ALK -rearranged Mesenchymal Neoplasms With Prominent Foamy/Pseudolipogenic Cell Morphology : Expanding the Phenotypic Spectrum of ALK Fusion Neoplasms and Report of Novel Fusion Partners.

IF 4.5 1区 医学 Q1 PATHOLOGY
American Journal of Surgical Pathology Pub Date : 2024-11-01 Epub Date: 2024-07-09 DOI:10.1097/PAS.0000000000002283
Abbas Agaimy, Robert Stoehr, Cyril Fisher, John S A Chrisinger, Elizabeth G Demicco, Lars Tögel, Michal Michal, Michael Michal
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引用次数: 0

Abstract

The category of ALK -rearranged mesenchymal neoplasms has been evolving rapidly, with reports of morphologically diverse lesions of cutaneous, soft tissue, and visceral origin. While some of these represent morphologically defined entities harboring recurrent ALK fusions (inflammatory myofibroblastic tumor and epithelioid fibrous histiocytoma), others are unclassified by morphology with variable overlap with the tyrosine kinase family of neoplasia and their underlying ALK fusions cannot be suspected based on morphology. We herein report 3 cases that expand the anatomic, morphologic, and genotypic spectrum of ALK -rearranged unclassified neoplasms. Patients were all adults aged 46 to 69 (median: 63) who presented with a mass located in the gingiva, subcutis of the back, and submucosal posterior pharyngeal wall. The tumor size ranged from 1 to 2.7 cm (median: 1.6). Conservative surgery was the treatment in all patients. Follow-up was available for one patient who remained disease-free at 14 months. Histologically, all tumors displayed large polygonal cells with foamy to granular and lipogenic-like microvacuolated copious cytoplasm and medium-sized round nuclei with 1 or 2 prominent nucleoli. Mitoses and necrosis were not seen. The initial diagnostic impression was PEComa, inflammatory rhabdomyoblastic tumor and unclassified pseudolipogenic neoplasm. Strong cytoplasmic ALK was detected by immunohistochemistry in all cases. Other positive markers include Cathepsin K (2/2), desmin (1/3), focal MyoD1 (1/1), focal SMA (1/3), and focal EMA (1/2). Targeted RNA sequencing revealed ALK fusions with exon 20 (2 cases) and exon 19 (one case) of ALK fused to RND3 (exon 3), SQSTM1 (exon 6), and desmin (intron 6). Methylation profiling in the desmin-fused case (initially diagnosed as inflammatory rhabdomyoblastic tumor) revealed an inflammatory myofibroblastic tumor match with a low confidence score of 0.5 and a flat copy number variation (CNV) profile. No NF1 mutation was detected in this case, altogether excluding an inflammatory rhabdomyoblastic tumor. Our study highlights and expands the morphologic and anatomic diversity of ALK- fused neoplasms and documents novel fusion partners ( RND3 and desmin).

ALK重排间充质肿瘤具有明显的泡沫/假脂肪细胞形态:扩大 ALK 融合肿瘤的表型范围并报告新型融合伙伴。
ALK重排间叶肿瘤的类别发展迅速,有报道称皮肤、软组织和内脏来源的病变形态各异。其中一些代表了形态学上明确的、携带复发性 ALK 融合的实体(炎症性肌纤维母细胞瘤和上皮样纤维组织细胞瘤),而另一些则是形态学上未分类的、与酪氨酸激酶家族肿瘤有不同程度重叠的肿瘤,而且根据形态学无法怀疑其潜在的 ALK 融合。我们在此报告了 3 个病例,这些病例扩大了 ALK 重组未分类肿瘤的解剖、形态和基因型范围。患者均为成年人,年龄在 46 岁至 69 岁之间(中位数:63 岁),表现为位于牙龈、背部皮下和咽后壁粘膜下的肿块。肿瘤大小从 1 厘米到 2.7 厘米不等(中位数:1.6 厘米)。所有患者均接受了保守性手术治疗。一名患者接受了随访,14 个月后仍未复发。从组织学角度看,所有肿瘤均为大的多角形细胞,具有泡沫状至颗粒状和脂原样微空泡的丰富细胞质,中等大小的圆形细胞核具有 1 至 2 个突出的核小体。未见有丝分裂和坏死。初步诊断印象是 PEComa、炎性横纹肌母细胞瘤和未分类的假脂源性肿瘤。免疫组化在所有病例中均检测到强细胞质 ALK。其他阳性标记物包括Cathepsin K(2/2)、desmin(1/3)、灶性MyoD1(1/1)、灶性SMA(1/3)和灶性EMA(1/2)。靶向 RNA 测序发现 ALK 与 RND3(3 号外显子)、SQSTM1(6 号外显子)和 desmin(6 号内含子)的 20 号外显子(2 例)和 19 号外显子(1 例)融合。对融合了 desmin 的病例(最初诊断为炎性横纹肌母细胞瘤)进行甲基化分析后发现,该病例与炎性肌纤维母细胞瘤相匹配,置信度低至 0.5 分,且拷贝数变异(CNV)曲线平坦。该病例未检测到 NF1 基因突变,因此完全排除了炎性横纹肌母细胞瘤的可能性。我们的研究强调并扩展了ALK融合肿瘤在形态学和解剖学上的多样性,并记录了新的融合伙伴(RND3和desmin)。
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来源期刊
CiteScore
10.30
自引率
5.40%
发文量
295
审稿时长
1 months
期刊介绍: The American Journal of Surgical Pathology has achieved worldwide recognition for its outstanding coverage of the state of the art in human surgical pathology. In each monthly issue, experts present original articles, review articles, detailed case reports, and special features, enhanced by superb illustrations. Coverage encompasses technical methods, diagnostic aids, and frozen-section diagnosis, in addition to detailed pathologic studies of a wide range of disease entities. Official Journal of The Arthur Purdy Stout Society of Surgical Pathologists and The Gastrointestinal Pathology Society.
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