Indian Journal of Pathology and Microbiology

: 2019  |  Volume : 62  |  Issue : 4  |  Page : 582--585

Metastatic hepatocellular carcinoma to the parotid gland: A diagnostic dilemma with review of the literature

Hema Malini Aiyer1, Sanjay Deb1, Garima Rawat2,  
1 Department of Pathology, Dharamshila Narayana Hospital, New Delhi, India
2 Department of Oral and Maxillofacial Pathology, Dharamshila Narayana Hospital, New Delhi, India

Correspondence Address:
Garima Rawat
Oral and Maxillofacial Pathologist, Department of Pathology, Dharamshila Narayana Superspciality Hospital, New Delhi


Hepatocellular carcinoma (HCC) is the most common primary hepatic malignancy and is a leading cause of cancer-related death worldwide. It has a very aggressive clinical course, with a mean survival rate of much less than a year if left untreated. Here, we present a case of a 68-year-old male with progressively enlarging painful right facial swelling, involving the ramus and condyle of mandible on contrast-enhanced computed tomography mimicking an osteosarcoma. Eventually, the final diagnosis of HCC metastatic to the right parotid gland was made. We report a case of a rare metastasis of HCC to the parotid gland. Furthermore, the present case demonstrates the importance of tissue biopsy and immunohistochemistry for obtaining an accurate final diagnosis.

How to cite this article:
Aiyer HM, Deb S, Rawat G. Metastatic hepatocellular carcinoma to the parotid gland: A diagnostic dilemma with review of the literature.Indian J Pathol Microbiol 2019;62:582-585

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Aiyer HM, Deb S, Rawat G. Metastatic hepatocellular carcinoma to the parotid gland: A diagnostic dilemma with review of the literature. Indian J Pathol Microbiol [serial online] 2019 [cited 2020 Aug 13 ];62:582-585
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Hepatocellular carcinoma (HCC) has become the most common primary hepatic malignancy, with average survival rates between 6 and 20 months.[1] Due to the rapid clinical course of this disease, the extrahepatic spread is rare. However, HCC can metastatize through the hematogenous route, lymphatic route, or by direct invasion into adjacent organs.[2],[3] The common extrahepatic metastatic sites of HCC are the lungs, peritoneum, adrenal glands, and bone, and there are rare reports of metastases to the nasal cavity, orbital cavity, skin, heart, external auditory canals, and pharynx.[2],[3],[4],[5] Very few cases of metastatic HCC to parotid gland have been reported in the past. Here, we present an unusual case of metastatic HCC to parotid gland. To the best of our knowledge, only six cases have been documented in the literature till date.

 Case Report

A 68-year-old male presented to the outpatient department with history of right jaw tooth extraction followed by bleeding from the right ear, swelling in the right side of the face, and numbness in the cheek since 1 week [Figure 1]. The patient was initially investigated outside where contrast-enhanced computed tomography of the neck was done which revealed large heterogeneously enhancing mass lesion in the right masticator space, infiltrating the ramus and condyle of the right hemimandible with other mass effect and extension, likely neoplastic mass (? sarcomatous change). Fine needle aspiration cytology (FNAC) was done outside which showed possibility of acinic cell carcinoma or adenocarcinoma not otherwise specified (NOS). The patient was referred to this hospital for further management. Positron emission tomography (PET) scan and contrast-enhanced magnetic resonance imaging revealed that the mass was 5.3 × 5.2 × 4.9 cm large superiorly extending/abutting the skull base infiltrating lateral pterygoid plate with extension in the right temporomandibular joint, posteriorly infiltrating the right parotid gland mass adherent to facial vessel, medially abutting parapharyngeal space suggestive of mitotic etiology [Figure 1]b. FNAC was performed from the right parotid swelling which showed cellular smears with tumor cells in sheets, loose aggregates, and singles having ample cytoplasm and pleomorphic nuclei, along with numerous salivary acinar structures in a hemorrhagic background, features suggestive of poorly differentiated carcinoma; morphology favoring adenocarcinoma [Figure 2]a. Histopathology examination with immunohistochemistry (IHC) for definitive characterization was advised. Sections from needle biopsy showed fragmented bits of tumor admixed with skin, fibrofatty tissue, and normal salivary gland. The tumor was composed of large polygonal cells with vacuolated cytoplasm, vesicular nuclei and prominent nucleoli, and interspersed lymphocytes. The tumor cells were in close proximity to normal salivary acini. Morphologic features were consistent with poorly differentiated carcinoma – favoring adenocarcinoma [Figure 2]b and [Figure 2]c. Advised IHC performed was suggestive of CK, CD-138, CD-38-positive poorly differentiated carcinoma, and undifferentiated involving salivary gland. Thereafter, the patient was referred to a medical oncologist where he was planned for two cycles of neoadjuvant chemotherapy (nanoxel + carboplatin-based) followed by radical chemotherapy radiotherapy (CTRT) to face and neck (dose of 70 Gy/35 fractions/7 weeks).{Figure 1}{Figure 2}

