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Bilateral Somatically Derived Germ Cell Tumors With 12p Gains Arising in High-grade Serous Carcinomas of the Ovary: A Case Report and Review of the Literature. 卵巢高级别浆液性癌中出现 12p 增益的双侧体细胞衍生生殖细胞瘤:病例报告和文献综述。
IF 1.6 4区 医学 Q3 OBSTETRICS & GYNECOLOGY Pub Date : 2024-10-30 DOI: 10.1097/PGP.0000000000001074
Amr H Masaadeh, Bilge Dundar, Megan I Samuelson, Evangeline Kadera, Amani Bashir

Epithelial ovarian neoplasms are commonly observed in older patients, while germ cell tumors (GCTs) typically present in young individuals. When GCTs are detected in patients over 35 yrs old, they often have an associated epithelial component, a phenomenon known as somatically derived GCTs. We report a unique case of mixed GCT involving bilateral ovaries with a background of high-grade serous carcinoma, including a yolk sac tumor and choriocarcinoma in the mixed GCT component. Somatically derived GCTs are rare with only 45 cases of ovarian carcinoma with somatic yolk sac tumor reported to date. Pathologists face diagnostic challenges in identifying somatically derived GCTs, as they can mimic high-grade epithelial neoplasms. Somatically derived GCTs have poor outcomes, therefore, precise diagnosis is crucial for prognostic and therapeutic considerations.

上皮性卵巢肿瘤常见于年龄较大的患者,而生殖细胞瘤(GCT)通常出现在年轻人身上。当在 35 岁以上的患者中发现生殖细胞瘤时,它们往往伴有上皮成分,这种现象被称为体细胞衍生型生殖细胞瘤。我们报告了一例涉及双侧卵巢的混合型 GCT,其背景是高级别浆液性癌,包括混合型 GCT 成分中的卵黄囊肿瘤和绒毛膜癌。体细胞衍生的 GCT 非常罕见,迄今为止仅有 45 例卵巢癌伴有体细胞卵黄囊肿瘤的报道。病理学家在鉴别体细胞衍生型 GCT 时面临着诊断难题,因为它们可能与高级别上皮肿瘤相似。体细胞衍生型 GCT 的预后较差,因此,精确诊断对预后和治疗至关重要。
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引用次数: 0
Clinicopathologic and Genomic Features of Invasive Stratified Mucin-producing Carcinoma of the Uterine Cervix Coexisting With High-grade Squamous Intraepithelial Lesion. 与高级别鳞状上皮内病变并存的侵袭性子宫颈分层粘液腺癌的临床病理和基因组特征
IF 1.6 4区 医学 Q3 OBSTETRICS & GYNECOLOGY Pub Date : 2024-10-30 DOI: 10.1097/PGP.0000000000001075
Xinyuan Long, Xiaoting Ma, Wei Xiao, Jinghuan Lv

Invasive stratified mucin-producing carcinoma (ISMC) is a specific type of adenocarcinoma of the cervix, which is associated with human papillomavirus infection and often coexists with other types of carcinomas. However, given its rarity, understanding of this disease remains insufficient. We present a unique case of ISMC of the cervix coexisting with a high-grade squamous intraepithelial lesion (HSIL). In addition to histologic and immunohistochemical feature observation, genomic profiling of the 2 lesions was performed. Histologically, the ISMC and HSIL lesions were independent of each other. Aside from the typical morphology, various architectural features of ISMC were observed. Immunohistochemically, the ISMC and HSIL lesions were strongly and diffusely positive for p16 and exhibited high Ki-67 expression. The ISMC lesion was also positive for CK7, MUC5AC, and MUC6, while it was negative for PAX-8. The HSIL lesion was positive for CK5/6 and p40. The combined positive score of PD-L1 was 55. The other markers were all negative in both lesions, and the p53 was wild-type. Next-generation sequencing analysis revealed multiple gene mutations in the ISMC and HSIL lesions. A total of 88 gene mutations were identified in the ISMC lesion, while 20 gene mutations were identified in the HSIL lesion. Three mutations (ERBB2, histidine decarboxylase gene [HDC], and BSN) were detected in the ISMC and HSIL lesions. Both lesions had a low tumor mutation burden and microsatellite-stable status. No copy number-associated variants or structural variations were identified in either lesion. These results suggest that patients with ISMC may benefit from PD-L1 immunotherapy and targeted therapy.

