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Multiple Pulmonary Sclerosing Pneumocytomas (PSPs): A Comprehensive Analysis of Clinicopathological Characteristics and Whole-exome Sequencing (WES) Results. 多发性肺硬化性肺细胞瘤(PSPs):临床病理特征和全外显子组测序 (WES) 结果的综合分析》。
IF 4.5 1区 医学 Q1 PATHOLOGY Pub Date : 2025-02-01 Epub Date: 2024-10-28 DOI: 10.1097/PAS.0000000000002328
Ying Wan, Ping Zhou, Yuqing Miao, Lili Jiang

Pulmonary sclerosing pneumocytoma (PSP) is a rare neoplasm with indolent clinical behavior and usually presents as a solitary nodule, while only a few cases involving multiple nodules. Recent studies have revealed frequent AKT1 mutations in PSP; however, the molecular genetics of multiple PSPs remain unclear. To better understand the genetic background, eleven patients (4.2%, 11/260) with multiple PSP nodules were identified, and whole-exome sequencing (WES) was performed on 6 patients. Among 5 patients with 2 or 3 PSP nodules, AKT1 alterations were the most common (50%, 7/14), and the predominant alteration was p.E17K (21.4%, 3/14). Novel ARID1A mutations were the second most common driver (14.3%, 2/14), and we first identified these mutations cooccurred with AKT1 p.E17K mutation. Moreover, we observed limited concordance in the mutation spectra and few comutated genes among different lesions from these 5 patients, indicating that PSP with 2 or 3 nodules were independent arising tumors. No AKT1 mutations were identified in 3 PSP samples from a patient with multiple diffuse nodules. However, there were 17 shared genetic alterations among the 3 lesions, but none were typical driver mutations. The findings on multiple diffuse PSP nodules may also have independent origins, but the potential that some of these nodules are metastatic nodules cannot be excluded. In conclusion, this retrospective study is the largest series of multiple PSP cases and provides new insights into the genomic underpinning of PSP. This work has a potential to broaden our understanding of the pathogenesis and development of these lesions and warrants analysis in larger cohorts.

肺硬化性肺细胞瘤(PSP)是一种罕见的肿瘤,临床表现不明显,通常表现为单发结节,只有少数病例涉及多发结节。最近的研究发现,PSP 中经常出现 AKT1 基因突变;然而,多发性 PSP 的分子遗传学仍不清楚。为了更好地了解其遗传背景,研究人员确定了11例(4.2%,11/260)多发性PSP结节患者,并对6例患者进行了全外显子组测序(WES)。在5名有2或3个PSP结节的患者中,AKT1基因改变最常见(50%,7/14),最主要的基因改变是p.E17K(21.4%,3/14)。新的ARID1A突变是第二常见的驱动因素(14.3%,2/14),我们首次发现这些突变与AKT1 p.E17K突变同时发生。此外,我们还观察到这5名患者的不同病变中突变谱的一致性有限,且合并基因较少,这表明有2或3个结节的PSP是独立发生的肿瘤。在一名多发弥漫性结节患者的 3 个 PSP 样本中未发现 AKT1 基因突变。不过,3个病变中有17个共同的基因改变,但都不是典型的驱动基因突变。多发性弥漫性 PSP 结节的发现也可能有独立的起源,但不能排除其中一些结节是转移性结节的可能性。总之,这项回顾性研究是最大规模的多发性 PSP 病例系列研究,为 PSP 的基因组基础提供了新的见解。这项工作有可能拓宽我们对这些病变的发病机制和发展的认识,值得在更大的群体中进行分析。
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引用次数: 0
Re: p53 Immunohistochemistry Defines a Subset of Human Papillomavirus-Independent Penile Squamous Cell Carcinomas With Adverse Prognosis. 回复:p53 免疫组化确定了具有不良预后的人类乳头状瘤病毒依赖性阴茎鳞状细胞癌亚群。
IF 4.5 1区 医学 Q1 PATHOLOGY Pub Date : 2025-02-01 Epub Date: 2024-09-26 DOI: 10.1097/PAS.0000000000002314
Burak Tekin, Ruifeng Guo, Lori A Erickson, John C Cheville, Sounak Gupta
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引用次数: 0
A Proposal for Revised and Simplified Renal Pelvic Urothelial Carcinoma Staging Criteria: A Clinicopathologic Study of 141 Tumors. 修订和简化肾盆腔尿路上皮癌分期标准的建议:141例肿瘤的临床病理研究。
IF 4.5 1区 医学 Q1 PATHOLOGY Pub Date : 2025-02-01 Epub Date: 2024-11-14 DOI: 10.1097/PAS.0000000000002331
Miranda E Machacek, Hanzhang Wang, Kyle Devins, Peter M Sadow, Chin-Lee Wu, Esther Oliva, Philip J Saylor, Kristine M Cornejo

