Ectopic Tumor Research Articles

Complication of Ectopic Lacrimal Gland Tumor on Long-term Follow-up: A Case Report.

Complication of Ectopic Lacrimal Gland Tumor on Long-term Follow-up: A Case Report.

Development of a novel modified vaccine (TheraVacM) for curative treatment of mouse solid tumors

Monotherapy with immune checkpoint blockade (ICB) antibodies (anti-CTLA4 and anti-PD1/PDL-1) is only effective for 20% to 30% of patients with certain cancers. Patients with cancers harboring few effector T cells (Teffs) are insensitive to ICB therapy. The lack of tumor-specific Teffs is predominantly caused by the paralysis of tumor-infiltrating dendritic cells (TiDCs) resulting from immunosuppression in the tumor microenvironment. We have identified a potent combination of high mobility group nucleosome binding domain 1 (HMGN1, N1) and fibroblast stimulating lipopeptide-1 (FSL-1) that can synergistically trigger maturation of both mouse and human DCs. Accordingly, we designed a combinational anti-cancer immunotherapy with two arms: an immune-activating arm consisting of N1 and FSL-1 to stimulate the generation of Teffs by triggering full maturation of TiDCs, and an ICB arm using anti-PDL-1 or anti-CTLA4 to prevent Teffs from being silenced in the tumor tissue. This combinational immunotherapeutic vaccination regimen dubbed modified TheraVac (TheraVacM) has proved particularly effective as it cured 100% of mice bearing established ectopic CT26 colon and RENCA kidney tumors. The resultant tumor-free mice were resistant to subsequent re-challenge with the same tumors, indicating the generation of long-term tumor specific protective immunity. Since the immune-activating arm also induces full maturation of human DCs, and anti-PDL-1 or anti-CTLA4 have been FDA-approved, this combinational immunotherapy has the potential to be an effective clinical therapy for patients with solid tumors.

Tumor-Induced Osteomalacia: A Case Report of Rare Disease and Literature review

Background Oncogenic osteomalacia term used for tumor-induced osteomalacia (TIO) is a paraneoplastic syndrome of abnormal phosphate metabolism secondary to ectopic endocrine tumors. The diagnosis often becomes difficult due to rarity of occurrence and deficient literature. The reconstruction following resection has its own technical difficulties, which are addressed in this article. Presentation of Case A 39-year-old female presented with pain in bilateral lower limbs and difficulty in mobilizing. The patient had unexplained hypophosphatemia which was diagnosed due to tumor (arising ectopically in greater trochanter), inducing osteomalacia. She was managed successfully with excision of tumor and reconstruction. The biochemical parameters improved drastically within 5 days and fracture healed in 6 weeks' time. Conclusion TIO is a debilitating disease with significant morbidity due to prolonged onset to diagnosis interval and difficulty in localizing the causative tumor. So thorough clinico-radiological and laboratory parameter correlation is a necessity. A rapid diagnosis followed by complete surgical excision, which remains the gold standard treatment modality that confers favorable prognosis in most patients, with strict vigilance for recurrence is required.

Vitamin k3-Loaded Magnetic Nanoparticle-Mediated Synergistic Magnetothermodynamic Therapy Evokes Massive ROS and Immune Modulation for Augmented Antitumor Potential.