浸润性分层粘液分泌癌(ISMC)是宫颈腺癌的一种特殊类型,与人类乳头状瘤病毒感染有关,并经常与其他类型的癌症并存。然而,由于其罕见性,人们对这种疾病的认识仍然不足。我们介绍了一例宫颈 ISMC 与高级别鳞状上皮内病变(HSIL)并存的独特病例。除了组织学和免疫组化特征观察外,我们还对这两种病变进行了基因组分析。从组织学角度看,ISMC和HSIL病变相互独立。除了典型的形态外,还观察到 ISMC 的各种结构特征。免疫组化结果显示,ISMC和HSIL病变的p16呈强弥漫阳性,Ki-67呈高表达。ISMC病灶的CK7、MUC5AC和MUC6也呈阳性,而PAX-8呈阴性。HSIL病灶的CK5/6和p40呈阳性。PD-L1的综合阳性分数为55分。其他标记物在两个病灶中均为阴性,p53为野生型。新一代测序分析显示,ISMC和HSIL病变中存在多种基因突变。在ISMC病变中总共发现了88个基因突变,而在HSIL病变中发现了20个基因突变。在ISMC和HSIL病变中发现了三种基因突变(ERBB2、组氨酸脱羧酶基因[HDC]和BSN)。这两个病变的肿瘤突变负荷较低,微卫星状态稳定。两种病变中均未发现拷贝数相关变异或结构变异。这些结果表明,ISMC 患者可能会从 PD-L1 免疫疗法和靶向疗法中获益。
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引用次数: 0
Diagnostic Utility of Deeper Level Tissue Sections of Negative Peritoneal Biopsies for Clinically Suspected Endometriosis. 阴性腹膜活检组织深层切片对临床疑似子宫内膜异位症的诊断作用
IF 1.6 4区 医学 Q3 OBSTETRICS & GYNECOLOGY Pub Date : 2024-10-30 DOI: 10.1097/PGP.0000000000001071
Constance V Chen, Megan S Orlando, Mary Kathryn Abel, Jessica Opoku-Anane, Joseph T Rabban

Definitive diagnosis of endometriosis is established by histologic confirmation in tissue from surgically visualized lesions; however, the diagnostic sensitivity of this approach varies widely. We hypothesized that incomplete tissue block sampling may contribute to false-negative diagnosis, particularly if the focus of endometriosis in the tissue section is scant. This study defined the diagnostic value of deeper level tissue sections in cases in which none of the specimen parts contained endometriosis on the initial tissue sections, using the World Health Organization essential criteria for diagnosis of endometriosis (presence of endometrial glands and endometrial stroma). Among 135 patients who underwent surgery for suspected endometriosis by a single surgeon at an academic institution from 2015 to 2019, the initial tissue sections resulted in a diagnosis of endometriosis in 73.3% (99/135), at an average diagnostic yield of 5.9 slides per diagnosis of endometriosis. An additional 9 patients were diagnosed with endometriosis by deeper level tissue sections, increasing the diagnostic rate to 80% (108/135). This 6.7% gain in the diagnostic rate came at an increase in resource utilization, with an overall overage diagnostic yield of 9.8 slides per diagnosis of endometriosis. Overall, 8.3% of patients had a false-negative diagnosis on the initial tissue sections. When extrapolated to a population level, the number of patients potentially affected by this source of false-negative diagnosis and the implications for patients merit consideration of the use of deeper level sections if none of the initial sections of any of the specimens contains endometriosis.

