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1.  The term "carcinoid" is a misnomer: the evidence based on local invasion 
Since Oberndorfer proposed the term "carcinoid" in 1907, over 100 years have passed. This attractive term was initially proposed for 6 cases of his own experience with 12 submucosal lesions in the small intestine.
Oberndorfer summarized the characteristic features of these lesions as follows: (1) small in size and often multiple, (2) histologically undifferentiated with a suggestion of gland-formation, (3) well-defined without any tendency to infiltrate the surroundings, (4) no metastases, and (5) apparently slow-growing reaching no significant size with a seemingly harmless nature.
This article stresses the malignant nature of "carcinoid" on the basis of local invasion prior to metastases in the first two sessions, (1) with Oberndorfer's original diagram, and (2) with an experimental observation on extraglandular microcarcinoid in a form of "budding".
Next, (3) a statistical comparison between a carcinoid group and a non-carcinoid ordinary carcinoma group is introduced on metastasis rates at an early stage with two prescribed factors of the depth of invasion restricted within the submucosa (sm-lesion) and a small tumor size category of 1 cm to 2 cm: the carcinoid group exhibited metastasis rates higher than those in the ordinary carcinoma group when calculated in the stomach and rectum.
In the author's experience, "carcinoids" are malignant not only in the gastrointestinal tract but also in the other sites on the basis of local invasion.
Lastly, (4) discussion on the terminology of "carcinoid" as a misnomer is carried out.
Adequate terms referring to the entity of this malignant tumor group are discussed. One of the most adequate and brief terms for "carcinoid" that is included now in neuroendocrine tumor group would be "endocrinocarcinoma" as per the author's proposal, followed by NEC (neuroendocrinocarcinoma) or GEC (gut endocrinocarcinoma).
The term "carcinoid" is a misnomer that can be confirmed on the basis of local invasion prior to metastases. "No metastases without local invasion" is not of a negligible importance.
PMCID: PMC2657123  PMID: 19208248
2.  Atypical presentation of carcinoid tumor with unresolved right shoulder pain: a case report 
Carcinoid tumors are variants of neuroendocrine tumors that typically arise from the gastrointestinal tract and the bronchus, but they can involve any organ. Unresolved right shoulder pain manifesting as the first clinical presentation of carcinoid tumor with unknown primary origin is a rare clinical entity. To the best of our knowledge, herein we present the first case report describing metastasis to the right shoulder joint in a patient who presented with bone pain as the first clinical manifestation of metastatic carcinoid tumor of unknown primary origin. Metastasis to the right scapula as the first presentation of an underlying carcinoid tumor in the primary bronchus has been reported previously.
Case presentation
A 72-year-old Caucasian woman presented with pain in her right shoulder after a fall. She delayed seeking medical attention for 4 weeks for personal reasons. Her physical examination revealed no erythema or swelling of the right shoulder. However, tenderness was noted on the right subacromial bursa and the right acromioclavicular joint. Her drop arm test was positive. An X-ray of the right upper extremity showed no fracture. She did not respond to methylprednisolone injections or physical therapy. Because of the unresolved right shoulder pain with disturbance of her daily activities, magnetic resonance imaging of the right shoulder was ordered, which revealed permeative destruction of the right scapula. Because the permeative destruction of the bone could have been an osteolytic malignant feature, positron emission tomography–computed tomography was performed, which produced a scan showing osseous metastasis to the right scapula, multiple liver metastases and a 1.7cm right-lower-lobe pulmonary nodule. Her serotonin and chromogranin A levels were significantly elevated. The patient was treated with palliative cisplatin and etoposide chemotherapy followed by locoregional treatments for metastatic carcinoid tumor. She had mild improvement in her right shoulder pain, as well as better range of motion and improved quality of life, before she died less than 2 years after her diagnosis.
Our present case report emphasizes the protean manifestations of carcinoid tumors with the importance of early diagnosis of bone metastases from these tumors, because early diagnosis plays a major role in choosing the therapeutic regimen and prognosticating the course of the disease. The treatment goals for high-grade, poorly differentiated carcinoid tumors of unknown origin are decreasing the tumor load while controlling symptoms with chemotherapy and local modality treatments.