Magnetic nanoparticle (MNP)-mediated magnetic hyperthermia (MHT) under an alternating magnetic field (AMF) causes tumor regression via reactive oxygen species (ROS) generation. However, less therapeutic efficacy has been reported due to the generation of low levels of ROS in a hypoxic tumor microenvironment. Therefore, improved treatments are required to generate relatively high levels of ROS to promote irreversible oxidative damage to the tumor cells. Herein, we report a magnetothermodynamic (MTD) therapy, as a robust and versatile approach for cancer treatment, by combining the magnetothermodynamic-related ROS and heat-related immunological effect in order to overcome the aforementioned obstacle. The synergistic therapy was achieved by the development of vitamin k3 (Vk3)-loaded copper zinc ferrite nanoparticles (Vk3@Si@CuZnIONPs) as an efficient MTD agent. The in vitro results unveiled that enhanced ROS production under the influence of AMF is a predominant aspect in yielding an assertive anticancer response. The in vivo antitumor response was assessed in an ectopic tumor model of A549 lung adenocarcinoma by MTD. The tumor inhibition rate of 69% was achieved within 20 days of MTD treatment, exhibiting complete tumor eradication within 30 days. The validation of antitumor response was marked by severe apoptosis (TUNEL, Caspase-3) in the Vk3@Si@CuZnIONPs + AMF-treated group. The higher expression level of heat shock proteins and proinflammatory cytokines (IL-6, TNF-α, IL-1α, IL-1β) was speculated to play a role in the activation of immune response for faster tumor regression in the MTD-treated group. Therefore, by implementing a dual ROS and heat-mediated immunogenic effect, the antitumor efficiency of future cancer magnetotherapies will be greatly enhanced.

The relationship of nutritional status with anticancer immunity and its prognostic value for head and neck cancer.

Malnutrition has been reported to be associated with reduced survival and deficient anticancer immunity, and undernourishment is a frequent comorbidity in head and neck cancer (HNC) patients. In this study, we evaluated the relationship between nutritional status and immunologic factors, and its prognostic value for HNC. We retrospectively reviewed 212 HNC patients who had undergone a nutrition evaluation based on the Patient-Generated Subjective Global Assessment (PG-SGA) and curative radiotherapy (RT). The role of nutritional status in the prognosis of HNC and its correlation with anticancer immune response was assessed in HNC patients, and in the 4-nitroquinoline 1-oxide (4NQO)-induced tongue tumor animal model. Our data revealed that malnutrition (high PG-SGA scores) was significantly associated with more advanced disease, lower body mass index, lower RT completion rates, and reduced survival. Patients in the group with high PG-SGA scores had a higher neutrophil-to-lymphocyte ratio, higher proportion of myeloid-derived suppressor cells (MDSCs), and elevated IL-6 levels in the peripheral circulation. Patients with increased PG-SGA scores following treatment were more likely to developing locoregional failure. In the 4NQO-induced tumor model, nutritional supplementation decreased the rate of invasive tumor formation and attenuated the immune-suppressive microenvironment. Following ectopic tumor implantation in an immunocompetent host, nutrition supplements decreased tumor growth in association with attenuated MDSC recruitment and lower IL-6 expression. In conclusion, malnutrition by PG-SGA was associated with poor prognosis in HNC patients. Based on the data of HNC patients and the 4NQO-tumor model, adequate nutritional supplementation might improve the prognosis associated with augmented anticancer immunity.

Management of Littre Hernia-Case Report and Systematic Review of Case Reports.

Littre hernia is a rare type of hernia in which a Meckel diverticulum is found in the hernia sac. Given the rare nature of this disease, little data on demographics and surgical management exists. In this article, we provide a case report of a strangulated inguinal Littre hernia and perform a systematic review of the literature. The PubMed database was searched on 5 March 2022, and all cases of Littre hernia in adults that had English abstracts or full-text were analyzed. Our primary objective was to evaluate the surgical management and outcomes of this particular type of hernia, and our secondary objectives were to assess demographic characteristics, presentation particularities, and recurrence rates. We identified 89 articles with 98 cases, including our own. Results show a high prevalence of complications described intraoperatively, with strangulation being present in up to 38.46% of patients. The laparoscopic approach was utilized in patients with femoral, inguinal, and umbilical hernias. The most commonly performed type of resection was MD resection, followed by bowel resection, while a minority of cases (5.48%) remained unresected. Mesh repair was more frequently performed in patients with MD resection. A mortality rate of 8.7% in patients who underwent bowel resection was found. A relatively high number of reports of ectopic tissue (21.21%), ulceration (12.12%), and tumors (9.09%) were found. The average follow-up was 19.5 ± 10.29 months, with no hernia recurrence. In conclusion, most cases are admitted in an emergency setting, and intestinal obstruction is frequently associated. A minimally invasive approach can be an option even for complicated hernias. MD resection or bowel resection is usually employed, depending on the extent of ischemic lesions. Patients undergoing bowel resection may be prone to worse outcomes.