子宫内膜异位症的明确诊断需要通过手术观察到的病灶组织进行组织学确认;然而,这种方法的诊断灵敏度差别很大。我们推测,不完整的组织块取样可能会导致假阴性诊断,尤其是在组织切片中子宫内膜异位症病灶较少的情况下。本研究根据世界卫生组织诊断子宫内膜异位症的基本标准(存在子宫内膜腺体和子宫内膜基质),确定了在初始组织切片中标本部位均不包含子宫内膜异位症的情况下,深层组织切片的诊断价值。2015 年至 2019 年期间,一家学术机构的一名外科医生对 135 名疑似子宫内膜异位症患者进行了手术,其中 73.3% 的患者(99/135)通过初始组织切片确诊为子宫内膜异位症,平均每次诊断子宫内膜异位症的诊断率为 5.9 张切片。另有 9 名患者通过更深层次的组织切片确诊为子宫内膜异位症,诊断率提高到 80%(108/135)。在诊断率提高 6.7% 的同时,资源利用率也有所提高,每次诊断子宫内膜异位症的总体超额诊断率为 9.8 张切片。总体而言,8.3% 的患者在最初的组织切片诊断中出现了假阴性。如果推断到人群层面,这种假阴性诊断可能影响的患者人数以及对患者的影响值得考虑,如果任何标本的初始切片都不包含子宫内膜异位症,则应考虑使用更深层次的切片。
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引用次数: 0
Origin of Peritoneal Cancer With Features of High-grade Serous Carcinoma: A Detailed Molecular Analysis. 具有高级别浆液性癌特征的腹膜癌的起源:详细的分子分析。
IF 2.4 4区 医学 Q3 OBSTETRICS & GYNECOLOGY Pub Date : 2024-09-10 DOI: 10.1097/pgp.0000000000001069
Tomo Yamagata,Koichi Watanabe,Koji Yamanoi,Nobuyuki Kakiuchi,Jumpei Ogura,Mana Taki,Ryusuke Murakami,Ken Yamaguchi,Junzo Hamanishi,Sachiko Minamiguchi,Seishi Ogawa,Masaki Mandai
Primary peritoneal cancer has characteristics similar to high-grade serous carcinomas of ovarian and fallopian tube origin. However, the relationship between endometriosis and primary peritoneal cancer is not well understood. This study focuses on a case of peritoneal cancer in a patient who had undergone hysterectomy and bilateral salpingo-oophorectomy 5 yr before. In addition to morphology, there was a positive for TP53 in immunohistochemistry and homologous recombination deficiency test, which were similar to high-grade serous carcinomas. However, WT1 was negative in the tumor, and extensive endometriosis coexisted. To reveal the clonal relationship between tumor and endometriosis, we dissected 3 sites each from the tumor and endometriosis and performed whole-exome sequencing analysis. As a result, we found that the tumors were of identical origin. Contrarily, no shared mutations were found in the 3 endometriosis sites. Furthermore, several shared mutations were found between the tumor and 1 endometriosis tissue, showing that the tumor and 1 ectopic endometrial gland originated from the same clone. This study indicates that several peritoneal cancers may be derived from endometriosis. We should consider the possibility of more diverse origins of peritoneal cancer than we speculated before.
原发性腹膜癌的特征与卵巢和输卵管来源的高级别浆液性癌相似。然而,人们对子宫内膜异位症与原发性腹膜癌之间的关系还不甚了解。本研究的重点是一例 5 年前接受过子宫切除术和双侧输卵管切除术的腹膜癌患者。除形态学外,免疫组化和同源重组缺失试验均显示 TP53 阳性,与高级别浆液性癌相似。然而,肿瘤中的 WT1 呈阴性,且同时存在广泛的子宫内膜异位症。为了揭示肿瘤和子宫内膜异位症之间的克隆关系,我们从肿瘤和子宫内膜异位症中各分离出3个位点,并进行了全外显子组测序分析。结果我们发现,肿瘤和子宫内膜异位症的起源完全相同。相反,在子宫内膜异位症的 3 个部位没有发现共同的突变。此外,我们还在肿瘤和一个子宫内膜异位组织之间发现了几个共享突变,这表明肿瘤和一个异位子宫内膜腺体来源于同一个克隆。这项研究表明,多种腹膜癌可能源自子宫内膜异位症。我们应该考虑到腹膜癌的来源可能比我们以前推测的更加多样化。
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引用次数: 0
Synchronous Bilateral Ovarian Carcinomas With Right Mesonephric-like Adenocarcinoma and Left High-grade Serous Carcinoma: A Case Report and Review of the Literature. 同步双侧卵巢癌伴右侧间质样腺癌和左侧高级别浆液性癌:病例报告和文献综述》(Synchronous Bilateral Ovarian Carcinomas with Right Mesonephric-like Adenocarcinoma and Left High-grade Serous Carcinoma: A Case Report and Review of the Literature)。
IF 2.4 4区 医学 Q3 OBSTETRICS & GYNECOLOGY Pub Date : 2024-09-10 DOI: 10.1097/pgp.0000000000001070
Daisy Maharjan,Katrina Collins,Tieying Hou,Brandon Umphress,Sharon E Robertson,Sheila Segura
Mesonephric-like adenocarcinomas (MLAs) are rare neoplasms of the uterus corpus and ovary, while high-grade serous carcinoma (HGSC) is the most common and lethal epithelial ovarian malignancy. We report a case of a 56-yr-old woman who presented with bilateral solid and cystic ovarian masses. She underwent a total abdominal hysterectomy with bilateral salpingo-oophorectomy, lymphadenectomy, omentectomy, and peritoneal biopsies. Histopathologic examination of the bilateral ovarian masses revealed 1 ovary with MLA, and the other ovary showed HGSC in association with serous tubal intraepithelial carcinoma. The morphology, immunophenotypes, and molecular profiling of the HGSC and the MLA were distinct and as expected for the different tumor types: HGSC was diffusely positive for WT-1, estrogen receptor, and p53 (mutant pattern), while negative for GATA-3 and TTF-1; MLA was positive for GATA-3 and TTF-1, while negative for WT1, estrogen receptor, and p53 (wild-type pattern); both tumors were diffusely positive for PAX-8. The HGSC revealed a TP53 c.659A>G (p.Y220C) mutation, and the MLA revealed a KRAS c. 34G>T (p. G12C) mutation and a PIK3CA c. 1034A>T (p. N345I) mutation. To the best of our knowledge, this is the first reported case of synchronous bilateral ovarian carcinomas with MLA and contralateral ovarian HGSC.
中肾样腺癌(MLA)是子宫体和卵巢的罕见肿瘤,而高级别浆液性癌(HGSC)则是最常见、最致命的卵巢上皮恶性肿瘤。我们报告了一例 56 岁女性的病例,她出现了双侧实性和囊性卵巢肿块。她接受了全腹子宫切除术、双侧输卵管切除术、淋巴结切除术、卵巢切除术和腹膜活检。双侧卵巢肿块的组织病理学检查显示,其中一个卵巢伴有MLA,另一个卵巢显示HGSC伴有浆液性输卵管上皮内癌。HGSC和MLA的形态、免疫分型和分子图谱均截然不同,符合不同肿瘤类型的预期:HGSC的WT-1、雌激素受体和p53(突变型)呈弥漫阳性,而GATA-3和TTF-1呈阴性;MLA的GATA-3和TTF-1呈阳性,而WT1、雌激素受体和p53(野生型)呈阴性;两种肿瘤的PAX-8均呈弥漫阳性。HGSC 发现了 TP53 c.659A>G (p.Y220C) 突变,MLA 发现了 KRAS c. 34G>T (p. G12C) 突变和 PIK3CA c. 1034A>T (p. N345I) 突变。据我们所知,这是首例同步双侧卵巢癌伴MLA和对侧卵巢HGSC的病例。
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引用次数: 0
Immunohistochemical Expression of Lymphoid Enhancer-binding Factor 1 in Low-grade Endometrial Stromal Tumors. 低级别子宫内膜间质瘤中淋巴增生结合因子 1 的免疫组化表达
IF 1.6 4区 医学 Q3 OBSTETRICS & GYNECOLOGY Pub Date : 2024-09-01 Epub Date: 2023-11-10 DOI: 10.1097/PGP.0000000000001001
Shuo Niu, Haiyan Lu, Wencheng Li, Yanjun Hou

