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1.
Cells ; 13(13)2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38994972

ABSTRACT

Understanding tumor-host immune interactions and the mechanisms of lung cancer response to immunotherapy is crucial. Current preclinical models used to study this often fall short of capturing the complexities of human lung cancer and lead to inconclusive results. To bridge the gap, we introduce two new murine monoclonal lung cancer cell lines for use in immunocompetent orthotopic models. We demonstrate how our cell lines exhibit immunohistochemical protein expression (TTF-1, NapA, PD-L1) and common driver mutations (KRAS, p53, and p110α) seen in human lung adenocarcinoma patients, and how our orthotopic models respond to combination immunotherapy in vivo in a way that closely mirrors current clinical outcomes. These new lung adenocarcinoma cell lines provide an invaluable, clinically relevant platform for investigating the intricate dynamics between tumor and the immune system, and thus potentially contributes to a deeper understanding of immunotherapeutic approaches to lung cancer treatment.


Subject(s)
Adenocarcinoma of Lung , Carcinoma, Non-Small-Cell Lung , Immunotherapy , Lung Neoplasms , Animals , Immunotherapy/methods , Humans , Cell Line, Tumor , Mice , Lung Neoplasms/immunology , Lung Neoplasms/therapy , Lung Neoplasms/pathology , Lung Neoplasms/genetics , Carcinoma, Non-Small-Cell Lung/therapy , Carcinoma, Non-Small-Cell Lung/immunology , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Non-Small-Cell Lung/genetics , Adenocarcinoma of Lung/immunology , Adenocarcinoma of Lung/therapy , Adenocarcinoma of Lung/pathology , Adenocarcinoma of Lung/genetics , Disease Models, Animal , Female
2.
Int J Gynecol Pathol ; 41(4): 320-326, 2022 07 01.
Article in English | MEDLINE | ID: mdl-34320530

ABSTRACT

Teratomas are tumors of germ cell origin, and in the female genital tract are subclassified as immature or mature based on the presence or absence, respectively, of immature elements. Somatic tumors may also develop in association with teratomas, and most commonly include thyroid tumors, carcinoids and carcinomas. We report herein 2 rare forms of gynecologic teratomas: 1 case of immature teratoma of the uterus and 1 case of a benign follicular hamartoma arising in association with mature cystic teratoma of the ovary.


Subject(s)
Dermoid Cyst , Ovarian Neoplasms , Teratoma , Female , Humans , Ovarian Neoplasms/pathology , Ovarian Neoplasms/surgery , Teratoma/pathology , Teratoma/surgery
3.
BMJ Case Rep ; 14(1)2021 Jan 19.
Article in English | MEDLINE | ID: mdl-33468635

ABSTRACT

The diagnosis via core needle biopsy of concurrent ductal carcinoma in situ and lobular carcinoma in situ within an enlarging previously biopsied benign fibroadenoma in women in their 40s is rare. Several case reports have described the occurrence of malignant changes within fibroadenomas, usually as an incidental finding following excision, and few reports have documented the transition of a fibroadenoma to malignancy. The current case report emphasises the importance of re-biopsying enlarging fibroadenomas, even with otherwise maintained benign appearing features on imaging, in women in their 40s, in order to exclude the possibility of malignancy.


Subject(s)
Breast Neoplasms/pathology , Carcinoma, Intraductal, Noninfiltrating/pathology , Carcinoma, Lobular/pathology , Fibroadenoma/pathology , Biopsy, Large-Core Needle , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/therapy , Carcinoma, Intraductal, Noninfiltrating/diagnostic imaging , Carcinoma, Intraductal, Noninfiltrating/therapy , Carcinoma, Lobular/diagnostic imaging , Carcinoma, Lobular/therapy , Female , Humans , Mammography , Middle Aged
4.
Int J Surg Pathol ; 27(4): 423-426, 2019 Jun.
Article in English | MEDLINE | ID: mdl-30238810

