Primary hepatic adenoid cystic carcinoma: A case report and review of literature

Abstract

BACKGROUND

Primary adenoid cystic carcinoma (ACC) of the liver is an exceedingly rare malignancy, with only two previously documented cases in the English-language literature. ACC most commonly arises in the salivary glands, and primary hepatic involvement is highly unusual. The scarcity of reported cases highlights the importance of each new case in advancing understanding of its clinical features and treatment strategies.

CASE SUMMARY

A 59-year-old woman presented with a mass in the right hepatic lobe, which was incidentally detected on contrast-enhanced abdominal computed tomography performed for low back pain. She had no specific symptoms. The lesion had initially been suspected to be a liver abscess at another hospital. She had a history of acute hepatitis C. Imaging studies revealed a cystic-solid mass in segment VII of the liver. Serum tumor marker levels were within normal limits. The diagnosis of ACC was confirmed by liver biopsy, supported by immunohistochemistry. A thorough systemic workup ruled out the possibility of metastatic disease. The patient underwent laparoscopic partial hepatectomy. Postoperative pathological examination confirmed hepatic ACC. Postoperatively, radiotherapy was omitted because the surgical margins were negative; however, given the delayed metastatic potential of ACC, adjuvant chemotherapy with oral capecitabine was administered. At the 7-month follow-up, no evidence of tumor recurrence or metastasis was observed.

CONCLUSION

As the third reported case, this report provides important insights into the diagnosis and management of primary ACC of the liver.

Key Words: Primary adenoid cystic carcinoma; Liver; Diagnosis; Delayed metastasis; Case report

Core Tip: The imaging features were nonspecific and could be mistaken for more common entities, such as a liver abscess. Primary adenoid cystic carcinoma of the liver typically presents with insidious clinical manifestations and lacks specific serological markers, contributing to a high rate of misdiagnosis. This case suggests that, for liver lesions of unknown nature, pathological examination should be considered to establish the diagnosis, even when imaging findings are nonspecific and tumor marker levels are within normal limits. As an aggressive malignancy with the potential for delayed metastasis, primary adenoid cystic carcinoma of the liver warrants increased clinical awareness to facilitate early diagnosis and improve patient prognosis.

INTRODUCTION

Adenoid cystic carcinoma (ACC) is a rare epithelial malignancy that most commonly arises in the salivary glands, accounting for approximately 10% of all salivary gland tumors[1,2]. However, it can also occur at other sites, including the lacrimal glands[3], respiratory system[4], breast[5], prostate[6], and female reproductive organs[7]. Primary ACC of the liver (PACCL) is exceptionally rare, with only two previously documented cases in the English-language literature[8,9]. The first, described by Ziarkiewicz-Wróblewska et al[8], involved a 21-year-old asymptomatic woman in whom a massive tumor, measuring approximately 30 cm and occupying nearly the entire liver, was incidentally discovered during pregnancy. The second case, reported by Zhang et al[9], occurred in a 44-year-old man who presented with epigastric distension and pain; the tumor measured approximately 21 cm and invaded the adjacent diaphragm and omentum. Despite surgical resection, the patient experienced recurrence at 26 months and died 33 months postoperatively. These previously reported cases highlight the potential for PACCL to present as a large, aggressive tumor with nonspecific symptoms.

The diagnosis of PACCL is particularly challenging because of its nonspecific clinical presentation, unclear pathogenesis, and extreme rarity, all of which often lead to misdiagnosis or delayed detection. This difficulty is further compounded by its nonspecific imaging characteristics. On imaging, PACCL typically appears as a heterogeneous mass with both solid and cystic components and can easily be mistaken for more common hepatic lesions such as biliary cystadenocarcinoma, hepatocellular carcinoma (HCC) with necrosis, or even a liver abscess. Consequently, PACCL is rarely suspected preoperatively, and histopathological examination with immunohistochemical staining remains the only reliable method for definitive diagnosis.

