scholarly journals Urinary bladder paraganglioma metastatic to the lung in a patient with SDHB gene mutation: A case report

2021 ◽  
Vol 8 (1) ◽  
pp. 5
Author(s):  
Chinelo P. Onyenekwu ◽  
Kenneth A. Iczkowski ◽  
Yuri Sheinin
Keyword(s):  
Primary Tumor ◽  
Wedge Resection ◽  
Lung Nodule ◽  
Gene Mutations ◽  
Pathogenic Mutation ◽  
The Body ◽  
Sustentacular Cells ◽  
S 100 ◽  
Sdhb Gene ◽  
Succinate Dehydrogenase Subunit B

Introduction: Paragangliomas are tumors originating from the neural crest. Most of them are benign and arise from various locations in the body. Extra-adrenal paragangliomas arise as sporadic cases in most settings or as part of heredofamilial syndromes in about one-quarter of cases. Succinate dehydrogenase subunit B (SDHB) gene mutations are associated with an aggressive clinical disease course of pheochromocytoma/paraganglioma.Methods: We present a 41-year-old male former smoker with a history of a growing right upper lung nodule on chest imaging. He had no cough or respiratory symptoms. Twenty-seven months prior, the patient underwent a cystoprostatectomy due to paraganglioma of the bladder. Genetic testing identified a pathogenic mutation in SDHB gene, c.166_170delCCTCA (p.Pro56Tyrfs*5). He underwent a wedge resection of the lung nodule.Results: Sectioning of the lung wedge revealed a well-circumscribed, firm tan nodule. Microscopically there were nests of large neoplastic cells with round nuclei and eosinophilic granular cytoplasm. Tumor cells were positive for synaptophysin and chromogranin and negative for pan-cytokeratin. S-100 protein highlighted sustentacular cells. Morphologically, the pulmonary neoplasm was similar to the primary tumor of the bladder. These features are consistent with a bladder paraganglioma metastatic to the lung, in a background of a hereditary paraganglioma syndrome.Conclusion: Extra-adrenal paraganglioma occurring in a setting of hereditary paraganglioma syndrome has a high risk of metastasis. Lifelong surveillance even after prompt resection of the primary tumor with negative margins is required to ensure early detection of metastasis and prevent complications associated with it.

Paraganglioma of the Urinary Bladder Metastatic to the Lung in a Patient with SDHB Gene Mutation: A Case Report

2020 ◽  
Vol 154 (Supplement_1) ◽  
pp. S32-S32
Author(s):  
C P Onyenekwu ◽  
K A Iczkowski ◽  
Y Sheinin
Keyword(s):  
Wedge Resection ◽  
Lung Nodule ◽  
Gene Mutations ◽  
Pathogenic Mutation ◽  
The Body ◽  
Sustentacular Cells ◽  
History Of ◽  
Paraganglioma Syndrome ◽  
Sdhb Gene ◽  
Succinate Dehydrogenase Subunit B

Abstract Introduction/Objective Paragangliomas are tumors originating from the neural crest. Most tumors are benign and arise from various locations in the body. Extra-adrenal paragangliomas arise as sporadic cases in most settings or as part of heredofamilial syndromes in about one-quarter of cases. Succinate dehydrogenase subunit B (SDHB) gene mutations are associated with an aggressive clinical disease course of pheochromocytoma/paraganglioma. Methods We present a 41-year-old male former smoker with a history of a growing right upper lung nodule on chest imaging. He had no cough or respiratory symptoms. Twenty-seven months prior the patient underwent a cystoprostatectomy due to paraganglioma of the bladder. Genetic testing identified a pathogenic mutation in SDHB gene, c.166_170delCCTCA (p.Pro56Tyrfs*5). He underwent a wedge resection of the lung nodule. Results Sectioning of the lung wedge revealed a well circumscribed, firm tan nodule. Microscopically there were nests of large neoplastic cells with round nuclei and eosinophilic granular cytoplasm. Tumor cells were positive for synaptophysin and chromogranin and negative for pan-cytokeratin. S100 highlighted sustentacular cells. The pulmonary neoplasm was morphologically similar to the prior tumor of the bladder. These features are consistent with a metastatic urothelial paraganglioma to the lung, in a background of a hereditary paraganglioma syndrome. Conclusion Extra-adrenal paraganglioma occurring in a setting of hereditary paraganglioma syndrome has a higher risk of metastasis. Lifelong surveillance even after prompt resection of primary tumor with negative margins is required to ensure early detection of metastasis and prevention of complications associated with it.