PMCID: PMC4031976  PMID: 24885024
Metastatic carcinoid tumor; Neuroendocrine tumor; Right shoulder pain
3.  Hypergastrinemia and recurrent type 1 gastric carcinoid in a young Indian male: Necessity for antrectomy? 
Carcinoid tumors are the most common neuroendocrine tumors. Gastric carcinoids represent 2% of all carcinoids and 1% of all gastric masses. Due to the widespread use of Esophagogastroduodenoscopy for evaluating a variety of upper gastrointestinal symptoms, the detection of early gastric carcinoids has increased. We highlight an alternative management of a young patient with recurrent type 1 gastric carcinoids with greater than 5 lesions, as well as lesions intermittently greater than 1 cm. Gastric carcinoids have a variable presentation and clinical course that is highly dependent on type. Type 1 gastric carcinoids are usually indolent and have a metastasis rate of less than 2%, even with tumors larger than 2 cm. There are a number of experts as well as organizations that recommend endoscopic resection for all type 1 gastric carcinoid lesions less than 1 cm, with a follow-up every 6-12 mo. They also recommend antrectomy for type 1 gastric carcinoids with greater than 5 lesions, lesions 1 cm or greater, or refractory anemia. However, the American Society of Gastrointestinal Endoscopy guidelines state that type 1 gastric carcinoid surveillance is controversial based on the evidence and could not make an evidence-based position statement on the best treatment modality. Our report illustrates a rare cause of iron deficiency anemia in a young male (without any medical history) due to multiple recurrent gastric carcinoid type 1 lesions in the setting of atrophic gastritis causing hypergastrinemia, and in the absence of a vitamin B12 deficiency. Gastric carcinoid type 1 can present in young males without an autoimmune history, despite the known predilection for women aged 50 to 70 years. Type 1 gastric carcinoids can be managed by endoscopic resection in patients with greater than 5 lesions, even with lesions larger than 1 cm. This course of treatment enabled the avoidance of early antrectomy in our patient, who expressed a preference against more invasive measures at his young age.
PMCID: PMC3199567  PMID: 22046097
Gastric carcinoid; Antrectomy; Endoscopic resection; Hypergastrinemia; Iron deficiency anemia
4.  AB 36. Primary lung carcinoid, a rare cause of paraparesis: report of a case and review of the literature 
Journal of Thoracic Disease  2012;4(Suppl 1):AB36.
Carcinoids are neuroendocrine tumors involving the gastrointestinal tract, lungs and bronchi. They are usually benign with slow growth, but they can be malignant (metastasizing to liver, lungs, bones, skin, etc). Endocrine activity results in carcinoid syndrome: Intestinal carcinoid [5-hydroxytryptamine (serotonin) to portal circulation]: abdominal cramps, diarrhea, bronchospasm, face/chest cyanotic flushes, and right-sided stenotic cardiac lesions. Lung carcinoid (histamine and 5-hydroxytryptophan to systemic circulation): red facial flush/oedema, salivation, lachrymation, potentially tachycardia, fever, anxiety, tremor, hypotension, left-sided cardiac lesions). We present an extremely rare case of primary lung carcinoid presented with paraparesis.
Patient and methods
A 69 year old man developed progressively deteriorating bilateral proximal muscular weakness of the legs that within 6 months led to paraparesis (inability to stand up and walk) with preserved sensation. Electromyography showed polyneuropathy. History, clinical and laboratory data excluded diabetic mellitus, hypothyroidism, renal/liver failure, cachexia, alcohol abuse, chemotherapy, drug or other toxicity. Magnetic resonance imaging excluded spinal cord or spinal nerve root compression. Computed tomography revealed a small peripheral paracardiac right-middle lobe tumor (maximal diameter: 1.8cm). Thoracoscopic wedged resection was performed (endo-stappler). Histology revealed lung carcinoid of low mitotic index (1-2%).
The patient had an uneventful recovery, was discharged on the 5th postoperative day to a rehabilitation centre, where he remained for 3 months. Progressive motor function improvement was noted; paraparesis resolved completely within 6 months. At 1-year follow-up normal respiratory and neurological status was noted, in the absence of carcinoid recurrence or metastasis.
Myopathy is common in endocrine disease and cancer can have endocrine and metabolic activities and cause neurological complications. Encephalopathy, myelopathy, and more often motor and sensory neuropathy, myopathy, or neuromyopathy of central distribution may occur in paraneoplastic syndromes. Neuromyopathy has been reported in 14% of lung cancer patients. There are reports of recurrent facial palsy in metastatic thymic carcinoid, proximal muscle weakness in ACTH-releasing thymic carcinoid, an ACTH-releasing bronchial carcinoid, and paraparesis 40 years after pneumonectomy for carcinoid adenoma induced by inflammatory contents of the pneumonectomy cavity. To the best of our knowledge there is no report of paraparesis induced by primary pulmonary carcinoid. Complete resolution after excision suggests “paraneoplastic” syndrome.
PMCID: PMC3537365
5.  Chromosomal instability is more frequent in metastasized than in non-metastasized pulmonary carcinoids but is not a reliable predictor of metastatic potential 
Experimental & Molecular Medicine  2009;41(5):349-353.
Pulmonary carcinoids are infrequent neoplasms of the lung that normally display a less aggressive biological behavior compared to small cell and non-small cell lung cancers. Approximately 15-25% of carcinoids, in particular atypical carcinoids, show lymph node metastasis and have a worse prognosis than their non-metastasized counterparts. To date, there is no morphological or molecular marker that may help to differentiate between carcinoids that metastasize and carcinoids of identical differentiation that show only local tumor growth. In this study, we analyzed 7 metastasized and 10 non-metastasized pulmonary carcinoids for chromosomal and microsatellite instability in order to determine whether microsatellite instability or chromosomal imbalances are associated with metastasis. Due to the rare occurrence of metastasized carcinoids we compared our results of chromosomal instability with the hitherto published comparative genomic hybridization (CGH) profiles of pulmonary carcinoids, for which information about the absence or presence of metastasis was available. While microsatellite instability was not detected we found chromosomal instability as a common event in pulmonary carcinoids with an increase of frequency and extent of chromosomal alterations in atypical and metastasized carcinoids. These findings are in accordance with the collected and herein compiled data of previous studies and indicate increasing numbers of chromosomal imbalances to play a role in the sequential process of tumor development and metastasis.
