a high Ki67 labeling index of more than 80% confirmed the diagnosis of grade 3 LCNEC; however, no other distinct carcinoma component could be recognized on cytology.

Non-Hodgkin lymphoma (NHL)

We encountered two interesting cases of primary lymphoma in the GB without any regional lymphadenopathy or hepatosplenomegaly.

USG-guided FNA from thickened GB wall in a 76-year-old woman showed a relatively monomorphic population of dissociated atypical large-sized atypical lymphoid cells. These cells had a moderate amount of pale cytoplasm, irregular nuclear contours, vesicular chromatin, and conspicuous 1–3 nucleoli. On immunohistochemistry (IHC), the tumor cells were positive for LCA, CD19, CD20, and bcl-2 and negative for CD3. A diagnosis of diffuse large B cell lymphoma was rendered.

A 48-year-old HIV-positive man presented with anorexia and weight loss with a heterogeneous mass involving the GB neck with infiltration into the adjacent liver. USG-guided FNA smears were cellular and revealed monomorphic large lymphoid cells with moderate-to-abundant pale basophilic cytoplasm, round nucleus, opened-up chromatin, and prominent nucleolus. Some of the tumor cells showed a plasmacytoid appearance and had eccentric round nuclei and cart wheel-like chromatin [Figure 5]. On IHC, these cells were negative for CD20, CD79a, CD3, synaptophysin, chromogranin, CK7, and Hep-par and showed cytoplasmic CD38 and CD138 expression. A diagnosis of plasmablastic lymphoma was suggested.
Figure 5: Smears from Non-Hodgkin's lymphoma with plasmablastic differentiation. (a) Dispersed population of monomorphic large lymphoid cells with moderate-to-abundant pale basophilic cytoplasm and round nucleus (Papanicolaou ×200), (b) some of these cells showed plasmacytoid appearance, had eccentric round nuclei and opened-up chromatin. (Papanicolaou ×400) CB (c) positive for CD138 (×400) and (d) negative for CD20

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Undifferentiated carcinoma

This group constituted 24 cases (5.7%) which did not reveal any evidence of glandular, squamous, or neuroendocrine differentiation on morphology as well as on IHC. Aspirate smears showed predominantly dispersed and occasional cohesive clusters of large undifferentiated tumor cells displaying marked nuclear pleomorphism, coarsely clumped chromatin, and macronucleoli. Scattered bizarre and pleomorphic multinucleated tumor giant cells along with foci of necrosis were seen. IHC on the CB could be performed in 16 cases. Positive expression of CK helped in confirming the diagnosis, whereas CK7, CK19, CK5/6, MOC31, p63, Hep-par, LCA, synaptophysin, and chromogranin were negative.

   Discussion Top

The rising incidence and high mortality rate of GBCa in North India demand urgent work for timely diagnosis and management. USG-guided FNAC is a safe, cost-effective, reliable, and simple preoperative investigation in the workup of GB lesions. It is valuable in taking preoperative decisions regarding the type and extent of surgical procedures. It can obviate the need for laparotomy, especially in advanced stages where curative resection is not possible and in patients who are poor surgical candidates.

Imaging-guided FNA is considered superior with a better diagnostic yield as seen in around 94.6% of our study. An experienced radiologist along with an on-site assessment of adequacy on unstained smears by a pathologist can significantly help in improving the diagnostic efficacy.[5] Rare complications reported in previous studies including biliary peritonitis, hemorrhage, and bacteremia[6] were not encountered in any of our patients.

According to recent WHO guidelines, recognition of certain uncommon variants of GBCa such as mucinous carcinoma, SCC, small cell carcinoma, signet ring cell carcinoma, and undifferentiated carcinoma has been recommended in view of their aggressive behavior and dismal prognosis.[7],[8],[9] Due to their advanced stage at the time of detection, surgical resection is not indicated, making the role of FNA with CBs even more imperative. Most of these variants can be diagnosed on cytology smears and confirmed on CBs as seen in our experience.

Adenocarcinoma NOS and unusual histologic variants accounted for 79.1% and 20.9% of GBCa in our study, respectively. The cytomorphological spectrum of GBCa found in our study is comparable to that reported previously in few institutional studies from North India. Unlike previous studies, we have tried to confirm the cytomorphological diagnosis of rare variants and the grading of NEN as per the latest WHO classification on CBs by IHC.

Grading of adenocarcinoma NOS was performed wherever possible. By convention, the predominant discohesive cell pattern, signet ring variant, mucinous, and poorly differentiated adenocarcinoma are high-grade tumors. The majority of the adenocarcinoma NOS comprising cohesive fragments, acini, and glandular architecture were moderately differentiated (83.3%). Notably, almost all papillary adenocarcinoma cases had well-differentiated morphology. Though the incidence of papillary adenocarcinoma is quite rare as reported in the literature (2–8%), it is believed to have a better prognosis owing to its predominant intraluminal bulk and the very low propensity of wall invasion.[10]