Staging of renal pelvic urothelial carcinoma can be challenging due to anatomic variation at the renal pelvis compared with ureter and bladder and calls into question the prognostic accuracy of the current TNM staging. In this study, we determined staging and cancer-specific survival (CSS) in 141 patients undergoing nephroureterectomy for renal pelvic urothelial carcinoma (pTa=50, pT1=29, pT2=10, pT3=36, and pT4=16). Under current staging criteria, we found no significant difference in CSS between adjacent staging categories step-wise across pTa, pT1, pT2, and pT3 tumors. When pT3 tumors were subcategorized into renal medulla, peripelvic adipose, or renal cortex invasion with or without peripelvic adipose invasion, we found that cortical invasion was associated with significantly worse CSS compared with medulla or peripelvic adipose invasion only. We next revised staging criteria such that pT1 correlated with invasion of lamina or muscularis propria (n=37), T2 with invasion of medulla or peripelvic adipose only (n=26), and pT3 with cortical invasion (n=12). Under the new criteria, better separation of survival curves was achieved; however, pT1 and pT2 remained statistically insignificant. When further redefining pT3 as invasive of cortex only (n=12) and combining medulla with lamina and muscularis propria invasion as a lower stage (pT1, n=63), there was further improvement in the prognostic stratification. Therefore, our data show that consideration of revised and simplified T staging criteria at the renal pelvis is warranted, wherein invasion of any anatomic structure up to the cortex shows a similar prognosis (combined pT1 category) and invasion of cortex showing significantly worse prognosis (pT3).

由于肾盂与输尿管和膀胱的解剖差异,肾盆腔尿路上皮癌的分期可能具有挑战性,并且对当前TNM分期的预后准确性提出了质疑。在这项研究中,我们确定了141例肾盆腔尿路上皮癌行肾输尿管切除术患者的分期和癌症特异性生存率(CSS) (pTa=50, pT1=29, pT2=10, pT3=36, pT4=16)。在目前的分期标准下,我们发现相邻分期类别在pTa、pT1、pT2和pT3肿瘤中的CSS无显著差异。当pT3肿瘤被细分为肾髓质、盆腔周围脂肪浸润或肾皮质浸润(伴或不伴盆腔周围脂肪浸润)时,我们发现皮质浸润与仅髓质或盆腔周围脂肪浸润相比,CSS明显更差。接下来,我们修订了分期标准,使pT1与椎板或固有肌层侵犯相关(n=37), T2仅与髓质或盆腔周围脂肪侵犯相关(n=26), pT3与皮质侵犯相关(n=12)。在新标准下,生存曲线分离效果较好;然而,pT1和pT2仍无统计学意义。当进一步将pT3重新定义为仅侵犯皮质(n=12),并将髓质合并板层和固有肌层侵犯作为较低阶段(n= 63)时,预后分层进一步改善。因此,我们的数据显示,考虑修订和简化的肾盂T分期标准是有必要的,其中侵犯任何解剖结构直至皮质的预后相似(合并pT1类别),而侵犯皮质的预后明显较差(pT3)。
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引用次数: 0
Impact of Implementing a Grossing Tumor-margin Distance Threshold for Frozen Section in Oncologic Lung Surgery. 在肿瘤肺外科冷冻切片中实施总肿瘤边缘距离阈值的影响。
IF 4.5 1区 医学 Q1 PATHOLOGY Pub Date : 2025-02-01 Epub Date: 2024-12-24 DOI: 10.1097/PAS.0000000000002337
Manal Kordahi, Andréanne Gagné, Hanie Abolfathi, Michèle Orain, Christian Couture, Patrice Desmeules, Sylvain Trahan, Sylvain Pagé, Jonathan Vaucher, Frederic Nicodème, Massimo Conti, Paula Ugalde Figueroa, Anne-Sophie Laliberté, Fabien C Lamaze, Yohan Bossé, Philippe Joubert

