Suchi, Mariko

Nodular fasciitis is a rapidly growing soft tissue tumor that typically arises in children and young adults. Histologically, it consists of short, sweeping, and intersecting fascicles of bland-appearing myofibroblasts. The majority of nodular fasciitis lesions harbor rearrangements involving the ubiquitin-specific protease 6 ( USP6 ) gene. Most lesions are benign, with a tendency to regress spontaneously or remain stable following conservative excision. However, rare cases have shown clinically aggressive behavior, including distant metastasis. More recently, morphologic variants with malignant features have also been reported. We present a 20-month-old boy who developed a rapidly enlarging facial mass following blunt trauma. The excised mass revealed a variant of nodular fasciitis displaying marked cellular pleomorphism and frequent atypical mitotic figures. Molecular analysis identified a COL3A1::USP6 fusion and a TP53 Y234C mutation. While the majority of facial lesions referred to plastic surgeons for excision are benign, this case highlights the need for a broad differential diagnosis that includes both benign and potentially malignant entities. It also emphasizes the importance of multidisciplinary evaluation and management in patients with complex and unusual pathologic diagnoses.

Abstract ALK-positive histiocytosis is a rare subtype of histiocytic neoplasm first described in 2008 in 3 infants with multisystemic disease involving the liver and hematopoietic system. This entity has subsequently been documented in case reports and series to occupy a wider clinicopathologic spectrum with recurrent KIF5B-ALK fusions. The full clinicopathologic and molecular spectra of ALK-positive histiocytosis remain, however, poorly characterized. Here, we describe the largest study of ALK-positive histiocytosis to date, with detailed clinicopathologic data of 39 cases, including 37 cases with confirmed ALK rearrangements. The clinical spectrum comprised distinct clinical phenotypic groups: infants with multisystemic disease with liver and hematopoietic involvement, as originally described (Group 1A: 6/39), other patients with multisystemic disease (Group 1B: 10/39), and patients with single-system disease (Group 2: 23/39). Nineteen patients of the entire cohort (49%) had neurologic involvement (7 and 12 from Groups 1B and 2, respectively). Histology included classic xanthogranuloma features in almost one-third of cases, whereas the majority displayed a more densely cellular, monomorphic appearance without lipidized histiocytes but sometimes more spindled or epithelioid morphology. Neoplastic histiocytes were positive for macrophage markers and often conferred strong expression of phosphorylated extracellular signal-regulated kinase, confirming MAPK pathway activation. KIF5B-ALK fusions were detected in 27 patients, whereas CLTC-ALK, TPM3-ALK, TFG-ALK, EML4-ALK, and DCTN1-ALK fusions were identified in single cases. Robust and durable responses were observed in 11/11 patients treated with ALK inhibition, 10 with neurologic involvement. This study presents the existing clinicopathologic and molecular landscape of ALK-positive histiocytosis and provides guidance for the clinical management of this emerging histiocytic entity.