Jonathan Melamed

Prostate cancer (PC) develops in a microenvironment where the stromal cells modulate adjacent tumor growth and progression. Here, we demonstrated elevated levels of monoamine oxidase B (MAOB), a mitochondrial enzyme that degrades biogenic and dietary monoamines, in human PC stroma, which was associated with poor clinical outcomes of PC patients. Knockdown or overexpression of MAOB in human prostate stromal fibroblasts indicated that MAOB promotes cocultured PC cell proliferation, migration, and invasion and co-inoculated prostate tumor growth in mice. Mechanistically, MAOB induces a reactive stroma with activated marker expression, increased extracellular matrix remodeling, and acquisition of a protumorigenic phenotype through enhanced production of reactive oxygen species. Moreover, MAOB transcriptionally activates CXCL12 through Twist1 synergizing with TGFβ1-dependent Smads in prostate stroma, which stimulates tumor-expressed CXCR4-Src/JNK signaling in a paracrine manner. Pharmacological inhibition of stromal MAOB restricted PC xenograft growth in mice. Collectively, these findings characterize the contribution of MAOB to PC and suggest MAOB as a potential stroma-based therapeutic target.

Myoepithelial carcinoma (MEC) of soft tissue, also known as malignant myoepithelial tumor, is an uncommon malignancy. Cytologic diagnosis of this entity is challenging due to its rarity and heterogeneous morphology. We report a case of MEC in a 22‐year‐old man, who presented with a 6.5 cm soft tissue mass on his right distal forearm that has been enlarging over the past 3 months. Ultrasound‐guided fine‐needle aspiration (FNA) revealed abundant isolated neoplastic cells ranging from spindled cells to epithelioid and plasmacytoid morphology in a myxoid background. These cells showed moderate cytologic atypia characterized by high‐nuclear/cytoplasmic ratio, irregular nuclear contours, and prominent nucleoli. The cytoplasm varied from dense to vacuolated and occasionally rhabdoid with intracytoplasmic inclusions. Scattered bi‐ and multinucleated cells were identified. A diagnosis of high‐grade malignancy was made with the differential diagnosis including rhabdomyosarcoma and melanoma. A subsequent core biopsy of the tumor showed immunoreactivity for pan‐cytokeratins, calponin, p63, and smooth muscle actin. INI‐1 was lost. SOX‐10 and Melan‐A were negative. Molecular studies showed loss of SMARCB1 (INI‐1) and CDKN2A . Gene fusion studies did not detect any fusion. A diagnosis of soft tissue MEC was made which is a challenge on FNA due to several cytologic mimickers including rhabdomyosarcoma, epithelioid sarcoma, extrarenal rhabdoid tumor, extra‐axial chordoma and melanoma. Recognition of the biphasic cell population in a myxoid background and a battery of immunohistochemical stains are crucial for accurate diagnosis.