Claudin-4 immunohistochemistry is a useful pan-carcinoma marker for serous effusion specimens.

OBJECTIVE: To evaluate the utility of claudin-4 as a pan-carcinoma marker in cell-blocks of effusion specimens and compare results with Ber-Ep4 staining. METHODS: Effusion cell-blocks (n = 284) were stained for claudin-4 and results compared with Ber-Ep4. Cases included 172 metastatic malignancies (137 adenocarcinomas, 20 small cell lung tumours, eight metastatic melanoma, four squamous cell carcinoma, three urothelial cell carcinoma), 49 benign reactive cases and 63 mesotheliomas. RESULTS: All 49 benign effusions were negative. Only 1/63 (1.6%) mesotheliomas was positive for claudin-4. Claudin-4 staining was positive in 131/137 (95.6%) adenocarcinoma cases. Cases negative for claudin-4 included single cases of metastases from breast, colon, stomach, prostate, kidney and ovary. Claudin-4 outperformed Ber-Ep4. Sensitivity (95.6% vs 85.4%), specificity (99.1% vs 86.6%), negative predictive value (94.9% vs 82.9%) and positive predictive value (99.2% vs 88.6%) were all higher for claudin-4 compared with Ber-Ep4, respectively. Only two cases were claudin-4-/Ber-Ep4+. Significantly (P < .0064) more cases of metastatic adenocarcinoma stained positive for claudin-4 (131/137; 95.6%) than Ber-Ep4 (117/137; 86.2%). Claudin-4 staining was present in 15/20 (75%) of neuroendocrine carcinomas, 3/4 (75%) squamous cell carcinoma and 3/3 (100%) urothelial cell carcinoma. All eight cases of melanoma were negative for both claudin-4 and Ber-Ep4. CONCLUSIONS: Claudin-4 staining is a useful addition to IHC panels for effusions specimens with superior performance to Ber-Ep4.

Investigation of lymphoid lesions of the head and neck using combined fine needle aspiration cytology and flow cytometry: Accuracy and pitfalls.

OBJECTIVE: We reviewed the diagnostic utility of combined fine needle aspiration cytology (FNAC) and flow cytometry (FC) in the diagnosis of lymphoid lesions of the head and neck. METHOD: In total, 1402 patients with combined FNAC-FC reports were correlated with follow-up information. Rapid on-site evaluation (ROSE) of cytological specimens was performed in 52% of cases. RESULTS: In total, 211 lymphoid malignancies were identified, including 198 non-Hodgkin lymphoma (NHL) and 13 Hodgkin lymphoma (HL). Accuracy measures for NHL were: sensitivity 95.5%; specificity 99.9%; PPV 99.5%; NPV 99.2%; accuracy 99.3%. Only seven of 13 cases of HL were detected by FNAC-FC. False negative cases included HL (six cases), diffuse large B-cell lymphoma (four), T-cell lymphoma (two), follicular lymphoma (one), marginal zone cell lymphoma (one) and B-cell NHL, not otherwise specified (one). Two false positive results were identified: one immunoblastic hyperplasia reported as suspicious for HL and one case reported as suggestive of NHL that was found to be reactive hyperplasia. Cases collected with ROSE had a significantly lower rate (P < 0.0001) of insufficient cells for FC analysis (7.0%) than cases where ROSE was not performed (16.4%). Sensitivity (P < 0.0001) and NPV (P = 0.0023) were significantly higher for ROSE-collected specimens. None of the false-negative NHL cases had ROSE performed. CONCLUSIONS: FNAC-FC is a highly sensitive and specific test for NHL. Diagnostic errors mostly involved HL, large cell lymphomas and T-cell lymphomas. ROSE results in a significantly higher adequacy rate for FC and higher sensitivity for NHL.

Gata3 Immunohistochemical Staining is A Useful Marker for Metastatic Breast Carcinoma in Fine Needle Aspiration Specimens.

AIMS: The utility of GATA3 immunohistochemistry (IHC) as an aid to the cytological diagnosis of metastatic breast carcinoma in fine needle aspiration (FNA) specimens was investigated. MATERIALS AND METHODS: Cell block sections from 111 FNA cases of metastatic malignancy were stained for GATA3, including metastases from 43 breast and 44 nonmammary adenocarcinomas, 19 melanomas, 4 urothelial carcinomas, and 1 thyroid medullary carcinoma. Sites sampled included lymph nodes (87), bone (8), liver (5), lung (6), superficial masses (4), and pelvic mass (1). RESULTS: Ninety-one percent (39/43) of metastatic breast carcinoma cases were positive for GATA3. All estrogen receptor (ER)-positive were also GATA3 positive cases. The majority (9/14; 64%) of ER-negative and 37% (3/8) of triple-negative cases were positive for GATA3. All nonmammary adenocarcinoma cases were negative with the exception of one case of metastatic pancreatic adenocarcinoma. Metastatic melanoma cases were all negative but 75% (3/4) urothelial carcinomas expressed GATA3. CONCLUSIONS: GATA3 IHC staining is a useful addition to IHC panels for FNA samples in specific settings such as distinguishing metastatic breast from lung carcinoma or melanoma.