Intraoperative frozen section (FS) examination of oncologic surgical specimens is frequently performed to ensure complete surgical resection. Data on the gross evaluation of surgical margins are limited. We recently published a study suggesting the use of a macroscopic 2.0 cm tumor-margin cutoff during intraoperative evaluation to decrease the number of unnecessary FS. This study aimed to validate the safety and the clinical impacts of implementing a 2.0 cm tumor-margin threshold for FS diagnosis in evaluating surgical margins during oncologic lung surgery. This retrospective analysis included patients who underwent lung resection for primary or metastatic neoplasms between 2018 and 2022 at the Institut Universitaire de Cardiologie et de Pneumologie de Québec, following the implementation of this practice. Clinicopathological data were retrieved from the medical files. Univariate and multivariate analyses were used to identify the variables associated with positive margins. This study included 1575 tumors in 1299 patients. FS evaluations were performed in 24.4% of patients. No positive margins were observed when the tumor-margin distance was >2.0 cm. The incidence rate of positive margins was 2.95%, with parenchymal margins being the most affected. Multivariate analysis identified the tumor-margin distance as a significant predictor of positive margin status. This practice led to a 79.9% reduction in FS evaluations without compromising the margin assessment accuracy or patient safety. A 2.0 cm tumor-margin distance threshold for intraoperative FS evaluation in oncologic lung surgery is safe and effective in reducing unnecessary FS evaluations while maintaining accurate margin assessments.

术中冷冻切片(FS)检查肿瘤手术标本经常进行,以确保手术完全切除。关于手术切缘大体评估的数据是有限的。我们最近发表了一项研究,建议在术中评估时使用宏观2.0 cm肿瘤边缘切除来减少不必要的FS数量。本研究旨在验证2.0 cm肿瘤边缘阈值在肺肿瘤手术中诊断FS的安全性和临床影响。这项回顾性分析纳入了2018年至2022年期间在心血管和肺部研究所(Institut Universitaire de Cardiologie et de Pneumologie de qubec)因原发性或转移性肿瘤接受肺切除术的患者。从医学档案中检索临床病理资料。采用单变量和多变量分析来确定与正边际相关的变量。这项研究包括1299名患者的1575个肿瘤。24.4%的患者进行了FS评估。当肿瘤与边缘距离为> ~ 2.0 cm时,未见阳性边缘。阳性切缘发生率为2.95%,以实质切缘发生率最高。多变量分析发现肿瘤边缘距离是肿瘤边缘阳性状态的重要预测因子。这种做法导致FS评估减少79.9%,而不影响差值评估的准确性和患者安全。在肺肿瘤性手术中,术中FS评估2.0 cm肿瘤边缘距离阈值是安全有效的,可以减少不必要的FS评估,同时保持准确的边缘评估。
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引用次数: 0
Interpretation of p16 and p53 in the Classification of Squamous Cell Carcinoma of the Vulva-An Interobserver Agreement Study. p16和p53在外阴鳞状细胞癌分类中的解释——一项观察者间的一致研究。
IF 4.5 1区 医学 Q1 PATHOLOGY Pub Date : 2025-02-01 Epub Date: 2024-12-06 DOI: 10.1097/PAS.0000000000002336
Susanne K Jeffus, Jacob T Wooldridge, Lynn Hoang, Carlos Parra-Herran, Mugahed Hamza, Miki Lindsey, Meredith Verret, Nicholas Zoumberos, Bradley Fogel, Autumn Wyeth, João Gama, Charles M Quick