scholarly journals Transaminitis Evaluation Leads to the Incidental Diagnosis of Familial Paraganglioma Due to SDHB Mutation

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A161-A162
Author(s):  
Anderson Okafor ◽  
Anitha Yelangi ◽  
Julie Samantray
Keyword(s):  
Succinate Dehydrogenase ◽  
Gene Mutations ◽  
Pet Scan ◽  
Retroperitoneal Mass ◽  
Sdhb Mutation ◽  
Elevated Liver Enzymes ◽  
History Of ◽  
Sdhb Gene ◽  
Succinate Dehydrogenase Subunit B ◽  
Subunit B

Abstract Background: Paragangliomas are rare neuroendocrine tumors. Patients with succinate dehydrogenase subunit B (SDHB) gene mutations are predisposed to developing paraganglioma/pheochromocytoma. We are presenting the case of an incidental finding of a paraganglioma during an evaluation for transaminitis. Clinical Case: A 23-year-old male with a medical history of right hydrocele repair as a teenager was evaluated with an ultrasound of the abdomen for elevated liver enzymes and right upper quadrant discomfort. The ultrasound revealed a large lobular solid vascular 13.8 x 8.1 x 11.3 cm mass in the mid abdomen. He underwent a CT of the chest, abdomen and pelvis which demonstrated a large retroperitoneal mass measuring 16 x 10 x 13.7 cm within the right mid abdomen. The mass was described as a large centrally necrotic peripherally enhancing right retroperitoneal mass displacing the IVC anteriorly. The patient subsequently underwent an image-guided biopsy of the mass and the pathology revealed it was a paraganglioma. The patient denied any history of hypertension, orthostasis, headaches or palpitations. Biochemical workup for plasma catecholamines, plasma metanephrines, 24-hour urine catecholamines and metanephrines and cortisol were unremarkable. His transaminitis also resolved. He underwent a retroperitoneal paraganglioma excision and the final pathology was consistent with paraganglioma and negative for capsular invasion. He was referred to a genetic counsellor for testing since paragangliomas can be inherited. He also mentioned a family history of breast cancer in his mother and HTN and prostate cancer in his father. His test revealed that he had a c.289A>T mutation in his SDHB gene. He was encouraged to share the information with his family to help them understand the implications of his genetic test result. He underwent a surveillance PET scan which showed multiple osseous lesions in his temporal calvarium, sphenoid, spine and sacrum suggestive of metastasis. Repeat imaging with a DOTATATE PET scan showed stable disease. His transaminitis was transient, and we did not find a correlation to his paraganglioma. His imaging tests showed no liver metastasis. A CT of the head showed no evidence of intracranial metastasis. The current plan is to continue surveillance. His older brother underwent a genetic testing. He tested positive for the same SDHB mutation and underwent biochemical and imaging tests which were unremarkable. He too will continue surveillance. Conclusions: Patients with a succinate dehydrogenase subunit B (SDHB) gene mutations are predisposed to developing paraganglioma/pheochromocytoma. The tumors produce catecholamines, but can be biochemically silent as in our patient. They are inherited in an autosomal dominant manner. Our case highlights the importance for genetic counseling which increases the chances of early screening and surveillance in affected family members for optimal multidisciplinary management of patients.

scholarly journals SAT-LB313 A Unicorn With Double Horns - Metastatic Paraganglioma in a Patient With Beckwith-Wiedemann Syndrome and Hereditary Paraganglioma Syndrome Iv

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Anand Narayanan ◽  
Myat Soe ◽  
Amber L Wheeler ◽  
Paul A Fitzgerald
Keyword(s):  
Genetic Testing ◽  
Abdominal Mass ◽  
Pathogenic Mutation ◽  
Abdominal Wall Defects ◽  
Sdhb Mutation ◽  
Imprinting Disorder ◽  
First Case ◽  
Increased Risk ◽  
Sdhb Gene ◽  
Succinate Dehydrogenase Subunit B