RBM38 Reverses Sorafenib Resistance in Hepatocellular Carcinoma Cells by Combining and Promoting lncRNA-GAS5.

Hepatocellular carcinoma (HCC) is a life-threatening human malignancy and the fourth leading cause of cancer-related deaths worldwide. Patients with HCC are often diagnosed at an advanced stage with a poor prognosis. Sorafenib is a multikinase inhibitor used as the first-line treatment for patients with advanced HCC. However, acquired resistance to sorafenib in HCC leads to tumor aggression and limits the drug's survival benefits; the underlying molecular mechanisms for this resistance remain unclear. This study aimed to examine the role of the tumor suppressor RBM38 in HCC, and its potential to reverse sorafenib resistance. In addition, the molecular mechanisms underlying the binding of RBM38 and the lncRNA GAS5 were examined. The potential involvement of RBM38 in sorafenib resistance was examined using both in vitro and in vivo models. Functional assays were performed to assess whether RBM38: binds to and promotes the stability of the lncRNA GAS5; reverses the resistance of HCC to sorafenib in vitro; and suppresses the tumorigenicity of sorafenib-resistant HCC cells in vivo. RBM38 expression was lower in HCC cells. The IC50 value of sorafenib was significantly lower in cells with RBM38 overexpression than in control cells. RBM38 overexpression improved sorafenib sensitivity in ectopic transplanted tumors and suppressed the growth rate of tumor cells. RBM38 could bind to and stabilize GAS5 in sorafenib-resistant HCC cells. In addition, functional assays revealed that RBM38 reversed sorafenib resistance both in vivo and in vitro in a GAS5-dependent manner. RBM38 is a novel therapeutic target that can reverse sorafenib resistance in HCC by combining and promoting the lncRNA GAS5.

Persistent Hypokalemia Induced by an Intracavernous Ectopic Pituitary Neuroendocrine Tumor.

Persistent Hypokalemia Induced by an Intracavernous Ectopic Pituitary Neuroendocrine Tumor.

A Photo-Activated Thermoelectric Catalyst for Ferroptosis-/Pyroptosis-Boosted Tumor Nanotherapy.

Phototherapy including photothermal therapy (PTT) and photodynamic therapy (PDT) has gradually come into the limelight for oncological treatment due to its noninvasiveness, high specificity, and low side effects. However, upregulated heat-shock proteins (HSPs) and reactive oxygen species (ROS)-defensing system such as glutathione (GSH) or MutT homolog 1 (MTH1) protein in tumor microenvironment counteract the efficiency of single-modality therapy either PTT or PDT. Herein, the well-defined bismuth telluride nanoplates (Bi2 Te3 NPs) are engineered with a high-performance photo-thermo-electro-catalytic effect for tumor-synergistic treatment. Upon near-infrared light illumination, Bi2 Te3 NPs induce a significant temperature elevation for PTT, which effectively inhibits MTH1 expression. Especially, heating and cooling alteration caused temperature variations result in electron-hole separation for ROS generation, which not only damages HSPs to reduce the thermotolerance for enhance PTT, but also arouses tumor cell pyroptosis. Additionally, Bi2 Te3 NPs conspicuously reduce GSH, further improving ROS level and leading to decrease glutathione peroxidase 4 (GPX4) activity, which triggers tumor cell ferroptosis. Due to the photo-thermo-electro-catalytic synergistic therapy, Bi2 Te3 NPs are gifted with impressive tumor suppression on both ectopic and orthotopic ocular tumor models. This work highlights a high-performance multifunctional energy-conversion nanoplatform for reshaping tumor microenvironment to boost the tumor-therapeutic efficacy of phototherapy.