Endometrial stromal tumors (ESTs) are uncommon uterine mesenchymal lesions. Nuclear expression of β-catenin, an indication of activated Wnt/β-catenin signaling pathway, was described in 50% to 92% of low-grade ESTs, including endometrial stromal nodule and low-grade endometrial stromal sarcoma. Activation of the Wnt/β-catenin signaling pathway leads to the translocation of β-catenin into the nucleus and interaction with the T-cell factor/lymphoid enhancer-binding factor-1 (LEF1) family of transcription factors to regulate cell proliferation, differentiation, migration, and survival. Immunohistochemical analysis of β-catenin and LEF1 was performed in 2 endometrial stromal nodules and 20 low-grade endometrial stromal sarcomas and demonstrated 90.9% and 81.8% positive rates for β-catenin and LEF1, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value of β-catenin and LEF1 were 90.9% versus 81.8%, 81.0% versus 85.7%, 83.3% versus 85.7%, 89.5% versus 81.8%, respectively, in the diagnosis of low-grade ESTs. There is no statistical significance of the performance of β-catenin and LEF1 in all ESTs ( P = 0.664) or in primary or metastatic/recurrent settings ( P = 0.515 and 0.999, respectively). Only 3 smooth muscle tumors showed focal and weak positivity for LEF1. Our results indicate LEF1 can be a useful marker in aiding a diagnosis of low-grade EST and differentiating from smooth muscle tumors alone or in combination with β-catenin.