GATA3: a promising marker for metastatic breast carcinoma in serous effusion specimens.

BACKGROUND: The usefulness of GATA3 (GATA-binding protein 3 to DNA sequence [A/T]GATA[A/G]) as a marker for metastatic breast carcinoma in serous effusion specimens was investigated. METHODS: Cell block sections from 74 serous effusion specimens (32 ascitic, 2 pericardial, and 40 pleural fluids) were stained with an anti-GATA3 murine monoclonal antibody. The specimens included 62 confirmed metastatic carcinomas from the breast (30 specimens), female genital tract (13 specimens), gastrointestinal tract (7 specimens), lung adenocarcinoma (9 specimens), pancreas (1 specimen), kidney (1 specimen), and bladder (1 specimen). The breast carcinoma cases included 15 ductal carcinomas and 8 lobular carcinomas; the histology subtype was not available for 7 specimens. Twelve cases containing florid reactive mesothelial cells were also stained. The breast carcinoma cases were also stained for mammaglobin and gross cystic disease fluid protein of 15 kilodaltons (GCDFP-15) to compare their sensitivity with GATA3. RESULTS: Positive nuclear staining for GATA3 was found to be present in 90% of metastatic breast carcinoma specimens (27 of 30 specimens). All nonbreast metastatic carcinomas tested were negative with the exception of the single case of metastatic urothelial carcinoma. No staining was observed in any of the benign reactive cases or in benign mesothelial cells present in the malignant cell block preparations. Two cases demonstrated weak positivity of benign lymphoid cells. Staining results were unambiguous because all positive cases demonstrated intense nuclear staining in > 50% of tumor cells. Mammaglobin (57% staining; 17 of 30 cases) and GCDFP-15 (33% staining; 10 of 30 cases) were found to be less sensitive markers of breast carcinoma. If used in a panel, mammaglobin and GCFP-15 staining would have identified only 1 additional case compared with those stained with GATA3. CONCLUSIONS: GATA3 may be a useful addition to immunostaining panels for serous effusion specimens when metastatic breast carcinoma is a consideration.

Expression profiling identifies genes involved in neoplastic transformation of serous ovarian cancer.

BACKGROUND: The malignant potential of serous ovarian tumors, the most common ovarian tumor subtype, varies from benign to low malignant potential (LMP) tumors to frankly invasive cancers. Given the uncertainty about the relationship between these different forms, we compared their patterns of gene expression. METHODS: Expression profiling was carried out on samples of 7 benign, 7 LMP and 28 invasive (moderate and poorly differentiated) serous tumors and four whole normal ovaries using oligonucleotide microarrays representing over 21,000 genes. RESULTS: We identified 311 transcripts that distinguished invasive from benign tumors, and 20 transcripts that were significantly differentially expressed between invasive and LMP tumors at p < 0.01 (with multiple testing correction). Five genes that were differentially expressed between invasive and either benign or normal tissues were validated by real time PCR in an independent panel of 46 serous tumors (4 benign, 7 LMP, 35 invasive). Overexpression of SLPI and WNT7A and down-regulation of C6orf31, PDGFRA and GLTSCR2 were measured in invasive and LMP compared with benign and normal tissues. Over-expression of WNT7A in an ovarian cancer cell line led to increased migration and invasive capacity. CONCLUSION: These results highlight several genes that may play an important role across the spectrum of serous ovarian tumorigenesis.

Fibroadenoma and intraduct papilloma--a common pathogenesis?

This report describes two cases, each showing fibroepithelial proliferation, admixed with intraduct papillomas. Case 1 was from a 13-year-old female who presented with a breast mass, while case 2 was from a 60-year-old female who also had a breast lump. Case 1 showed proliferative breast disease with multiple small papillomas, some with leaf-like contours. Broad-based parenchymal proliferations protruding into ducts were also seen, and there were overlap features between the two ends of this spectrum. Case 2, similarly, demonstrated a mixed intraductal proliferation, with papillomas on narrow stalks together with low-grade phyllode areas extending into ducts from a wider base. That fibroadenoma and intraduct papilloma may have a common pathogenesis is discussed.