Given these diagnostic challenges and the absence of established management guidelines, documentation of individual PACCL cases is of substantial clinical value. First, increasing awareness of its imaging mimics may help reduce diagnostic delay. Second, recognition of its potential for late recurrence despite indolent growth highlights the need for long-term surveillance even after complete resection. Finally, sharing therapeutic experience is invaluable for informing clinical decision-making in the absence of a standard treatment protocol. Therefore, we present a new case of PACCL together with a systematic literature review to summarize its clinical and imaging features, discuss the diagnostic and therapeutic challenges, and contribute to the limited evidence base for this rare malignancy.

CASE PRESENTATION

Chief complaints

A 59-year-old woman was found to have a liver mass more than 10 days earlier.

History of present illness

On July 19, 2024, the patient underwent contrast-enhanced whole-abdomen computed tomography (CT) at a local hospital for low back pain. The scan revealed an occupying lesion measuring 64 mm × 62 mm in the right hepatic lobe, which was considered to represent a “liver abscess”. The patient denied abdominal pain, abdominal distension, fever, chills, or significant weight loss and was otherwise in good general health.

History of past illness

Her medical history included a diagnosis of acute hepatitis C at 22 years of age, which was treated with a 6-month course of oral medication, with no subsequent follow-up evaluation.

Personal and family history

The patient denied any relevant family history.

Physical examination

Physical examination revealed no hepatic tenderness or jaundice of the skin or sclera.

Laboratory examinations

Laboratory testing showed an elevated ferritin level of 198.00 μg/L, whereas other parameters, including carbohydrate antigen 19-9, alpha-fetoprotein, carcinoembryonic antigen, alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyl transpeptidase, were within normal ranges.

Imaging examinations

Ultrasound revealed a cystic-solid mass in the right hepatic lobe, with a centrally located anechoic area showing poor internal sound transmission and peripheral blood flow signals (Figure 1). Magnetic resonance imaging demonstrated a heterogeneous mass in segment VII of the liver. On T1-weighted imaging, the lesion was predominantly hypointense, with internal iso- to hyperintense foci (Figure 2A). T2-weighted imaging showed predominant hyperintensity with internal hypointense areas (Figure 2B). The peripheral portion of the lesion demonstrated restricted diffusion, with marked hyperintensity on diffusion-weighted imaging (DWI) and corresponding hypointensity on the apparent diffusion coefficient map (Figure 2C and D). In-phase and opposed-phase T1-weighted imaging showed no significant signal loss on the opposed-phase images (Figure 2E). On contrast-enhanced imaging, the lesion exhibited patchy, heterogeneous enhancement (Figure 2F and G). In the hepatobiliary phase, the lesion appeared distinctly hypointense relative to the surrounding liver parenchyma (Figure 2H). 18F-fluorodeoxyglucose positron emission tomography/CT revealed a heterogeneous mass in segment VII of the liver. The 18F-fluorodeoxyglucose positron emission tomography uptake showed an uneven annular increase, with a maximum standardized uptake value of 7.43. No other significant abnormal lesions were identified elsewhere in the body (Figure 3). Based on the clinical presentation and imaging findings described above, the preliminary diagnosis was a malignant hepatic tumor.

Figure 1 Ultrasound revealed a cystic-solid mass measuring approximately 68 mm × 59 mm in the right lobe of the liver. A central fluid-dark area with poor internal sound transmission (indicative of necrosis) and peripheral blood flow signals were observed. These features are non-specific and may mimic benign lesions such as a liver abscess.

Figure 2 Magnetic resonance imaging revealed a heterogeneous signal mass in segment VII of the liver, measuring approximately 64 mm × 62 mm. A: T1-weighted image shows predominant hypointensity with internal iso- to hyperintense foci; B: T2-weighted image shows predominant hyperintensity with internal hypointense areas; C and D: Diffusion-weighted imaging (C) and apparent diffusion coefficient (D) demonstrate peripheral restricted diffusion, indicating high cellularity at the viable tumor rim; E: Opposed-phase imaging shows no significant signal loss, arguing against microscopic fat; F and G: Contrast-enhanced imaging reveals patchy, heterogeneous enhancement; H: Hepatobiliary phase shows distinct hypointensity relative to background liver, indicating a lack of functioning hepatocytes.

