Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA.
Department of Pathology & Laboratory Medicine, Mount Sinai Hospital.
Am J Surg Pathol. 2022 Jan 1;46(1):33-43. doi: 10.1097/PAS.0000000000001751.
The number of recognized epithelioid soft tissue neoplasms continues to increase and includes epithelioid schwannoma, sclerosing epithelioid fibrosarcoma, and emerging entities such as sarcomas with GLI1 alterations. Here, we describe 23 cases of a previously unrecognized entity, provisionally termed "pseudoendocrine sarcoma." Pseudoendocrine sarcoma is a rare, distinctive tumor of uncertain lineage with a predilection for paravertebral soft tissue in older adults. Fifteen patients (65%) were male and 8 were female. Age at presentation ranged from 29 to 78 years (median: 62 y). Nineteen tumors (83%) occurred in truncal locations, including 15 tumors (65%) in paravertebral soft tissue; other locations included the posterior head (2 tumors), thigh (1), and orbit (1). Tumor size ranged from 2 to 19 cm (median: 6.35 cm). Pseudoendocrine sarcoma is composed of sheets, trabeculae, and nests of epithelioid or ovoid cells with indistinct borders, palely eosinophilic cytoplasm, and highly monomorphic, round nuclei with speckled chromatin. Pseudoglandular architecture was at least focally present in 16 tumors (70%), large extracellular hyaline globules were identified in 12 tumors (52%), and psammomatous calcifications were present in 8 (35%). Metaplastic ossification was identified in 2 tumors, and myxoid stroma was present in 1. Lymphovascular invasion was present in 5 of 18 tumors (28%). Immunohistochemistry demonstrated that most tumors showed nuclear positivity for β-catenin (20/21 tumors; 95%), and some showed at least focal positivity for S-100 (9/22; 41%), desmin (3/8; 38%), or CD34 (2/8; 25%). All tumors were negative for neuroendocrine and epithelial markers, including synaptophysin (21 tumors), chromogranin (19), INSM1 (4), pan-K (16), CAM5.2 (13), AE1/AE3 (6), epithelial membrane antigen (20), and E-cadherin (13). DNA sequencing detected CTNNB1 point mutations in all 6 sequenced tumors: D32H, S33C, S33F, S37A, S37C, and S37F. RNA sequencing was negative for gene fusions in all 6 sequenced tumors. Clinical follow-up was available for 17 patients (74%; range: 4 mo to 20 y; median: 3.5 y), including 14 patients with >1 year of follow-up. Six of 14 patients with long-term follow-up experienced local recurrence (43%, at intervals of 3 to 6 y). One tumor showed a local lymph node metastasis within the primary excision specimen, and 3 patients developed distant lung metastases (21%). No patient died of the disease as yet. Despite its bland morphology and resemblance to the well-differentiated neuroendocrine tumor, pseudoendocrine sarcoma is best considered an intermediate-grade sarcoma, given its pathologic characteristics and clinical behavior.
被识别的上皮样软组织肿瘤的数量持续增加，包括上皮样神经鞘瘤、硬化性上皮样纤维肉瘤和新兴实体，如具有 GLI1 改变的肉瘤。在这里，我们描述了 23 例以前未被识别的实体，暂时称为“假内分泌肉瘤”。假内分泌肉瘤是一种罕见的、具有独特特征的肿瘤，其谱系不确定，多见于老年患者的椎旁软组织。15 名患者（65%）为男性，8 名患者为女性。发病年龄为 29 至 78 岁（中位数：62 岁）。19 个肿瘤（83%）发生在躯干部位，包括 15 个（65%）位于椎旁软组织；其他部位包括头部（2 个）、大腿（1 个）和眼眶（1 个）。肿瘤大小为 2 至 19cm（中位数：6.35cm）。假内分泌肉瘤由上皮样或卵圆形细胞的片层、小梁和巢组成，边界不明显，胞浆淡嗜酸性，核高度单一形，染色质呈斑点状。至少有 16 个肿瘤（70%）存在假腺样结构，12 个肿瘤（52%）存在大细胞外透明小体，8 个肿瘤（35%）存在砂粒体样钙化。2 个肿瘤存在骨化，1 个肿瘤存在黏液样基质。5 个肿瘤（28%）存在淋巴管浸润。免疫组织化学显示，大多数肿瘤核阳性表达β-连环蛋白（21 个肿瘤中的 20 个；95%），部分肿瘤至少局灶性表达 S-100（22 个肿瘤中的 9 个；41%）、结蛋白（8 个肿瘤中的 3 个；38%）或 CD34（8 个肿瘤中的 2 个；25%）。所有肿瘤均为神经内分泌和上皮标志物阴性，包括突触素（21 个肿瘤）、嗜铬粒蛋白 A（19 个肿瘤）、INSM1（4 个肿瘤）、泛角蛋白（16 个肿瘤）、CAM5.2（13 个肿瘤）、AE1/AE3（6 个肿瘤）、上皮膜抗原（20 个肿瘤）和 E-钙黏蛋白（13 个肿瘤）。在所有测序的 6 个肿瘤中均检测到 CTNNB1 点突变：D32H、S33C、S33F、S37A、S37C 和 S37F。在所有测序的 6 个肿瘤中，RNA 测序均未检测到基因融合。17 例患者（74%）可获得临床随访（4 个月至 20 年；中位数：3.5 年），包括 14 例随访时间>1 年的患者。14 例长期随访患者中有 6 例出现局部复发（43%，间隔 3 至 6 年）。1 个肿瘤在原发切除标本中出现局部淋巴结转移，3 例患者出现远处肺转移（21%）。目前尚无患者死于该病。尽管假内分泌肉瘤的形态学表现温和，与分化良好的神经内分泌肿瘤相似，但鉴于其病理特征和临床行为，最好将其视为一种中等级别的肉瘤。