PMCID: PMC2701984  PMID: 19307755
biological markers; carcinoid tumor; comparative genomic hybridization; lung neoplasms; microsatellite instability; neoplasm metastasis
6.  The Rare Malignancy of the Hepatobiliary System: Ampullary Carcinoid Tumor 
Case Reports in Medicine  2011;2011:173036.
Introduction. Carcinoid tumors are low-grade tumors originating from endoderm and mostly involving the gastrointestinal system. However; they may be seen in any site within the gastrointestinal system. Case Presentation. A 69-year-old female patient. The results of blood tests were observed to be consistent with obstructive jaundice. A mass appearance was not encountered on tomographic examination. Papilla that was tumor-like macroscopically was seen in the second part of the duodenum in diagnostic endoscopy. Pylorus—preserving pancreaticoduodenectomy surgical procedure was applied. On pathological examination of the mass, a tumoral mass was detected in ampulla vateri localization, 1.5 × 1 × 0.8 cm in size, which, in immunohistochemical staining, was evaluated as a neuroendocrine tumor. Also, Metastasis was observed. Conclusion. The rarest type of carcinoid tumor is ampullary located carcinoid tumor, and tumor size is not a reliable indicator for tumor aggressivity in ampullary carcinoid tumors.
PMCID: PMC3114376  PMID: 21687583
7.  Imaging features of carcinoid tumors metastatic to the breast 
Cancer Imaging  2011;11(1):109-115.
The objective of this study was to describe the imaging findings of carcinoid tumors metastatic to the breast, with pathologic and clinical correlations. We searched our surgical database for cases of pathologically proven carcinoid tumors metastatic to the breast from October 1, 2000, to May 31, 2010. Of the approximate 10,000 breast biopsies identified, 7000 had malignant findings. Ten cases of metastatic carcinoid (0.1% of all malignancies), all with imaging studies available for review, were included in the study. All patients were women and had their primary carcinoid in the gastrointestinal tract (n=9) or lung (n = 1). One patient presented with a palpable breast mass and no history of carcinoid tumor; an ileal carcinoid was discovered after the pathologic diagnosis of metastatic carcinoid was established. In the breast, tumors presented as solitary lesions in half the cases. Metastases to the breast typically presented as circumscribed masses mammographically and as hypoechoic circumscribed masses ultrasonographically; some showed increased through-transmission and increased vascularity with color Doppler evaluation. Five patients had octreotide scans; of these, 4 had increased focal activity in the region of metastasis within the breast. Six patients underwent computed tomography. Without contrast, nodular masses were observed; with contrast, the masses showed rapid enhancement during arterial phase imaging. Magnetic resonance imaging (n = 4) also showed rapid enhancement and washout kinetics after contrast administration. Recognition of carcinoid metastases to the breast in patients with known or occult primary carcinoid tumors is important to avoid unnecessary treatment for primary breast cancer.
PMCID: PMC3205760  PMID: 21771708
Biopsy; pathology; treatment
8.  Utility of the Serum ProGRP Level for Follow-up of Pulmonary Carcinoid Tumors 
Patient: Female, 67
Final Diagnosis: Pulmonary carcinoid tumor
Symptoms: Abnormal shadow on chest X-ray
Medication: —
Clinical Procedure: —
Specialty: Pulmonology
Rare disease
Although pulmonary carcinoid tumors are generally considered to represent a low-grade malignancy, atypical carcinoids are more aggressive than typical carcinoids, metastasizing more commonly to both regional lymph nodes and distant sites. The treatment of choice for localized disease is surgery. In cases of advanced or metastatic disease, medical treatments, including chemotherapy, have not been proven to be very successful. Therefore, providing careful follow-up is extremely important. In general, tumor markers, such as the level of CYFLA21-1, are often useful for monitoring lung cancer. However, there are currently no sensitive tumor markers for carcinoid tumors. We herein report a rare case of an atypical carcinoid of the lung with the elevation of the serum ProGRP level.
Case Eeport:
A 67-year-old female was referred to our hospital for an abnormal chest X-ray. CT revealed an 18×13 mm nodule in the right middle lobe with no significant mediastinal lymphadenopathy. The serum tumor marker, the ProGRP level, was significantly elevated (161 ng/ml). We performed a right middle lobectomy, because the pathological diagnosis of lung cancer was confirmed according to the results of a rapid frozen section biopsy of the lesion, although the pathological type could not be precisely determined by the frozen section alone. The final pathological diagnosis was atypical carcinoid. The level of ProGRP decreased (69 ng/ml) within 1 month after the surgery.
