Barbro Nilsson

Combined hepatocellular-cholangiocarcinoma : Diagnostic challenge in hepatic fine needle aspiration biopsy

OBJECTIVE To study the cytohistologic features of combined hepatocellular-cholangiocarcinoma (CHCC-CC) in fine needle aspiration biopsy (FNAB) material. STUDY DESIGN Six hepatic FNAB cases with cell blocks (five) and hepatic resections (two) were analyzed cytohistologically and immunohistochemically. RESULTS The six cases were diagnosed as CHCC-CC based on clinicopathologic correlation. Unequivocal hepatocellular carcinoma (HCC) cells corresponding to Edmondson and Steiners grade 3 lesions were identified in the FNAB in three instances. Adenocarcinoma, represented by cohesive columnar cells with ovoid, basal nuclei displaying nuclear palisading, acini and/or papillary structures with variable intracytoplasmic intraacinar or brush border mucin production, was identified in all cases. Intermediate cells with hybrid/polymorphic cytologic features straddling malignant hepatocytes and glandular cells were identified in five instances. Tissue alpha-fetoprotein was negative. There was brush border and/or diffuse cytoplasmic p-carcinoembryonic antigen immunoreactivity in the glandular elements. CONCLUSION FNAB diagnosis of CHCC-CC is possible if the clinical, cytohistologic and immunohistochemical findings support the presence of HCC and adenocarcinoma. Intermediate cells pose a great challenge to recognize and define: they tend to lose the classic cytologic features of malignant hepatocytes and acquire glandular characteristics. At the very least, there should be a high index of suspicion. These cases underscore the necessity for clinicopathologic correlation in enhancing the precision of FNAB diagnoses.

Highly well differentiated hepatocellular carcinoma and benign hepatocellular lesions. Can they be distinguished on fine needle aspiration biopsy

OBJECTIVE To determine whether highly well differentiated hepatocellular carcinoma can be distinguished from benign hepatocellular lesions on fine needle aspiration biopsy (FNAB). STUDY DESIGN Ninety-five FNABs from 88 patients with hepatic masses/diffuse conditions were reviewed according to new cytologic criteria established by Takenaka et al. They were classified into well-, moderately and poorly differentiated hepatocellular carcinomas (W-, M- and P-HCC) and benign aspirates and histologically verified. RESULTS There were 21 W-HCC, 39 M-HCC, 10 P-HCC, 3 problematic and 22 benign aspirates. The most useful criteria for diagnosing highly W-HCC were architectural features on the smears/cell block sections, including hypercellularity; arborescent, cohesive clusters; broad trabeculae; transgressing and peripheral endothelium; and cytologic details of small, monotonous hepatocytes with nuclear crowding, decreased cytoplasm, increased nuclear/cytoplasmic ratio, atypical naked nuclei and tumor giant cells. Well-defined cytoplasmic borders, abundant thick and monotonous cytoplasm, eccentric nuclei, thick nuclear membranes, irregular nuclear contours, increased chromatin density, irregular chromatin distribution and macronucleoli were not always detectable in highly W-HCC. In fact, some of them were seen in dysplastic hepatocytes. Deficient reticulin patterns and diffuse sinusoidal CD34 reactivity were helpful. CONCLUSION Experience, attention to architectural and cytologic details in smears/cell blocks and clinicopathologic correlation should reduce the number of indeterminate reports. However, there will always remain some cytohistologically challenging cases.

pCEA Canalicular immunostaining in fine needle aspiration biopsy diagnosis of hepatocellular carcinoma

OBJECTIVE To assess the usefulness of bile canalicular polyclonal carcinoembryonic antigen (pCEA) immunostaining in fine needle aspiration biopsy (FNAB) diagnosis of hepatocellular carcinoma (HCC). STUDY DESIGN Hepatic FNAB with cell blocks of 72 confirmed and 6 possible HCC and 23 non-HCC malignancies (controls) were analyzed. Sections were stained with antibody to pCEA using the streptavidin biotin-immunoperoxidase method and results correlated with tumor grade and other parameters used in HCC diagnosis. RESULTS Canalicular pCEA staining was observed in 60 (83%) of the 72 HCC. This category comprised 29%, 31%, 36% and 4% grade 1-4 tumors, including 7 small cell, 4 clear cell and 1 giant cell variants. With increasing anaplasia, the canaliculi became infrequent, irregularly distributed, and increasingly distorted and interrupted. Canalicular staining helped distinguish clear and small cell variants from metastatic renal cell carcinomas and neuroendocrine tumors, respectively. Of the six problematic cases, one was confirmed to be HCC with plasmacytoid features and five to be adenocarcinomas, of which three could have been combined hepatocellular-cholangiocarcinomas. Liver cell dysplasia also displayed an abnormal canalicular pattern. No cytoplasmic staining was seen in pure HCC. CONCLUSION pCEA immunostaining cannot separate malignant, dysplastic or benign hepatocytes. It is usually not required in cytodiagnosis of most HCC. However, it is most helpful in confirming atypical variants of HCC, which may mimic other tumors.

