Rare case of hepatic granuloma induced by paclitaxel

Clinical History

A 55-year-old man with a relapse of cutaneous leg kaposi's sarcoma, not an AIDS-related form and treated previously with 3 cycles of paclitaxel, presented to our department for hepatic enzyme alteration. No coexistent infections were discovered. The previous abdominal instrumental examinations of follow-up were negative.

Imaging Findings

US detected a 3 cm hypoechoic-area at the VIII-segment of the liver, without vascular signal (fig 1). Because of an established iodinated contrast-agent allergy, MRI was consequently performed. The T2-weighted sequence showed a hyperintense nodular lesion, suggestive of cellularity (fig 3). Nevertheless, the dynamic sequences after hepatospecific contrast agent injection (gadobenate dimeglumine) did not demonstrate a remarkable vascularization (fig 4). In the hepatospecific phase (40'), the area was hypointense, significant of functioning hepatocytes absence (fig 4). PET-CT with 18-FDG showed low liver uptake (examination not shown).
A US-guided-biopsy was performed discovering many epithelioid cells and T-lynfocytes (fig 5). The immunoistochemical study of the specimen was negative for the presence of HHV-8, excluding a Kaposi's sarcoma location in the liver. The diagnosis was hepatic granuloma.

Discussion

Paclitaxel is a chemotherapeutic agent that acts against a wide range of neoplasms that are refractory to conventional chemotherapy, like breast, ovarian, and non–small cell lung cancers. Derived from the bark of the Pacific yew, Paclitaxel acts through both activation of microtubule assembly and inhibition of microtubule disassembly, resulting in cell mitosis and cell apoptosis deregulation [1]. Hypersensitivity reactions are a well-recognized side-effect of paclitaxel therapy and typically occur with the first or second dose and most frequently manifest as dyspnoea, bronchospasm, urticaria, hypotension, and erythematous rashes [7].
With paclitaxel, alteration of hepatic functions (bilirubin, 8%; alkaline phosphatase, 23%; transaminase, 33%), pancreatitis and steatosis has been observed [2, 3]. Mechanism of paclitaxel-induced hypersensitivity reactions remains unclear. It may be mediated by the release of histamines or other vasoactive substances similar to anaphylactoid reactions observed with IV contrast agents, or it may result from a delayed hypersensitivity response [1, 4].
Well-know drug causes of hepatic granulomas are allopurinol, phenylbutazone, quinidine and sulfonamides. However, the literature does not report cases of hepatic granuloma induced by paclitaxel, but exclusively subungual pyogenic granulomas and hypersensitivity pneumonitis [1, 5].
Granulomas are aggregates of modified macrophages (epithelioid cells) and other inflammatory cells that accumulate after chronic exposure to antigens [6].
The imaging role in this disease is limited to identify the lesion and search for the no-malignancy features (absent enhancement, regular shape). However, findings are non specific and imaging can not be conclusive in the diagnostic process, taking into account the broad range of differential diagnosis, like autoimmune disorders (sarcoidosis), systemic infections (tuberculosis, Histoplasmosis, Hepatitis B/C), medications, malignancy (Hodgkin/non-Hodgkin lymphoma, renal cell carcinoma), idiopathic causes and, rarely, connective tissue diseases causing systemic inflammatory disorder (Wegener's disease), and digestive disorders [6].
Ultrasound could be a first step in the diagnostic process, necessarily followed by CT/MRI. They can disclose hepatomegaly, multiple nodular lesions or, less commonly, isolated hepatic granulomas, absent or low peripheral enhancement, calcifications, and internal caseous tranformation which is however more frequent in tuberculosis. Using MR hepatospecific contrast agents the presence of functioning hepatocytes within the lesion is excluded [8].
Although laboratory tests can provide helpful clues as to the possible existence of granulomatous liver disease, the diagnosis remains exclusively histological. There is no characteristic pattern of biochemical abnormalities suggestive of any specific cause of granulomatous liver disease [6].
Literature describes Paclitaxel's suspension effects with progressive regression of subungual and pulmonary granuloma, but in the present case it remained unchanged on follow-up [1, 5].

Differential Diagnosis List

Final Diagnosis

Hepatic granuloma induced by Paclitaxel therapy.

URL:	https://www.eurorad.org/case/13188
DOI:	10.1594/EURORAD/CASE.13188
ISSN:	1563-4086