The ProGRP level may be useful for monitoring carcinoid tumors, although no serum tumor markers are highly specific or sensitive for detecting recurrences and/or distant metastasis of pulmonary carcinoid tumors. In conclusion, ProGRP should be further evaluated as biomarker in a larger series of patients to determine whether it demonstrates any significant correlation with cancer recurrence.
PMCID: PMC4138068  PMID: 25109370
Carcinoid Tumor; Lung Neoplasms; Tumor Markers, Biological
9.  Clinicopathologic characteristics of colonic carcinoid tumors 
The Journal of surgical research  2013;184(1):183-188.
Extraappendiceal colonic carcinoids are uncommon neuroendocrine tumors with a poor prognosis compared to carcinoids of other gastrointestinal origins. Few studies have examined the clinicopathologic profile and behavior of this rare tumor.
Materials and Methods
A retrospective analysis was performed on patients with colonic carcinoid tumors evaluated at a single tertiary care center between 1996 and 2012. Collected data included patient and tumor characteristics, presentation, treatment, recurrence and survival. Results were integrated into a comprehensive review of the colonic carcinoid literature.
In total, 114 patients with colorectal carcinoid tumors were identified, and 15 patients with extraappendiceal tumors were analyzed. The mean age was 58.6±3.0 years, and subjects were predominantly male (73.3%). The most common presenting complaint was abdominal pain (33.3%), although 26.7% of patients were asymptomatic. Cecal tumors were the most prevalent (73.3%), and the majority of patients underwent right hemicolectomy. Three patients with lesions <1 cm were treated endoscopically. The mean tumor diameter was 2.9±0.5 cm, with lymph node or distant metastasis present in 53.3% and 26.7%, respectively. All but 2 patients underwent a presumed curative resection. During a mean follow-up of 4.2±1.0 years, there was only one death (non-carcinoid specific). Eleven patients were alive without evidence of disease at last follow-up, and 3 patients were alive with disease, one of which initially had a presumed curative resection but recurred.
This case series further elucidates the clinicopathologic characteristics of colonic carcinoid tumors, which aids physicians in guiding the diagnosis and management of these rare tumors.
PMCID: PMC3759590  PMID: 23830363
California Medicine  1963;99(3):157-160.
Carcinoid tumors are diminutive growths found along the gastrointestinal tract, in the lungs and, occasionally, within the confines of teratomas. Carcinoid tumors of the intestinal tract are found in decreasing order of frequency in the rectum, the appendix, the ileum, the jejunum, the lung, the stomach and the duodenum. Arising from argentaffin elements in the crypts of Lieberkuehn, and secreting serotonin, carcinoid tumors belong to the order of functioning neoplasms. Their indolent growth seems to place them between benign neoplasms and carcinomas. However, they possess propensities for metastasis that correlate with increase in size.
The symptoms that are produced are almost always due to the presence of metastatic lesions. In ileal and gastric carcinoid tumors, the tendency to metastasis is augmented and the metastatic masses are sometimes of sufficient bulk to cause the carcinoid syndrome or to interfere with the supply of blood to the affected segment. More often they produce the clinical picture of intestinal obstruction.
The unusually long interval from onset to death associated with carcinoid tumors makes palliative subtotal resections and short-circuiting operations in symptomatic patients with advanced disease worthwhile, for by such unorthodox procedures the patients may be afforded many additional years of useful life.
PMCID: PMC1515252  PMID: 14047626
11.  Prognosis and risk factors of metastasis in colorectal carcinoids: results of a nationwide registry over 15 years 
Gut  2007;56(6):863-868.
Colorectal carcinoids are often described as low‐grade malignant. However, no study has compared the survival between patients with colorectal carcinoids and those with carcinomas, in a large series. In addition, no global consensus has been established on the crucial determinants of metastasis in colorectal carcinoids.
To determine the predictive factors for metastasis in colorectal carcinoids and clarify their prognosis compared with adenocarcinomas.
Data of all patients diagnosed as having colorectal carcinoids were extracted from a large nationwide database of colorectal tumours, the Multi‐Institutional Registry of Large‐Bowel Cancer in Japan, for the period from 1984 to 1998. Risk factors for lymph node (LN) metastases and distant metastases were analysed among those who were undergoing surgery, by univariate and multivariate analysis. Cancer‐specific survival was also compared between patients with colorectal carcinoids and those with adenocarcinomas registered in the same period.
Among the 90 057 cases of colorectal tumours that were diagnosed, a total of 345 cases of carcinoids were identified, including 247 colorectal carcinoids of those undergoing surgery. Risk factors for LN metastasis were tumour size ⩾11 mm and lymphatic invasion, whereas those for distant metastasis were tumour size ⩾21 mm and venous invasion. Colorectal carcinoids without these risk factors exhibited no LN metastasis or distant metastasis. Cancer‐specific survival of patients with colorectal carcinoids without metastasis was better than that of those with adenocarcinomas. However, the survival was similar between carcinoids and adenocarcinomas if the tumours had LN metastasis or distant metastasis.
The presence of metastasis in colorectal carcinoids could lead to survival that is as poor as in adenocarcinomas. Tumours ⩽10 mm and without lymphatic invasion could be curatively treated by local resection, but others would need radical LN dissection.
