早期蕈样真菌病临床定义斑块和斑块中淋巴浸润密度和深度的组织病理学评估。

IF 1.6 4区 医学 Q3 DERMATOLOGY
Juliette M. Kersten, Rosanne Ottevanger, Thom Doeleman, Pieter A. Valkema, Anne M. R. Schrader, Patty M. Jansen, Maarten H. Vermeer, Rein Willemze
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Several studies reported that patients presenting with both patches and plaques have a higher risk of progression to advanced-stage MF and a worse survival than patients presenting with only patches [<span>3-5</span>]. Therefore, the distinction between patches and plaques is clinically relevant, but it can be difficult due to a lack of standardized and reproducible criteria [<span>6</span>]. In the current classification system, differentiation between patches and plaques is based exclusively on clinical examination. Patches are defined as skin lesions without significant elevation or induration, while plaques are defined as skin lesions with elevation or induration [<span>7</span>]. However, this definition is subjective and prone to considerable inter-observer variability [<span>6</span>]. Previous studies on folliculotropic MF (FMF) found that a clinicopathologic approach, combining clinical and histopathological criteria, can facilitate the distinction between early and advanced plaque-stage disease [<span>8, 9</span>]. At recent meetings, the question was raised whether histopathologic criteria, in particular the extent and depth of the infiltrates, could also facilitate the distinction between patches and plaques in classical MF. The infiltrates in plaques in classical MF are indeed generally denser and deeper than in patches [<span>6, 10</span>]. However, studies investigating whether these differences may contribute to a more reliable distinction between patches and plaques have not been published thus far. 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Previous studies on folliculotropic MF (FMF) found that a clinicopathologic approach, combining clinical and histopathological criteria, can facilitate the distinction between early and advanced plaque-stage disease [<span>8, 9</span>]. At recent meetings, the question was raised whether histopathologic criteria, in particular the extent and depth of the infiltrates, could also facilitate the distinction between patches and plaques in classical MF. The infiltrates in plaques in classical MF are indeed generally denser and deeper than in patches [<span>6, 10</span>]. However, studies investigating whether these differences may contribute to a more reliable distinction between patches and plaques have not been published thus far. In the present study, we investigated the extent and depth of the infiltrate in patches and plaques in classic MF to find out if these histopathological criteria can serve as an adjunct to differentiate between these two types of lesions.</p><p>Using a database of scanned HE stained sections obtained from pretreatment biopsies of patients with early-stage classical MF, 100 cases with variable extent and depth of the infiltrates were selected without knowledge of the clinical data. Corresponding clinical records and clinical images of the biopsied lesions were evaluated and, blinded to the histopathologic characteristics, scored as either patch or plaque by three individual dermatologists using ISCL/EORTC criteria described previously [<span>7</span>]. In case of discrepancy (&lt; 5% of lesions) cases were discussed together and consensus was reached. In the total group of 100 cases with early-stage classical MF, 66 lesions were classified as patches and 34 as plaques. 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引用次数: 0

