Development of 3D-iNET ORION: a novel, pre-clinical, three-dimensional in vitro cell model for modeling human metastatic neuroendocrine tumor of the pancreas.

Neuroendocrine tumors (NETs) of the pancreas are rare neoplasms that present complex challenges to diagnosis and treatment due to their indolent course. The incidence of pancreatic neuroendocrine tumors has increased significantly over the past two decades. A limited number of pancreatic neuroendocrine cell lines are currently available for the research.

Charting oncogenicity of genes and variants across lineages via multiplexed screens in teratomas.

Deconstructing tissue-specific effects of genes and variants on proliferation is critical to understanding cellular transformation and systematically selecting cancer therapeutics. This requires scalable methods for multiplexed genetic screens tracking fitness across time, across lineages, and in a suitable niche, since physiological cues influence functional differences. Towards this, we present an approach, coupling single-cell cancer driver screens in teratomas with hit enrichment by serial teratoma reinjection, to simultaneously screen drivers across multiple lineages in vivo.

Defining the Teratoma as a Model for Multi-lineage Human Development.

We propose that the teratoma, a recognized standard for validating pluripotency in stem cells, could be a promising platform for studying human developmental processes. Performing single-cell RNA sequencing (RNA-seq) of 179,632 cells across 23 teratomas from 4 cell lines, we found that teratomas reproducibly contain approximately 20 cell types across all 3 germ layers, that inter-teratoma cell type heterogeneity is comparable with organoid systems, and teratoma gut and brain cell types correspond well to similar fetal cell types. Furthermore, cellular barcoding confirmed that injected stem cells robustly engraft and contribute to all lineages.

Adult Stem Cell-derived Complete Lung Organoid Models Emulate Lung Disease in COVID-19.

SARS-CoV-2, the virus responsible for COVID-19, causes widespread damage in the lungs in the setting of an overzealous immune response whose origin remains unclear. We present a scalable, propagable, personalized, cost-effective adult stem cell-derived human lung organoid model that is complete with both proximal and distal airway epithelia. Monolayers derived from adult lung organoids (ALOs), primary airway cells, or hiPSC-derived alveolar type-II (AT2) pneumocytes were infected with SARS-CoV-2 to create in vitro lung models of COVID-19.

Regional variation in bone turnover at the iliac crest versus the greater trochanter.

Background: Iliac crest bone biopsy with histomorphometry is the gold standard for diagnosis of abnormalities in bone turnover, yet fractures more frequently occur at the greater trochanter of the hip. Whether bone turnover is similar at these two anatomic sites within individuals is uncertain.

Methods: We collected bone biopsy samples from the ipsilateral iliac crest and greater trochanter in 9 deceased individuals undergoing autopsies at an academic medical center between March-August 2018.

Intranodal palisaded myofibroblastoma of para-esophageal lymph node: Case report with cytologic and histologic findings.

Intranodal palisaded myofibroblastoma is a rare lymph node mesenchymal neoplasm that most commonly arises in inguinal lymph nodes. There is limited data about cytologic features of this tumor and its diagnostic pitfalls. The combination of bland appearing spindle cells, fibrillary matrix, and hemosiderin pigments are the characteristic features of this neoplasm in cytologic specimens.

Osteosarcomatous Divergence in Dedifferentiated Liposarcoma Presenting as a Colonic Mass.

Dedifferentiated liposarcomas most commonly arise in the retroperitoneum, accounting for 10% of liposarcomas. Heterologous differentiation occurs in 5-10% of dedifferentiated liposarcomas; however, divergent osteosarcomatous differentiation is rare. We report a rare case of initial presentation of dedifferentiated liposarcoma with osteosarcomatous component as a colonic mass in a 72-year-old man.

Overinterpretation is common in pathological diagnosis of appendix cancer during patient referral for oncologic care.

Context: Low-grade appendiceal mucinous neoplasm (LAMN) and appendiceal adenocarcinoma are known to cause the majority of pseudomyxoma peritonei (PMP, i.e. mucinous ascites); however, recognition and proper classification of these neoplasms can be difficult despite established diagnostic criteria.

Adenocarcinoma Ex-Goblet Cell Carcinoid of the Appendix With Metastatic Peritoneal Spread to Meckel's Diverticulum and Endometriosis.

Adenocarcinoma ex-goblet cell carcinoid is a very rare and histologically unique appendiceal malignancy with dual glandular and neuroendocrine differentiation. There is a high incidence of this tumor among middle-aged women with metastasis to the gynecologic tract with the mode of metastasis following peritoneal spread rather than hematogenous distribution. Adenocarcinoma ex-goblet cell carcinoid can spread to any peritoneal site including ovaries or omentum.