PMCID: PMC1954860  PMID: 17213340
12.  Primary carcinoid tumor arising within mature teratoma of the kidney: report of a rare entity and review of the literature 
Diagnostic Pathology  2007;2:15.
Primary carcinoid tumor arising within mature teratoma of the kidney is extremely rare, and their clinicopathologic features are not well described. Our objective was to further define the clinical features and pathologic spectra of primary carcinoid tumor arising within mature teratoma of the kidney.
Six previously reported case reports were identified using MEDLINE and a subsequent bibliographic search of all pertinent reports and reviews was performed. We also searched the electronic medical archival records of our institution and identified one additional unreported case. Data were extracted on the demographics, predisposing factors, clinical presentation, radiographic features, gross pathology, microscopic pathology, immunophenotype, therapy, and outcome of each of these seven cases.
Primary carcinoid tumor arising within mature teratoma of the kidney was found at a mean age of 41.4 years. Of the 7 cases, 3 were female and 4 were male. Two of the 7 cases (28.6%) were associated with horseshoe kidney. It typically presented with abdominal pain without carcinoid syndrome. It typical radiologic appearance was well circumscribed partly calcified Bosniak II-III lesion. Histologically, the carcinoid tumor showed monotonous small round cells arranged in classic anastomosing cords/ribbons intermixed with solid nests. Surgery was curative, no additional treatment was required, no local recurrences occurred, and no metastases occurred in all 7 cases. The 3 cases with available outcome data were alive at the time of publication of their respective cases (mean, 5 months).
Primary carcinoid tumor arising within mature teratoma of the kidney is a rare tumor that typically presents with abdominal pain without carcinoid syndrome. It is not associated with local recurrence and metastasis, is surgically curable, and has excellent prognosis.
PMCID: PMC1884130  PMID: 17509135
13.  A case series of neuroendocrine (carcinoid) tumor metastasis to the orbit 
Oman Journal of Ophthalmology  2011;4(3):125-128.
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.
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.
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.
PMCID: PMC3263165  PMID: 22279400
Carcinoid tumor; magnetic resonance imaging; metastasis; neuroendocrine tumor; octreoscan
14.  Gastric collision tumor: Case report of a rare adenocarcinoma and a typical carcinoid tumor 
Oncology Letters  2013;6(1):212-214.
We report a case with features of gastric adenocarcinoma colliding with a typical carcinoid component. A 51-year-old female was admitted to the Department of Internal Medicine with complaints of epigastric pain. On physical examination of the patient there was significant epigastric tenderness and the CA19-9 level was higher than the normal titer value. An upper gastrointestinal endoscopy showed an ulcerated polypoid mass located on the cardiac region of the stomach. Pathological and immunohistochemical findings diagnosed as a collision tumor comprising both adenocarcinoma and carcinoid tumor. Metastasis of adenocarcinoma was found in 7 perigastric lymph nodes, while metastasis of the carcinoid was not detected. The admixture of neoplastic endocrine and nonendocrine cells, have been found infrequently in gastric tumors. The mixed tumors can be further classified into composite tumors that show an admixture of two histological components with histological transitions and collision tumors where the two components are not intermixed In general it is not easy to morphologically distinguish a collision tumor, from composite tumor. Microscopically, hematoxylin and eosin-stained tissue sections from two different areas of the mass revealed two different types of tumor; an intestinal type adenocarcinoma and a carcinoid tumor. We report a case with features of adenocarcinoma colliding with a typical carcinoid component, along with a review of the literature.
PMCID: PMC3742811  PMID: 23946806
collision tumor; gastric adenocarcinoma; carcinoid
15.  Surgical management and outcome of rectal carcinoids in a university hospital 
Rectal carcinoids are an uncommon entity comprising only 1%–2% of all rectal tumors. Rectal carcinoids are frequently diagnosed during colonoscopy, but management after polypectomy is still controversial. The aims of this study were to review the surgical procedures for rectal carcinoids and to compare the outcomes of patients after different treatment modalities in a university hospital in Hong Kong.
All rectal carcinoids diagnosed between January 2003 and September 2012 were reviewed retrospectively, including clinicopathological characteristics, their management, and surgical outcomes.
There were 54 patients with a median age of 60 years, and 32 were males (59.3%). All patients underwent colonoscopy, and the most had rectal bleeding (53.7%). Two patients were diagnosed incidentally in the surgical specimens of rectal tissues. Eighteen patients were diagnosed to have rectal carcinoids after snaring polypectomy, and no further intervention was required. Twenty-five patients had local resection either by means of transanal resection or transanal endoscopic operation. Radical resection was performed in seven patients in which one had T3N1 disease and the others did not have any lymph node metastasis.
In the median follow-up of 30 months (10–108 months), there was no recurrence in the “incidental” or post-polypectomy group. However, two patients with transanal resection and two patients with radical resection developed hepatic metastases after 13–24 months post-treatment. The 5-year overall survival was 100% in patients having snaring polypectomy only, 83% for those with local resection, and 63% in patients who underwent radical surgery (p = 0.04).
