BackgroundFocal liver lesions with spindle cell morphology are rare in the daily practice of pathology. The differential diagnosis is broad, including both tumors and tumor-like lesions. Initial radiologic assessment is sometimes inaccurate. Histopathology is needed to arrive at the correct diagnosis. This study analyzed discrepancies between histopathology and radiologic findings of focal liver lesions with spindle cell morphology. MethodsA six-year retrospective analysis was conducted at a tertiary hospital in Thailand. All focal liver lesions with spindle cell morphology were retrieved. Clinicopathologic features of these cases were analyzed. The pathological diagnosis was rendered primarily based on routine histopathology, using other ancillary studies as an adjunct. Results287 biopsies and 151 resection specimens with focal liver lesions were identified. In 12 (2.7%) cases, tumors or tumor-like lesions with spindle cell morphology were retrieved. A total of five cases had discrepancies between histopathology and radiologic findings. These lesions encompassed primary liver tumors (EBV-associated smooth muscle tumor and leiomyosarcoma); metastatic tumors (gastrointestinal stromal tumor, small cell neuroendocrine carcinoma); and a tumor-like lesion (endometriosis). Several morphologic findings (i.e., cytologic grades, dense and loose areas, intratumoral lymphocytes, distinct perinuclear vacuoles, and hemosiderin) are important clues to diagnose these spindle cell lesions. ConclusionsPathologists play a critical role in diagnosing focal liver lesions with spindle cell morphology, particularly those with limited clinical data at the initial presentation. A thorough evaluation of histomorphology on routine hematoxylin and eosin-stained slides is essential for correct diagnosis.