Squamous cell carcinoma of the vulva (vSCC) is currently categorized either as human papillomavirus (HPV) associated or independent. Immunohistochemical stains, p16 INK4a (p16) and p53 are helpful biomarkers to support the designation of vSCC into 1 of the 3 tumor pathways: (1) HPV-associated, (2) HPV-independent, TP53 mutant, or (3) HPV-independent, TP53 wild type. Recently, a framework of p53 expression patterns in vSCC was proposed. In this international and multi-institutional study, we evaluated the interrater agreement for p53 and p16 and tumor pathway classification in a cohort of 50 invasive vSCC across a variety of practice settings (private practice, academic medicine) and levels of expertise (trainees, gynecologic pathologists, dermatopathologists, private practice pathologists). Our study shows that the overall interrater agreement for the interpretation of p16 in vSCC is strong to near perfect, while the agreement for p53 and tumor pathway assignment is overall moderate. Interrater agreement for p53 and tumor pathway is higher (strong) in the academic practice setting. Pathologists without gynecologic subspecialty expertise benefited the most from a brief educational module, which fostered a better understanding and improved comfort level with the p16/p53 stain interpretation and tumor pathway designation in the diagnosis of vSCC. Some interpretative challenges remain, particularly in regard to select p53 patterns and high-risk HPV-in situ hybridization utilization, warranting additional research.

外阴鳞状细胞癌(vSCC)目前被归类为人类乳头瘤病毒(HPV)相关或独立。免疫组织化学染色,p16INK4a (p16)和p53是有用的生物标志物,支持将vSCC划分为3种肿瘤途径中的1种:(1)hpv相关,(2)hpv非依赖性,TP53突变型,或(3)hpv非依赖性,TP53野生型。最近,研究人员提出了vSCC中p53表达模式的框架。在这项国际和多机构的研究中,我们评估了50例侵袭性vSCC患者中p53和p16和肿瘤通路分类的一致性,这些患者来自不同的执业环境(私人执业、学术医学)和专业水平(实习生、妇科病理学家、皮肤病理学家、私人执业病理学家)。我们的研究表明,vSCC中解释p16的解释器的整体一致性很强,接近完美,而p53和肿瘤通路分配的一致性总体上是中等的。在学术实践中,p53和肿瘤通路的一致性更高(强)。没有妇科亚专科经验的病理学家从一个简短的教育模块中获益最多,该模块培养了他们对vSCC诊断中p16/p53染色解释和肿瘤通路指定的更好理解和舒适度。一些解释性的挑战仍然存在,特别是关于选择p53模式和高危hpv原位杂交利用,需要进一步的研究。
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引用次数: 0
Sarcoid Vasculitis in the Skin: A Clinicopathologic Study of 8 Cases With Various Skin Lesions but the Common Unique Cannonball-like Vessel Destruction by Sarcoid Granulomas. 皮肤肉样瘤血管炎:8例皮肤病变各异但肉瘤肉芽肿破坏血管的共同特征的临床病理学研究。
IF 4.5 1区 医学 Q1 PATHOLOGY Pub Date : 2025-02-01 Epub Date: 2024-11-27 DOI: 10.1097/PAS.0000000000002333
Ko-Ron Chen, Keiko Miura, Toyoko Inazumi, Yoshio Nakamura, Hideki Nakajima, Hayato Takahashi, Toshiyuki Yamamoto

