Recent work has identified distinct molecular subgroups of acute myeloid leukemia (AML) with implications for disease classification and prognosis. AML with mutated NPM1 (AML-NPM1) represents a distinct entity in the revised 2017 World Health Organization classification, but relatively little work has examined the clinical significance of phenotypic and genetic heterogeneity within this group. A multi-institutional cohort of 239 AML-NPM1 cases included 3 phenotypic groups: cases with blasts showing monocytic differentiation (n = 93; monocytic AML-NPM1), cases lacking monocytic differentiation (n = 72; myeloid AML-NPM1), and cases where blasts were negative for both CD34 and HLA-DR (n = 74; double-negative [DN] AML-NPM1). Genotypic diversity typical of AML-NPM1 was seen, with comutations occurring most commonly in DNA methylation genes (81% of cases), FLT3 (48%; including internal tandem duplication and tyrosine kinase domain mutations), and RAS pathway genes (30%). However, the comutation pattern differed by blast phenotype. TET2 and IDH1/2 mutations were significantly more common in DN AML-NPM1 (96% of cases) than in myeloid (39%) or monocytic AML-NPM1 (48%; P < .0001). Conversely, DNMT3A mutations were significantly less common in DN AML-NPM1 (27%) than in myeloid (44%) or monocytic cases (54%; P = .002). Furthermore, the 3 phenotypic groups showed significant differences in outcome, with DN AML-NPM1 showing significantly longer relapse-free (RFS) and overall survival (OS) (64.7 and 66.5 months, respectively) than monocytic AML-NPM1 (RFS, 20.6 months; OS, 44.3 months) or myeloid AML-NPM1 (RFS, 8.4 months; OS, 20.2 months; P < .0001 and P = .01 for RFS and OS, respectively). Our findings highlight biologic differences within immunophenotypically defined subgroups of NPM1-mutated AML that may impart prognostic significance.

Spermatocytic seminoma is a rare germ cell tumor distinct from classical seminoma, both clinically and pathologically. It affects older men, has not been associated with a history of cryptorchidism, and has no known counterpart in ovary or any other site. Pathologically, it is characterized by 3 distinct cell types, lack of cytoplasmic glycogen, and scant to absent lymphocytic infiltrate. Gain of chromosome 9 is the most consistent genetic abnormality. There have been few case reports of sarcomas arising in spermatocytic seminoma and only an occasional report of metastasis. It is important to differentiate this condition from its frequent mimics, such as classic seminoma and embryonal carcinoma, because patients with spermatocytic seminoma may not require further treatment after surgery.