Figure 3 ¹⁸F-Fluorodeoxyglucose positron emission tomography/computed tomography imaging revealed a heterogeneous density mass in segment VII of the liver, measuring approximately 63 mm × 61 mm. A: The maximum intensity projection of 18F-Fluorodeoxyglucose positron emission tomography (¹⁸F-FDG PET) shows the lesion with no evidence of extrahepatic primary tumors; B: Computed tomography cross-sectional image demonstrates the mass is hypodense; C: ¹⁸F-FDG PET image shows uneven annular hypermetabolism; D: Fused ¹⁸F-FDG PET/computed tomography image demonstrates annular fluorodeoxyglucose uptake (maximum standardized uptake value 7.43) corresponding to the viable tumor rim.

FINAL DIAGNOSIS

To clarify the nature of the hepatic mass, a liver biopsy was performed on August 2, 2024. The lesion was biopsied under ultrasound guidance using an 18-gauge core needle biopsy system. Three separate passes were made to obtain adequate tissue samples from different areas of the peripheral enhancing component of the mass while avoiding the central necrotic region. Each core specimen measured approximately 1.5 cm in length and was immediately fixed in 40 g/L formaldehyde for histopathological examination and immunohistochemical staining. Immunohistochemical analysis showed focal positivity for cytokeratin 7 (CK7), cluster of differentiation 117 (CD117), CK5/6, and tumor protein p63 (p63). Combined with the morphologic features, these findings supported the diagnosis of a biphasic epithelial tumor, ACC. Because primary ACC typically arises in sites such as the salivary glands, breast, reproductive organs, and gastrointestinal tract, and because PACCL is exceedingly rare, with only isolated cases reported in the literature, metastatic disease had to be excluded. Further color Doppler ultrasonography of the parotid glands and breasts showed no obvious masses. positron emission tomography (PET)/CT also revealed no other suspicious primary lesions, thereby excluding hepatic metastasis.

TREATMENT

The tumor was treated with laparoscopic partial hepatectomy on August 7, 2024. Intraoperatively, palpation of the posterior segment of the right hepatic lobe revealed a firm, irregular mass measuring approximately 6 cm in diameter with poorly defined margins. Thorough exploration of the abdominal cavity showed no other significant abnormalities.

Postoperative pathological findings showed that, histologically, the tumor exhibited a predominantly cribriform growth pattern and was poorly circumscribed, with adjacent normal liver parenchyma visible on one side (Figure 4A). The cribriform structures contained pseudocysts, pseudoglands, and pseudolumina filled with blue-stained mucoid material and eosinophilic basement membrane-like substance (Figure 4B). Focal areas showed tubular structures and solid growth patterns (Figure 4C and D).

Figure 4 Microscopic characteristics. A: The tumor was poorly demarcated from the adjacent liver parenchyma, × 20; B: The tumor predominantly exhibited a cribriform growth pattern, × 100; C: Focal areas showing tubular structures were present, × 100; D: Focal areas of solid growth pattern were observed, × 100. The presence of multiple architectural patterns is consistent with the diagnosis of adenoid cystic carcinoma.

Immunohistochemically, the luminal epithelial cells were positive for CK7 and CD117 (Figure 5A and B), whereas the abluminal/myoepithelial cells were positive for p63 (Figure 5C). The Ki-67 proliferation index was approximately 20% (Figure 5D). This immunohistochemical profile is characteristic of ACC and is crucial for confirming the diagnosis. Co-expression of CK7 and CD117 in the luminal epithelial cells, together with p63 positivity in the abluminal/myoepithelial cells, reflects the hallmark biphasic differentiation of ACC[10,11] and helps distinguish it from other hepatic tumors, such as HCC or cholangiocarcinoma. The pathological findings were consistent with ACC of the liver.

Figure 5 Immunohistochemical findings. A: Cytokeratin 7 showed diffuse membranous positivity, supporting a glandular epithelial origin, × 100; B: Cluster of differentiation 117 demonstrated cytoplasmic and membranous positivity, a characteristic immunophenotype of adenoid cystic carcinoma, × 100; C: P63 exhibited nuclear positivity, indicating the presence of myoepithelial cells, × 100; D: The Ki-67 proliferation index was approximately 20% in the tumor cells, suggesting moderate proliferative activity, × 100. The immunohistochemical profile (cytokeratin 7+, cluster of differentiation 117+, p63+) is consistent with the diagnosis of adenoid cystic carcinoma.

