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Tissue pathogens are commonly encountered in histopathology and cytology practice, where they can present as either benign mimickers of malignancy or true malignancies. The aim of this review is to provide a timely synthesis of our understanding of these tissue pathogens, with an emphasis on pertinent diagnostic conundrums associated with the benign mimickers of malignancy that can be seen with viral infections and those which manifest as granulomas. The oncogenic pathogens, including viruses, bacteria, and parasites, are then discussed with relationship to their associated malignancies. Although not exhaustive, the epidemiology, clinical manifestations, pathogenesis, and histological findings are included, along with a short review of emerging therapies.

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Objectives NTRK-rearranged spindle cell neoplasms (other than infantile fibrosarcoma) are an emerging entity of tumors that demonstrate wide variation in clinical and histopathologic features. We report a case of an NTRK-rearranged spindle cell neoplasm bearing a deceptively bland morphology. Methods We performed histopathologic, immunohistochemical, and molecular evaluation on resection tissue. We also conducted a literature review on adult NTRK3-rearranged spindle cell neoplasms. Results The tumor presented as a recurrent ankle mass in an elderly patient. Histologically, it was composed of bland spindle cells set in a fibrous to edematous stroma. Blood vessels were interspersed with subtle perivascular hyalinization and scattered lymphoid aggregates. Immunohistochemically, the spindle cells expressed CD34 and S100 while being negative for SOX10. The tumor also showed cytoplasmic reactivity for pan–tyrosine receptor kinase immunohistochemistry. Next-generation sequencing identified an NTRK3-SQSTM1 fusion. To the best of our knowledge, this fusion pair has not been previously reported in adult NTRK-rearranged mesenchymal tumors. Conclusions Altogether, this rare and diagnostically challenging case of an NTRK3-rearranged spindle cell tumor with low-grade morphology is in contrast to many of the reported adult NTRK3-rearranged mesenchymal tumors. Recognition of low-grade NTRK-rearranged tumors demands close attention to clues in morphology and immunoprofiles.