MOC31 immunoreactivity in primary and metastatic carcinoma of the liver. Report of findings and review of other utilized markers.

Differentiating between primary tumors of the liver and metastatic lesions can, at times, be difficult. Various histochemical and immunohistochemical methods have been used in an effort to better delineate between hepatocellular carcinoma (HCC), especially the microglandular variant, primary cholangiocarcinoma, and metastatic adenocarcinoma; these ancillary studies can yield less than satisfactory results. Recently, anti-MOC31, a monoclonal antibody directed against a cell surface glycoprotein, has been shown to be helpful in distinguishing between adenocarcinoma and mesothelioma. This study addresses whether this antibody might be helpful in distinguishing between HCC, primary cholangiocarcinoma, and metastatic adenocarcinoma in the liver. Formalin-fixed, paraffin-embedded tissue sections from 15 HCC (including 10 microglandular variants), 14 primary cholangiocarcinomas, and 33 metastatic adenocarcinomas (7 colon, 1 lung, 8 breast, 4 GE jct/gastric, 9 pancreas, 2 small intestine, 1 renal, 1 ovary) were immunostained with anti-MOC 31 (1:40, Dako) after protease digestion and biotin block using a modified ABC technique. Positive staining was limited to membrane based reactivity; controls stained appropriately. Immunoreactivity for MOC31 was observed in 14 of 14 cholangiocarcinomas and 33 of 33 metastatic tumors. Staining was diffuse, intense, and readily interpretable, with rare exceptions. All 15 cases of HCC were negative. We conclude that cholangiocarcinoma and metastatic adenocarcinoma from a variety of sites express MOC31; HCC is uniformly negative for this marker. Anti-MOC31 may prove useful in the evaluation of liver neoplasms where primary hepatocellular and adenocarcinoma enter the differential diagnosis; it is not useful in separating primary cholangiocarcinoma from metastatic adenocarcinoma.

Immunohistochemical analysis of hepatocellular and adenocarcinoma in the liver: MOC31 compares favorably with other putative markers.

Distinguishing hepatocellular carcinoma (HCC) from metastatic adenocarcinoma (MA) and cholangiocarcinoma (CC) can, at times, be difficult and sometimes requires immunohistochemical analysis. Recently, MOC31, an antibody directed against a cell surface glycoprotein, has been shown to be useful in separating HCC from both MA and CC; however, no study has compared MOC31 and other frequently used immunostains. We compare MOC31 with other commonly used immunostains for HCC, MA, and CC. Formalin-fixed, paraffin-embedded tissue sections from 57 previously characterized hepatic neoplasms (13 HCC, 14 CC, 3 combined HCC-CC, and 27 MA) were immunostained with antibodies directed against MOC31, cytokeratin (CK) 7, CK20, alpha-fetoprotein (AFP), polyclonal carcinoembryonic antigen, Ber-EP4, and Factor XIII-A. Two pathologists reviewed slides, and positivity was defined as more than 1% of cells staining with the appropriate pattern. Positive MOC31 immunostaining was seen in 0 of 13 HCC, 13 of 14 CC, 3 of 3 HCC-CC, and 27 of 27 MA; the staining was strong and diffuse. CK20 reactivity was observed in 0 of 13 HCC, 2 of 14 CC, 0 of 3 HCC-CC, and 12 of 27 MA; CK7 immunostained 4 of 13 HCC, 13 of 14 CC, 3 of 3 HCC-CC, and 15 of 27 MA; AFP was detected in 4 of 13 HCC and 2 of 3 HCC-CC, whereas all CC and MA were negative; polyclonal carcinoembryonic antigen showed immunoreactivity in 12 of 13 HCC and 3 of 3 HCC-CC in a canalicular pattern, whereas diffuse positivity was identified in 13 of 14 CC and 26 of 27 MA; Ber-EP4 immunostained 1 of 13 HCC, 14 of 14 CC, 2 of 3 HCC-CC, and 26 of 27 MA; and Factor XIII-A was negative in all HCC, CC, and MA. MOC31 expression distinguished HCC from adenocarcinoma in 56 of 57 cases. AFP was specific for HCC but was not sensitive. CK7 and CK20 have limited utility in distinguishing HCC from CC or MA, and Factor XIII-A is not useful. Ber-EP4 staining was similar to MOC31, but one HCC did stain with Ber-EP4. Polyclonal CEA yields similar numerical results as MOC31, but the focal nature of the staining and occasional difficulty in evaluating the pattern can make interpretation problematic. We conclude that MOC31 should be a component of the immunohistochemical panel to distinguish HCC from CC and MA.

Use of immunohistochemistry in fine needle aspiration of thyroid nodules in patients with a history of malignancy. A report of two cases.

BACKGROUND: A history of a nonthyroid malignancy may present a diagnostic dilemma in the assessment of fine needle aspiration (FNA) of thyroid nodules. One reported series, on patients with prior malignancies and a thyroid nodule, indicated that in 17% of patients, the thyroid nodule represented metastatic malignancy, 6% were classified as primary thyroid cancers, and the remainder were benign or inconclusive lesions. The resolution of this problem is essential to patient management. CASES: We report two cases in which patients with a history of renal cell carcinoma presented with a thyroid nodule. The first patient was an 80-year-old female whose Papanicolaou-stained FNA demonstrated clusters of round to polygonal cells with round to ovoid, hyperchromatic nuclei and abundant, wispy cytoplasm. The second patient was a 55-year-old female with clusters and single cells with round to oval, eccentric nuclei and copious, granular, gray cytoplasm noted on Papanicolaou-stained material. In each case, the diagnosis was inconclusive on initial review of Papanicolaou-stained slides, and immunohistochemical staining was ordered to better characterize the lesions. Tumor cells from case 1 were positive for cytokeratin cocktail and vimentin and negative for thyroglobulin, epithelial membrane antigen and calcitonin, suggestive of metastatic renal cell carcinoma. In contrast, the tumor cells from case 2 expressed cytokeratin, thyroglobulin and vimentin, consistent with a primary thyroid neoplasm. In each case, the cytologic diagnoses were confirmed in the resected specimens. CONCLUSION: Immunohistochemistry is a helpful adjunct in the evaluation of thyroid nodules in patients with a past history of malignancy.