OUTCOME AND FOLLOW-UP

The patient recovered well postoperatively. Because the surgical margins were negative, radiotherapy was not pursued. The patient then began adjuvant chemotherapy with oral capecitabine. Follow-up magnetic resonance imaging at 7 months (Figure 6) revealed no evidence of local recurrence or metastasis. Postoperative laboratory findings, summarized in Table 1, showed that all liver function test results and tumor marker levels were within the normal reference ranges.

Figure 6 Postoperative follow-up magnetic resonance imaging at 7 months, no evidence of local recurrence or metastasis was observed. A: T1-weighted image; B: T2-weighted image; C: Contrast-enhanced image.

Table 1 Postoperative laboratory findings at 7-month follow-up.

Parameter	Result	Reference range
Liver function tests
ALT	11 U/L	7-40 U/L
AST	22 U/L	13-35 U/L
ALP	109 U/L	50-135 U/L
GGT	19 U/L	7-45 U/L
Total bilirubin	10.8 μmol/L	0.0-21.0 μmol/L
Tumor markers
AFP	2.84 ng/mL	0.00-8.78 ng/mL
CA19-9	6.09 IU/mL	< 37.00 IU/mL
CA125	5.71 U/mL	< 35.00 U/mL
CA15-3	19.20 U/mL	< 25.00 U/mL
CEA	1.22 ng/mL	0.00-5.00 ng/mL

ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; ALP: Alkaline phosphatase; GGT: Gamma-glutamyl transferase; AFP: Alpha-fetoprotein; CA19-9: Cancer antigen 19-9; CA125: Cancer antigen 125; CA15-3: Cancer antigen 15-3; CEA: Carcinoembryonic antigen.

DISCUSSION

This case uniquely documents the clinical presentation, imaging findings, surgical management, and short-term follow-up of histopathologically confirmed PACCL after thorough exclusion of metastatic disease. The tumor in this case exhibited the classic morphologic and immunohistochemical features of ACC[12]. Although ACC most commonly arises in the salivary glands[13], it can occur in virtually any glandular tissue, including exocrine gland-bearing sites such as the tracheobronchial tree[14], breast[15], and uterine cervix[16]. Therefore, the key differential diagnostic consideration in this setting is exclusion of metastatic ACC from another primary site. In this patient, whole-body PET/CT revealed no evidence of tumors in the salivary glands, head and neck region, or elsewhere. Based on the pathological and imaging findings, the diagnosis was consistent with PACCL.

The imaging findings of PACCL can mimic those of more common hepatic lesions, and a systematic comparison of imaging features is essential for accurate diagnosis. A liver abscess typically appears as a cystic lesion with peripheral rim enhancement and perilesional edema. On DWI, restricted diffusion is usually observed within the central purulent content[17]. In contrast, the present case showed peripheral rather than central diffusion restriction, with the internal fluid-containing area corresponding to necrosis rather than pus. The absence of clinical signs of infection further supported a neoplastic process. Biliary cystadenocarcinoma typically presents as a multilocular cystic mass with internal septations and mural nodules, with progressive enhancement of the solid components[18]. Although the present case shared some overlapping features, its predominantly solid nature with central necrosis is more consistent with a solid tumor showing cystic degeneration than with a primarily cystic neoplasm. HCC typically demonstrates arterial-phase hyperenhancement followed by washout in the portal venous and delayed phases[19]. The present case lacked this characteristic vascular pattern, arguing against a diagnosis of HCC. The most valuable discriminating feature was the PET/CT finding. The absence of evidence of an extrahepatic primary tumor effectively ruled out metastatic ACC from salivary or other glandular origins. This peripheral hypermetabolism corresponded to the viable tumor rim identified on DWI and contrast-enhanced imaging. In summary, the combination of peripheral diffusion restriction, heterogeneous enhancement, and annular fluorodeoxyglucose uptake without an extrahepatic primary lesion should raise suspicion for this rare entity, and histopathological confirmation is strongly recommended.

