Metastatic High-Grade Endometrioid Carcinoma to the Lung With Pilomatrix Carcinoma-Like Morphology: Potential for Misdiagnosis as Non-Small Cell Carcinoma.

Abstract

Pilomatrix-like high-grade endometrioid carcinoma (PiMHEC) is a recently described aggressive variant of endometrioid carcinoma characterized by solid nests of basaloid cells with abrupt keratinization, geographic necrosis, and anucleated ghost cells. PiMHEC shows aberrant nuclear and cytoplasmic β-catenin staining, loss of PAX8 and hormone receptor expression, and aberrant expression of CDX2 and neuroendocrine markers. As a result, when presenting as metastatic disease, particularly in the lung, PiMHEC can be misdiagnosed as primary pulmonary non-small cell carcinoma or metastatic carcinoma of nongynecologic origin. We identified 7 cases of metastatic PiMHEC to the lung through our institution's thoracic consultation service. None, including those with a known history, were initially diagnosed with metastatic endometrial carcinoma. All cases demonstrated aberrant β-catenin staining and loss of PAX8, ER, and PR. Radiographically, all cases presented with multiple to innumerable bilateral lung masses. In conclusion, in female patients presenting with multiple lung masses, morphologic features resembling pilomatrix carcinoma, and aberrant β-catenin staining, metastatic PiMHEC should remain high on differential diagnosis even without Mullerian marker immunoreactivity or a history of Mullerian malignancy. Our case series further confirms the aggressive nature of PiMHEC: 3 patients developed lung metastases within 3 months of their initial diagnosis of endometrial carcinoma, 2 presented with postmenopausal bleeding or endometrial thickening and simultaneous lung metastases, and in 1 case, a lung biopsy led to endometrial sampling without clinical suspicion of endometrial carcinoma. Recognizing the morphologic and immunophenotypic features of pulmonary metastases of PiMHEC is crucial to avoid misdiagnosis.