2014-由闰细胞和嗜酸细胞成分组成的KIAA1217::RET基因融合的支气管唾液腺型导管内癌
摘要
涎腺型导管内癌Salivary gland–type intraductal carcinoma(IC)是一种罕见的涎腺恶性肿瘤。原发性唾液腺-IC型从未在肺部被描述过。在此，我们报告一例63岁女性的原发性肺部IC。肿瘤起源于右中叶的支气管壁。肿瘤由两种组织类型组成，即闰细胞成分和嗜酸细胞成分。呈管状/囊性，由柱状至立方形细胞和散在的粘液细胞组成。嗜酸细胞成分显示由具有丰富嗜酸性颗粒细胞质的大细胞组成的实性巢。免疫组织化学显示，两种组织成分均为细胞角蛋白7 (CK7)、S-100蛋白、SOX10和mammaglobin阳性。p63和平滑肌肌动蛋白(SMA)突出边缘肌上皮细胞。肿瘤细胞对雄激素受体(AR)、HER-2、Dog-1、TTF-1、napsin A、GCDFP-15和GATA3呈阴性。在目前的病例中，我们通过基于DNA的新一代测序(NGS)和RT-PCR检测到KIAA1217::RET融合，这在分子水平上建立了IC的诊断。本病例扩展了支气管肺唾液腺型肿瘤的分类。
图1胸部CT、肺窗(A)和软组织窗(B)显示一个16毫米的支气管内肿块(箭头)几乎完全阻塞了支气管腔。
图2组织病理学特征。肿瘤显示腺泡和腺结构在支气管镜活检(A)。低倍镜下，肿瘤图案(D)。显示低级别核异型性的巢中肿瘤细胞具有推进的边界，不涉及肺实质(B)。和丰富的嗜酸性颗粒细胞质(突出显示的是肿瘤附近的正常浆液粘液腺(右)(左)(C)。高倍)(E)。管状/囊状区由粘液细胞组成。肿瘤呈两种生长方式:实性巢状和管状/囊状、立方体状细胞和一些散在的粘液细胞(箭头)。在管腔中可以发现嗜酸性分泌物(F)
图3免疫组织化学染色。肿瘤细胞对CK7 (A)、S-100蛋白(B)、SOX10 (C)和mammaglobin呈阳性，p63在管状/囊性区域(E)和实体巢(F)中突出显示。(四)。粘液细胞的S-100蛋白、SOX10呈阴性，肌上皮细胞的SMA呈阳性(G)。肿瘤细胞是mammaglobin(B、C和D中的箭头)。肌上皮细胞AR (H)阴性。Ki-67染色了5%的肿瘤细胞(I)。
图4 KIAA1217::RET融合。NGS检测到KIAA1217::RET的融合(KIAA1217外显子10与RET外显子11融合)(A)。基于RNA的Sanger测序证实KIAA1217::RET融合(B)。
讨论：
支气管壁的浆液粘液腺可产生与头颈部的唾液腺型肿瘤组织学上相同的肿瘤。原发性肺唾液腺型癌是一种罕见的恶性肿瘤。仅占所有原发性肺肿瘤的1%。MEC和腺样囊性癌是肺唾液腺型肿瘤中最常见的亚型；一些罕见的亚型，如上皮-肌上皮癌，SC ，涎腺导管癌(SDC) ，肌上皮癌，乳头状涎腺腺瘤和透明细胞癌可以在以前的报告中找到。IC传统上发生在头颈部的腮腺。在此，我们首次报告一例原发性支气管唾液腺-IC型。
先前的研究已经认识到IC的三种不同的形态学亚型:闰管型、顶泌型和闰顶泌混合型。最近，嗜酸细胞型被认为是IC的一种新亚型。在本例中，管状/囊性成分位于IC型闰管。
我们病例中的实性巢含有丰富的嗜酸性颗粒细胞质嗜酸细胞型IC的组织学特征。S-100蛋白和SOX10在腺细胞中的阳性染色也提示闰管型和嗜酸细胞型IC的诊断。顶泌分化，如顶端开口和管腔细胞质断头，在本例中没有发现。免疫组织化学方面，与闰管型和嗜酸细胞型不同，顶泌型IC通常AR和GCDFP-15阳性，S-100蛋白、SOX10和mammaglobin阴性。
大多数涎腺IC含有重复性RET基因重排，这在其他涎腺型肿瘤中几乎不存在。NCOA4::RET融合在大约一半具有润管形态的ICs中被发现。此外，混合闰管/顶泌型或顶泌型ICs的一个子集显示TRIM27::RET融合。最近，新的融合，TUT1::ETV5，KIAA1217::RET ，TRIM33::RET和STRN::ALK 和BRAF V600E突变在ICs 中被鉴定。在我们的病例中，KIAA1217::RET融合蛋白被NGS和RT-PCR证实，这在分子水平上建立了IC的诊断。BRAF V600E突变可能是嗜酸细胞的潜在特征。我们在本案中没有发现这种变化。
Bronchial salivary gland-type intraductal carcinoma with KIAA1217::RET gene fusion composed of intercalated and oncocytic components
Lin Song et al. Virchows Arch. 2022.
2015-Spitz nevus, chubby cell type, with ALK rearrangement
Details: 13, XY, malar. Impression was irritated nevus vs. PG.
Immunostains: p16, ROS1, ALK.
When I encounter a papular melanocytic tumor with long sweeping fascicles of fusiform melanocytes, my first thought is ALK rearrangement. It's actually a situation of ALK vs. ROS1 rearrangement, since the two can be lookalikes. With that in mind, a pattern that can throw you off your game in terms of Spitz nevus recognition is the chubby cell type (or plump cell type, if you prefer) of ALK fused Spitz nevus. Because the pattern is not long and streaming, things can be quite a bit different.