Abstract Introduction: Beckwith-Wiedemann syndrome (BWS), a multisystem genomic imprinting disorder in chromosome 11p15.5 region, is an overgrowth syndrome often presenting with macroglossia, abdominal wall defects, hemihyperplasia, enlarged abdominal organs and an increased risk of tumors including neuroblastoma, rhabdomyosarcoma, unilateral Wilm’s tumor, hepatoblastoma, adrenal cortical carcinoma and pheochromocytoma. Six cases of benign bilateral pheochromocytomas and one case of pheochromocytoma with lymph node metastasis in BWS have been described in the literature. We describe the first case of BWS with distant metastatic paraganglioma harboring an SDHB (succinate dehydrogenase subunit B) mutation. Presentation: A 28-year-old male with BWS whose history included an omphalocele and diaphragmatic hernia in infancy, neuroblastoma resected at age 2, and left carotid paraganglioma (PGL) resected at age 22 presented with abdominal pain. CT A/P with contrast revealed a 3.3 x 4.4 cm hypervascular mass and multiple bone metastases. Workup revealed normal plasma/urine metanephrines, elevated plasma dopamine of 178 pg/ml (normal <20) and elevated chromogranin A of 190 ng/ml (normal <90). 68Ga-dotatate PET CT showed hypermetabolic 4.4 cm mass (SUV 83), right hypopharynx mass (SUV 49), and many dota avid areas throughout the skeleton. The abdominal mass was resected and pathology was consistent with PGL. Due to unusual presentation, patient underwent hereditary cancer genetic testing (67 gene panel) and pathogenic mutation (c.713delT) in the SDHB gene was identified, consistent with hereditary PGL syndrome IV. Conclusion: While pheochromocytomas and other tumors are commonly found in association with BWS, PGLs are not. This is the first documented case of a patient with BWS having distant metastatic PGL. Malignant transformation of hereditary and sporadic pheochromocytomas and paraganglioma (PPGLs) is more common in SDHx associated PPGLs (>40% of metastatic PPGLs are related to an SDHB mutation). Hereditary PGL syndromes should be suspected in the case of PGLs that are recurrent, early onset (<45 years), extra-adrenal and/or metastatic. With additional genetic testing, our patient with an already rare growth disorder was found to have hereditary PGL syndrome IV caused by a pathogenic mutation in the SDHB gene. This unique case highlights the rationale and importance of systematic genetic cancer screening in the diagnostic evaluation of PPGLs.

scholarly journals Inflammation-Related Carcinogenesis: Lessons from Animal Models to Clinical Aspects

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 921
Author(s):  
Futoshi Okada ◽  
Runa Izutsu ◽  
Keisuke Goto ◽  
Mitsuhiko Osaki
Keyword(s):  
Animal Models ◽  
Tissue Injury ◽  
Economic Status ◽  
Gene Mutations ◽  
Inflammatory Cells ◽  
The Body ◽  
Clinical Aspects ◽  
Promote Cell Proliferation ◽  
Organ Specific ◽  
Altered Gene

Inflammation-related carcinogenesis has long been known as one of the carcinogenesis patterns in humans. Common carcinogenic factors are inflammation caused by infection with pathogens or the uptake of foreign substances from the environment into the body. Inflammation-related carcinogenesis as a cause for cancer-related death worldwide accounts for approximately 20%, and the incidence varies widely by continent, country, and even region of the country and can be affected by economic status or development. Many novel approaches are currently available concerning the development of animal models to elucidate inflammation-related carcinogenesis. By learning from the oldest to the latest animal models for each organ, we sought to uncover the essential common causes of inflammation-related carcinogenesis. This review confirmed that a common etiology of organ-specific animal models that mimic human inflammation-related carcinogenesis is prolonged exudation of inflammatory cells. Genotoxicity or epigenetic modifications by inflammatory cells resulted in gene mutations or altered gene expression, respectively. Inflammatory cytokines/growth factors released from inflammatory cells promote cell proliferation and repair tissue injury, and inflammation serves as a “carcinogenic niche”, because these fundamental biological events are common to all types of carcinogenesis, not just inflammation-related carcinogenesis. Since clinical strategies are needed to prevent carcinogenesis, we propose the therapeutic apheresis of inflammatory cells as a means of eliminating fundamental cause of inflammation-related carcinogenesis.

scholarly journals A Case of Benign Schwannoma of the Ascending Colon Treated With Laparoscopic-Assisted Wedge Resection