ABSTRACT

BACKGROUND: Epithelioid hemangioendothelioma (EHE) is an uncommon malignant endothelial neoplasm that most commonly arises in soft tissue, bone, lung, and liver. Crohn's disease (CD) is an inflammatory bowel disease of unknown etiology that is frequently associated with complications including strictures, fistulas/fissures, and neoplasms. CASE DESCRIPTION: A 43-year-old woman with a 6-year history of severe CD presented with anal pain and bleeding. She had prior partial colectomy for a stricture and a diverting ileostomy for perianal fissures and stricture. Colonoscopy showed severe chronic active colitis, stricture at 30 cm of anal verge, and a perianal fistula. The patient underwent total proctocolectomy. The colonic mucosa exhibited segmental ulceration and irregular thickening of the colon wall. Beneath an ulcer of the anal canal within the muscularis propria was a 1.2-cm poorly circumscribed, firm, white-tan mass. The mass was composed of cords and groups of large epithelioid endothelial cells with intracytoplasmic vacuoles enmeshed in a myxohyaline stroma. Immunohistochemically, the tumor cells were positive for ERG, CD31, and CAMTA1 and focally positive for keratin and SMA. Next-generation sequencing revealed a WWTR1-CMATA1 fusion. The morphology, immunoprofile, and molecular genetics were diagnostic of EHE. DISCUSSION: Long-standing inflammatory bowel disease is associated with significant risk for developing neoplasms, usually carcinomas, which can be indistinguishable radiologically and clinically from nonneoplastic complications. These tumors are often identified as an incidental finding in specimens resected for clinically severe disease. This is the first report of EHE arising in the bowel affected by CD, and it mimicked mural fibrosis and fissures.


Subject(s)
Anal Canal/pathology , Anus Neoplasms/diagnosis , Crohn Disease/complications , Hemangioendothelioma, Epithelioid/diagnosis , Intestinal Mucosa/pathology , Adult , Anus Neoplasms/genetics , Anus Neoplasms/pathology , Anus Neoplasms/surgery , Biomarkers, Tumor/analysis , Calcium-Binding Proteins/genetics , Colon/diagnostic imaging , Colon/pathology , Colonoscopy , Diagnosis, Differential , Female , Fibrosis/diagnosis , Fissure in Ano/diagnosis , Hemangioendothelioma, Epithelioid/genetics , Hemangioendothelioma, Epithelioid/pathology , Hemangioendothelioma, Epithelioid/surgery , Humans , Intestinal Mucosa/diagnostic imaging , Intracellular Signaling Peptides and Proteins/genetics , Proctocolectomy, Restorative , Trans-Activators/genetics , Transcription Factors , Transcriptional Coactivator with PDZ-Binding Motif Proteins
5.
J Endocr Soc ; 2(2): 106-111, 2018 Feb 01.
Article in English | MEDLINE | ID: mdl-29379898

ABSTRACT

Lymphocytic hypothalamitis (LHT) is a rare disease characterized by pituitary dysfunction, autonomic instability, metabolic disturbances, and neuropsychiatric disorders. We report the case of a 30-year-old man found to have LHT that progressed despite treatment with methylprednisolone and intravenous immunoglobulin (IVIG). A literature review was conducted to identify prior studies pertaining to LHT. Our patient presented with several weeks of fatigue, cold intolerance, weight loss, confusion, and headache. Laboratory tests were consistent with panhypopituitarism. Brain magnetic resonance imaging revealed an infiltrative enhancing mass in the area of the hypothalamus, and stereotactic biopsy findings showed reactive inflammatory changes. A course of hormone replacement (levothyroxine), methylprednisolone, and IVIG was initiated. The patient's course was complicated by a fatal tonsillar herniation. Autopsy revealed LHT. The diagnosis and management of autoimmune LHT are challenging. The entity should be considered in the setting of panhypopituitarism with a hypothalamic mass. Differentiating paraneoplastic and nonparaneoplastic hypothalamitis should be established for management and prognosis. Definitive treatment remains unclear; treatment with corticosteroids should be attempted, followed by consideration of other immunosuppressive agents, such as rituximab. If a paraneoplastic syndrome is suspected, management should also be directed toward the primary tumor.

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