Cytomorphology of monomorphic spindle epithelial tumor with thymus-like elements: A case with local recurrence after subtotal resection.

Spindle epithelial tumor with thymus-like elements (SETTLE) is a rare biphasic thyroid tumor with low malignant potential that has a distinct morphology. Despite fine needle aspiration (FNA) being a common method for evaluating thyroid nodules and lymph nodes, there are limited cytologic descriptions of SETTLE in the literature due to its rarity. As a result, SETTLE is frequently underdiagnosed or misdiagnosed as medullary carcinoma, thymoma, teratoma, synovial sarcoma, or solitary fibrous tumor, among others. We present a case of a 28-year-old man with a history of a hemithyroidectomy diagnosed as SETTLE found to have a neck nodule along the strap muscle suspicious for recurrence 5 years post-surgery. The ultrasound-guided FNA cytology specimen of the neck nodule showed loosely cohesive, monomorphous ovoid to spindled cells with scant cytoplasm and nuclei with fine to granular chromatin. In addition, there were occasional clusters of cells with a papillary configuration. The tumor cells were associated with magenta, amorphous extracellular material. Immunocytochemical staining of the cell block material revealed that tumor cells were positive for p63, cytokeratin AE1/3, and CK8/18 and negative for TTF-1 and thyroglobulin. Overall, the morphological and immunocytochemical findings were consistent with a local recurrence of SETTLE. The subsequent left anterior strap mass excision revealed a 4 cm encapsulated tumor consistent with SETTLE. Because ofits rarity and low level of awareness, SETTLE poses a diagnostic and therapeutic challenge. We herein present the cytologic findings of monomorphic SETTLE and highlight the potential cytomorphologic and immunophenotypic pitfalls. We also highlight how tumors with high-risk features can be a therapeutic challenge.

Undifferentiated component of dedifferentiated endometrial carcinoma presenting as a "small round cell" malignancy in a mediastinal lymph node, mimicking small cell carcinoma.

Undifferentiated/dedifferentiated endometrial carcinoma is an uncommon malignant neoplasm of the endometrium that can present as a diagnostic challenge, especially in a metastatic setting. We present a case of a 70-year-old woman with a prior endometrial biopsy diagnosed as endometrioid carcinoma, FIGO Grade 2. Chest computerized tomography showed moderate to severe centrilobular emphysema with a 3 mm nodule in the right upper lobe and posterior mediastinal lymphadenopathy. Fine needle aspiration smears of the mediastinal lymph node showed predominantly single and loosely cohesive tumor cells with scant basophilic cytoplasm, prominent nuclear streaking, and molding. Inconspicuous nucleoli and mitotic figures were present. Immunohistochemical (IHC) stains showed the tumor cells were positive for CD56 and synaptophysin but negative for AE1/AE3, CAM5.2, CK7, CK20, TTF-1, INSM1, chromogranin, CD99, HMB45, SOX10, EBV-LMP1, and desmin. Flow cytometry was negative for lymphoma. Based on the overall cytologic findings and significant smoking history, a small cell carcinoma could not be excluded. Similar morphologic findings were identified on the corresponding lymph node biopsy. Because of the history of endometrial carcinoma, additional IHC stains (PAX 8, ER, and EMA) were done but were negative. However, the mismatch repair proteins revealed loss of MLH1 and PMS2 with retained MSH2 and MSH6 nuclear expression. Hence, a metastatic undifferentiated component of a dedifferentiated carcinoma from the patients' endometrial primary was favored and subsequently confirmed on the hysterectomy specimen.

Intravascular Endothelial Hyperplasia of the Foot.