Primary neuroendocrine neoplasms of the GB are rare, aggressive tumors with poor prognosis. They are thought to arise from multipotent stem cells in intestinal metaplasia consequent to chronic inflammation as native GB is deficient in neuroendocrine cells.[11] It is difficult to count mitoses in a 2 mm2 area (around 50 hpf) in cytology smears or CBs; therefore, Ki67 IHC is easier to evaluate and is recommended on CB preparations. Morphologically, relatively monomorphic cells arranged in sheets and loose cohesive rosettes, having sudden dramatic anisonucleosis, round to oval nuclei with salt and pepper chromatin, and rare mitosis favor the diagnosis of WDNET. The Ki67 grading in WDNET and distinction from NEC is an important prognostic parameter and bears an impact on the treatment strategy. Small cell carcinoma is characterized by a singly dispersed population of small, hyperchromatic cells with minimal cytoplasm, no nucleoli, prominent nuclear molding, frequent mitoses, apoptosis, and necrosis.[12],[13] Irrespective of treatment modality, the outcome of GB NEC is poor with a mean survival of 5 to 9 months.[11],[14] As most NECs present at an unresectable stage, palliative chemotherapy forms the mainstay of treatment.

Overall GBCa with squamous differentiation was seen in 18 cases (4.3%) in our study. Roa et al.[7] have reported adenosquamous carcinoma in 4.3% and pure SCC in 1% of cases on histopathology in their series on 606 GBCa Chilean patients. The diagnosis of pure SCC can only be suggested on cytology as confirmation requires examination of the entire tumor, and the presence of even a small microscopic focus of adenocarcinoma qualifies for the adenosquamous type. SCC of the GB is usually locally advanced at the time of presentation with the frequent invasion of surrounding organs and is therefore difficult to resect.[15] The advanced stage has an extremely poor prognosis with a mean survival of 6–12 months.[16] Postoperative radiotherapy seems to be beneficial.

We encountered two cases of NHL which were confirmed on immunohistochemistry on the CB. Primary extranodal GB lymphomas are exceedingly rare with very few case reports available.[17] In the single largest series of primary GB NHLs on histopathology of 106 patients, DLBCL was the most common type (33%). The median overall survival (OS) was 41 months with a 5-year survival rate of 40%.[17] Currently, there are no defined management guidelines for GB lymphomas with limited data on the role of surgery and adjuvant treatment options. Preoperative FNA diagnosis can be useful in providing the alternative option of neoadjuvant chemotherapy in such patients. A good long-term outcome has been reported for lymphomas treated by surgery with adjuvant RT.[17]

Many benign conditions, such as tuberculosis, XGC, and unsuspected acute suppurative lesions, often radiologically mimic malignancy.[8],[18],[19] These can be accurately diagnosed on cytology, leading to timely and effective surgical and medical management. In our study, of all radiologically suspected cases of GBCa, 35 cases (7.5%) turned out to be inflammatory on cytology.

XGC was the most common inflammatory lesion encountered in our study (n = 8) which displays wall thickening and adhesions with liver bed, mimicking malignancy on imaging. At times, reactive nuclear atypia seen within the foamy histiocytes in XGC can be misinterpreted as malignancy and result in unwarranted extended surgery.[8],[19] Furthermore, coexisting adenocarcinoma in a background of XGC can often be missed on cytology in lieu of reactive atypia.[8]

Of the available 33 cases, histopathology was discordant in five cases and was reported as malignant. Of these, two aspirates were inadequate and three showed features suspicious but inconclusive for malignancy. Therefore, a repeat guided FNA is recommended in all nondiagnostic and inconclusive aspirates with radiological suspicion of malignancy.

Two rare cases of GB tuberculosis were encountered in our study, which on radiology were suspected to be malignant with liver infiltration. Tuberculosis in the GB is very rare (<1%) with around 120 cases reported to date[20],[21],[22] as the alkaline nature of the bile inhibits the growth of mycobacterium in the GB. Diagnosis can be confirmed in such cases by necrotizing granulomas and the presence of acid fast bacilli (AFB) on cytosmears. The role of cytology in such cases cannot be overemphasized as surgery can be avoided and antitubercular treatment (ATT) can be started immediately.

The present study shows a wide cytologic spectrum of various GB entities along with the typing and grading of malignant lesions on CBs by IHC as per the latest WHO classification in 489 patients of suspected GBCa. The limitation of this study was the non-availability of histopathological correlation as most cases of the patients presented at an advanced stage and hence curative resection was not possible. Palliative treatment with or without chemotherapy was the mainstay of treatment, thereby further emphasizing the role of FNA in timely diagnosis, patient management, and prognostication.

To conclude, we evaluated the diagnostic utility of guided FNA from the primary site as well as liver SOL in 489 radiologically suspected cases of GBCa. FNAC is a safe, sensitive, and cost-effective investigation that plays a crucial role in confirming the diagnosis and deciding further treatment options in advanced-stage GBCa patients. The uncommon variants of GBCa can be reliably diagnosed and categorized on cytomorphology and confirmed by immunohistochemistry on CBs. Larger validation studies with histopathological correlation and long-term follow-up are needed so as to formulate the risk stratification-based uniform reporting system for the categorization of GBCa FNA, which will be helpful in management and prognostication.

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Conflicts of interest

There are no conflicts of interest.

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Correspondence Address:
Puja Sakhuja,
Director Professor and Head, Department of Pathology, GIPMER, New Delhi
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/joc.joc_224_21


  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]

  [Table 1], [Table 2], [Table 3]


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