While the skin is a common target organ for sarcoidosis, cutaneous granulomatous vasculitis is rare among patients with sarcoidosis. Due to the lack of detailed studies on cutaneous sarcoid vasculitis, both dermatologists and pathologists remain unfamiliar with this rare but important vasculitic disorder. We clinicopathologically evaluated eight cases with biopsy-proven cutaneous vasculitis and cutaneous sarcoidosis and analyzed morphologic changes in the process of vasculitis for both small vessels and muscular vessels in detail. The various skin lesions ranged from papulonodular erythema, annular erythema, maculopapular erythema, livedo reticularis-like eruptions, erythema nodosum-like lesions, subcutaneous nodules to ulcerative lesions. The extremities were the most frequently affected sites. Bilateral hilar lymphadenopathy with pulmonary sarcoidosis was the most common extracutaneous comorbidity. Skin-limited sarcoidosis was identified in 3 cases. All cases demonstrated a common histopathologic feature with sarcoid granulomas impinging on the target vessels with resultant vessel destruction. Perivascular infiltration of sarcoid granulomas resulted in compression and destruction of small vessels. In muscular arteries and veins, sarcoid granulomas closely attached to the muscular vessel wall, infiltrated the muscular layers and either occupied or penetrated the vessel walls, eventually invading the vascular lumen and replacing the entire muscular layers. The intimal infiltration of sarcoid granulomas resulted in a marked luminal narrowing. The scarcity of reports on cutaneous sarcoid vasculitis may be due to the overlooking or misinterpretation of vascular destruction caused by sarcoid granuloma infiltration as a feature of sarcoid granuloma masses.

虽然皮肤是肉样瘤病的常见靶器官,但皮肤肉芽肿性血管炎在肉样瘤病患者中却很少见。由于缺乏对皮肤肉芽肿性血管炎的详细研究,皮肤科医生和病理学家对这种罕见但重要的血管炎疾病仍不熟悉。我们对 8 例经活检证实的皮肤血管炎和皮肤肉样瘤病进行了临床病理评估,并详细分析了血管炎过程中小血管和肌肉血管的形态变化。各种皮肤病变包括丘疹性红斑、环状红斑、斑丘疹性红斑、网状组织样糜烂、结节样红斑、皮下结节和溃疡性病变。四肢是最常受累的部位。双侧肺门淋巴结病伴肺肉样肿是最常见的皮肤外合并症。皮肤局限性肉样瘤病有3例。所有病例都有一个共同的组织病理学特征,即肉样肉芽肿侵犯靶血管,导致血管破坏。肉毒肉芽肿的血管周围浸润导致小血管受压和破坏。在肌肉发达的动脉和静脉中,肉芽肿紧贴肌肉发达的血管壁,浸润肌肉层,占据或穿透血管壁,最终侵入血管腔,取代整个肌肉层。肉芽肿的内膜浸润导致管腔明显狭窄。有关皮肤肉样瘤血管炎的报道很少,这可能是由于人们忽视或误解了肉样瘤肉芽肿浸润造成的血管破坏是肉样瘤肿块的一个特征。
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引用次数: 0
Clinicopathologic Features and Viral Status of Low-risk HPV6 and HPV11-Associated Squamous Cell Carcinoma of the Uterine Cervix and Vulva.
IF 4.5 1区 医学 Q1 PATHOLOGY Pub Date : 2025-01-31 DOI: 10.1097/PAS.0000000000002367
Guy A Williams, Annie A Wu, Henrietta C Eugene, Ya-Chea Tsai, Margaret Wong, Hiro Nonogaki, Richard B S Roden, Chien-Fu Hung, Tzyy-Choou Wu, Russell Vang, Deyin Xing

Despite being designated as "noncarcinogenic" human papillomavirus (HPV) types, mono-infection with HPV6 or HPV11 has been found in squamous cell carcinomas (SCCs) at specific sites, including the larynx, penis, anus, and rarely, the lower female genital tract. The association between clinicopathologic features, viral status, and the carcinogenic mechanisms related to these low-risk HPVs remains unclear. The current study characterizes a series of low-risk HPV6 and HPV11-associated SCCs of the uterine cervix (6 cases) and vulva (2 cases). The diagnosis of SCC was made through the identification of stromal invasion in 6 cases. In case 2, the diagnosis of cancer was made after metastases to the sigmoid colon and liver. The patient in case 6 was diagnosed with intramucosal papillary SCC given multiple recurrences. While all tumors displayed a similar verruco-papillary architecture, the cytologic features, and immunostaining patterns suggest 2 groups of lesions: one with high-grade cytology and a high Ki-67 proliferation index (>60% of lesional cells), and the other with low-grade cytology and a low Ki-67 (20% to 30% of lesional cells). The detection of HPV6 in 7 of 8 cases underscores its critical role in carcinogenesis at these anatomic sites. Case 8 represented the only patient who was infected with HPV11 and who had a well-controlled human immunodeficiency virus infection. Correlating with viral status, all cases, except case 7, demonstrated a negative or focal p16 staining pattern. In case 7, despite a block pattern of p16 staining often seen in predicting high-risk HPV, we employed several methods to confirm HPV6 as the sole HPV infection. Although this descriptive study does not establish an etiological mechanism for how HPV6/11 leads to malignant transformation, our results exclude the possibility of viral integration through a quantitative polymerase chain reaction-based analysis of the E2/E6 ratio. Our study highlights and expands upon the clinicopathologic features of a distinct group of low-risk HPV6/11-associated SCCs in the cervix and vulva. Although rare, recognizing this group of lesions is important for pathologists and oncologists, as it provides a basis for guiding appropriate prevention strategies and treatment modalities based on the viral type.

