Metastasis Of Carcinoid Tumor Research Articles

Multiomic sequencing of paired primary and metastatic small bowel carcinoids

Background: Small bowel carcinoids are insidious tumors that are often metastatic when diagnosed. Limited mutation landscape studies of carcinoids indicate that these tumors have a relatively low mutational burden. The development of targeted therapies will depend upon the identification of mutations that drive the pathogenesis and metastasis of carcinoid tumors. Methods: Whole exome and RNA sequencing of 5 matched sets of normal tissue, primary small intestine carcinoid tumors, and liver metastases were investigated. Germline and somatic variants included: single nucleotide variants (SNVs), insertions/deletions (indels), structural variants, and copy number alterations (CNAs). The functional impact of mutations was predicted using Ensembl Variant Effect Predictor. Results: Large-scale CNAs were observed including the loss of chromosome 18 in all 5 metastases and 3/5 primary tumors. Certain somatic SNVs were metastasis-specific; including mutations in ATRX, CDKN1B, MXRA5 (leading to the activation of a cryptic splice site and loss of mRNA), SMARCA2, and the loss of UBE4B. Additional mutations in ATRX, and splice site loss of PYGL, leading to intron retention observed in primary and metastatic tumors. Conclusions: We observed novel mutations in primary/metastatic carcinoid tumor pairs, and some have been observed in other types of neuroendocrine tumors. We confirmed a previously observed loss of chromosome 18 and CDKN1B. Transcriptome sequencing added relevant information that would not have been appreciated with DNA sequencing alone. The detection of several splicing mutations on the DNA level and their consequences at the RNA level suggests that RNA splicing aberrations may be an important mechanism underlying carcinoid tumors.

Atypical thymic carcinoid associated with rapidly progressive symptoms of Cushing's syndrome in a child

Atypical thymic carcinoid in children is rare and its prognosis principally depends on the completeness of the surgical resection. We report a case of atypical thymic carcinoid with lymph node metastasis that had not been identified prior to surgery. An 8-year-old boy was referred because of Cushing's syndrome and a worsening of his symptom, which included facial edema, fatigue, and headache, over 3 weeks. Blood testing revealed high plasma cortisol and adrenocorticotropic hormone (ACTH), and chest computed tomography demonstrated two tumors in his anterior mediastinum, but no findings suggestive of lymph node metastasis. We suspected the presence of an ACTH-producing thymic carcinoid tumor; therefore, the patient underwent total thymectomy and dissection of his anterior mediastinal and bilateral deep cervical lymph nodes. Histopathological examination revealed an atypical carcinoid tumor and left cervical lymph node metastasis. The patients' plasma cortisol and ACTH concentrations decreased after surgery, and he was further treated with radiotherapy and combination chemotherapy. Thus, it is possible that the development of symptoms may indicate more rapid progression of atypical thymic carcinoid, and deep cervical lymphadenectomy is necessary for its complete resection.

Solitary late metastasis of primary renal cell carcinoid tumor to the extraocular muscles imaged with indium-111 octreotide

A 75-year-old male presented with right eye pain and proptosis. His history was significant for renal cell carcinoma treated with left nephrectomy 2 years previously. Computed tomography (CT) imaging demonstrated a 1.6-cm enhancing lesion in the right retrobulbar space. Surgical biopsy revealed a low-grade metastatic carcinoid tumor. At retrospective review, the primary renal lesion from 2 years prior was rediagnosed as consistent with a renal carcinoid tumor. Indium-111 octreotide single photon emission CT/CT imaging demonstrated a solitary metastasis within the right extraocular muscles. The patient subsequently developed additional metastases within the remaining right kidney and lung.

Pituitary Metastasis of Bronchial Carcinoid Tumor Mimicking Pituitary Adenoma: a Case Report

Pituitary Metastasis of Bronchial Carcinoid Tumor Mimicking Pituitary Adenoma: a Case Report

A concealed carcinoid cardiac metastasis uncovered by comprehensive cardiovascular magnetic resonance-based tissue characterization: a case report.