子宫内膜间质瘤(EST)是一种不常见的子宫间质病变。在50%至92%的低级别EST(包括子宫内膜间质结节和低级别子宫内膜间质肉瘤)中发现了β-catenin的核表达,这是Wnt/β-catenin信号通路活化的标志。Wnt/β-catenin信号通路的激活导致β-catenin转位至细胞核,并与T细胞因子/淋巴细胞增强子结合因子-1(LEF1)家族转录因子相互作用,从而调节细胞的增殖、分化、迁移和存活。对2例子宫内膜间质结节和20例低度子宫内膜间质肉瘤进行了β-catenin和LEF1免疫组化分析,结果显示β-catenin和LEF1的阳性率分别为90.9%和81.8%。在低分级EST的诊断中,β-catenin和LEF1的敏感性、特异性、阳性预测值和阴性预测值分别为90.9%对81.8%、81.0%对85.7%、83.3%对85.7%、89.5%对81.8%。β-catenin和LEF1在所有EST(P = 0.664)或原发性或转移性/复发性EST(P = 0.515和0.999)中的表现均无统计学意义。只有 3 例平滑肌瘤的 LEF1 呈局灶性弱阳性。我们的研究结果表明,LEF1可作为一种有用的标记物,单独或与β-catenin结合使用可帮助诊断低级别EST并与平滑肌瘤相鉴别。
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引用次数: 0
Does "One Size Fits All"? Rethinking FIGO Depth of Invasion Measurements in Vulvar Cancer. 是否 "一刀切"?反思外阴癌的 FIGO 侵袭深度测量。
IF 1.6 4区 医学 Q3 OBSTETRICS & GYNECOLOGY Pub Date : 2024-09-01 Epub Date: 2024-02-02 DOI: 10.1097/PGP.0000000000001009
Maaike C G Bleeker, Tjalling Bosse, Koen K van de Vijver, Joost Bart, Hugo Horlings, Trudy G N Jonges, Nicole C M Visser, Loes F S Kooreman, Johan Bulten, Patricia C Ewing-Graham

Depth of invasion (DOI) is an important diagnostic parameter in patients with vulvar carcinoma, where a cutoff value of 1 mm largely determines the tumor stage and the need for groin surgery. DOI measurement should be reproducible and straightforward. In light of the new recommendation on how to measure DOI in the International Federation of Gynecology and Obstetrics (FIGO) staging system 2021, an exploratory study was conducted on the current practice of DOI measurement in vulvar cancer. In this study of 26 selected cases, 10 pathologists with high exposure to vulvar cancer cases in daily practice assessed both the conventional (FIGO 2009) and alternative (FIGO 2021) DOI methods for applicability and preference. In this set of cases, the DOI measurement according to FIGO 2009 was generally considered easier to apply than the measurement according to FIGO 2021, with applicability being rated as "easy to reasonable" in 76.9% versus 38.5% of cases, respectively ( P =0.005). The preferred method was FIGO 2009 or tumor thickness in 14 cases and FIGO 2021 in 6 cases. No invasion was preferred in 1 case. For the remaining 5 cases, half of the pathologists opted for the FIGO 2009 method and half for the FIGO 2021 method. Although the FIGO 2009 method proved to be more readily applicable in most of the cases studied, the method may differ for each case. There may not be a "one size fits all" solution for all cases of vulvar cancer.