Mechanism of hypoxia-induced exosome circ_0051799 regulating the progression of lung adenocarcinoma.

This study attempted to investigate the effect of circ_0051799 on the immune microenvironment of lung adenocarcinoma (LUAD) and the relationship between circ_0051799 and exosomes. The number and morphology of exosomes were verified by nanoparticle tracking, transmission electron microscopy and western blotting. CCK8, EdU, Transwell and flow cytometry were used to verify the regulatory role of exosomes and circ_0051799 on tumor progression. Dual luciferase reporting and RNA immunoprecipitation were used to verify the targeted regulatory relationship between circ_0051799, miR-214-3p and IGF2BP3. WB was used to verify the role of the JAK/STAT pathway in circ_0051799 regulation. Ectopic tumor grafts and in situ models were used to validate invivo their role in regulating LUAD progression. Hypoxic environment could alter but does not alter its shape. Exosomes can participate in the regulation of macrophage polarization by circ_0051799. In vitro and invivo assays had shown that circ_0051799 could affect the proliferation and metastasis of LUAD through targeting miR-214-3p mediated IGF2BP3 regulated JAK/STAT pathway. This study found that hypoxia can affect LUAD process by promoting the regulation of macrophage polarization by exosome circ_0051799.

A case of Cushing's secondary to ectopic ACTH secreting neuroendocrine tumour

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Abstract #1380270: Struma Ovarii: A Rare Cause of Hyperthyroidism That Can Be Missed

Struma ovarii is an extremely rare monodermal teratoma of the ovaries that produce thyroid hormone. We report a case of unexplained hyperthyroidism in a female patient that was found to have struma ovarii of the right ovary. A 59-year-old woman with a past medical history of hyperthyroidism was diagnosed 4 years ago. She started taking Methimazole approximately 2 years ago when she developed palpitations and was diagnosed with atrial fibrillation with rapid ventricular response. The patient was being evaluated for Graves' disease with a thyroid scintigraphy scan. The result showed decreased iodine uptake in the thyroid. She was also being evaluated for radioactive iodine ablation. The patient was admitted to the hospital due to atrial fibrillation with rapid ventricular response secondary to hyperthyroidism. Thyroid-stimulating hormone (TSH) was suppressed, free T4 and T3 were elevated. The thyroid ultrasound showed unremarkable findings and the nuclear medicine thyroid uptake scan showed decreased uptake in the thyroid. Thyroid peroxidase antibody (TPO-Ab), thyroid stimulating hormone receptor antibody (TSH-receptor Ab), thyroglobulin antibody, thyroid-stimulating immunoglobulin (TSI) were all negative. Due to unexplained hyperthyroidism, there was a concern about ectopic thyroid hormone production. The patient had pelvic ultrasound which showed a 4.5 x 4.1 x 3.4 cm right ovarian cyst. She underwent salpingo-oophorectomy of the right ovary. Pathology results confirmed struma ovarii. After the surgery, hyperthyroidism resolved, and she was taken off Methimazole. This patient presented with primary hyperthyroidism in the setting of normal thyroid ultrasound, thyroid uptake scan, and negative thyroid antibodies. The possibility of ectopic thyroid-producing tissue or tumor should be considered in the differential diagnosis. Struma ovarii is a specialized or monodermal teratoma predominantly composed of more than 50% of mature thyroid tissue or sufficient thyroid hormone production to cause hyperthyroidism. The most common presenting symptoms at the time of diagnosis was lower abdominal pain and palpable lower abdominal mass, but patients can be asymptomatic on presentation. Struma ovarii may mimic malignant ovarian tumors or sometimes can present with symptoms of hyperthyroidism. The treatment is surgical resection of the tumor. In rare cases, this tumor could be malignant and must be ruled out by histology.

