Department of Pathology, Stanford University School of Medicine, Stanford, CA.
Am J Surg Pathol. 2019 Jan;43(1):64-74. doi: 10.1097/PAS.0000000000001083.
Smooth muscle tumor of uncertain malignant potential (STUMP) is a rare diagnosis rendered when there is uncertainty concerning the biological potential of a smooth muscle tumor. The initial differential diagnosis is often broad, as tumors in this subgroup are morphologically heterogenous. Recent data suggest uterine inflammatory myofibroblastic tumors (IMTs) with anaplastic lymphoma kinase (ALK) rearrangement may be misclassified as STUMPs, but the extent to which this occurs has not been examined. We identified 60 female patients with tumors previously diagnosed as STUMP (48 cases) or prospectively considered for the diagnosis of STUMP (12 cases). Each case underwent histologic review, ALK immunohistochemistry (IHC) and confirmatory break-apart fluorescence in situ hybridization (FISH) for ALK if immunoreactive. Six of the 43 (14%) uterine and cervical tumors were ALK IHC positive, whereas tumors at all other sites were ALK IHC negative. Myxoid features, although limited in some cases, were present in all 6 ALK IHC positive tumors, representing 35% (6/17) of tumors displaying myxoid features at uterine and cervical sites. All ALK immunoreactive tumors were confirmed to have ALK rearrangements by FISH with 1 tumor showing numerous (3 to 8) 3' ALK signals, an unusual FISH pattern not previously described in uterine IMTs. Two patients developed recurrent disease and were treated with ALK-targeted therapy with initial response. Our data demonstrate that a significant proportion of uterine and cervical tumors considered to be STUMPs are ALK-positive by IHC and FISH. Future screening of all uterine and cervical mesenchymal tumors under consideration for the diagnosis of STUMP, particularly those with myxoid features, is recommended to identify ALK-rearranged IMTs that could potentially be treated with targeted therapy using tyrosine kinase inhibitors.
平滑肌肿瘤的恶性潜能不确定（STUMP）是一个罕见的诊断，当平滑肌肿瘤的生物学潜能存在不确定性时就会做出这个诊断。最初的鉴别诊断通常很广泛，因为该亚组的肿瘤在形态上存在异质性。最近的数据表明，具有间变性淋巴瘤激酶（ALK）重排的子宫炎性肌纤维母细胞瘤（IMT）可能被错误地分类为 STUMP，但这种情况的发生程度尚未得到检验。我们鉴定了 60 名女性患者，这些患者的肿瘤之前被诊断为 STUMP（48 例）或前瞻性考虑诊断为 STUMP（12 例）。每个病例都进行了组织学复习、ALK 免疫组化（IHC）检查，如果免疫反应阳性，则进行 ALK 断裂分离荧光原位杂交（FISH）检查。43 例子宫和宫颈肿瘤中有 6 例（14%）ALK IHC 阳性，而所有其他部位的肿瘤均为 ALK IHC 阴性。虽然在某些病例中有限，但粘液样特征存在于所有 6 例 ALK IHC 阳性肿瘤中，占子宫和宫颈部位显示粘液样特征的肿瘤的 35%（6/17）。所有 ALK 免疫反应性肿瘤均通过 FISH 证实存在 ALK 重排，其中 1 例肿瘤显示大量（3 至 8）3'ALK 信号，这是以前在子宫 IMT 中未描述的不寻常 FISH 模式。两名患者出现复发性疾病，并接受了 ALK 靶向治疗，初始反应良好。我们的数据表明，相当一部分被认为是 STUMP 的子宫和宫颈肿瘤通过 IHC 和 FISH 呈 ALK 阳性。建议对所有考虑诊断为 STUMP 的子宫和宫颈间叶性肿瘤进行筛查，特别是那些具有粘液样特征的肿瘤，以识别可能通过使用酪氨酸激酶抑制剂的靶向治疗来治疗的 ALK 重排 IMT。