浸润深度(DOI)是外阴癌患者的一个重要诊断参数,1 毫米的临界值在很大程度上决定了肿瘤的分期和腹股沟手术的必要性。DOI的测量应具有可重复性且简单明了。鉴于国际妇产科联盟(FIGO)2021年分期系统对如何测量DOI提出了新的建议,我们对目前外阴癌DOI的测量方法进行了一项探索性研究。在这项针对 26 个选定病例的研究中,10 位在日常工作中接触外阴癌病例较多的病理学家对传统 DOI 方法(FIGO 2009)和替代 DOI 方法(FIGO 2021)的适用性和偏好进行了评估。在这组病例中,根据 FIGO 2009 测量 DOI 被普遍认为比根据 FIGO 2021 测量更易于应用,分别有 76.9% 和 38.5% 的病例将其适用性评为 "易于合理"(P=0.005)。14例首选 FIGO 2009 或肿瘤厚度法,6例首选 FIGO 2021。1例首选无侵犯。在其余 5 个病例中,一半病理学家选择了 FIGO 2009 方法,一半选择了 FIGO 2021 方法。虽然事实证明 FIGO 2009 方法在大多数研究病例中更容易应用,但每个病例的方法可能都不尽相同。对于所有外阴癌病例,可能没有 "一刀切 "的解决方案。
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引用次数: 0
Clinicopathologic Characteristics of a Single-institution Cohort of Ovarian Adult Granulosa Cell Tumors, With Biomarker and Therapeutic Implications Utilizing the Detection of Androgen, Estrogen, and Progesterone Hormone Receptor Expression by Immunohistochemistry. 利用免疫组化法检测雄激素、雌激素和孕激素受体表达的单机构卵巢成人颗粒细胞瘤队列的临床病理特征及其生物标记和治疗意义。
IF 1.6 4区 医学 Q3 OBSTETRICS & GYNECOLOGY Pub Date : 2024-09-01 Epub Date: 2024-03-27 DOI: 10.1097/PGP.0000000000001032
Michelle Moh, Andrii Puzyrenko, Rebekah Summey, Janet S Rader, Genaro Enrique Herrera Cano, Jennifer V Gavina, Hallgeir Rui, Yunguang Sun, Elizabeth Hopp

Adult granulosa cell tumors (AGCTs) are rare ovarian tumors with generally good prognosis after surgical resection; however, they do have recurrence potential. Therapeutic and management options for recurrences are currently limited, and the need for expanded adjuvant therapies is increasingly recognized. Anti-hormonal therapy is being explored as an option, which relies on the detection and assessment of hormone receptor expression (androgen, estrogen, and progesterone receptors) as a biomarker and therapeutic target. Our study identifies several clinicopathologic characteristics with significant associations for recurrence of AGCT, which were younger age, higher stage, and larger tumor size. Our study also demonstrates that androgen receptor (AR) expression may be utilized as a potential biomarker for hormonal therapy and that detection of AR expression in AGCT by immunohistochemistry (IHC) varies depending on the antibody clone used for testing. AR was detected in 95% of samples tested with antibodies derived from clone AR27. This detection rate is much higher than previously reported.

成人颗粒细胞瘤(AGCT)是一种罕见的卵巢肿瘤,手术切除后一般预后良好,但也有复发的可能。目前,针对复发的治疗和管理方案十分有限,人们日益认识到需要扩大辅助治疗范围。抗荷尔蒙疗法正在作为一种选择进行探索,这种疗法依赖于检测和评估荷尔蒙受体(雄激素、雌激素和孕激素受体)的表达,将其作为一种生物标志物和治疗靶点。我们的研究发现了一些与 AGCT 复发有显著关联的临床病理特征,包括年龄较小、分期较高和肿瘤较大。我们的研究还表明,雄激素受体(AR)的表达可作为激素治疗的潜在生物标记物,而且通过免疫组织化学(IHC)检测AGCT中AR的表达因检测所用的抗体克隆而异。使用来自克隆 AR27 的抗体检测的样本中,95% 都能检测到 AR。这一检测率远远高于之前的报道。
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引用次数: 0
Improved Risk Prediction in Human Papillomavirus-Associated Endocervical Adenocarcinoma Through Assessment of Binary Silva Pattern-based Classification: An International Multicenter Retrospective Observational Study Led by the International Society of Gynecological Pathologists (ISGyP). 通过评估基于二元席尔瓦模式的分类,改进人乳头状瘤病毒相关宫颈内膜腺癌的风险预测:由国际妇科病理学家协会 (ISGyP) 主导的一项国际多中心回顾性观察研究。
IF 1.6 4区 医学 Q3 OBSTETRICS & GYNECOLOGY Pub Date : 2024-09-01 Epub Date: 2024-05-20 DOI: 10.1097/PGP.0000000000001033
Aime Powell, Anjelica Hodgson, Paul A Cohen, Joseph T Rabban, Kay J Park, W Glenn McCluggage, C Blake Gilks, Naveena Singh, Esther Oliva