BackgroundCardiac metastases of carcinoid tumours are extremely rare, and their diagnosis poses a significant challenge. A variety of techniques has been reported in the literature for this purpose, ranging from echocardiogram to the Indium-111 Octreotide, positron emission tomography using specific tracers, and biopsy. Occasionally, the diagnosis is only made post-mortem. Recently, CMR (cardiovascular magnetic resonance) has been added to the diagnostic toolkit. This case report describes the CMR sequences that can be used to characterize cardiac metastases of carcinoid tumours.Case summaryA 55-year-old woman with an antecedent history of resected carcinoid tumour of the ileocecal junction underwent whole-body In-111 Octreoscan single-photon emission computed tomography in the context of her follow-up. This raised the suspicion of pericardial involvement, which prompted a CMR study. Comprehensive CMR findings were consistent with isolated carcinoid tumour metastasis embedded within the anterior papillary muscle. We describe the CMR sequences that were used to characterize the metastasis.DiscussionThe rarity of cardiac metastasis of carcinoid tumour makes its diagnosis challenging and warrants a high level of clinical suspicion. Cardiovascular magnetic resonance imaging proves to be an indispensable tool in the tissue characterization of such tumours.

Prevalence of metastasis and survival of 788 patients with T1 rectal carcinoid tumors

Prevalence of rectal carcinoids is increasing, partly because of increased colorectal cancer screening. Local excision (endoscopic or transanal excision) is usually performed for small (<1-2 cm) rectal carcinoids, but data on clinical outcomes from large population-based U.S. studies are lacking. The aims of this study were to determine the prevalence of metastasis of resected small rectal carcinoid tumors using a large national cancer database and to evaluate the long-term survival of patients after local resection as compared with radical surgery. The Surveillance Epidemiology and End Results database was used to identify 788 patients with rectal T1 carcinoids<2 cm in size. Prevalence of metastases at initial diagnosis and risk factors for metastases were analyzed. Cancer-specific survival (CSS) was calculated. A total of 727 patients (92.3%) had tumors≤10mm in diameter and 61 (7.7%) had tumors 11 to 19mm. Overall, 12 patients (1.5%) had metastasis at the time of diagnosis with prevalence of 1.1% in lesions≤10mm and 6.6% in lesions 11 to 19mm (P= .01). Survival of patients with T1 rectal carcinoids without metastasis was significantly better than those with metastasis (5-year CSS of 100% vs 78%, P< .001). Of 559 patients with T1N0M0 rectal carcinoids≤10mm, 5-year CSS was 100% in both groups who underwent local excision and those who underwent radical surgery. Larger T1 rectal carcinoid tumors (11-19mm) have significantly higher risk of lymph node metastases compared with those≤10mm. Survival is worse with metastatic disease. Local therapy is adequate for T1N0M0 rectal carcinoids≤10mm in size with excellent long-term outcomes.

The clinical outcomes and risk factors associated with incomplete endoscopic resection of rectal carcinoid tumor.

The risk of lymph node metastasis of a small rectal carcinoid tumor (<10mm) is known to be lower than that of tumors at other gastrointestinal sites. Although rectal carcinoid tumors can be treated by endoscopic resection, the resected specimen may be incomplete. The consequences of an incomplete resection are not well known. From December 2008 to November 2015, cases of rectal carcinoid tumors resected by endoscopic resection techniques such as endoscopic submucosal dissection (ESD), or endoscopic mucosal resection using band ligation device (EMR-L), or cap aspiration (EMR-C) were enrolled. The factors associated with incomplete endoscopic resection and clinical outcomes were retrospectively analyzed. During the study period, a total of 134 rectal carcinoid tumors were resected by endoscopic techniques; ESD (n = 53), EMR-C (n = 65), and EMR-L (n = 16). The mean tumor size was 5.5 ± 2.4mm. The mean follow-up period was 835 ± 501 days. The en bloc resection and complete resection rates were 100 and 85.8%, respectively. Procedure time was longer and the size of the resected tumor was larger in the ESD group than in the EMR-C or EMR-L (p < 0.001) group by the univariate analysis. A factor related to incomplete resection was central depression on the surface (OR 11.529, 95% CI 2.377-55.922, p = 0.002), as revealed by the multivariate analysis. Nineteen patients had an incomplete resection status and did not undergo additional resection treatment; none of these patients had recurrence during the study period. A rectal carcinoid tumor with a central depression on the surface was associated with a higher incomplete resection rate. After an incomplete resection of small rectal carcinoid tumors, without evidence of lymphovascular invasion, a periodic follow-up examination without additional resection may be recommended.