Our data suggested that that local resection was an effective treatment for small rectal carcinoids and generally brought about good oncological and surgical outcomes. For larger tumors, radical resection seemed to provide acceptable oncological outcomes. Regular surveillance with colonoscopy and endorectal ultrasound is highly recommended for high-risk patients for long-term management. By sharing our experience, we hope to provide more evidence on the management on rectal carcinoids which, together with evidence from further studies, may guide us in the long-term management of these patients in the future.
PMCID: PMC4327791
16.  Carcinoid Tumor with Localized Bronchiectasis 
Tanaffos  2013;12(2):56-60.
Bronchial carcinoid tumor comprises 1 to 3% of lung neoplasms. The common age of onset is mainly post-puberty although atypical carcinoid tumors occur at ages 44 to 55. Carcinoid tumors cause two groups of symptoms in patients: symptoms due to obstruction and symptoms due to the production and release of active neuropeptides. Histologically, carcinoid tumors are categorized into two groups of typical and atypical while in terms of location of lesion, they are grouped into central and peripheral types. Differentiation between malignant and benign carcinoid tumors is based on presence or absence of metastasis.
Bronchoscopy and endobronchial biopsy are the best diagnostic measures in these patients. Serologic evaluation and assessment of active metabolites in case of liver metastasis also help the diagnosis. Surgical resection is the treatment of choice for this condition.
This report discusses a patient with carcinoid tumor who was receiving bronchodilator treatment for a couple of months because of chronic cough with possible diagnosis of asthma and had received several courses of antibiotic therapy with possible diagnosis of lung infection until he eventually developed bronchiectasis in the right lower lobe.
In patients with chronic pulmonary symptoms especially with localized bronchiectasis, diagnostic bronchoscopy must be included in the diagnostic work-up to rule out intrabronchial lesions.
PMCID: PMC4153246  PMID: 25191464
Carcinoid tumor; Pulmonary neoplasm; Bronchiectasis; Recurrent pneumonia
17.  A rare case of metastatic renal carcinoid 
BMC Urology  2010;10:22.
Carcinoid is an endocrine cell tumor with low-grade atypia, which is generally a low-grade malignant cancer with a good prognosis. Metastatic renal carcinoid is even rarer than primary carcinoids.
Case presentation
We present our experience of a patient with metastatic renal carcinoid from the gastrointestinal tract.
The carcinoid tumor of the kidney in our patient, who had a history of liver metastasis from rectal carcinoid, was considered metastatic based on the pathological findings.
PMCID: PMC3016340  PMID: 21144059
18.  18F-FDG PET/CT rarely provides additional information other than primary tumor detection in patients with pulmonary carcinoid tumors 
Annals of Thoracic Medicine  2014;9(4):227-231.
The purpose of this study was to assess the contribution of 18F-fluorodeoxyglucose (FDG) Positron Emission Tomography (PET)/Computed Tomography (CT) in detection and staging of pulmonary carcinoid tumors.
A total of 22 patients with pulmonary carcinoid tumors (14 typical, 8 atypical) were reviewed in this retrospective study. PET/CT images of all patients were evaluated for primary tumor as well as metastatic regional lymph nodes, bone and other distant metastases. PET/CT positivity of primary tumors was determined by visual interpretation. Tumor size, SUVmax and Hounsfield Unit (HU) values of the tumors were used to test for differences between tumor groups (typical carcinoids and atypical carcinoids).
SUVmax of carcinoids ranged from 1.24 to 11.1 (mean, 5.0; median, 2.67). The mean largest diameter of primary tumors was 2.7 ± 1.3 cm, ranging from 1 to 5.5 cm. The overall sensitivity of FDG PET/CT for detection of pulmonary carcinoid tumors was 81.8%. Tumor size, SUVmax and Hounsfield Unit (HU) values of the atypical carcinoids were higher than those for typical carcinoids. However, the results were not statistically meaningful (P > 0.05). The sensitivity and specificity of FDG PET/CT in the detection of mediastinal and hilar lymph nodes metastases were 25% and 83% respectively. One patient had bone metastasis.
Although FDG PET/CT can be a useful tool for the detection of pulmonary carcinoid tumors and distant metastasis, it cannot discriminate typical carcinoids from atypical ones and absence of an FDG avid lesion cannot exclude pulmonary carcinoid tumors. Moreover, PET/CT is not a reliable tool in the staging of mediastinal and hilar lymph nodes especially for those patients with typical carcinoids.
PMCID: PMC4166070  PMID: 25276242
FDG PET/CT; pulmonary carcinoid tumor; synchronous pulmonary carcinoids
19.  Carcinoid Syndrome Symposium on Treatment Modalities for Gastrointestinal Carcinoid Tumours: symposium summary 
Canadian Journal of Surgery  2001;44(1):25-32.
To develop a collaborative approach for the treatment of gastrointestinal carcinoid tumours and carcinoid syndrome.
Leaders in the medical, endocrine, radiologic and surgical treatment of carcinoid disease were selected to present papers at the Carcinoid Syndrome Symposium on Treatment Modalities for Gastrointestinal Carcinoid Tumours and participate in the workshop that followed.