Endocervical adenocarcinomas (EACs) are a group of malignant neoplasms associated with diverse pathogenesis, morphology, and clinical behavior. As a component of the International Society of Gynecological Pathologists International Endocervical Adenocarcinoma Project, a large international retrospective cohort of EACs was generated in an effort to study potential clinicopathological features with prognostic significance that may guide treatment in these patients. In this study, we endeavored to develop a robust human papillomavirus (HPV)-associated EAC prognostic model for surgically treated International Federation of Gynecology and Obstetrics (FIGO) stage IA2 to IB3 adenocarcinomas incorporating patient age, lymphovascular space invasion (LVSI) status, FIGO stage, and pattern of invasion according to the Silva system (traditionally a 3-tier system). Recently, a 2-tier/binary Silva pattern of invasion system has been proposed whereby adenocarcinomas are classified into low-risk (pattern A/pattern B without LVSI) and high-risk (pattern B with LVSI/pattern C) categories. Our cohort comprised 792 patients with HPV-associated EAC. Multivariate analysis showed that a binary Silva pattern of invasion classification was associated with recurrence-free and disease-specific survival (P < 0.05) whereas FIGO 2018 stage I substages were not. Evaluation of the current 3-tiered system showed that disease-specific survival for those patients with pattern B tumors did not significantly differ from that for those patients with pattern C tumors, in contrast to that for those patients with pattern A tumors. These findings underscore the need for prospective studies to further investigate the prognostic significance of stage I HPV-associated EAC substaging and the inclusion of the binary Silva pattern of invasion classification (which includes LVSI status) as a component of treatment recommendations.

宫颈内膜腺癌(EAC)是一类恶性肿瘤,其发病机制、形态和临床表现各不相同。作为国际妇科病理学家协会国际宫颈内膜腺癌项目的一部分,我们建立了一个大型的国际 EAC 回顾性队列,以研究潜在的具有预后意义的临床病理特征,从而为这些患者的治疗提供指导。在这项研究中,我们努力为接受手术治疗的国际妇产科联盟(FIGO)IA2 至 IB3 期腺癌建立一个强大的人乳头状瘤病毒(HPV)相关 EAC 预后模型,该模型结合了患者年龄、淋巴管间隙侵犯(LVSI)状态、FIGO 分期以及根据 Silva 系统(传统的 3 级系统)确定的侵犯模式。最近,有人提出了一种2级/二元席尔瓦侵袭模式系统,将腺癌分为低危(无LVSI的A/B模式)和高危(有LVSI的B/C模式)两类。我们的队列包括 792 例与 HPV 相关的 EAC 患者。多变量分析表明,二元席尔瓦侵袭模式分类与无复发生存率和疾病特异性生存率相关(P < 0.05),而 FIGO 2018 I 期亚型与之无关。对目前3级系统的评估显示,与A型肿瘤患者相比,B型肿瘤患者的疾病特异性生存率与C型肿瘤患者的疾病特异性生存率没有显著差异。这些研究结果突出表明,有必要开展前瞻性研究,进一步探讨I期HPV相关EAC亚分期的预后意义,并将二元席尔瓦侵袭模式分类(包括LVSI状态)作为治疗建议的一个组成部分。
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引用次数: 0
Evaluation of Combined p57KIP2 Immunohistochemistry and Fluorescent in situ Hybridization Analysis for Hydatidiform Moles Compared with Genotyping Diagnosis. p57KIP2免疫组化和荧光原位杂交联合分析法与基因分型诊断法对水滴形痣的比较评估
IF 1.6 4区 医学 Q3 OBSTETRICS & GYNECOLOGY Pub Date : 2024-09-01 Epub Date: 2024-01-31 DOI: 10.1097/PGP.0000000000001000
Hirokazu Usui, Kazufusa Hoshimoto, Asuka Sato, Motofumi Kano, Toshio Fukusato, Yukio Nakatani, Makio Shozu