Systematic elucidation and pharmacological targeting of tumor-infiltrating regulatory Tcell master regulators.

Due to their immunosuppressive role, tumor-infiltrating regulatory Tcells (TI-Tregs) represent attractive immuno-oncology targets. Analysis of TI vs. peripheral Tregs (P-Tregs) from 36 patients, across four malignancies, identified 17 candidate master regulators (MRs) as mechanistic determinants of TI-Treg transcriptional state. Pooled CRISPR-Cas9 screening invivo, using a chimeric hematopoietic stem cell transplant model, confirmed the essentiality of eight MRs in TI-Treg recruitment and/or retention without affecting other Tcell subtypes, and targeting one of the most significant MRs (Trps1) by CRISPR KO significantly reduced ectopic tumor growth. Analysis of drugs capable of inverting TI-Treg MR activity identified low-dose gemcitabine as the top prediction. Indeed, gemcitabine treatment inhibited tumor growth in immunocompetent but not immunocompromised allografts, increased anti-PD-1 efficacy, and depleted MR-expressing TI-Tregs invivo. This study provides key insight into Treg signaling, specifically in the context of cancer, and a generalizable strategy to systematically elucidate and target MR proteins in immunosuppressive subpopulations.

Abstract 6434: A precision probiotic therapeutic promotes a more efficacious type I immune response and limits breast cancer growth in mice

Abstract High levels of Type I T-cells are needed to eradicate breast cancer. Few cancers induce Type I immunity except those that contain a high mutational burden. The majority of solid tumor patients develop a Type II immune response to commonly recognized tumor antigens, which are aberrantly expressed non-mutated tumor associated proteins. We found that within the amino acid sequence of non-mutated tumor associated antigens are class II binding epitopes that preferentially elicit a T-helper 1 interferon-gamma (g) or an IL-10 T-helper-2 response. We have identified high levels of IL-10 secreting T-cells present in the peripheral blood of both humans and mice, specific for non-mutated tumor antigens, which share significant sequence homologies with bacterial organisms found in the human gut microbiome. These lymphocytes, cross-reactive for both bacterial and tumor antigens (BAC-TA), are enriched for memory T-cells. In mice, the BAC-TA cross-reactive T-cells traffic to tumors and accelerate cancer growth. We have identified a selected number of bacterial species that are most commonly associated with numerous TA homologies (bacteriahigh) and certain species that are rarely homologous to any TA sequences (bacterialow). We hypothesized that bacterialow species can safely be enriched in the gut microbiome. TgMMTV-neu mice, a transgenic model of luminal B murine mammary cancer, pre-treated with vancomycin and metronidazole in the drinking water, received six weekly oral treatments of 109 CFU of a combination of Lactobacillus acidophilus and Ruminococcus albus, both bacterialow species. Metagenomic sequencing of stool examined one week after the last treatment revealed a mean 28% increase in R. albus (p=0.07) and a mean 38% increase in L. acidophilus (p=0.08) as compared to untreated stool. The increase in these two bacterialow species corresponded with ≥30% reduction of 10 bacteriahigh species. This oral treatment regimen also inhibited the growth of a syngeneic ectopic tumor by 36% (p=0.002). Enriching the microbiome with these bacterialow species also enhanced the immunogenicity of a previously reported non-efficacious whole protein vaccine. Immunization with a full-length plasmid-DNA based vaccine targeting IGFBP-2 demonstrated no IFN-g response in control mice (p=0.012). However, after mice were treated with L. acidophilus/R. albus, the full-length vaccine significantly induced IFN-g secretion (p=0.02). These data provide preliminary evidence that reduction of bacteriahigh species can inhibit tumor growth and augment immune responses, providing a basis for using a precision probiotic for the treatment of cancer. Future studies will address whether modulating bacteriahigh species in the gut reduces BAC-TA T-cells in the blood. Citation Format: Denise L. Cecil, Erin Rodmaker, Susan Strenk, Lauren Corulli, David N. Fredricks, Mary L. Disis. A precision probiotic therapeutic promotes a more efficacious type I immune response and limits breast cancer growth in mice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6434.