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引用次数: 0
SALL4 as a Useful Marker for the Distinction of Various Gestational Trophoblastic Disease Subtypes: Choriocarcinoma From Other Trophoblastic Lesions and Early Complete Hydatidiform Mole From Partial Mole and NonMolar Villi.
IF 4.5 1区 医学 Q1 PATHOLOGY Pub Date : 2025-01-29 DOI: 10.1097/PAS.0000000000002358
Alexis Trecourt, Marie Donzel, Lucie Gaillot-Durand, Pierre A Bolze, François Golfier, Pierre Descargues, Touria Hajri, Claire Mauduit, Mojgan Devouassoux-Shisheboran, Fabienne Allias

The distinction between choriocarcinoma and residual trophoblastic cell proliferation from a complete hydatidiform mole/invasive mole (CHM/IM) without villi is challenging on curettage materials. We investigated whether SALL4 immunostaining could help differentiate various gestational trophoblastic diseases. Placental site nodules (PSN; n=10), atypical PSN (APSN; n=8), placental site trophoblastic tumors (PSTT; n=9), epithelioid trophoblastic tumors (ETT; n=5), gestational choriocarcinomas (n=31), partial hydatidiform moles (PHM; n=13), CHM/IM (n=47), and nonmolar products of conception (POC) (n=26) were included. SALL4 immunostaining was quantified (0 [1% to 10%], [11% to 100%]) and characterized (scattered single-cell or clustered nuclear positivity) in 2 locations: cytotrophoblast/intermediate trophoblast and villous stromal fibroblasts. A diffuse (11% to 100%) and clustered pattern of SALL4 immunostaining in cytotrophoblast/intermediate trophoblast was statistically associated with choriocarcinomas (74.2%, 23/31) as compared with PSN (0/10; P<0.0001), APSN (0/8; P=0.0002), PSTT (0/9; P<0.0001), ETT (0/5; P=0.0034), PHM (0/13; P<0.0001), CHM/IM (0/47; P<0.0001), and nonmolar POC (0/26; P<0.0001). Most nonchoriocarcinoma samples showed no SALL4 expression; when present, it was of low level (1% to 10%) and with a scattered single-cell staining in 3/9 PSTT (33%), 1/13 PHM (7.7%), 19/47 CHM/IM (40%), and 1/26 nonmolar POC (1.7%). These results were confirmed using a validation cohort. In addition, 66% (31/47) of CHM/IM villous stromal fibroblasts showed SALL4 expression (11% to 100%) (all before 14 gestational weeks), whereas this level of expression was never observed in PHM (0/13), nor in nonmolar POC (0/26; P<0.0001). Finally, a clustered and >10% SALL4 immunostaining in cytotrophoblast/intermediate trophoblast favors choriocarcinoma diagnosis. SALL4 expression in >10% villous stromal fibroblasts before 14 gestational weeks favors CHM/IM rather than PHM and nonmolar POC.

