Many postchemotherapy sarcomatous tumors in patients with testicular germ cell tumors are sarcomatoid yolk sac tumors: A study of 33 cases

Brooke E. Howitt, Martin J. Magers, Kevin R. Rice, Cristina D. Cole, Thomas M. Ulbright

Research output: Contribution to journalArticle

12 Scopus citations


Sarcomatoid neoplasms in patients with testicular germ cell tumors (TGCTs) may show diverse lineages and are usually attributed to "transformation" of teratoma, although origin from yolk sac tumor (YST) has also been suggested. We evaluated 33 sarcomatoid tumors from 23 TGCT patients that lacked specific features of a defined sarcoma subtype for a number of features, including: atypia (mild, moderate, severe), cellularity, tumor necrosis, mitotic index, stromal vascularity, cell profile (spindle or epithelioid), and stromal quality (myxoid and/or fibrous). Immunohistochemical staining analyses directed against cytokeratin (AE1/AE3), SALL4, glypican-3 (GPC3), α-fetoprotein (AFP), p63, glial fibrillary acidic protein (GFAP), CD34, MUC4, smooth muscle actin (SMA), desmin, caldesmon, and myogenin were performed. Staining intensity (0=negative, 1=weak, 2=moderate, 3=strong) and extent (0=<1%, 1=1% to 10%, 2=10% to 50%, 3=>50%) were scored. Tumor grade based on the French sarcoma grading system was assessed, with grades 2-3 considered high grade. Tumors with at least moderate intensity and >10% (+) cells for both AE1/AE3 and GPC3 were considered to be sarcomatoid YST (SYST); 22 tumors from 14 patients (ages 18 to 38 y, mean 27 y) met these criteria and were the focus of this study. All SYSTs occurred after chemotherapy (3 to 132 mo after TGCT diagnosis; mean 42.5 mo, median 30.5 mo). They had spindled (100%; 19 predominant) and epithelioid cells (77%; 3 predominant) in myxoid to fibrous stroma. Thirteen exhibited at least focally severe nuclear atypia. Distinctive tumor "ringlets" and intercellular basement membrane deposits (parietal YST differentiation) were common. In addition to positivity for AE1/AE3 and GPC3, 15/22 were SALL4 (+), 10/22 were at least focally CD34 (+), and 2/22 were focally p63 (+). Fifty percent exhibited smooth muscle differentiation as evidenced by desmin (8/19), caldesmon (2/4), and/or SMA (4/6) reactivity. AFP, MUC4, GFAP, and myogenin were negative in all cases. On follow-up, 8/14 patients died of disease at 7 to 217 months (mean 58 mo) after the initial SYST diagnosis, whereas 5/14 were alive and had no evidence of disease (ANED) at 1 to 259 months (mean 83 mo). One patient died of unrelated causes at 39 months. Of the 11 patients with high-grade tumors, 8 were dead of disease, 1 died of an unrelated cause, and 2 were ANED; all 3 patients with low-grade tumors were ANED at 41 to 262 months (mean 128 mo). We conclude that a high proportion of sarcomatoid tumors in postchemotherapy resections of TGCT patients are SYSTs. These typically occur several years after diagnosis and behave aggressively when high grade.

Original languageEnglish (US)
Pages (from-to)251-259
Number of pages9
JournalAmerican Journal of Surgical Pathology
Issue number2
StatePublished - Feb 2 2015


  • chemotherapy
  • germ cell tumor
  • glypican-3
  • immunohistochemistry SALL4
  • sarcoma
  • sarcomatoid
  • testicular neoplasms
  • yolk sac tumor

ASJC Scopus subject areas

  • Anatomy
  • Pathology and Forensic Medicine
  • Surgery
  • Medicine(all)

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