Following this, the patient developed complaints of fever, cough, decreased oral intake, and abdominal pain. PET scan was advised which revealed two fluorodeoxyglucose (FDG)-avid space occupying lesions (SOLs) in segment VIII of liver (1.6 cm). From these SOLs, computed tomography–guided FNAC done showed cellular aspirates with atypical cells singly and in clusters with bare nuclei in the background. Atypical cells were pleomorphic with vesicular nuclei, prominent nucleoli, and scant to moderate cytoplasm and focal areas of necrosis in background. Features were suggestive of adenocarcinoma [Figure 3]a. Serum alpha-fetoprotein (AFP) levels were >40,000. Sections of biopsy from liver mass showed that the tumor was composed of large polygonal pleomorphic cells with prominent nucleoli in a trabecular sinusoidal pattern with mitoses and necrosis admixed with nodules of hepatocytes with fibrosis and bile ductular proliferation [Figure 3]b. These features were suggestive of HCC Grade 3: poorly differentiated immunopositive for hepatocyte paraffin antibody 1 (HepPar 1) [Figure 3]c, AFP, Arginase-1, CK8/18, Ber Ep4, CK-19, and Glypican [Figure 4]a, [Figure 4]b, [Figure 4]c, [Figure 4]d, [Figure 4]e, [Figure 4]f, respectively]. HepPar 1 was also performed on the parotid biopsy tissue in which the tumor cells showed immunopositivity for it [Figure 2]d. Hence, the final diagnosis of HCC Grade 3: poorly differentiated, metastatic to right parotid was made.{Figure 3}{Figure 4}


HCC is an aggressive cancer and has become the most common primary hepatic malignancy, with average survival rates between 6 and 20 months.[1] Metastases of HCC occur in more than 50% of patients over a long-term follow up, although most metastases are not clinically evident at the time of initial presentation. HCC spreads through the hematogenous route, the lymphatic route, or by direct invasion into adjacent organs. The most common sites of extrahepatic metastatic HCC include the abdominal lymph nodes, lungs, bone, and adrenal glands,[6],[7],[8],[9],[10] but rarely the head and neck region, including the oral cavity and parotid glands.[4] HCC metastases to the oral cavity have been reported in 71 cases,[11] but those to the parotid gland in only 6 cases till date.[2],[5],[9],[12] HCC with oral metastases typically present clinically as ulcerated symptomatic masses. The common oral sites of occurrence include the jaws with a predilection for the mandible and gingival.[11] The angle of the mandible is a common site of metastasis, probably due to its rich hematopoietic marrow. These lesions are very hemorrhagic and any surgical procedure – even biopsy – should be attempted with precaution. The histology of the osseous metastasis varied from well-differentiated to anaplastic.[11]

Metastatic involvement of the salivary glands is rare, comprising 10%–16% of all salivary gland malignancies, excluding lymphomas. These metastases usually originate from head and neck malignancies.[2] Among salivary glands, the parotid gland is an uncommon site of metastases, and the most common tumors to metastasize to the parotid region are skin malignancies of the scalp and face. Involvement of the parotid gland as a first site of presentation or relapse is even less frequently reported. Most metastases arise from a primary lesion in the head and neck region (mucosal or cutaneous). The most common sites of primary tumors outside the head and neck region include the lung carcinomas, breast carcinomas, prostate carcinomas, and kidney and gastrointestinal tumors.[13],[14] Typically, metastasis of HCC proceeds first to the lungs through the portal venous system. However, the present case, like that reported by Romanas et al.,[8] was exceptional because of the parotid site and there was no evidence for lung parenchymal involvement.[8] Typically, metastases from the liver to the maxillofacial area reach the lungs first, through the hepatic artery and the portal vein, and later reach the maxillofacial area. To explain the parotid involvement without lung involvement, it has been suggested that HCC could be disseminated into Batson's plexus (a connection between the azygos and hemiazygos veins and the vertebral venuous plexus) bypassing filtration through the lungs.[15] The solitary parotid metastasis in this case may confirm this hypothesis.

Establishing a diagnosis of metastatic HCC in the maxillofacial region may be difficult. The earlier cases of metastasis from HCC and the present case were initially investigated by FNAC. Although in the current case the FNAC from the parotid lesion showed malignant cells but was not typical of metastatic HCC. Primary or metastatic HCC often has a cytologic appearance sufficiently characteristic to allow its presumptive diagnosis. The tumor is typically composed of sheets and trabeculae of large polyhedral cells with round nuclei, prominent single nucleoli, and abundant granular eosinophilic cytoplasm. In all cases, including our case, biopsy from the parotid lesion confirmed the diagnosis.[1],[5] In this case, biopsy and IHC on tissue from liver lesion was characteristic of HCC. The monoclonal antibody HepPar 1 is often required to aid in distinguishing metastatic HCC from other parotid metastatic tumors.[2] HepPar-1 was strongly positive in our case in tumor cells of both parotid and liver lesion.

The recurrence of HCC can be detected by an elevated serum AFP or imaging findings. AFP is also known as an independent prognostic factor for HCC and a markedly elevated serum AFP level may reflect advanced HCC in terms of its large size or metastasis.[2] Similar to these, AFP levels were markedly raised in our case also. However, on reviewing the earlier reported cases of metastatic HCC to the parotid gland [Table 1], the AFP level was not elevated.{Table 1}

The treatment for metastatic HCC cases is usually chemotherapy and palliative radiotherapy. In the present case, the patient underwent two cycles of neoadjuvant chemotherapy (nanoxel + carboplatin-based) followed by radical CTRT to face and neck (dose of 70 Gy/35 fractions/7 weeks). However, in one of the reported cases, superficial parotidectomy was performed.[2],[8] In some cases, the condition of the patient allowed only palliative care.

Thus, early prompt diagnosis and appropriate management can help in improving the prognosis to some extent.


Albeit rare, oral metastatic HCC should be considered in the differential diagnosis of rapidly growing oral lesions, especially in patients with a history of liver disorders. As malignant lesions of the oral cavity are not always primary lesions but sometimes can be metastatic lesions of a distant undisclosed primary site. Thorough clinical, radiological, and histopathological evaluations are key factors in determining the diagnosis and management of such lesions. Immunohistochemical analysis is a mandate to identify hepatocyte markers and to exclude other sources of metastatic disease. At present, the prognosis for these patients is dismal regardless of the treatment used.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.


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