Ovarian serous borderline tumors (SBTs) have a generally favorable prognosis. Although the risk of progression to low-grade serous carcinoma is well documented, progression to high-grade carcinoma is rare. We report the clinicopathologic features of seven SBTs, each associated with the presence of a morphologically unique high-grade component with an extremely dismal prognosis. All of the SBTs exhibited typical hierarchical branching and scattered eosinophilic cells, whereas the high-grade component consisted of a profuse proliferation of epithelioid cells with abundant dense, eosinophilic cytoplasm, variable nuclear pleomorphism, and evident loss of WT1, estrogen receptor, and p16 positivity. In most cases, the SBT demonstrated an abrupt transition to the high-grade component, but one patient initially presented with the usual SBT and developed a recurrent disease that was composed entirely of the high-grade component. Targeted next-generation sequencing revealed identical driver mutations in both the SBT and high-grade components (BRAF in 3, KRAS in 1), confirming clonality. Three cases, in addition, harbored telomerase reverse transcriptase promoter mutations in both components. One case, despite insufficient material for sequencing, was BRAF V600E-positive by immunohistochemistry. Most patients with available follow-up data died within 9 months of diagnosis. This study confirms prior reports of ovarian SBT transformation to high-grade carcinoma and further characterizes a distinct subset with abundant dense eosinophilic cytoplasm and an extremely dismal prognosis. The presence of BRAF mutations in a major subset of these tumors questions the notion that BRAF is associated with senescent eosinophilic cells and improved outcomes in SBT. The role of the additional telomerase reverse transcriptase promoter mutations merits further investigation.

中文翻译：

---

卵巢浆液界性肿瘤的高级别间变性转化：一种独特的形态，具有丰富致密的嗜酸性粒细胞质和不良预后。


卵巢浆液界性肿瘤 （SBT） 的预后通常良好。尽管进展为低级别浆液性癌的风险有据可查，但进展为高级别癌的情况很少见。我们报告了 7 个 SBT 的临床病理特征，每个 SBT 都与形态学上独特的高级别成分的存在有关，预后极其糟糕。所有 SBT 均表现出典型的分层分支和分散的嗜酸性粒细胞，而高级成分包括上皮样细胞的大量增殖，具有丰富致密的嗜酸性粒细胞质、可变的核多形性以及 WT1 、雌激素受体和 p16 阳性的明显缺失。在大多数情况下，SBT 表现出突然过渡到高级别成分，但一名患者最初表现为通常的 SBT，并发展为完全由高级别成分组成的复发性疾病。靶向下一代测序显示 SBT 和高级别组分 （BRAF 为 3，KRAS 为 1） 具有相同的驱动突变，证实了克隆性。此外，3 例在两种成分中都含有端粒酶逆转录酶启动子突变。1 例尽管测序材料不足，但免疫组化显示 BRAF V600E 阳性。大多数有可用随访数据的患者在诊断后 9 个月内死亡。本研究证实了先前关于卵巢 SBT 转化为高级别癌的报道，并进一步表征了一个具有丰富致密嗜酸性粒细胞质和极度不良预后的独特亚群。在这些肿瘤的主要亚群中存在 BRAF 突变，这质疑了 BRAF 与衰老嗜酸性粒细胞和 SBT 结局改善相关的观点。 额外的端粒酶逆转录酶启动子突变的作用值得进一步研究。