Kupryjańczyk J, Dansonka-Mieszkowska A, Moes-Sosnowska J, Plisiecka-Hałasa J, Szafron L, Podgórska A, Rzepecka I K, Konopka B, Budziłowska A, Rembiszewska A, Grajkowska W, Spiewankiewicz B
Jolanta Kupryjańczyk MD, PhD, Department of Pathology, The Maria Sklodowska-Curie, Memorial Cancer Centre and Institute of Oncology, Roentgena 5, 02-781 Warsaw, Poland, tel. +48 22 546 27 26, fax +48 22 546 21 81, e-mail:
Pol J Pathol. 2013 Dec;64(4):238-46. doi: 10.5114/pjp.2013.39331.
Ovarian tumors from two patients, compatible by histological and immunohistochemical criteria with small cell carcinoma of hypercalcemic type (SCCHT) (WT1+, EMA dispersed+, synaptophysin+ or dispersed+), were extensively sampled in order to find clues to their histogenesis. Subsequently, small foci of immature teratoma were found in both of them (in 1/122 and in 3/80 tumor sections). In one case, microfoci of yolk sac tumor were also present within the teratoma area as well as in the background of the small cell tumor population - in the primary tumor and in omental metastasis. We found a resemblance of the microscopic patterns of SCCHT and atypical teratoid/rhabdoid tumor (AT/RT) of the central nervous system, and this prompted us to evaluate INI-1 and SMARCA4 immunohistochemical expression, because their alternative loss is regarded as a molecular hallmark of AT/RT. INI-1 expression was retained, while that of SMARCA4 was lost. We therefore analyzed tumor DNA by PCR amplification and sequencing for mutations in the SMARCA4 gene (NG_011556.1), which were identified in both tumors (c.2184_2206del; nonsense c.3277C>T - both in one tumor; nonsense c.3760G>T in another tumor). These data suggest that SCCHT is most likely an embryonal tumor originating from immature teratoma and related to malignant rhabdoid tumor. Further analyses are necessary to determine whether the tumors diagnosed as SCCHT constitute a homogeneous group or represent more than one entity.
对两名患者的卵巢肿瘤进行了广泛取材，根据组织学和免疫组化标准，这些肿瘤与高钙血症型小细胞癌（SCCHT）相符（WT1阳性、EMA呈散在阳性、突触素阳性或呈散在阳性），以便找到其组织发生的线索。随后，在这两名患者的肿瘤中均发现了不成熟畸胎瘤的小灶性病变（分别在1/122和3/80个肿瘤切片中）。在1例患者中，卵黄囊瘤的微灶性病变也存在于畸胎瘤区域内以及小细胞肿瘤群体的背景中——存在于原发性肿瘤和网膜转移灶中。我们发现SCCHT的微观模式与中枢神经系统的非典型畸胎样/横纹肌样肿瘤（AT/RT）相似，这促使我们评估INI-1和SMARCA4的免疫组化表达，因为它们的交替缺失被视为AT/RT的分子标志。INI-1表达保留，而SMARCA4表达缺失。因此，我们通过PCR扩增和测序分析肿瘤DNA，以检测SMARCA4基因（NG_011556.1）的突变，在这两个肿瘤中均检测到了突变（一个肿瘤中为c.2184_2206del；无义突变c.3277C>T；另一个肿瘤中为无义突变c.3760G>T）。这些数据表明，SCCHT很可能是一种起源于不成熟畸胎瘤并与恶性横纹肌样肿瘤相关的胚胎性肿瘤。需要进一步分析以确定诊断为SCCHT的肿瘤是构成一个同质群体还是代表不止一种实体。