Fine needle aspiration biopsy of small/intermediate cell tumors in the liver : Considerations in a southeast Asian population

OBJECTIVE To assess the diagnostic problems and accuracy involved in rendering an exact cytologic diagnosis, including reference to a primary site of origin, on fine needle aspiration biopsies (FNABs) of small/intermediate cell tumors of the liver. STUDY DESIGN Thirty-five hepatic FNABs of small/ intermediate tumors, neuroendocrine tumors (NETs) and poorly differentiated or undifferentiated cancers occurring in adults were analyzed. Ancillary studies, including immunohistochemistry, were performed whenever necessary. All other relevant histopathologic sections and medical records were reviewed. RESULTS There were 26 metastases, while 9 were considered primary lesions. The aspirates were categorized into 11 NETs (pancreas 5, lung 1, liver 2, unknown primary 3); 9 undifferentiated nasopharyngeal carcinomas; 2 small cell undifferentiated carcinomas (lung 2); 4 undifferentiated carcinomas, not otherwise specified (lung 1, pancreas 1, liver 1, unknown 1); 1 lobular-ductal carcinoma (breast); 1 glioblastoma multiforme (brain); 1 ovarian carcinoma; 1 non-Hodgkins lymphoma (liver); and 5 primary hepatocellular carcinomas. CONCLUSION There was histologic and/or immunohistochemical confirmation in 25 cases (71%). Some of the limitations in categorization of such tumors obtained by FNAB can be overcome by immunohistochemistry. Information gleaned from a precise cytologic diagnosis can sometimes only favor a particular primary site.

Fine Needle Aspiration Biopsy of Hepatic Leiomyosarcoma

OBJECTIVE: To study the cytomorphologic features of hepatic smooth muscle tumors on fine needle aspiration biopsy (FNAB) material in a hepatocellular carcinoma (HCC)-prevalent population, in which a potential diagnostic pitfall is an unusual variant of metastatic epithelioid leiomyosarcoma seen on aspiration cytology. STUDY DESIGN: FNABs of five cases of metastatic hepatic leiomyosarcomas were studied cytohistologically and immunocytochemically. In addition, ultrastructural studies were performed in one unusual case. Resected hepatic specimens and all other relevant histopathologic specimens were reviewed. RESULTS: Classically, aspirates of leiomyosarcoma produced syncytial masses of spindle cells characterized by overlapping, cigar-shaped nuclei and truncated ends. An unusual variant of metastatic epithelioid leiomyosarcoma was studied, with cytohistologic, immunohistochemical and ultrastructural correlation. CONCLUSION: Hepatic spindle cell lesions consist mainly of metastatic leiomyosarcomas. The diagnosis of malignancy and metastatic status of hepatic smooth muscle tumors is facilitated by the presence of an extra-hepatic primary tumor. In a hepatitis B virus-endemic population, HCC, sarcomatoid type, has to be considered in the differential diagnosis of hepatic spindle cell lesions and the classic type, in epithelioid variants of smooth muscle tumors.

Immunocytochemistry versus molecular fingerprinting of metastases.

Examination of cytological samples of cancer to suggest a possible primary site of origin is one of the commonest and most difficult tasks of diagnostic cytopathologists. Currently, both cytomorphology and immunocytochemistry are the main approaches to this diagnostic dilemma. We report the application of microsatellite analysis in cytological samples in a patient with a primary colonic tumour and two subsequent lung nodules, which were suspected on CT scans of the chest, and compared the findings with those obtained with conventional immunocytochemistry. The molecular results were in agreement with the radiological impression and conflicted with the immunocytochemistry. We conclude that immunocytochemical and molecular biology approaches to the diagnosis of tumours may give rise to contradictory results.