Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Department of Pathology, University Hospitals Cleveland Medical Center, Case Western Reserve University, Cleveland, OH, USA.
Endocr Pathol. 2021 Sep;32(3):327-335. doi: 10.1007/s12022-021-09683-0. Epub 2021 May 21.
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.
具有乳头状筛状和微滤泡结构的肿瘤最初被认为是甲状腺乳头状癌的变体；然而，最近的观察结果对这一观点提出了挑战。在这项研究中，我们回顾了最大的病例系列的人口统计学、组织病理学和免疫组织化学特征，该系列由 33 例肿瘤组成。病理诊断时的年龄为 18 至 59 岁（平均 33 岁），除 1 例外，所有患者均为女性。16 例为多灶性，15 例为单灶性。2 例患者的病灶情况不详。肿瘤边界清楚，大小为 0.1 至 8.0 厘米。大多数肿瘤的筛状成分与微滤泡混合，除 7 例以筛状为主外，2 例以实性生长为主。可见不同程度的核增大、伸长、重叠和沟，但未见明显核卷曲、核内假包涵体和因染色质边缘化导致的透明核。筛状间隙内无或几乎无胶体物质。2 个实性肿瘤具有高级别特征。免疫组织化学研究显示所有病例均有β-连环蛋白核和细胞质阳性。筛状成分对 TTF1 呈阳性，对甲状腺球蛋白呈阴性。这些肿瘤中有一半的 PAX8 缺失，其余的为局灶性缺失。微滤泡对角蛋白 5 和 CD5 呈阳性，对 p63、p40、TTF1 和 PAX8 呈阴性。分子研究显示在 12 例肿瘤中存在胚系 APC 突变，在亚组测试的 5 例散发性肿瘤中为阴性。在本研究中，无论使用哪种抗体，所有的筛状-微滤泡癌均表达 TTF1；然而，PAX8 免疫反应性较弱、局灶性或阴性，所有肿瘤均缺乏甲状腺球蛋白反应性；这些发现对肿瘤细胞起源提出了质疑，并可能表明它们不是甲状腺滤泡上皮分化而来。我们推测微滤泡可能代表胸腺/终末鳃囊相关分化的分歧。鉴于其独特的细胞形态学、免疫组织化学特征和与传统滤泡细胞来源的甲状腺癌很少重叠的遗传特征，我们提出这些肿瘤代表一种与其他甲状腺滤泡细胞肿瘤无关的独特甲状腺癌形式。