A multidisciplinary symposium with experts in the field of carcinoid syndrome was organized at the University of Calgary. Data presented, participation of the attendees and a review of the literature were used in the workshop to develop a collaborative approach to the management of carcinoid tumours.
Carcinoid tumours are rare and few centres have large experiences in their treatment. Before the development of this collaboration, patients with carcinoid tumours received a unidisciplinary approach depending on referral patterns. The development of a multidisciplinary neuroendocrine clinic helped to unify the approach to these patients, yet a consensus on the treatment of carcinoid tumours was lacking. The expertise at the symposium allowed for consensus and the development of treatment algorithms, including biochemical screening, radiographic localization and surgical intervention, for gastrointestinal carcinoid tumours. The role of medical and hormonal therapy after cytoreducion is presented.
Patients with carcinoid tumours require a multidisciplinary approach to their care.
PMCID: PMC3695180  PMID: 11220795
20.  Clinicopathological analysis of colorectal carcinoid tumors and patient outcomes 
Colorectal carcinoid tumors are often described as being low-grade malignant. The objective of the current study was to address the clinicopathological features and outcomes of patients with colorectal carcinoid tumors.
A total of 63 patients with colorectal carcinoid tumors were identified and evaluated using surgical pathology files and medical records between January 2000 and June 2012 at the Veterans General Hospital, Taipei, Taiwan.
The median age of the 63 patients was 57.0 years; 38 (60.3%) were male and 25 (39.7%) female. The rectum was the most common tumor site (90.5%). Tumor size was 10.8 ± 7.4 mm, ranging from 2 to 50 mm in diameter. There were 40 patients (63.5%) who received endoscopic treatment for a tumor size of 7.7 ± 4.0 mm, 15 (23.8%) who underwent transanal excision for a mean size of 9.2 ± 4.5 mm and eight (12.7%) who underwent radical surgical resection (mean size: 29.5 ± 13.0 mm). Lymph node metastasis was significantly associated with tumor size. Totally distant metastases (liver) were demonstrated in four (6.3%), patients with mean tumor size of 31.3 ± 9.4 mm (20 to 50 mm). The extent of the disease was associated with survival and the five-year overall survival rate was 92.1%.
With widespread colorectal cancer screening, heightened awareness and improved diagnostic modalities, the incidence of colorectal carcinoid tumors will continue to increase. We demonstrated that small-sized colorectal carcinoid tumors and those localized in the mucosa or submucosa may be safely and effectively removed via endoscopic or transanal local excision.
PMCID: PMC4258265  PMID: 25433951
Colorectal; Carcinoid tumor; Lymph node metastasis; Clinicopathological
21.  Goblet cell carcinoid of the appendix 
Goblet cell carcinoid (GCC) of the appendix is a rare neoplasm that share histological features of both adenocarcinoma and carcinoid tumor. While its malignant potential remains unclear, GCC's are more aggressive than conventional carcinoid. The clinical presentations of this neoplasm are also varied. This review summarizes the published literature on GCC of the appendix. The focus is on its diagnosis, histopathological aspects, clinical manifestations, and management.
Published studies in the English language between 1966 to 2004 were identified through Medline keyword search utilizing terms "goblet cell carcinoid," "adenocarcinoid", "mucinous carcinoid" and "crypt cell carcinoma" of the appendix.
Based on the review of 57 published papers encompassing nearly 600 diagnosed patients, the mean age of presentation for GCC of the appendix was 58.89 years with equal representation in both males and females. Accurate diagnosis of this neoplasm requires astute observations within an acutely inflamed appendix as this neoplasm has a prominent pattern of submucosal growth and usually lacks the formation of a well-defined tumor mass. The mesoappendix was involved in 21.64% followed by perineural involvement in 2.06%. The most common clinical presentations in order of frequency were acute appendicitis in 22.5%; asymptomatic in 5.4%; non-localized abdominal pain in 5.15% and an appendicular mass in 3.09%. The most common surgical treatment of choice was appendectomy with right hemicolectomy in 34.70% followed by simple appendectomy in 24.57%. Concomitant distant metastasis at diagnosis was present in 11.16% of patients with the ovaries being the most common site in 3.60% followed by disseminated abdominal carcinomatosis in 1.03%. Local lymph node involvement was seen in 8.76% of patients at the time of diagnosis. The reported 5-year survival ranges from 60 % to 84%. GCC's of the appendix remains a neoplasm of unpredictable biological behavior and thus warrants lifelong surveillance for recurrence of the disease upon diagnosis and successful surgical extirpation.
GCC of the appendix is a rare neoplasm. Due to its wide range of presentation, this tumor should be considered as a possible diagnosis in many varied situations leading to abdominal surgery. Histopathological features such as increased number of Paneth cells, increased amount of mucin secretion and presence of pancreatic polypeptide may predict a more aggressive behavior. The advocated plan of management recommended for patients with tumors that involve the adjacent caecum or with high-grade tumors with histological features such as an increased mitotic rate involve initial appendectomy with completion right hemicolectomy due to the high possibility of local recurrence with intraperitoneal seeding prior to lymph node involvement and a 20% risk of metastatic behavior. In female patients with GCC of the appendix regardless of age, bilateral salpingo-oophorectomy is advocated. In cases with obvious spread of the disease chemotherapy, mostly with 5-FU and leucovorin is advised. Cytoreductive surgery with adjuvant intraperitoneal chemotherapy can offer improved survival in cases with advanced peritoneal dissemination.