摘要

蕈样真菌病(MF)是最常见的皮肤t细胞淋巴瘤(CTCL)。在大多数患者中,MF的临床病程为数年至数十年,但在大约25%的患者中,可以观察到进展为晚期MF[2,3]。MF的预后取决于皮肤病变的类型和程度以及皮外疾病的存在。早期MF的特征是存在斑块和/或斑块,覆盖不到10% (IA期)或10%或更多的体表面积(IB期)。几项研究报道,与仅使用贴片的患者相比,同时使用贴片和斑块的患者进展为晚期MF的风险更高,生存期更差[3-5]。因此,斑块和斑块之间的区别与临床相关,但由于缺乏标准化和可重复的标准,可能很难区分。在目前的分类系统中,斑块和斑块的区分完全基于临床检查。斑块被定义为没有明显升高或硬化的皮肤病变,而斑块被定义为具有升高或硬化[7]的皮肤病变。然而,这一定义是主观的,容易在观察者之间产生相当大的差异。以往对嗜滤泡性MF (FMF)的研究发现,结合临床和组织病理学标准的临床病理学方法可以促进早期和晚期斑块期疾病的区分[8,9]。在最近的会议上,提出了一个问题,即组织病理学标准,特别是浸润的程度和深度,是否也有助于区分经典MF中的斑块和斑块。典型MF患者斑块内的浸润确实通常比斑块内的浸润更密集、更深[6,10]。然而,调查这些差异是否有助于更可靠地区分斑块和斑块的研究迄今尚未发表。在本研究中,我们研究了典型MF中斑块和斑块浸润的程度和深度,以了解这些组织病理学标准是否可以作为区分这两种类型病变的辅助标准。在不了解临床数据的情况下,使用早期经典MF患者预处理活检获得的扫描HE染色切片数据库,选择100例浸润程度和深度不同的病例。对活检病变的相应临床记录和临床图像进行评估,并在对组织病理学特征不知情的情况下,由三位皮肤科医生使用先前描述的ISCL/EORTC标准将其评分为斑块或斑块。如有差异(&lt; 5%的病变),一起讨论并达成共识。100例早期经典MF患者中,斑块66例,斑块34例。所有病例的诊断均由荷兰皮肤淋巴瘤肿瘤组的专家小组确认。根据浸润的程度和深度,可分为四种组织病理学类型:(1)真皮上部轻度或轻度浸润;(2)真皮上部中度致密浸润;(3)真皮上部厚带状浸润;(4)浸润延伸至真皮深层/皮下(图1)。所有扫描的he染色切片由5名对皮肤淋巴瘤(TD, PV, AS, PJ和RW)有丰富经验的皮肤病理学家独立评分为这四类之一,他们对临床数据不了解。对于没有初步共识的he染色切片,召开病理会议达成共识。结果显示,1类占17%,2类占45%,3类占16%,4类占22%。临床和组织病理学评分的相关性显示,17例1类病例中有15例(88%)来自临床定义的斑块,17例中只有2例(12%)来自临床定义的斑块。此外,分类为2类的病例主要来自补丁(30/45;67%)与斑块相比(15/45;33%)。值得注意的是,3类病例和4类病例在斑块之间分布均匀(3类:8/16;50%;类别4:12/22;55%)和斑块(第3类:8/16;50%;类别4:10/22;45%)(图2)。这些结果表明,在真皮上部有轻微至轻度浸润的病变(1类)最有可能代表斑块(88%)。然而,观察到浸润延伸到深部真皮/皮下(第4类)不仅在斑块中发现,而且在斑块中也发现,这意味着浸润的范围和深度不能被认为是区分斑块和斑块的可靠标准。值得注意的是,我们的研究集中在淋巴组织细胞浸润总量上,包括肿瘤细胞和反应细胞。 仅研究肿瘤t细胞的范围和深度将更有意义,但由于缺乏肿瘤特异性标记物,通常不可能。在最近的一项调查中,皮肤淋巴瘤专家指出,薄斑块和厚斑块之间的区别可能很重要,因为它可能具有FMF中所描述的预后和治疗意义[6,8,9]。在本研究中,没有尝试区分薄斑块和厚斑块,主要是因为这些病变的定义标准缺乏[6]。由于本组病例的发生率较低,因此无法评估显示真皮深部浸润的贴片是否比轻度表皮浸润的贴片有更高的疾病进展风险。总之,一个广泛的皮肤淋巴瘤专家小组最近强调需要明确的和可重复的组织病理学标准来区分早期MF[6]斑块和斑块。然而,本研究的结果表明,仅通过组织病理学来评估总浸润的范围和深度在区分这两种类型的病变方面价值有限。其他组织病理学标准,如胚细胞数量、CD30表达或炎症浸润的组成也可能很重要。组织病理学是否与超声、磁共振成像或基于人工智能的模型等其他诊断工具相结合,有助于更好地定义斑块及其与斑块的区分,还需要进一步研究[7,11,12]。该研究由莱顿大学医学中心的伦理委员会评估,并提供了放弃同意。作者声明无利益冲突。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Histopathologic Evaluation of Density and Depth of the Lymphoid Infiltrate in Clinically Defined Patches and Plaques in Early Stage Mycosis Fungoides

Histopathologic Evaluation of Density and Depth of the Lymphoid Infiltrate in Clinically Defined Patches and Plaques in Early Stage Mycosis Fungoides

Mycosis fungoides (MF) is the most common type of cutaneous T-cell lymphoma (CTCL) [1]. In most patients, MF runs an indolent clinical course for years to decades, but in approximately 25% of patients, progression to advanced-stage MF is observed [2, 3]. The prognosis of MF depends on the type and extent of skin lesions and the presence of extracutaneous disease. Early-stage MF is characterized by the presence of patches and/or plaques covering less than 10% (stage IA) or 10% or more of the body surface area (stage IB). Several studies reported that patients presenting with both patches and plaques have a higher risk of progression to advanced-stage MF and a worse survival than patients presenting with only patches [3-5]. Therefore, the distinction between patches and plaques is clinically relevant, but it can be difficult due to a lack of standardized and reproducible criteria [6]. In the current classification system, differentiation between patches and plaques is based exclusively on clinical examination. Patches are defined as skin lesions without significant elevation or induration, while plaques are defined as skin lesions with elevation or induration [7]. However, this definition is subjective and prone to considerable inter-observer variability [6]. Previous studies on folliculotropic MF (FMF) found that a clinicopathologic approach, combining clinical and histopathological criteria, can facilitate the distinction between early and advanced plaque-stage disease [8, 9]. At recent meetings, the question was raised whether histopathologic criteria, in particular the extent and depth of the infiltrates, could also facilitate the distinction between patches and plaques in classical MF. The infiltrates in plaques in classical MF are indeed generally denser and deeper than in patches [6, 10]. However, studies investigating whether these differences may contribute to a more reliable distinction between patches and plaques have not been published thus far. In the present study, we investigated the extent and depth of the infiltrate in patches and plaques in classic MF to find out if these histopathological criteria can serve as an adjunct to differentiate between these two types of lesions.

