Abdominal Inflammatory Myofibroblastic Tumor: Minimal Inflammatory Infiltrate and Diffuse Immunoreactivity for Caldesmon are Potential Diagnostic Pitfalls

Introduction/Objective Inflammatory myofibroblastic tumor (IMT) is an uncommon spindle cell lesion that can involve various organs and occurs in multiple body sites. While older terminology (i.e. inflammatory pseudotumor) suggested otherwise, recent molecular studies point toward a neoplastic pathogenesis for IMTs. Herein, we report a case of an abdominal IMT and discuss the morphologic and immunohistochemical pitfalls pertaining to this entity. Methods A 75-year-old woman presented with complaints of generalized abdominal pain and distention. An abdominal CT scan showed multiple peritoneal masses, the largest of which measured 23 cm. Biopsy revealed compact fascicles of bland spindle cells exhibiting diffuse actin and caldesmon immunoreactivity, consistent with a spindle cell tumor with smooth muscle differentiation. Mitotic activity was low-to-unapparent. Surgical excision was performed. The cut surface of the tumor was tan-white with hemorrhagic foci. Histopathologic examination of the tumor showed elongated spindle cells set in a loose myxoid stroma rich in blood vessels and a mixed inflammatory infiltrate. Deeper sections of the tumor were more cellular, showing a similar morphology to that seen in the original biopsy, which was virtually devoid of inflammatory cells. Immunohistochemistry showed diffuse staining for desmin, caldesmon, smooth muscle actin, and ALK. FISH analysis showed ALK gene rearrangement in 52% of tumor cells, confirming the diagnosis of IMT. Results Studies in the literature show that IMTs express smooth muscle markers such as SMA (90%) and desmin (50%). However, immunoreactivity for caldesmon is rarely reported. ALK immunoreactivity is seen in about 35–60% of cases, and when gene rearrangement involving ALK is detected the diagnosis can be confirmed. Conclusion Historically, several terms have been used to describe IMTs, including inflammatory pseudotumor and inflammatory pseudosarcomatous fibromyxoid tumor. While the nomenclature consistently implies an inflammatory infiltrate, this tumor could have various morphological patterns with some areas showing very little to absent inflammation, as demonstrated in our case. Hence, making an accurate diagnosis could be challenging on a limited biopsy. Therefore, ALK testing should be included as part of the diagnostic workup of spindle cell neoplasms with smooth muscle differentiation.

Patterning the embryonic pulmonary mesenchyme

Smooth muscle guides morphogenesis of epithelia during development of several organs, including the mammalian lung. However, it remains unclear how airway smooth-muscle differentiation is spatiotemporally patterned and whether it originates from distinct mesenchymal progenitors. Using single-cell RNA-sequencing of embryonic mouse lungs, we show that the pulmonary mesenchyme contains a continuum of cell identities, but no distinct progenitors. Transcriptional variability correlates with sub-epithelial and sub-mesothelial mesenchymal compartments that are regulated by Wnt signaling. Live-imaging and tension sensors reveal patterned migratory behaviors and cortical forces in each compartment, and show that sub-epithelial mesenchyme gives rise to airway smooth muscle. Differentiation trajectory reconstruction reveals that cytoskeleton, adhesion, and Wnt signaling pathways are activated early in differentiation. Finally, we show that Wnt activation stimulates the earliest stages of differentiation and induces local accumulation of mesenchymal F-actin, which influences epithelial morphology. Our work provides the first single-cell view of pulmonary mesenchymal patterning during branching morphogenesis.