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引用次数: 0
Sialadenopapillary Ductal Tumors: Unifying the Spectrum of Sialadenoma Papilliferum-like Tumors With Low Malignant Potential. Sialadenopapillary 导管肿瘤:统一恶性可能性低的乳头状窦状腺瘤样肿瘤的范围
IF 4.5 1区 医学 Q1 PATHOLOGY Pub Date : 2025-01-01 Epub Date: 2024-10-30 DOI: 10.1097/PAS.0000000000002325
Elan Hahn, Ilan Weinreb, Raja R Seethala, Esther O'Regan, Daniel Baumhoer, Elizabeth Ann Bilodeau, Jeffrey Gagan, Peter J B Sabatini, Yen Chen Kevin Ko, Nada Binmadi, R John McComb, Iona T Leong, Justin A Bishop

Sialadenoma papilliferum is a tumor characterized by surface papillary projections and glandular/microcystic proliferation at the lesion base. Cases in which surface involvement is absent have been termed "sialadenoma papilliferum-like intraductal papillary tumor." Similar tumors that are present in the mandible have been termed "tubulopapillary hidradenoma-like tumor of the mandible." While previously considered benign, these tumors demonstrate variable clinical behavior and likely exist on a spectrum, rather than as discrete entities. In this study, we present a detailed clinicopathologic and molecular analysis of these lesions and propose a unifying diagnostic term: sialadenopapillary ductal tumor (SDT). Twenty-two cases with similar histologic features were reviewed, with special attention being paid to the clinicopathologic features. Immunohistochemistry for BRAF V600E and molecular testing were performed where material was available. The cases had varying diagnoses, ranging from benign to malignant. Six cases involved bone, 1 of which metastasized to a local lymph node. Of the 20 cases tested for BRAF V600E by immunohistochemistry, 18 were positive. Molecular testing was performed in 5 cases, where BRAF, PTPN11, and PIK3CA mutations were identified, predominantly members of the RAS-RAF-MEK-ERK pathway. In addition, 1 case was reclassified as an intraductal carcinoma after the identification of an NCOA4::RET gene fusion. Tumors on the SDT spectrum all share morphologic and molecular commonalities with unreliable distinguishing features. These tumors demonstrate the potential for aggressive local growth and regional metastasis. We propose a unifying diagnostic term for these lesions to reflect their common morphologic and molecular features and, most importantly, low malignant potential.

乳头状唾液腺瘤是一种以表面乳头状突起和病变基底部腺体/微囊增生为特征的肿瘤。表面不受累的病例被称为 "乳头状唾液腺瘤样导管内乳头状肿瘤"。出现在下颌骨的类似肿瘤被称为 "下颌骨管状乳头状乳头状瘤样肿瘤"。虽然这些肿瘤以前被认为是良性的,但它们的临床表现各不相同,很可能存在于一个谱系中,而不是作为独立的实体存在。在本研究中,我们对这些病变进行了详细的临床病理和分子分析,并提出了一个统一的诊断术语:下颌腺乳头状导管瘤(SDT)。我们对 22 例组织学特征相似的病例进行了回顾,并特别关注了临床病理学特征。在有材料的情况下,还进行了 BRAF V600E 免疫组化和分子检测。这些病例的诊断各不相同,从良性到恶性不等。其中 6 例累及骨骼,1 例转移至局部淋巴结。在通过免疫组化检测 BRAF V600E 的 20 个病例中,有 18 例呈阳性。对 5 例病例进行了分子检测,发现了 BRAF、PTPN11 和 PIK3CA 突变,主要是 RAS-RAF-MEK-ERK 通路的成员。此外,1 个病例在发现 NCOA4::RET 基因融合后被重新归类为导管内癌。SDT谱系上的肿瘤在形态和分子上都有共同之处,但鉴别特征并不可靠。这些肿瘤具有侵袭性局部生长和区域转移的潜能。我们为这些病变提出了一个统一的诊断术语,以反映它们共同的形态和分子特征,最重要的是,它们的恶性可能性较低。
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引用次数: 0
Reappraisal of Oncocytic Adenocarcinoma: Unveiling Its Connection to Oncocytic Variants of Salivary Duct Carcinoma and Mucoepidermoid Carcinoma Through ImmunoHisto-Molecular Perspectives. 重新评估肿瘤细胞腺癌:从免疫组织分子角度揭示其与唾液腺管癌和褐上皮样癌的肿瘤细胞变异的联系。
IF 4.5 1区 医学 Q1 PATHOLOGY Pub Date : 2025-01-01 Epub Date: 2024-11-08 DOI: 10.1097/PAS.0000000000002324
Lucas Vial, Françoise Descotes, Jonathan Lopez, Ziyad Alsugair, Philippe Céruse, Pierre Philouze, Maxime Fieux, Michel Wassef, Anne-Catherine Baglin, Mihaela Onea, Claire Castain, Philippe Delvenne, Gaelle Fromont-Hankard, Hugot Gilles, Franck Monnien, Olivier Mauvais, Charles Lépine, Francois Le Gall, Marie-Christine Rousselet, Anne Sudaka, Emmanuelle Uro-Coste, Odile Casiraghi, Valérie Costes-Martineau, Nazim Benzerdjeb

