Specificity of brachyury in the distinction of chordoma from clear cell renal cell carcinoma and germ cell tumors: a study of 305 cases

Abstract

Brachyury is recognized as a specific marker for notochord-derived tissues and neoplasms, and has become a defining immunohistochemical feature of chordoma. The main differential diagnostic consideration for chordoma is chondrosarcoma, which is known to lack brachyury expression. However, within the spectrum of genitourinary neoplasia, metastatic germ cell tumors and clear cell renal cell carcinoma may also be close morphological mimics of chordoma, particularly given the increasing prevalence of small tissue samples from image-guided biopsies. Although immunoreactivity for brachyury has been reported in a few germ cell tumors, a thorough characterization of staining by specific subtype has not been performed in a large series. Additionally, brachyury expression in clear cell renal cell carcinoma has not been well studied. In this study, immunohistochemical expression with the brachyury antibody was evaluated in 111 germ cell tumors, 30 non-neoplastic and neoplastic (non-germ cell) testicular tissues, and 184 metastatic clear cell renal cell carcinomas using tissue microarray technology. In addition, immunoreactivity for PAX-8 and SALL-4 was evaluated in 12 chordomas on whole section. No nuclear brachyury expression was identified in any of the 101 germ cell tumors within the tissue microarray (including choriocarcinoma (1), embryonal carcinoma (20), intratubular germ cell neoplasia unclassified (2), seminoma (64), spermatocytic seminoma (1), teratoma (5) and yolk sac tumor (8)), in any of the 30 non-neoplastic and neoplastic (non-germ cell) testicular tissues, or in any of the 10 whole-section seminomas. All 184 metastatic clear cell renal cell carcinomas were also non-reactive for brachyury. All 12 chordomas showed strong nuclear immunoreactivity for brachyury, but no expression of SALL-4. In all, 1 of 12 chordoma cases showed patchy, 1 þ nuclear immunoreactivity for PAX-8. This study confirms the specificity of brachyury for chordoma in the differential diagnostic distinction from the potential genitourinary mimics, germ cell tumors and metastatic clear cell renal cell carcinoma. Modern Pathology (2011) 24, 425-429; doi:10.1038/modpathol.2010 published online 19 November 2010 Keywords: brachyury; chordoma; germ cell tumor; metastatic; renal cell carcinoma Brachyury is recognized as a key transcription factor expressed in notochord-derived tissues and neoplasms. Although expression of the novel antigen brachyury has come to be considered a defining diagnostic feature of chordoma, 1-6 few studies have thoroughly addressed specificity of the antibody. Chondrosarcoma, the most recognized differential diagnostic consideration for chordoma, has been thoroughly evaluated in previous studies and does not express brachyury. 2,5-9 However, within the spectrum of genitourinary neoplasia, metastatic germ cell tumors and clear cell renal cell carcinomas may also be close morphological mimics of chordoma, particularly on a small biopsy sample. Immunoreactivity with the brachyury antibody has been reported in a few germ ...

Novel uses of immunohistochemistry in the diagnosis and classification of soft tissue tumors

“…14 Nuclear expression of brachyury is a consistent feature of chordoma ( Figure 3), which is a helpful diagnostic immunohistochemical finding to distinguish this tumor type from potential histologic mimics, including chondrosarcoma, metastatic carcinoma, and myoepithelial tumors. [14][15][16][17] No other consistently brachyury-positive tumor types have been identified. Of note, a subset of chordomas show copy number gains at the T locus.…”

AMOR Vol. 2, Issue 3, 2016

“…A few cases of conventional chordomas and chondroid chordomas demonstrated the absence of brachyury staining, which was presumed to be due to inadequate fixation of tissue and poor antibody penetration [30,42] . Brachyury expression has reportedly not been observed in chondrosarcoma, liposarcoma, myoepithelial tumors, germ cell tumors, or clear cell renal cell carcinoma [35,38,42,43] . However, Miettinen et al immunohistochemically evaluated 5,229 different tumors for nuclear brachyury expression (rabbit monoclonal antibody; 1:2000 antibody dilution) and had shown that brachyury expression is prevalent in embryonal carcinoma, seminoma, and small cell carcinoma of the lung, but very rarely in common carcinomas such as ductal carcinomas of the breast or adenocarcinomas of the prostate, sarcomas, and melanoma [39] .…”

“…Patients with no gross RD after primary cytoreduction had a median survival of 106 months, and it was proposed that the resection of all visible disease significantly improved survival and should be the primary surgical goal of CS [9] . The impact of radical abdominal CS procedures (splenectomy, liver resection, extensive peritonectomy) on RD and the associated survival outcome of 194 patients with stage IIIC epithelial ovarian cancer receiving adjuvant platinum-based chemotherapy (including paclitaxel or cyclophosphamide) for six to eight cycles after undergoing primary surgery were analyzed [43] . A total of 131 (67.5%) patients were found to have RD ≤1 cm in maximal diameter.…”

“…These features have led to the use of MSCs as gene delivery transporters for tumor cells [42] . NSCs have an inherent tumor tropism and are therefore reliable delivery agents for target therapeutic gene products to primary and metastatic tumors [43] . Blood outgrowth endothelial cells are withdrawn to the tumor vasculature.…”

Phosphaturic Mesenchymal Tumor Involving the Head and Neck: A Report of Five Cases with FGFR1 Fluorescence In Situ Hybridization Analysis

“…The neoplastic cells are embedded in extensive myxoid stroma that lacks the 'grungy' calcification of PMT. Immunohistochemistry is particularly useful in making this diagnosis with chordomas being positive for S-100, cytokeratin, EMA, and brachyury [13].…”