Clinicopathological and molecular features of indolent natural killer‐cell lymphoproliferative disorder of the gastrointestinal tract

Abstract

Clinicopathological and molecular features of indolent natural killer-cell lymphoproliferative disorder of the gastrointestinal tractAims: Indolent natural killer (NK) cell lymphoproliferative disorder of the gastrointestinal (GI) tract (iNKLPD) is a rare, recently recognised neoplasm. Most of the reported tumours are confined to the GI tract, while a small subset of the tumours harbour JAK3 mutations. We collected four cases of iNKLPD with the goal of adding additional information to the current knowledge of this disease regarding the clinicopathological, immunohistochemical and molecular features. Methods and results: Similar features including medium-to large-sized lymphoid cells with variable amounts of pale or slightly eosinophilic cytoplasm, and no evidence of EBER, TCR rearrangement were found in four cases. JAK3 K563_C565del mutation was found in one of three cases that were subjected to targeted next-generation sequencing. Unique findings of our study include one iNKLPD encountered for the first time in nasopharynx, where lesions could be inadvertently diagnosed as extranodal NK/T cell lymphoma, and one iNKLPD located in the gallbladder extended deeply into muscular and adventitial layers. Exceptional CD8-positive expression was observed in one iNKLPD. In addition, positive staining of phospho-STAT5, phospho-STAT3 and phospho-p38 were found in our cases. None of the four patients received therapy for lymphoma, but all had a benign clinical outcome during a follow-up time of 20-99 months. Conclusions: We present four iNKLPDs with clinical, immunohistochemical and molecular features similar to the reported cases, as well as some unusual characters, which expand our knowledge on this disease, and further support the neoplastic nature of iNKLPDs.

A case of excisionally remitted indolent NK‐cell enteropathy in the oral cavity and a mini‐review

“…Nevertheless, studies have identified JAK3 K563_C565del mutations in 30% of patients with NKCE. 17,21 However, JAK3 mutations have also been observed in various types of T-and NK-cell lymphomas, indicating that they are not specific to the NKCE process.…”

“…Furthermore, the clonality of NK cells makes it difficult to determine whether NKCE represents reactive or neoplastic growth. Nevertheless, studies have identified JAK3 K563_C565del mutations in 30% of patients with NKCE 17,21 . However, JAK3 mutations have also been observed in various types of T‐ and NK‐cell lymphomas, indicating that they are not specific to the NKCE process.…”

B- and T-/NK-Cell Lymphomas in the 2022 International Consensus Classification of Mature Lymphoid Neoplasms and Comparison with the WHO Fifth Edition

“…Both systems recognized indolent NK-cell lymphoproliferative disorder, which is newly added to both classification systems and replaces the term NK-cell enteropathy and lymphomatoid gastropathy [33,34]. Recent mutational studies have provided evidence that this is indeed a neoplasm associated with recurrent mutations in JAK3 [35,36].…”