Anesthetic management of patients undergoing resection of carcinoid metastasis to the brain

BackgroundCarcinoid tumors are derived from enterochromaffin cells and may release physiologically active compounds into the systemic circulation, leading to the development of carcinoid syndrome. Occasionally, these tumors metastasize to the brain, warranting biopsy or resection. In these surgical patients, the perioperative implications for anesthetic management are not heretofore defined in the indexed literature. MethodsPatients who had craniotomy for biopsy or resection of intracranial carcinoid tumors were retrospectively identified at a single medical center. Patient demographics, perioperative anesthetic management, adverse events, and outcome were summarized in this case series. ResultsEleven patients were identified; median age was 60 years (range = 42-78 years), and 45% were male. Immediately before surgery, 4 patients (36%) were receiving a somatostatin analog drug, and no patient had unchecked carcinoid syndrome. All patients received general anesthesia that included inhaled isoflurane and nitrous oxide, and all had invasive arterial blood pressure monitoring. One patient developed sustained hypotension after induction of anesthesia, likely related to hypovolemia and anesthetic drugs, but the possibility of carcinoid mediator release cannot be excluded. There were no other signs or symptoms of carcinoid syndrome in this or any other patient. Of all 11 patients, 10 (91%) experienced either significant disease progression (n = 2; 18%) or death (n = 8; 73%) from carcinoid disease, its sequelae, or an undetermined cause within 3 years after surgery. Of note, 3 of the deaths occurred shortly after surgery, on postoperative days 3, 7, and 8. ConclusionsIn our experience, carcinoid tumor metastasis to the brain—whether because of tumor makeup or prior treatment—is unlikely to produce symptoms of new-onset carcinoid syndrome intraoperatively; however, the risk cannot be completely excluded. Postsurgical prognosis was poor, both within the hospital and after hospital discharge.

低位前方切除後24年目に肝転移を認めた直腸カルチノイドの1例

症例は90歳，男性．24年前に直腸カルチノイドに対して直腸低位前方切除術施行歴があった．無症状であったが，健診目的の胸部レントゲンで右胸水疑いと指摘されたのをきっかけにCTが施行され，肝S5に腫瘤性病変を認めた．CT上胸部には異常所見を認めなかった．当初は肝内胆管癌を考慮したが，高齢であることを踏まえ肝S5部分切除術を施行した．病理組織学的検査で直腸neuroendocrine tumor （NET）と診断され，24年前に手術施行した直腸カルチノイドの肝転移と判断された．術後7カ月経過現在，無再発生存中である．直腸カルチノイドは一般に低悪性度といわれるが進行が緩徐であることを踏まえ，直腸カルチノイド治療歴のある患者に対しては長期経過後の再発もありうることを念頭に置きつつ診療にあたることが重要と思われる．

中耳カルチノイド例

We report herein on the 20th case in Japan of a carcinoid tumor observed in the middle ear. The patient was a 71-year-old man who was first seen in our hospital in November 2012 for tinnitus of 3 years’ duration. On otoscopic examination, a white mass could be observed through the tympanic membrane. High computed tomography demonstrated a tumor like lesion with no evidence of bone destruction. We first performed a probe tympanotomy and pathologically the lesion was diagnosed as a carcinoid tumor of the middle ear. We subsequently performed a tympanoplasty and completely removed the tumor. Recently, somatostatin receptor imaging has become available to detect metastasis or recurrence of carcinoid tumors. We think somatostatin receptor imaging may be appropriate for assessing carcinoid tumors of the middle ear.