2013 ◽  
Vol 98 (4) ◽  
pp. 315-318 ◽  
Author(s):  
Se-Jin Baek ◽  
Won Hwangbo ◽  
Jin Kim ◽  
In-Sun Kim
Keyword(s):  
Submucosal Tumor ◽  
Wedge Resection ◽  
Ascending Colon ◽  
Mesenchymal Tumors ◽  
Benign Schwannoma ◽  
S 100 ◽  
Colon And Rectum ◽  
Laparoscopic Assisted ◽  
Specific Symptoms ◽  
Diffuse Positivity

Abstract Isolated colonic schwannomas are rare gastrointestinal mesenchymal tumors. Only a small number of cases have been reported. Occurrence of these tumors is more common in the stomach than in the large intestine. These spindle cell lesions are distinct from leiomyoma, leiomyosarcoma, and gastrointestinal stromal tumors because the tumor cells have a distinct immunophenotype, with strong diffuse positivity for S-100 and vimentin, as well as corroborative negative staining of CD117 and smooth muscle markers. We present a case of colonic schwannoma in a 70-year-old woman who had no specific symptoms. The patient was diagnosed with a submucosal tumor in the ascending colon on colonoscopy and abdominal computed tomography. Laparoscopic-assisted wedge resection of colon was performed. The very rare pathologic diagnosis of ascending schwannoma was made postoperatively. This case is interesting because schwannomas of the colon and rectum are extremely rare and are treated by laparoscopic-assisted wedge resection.

Functional Ulnar Nerve Paraganglioma: First Documented Occurrence in the Extremity With Hitherto Undescribed Associated Extensive Glomus Cell Hyperplasia and Tumorlet Formation

2017 ◽  
Vol 26 (1) ◽  
pp. 64-72 ◽  
Author(s):  
Louis Tsun Cheung Chow ◽  
Michael Ho Ming Chan ◽  
Simon Kwok Chuen Wong
Keyword(s):  
Ulnar Nerve ◽  
Nerve Biopsy ◽  
Vascular Tumor ◽  
The Body ◽  
Glomus Cell ◽  
Cell Hyperplasia ◽  
Chief Cells ◽  
Sustentacular Cells ◽  
History Of ◽  
The Right

Extra-adrenal paraganglioma has never been described in the extremities. A 34-year-old woman complained of an enlarging mass in the right forearm for 18 months. Imaging showed a circumscribed vascular tumor attached to the ulnar nerve; biopsy revealed features of paraganglioma. The resected tumor consisted of zellballen pattern of chief cells staining positively for chromogranin with surrounding S100-positive sustentacular cells. The chief cells contained many neurosecretory granules and mitochondria, whereas the sustentacular cells contained a large amount of rough endoplasmic reticulum and some microfilaments. There was adjacent extensive glomus cell hyperplasia and tumorlet formation. The intraoperative blood pressure dropped abruptly on tumor removal. The serum normetanephrine level decreased from a preoperative level of 1987 pg/mL (normal < 149 pg/mL) to normal after operation. The patient admitted on questioning to a history of paroxysmal attacks of transient palpitation, hand tremors, and sweating; imaging showed no evidence of tumor in other parts of the body, and there was no family history of similar tumor; she remained well 33 months after the operation. This occurrence of functional ulnar nerve paraganglioma with the hitherto undescribed associated glomus cell hyperplasia and tumorlet formation attests to the probable existence of normal sympathetic paraganglia in the extremity and their intimate functional relationship with glomus bodies.

scholarly journals Transcriptional Regulation of Dental Epithelial Cell Fate

2020 ◽  
Vol 21 (23) ◽  
pp. 8952
Author(s):  
Keigo Yoshizaki ◽  
Satoshi Fukumoto ◽  
Daniel D. Bikle ◽  
Yuko Oda
Keyword(s):  
Stem Cells ◽  
Cell Fate ◽  
Gene Mutations ◽  
Dental Enamel ◽  
The Body ◽  
Epithelial Stem Cells ◽  
Cell Fates ◽  
Chromatin Regulators ◽  
Dental Epithelium ◽  
Potential Tool

