A total of 624 cases were identified (Table I). Metastases (448/624; 71.8%) were much more common than primary liver tumors (176/624; 28.2%). For metastases, adenocarcinoma originating from gastrointestinal tract and pancreas were the two most common neoplasms; while adenocarcinoma from thyroid, prostate, and adrenal cortex were rare in the liver. For primary liver neoplasms, HCC (97/176; 55.1%) was the most common neoplasm, followed by cholangiocarcinoma (73/176; 41.5%) and combined hepatocellular-cholangiocarcinoma (3/176, 1.7%). Rare primary liver neoplasms seen in this study included embryonal sarcoma and hepatoblastoma, both from pediatric patients; and EBV-associated leiomyosarcoma from an adult patient.
In recent years, there has been a significant number of HCC diagnosed by FNB in our institution. Indications for FNB include confirming HCC diagnosis in patients with cirrhosis (63/97, 65%); distinguishing metastasis versus HCC for patients with prior history of malignancy (18/97; 18.6%); distinguishing cholangiocarcinoma or combined cholangiocarcinoma and HCC versus HCC (2/97, 2.1%); diagnosing a liver mass in non-cirrhotic liver (9/97; 9.3%); and determining the primary site for carcinoma of unknown primary in patients with widespread disease at presentation (4/97; 4.1%). One patient had a history of sarcoidosis and hepatitis C virus-associated cirrhosis. He presented with multiple lesions with calcification. The clinical impression based on imaging was sarcoidosis involving liver; however, biopsy turned out to be HCC.
Neuroendocrine neoplasms (9.3%, 58/624), including well-differentiated neuroendocrine tumors (NETs) and poorly-differentiated neuroendocrine carcinomas (NECs), were among the most common malignant liver lesions. A majority of cases (72.4%, 42/58) were poorly-differentiated NECs, while well-differentiated NETs accounted for 27.6% (16/58) of cases. For poorly-differentiated NECs, small cell (26.2%, 11/42) and large cells carcinoma (4.8%, 2/42) of the lung accounted for 31.0% of these cases (13/42). For well-differentiated NETs, gastrointestinal (GI) tract (81.3%, 13/16) with the diagnosis of grade 1 or grade 2 NET was the predominant site of origin.
Metastatic squamous cell carcinoma was identified in 3.8% (24/624) of case. The most common primary sites were uterine cervix (29.2%; 7/24), followed by head and neck, including one HPV-related oropharyngeal squamous cell carcinoma (25.0%; 6/24), esophagus (16.7%; 4/24), lung (8.3%, 2/24)), penile (4.2%, 1/21), anus (4.2%, 1/21), and pancreatobiliary (4.2%, 1/24). The primary sites for the remaining two cases were undetermined (8.3%, 2/24).
Sarcoma (11/624; 1.8%) was uncommon compared with carcinoma. In our study, there were three cases of metastatic leiomyosarcoma to the liver and one case of primary EBV-associated leiomyosarcoma in a Human Immunodeficiency Virus (HIV) - positive patient. Other sarcomas that metastasized to the liver include gastrointestinal stroma tumor (GIST), undifferentiated pleomorphic sarcoma (UPS), malignant solitary fibrous tumor (SFT), myxoid liposarcoma, and primary embryonal sarcoma from a pediatric patient.
Twelve (1.9%, 12/624) cases were diagnosed as carcinoma of unknown primary (CUP), due to lack of specific protein expression or limited biopsy tissue. The primary site could not be determined both clinically and pathologically. Patient’s ages ranged from 31 to 81 years. Male patients were more common than female patients (9: 3). The majority of patients presented with wide spread disease involving multiple organs, including liver, lung, lymph nodes, bone, and others (Table 2). Two patients had a history of malignancy, however the histomorphological as well as immunohistochemical characterization of the liver masses were different from the patients’ known malignancies. Morphologically, 3 cases were high grade small blue cell tumor; 3 cases are high grade large eosinophilic cell tumor; 2 cases were high grade adenocarcinoma; 1 case had spindle cell morphology; the remaining 3 cases were unclassifiable due to few viable cells present (Fig. 1). Extensive immunohistochemical workups were performed, except for cases without enough material. The tumor cells were positive for pancytokeratin and/or CK7, while other lineage specific markers including TTF-1, CDX2, PAX8, GATA3, synaptophysin, chromogranin, et al. were all negative. Molecular testing was performed only for one case (case11). Prognosis was poor for these patients (Table 2). More than half of these patients gave up treatment or received palliative care only.