Liver Metastasis or Granulomatous Hepatitis: A Diagnostic Dilemma

Abstract

Granulomatous liver involvement, which may occur in a variety of infective, inflammatory, and malignant cases, is a rare condition. We present an interesting case of prostate carcinoma presenting as a localized, ill-defined FDG-avid liver lesion, which turned out to be nonmalignant granulomatous hepatitis. Correct histological diagnosis changed a probable dismal prognosis to a completely curable cause.

Keywords

FDG-avid liver lesion - granulomatous hepatitis - hepatic tuberculosis

Introduction

Granulomatous hepatitis is a rare condition characterized by the formation of granulomas in the liver, often due to infectious processes (notably tuberculosis [TB]), sarcoidosis, primary biliary cirrhosis, Hodgkin's lymphoma, or drug-induced liver injury.[1] In some cases, this condition can mimic metastatic deposits, leading to a diagnostic dilemma, particularly in patients with a history of malignancy. A definitive diagnosis typically requires histopathological examination, where the presence of granulomas can confirm the underlying cause.

Case Detail

We present a case of a 67-year-old man who was a known case of ankylosing spondylitis and was well controlled on sulfasalazine and secukinumab since 2023. In 2018, he was diagnosed with prostate carcinoma for which he underwent radical prostatectomy followed by hormonal treatment (degarelix). On routine follow-up, he was found to have a rising trend of serum prostate-specific antigen (PSA), from 8.22 to 13.6 ng/mL. He was advised to undergo fluorodeoxyglucose positron emission tomography (FDG-PET) scan to investigate the same ([Fig. 1]). The PET-computed tomography (CT) revealed diffuse uptake in an ill-defined hypodense area within segments IV and V of the right lobe of the liver, which persisted on delayed imaging (maximum standardized uptake value of 9.3). He was referred to us for the same. Notably, there was no history of jaundice, pruritus, fever, or weight loss. Systemic examination was also unremarkable. His liver biochemistry was as follows: serum total bilirubin—0.7 mg/dL, aspartate transaminase—35 IU/L, alanine transaminase—30 IU/L, gamma glutamyl transpeptidase—146 IU/L, and albumin—3.6 gm/dL. Other lab investigations were as follows: hemoglobin—17.7 mg/dL, total leukocyte count—4,400 cells/cu mm, platelets—159,000/mL, serum creatinine—1.4 mg/dL.

Fig. 1 FDG-PET-CT showed diffuse FDG uptake in an ill-defined hypodense area within segments IV and V of the right lobe of the liver (solid black arrow), which persisted in delayed imaging.

Given his oncological history and the increasing PSA levels, metastasis to the liver was our first differential diagnosis. Other possible differentials included a second primary of the liver such as hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (IHCC). Serum alfa fetoprotein and cancer antigen 19-9 (CA19-9) were 4.04 ng/mL and 27.4 U/mL, respectively. Chest X-ray and CT of the chest showed no abnormality. Consequently, CT-guided biopsy from the liver space-occupying lesion was performed. Histological examination revealed multiple non-caseating epithelioid cell granulomas accompanied by Langhans giant cells and dense lymphocytic infiltration suggestive of granulomatous hepatitis ([Fig. 2]). Notably, Zeihl-Neelsen staining identified a pink rod-like single aggregate of AFB-positive organisms ([Fig. 3]).

Fig. 2 Liver biopsy (hematoxylin and eosin stain under 40 × ) shows multiple non-caseating epithelioid cell granuloma (dotted black arrow), Langhans giant cell (solid black arrow), and dense lymphocytic infiltration.

Fig. 3 ZN stain (oil immersion) showed pink rod-like single aggregate of acid-fast bacilli (solid black arrow).

As a result, the diagnosis of granulomatous hepatitis due to Mycobacterium tuberculosis was established, and antitubercular therapy (ATT) was initiated. Follow-up PET-CT done 6 months later demonstrated resolution of the FDG-avid liver space-occupying lesion ([Fig. 4]) and ATT was stopped.

Fig. 4 Follow-up FDG-PET-CT after 6 months showed resolution of the FDG-avid liver lesion.

Discussion

We highlight the presence of an inflammatory tubercular lesion in a patient who had a past history of ankylosing spondylitis and prostate carcinoma.

