Primary Cutaneous Neoplasm With Rhabdomyosarcomatous Differentiation and a Melanoma-Like Mutational Landscape.

IF 1.6 4区 医学 Q3 DERMATOLOGY
Maximillian A Weigelt, Shinoj Pattali, Josephine K Dermawan, Jennifer S Ko, Karen J Fritchie, Steven D Billings
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Abstract

Malignant melanoma (MM) is notorious for its wide range of morphologic variability. Rarely, MM may lose all melanocytic markers and adopt the morphologic and immunophenotypic characteristics of a different neoplasm in a process known as trans-differentiation (TMM). Distinguishing TMM from primary cutaneous neoplasms may be challenging and is often dependent on the identification of an adjacent conventional melanoma. In particularly difficult cases, molecular analysis may be helpful; TMMs are known to exhibit highly similar mutational landscapes to conventional melanomas (e.g., mutations in NF1, NRAS; variable BRAF V600E). Herein, we present an exceedingly rare case of likely TMM with rhabdomyosarcomatous differentiation in which high tumor mutational burden (TMB) was an important clue to the diagnosis. An 83-year-old woman presented with an 8.2 cm fungating mass on the upper arm. Biopsy revealed a sheet-like proliferation of mitotically active pleomorphic cells which were positive for myogenin/MyoD1 and negative for S100/SOX10. A diagnosis of epithelioid rhabdomyosarcoma was rendered. Subsequent axillary lymph node metastasis prompted whole exome sequencing, which revealed a molecular signature more indicative of MM, including: high TMB (19 mutations/Mb); ultraviolet mutational signature (i.e., preponderance of C>T base changes); TERT promoter mutation; and ARID2 mutation. After discussion at the interdisciplinary tumor board, a diagnosis of TMM was considered most likely, and the patient was initiated on pembrolizumab. Morphologic features more typical of MM than cutaneous sarcomas, such as tumor-infiltrating lymphocytes, junctional epidermal tumor nests, and satellitosis, may provide further clues to the accurate diagnosis of TMM, which has important prognostic and therapeutic implications for the patient.

原发性皮肤肿瘤伴横纹肌肉瘤分化和黑色素瘤样突变景观。
恶性黑色素瘤(MM)是臭名昭著的广泛的形态变异性。罕见的是,MM可能会失去所有的黑素细胞标记物,并在称为反式分化(TMM)的过程中采用不同肿瘤的形态学和免疫表型特征。区分TMM与原发性皮肤肿瘤可能具有挑战性,并且通常依赖于相邻传统黑色素瘤的识别。在特别困难的情况下,分子分析可能会有所帮助;已知TMMs表现出与传统黑色素瘤高度相似的突变景观(例如,NF1, NRAS;可变BRAF V600E)。在此,我们报告一例极为罕见的可能为横纹肌肉瘤分化的TMM病例,其中高肿瘤突变负荷(TMB)是诊断的重要线索。一位83岁女性,上臂有一个8.2厘米的真菌性肿块。活检显示有丝分裂活性多形性细胞呈片状增生,肌原素/MyoD1阳性,S100/SOX10阴性。诊断为上皮样横纹肌肉瘤。随后的腋窝淋巴结转移促使全外显子组测序,揭示了更能指示MM的分子特征,包括:高TMB(19个突变/Mb);紫外突变特征(即c>t碱基的优势改变);TERT启动子突变;和ARID2突变。在跨学科肿瘤委员会讨论后,TMM的诊断被认为是最有可能的,并且患者开始使用派姆单抗。与皮肤肉瘤相比,MM更典型的形态学特征,如肿瘤浸润淋巴细胞、表皮结瘤巢、卫星状增生等,可能为TMM的准确诊断提供进一步的线索,对患者的预后和治疗具有重要意义。
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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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