Misdiagnosis of PACCL as a benign lesion, such as a liver abscess, may lead to unnecessary antibiotic therapy, delayed referral, and a missed opportunity for timely surgical resection. In the present case, the lesion was initially suspected to be a liver abscess at another hospital, highlighting this diagnostic challenge. Therefore, when imaging reveals an atypical cystic-solid liver lesion, rare malignancies should be considered.

Based on the diagnostic experience from this case, evaluation of an atypical cystic-solid liver lesion with the abovementioned imaging features should first focus on excluding metastatic ACC. Whole-body PET/CT should be performed to assess the salivary glands, head and neck region, and other potential primary sites. Once metastasis has been excluded, a core needle biopsy with immunohistochemistry is required to confirm the histology of ACC. Multidisciplinary involvement is recommended to guide management and ensure appropriate long-term surveillance.

The liver is an exceedingly rare primary site for ACC. Regarding the pathogenesis of primary salivary gland-type tumors in the liver, two main hypotheses have been proposed: One is that stem/progenitor cells undergo malignant transformation into salivary gland-type tumors[20]; the other is that the tumor originates from ectopic salivary gland tissue[21,22]. Although no cases of ectopic salivary gland tissue in the liver or biliary system have been reported to date, this hypothesis cannot be definitively excluded.

As of this writing, only two cases of PACCL have been reported in the English-language literature. Ziarkiewicz-Wróblewska et al[8] described a 21-year-old woman whose lesion, incidentally discovered during pregnancy, was a massive tumor measuring approximately 30 cm in diameter and occupying nearly the entire liver. The patient was asymptomatic, with only mildly abnormal liver function test results, and the pathological findings suggested that the tumor might have originated from the bile ducts. Zhang et al[9] reported a 44-year-old man with a tumor measuring approximately 21 cm in diameter. The tumor invaded the liver capsule and involved the adjacent diaphragm and omentum. This patient presented with epigastric distension and pain, together with elevated gamma-glutamyl transpeptidase and carbohydrate antigen 19-9 levels. Postoperatively, the patient declined radiotherapy and chemotherapy. Tumor recurrence was observed in the right hepatic lobe, diaphragm, omentum, and retroperitoneum 26 months after surgery, and the patient died 33 months postoperatively. The present case involved a 59-year-old woman with a tumor measuring approximately 6 cm in diameter who presented only with low back pain. Both tumor marker levels and liver function test results were within normal ranges.

A systematic comparison of the three reported PACCL cases (Table 2) reveals several notable patterns. First, tumor size at presentation has varied considerably, ranging from 6 cm in the present case to approximately 30 cm in the case described by Ziarkiewicz-Wróblewska et al[8], suggesting that PACCL can remain asymptomatic until it reaches a large size. Second, although two cases presented with nonspecific abdominal or back pain, one was discovered incidentally during pregnancy, further highlighting the indolent nature of this tumor. Third, laboratory findings have been nonspecific, with tumor marker levels and liver function test results showing no consistent abnormalities across cases. Notably, serum tumor markers, including alpha-fetoprotein, carcinoembryonic antigen, and cancer antigen 125, were within normal limits despite histopathologically confirmed malignancy. This finding highlights that normal tumor marker levels do not exclude malignancy, particularly in rare tumors such as PACCL, and overreliance on these markers may delay diagnosis. Clinicians should maintain a high index of suspicion based on imaging findings and should not be dissuaded from obtaining histopathological confirmation when tumor marker levels are normal. Additionally, the aggressive potential of PACCL is illustrated by the case reported by Zhang et al[9], in which local invasion and distant recurrence occurred despite surgical resection, ultimately resulting in death 33 months postoperatively. These observations highlight the need for long-term surveillance even after apparently complete resection.

Table 2 Summary of reported cases of primary adenoid cystic carcinoma of the liver.

	Ziarkiewicz-Wróblewska et al[8]1	Zhang et al[9]	Present case
Age/sex	21/female	44/male	59/female
Presentation	Incidental (pregnancy)	Epigastric pain, distension	Lower back pain
Tumor size (cm)	30	21	6
Tumor location	Nearly entire liver	Right lobe	Posterior segment, right lobe
Extent of disease	Confined to liver	Invasion of diaphragm and omentum	Confined to liver
Tumor markers	Within normal range	Elevated GGT, CA19-9	Within normal range
Treatment	Surgery	Surgery	Surgery + capecitabine
Follow-up (month)	NA	33	7
Outcome	NA	Death	No recurrence to date

¹Information for this case is derived from the English abstract, as the full-text article was not accessible.

