Tumors with papillary cribriform and morular architecture were initially considered to be variants of papillary thyroid carcinoma; however, recent observations have challenged this view. In this study, we reviewed the demographical, histopathological, and immunohistochemical features of the largest case series, consisting of 33 tumors. The age at time of pathological diagnosis ranged from 18 to 59 (mean 33) years, and all patients except one were female. Sixteen patients had multifocal and fifteen had unifocal disease. The status of focality was unavailable in two patients. Tumors were well-circumscribed, ranging in size from 0.1 to 8.0 cm. The cribriform component was admixed with morulae in the majority, except seven had a cribriform-predominant architecture and two had predominantly solid growth. Variable degrees of nuclear enlargement, elongation, overlapping, and grooves were seen but florid nuclear convolution, intranuclear pseudoinclusions, and optically clear nuclei due to chromatin margination were not appreciated. There was no or little colloid material within the cribriform spaces. Two solid tumors had high-grade features. Immunohistochemical studies showed beta-catenin nuclear and cytoplasmic positivity in all cases. The cribriform component was positive for TTF1 and negative for thyroglobulin. PAX8 was absent in half of these tumors and focal in the remainder. Morulae were positive for keratin 5 and CD5 and negative for p63, p40, TTF1, and PAX8. Molecular studies revealed germline APC mutations in 12 tumors and were negative in 5 sporadic tumors in a subset of tested tumors. Irrespective of the antibody used in this cohort, all cribriform-morular carcinomas express TTF1; however, PAX8 immunoreactivity is weak, focal or negative, and all tumors lack thyroglobulin reactivity; these findings raise questions about tumor cell origin and may indicate that these are not of thyroid follicular epithelial differentiation. We postulate that morulae may represent divergent thymic/ultimobranchial pouch-related differentiation. Given their unique cytomorphology, immunohistochemical profiles, and genetic features that have little overlap with traditional follicular cell-derived thyroid carcinomas, we propose that these tumors represent a distinct form of thyroid carcinoma unrelated to other neoplasms of thyroid follicular cells.

具有乳头状筛状和桑椹状结构的肿瘤最初被认为是甲状腺乳头状癌的变异型。然而，最近的观察对这一观点提出了质疑。在这项研究中，我们回顾了由 33 个肿瘤组成的最大病例系列的人口统计学、组织病理学和免疫组织化学特征。病理诊断年龄18～59岁（平均33岁），除1例外均为女性。16 名患者患有多灶性疾病，15 名患者患有单灶性疾病。两名患者的病灶状态不可用。肿瘤界限清楚，大小从 0.1 到 8.0 厘米不等。筛状成分大部分与桑椹混合，除了七个具有以筛状为主的结构，两个具有主要的固体生长。不同程度的核扩大，可见伸长、重叠和凹槽，但未发现由于染色质边缘导致的华丽核回旋、核内假包涵体和光学清晰的核。在筛状空间内没有或几乎没有胶体材料。两个实体瘤具有高级特征。免疫组织化学研究显示，所有病例的 β-连环蛋白核和细胞质均呈阳性。筛状成分对 TTF1 呈阳性，对甲状腺球蛋白呈阴性。这些肿瘤中有一半不存在 PAX8，其余肿瘤为局灶性。Morulae 对角蛋白 5 和 CD5 呈阳性，对 p63、p40、TTF1 和 PAX8 呈阴性。分子研究揭示了种系 在筛状空间内没有或几乎没有胶体材料。两个实体瘤具有高级特征。免疫组织化学研究显示，所有病例的 β-连环蛋白核和细胞质均呈阳性。筛状成分对 TTF1 呈阳性，对甲状腺球蛋白呈阴性。这些肿瘤中有一半不存在 PAX8，其余肿瘤为局灶性。Morulae 对角蛋白 5 和 CD5 呈阳性，对 p63、p40、TTF1 和 PAX8 呈阴性。分子研究揭示了种系 在筛状空间内没有或几乎没有胶体材料。两个实体瘤具有高级特征。免疫组织化学研究显示，所有病例的 β-连环蛋白核和细胞质均呈阳性。筛状成分对 TTF1 呈阳性，对甲状腺球蛋白呈阴性。这些肿瘤中有一半不存在 PAX8，其余肿瘤为局灶性。Morulae 对角蛋白 5 和 CD5 呈阳性，对 p63、p40、TTF1 和 PAX8 呈阴性。分子研究揭示了种系 Morulae 对角蛋白 5 和 CD5 呈阳性，对 p63、p40、TTF1 和 PAX8 呈阴性。分子研究揭示了种系 Morulae 对角蛋白 5 和 CD5 呈阳性，对 p63、p40、TTF1 和 PAX8 呈阴性。分子研究揭示了种系装甲运兵车12 个肿瘤发生突变，在一部分测试肿瘤中 5 个散发性肿瘤呈阴性。无论该队列中使用的抗体如何，所有筛状-桑椹状癌都表达 TTF1。但PAX8免疫反应较弱，呈局灶性或阴性，所有肿瘤均缺乏甲状腺球蛋白反应性；这些发现提出了关于肿瘤细胞起源的问题，并可能表明这些不是甲状腺滤泡上皮分化。我们假设桑椹可能代表不同的胸腺/超鳃囊相关分化。鉴于它们独特的细胞形态学、免疫组织化学特征和与传统滤泡细胞衍生甲状腺癌几乎没有重叠的遗传特征，我们认为这些肿瘤代表了一种与其他甲状腺滤泡细胞肿瘤无关的甲状腺癌的独特形式。