A Severe Case of Hypokalemic Metabolic Alkalosis: A Quiz

A Severe Case of Hypokalemic Metabolic Alkalosis: A Quiz

Cinobufacini injection suppresses the proliferation of human osteosarcoma cells by inhibiting PIN1-YAP/TAZ signaling pathway.

Cinobufacini injection (CI), an aqueous extract of Cutis Bufonis, is clinically used for cancer therapy in China, but its molecular mechanism for the treatment of osteosarcoma (OS) remains unclear. We constructed U2OS ectopic subcutaneous tumor model to verify the anti-OS effect of CI in vivo. Meanwhile, cell proliferation of U2OS and MG63 cells was monitored in vitro using the CCK-8 assay, colony formation and morphological changes. Cell cycle arrest and apoptosis were detected by flow cytometry and western blot, which showed that CI significantly inhibited proliferation, induced cell cycle arrest and apoptosis in human OS cells. The further RNA-seq results identified that the Hippo signaling pathway was involved in the anti-OS effect of CI. YAP/TAZ are two major components of the Hippo pathway in breast cancer and are positively regulated by prolyl isomerase PIN1, we assessed their role in OS using both clinicopathological sections and western blots. CI also inhibited PIN1 enzyme activity in a dose-dependent manner, which resulted in impaired PIN1, YAP, and TAZ expression in vitro and in vivo. Additionally, 15 potential compounds of CI were found to occupy the PIN1 kinase domain and inhibit its activity. In summary, CI plays an anti-OS role by down-regulating the PIN1-YAP/TAZ pathway.

Development of an ectopic huLiver model for Plasmodium liver stage infection.

Early Plasmodium falciparum and P. vivax infection requires parasite replication within host hepatocytes, referred to as liver stage (LS). However, limited understanding of infection dynamics in human LS exists due to species-specificity challenges. Reported here is a reproducible, easy-to-manipulate, and moderate-cost in vivo model to study human Plasmodium LS in mice; the ectopic huLiver model. Ectopic huLiver tumors were generated through subcutaneous injection of the HC-04 cell line and shown to be infectible by both freshly dissected sporozoites and through the bite of infected mosquitoes. Evidence for complete LS development was supported by the transition to blood-stage infection in mice engrafted with human erythrocytes. Additionally, this model was successfully evaluated for its utility in testing antimalarial therapeutics, as supported by primaquine acting as a causal prophylactic against P. falciparum. Presented here is a new platform for the study of human Plasmodium infection with the potential to aid in drug discovery.

Top 10 Nested Pattern Head and Neck Lesions to Notice.

Nested is defined as "cellular clusters arranged in small groupings with intervening vascular or stromal networks, lacking lumens or glandular formation." Using this definition, multiple neoplastic and non-neoplastic lesions of the head and neck come into the differential. We have broadly organized the differential diagnosis of "nested" tumors into entities with neuroendocrine differentiation, squamous differentiation, thyroid follicular cell differentiation, and other lesions. Review. Many different entities have a nested appearance and the morphologic, immunohistochemical, clinical, and radiographic features contribute to the differential diagnosis. The different tumors covered in this review include neuroendocrine neoplasms, paraganglioma, middle ear neuroendocrine tumor (formerly known as middle ear adenoma), medullary thyroid carcinoma, poorly differentiated thyroid carcinoma, olfactory neuroblastoma, ectopic pituitary neuroendocrine tumor, hyalinizing trabecular tumor, solid subtype of papillary thyroid carcinoma, solid cell nests/C-cell hyperplasia, necrotizing sialometaplasia, and meningioma. In this review, we discuss the morphologic and immunohistochemical features of the covered entities as a guide to differential diagnosis when nested-patterned head and neck lesions are encountered.