Liver metastasis in a case of prostate cancer can be seen in up to 25% cases.[2] An FDG-avid liver lesion can be malignant or nonmalignant. Malignant lesions include primary liver tumors (HCC or IHCC) or metastasis. The most common metastatic lesions are from colorectal, gastric, pancreatic, lung, and breast carcinomas. Nonneoplastic causes include infections such as abscesses and secondary inflammation from cholecystitis.[3] Though a cut-off of 2.5 SUV max (maximum standardized uptake value) differentiates between benign and malignant lesions,[4] tubercular lesions can also have high SUV max up to 21.0.[5] Thus, SUV max cannot be a reliable marker for differentiating malignancy from benign inflammatory lesions.

Liver biopsy is essential to differentiate between neoplastic and nonneoplastic lesions. Liver biopsy from our case showed the presence of granulomas. The prevalence of granulomas on liver biopsy ranges from 2 to 15%.[6] The etiology may vary geographically, while in the developed countries, noninfectious autoimmune conditions like primary biliary cholangitis may be more prevalent.[7] In the developing countries, infectious causes are more common. In India, granulomas are most often reported in TB (55%), followed by leprosy, sarcoidosis, histoplasmosis, brucellosis, amoebic liver abscess, lymphoma, and malignant granuloma.[8]

Hepatic granulomas can result from a number of conditions, such as infections (TB, cryptococcosis), malignancy (non-Hodgkin's lymphoma, liver metastasis), drugs (allopurinol, sulfonamide), hepatic diseases (primary biliary cholangitis, primary sclerosing cholangitis), and autoimmune conditions (sarcoidosis, Crohn's disease).[9] Non-caseating granulomas are seen in sarcoidosis, while central caseous necrosis suggests TB. Additional staining, such as ZN stain, showed pink rod-like acid-fast bacilli, which confirmed TB as in our case.

Hepatic tuberculosis (HTB) is an uncommon manifestation of TB with variable presentation. Risk factors for hepatic TB include immunocompromised states such as human immunodeficiency virus infection, malignancy, alcohol intake, intravenous drug use, past TB, and smoking.[10] Our patient had a history of prostate carcinoma and was also being treated for ankylosing spondylitis.

Studies have shown that reactivation of latent tubercular infection as a side effect of secukinumab (anti-IL-17) treatment in patients with ankylosing spondylitis, psoriasis, and psoriatic arthritis is uncommon.[11] Secukinumab use was considered safe in psoriasis patients with latent TB.[12] So, biological treatment appears to be less likely a cause of tubercular liver granulomas in our case.

HTB is rare and mimics neoplastic liver lesions, leading to misdiagnosis and even unnecessary surgery.[13] In a case report by Hu et al, HTB was mimicking primary liver cancer.[14] In another case report by Maguire et al, an incidentally identified liver lesion on imaging with suspicion of malignancy underwent surgery. However, histopathology of the lesion was suggestive of HTB.[15]

Hodgkin's lymphoma, non-Hodgkin's lymphoma, and renal cell carcinoma are some of the common malignant causes of hepatic granulomas. These granulomas are non-caseating with a less well-defined arrangement of epithelioid histiocytes seen anywhere in the liver where tumor deposits occur, compared to sarcoidosis which has non-caseating granuloma mostly in the portal and periportal locations.[1] Hepatic granulomas due to malignant causes do not correlate with the prognosis of the tumor.[16]

Hence, recognizing granulomatous hepatitis masquerading as metastatic disease is crucial, as the management differs significantly; while metastatic lesions may require oncological interventions, granulomatous hepatitis necessitates specific treatment for the underlying cause.

Similarly, in our case correct histological diagnosis changed a probable dismal prognosis to a completely curable cause.

Conflict of interest

None declared.

Discloser

• All authors disclosed no financial relationships relevant to this publication.

• This case report is not a part of any research trial. Informed consent was obtained from the patient for the publication of their information and imaging.

Authors' Contributions

S.S. and C.S.: drafting of the article, acquisition of data, and final approval of the manuscript.

P.G., V.S., R.B., K.M.: patient management, acquisition of data, critical revision of the manuscript, and final approval of the manuscript.

P.G., R.B., K.M.: analysis and interpretation of data, critical revision of the manuscript, and final approval of the manuscript.

Data Availability Statement

There are no data associated with this work.

Ethical Approval

Written informed consent was obtained from the patient.

Consent for Publication

Written informed consent was obtained from the patient.

• References

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Publication History

Received: 21 April 2025

Accepted: 28 July 2025

Article published online:
09 October 2025