Intravascular endothelial hyperplasia is a benign soft tissue mass rarely reported in the foot. Advanced imaging and confirming a benign diagnosis are critical for any soft tissue mass. This paper identifies 2 patients that developed intravascular endothelial hyperplasia tumors which required surgical excision. A 17-year-old male patient presented to clinic complaining of a painful bump to the arch of his right foot which he related to an injury 9 months prior. Magnetic resonance imaging of the right foot revealed a mass within the plantar subcutaneous fat that was serpiginous in nature similar to adjacent branching vessels favoring a low-flow vascular malformation. A 38-year-old female with Multiple Sclerosis presented with complaints of persistent symptoms of pain to the 1st interspace, difficult ambulation and neuritis. Ultrasound and MRI observed solid, multilobulated mass, with internal vascular malformation, MRI describing intrinsic involvement along the abductor musculature and flexor tendons. Both lesions were surgically excised and sent for pathology. Pathology report indicated a diagnosis of intravascular papillary endothelial hyperplasia or Masson's tumor in both cases. Pathology diagnosis of intravascular papillary endothelial hyperplasia is generally good with wide resection leading to low recurrence rates. Both patients in the current study have progressed postoperatively with resolution of symptoms and without recurrence.

De novo construction of T cell compartment in humanized mice engrafted with iPSC-derived thymus organoids.

Hematopoietic humanized (hu) mice are powerful tools for modeling the action of human immune system and are widely used for preclinical studies and drug discovery. However, generating a functional human T cell compartment in hu mice remains challenging, primarily due to the species-related differences between human and mouse thymus. While engrafting human fetal thymic tissues can support robust T cell development in hu mice, tissue scarcity and ethical concerns limit their wide use. Here, we describe the tissue engineering of human thymus organoids from inducible pluripotent stem cells (iPSC-thymus) that can support the de novo generation of a diverse population of functional human T cells. T cells of iPSC-thymus-engrafted hu mice could mediate both cellular and humoral immune responses, including mounting robust proinflammatory responses on T cell receptor engagement, inhibiting allogeneic tumor graft growth and facilitating efficient Ig class switching. Our findings indicate that hu mice engrafted with iPSC-thymus can serve as a new animal model to study human T cell-mediated immunity and accelerate the translation of findings from animal studies into the clinic.

Axillary lymphadenopathy in a liver transplant recipient: Initial manifestation of disseminated cryptococcosis.

Immunocompromised patients, especially organ transplant recipients, are at risk for opportunistic infections. Cryptococcus, a ubiquitous environmental fungus, can cause potentially fatal infection in such hosts. While it can involve any organ in the human body, respiratory and central nervous systems are commonly affected. We present a case of disseminated cryptococcal infection in a liver transplant recipient in whom the initial presentation was bilateral axillary lymphadenopathy, a relatively rare clinical manifestation. Rapid diagnosis and targeted antimicrobial therapy are paramount for favorable clinical outcomes, particularly in this patient population.

Case of a 57-Year-Old Man With Malignant Mesothelioma Presenting With Miliary Nodules on Chest Imaging.

CASE PRESENTATION: A 57-year-old man with history of stage IIIB right-sided malignant pleural mesothelioma was admitted from his oncologist's office for progressive dyspnea of two weeks duration. He had associated dyspnea at rest and a new dry cough. He denied sputum production, hemoptysis, or fevers, but he did endorse chills, fatigue, and weight loss. The patient was a veteran of the Navy and had extensive international travel in his 20s. He had never been incarcerated and denied any sick contacts or recent travels. He had received a diagnosis of mesothelioma 11 months earlier after presenting to his physician's office with complaints of shortness of breath on exertion. Initial imaging revealed a large right-sided pleural effusion with irregular pleural thickening. He underwent right-sided thoracoscopy, and the pleural biopsy result was consistent with epithelioid mesothelioma. Because of invasion of his seventh rib, he was not a candidate for surgery and underwent palliative radiation and chemotherapy with cisplatin, pemetrexed, and bevacizumab. He was undergoing his eighth cycle of chemotherapy at the time of presentation.

Association of Celiac Disease With Pembrolizumab.

Immune checkpoint inhibitors (ICIs) in the recent times have transformed the landscape of the management of many solid tumors. Unfortunately, many immune-related adverse effects are associated with ICIs, which lead to a negative outcome in cancer treatment. We present a case of a 63-year-old female with metastatic adenocarcinoma of unknown origin, who developed celiac disease during the course of treatment with pembrolizumab. Association of celiac disease with this form of immunotherapy has never been documented before.