Using a database of scanned HE stained sections obtained from pretreatment biopsies of patients with early-stage classical MF, 100 cases with variable extent and depth of the infiltrates were selected without knowledge of the clinical data. Corresponding clinical records and clinical images of the biopsied lesions were evaluated and, blinded to the histopathologic characteristics, scored as either patch or plaque by three individual dermatologists using ISCL/EORTC criteria described previously [7]. In case of discrepancy (< 5% of lesions) cases were discussed together and consensus was reached. In the total group of 100 cases with early-stage classical MF, 66 lesions were classified as patches and 34 as plaques. In all cases, the diagnosis was confirmed by an expert panel from the Dutch Cutaneous Lymphoma Tumor Group. Based on the extent and depth of the infiltrates, four histopathological categories were distinguished: (1) minimal or mild infiltrate in the upper dermis; (2) moderately dense infiltrate in the upper dermis; (3) thick band-like infiltrate in the upper dermis; (4) infiltrate extending into the deep dermis/subcutis (Figure 1). All scanned HE-stained sections were independently scored into one of these four categories by five dermatopathologists with ample experience in cutaneous lymphoma (TD, PV, AS, PJ, and RW), who were blinded to the clinical data. For HE-stained sections where there was no initial consensus, a pathologist meeting was held and consensus was reached.

The results showed that 17% of cases were classified as category 1, 45% as category 2, 16% as category 3, and 22% as category 4. Correlation between clinical and histopathological scores showed that 15 of 17 (88%) cases in category 1 originated from clinically defined patches and only 2 of 17 (12%) from clinically defined plaques. Also, cases classified as category 2 predominantly arose from patches (30/45; 67%) compared to plaques (15/45; 33%). Cases classified as category 3 and, remarkably, also cases classified as category 4 were distributed equally between patches (category 3: 8/16; 50%; category 4: 12/22; 55%) and plaques (category 3: 8/16; 50%; category 4: 10/22; 45%) (Figure 2). These results suggest that lesions with a minimal to mild infiltrate in the upper dermis (category 1) most likely represent a patch (88%). However, the observation that infiltrates extending into the deep dermis/subcutis (category 4) are found not only in plaques but also in patches implies that the extent and depth of the infiltrate cannot be considered reliable criteria in differentiating between patches and plaques.

Notably, our study focused on the total lymphohistiocytic infiltrate, including both tumor and reactive cells. The study of the extent and depth of only neoplastic T-cells would be of more interest but is generally not possible due to a lack of tumor-specific markers.

In a recent survey, cutaneous lymphoma experts indicated that the distinction between thin and thick plaques may be important, since it may have prognostic and therapeutic significance as described in FMF [6, 8, 9]. In the present study, no attempt was made to differentiate between thin and thick plaques, mainly because defining criteria for these lesions are lacking [6]. Whether patches showing infiltration of the deep dermis have an increased risk of disease progression compared with patches with a minimal to mild superficial infiltrate could not be evaluated because of the low number of events in this group.

In summary, a broad panel of cutaneous lymphoma experts emphasized recently the need for well-defined and reproducible histopathological criteria to differentiate between patches and plaques in early-stage MF [6]. However, the results of the present study suggest that assessment of the extent and depth of the total infiltrate solely by histopathology has limited value in differentiating these two types of lesions. Other histopathological criteria, such as the number of blast cells, CD30 expression, or composition of the inflammatory infiltrate may be important as well. Whether histopathology combined with other diagnostic tools as ultrasound, magnetic resonance imaging, or artificial intelligence-based models can contribute to a better definition of plaques and their differentiation from patches requires further studies [7, 11, 12].

The study was evaluated by the ethics committee of the Leiden University Medical Center and provided with a waiver of consent.

The authors declare no conflicts of interest.

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来源期刊
CiteScore
3.20
自引率
5.90%
发文量
174
审稿时长
3-8 weeks
期刊介绍: Journal of Cutaneous Pathology publishes manuscripts broadly relevant to diseases of the skin and mucosae, with the aims of advancing scientific knowledge regarding dermatopathology and enhancing the communication between clinical practitioners and research scientists. Original scientific manuscripts on diagnostic and experimental cutaneous pathology are especially desirable. Timely, pertinent review articles also will be given high priority. Manuscripts based on light, fluorescence, and electron microscopy, histochemistry, immunology, molecular biology, and genetics, as well as allied sciences, are all welcome, provided their principal focus is on cutaneous pathology. Publication time will be kept as short as possible, ensuring that articles will be quickly available to all interested in this speciality.
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