Newly Diagnosed Colonic Adenocarcinoma: The Presenting Sign in a Young Woman with Undiagnosed Crohn's Disease in the Absence of Primary Sclerosing Cholangitis and a Normal Microsatellite Instability Profile.

Ulcerative colitis has long been linked with an increased risk for colonic adenocarcinoma, whereas Crohn's disease (CD) has recently been reported to pose a similar increased risk. We report a 33-year-old healthy female with no family history who presented with abdominal pain and a colon mass. Histopathology revealed a moderately differentiated adenocarcinoma extending through the muscularis propria with metastatic lymph nodes and intact mismatch repair proteins by immunohistochemical expression and gene sequencing.

Successful Treatment of Multifocal Histiocytic Sarcoma Occurring after Renal Transplantation with Cladribine, High-Dose Cytarabine, G-CSF, and Mitoxantrone (CLAG-M) Followed by Allogeneic Hematopoietic Stem Cell Transplantation.

Histiocytic sarcoma (HS) is a rare, aggressive malignancy. Lesions previously called HS were typically non-Hodgkin lymphomas, not HS. As such, chemotherapy directed at lymphoid neoplasms was frequently successful, but it is unclear if these regimens are ideal for HS.

Rapidly progressive subcutaneous metastases from gallbladder cancer: insight into a rare presentation in gastrointestinal malignancies.

Background: Gallbladder cancer (GBCA) is the most common malignancy of the biliary tract. It has an aggressive biology that results in the ability to spread, seed and grow in disparate environments. It can metastasize via lymphatic, hematogenous, and peritoneal seeding.

Examination of sources of diagnostic error leading to cervical cone biopsies with no evidence of dysplasia.

At our institution, 17% of cervical conization specimens are reported as negative for dysplasia or malignancy. To identify sources of error, we reviewed 53 negative conization specimens and their prior and follow-up cytology, biopsy, and endocervical curettage specimens. Examination of deeper-level sections and p16 immunostaining were performed on all conization specimens and selected biopsy specimens.

Prognostic implications of parathyroid hormone-related protein in males and females with non--small-cell lung cancer.

Background: Non-small-cell lung carcinoma immunoreactivity for parathyroid hormone-related protein has been associated with increased survival in female patients but not in male patients. The current investigation attempted to substantiate this finding in 2 new patient groups.

Methods: Patients were divided into groups with and without immunoreactivity for a carboxyl-terminal parathyroid hormone-related protein epitope assessed in deparaffinized sections by a blinded observer.

Reliability of Her2/neu, estrogen receptor, and progesterone receptor testing by immunohistochemistry on cell block of FNA and serous effusions from patients with primary and metastatic breast carcinoma.

The prognostic and predictive value of Her2/neu and the hormone receptors in patient with primary or metastatic breast cancer is essential for a favorable outcome of treatment. We have been experiencing increasing requests to test cytologic specimens for these markers in patients with metastatic breast carcinoma. A recent study threw some doubts on the validity of such testing using cell blocks.

Anaplastic lymphoma kinase-positive diffuse large B-cell lymphoma presenting as an isolated nasopharyngeal mass: a case report and review of literature.

Anaplastic lymphoma kinase (ALK)-positive diffuse large B-cell lymphoma is a rare and distinct variant of diffuse large B-cell lymphoma with characteristic morphologic, immunophenotypic, and cytogenetic features. We report a case of ALK-positive diffuse large B-cell lymphoma in a 44-year-old male with progressively worsening unilateral nasal congestion and obstruction secondary to a nasopharyngeal mass. Radiologically, the mass was showed to extend to orophanrynx from nasopharynx.

Colonization of intestinal endometriosis by benign colonic mucosa: a pattern potentially misdiagnosed as invasive mucinous carcinoma.

Endometriosis is well known for creating diagnostic pitfalls for pathologists. It may produce masses mimicking neoplasms or cause diagnostic quandaries, particularly when the patient age, location, and/or epithelial appearance are atypical. This study reports a patient with endometriosis causing rectal bleeding and involving the cecum.

Endometrioid carcinoma with a low-grade spindle cell component: a tumor resembling an adnexal tumor of probable Wolffian origin.

Endometrioid carcinoma is known to have many histopathologic variants, which may cause diagnostic difficulty. One rare variant resembles Wolffian adnexal tumor (female adnexal tumor of probable Wolffian origin). This pattern can produce a significant solid component within the tumor.