That's the situation here. After seeing these slides, my immediate impression was that it must be a fascicular Spitz, even though fascicular morphology is not as striking as it can be in many other tumors. As you review the 4 fixed pics of the H/E and the p16 stain, and also as you manipulate the WSI, you can see an occasional fascicle as the morphologic clue to what's going on.
What I opted to add was both ROS1 and ALK immunostains. I figured the ROS1 was a longshot, but since the two entities are lookalikes, I figured it was better to complete both. ALK immunostaining ended up +++ and ROS1 was not expressed, and the diagnosis of chubby cell subtype of ALK-fused Spitz nevus was formulated.
2016-Acral CMN with partial PRAME positivity
Details: 70, XX, dorsal 2nd toe. Impression was 3 mm gray-brown macule; nevus, R/O atypia.
Immunostaining: PRAME.
You can manipulate the WSI and make your own diagnostic conclusions. This case ended up with me to sort out the significance of the PRAME positivity, and my take is that there is not enough atypicality to support a diagnosis of MIS over a melanocytic nevus. Rather, this represents a melanocytic nevus with anomalous (or perhaps is is more accurate to say non-meaningful) expression of PRAME. An unordered list of quick points is below.
It's pretty common to find non-meaningful expression of PRAME in conjunction with lentiginous melanocytic nevi or acral melanocytic nevi.
In the two H/E photomicrographs, notice that it's challenging to see intracorneal pigment columns. I like to look for this feature, since it's a significant criterion to support a diagnosis of acral melanocytic nevus. If you have evenly spaced, well-formed columns, you know the structure of the tumor is orderly. Even though the columns are not easily seen in routine stains, they are often easy to see (or at least easier to see) in immunostains.
I would not have been inclined to complete PRAME staining in this kind of case. My concern for a second population, based on the H/E, is low. If I did any staining, it might have been a p16. Or perhaps the case would have been reported with no immunohistochemistry at all.
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