Diagnosis and Discussion - Case 1127

Final Diagnosis

The case was diagnosed as superficial ALK-rearranged myxoid spindle cell neoplasm (SAMS).

Discussion

In 1994, Anaplastic lymphoma kinase (ALK) was first described in anaplastic large-cell lymphoma (ALCL)1. ALK is involved in normal brain development and tumorigenesis. ALK gene is located at chromosome region 2p23.2 and encodes a receptor tyrosine kinase (RTK)2. Many epithelioid and spindle cell neoplasms are related to ALK gene rearrangement ( point mutation, gene amplification, and gene fusions. Carcinomas involving thyroid, lung, kidney and others in addition to mesenchymal neoplasms such as gastrointestinal stromal tumor (GIST), inflammatory myofibroblastic tumor, epithelioid fibrous histiocytoma (EFH), and melanocytic neoplasms3,4,5.

Superficial ALK-rearranged myxoid spindle cell neoplasm (SAMS) is a recently described entity by Dermawan et al, characterized by a whorly concentric pattern, set in myxoid or myxocollagenous stroma. The tumor cells are spindled, ovoid to epithelioid-like- cells with minimal to mild nuclear atypia and low mitotic activity (<1/10 high power fields). Other morphologic features such as hyalinized blood vessels, tumor-infiltrating lymphocytes, and lipofibromatosis-like areas were also identified in this series. The tumor cells coexpress CD34 and S100 immunostains while lacking SOX10 staining. Next-generation Sequencing (NGS) detected ALK gene fusions with partner genes including ( FLNA, MYH10, and HMBOX1). Most of the reported SAMS cases show indolent behavior with no recurrence6.

Our case showed a similar morphologic and immunophenotype of SAMS, confirmed by  FISH studies for ALK gene rearrangement.

References

  1. Shiota M, Fujimoto J, Semba T, Satoh H, Yamamoto T, Mori S.Hyperphosphorylation of a novel 80k Da protein-tyrosine kinase similar to Ltkina  humanKi-1 lymphoma cellline,  AMS3.Oncogene1994,9, 1567–1574. [PubMed]

  2. Lin, J.J.; Riely, G.J.; Shaw, A.T. Targeting ALK: Precision MedicineTakes on Drug  Resistance.CancerDiscov. 2017; (7)137–155. [CrossRef][PubMed].

  3. Galea LA, Hildebrand MS, Witkowski T, et al. ALK-rearranged renal cell carcinoma with TPM3::ALK gene fusion and review of the literature. Virchows Arch. 2023;482(3):625e633.

  4. Young LC, Takeuchi K, Soda M, et al. Identification of novel isoforms of the EML4-ALK transforming gene in non-small cell lung cancer. Cancer Res. 2008;68(13):4971-4976. doi:10.1158/0008-5472.CAN07-6158

  5. Sugawara E, Togashi Y, Kuroda N, et al. Identification of anaplastic lymphoma kinase fusions in renal cancer: large-scale immunohistochemical screening by the intercalated antibody-enhanced polymer method. Cancer. 2012;118(18):4427-4436. doi:10.1002/CNCR. 27391

  6. Dermawan JK, Azzato EM, Goldblum JR, Rubin BP, Billings SD, Ko JS, et al. Superficial ALK-rearranged myxoid spindle cell neoplasm: a cutaneous soft tissue tumor with distinctive morphology and immunophenotypic profile. Mod Pathol.2021; 34(9):1710–8. doi: 10.1038/s41379-021-00830-w