Pulmonary epithelial-myoepithelial carcinoma (P-EMC) with focal high grade transformation: Molecular and cytologic findings.

BACKGROUND: Pulmonary epithelial-myoepithelial carcinoma (P-EMC) is a rare type of salivary gland tumor of the lung. Diagnosis from preoperative biopsies or fine needle aspiration (FNA) cytology specimens is difficult given the rarity of the tumor and overlapping cytomorphology with other entities. These tumors generally have a good prognosis, however prior reports of recurrence and metastasis to lymph nodes have been reported. Further, little is known about the malignant potential of high grade transformation. The molecular characteristics of this entity are unknown, with only a few case reports commenting on molecular findings. Here, we report a case of P-EMC with focal high grade transformation. We present its diagnostic pitfalls on cytology specimens, surgical pathology, immunohistochemistry, and molecular findings. CASE PRESENTATION: A 72 year old female presented with an incidentally detected lung mass. A chest computed tomography (CT) demonstrated a left hilar mass measuring 4.1 cm with endobronchial extension into the left upper lobe. On the initial endobronchial core needle biopsy and cytology FNA, the tumor was misinterpreted as squamous cell carcinoma. The patient subsequently underwent a left pneumonectomy along with mediastinal lymph node dissection. Final surgical pathology of the resection specimen indicated a P-EMC with focal high grade transformation. The patient is disease-free 1 year post-surgery. CONCLUSIONS: Due to the rarity of P-EMC, insufficient sampling and histologic heterogeneity, diagnosis of P-EMC on preoperative core needle biopsy or FNA specimen is difficult. Herein, we present a rare case of P-EMC, with a pre-operative FNA cytology specimen that consisted of tumor cells with dense cytoplasm and moderate cytologic atypia, strong positive staining pattern of p40, that was misdiagnosed as squamous cell carcinoma. Follow up surgical resection showed P-EMC with focal high grade transformation. Salivary gland EMCs with high grade transformation have previously been reported to have a worse prognosis, however, little is known about the malignant potential in the lung. Next generation sequencing (NGS) using a 397-gene solid tumor panel identified variants in DNMT3A, APC, STAT3 in both low and high grade components, while KDM5C was present only in the high grade transformation.

Epstein Virus Barr-Positive Diffuse Large B-Cell Lymphoma Associated with Hemophagocytic Lymphohistiocytosis.

Hemophagocytic lymphohistiocytosis (HLH) is a rare and often fatal disease if not diagnosed and treated promptly. HLH can be due to genetic factors or infections, malignancies and collagen-associated vascular diseases. Malignancy-associated HLH is not only more common in the setting of T/NK-cell lymphomas, but may also rarely be seen in the setting of B-cell lymphoma. Here, we describe a unique case of a patient who initially was diagnosed with HLH secondary to Epstein Barr virus (EBV) infection and subsequently developed EBV-positive diffuse large B-cell lymphoma affecting the brain. This case highlights the spectrum of findings associated with EBV infections and the challenges in diagnosing underlying diseases associated with HLH.

Infratentorial Glioblastoma Metastasis to Bone.

BACKGROUND: Glioblastoma multiforme (GBM) is a rapid-growing central nervous system neoplasm. We report a case of GBM with extensive intramedullary lumbar drop metastasis and highly unusual osseous spine metastasis from a primary infratentorial GBM occurring 10 years after the initial diagnosis, which to our knowledge has not been described previously. CASE DESCRIPTION: This 37-year-old man presented with new-onset headaches of increasing severity. Brain magnetic resonance imaging (MRI) demonstrated a heterogeneously enhancing mass in the left superior temporal lobe with adjacent edema. The lesion was initially biopsied in December 2006 and diagnosed as GBM (World Health Organization grade IV) with characteristic features of a highly cellular infiltrating glial neoplasm with nuclear pleomorphism, abundant microvascular proliferation, and abundant necrosis with pseudopalisading nuclei. Ki-67 immunostaining revealed that 15%-20% tumor cell nuclei were positive, indicating a high proliferative index. Histologically, this neoplasm demonstrated characteristic "cell wrapping." Immunoreactivity was variably but strongly positive for glial fibrillary acidic protein in neoplastic cells. In 2018, additional MRI revealed disease throughout the spine and bone biopsy of the thoracic spine showed the same glial neoplasm with primitive neuroectodermal tumor-like components (GBM-PNET). CONCLUSIONS: This case is meant to highlight that, although rare, infratentorial GBM-PNET has a higher frequency of isocitrate dehydrogenase 1 (IDH1) mutation and may metastasize to the spine years after the initial diagnosis despite the likely better prognosis.

HDL surface lipids mediate CETP binding as revealed by electron microscopy and molecular dynamics simulation.

Cholesteryl ester transfer protein (CETP) mediates the transfer of cholesterol esters (CE) from atheroprotective high-density lipoproteins (HDL) to atherogenic low-density lipoproteins (LDL). CETP inhibition has been regarded as a promising strategy for increasing HDL levels and subsequently reducing the risk of cardiovascular diseases (CVD). Although the crystal structure of CETP is known, little is known regarding how CETP binds to HDL. Here, we investigated how various HDL-like particles interact with CETP by electron microscopy and molecular dynamics simulations. Results showed that CETP binds to HDL via hydrophobic interactions rather than protein-protein interactions. The HDL surface lipid curvature generates a hydrophobic environment, leading to CETP hydrophobic distal end interaction. This interaction is independent of other HDL components, such as apolipoproteins, cholesteryl esters and triglycerides. Thus, disrupting these hydrophobic interactions could be a new therapeutic strategy for attenuating the interaction of CETP with HDL.