Immunostaining with p57KIP2 is a widely used diagnostic technique to differentiate complete hydatidiform moles (CHMs) from partial hydatidiform moles (PHM) and non-molar hydropic abortion. However, distinguishing between PHMs and non-molar hydropic abortions using histopathology alone is often challenging. This study aimed to evaluate the technical validity and additional benefits of using fluorescence in situ hybridization (FISH) in combination with p57KIP2 immunostaining to diagnose molar and non-molar conceptuses. The study involved 80 specimens, which underwent genetic diagnosis using short tandem repeat analysis, including 44 androgenetic CHMs, 20 diandric monogynic PHMs, 14 biparental non-molar hydropic abortions, 1 monoandric digynic triploid abortion, and 1 vaginal specimen of gestational trophoblastic neoplasia. Two pathologists independently diagnosed the cases based on morphology and p57KIP2 immunostaining while the clinical information was masked. FISH analysis was performed using 3 probes (CEP17, CEPX, and CEPY), which revealed that all androgenetic CHM and biparental diploid non-molar hydropic abortion specimens were diploid. Among the 20 diandric monogynic PHM cases examined by analyzing short tandem repeat polymorphisms, 18 were triploid, and the remaining 2 were diploid. These two specimens were possibly androgenetic/biparental mosaics based on FISH analysis, where the three-signal ratios counting 50 cells were clearly within the diploid ranges. Eight of the 20 genetic PHMs and 2 of the 14 genetically confirmed non-molar hydropic abortions that were falsely diagnosed based on morphology and immunohistochemistry by at least 1 pathologist were correctly diagnosed as PHM and non-molar hydropic abortion, respectively, by FISH analysis. However, 1 monoandric digynic villus was classified as triploid by FISH analysis, leading to a false PHM diagnosis. In conclusion, the combination of FISH analysis with p57KIP2 immunostaining helps in diagnosing molar and non-molar conceptuses in numerous cases; nevertheless, exceptional cases should be considered.

p57KIP2 免疫染色是一种广泛使用的诊断技术,用于区分完全水样痣(CHM)与部分水样痣(PHM)和非摩尔水样流产。然而,仅使用组织病理学来区分 PHM 和非摩尔性水肿性流产往往具有挑战性。本研究旨在评估使用荧光原位杂交(FISH)结合 p57KIP2 免疫染色诊断磨性和非磨性受孕流产的技术有效性和额外优势。这项研究涉及 80 份标本,这些标本通过短串联重复分析进行了遗传学诊断,其中包括 44 个雄激素性 CHM、20 个双阴道单阴道 PHM、14 个双亲非臼齿水肿性流产、1 个单阴道双阴道三倍体流产和 1 个妊娠滋养细胞肿瘤阴道标本。两名病理学家根据形态学和 p57KIP2 免疫染色独立诊断病例,临床信息则被屏蔽。使用 3 个探针(CEP17、CEPX 和 CEPY)进行 FISH 分析,结果显示所有雄激素性 CHM 和双亲二倍体非极性水肿流产标本均为二倍体。在通过分析短串联重复多态性检测的 20 例双子单雌性 PHM 中,18 例为三倍体,其余 2 例为二倍体。根据 FISH 分析,这两个标本可能是雄性/双亲镶嵌体,其中计数 50 个细胞的三信号比明显在二倍体范围内。至少有一名病理学家根据形态学和免疫组化误诊的 20 例遗传性 PHM 中的 8 例和 14 例经遗传学证实的非摩尔水样流产中的 2 例,通过 FISH 分析分别被正确诊断为 PHM 和非摩尔水样流产。然而,FISH 分析将 1 个单核双腺绒毛归类为三倍体,导致 PHM 的错误诊断。总之,FISH 分析与 p57KIP2 免疫染色相结合有助于诊断许多病例中的臼齿胎和非臼齿胎;不过,特殊病例也应考虑在内。
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引用次数: 0
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International Journal of Gynecological Pathology
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