Cushing's syndrome due to atypical carcinoid of the mediastinum

Ectopic Cushing's syndrome, caused by a neuroendocrine tumor (NET), is a rare finding. NETs of the mediastinum are extremely rare. NETs arising from the anterior mediastinum are generally aggressive. They are widely characterized at clinical presentations, and may be asymptomatic or present with atypical symptoms. Prognosis is often poor due to their local recurrence and distant metastasis despite a multimodal approach. A 33-year-old male patient was admitted to our department with a femoral soft tissue abscess, diabetes, and hypokalemia. He had no typical features of Cushing's syndrome. However, with a few simple tests, that is, a basal hormone profile, and low-dose and high-dose dexamethasone suppression tests, we diagnosed this complicated condition of ectopic adrenocorticotrophic hormone (ACTH) secretion. Thoracic computed tomography revealed an anterior mediastinal mass of 35×22 mm. A surgical excision of the tumor was proposed, and intra-operative pathology consultation returned positive for the suspected NET. Immunohistochemically, the tumor cells were positive for CK, CD56, Chromogranin, Synaptophysin, S100, and CD117. No thymic tissue was found. The Ki-67 was 4%. A diagnosis of primary NETs of the mediastinum, intermediate grade (G2), of atypical carcinoids according to WHO 2015 was established. This patient survived with no sequelae, no distant metastasis, no recurrence, and without adjuvant radiotherapy or chemotherapy 2 years after surgery thanks to earlier diagnosis and prompt surgical intervention. Mediastinum ectopic ACTH-secreting tumors are a rare type of cancer. According to recent research, these tumors frequently display more aggressive behavior and are linked to endocrinopathies. It is noted that patient might have a better outcome and a longer survival time due to earlier detection and complete resection of malignancies.

Ectopic sphenoidal ACTH-secreting adenoma revealed by 11C Methionine PET scan: case report

BackgroundEctopic ACTH pituitary adenomas (EAPA), located outside the sella turcica and deriving from cellular remnants of Rathke’s pouch are a very rare cause of Cushing’s syndrome (CS). The diagnosis is often difficult and delayed, even after comprehensive work-up. To our knowledge, we report for the first time an ectopic corticotroph tumor of the posterior wall of the sphenoid sinus, leading to false positive results of bilateral inferior petrosal sinus sampling (BIPPS) and which was finally localized by a co-registered11 C Methionine PET/MR imaging.Case presentationA 48-year-old woman was referred for a high clinical suspicion of ACTH-dependent CS. Biological testing comprising low dose dexamethasone suppression and CRH stimulation tests were indicative of pituitary Cushing’s disease, but comprehensive pituitary MRI did not reveal any pituitary adenoma. BIPSS confirmed however a central origin of ACTH secretion (central-to-peripheral ACTH ratio > 100) and revealed a significant right-to-left gradient (6.2), leading to a first right-sided exploratory hypophysectomy, that did not cure the patient. BIPSS images were reviewed and revealed preferential drainage of the left pituitary to the right petrosal sinus, leading us to a left sided exploratory hypophysectomy, which was again unsuccessful. A11 C Methionine PET/MRI was performed and revealed a hypermetabolic lesion adjacent to the posterior wall of the sphenoidal sinus. After surgical resection, this polypoid mass was identified as an ectopic ATCH-secreting pituitary adenoma expressing ACTH and T-Pit and complete remission of hypercortisolism was observed.ConclusionsIn conclusion, we report a case of ACTH-dependent Cushing’s syndrome, caused by an ectopic corticotroph adenoma located in the sphenoidal sinus, which perfectly mimicked the biological features of a classical pituitary ACTH adenoma on a comprehensive hormonal evaluation including BIPPS, and the features of a benign naso-sinusal polyp at MRI. We report for the first time a key role of11 C Methionine PET co-registered to high resolution MRI for localizing ectopic adenomas, efficiently guiding surgical removal and leading to complete remission of hypercortisolism.