Osteolytic spinal metastasis of carcinoid tumors; Long-term follow-up

Osteolytic spinal metastasis of carcinoid tumors; Long-term follow-up

Primary pulmonary carcinoid tumor with metastasis to endometrial polyp

INTRODUCTIONA carcinoid tumor occurring in the endometrium has been documented in the literature, but there is no report in regard to carcinoid tumor metastasis to endometrium. PRESENTATION OF CASEWe report a case of a malignant carcinoid metastasis to an endometrial polyp. Patient underwent hysteroscopy, and polypectomy. The pathology demonstrated an endometrial polyp containing a 4 mm x 5 mm nodule of metastatic carcinoid tumor, consistent with metastasis from patient's known pulmonary carcinoid. The tumor was morphologically similar to the tumors of the right lung, with similar immune-profile. DISCUSSIONThis patient presented with a suspicious pelvic ultrasound. Due to her age, the first priority was to exclude uterine cancer. The endometrial polyp, which was found, had a small focus of metastatic carcinoid tumor. To the best of our knowledge, this finding has not been previously recorded in the literature. Our patient also had a history of metastatic carcinoid tumor to breast. This finding is also very uncommon. CONCLUSIONThis is the first case in the literature described a malignant carcinoid metastasis to an endometrial polyp.

Bronchial carcinoid tumors metastatic to the sella turcica and review of the literature

We review here the literature on neuroendocrine neoplasms metastatic to the pituitary and present an example of the disease. Metastasis of bronchial carcinoid tumors to the sellar region are rare. Herein, we describe the case of a 63-year-old woman who presented with constant cough and headaches. She had previously been operated for carcinoid tumor of the lung. During the preoperative investigation, a CT scan of the head revealed a sellar mass. Six months after a left lower lobectomy, the sellar lesion was removed by transsphenoidal surgery. The two tumors were evaluated by histology, immunohistochemistry and electron microscopy. Both showed identical morphologic features, those of carcinoid tumor. Immunohistochemistry revealed immunoreactivity for the endocrine markers, synaptophysin and chromogranin, as well as CD-56, serotonin, bombesin and vascular endothelial growth factor. The sellar neoplasm showed nuclear immunopositivity for thyroid transcription factor-1, supporting the diagnosis of a metastatic bronchial carcinoid tumor. In conclusion, this is the first report of a serotonin- and bombesin-immunopositive atypical bronchial carcinoid tumor metastatic to the sella.

Skeletal metastasis of carcinoid tumors: Two case reports and review of the literature.

Carcinoid tumors are neuroendocrine neoplasms derived from enterochromaffin cells. Skeletal metastases from carcinoid tumors are considered to be extremely rare. In this study, we present two cases of carcinoid tumors that metastasized to the bone. Furthermore, we review 50 published case reports and reveal the features of skeletal metastasis of carcinoid tumors. The first case involved a 59-year-old man with a history of multiple metastases of a lung carcinoid tumor. The patient complained of back pain and numbness in the lower limbs. Magnetic resonance imaging revealed metastases in the thoracic spine. A spinal decompression was performed and the symptoms were resolved. The second case involved a 74-year-old man had been diagnosed with a lung carcinoid tumor 15 years previously and complained of left thigh pain. A radiograph showed osteolytic lesions in the shaft of the left femur. We repaired the femur using an intramedullary nail following curettage of the tumor. A radiograph of the femur revealed a callus on the pathological fracture. The patient was able to walk using a crutch 3 months after surgery. We reviewed 50 cases that described skeletal metastasis from carcinoid tumors. The average age of the patients was 54.9 years and 33 patients (66%) were male. The most common site of skeletal metastasis was the spine. We also investigated the survival rate of patients who developed skeletal metastasis from carcinoid tumors. The findings showed that survival of patients who developed osteolytic skeletal metastasis was worse than that of patients who developed osteosclerotic skeletal metastasis.

原発巣術後16年目に異時性肝転移を切除した腎カルチノイドの1例

症例は，70歳，女性．平成7年1月に右腎摘出術を施行され，腎細胞癌と診断された．平成22年4月に腹部CT上肝S8に約4cm大の腫瘤を指摘され，当院内科にて肝生検施行された．その結果，肝カルチノイドと診断され，同年7月当科にて肝S8部分切除施行した．摘出腫瘍は，約4×3cmの皮膜を有する境界明瞭な結節性病変で，肝被膜への浸潤もなく，ごく一部でわずかな血管侵襲を認めるのみであった．転移性肝カルチノイドを疑い，原発巣検索のため，平成7年の摘出腎の再検討を行った結果，腎カルチノイドであったことが判明した．腎カルチノイドは非常に稀で1)，その異時性肝転移の切除報告は，われわれの調べ得る限りでは無かった．また，カルチノイド腫瘍は，経過観察期間を過ぎて再発・転移をきたす可能性もあると考えられた．

