Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL.
Am J Surg Pathol. 2024 Jul 1;48(7):813-824. doi: 10.1097/PAS.0000000000002220. Epub 2024 Apr 17.
Uterine inflammatory myofibroblastic tumors (IMTs) are rare mesenchymal neoplasms of uncertain malignant potential. Aside from the recently described risk stratification score, which has not been validated by other studies, and rare reports of aberrant p16 expression in malignant tumors, there are no criteria to reliably predict behavior. Herein, we evaluated the clinicopathologic features and p16 expression patterns in 30 IMTs, with genomic profiling performed in a subset (13 malignant, 3 benign). Fifteen patients had malignant IMTs, defined by extrauterine disease at diagnosis (n=5) or recurrence (n=10; median: 24 mo). Patients ranged from 8 to 65 (median: 51) years and tumors from 6 to 22 (median: 12.5) cm. In primary tumors (n=13), infiltrative borders were noted in 10, moderate/severe cytologic atypia in 9, tumor cell necrosis in 7, and lymphovascular invasion in 6, while mitoses ranged from 0 to 21 (median: 7) per 10 high-power fields. In contrast, 15 patients with benign IMTs ranged from 28 to 65 (median: 44) years, with follow-up of 18 to 114 (median: 41) months. Tumors ranged from 1.9 to 8.5 (median: 5.5) cm, 2 demonstrated infiltrative borders, and 1 had moderate cytologic atypia. No other high-risk histologic features were observed. Application of the previously described clinicopathologic risk stratification score in all primary IMTs with complete data (n=18) classified 8 as high-risk (all malignant), 8 as intermediate-risk (3 malignant, 5 benign), and 2 as low-risk (benign). p16 was aberrant in all malignant IMTs, with <1% expression noted in 10, overexpression (>90%) in 4, and subclonal loss in 1; all benign tumors had patchy staining (20% to 80%; median 50%). Molecular analysis detected CDKN2A deletions in 8 of 9 tumors with <1% p16 expression, while the other harbored a TERT promoter mutation. TERT promoter mutations were also identified in 2 of 3 IMTs with p16 overexpression. Neither of these alterations was detected in the 3 sequenced benign IMTs. Thus, we recommend performing p16 on all uterine IMTs, which, combined with the risk stratification score, is a promising and cost-effective tool for predicting CDKN2A status and outcome in these patients. It may be particularly useful for tumors with incomplete information for risk stratification (ie, morcellated tumors) and for further stratifying intermediate-risk IMTs when sequencing is unavailable.
子宫炎性肌纤维母细胞瘤（IMT）是一种罕见的具有不确定恶性潜能的间叶性肿瘤。除了最近描述的风险分层评分（尚未被其他研究验证）和恶性肿瘤中罕见的 p16 表达异常外，目前尚无可靠预测行为的标准。在此，我们评估了 30 例 IMT 的临床病理特征和 p16 表达模式，其中一部分（13 例恶性，3 例良性）进行了基因组分析。15 例患者患有恶性 IMT，诊断时（n=5）或复发时（n=10；中位：24 个月）存在子宫外疾病。患者年龄 8-65 岁（中位：51 岁），肿瘤大小 6-22cm（中位：12.5cm）。在原发性肿瘤（n=13）中，10 例存在浸润性边界，9 例存在中度/重度细胞异型性，7 例存在肿瘤细胞坏死，6 例存在血管淋巴管浸润，而有丝分裂象为 0-21（中位数：7）/10 高倍视野。相比之下，15 例患有良性 IMT 的患者年龄为 28-65 岁（中位：44 岁），随访时间为 18-114 个月（中位：41 个月）。肿瘤大小为 1.9-8.5cm（中位数：5.5cm），2 例存在浸润性边界，1 例存在中度细胞异型性。未观察到其他高危组织学特征。对所有具有完整数据的原发性 IMT（n=18）应用先前描述的临床病理风险分层评分进行分类，结果显示 8 例为高危（均为恶性），8 例为中危（3 例恶性，5 例良性），2 例为低危（良性）。所有恶性 IMT 的 p16 均异常，10 例的表达＜1%，4 例的表达过强（＞90%），1 例存在亚克隆缺失；所有良性肿瘤均存在局灶性染色（20%-80%；中位数 50%）。分子分析检测到 9 例＜1% p16 表达肿瘤中有 8 例存在 CDKN2A 缺失，而另 1 例存在 TERT 启动子突变。在 3 例 p16 过表达的 IMT 中也发现了 TERT 启动子突变。这两种改变在 3 例测序的良性 IMT 中均未检测到。因此，我们建议对所有子宫 IMT 进行 p16 检测，这与风险分层评分相结合，是一种有前途且具有成本效益的工具，可用于预测这些患者的 CDKN2A 状态和结局。当无法进行测序时，它可能对风险分层信息不完整的肿瘤（即切碎的肿瘤）特别有用，并且对中间风险 IMT 进一步分层也很有用。