Long-term follow-up information was not available in the English abstract. NA: Not available; GGT: Gamma-glutamyl transpeptidase; CA19-9: Carbohydrate antigen 19-9.

ACC can occur at any age, with the highest incidence in individuals aged 50-60 years and a median age at diagnosis of 57 years[23]. The incidence is higher in women than in men, with a ratio of approximately 1.5:1[24]. The clinical course of ACC is characterized by slow growth, but it also shows a tendency for perineural invasion and hematogenous spread, particularly in older adults[25]. In the early stages, it typically progresses indolently and often presents without obvious symptoms. In most cases, symptoms emerge only when the tumor invades local nerves, with the manifestations depending on the specific site of involvement[26]. All three reported cases of PACCL were asymptomatic in their early stages, which is consistent with the typical clinical presentation of ACC.

Currently, there is no standardized treatment protocol for PACCL, and surgery remains the mainstay of treatment. In this case, the patient received postoperative oral capecitabine chemotherapy, whereas radiotherapy was not administered because the surgical margins were negative. Studies have shown that radiotherapy does not significantly improve overall survival in patients with ACC[27]. The decision to administer adjuvant capecitabine in this case was based on clinical reasoning and the absence of a standardized therapeutic protocol for PACCL. First, although the surgical margins were negative, the known aggressive biological behavior of the tumor, including its potential for perineural invasion and distant metastasis, justified consideration of systemic therapy to reduce the risk of recurrence. Second, among the available chemotherapeutic options, capecitabine was selected because of its manageable toxicity profile[28], the convenience of oral administration, and its established use in the palliative treatment of advanced ACC arising from other primary sites, where it has shown modest disease-control activity[29]. Tumor stage and histological grade are important prognostic factors. In addition, various biomarkers have been considered potential prognostic indicators in ACC. Increased Ki-67 expression is associated with a higher proportion of solid components and suggests a poorer prognosis[30]. Immunohistochemical positivity for CD117 has also been associated with greater tumor aggressiveness[31]. The most common metastatic sites of ACC are the lungs, followed by bone, although the liver and brain are also frequent sites of metastasis[32,33]. Therefore, long-term close surveillance is necessary.

Despite the important findings presented in this case report, several limitations should be acknowledged. The primary limitation is the relatively short follow-up period of only 7 months. As is well documented, ACC is characterized by indolent growth but a high propensity for late recurrence and delayed distant metastasis, which may occur years or even decades after initial treatment[34]. Therefore, a 7-month observation period is insufficient to fully assess the patient’s long-term prognosis. Future studies with extended longitudinal follow-up are needed to better understand the biological behavior of PACCL and to evaluate the true efficacy of therapeutic interventions. Long-term surveillance remains imperative in patients with this rare, indolent, yet potentially aggressive malignancy.

CONCLUSION

PACCL is an extremely rare malignancy with nonspecific clinical and imaging features that often mimic more common hepatic lesions, such as a liver abscess. Therefore, histopathological and immunohistochemical examinations are essential for definitive diagnosis in cases of atypical cystic-solid liver lesions. Surgical resection remains the mainstay of treatment, whereas distant metastasis is a critical adverse prognostic factor. Given the indolent yet aggressive nature of this tumor, early pathological confirmation, timely surgical intervention, and diligent long-term surveillance are crucial for optimizing patient outcomes.

Systematic documentation and reporting of rare entities such as PACCL are essential for accumulating clinical experience and expanding the limited evidence base. Each reported case enhances recognition of its variable presentation, refines diagnostic pathways, and informs therapeutic strategies. Ultimately, this collective knowledge is fundamental to improving early detection, reducing diagnostic delay, and guiding optimal management for future patients.

ACKNOWLEDGEMENTS

We are grateful to the patient for their kind permission to publish this case report and associated images.