Dental enamel is hardest tissue in the body and is produced by dental epithelial cells residing in the tooth. Their cell fates are tightly controlled by transcriptional programs that are facilitated by fate determining transcription factors and chromatin regulators. Understanding the transcriptional program controlling dental cell fate is critical for our efforts to build and repair teeth. In this review, we describe the current understanding of these regulators essential for regeneration of dental epithelial stem cells and progeny, which are identified through transgenic mouse models. We first describe the development and morphogenesis of mouse dental epithelium in which different subpopulations of epithelia such as ameloblasts contribute to enamel formation. Then, we describe the function of critical factors in stem cells or progeny to drive enamel lineages. We also show that gene mutations of these factors are associated with dental anomalies in craniofacial diseases in humans. We also describe the function of the master regulators to govern dental lineages, in which the genetic removal of each factor switches dental cell fate to that generating hair. The distinct and related mechanisms responsible for the lineage plasticity are discussed. This knowledge will lead us to develop a potential tool for bioengineering new teeth.

scholarly journals Resectable lung lesions malignancy assessment and cancer detection by ultra-deep sequencing of targeted gene mutations in plasma cell-free DNA

2019 ◽  
Vol 56 (10) ◽  
pp. 647-653 ◽  
Author(s):  
Muyun Peng ◽  
Yuancai Xie ◽  
Xiaohua Li ◽  
Youhui Qian ◽  
Xiaonian Tu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Patients ◽  
Cancer Detection ◽  
Deep Sequencing ◽  
Lung Diseases ◽  
Early Cancer ◽  
Lung Nodule ◽  
Gene Mutations ◽  
Tumour Tissue ◽  
Early Cancer Diagnosis

BackgroundEarly detection of lung cancer to allow curative treatment remains challenging. Cell-free circulating tumour (ct) DNA (ctDNA) analysis may aid in malignancy assessment and early cancer diagnosis of lung nodules found in screening imagery.MethodsThe multicentre clinical study enrolled 192 patients with operable occupying lung diseases. Plasma ctDNA, white cell count genomic DNA (gDNA) and tumour tissue gDNA of each patient were analysed by ultra-deep sequencing to an average of 35 000× of the coding regions of 65 lung cancer-related genes.ResultsThe cohort consists of a quarter of benign lung diseases and three quarters of cancer patients with all histopathology subtypes. 64% of the cancer patients are at stage I. Gene mutations detection in tissue gDNA and plasma ctDNA results in a sensitivity of 91% and specificity of 88%. When ctDNA assay was used as the test, the sensitivity was 69% and specificity 96%. As for the lung cancer patients, the assay detected 63%, 83%, 94% and 100%, for stages I, II, III and IV, respectively. In a linear discriminant analysis, combination of ctDNA, patient age and a panel of serum biomarkers boosted the overall sensitivity to 80% at a specificity of 99%. 29 out of the 65 genes harboured mutations in the patients with lung cancer with the largest number found in TP53 (30% plasma and 62% tumour tissue samples) and EGFR (20% and 40%, respectively).ConclusionPlasma ctDNA was analysed in lung nodule assessment and early cancer detection, while an algorithm combining clinical information enhanced the test performance.Trial registration numberNCT03081741.

scholarly journals Isolated Langerhans Cell Histiocytosis of Orbit: A Case Report and Review of the Literature

2018 ◽  
Vol 2018 ◽  
pp. 1-6
Author(s):  
Mayuresh Naik ◽  
Anuj Mehta ◽  
Neha Mehrotra ◽  
Anil Solanki
Keyword(s):  
Body Weight ◽  
Langerhans Cell Histiocytosis ◽  
Bone Erosion ◽  
Histopathological Examination ◽  
Oral Prednisolone ◽  
Langerhans Cell ◽  
The Body ◽  
S 100 ◽  
Immunohistochemical Studies ◽  
Incision Biopsy

A 2-year-old male child presented with a painless progressive mass in the inferolateral aspect of right orbit of three-month duration. Differential leucocyte count revealed raised eosinophil count (13%). On radiological examination, CT scan showed 25 × 27 mm round well-defined smooth-outlined homogenously enhancing extraconal mass arising from the zygomatic bone at the inferotemporal periorbital area of right orbit with bone erosion. Histopathological examination of the incision biopsy revealed characteristic Langerhans cells and immunohistochemical studies were positive for S-100 protein and adenosine deaminase. A diagnosis of Langerhans Cell Histiocytosis (LCH) was made and PET-CT revealed no other foci of uptake anywhere else in the body. The patient received 12 cycles of vinblastine, 0.2 mg/kg body weight, along with oral prednisolone, 1 mg/kg body weight. On completion of three cycles of chemotherapy, a reduction in size of the mass was noticed. A repeat PET scan was done 3 months after completion of chemotherapy did not reveal any activity noted previously.

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