ABSTRACT
We report the histological, immunohistochemical, and molecular findings of a dedifferentiated liposarcoma with inflammatory myofibroblastic tumor-like features occurring in the paratesticular region. Histologically, the dedifferentiated component closely resembled an inflammatory myofibroblastic tumor. The neoplastic cells were positive for smooth muscle actin with focal CD56, CD99, Bcl2 and EMA expression. WT1, calretinin, myogenin, CK(AE1/AE3), desmin, H-caldesmon, CD34, ALK, CKIT, DOG1, MUC4 and STAT6 were negative. MDM2 showed diffuse and strong nuclear positivity in neoplastic cells and fluorescence in situ hybridization (FISH) revealed amplified MDM2 (high level) but no SYT rearrangement. Although a lipomatous component was evident macroscopically, well-differentiated liposarcomatous components were not evident in the section examined. Dedifferentiated liposarcoma can have prominent inflammatory myofibroblastic tumor-like features. Pathologists should be aware of this histological variant in order to avoid misdiagnosing dedifferentiated liposarcoma as inflammatory myofibroblastic tumor or other spindle cell tumors which have different behavioral patterns and treatment requirements.
Subject(s)
Lipoma , Liposarcoma , Antigens, CD34 , Chromosome Aberrations , Humans , In Situ Hybridization, FluorescenceABSTRACT
Non-Langerhans cell histiocytosis, including Rosai-Dorfman disease (RDD) and xanthogranuloma are rare disorders with occasional overlapping in the histopathological and immunohistochemical (IHC) findings. We report the case of a 53-year-old woman with erythematous-violaceous plaques on the cheeks and edema in the auricular pavilions. A biopsy was performed and the histopathological examination revealed a histiocytic proliferation with emperipolesis characteristic of RDD and lymphoplasmocitic infiltrate. IHC analysis showed S100 and CD68 positivity in the histiocytes but was negative for CD1a, supporting the diagnosis of RDD. Molecular analysis failed to detect BRAF-V600, NRAS or KRAS mutation. We discuss the differential diagnosis of cutaneous non-Langerhans cell histiocytosis. Pathologist must be aware of unusual presentations of RDD and further treatment options must be explored for patients with unresectable lesions and/or resistance to the classical management of RDD.
Subject(s)
Histiocytosis, Sinus , Proto-Oncogene Proteins B-raf , Female , GTP Phosphohydrolases/genetics , Histiocytes/pathology , Histiocytosis, Sinus/diagnosis , Histiocytosis, Sinus/genetics , Histiocytosis, Sinus/pathology , Humans , Membrane Proteins , Middle Aged , Mutation , Proto-Oncogene Proteins B-raf/genetics , Proto-Oncogene Proteins p21(ras)/geneticsABSTRACT
Although EGFR mutant-selective tyrosine kinase inhibitors (TKI) are clinically effective, acquired resistance can occur by reactivating ERK. We show using in vitro models of acquired EGFR TKI resistance with a mesenchymal phenotype that CXCR7, an atypical G protein-coupled receptor, activates the MAPK-ERK pathway via ß-arrestin. Depletion of CXCR7 inhibited the MAPK pathway, significantly attenuated EGFR TKI resistance, and resulted in mesenchymal-to-epithelial transition. CXCR7 overexpression was essential in reactivation of ERK1/2 for the generation of EGFR TKI-resistant persister cells. Many patients with non-small cell lung cancer (NSCLC) harboring an EGFR kinase domain mutation, who progressed on EGFR inhibitors, demonstrated increased CXCR7 expression. These data suggest that CXCR7 inhibition could considerably delay and prevent the emergence of acquired EGFR TKI resistance in EGFR-mutant NSCLC. SIGNIFICANCE: Increased expression of the chemokine receptor CXCR7 constitutes a mechanism of resistance to EGFR TKI in patients with non-small cell lung cancer through reactivation of ERK signaling.