PMCID: PMC1182398  PMID: 15967038
22.  Treatment of solitary gastric carcinoid tumor by endoscopic polypectomy in a patient with pernicious anemia 
Type I gastric carcinoid tumors result from hypergastrinemia in 1%-7% of patients with pernicious anemia. We diagnosed pernicious anemia in a 48-year-old female patient with complaint of fatigue for three months. She had no gastrointestinal symptoms. Endoscopic examination ot the upper gastrointestinal tract revealed atrophic gastritis and a polypoid lesion in the corpus of 3-4 mm in size. Endoscopic polypectomy was performed. Histopathological examination of the specimen revealed positive chromogranin A and synaptophysin stainings compatible with the diagnosis of a carcinoid tumor. Serum gastrin level was increased, urinary 5-hydroxyindoleacetic acid was within the normal range. There was no other symptom, sign, or laboratory finding of a carcinoid syndrome in the patient. No metastasis was found with indium-111 octreotide scan, computed tomographies of abdomen and thorax. Type I gastric carcinoid tumors are only rarely solitary and patients with tumors < 1 cm in size may benefit from endoscopic polypectomy.
PMCID: PMC4087391  PMID: 16830392
Solitary; Pernicious anemia; Gastric carcinoid tumor; Endoscopic polypectomy
23.  Clinicopathological characteristics of rectal carcinoid patients undergoing surgical resection 
Oncology Letters  2012;4(5):910-914.
The aim of this study was to clarify the clinical aspects, histopathological features and prognosis of patients with rectal carcinoids, focusing on properties associated with metastasis, in order to gain insights into appropriate management. A total of 20 patients (15 males, 5 females; mean age, 54.9 years; range, 23–71) who underwent surgery for rectal carcinoid tumors at the Department of Colorectal Surgery, Hyogo College of Medicine, between May 2000 and January 2011 were analyzed. Ki-67 immunostaining was performed in 13 cases with available tumor tissue specimens. Of the 20 patients, a radical operation including rectal resection with a lymphadenectomy was performed in 16. The mean tumor size was 11.9 mm (3–25 mm) and lymph node metastasis was confirmed in 9 cases, including 3 with lesions no greater than 7 mm in diameter. Overall, 16 (80%) of the tumors were localized in the submucosal layer and 4 (20%) involved the proper muscle layer. Ki-67 labeling index and lymphovascular invasion were shown to be associated with lymph node and/or distant metastasis by multiple logistic regression analysis, but were not statistically significant in ANOVA findings. Lymph node metastasis from rectal carcinoids, even those smaller than 10 mm in diameter, was not a rare event. More attention should be given to decision-making, including the possibility of endoscopic resection for the treatment of rectal carcinoid tumors regardless of size.
PMCID: PMC3499485  PMID: 23162621
rectal carcinoid; metastasis; Ki-67; lymphovascular invasion
24.  Treatment of colorectal carcinoids: A new paradigm 
It is often difficult to evaluate the grade of malignancy and choose an appropriate treatment for colorectal carcinoids in clinical settings. Although tumor size and depth of invasion are evidently not enough to stratify the risk of this rare tumor, the present guidelines or staging systems do not mention other clinicopathological variables. Recent studies, however, have shed light on the impact of lymphovascular invasion on the outcome of colorectal carcinoids. It has been revealed that the presence of lymphovascular invasion was among the strongest risk factors for metastasis along with tumor size and depth of invasion. Furthermore, tumors smaller than 1 cm, within submucosal invasion and without lymphovascular invasion, carry minimal risk for metastasis with 100% 5-year survival in the studies from Japan as well as from the USA. This would suggest that these tumors could be curatively treated by endoscopic resection or transanal local excision. On the other hand, colorectal carcinoids with either lymphovascular invasion or tumor size larger than 1 cm carry the risk for metastasis equivalent to adenocarcinomas. Therefore, it should be emphasized that histological examination of lymphovascular invasion is mandatory in the specimens obtained by endoscopic resection or transanal local excision, as this would provide useful information for determining the need for additional radical surgery with regional lymph node dissection. Although the present guidelines or TNM staging system do not mention the impact of lymphovascular invasion, this would be among the next promising targets in order to establish better guidelines and staging systems, particularly in early-stage colorectal carcinoids.
PMCID: PMC2999232  PMID: 21160865
Lymphovascular invasion; Neuroendocrine tumor; Carcinoid; Colorectal cancer
25.  Skeletal metastasis of carcinoid tumors: Two case reports and review of the literature 
Oncology Letters  2012;3(5):1105-1108.
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.
PMCID: PMC3389625  PMID: 22783400
carcinoid tumor; skeletal metastasis; prognosis

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