Oncocytic adenocarcinoma (OC) of the salivary glands is a rare and controversial entity. It was recently reclassified as "salivary carcinoma NOS and emerging entities" in the 2022 WHO classification of head and neck tumors. The lack of specific molecular alterations and its potential affiliation with other salivary gland carcinomas, such as the oncocytic mucoepidermoid carcinomas (OMEC) or the oncocytic subtype of salivary duct carcinomas (OSDC) justified this reclassification. It is becoming essential to clarify the complex spectrum of potential diagnoses surrounding oncocytic tumors. The objective of this study was to explore the histologic features, as well as the immunohistochemical and molecular profiles, of cases previously diagnosed as OC or OMEC of the salivary glands. This study involved 28 cases of carcinomas with a predominantly oncocytic component. The sex distribution was equal. The median age was 59 years (range 10 to 89). Most of these cases originated from the parotid gland (25/28). The mean tumor size was 2.4 cm (range 0.5 to 6.5). Primary immuno-morphological and mutation/gene fusion profiles reclassified mainly (64.3%, 18/28). Most of them were reclassified in descending order as OSDC (8/18), OMEC (5/18), and OC (2/18). But 3 cases remained unclassified (3/18). The transcriptomic analysis found a proximity of their transcriptomic profile with the OMEC group and a distance from the OSDCs. These findings imply that OC is not distinct but represents oncocytic variants of other salivary carcinomas. It underscores the importance of thorough morphologic, immunohistochemical, and molecular examinations to accurately diagnose carcinomas with predominant oncocytic components in the salivary glands.

唾液腺肿瘤细胞腺癌(OC)是一种罕见且有争议的肿瘤。最近,在 2022 年世界卫生组织头颈部肿瘤分类中,它被重新归类为 "唾液腺癌 NOS 和新出现实体"。由于缺乏特异性分子改变,且可能与其他唾液腺癌(如肿瘤细胞粘液表皮样癌(OMEC)或肿瘤细胞亚型唾液腺导管癌(OSDC))有关联,因此被重新归类。澄清围绕肿瘤细胞肿瘤的潜在诊断的复杂范围变得越来越重要。本研究的目的是探讨以前被诊断为唾液腺肿瘤(OC)或肿瘤细胞癌(OMEC)的病例的组织学特征以及免疫组化和分子特征。这项研究涉及 28 例以肿瘤细胞成分为主的癌肿。性别分布相同。中位年龄为59岁(10至89岁不等)。这些病例大多来自腮腺(25/28)。肿瘤平均大小为2.4厘米(0.5至6.5厘米不等)。原发性免疫形态学和突变/基因融合图谱主要是重新分类(64.3%,18/28)。其中大部分病例从高到低依次被重新分类为OSDC(8/18)、OMEC(5/18)和OC(2/18)。但有 3 例仍未分类(3/18)。转录组分析发现,他们的转录组特征与 OMEC 组接近,而与 OSDCs 相距甚远。这些研究结果表明,OC 并非与众不同,而是其他唾液腺癌的癌细胞变异体。这强调了全面的形态学、免疫组化和分子检查对于准确诊断唾液腺中以肿瘤细胞成分为主的癌症的重要性。
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American Journal of Surgical Pathology
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