Carcinoid Tumor Metastases to the Extraocular Muscles: MR Imaging and CT Findings and Review of the Literature

Carcinoid Tumor Metastases to the Extraocular Muscles: MR Imaging and CT Findings and Review of the Literature

Severe intestinal ischemia as a presenting feature of metastatic ileal carcinoid tumor: role of MDCT with coronal reformation in the early diagnosis

Intestinal ischemia is a rare but potentially fatal complication of mesenteric metastasis of intestinal carcinoid tumor and its mechanism isn't entirely clear. We present a case of intestinal ischemia secondary to metastatic ileal carcinoid tumor diagnosed by CT that showed a small mesenteric mass with an extensive desmoplastic reaction causing an intense involvement of the small bowel. Improvements in CT technology with the use of MDCT scanners and advanced reformatting capabilities play an important role in the early diagnosis and accurate recognition of this entity and its need for immediate treatment.

An Unusual Muscular Metastasis in a Patient Affected by Ileal Carcinoid Imaged With a 111In-Pentetreotide SPECT/CT Scan and Confirmed by Biopsy

¹¹¹In-Pentetreotide SPECT/CT scan has been widely validated in diagnosis and follow-up of carcinoid and other neuroendocrine tumors. A 70-year-old man, who underwent an ileal resection for carcinoid 5 years ago, came to our observation during follow-up. We performed a In-DTPA-Pentetreotide (150 MBq) SPECT/CT scan. Images taken after 2 hours showed a focal, pathologic uptake on the left leg, confirmed at later acquisitions. Lateral projection showed that the uptake area was located in a leg muscle; the lesion was confirmed as an intramuscular metastasis by biopsy. Intramuscular metastasis of carcinoid tumors is an extremely rare manifestation, particularly if not adjacent to the primary tumor, because the muscle is a very uncommon location of hematogenous metastases.

Disseminated lung metastasis of atypical carcinoid tumor of thymic origin?

Disseminated lung metastasis of atypical carcinoid tumor of thymic origin? Chee Hwee Lee , Chien-Jui Cheng , Wing P. Chan a,c,* Department of Radiology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan, Republic of china Department of Pathology, School of Medicine, Taipei Medical University, Taipei, Taiwan, Republic of china Department of Radiology, School of Medicine, Taipei Medical University, Taipei, Taiwan, Republic of china

A case series of neuroendocrine (carcinoid) tumor metastasis to the orbit

Purpose/Background:To report the clinical and radiographic features and treatment outcome of neuroendocrine tumor (carcinoid) metastasis to the orbit.Materials and Methods:Retrospective chart review of four cases.Results:Mean patient age at the time of diagnosis of the primary neuroendocrine tumor and orbital metastasis was 58 and 66 years, respectively, with a mean duration of 8 years between diagnosis of primary tumor and orbital metastasis. Primary neuroendocrine tumor sites were gastrointestinal tract (n = 2), lung (n = 1), and testicle (n = 1). The most common presenting symptom was diplopia (three cases). Magnetic resonance imaging revealed orbital tumor in all cases. Octreotide scan was positive in one case. Treatment was tumor excision in three cases followed by external beam radiotherapy in two cases and one patient was followed without treatment. Tumor cells showed immunoreactivity to chromogranin, synaptophysin, and neuron-specific enolase in all cases. Mean follow-up after orbital tumor diagnosis was 39 months. Three patients had known systemic extraorbital metastasis before orbital involvement (mean interval of 5.9 years) and one case had immediately after development of orbital metastasis. One patient had multiple recurrences of orbital metastasis and eventually underwent exenteration. Two patients died of disseminated metastasis between 2 and 3 years after diagnosis of orbital metastasis.Conclusion:All four patients with orbital metastasis from neuroendocine tumor had evidence of systemic extraorbital metastasis. Aggressive metastatic neuroendocine tumors of orbit can lead to local recurrence even after surgical excision and radiation. Imaging tests were helpful in allowing early diagnosis and for monitoring after treatment.