Njei B, Sanchez H
Neurofibromatosis type 1, recurrent pulmonary embolism, and a periampullary carcinoid tumor: is there a link?
Conn Med. 2013; 77(2):77-80 [PubMed]

Neurofibromatosis type 1 (NF1), a relatively common autosomal dominantly inherited condition with complete penetrance but extremely variable phenotypic expressivity, is caused by mutations in the NF1 gene. The disease is defined clinically by its cutaneous (cafe-au-lait macules, inguinal and axillary freckles) and neural (neurofibromas, plexiform neurofibromas, Lisch spots, optic nerve gliomas) signs, but it can involve many other systems including the gastrointestinal, pulmonary, respiratory, skeletal and vascular systems. Involvement of these other systems can sometimes manifest itself in clinically confusing ways. For example, the literature includes reports of patients with NF1 that has caused pulmonary hypertension, spontaneous hemothorax, and gastrointestinal bleeding. We present the case of a man with NF1 who presented with recurrent unexplained thromboembolic disease and died suddenly in the hospital. In addition to confirming his suspected massive pulmonary thromboembolus (PE), an autopsy revealed an unsuspected periampullary duodenal carcinoid tumor. The potential connections between the patient's NF1, duodenal tumor, and fatal PE are discussed. The case highlights the importance of bearing in mind the protean clinical manifestations of NF1.

Taylor WS, Vaughan P, Trotter S, Rajesh PB
A rare association of pulmonary carcinoid, lymphoma, and sjögren syndrome.
Ann Thorac Surg. 2013; 95(3):1086-7 [PubMed]

Pulmonary carcinoid and pulmonary lymphoma are both rare cancers and are seldom seen together. Cases have been reported of their coexistence in the gastrointestinal tract, but our literature searches only found a single case of their coexistence in the lung. We discuss our case as well as the literature to try to find a connection and explanation for this occurrence.

Sofka S, Jackson T
Bronchopulmonary carcinoid presenting as dexamethasone suppressible Cushing's syndrome.
W V Med J. 2013 Jan-Feb; 109(1):26-8 [PubMed]

INTRODUCTION: Cushing's Syndrome is an endocrine condition with complex diagnostic pathways. Cortisol suppression from high dose dexamethasone usually points to the pituitary as the cause. We present the case of a patient with dexamethasone suppressible Cushing's Syndrome from a bronchopulmonary carcinoid tumor. The tumor was only able to be localized with bronchoscopy. Our objective is to inform other physicians of dexamethasone suppressible carcinoid tumors which may require bronchoscopy to localize.
CASE REPORT: A 52-year-old female presented with signs and symptoms of Cushing's Syndrome. Cortisol and ACTH levels were significantly elevated. High dose dexamethasone suppressed cortisol production. However, no pituitary source was found. Standard imaging did not localize an ectopic source. The patient continued to have significant morbidity from the hypercortisolism. In order to avoid adrenalectomy, a bronchoscopy was empirically performed which revealed a bronchopulmonary carcinoid tumor.
DISCUSSION: Bronchopulmonary carcinoid tumor should be in the differential diagnosis of dexamethasone suppressible Cushing's Syndrome if a pituitary source is not localized. Also, we suggest that bronchoscopy be added to the diagnostic algorithm when conventional imaging studies fail to reveal the ectopic source. This may result in cure of the carcinoid malignancy as well as the Cushing's Syndrome.

Salaria SN, Abu Alfa AK, Alsaigh NY, et al.
Composite intestinal adenoma-microcarcinoid clues to diagnosing an under-recognised mimic of invasive adenocarcinoma.
J Clin Pathol. 2013; 66(4):302-6 [PubMed]

AIMS: Microcarcinoids refer to microscopic nests of monotonous cells with endocrine and squamoid features. Their peculiar morphology can appear infiltrative with a desmoplastic-like background, raising concerns for an infiltrating adenocarcinoma. To further characterise microcarcinoids, we undertook a prospective clinicopathological study.
METHODS: 11 specimens originating from five men and six women (average age=58.9 years) were prospectively collected from December 2004 to December 2011.
RESULTS: Microcarcinoids were most commonly identified in high-risk adenomas (size ≥10 mm (n=10), villous components (n=8) and/or high-grade dysplasia (n=4)). All polyps had mucosal prolapse and four displayed background fibrosis reminiscent of desmoplasia. The microcarcinoid component was most often multifocal (n=7) within the individual polyp and extended over an average length of 3.9 mm. The individual microcarcinoid cells were cuboidal with abundant eosinophilic cytoplasm. All cases had monotonous nuclei which lacked pleomorphism, hyperchromasia and mitotic activity. All available microcarcinoids were β-catenin and synaptophysin reactive and non-reactive for chromogranin and p53 with a negligible Ki-67 proliferation index (<2%). In addition, the microcarcinoids were variably reactive for p63 and/or CK 5/6, thereby demonstrating focal squamoid features. Two of the study cases were submitted with a concern for invasive carcinoma. Clinical information was available in 10 patients with up to 24 months of follow-up: all patients are alive and well and no subsequent malignancy has been reported.
CONCLUSIONS: Awareness of this unique morphology is important to avoid overdiagnosing microcarcinoids as invasive adenocarcinoma. Moreover, this immunohistochemical panel can be helpful in discriminating microcarcinoids from its malignant mimic in challenging cases.

Kumar AS, Coralic J, Kelleher DC, et al.
Complications of transanal endoscopic microsurgery are rare and minor: a single institution's analysis and comparison to existing data.
Dis Colon Rectum. 2013; 56(3):295-300 [PubMed]

BACKGROUND: Transanal endoscopic microsurgery, a minimally invasive procedure for treatment of early-stage rectal cancer, carcinoid tumors, and adenomas, is shown to be a safe procedure with very low perioperative morbidity.
OBJECTIVE: We aimed to compare the outcomes of transanal endoscopic microsurgery at a large volume tertiary care center with the existing literature.
DESIGN: We retrospectively reviewed a prospectively collected database of 325 transanal endoscopic microsurgery procedures and looked for risk factors associated with complications. Indications for transanal endoscopic microsurgery included rectal adenocarcinomas, adenomas, and carcinoids.
SETTING: Procedures were performed by a single surgeon at a large-volume tertiary care center.
PATIENTS: Patients were enrolled over a 20-year period, and data were collected on demographics, perioperative details, tumor characteristics, and complications.
INTERVENTIONS: Transanal endoscopic microsurgery was performed on all 325 patients.
MAIN OUTCOME MEASURES: Main outcome measures were urinary retention, late bleeding requiring intervention, dehiscence, peritoneal cavity entry, conversion to abdominal approach, fecal soiling, and rectovaginal fistula.
RESULTS: Intraoperative bleeding was associated with larger tumor size, whereas postoperative bleeding requiring intervention was not associated with any factors studied. Peritoneal cavity entry and urinary retention were more likely if the tumor was in either the anterior or lateral position in the rectum. The peritoneal cavity was entered in 9 patients, and conversion to abdominal approach occurred in 1 patient. Intraoperative bleeding, by surgeon's choice, and urinary retention, by patient's choice, were associated with a greater likelihood of admission to the inpatient ward. Fecal soiling was not reported by patients and not recorded.
LIMITATIONS: This study was limited because it was a retrospective analysis
CONCLUSIONS: Transanal endoscopic microsurgery is an extremely safe procedure, offering very low perioperative morbidity. The overall morbidity found in our study was 10.5%, on par with published data for large series of 21%, 7.7%, and 14.9%. In contrast, complications from radical resection are reported at 18% to 55%.

Pavel M, Kidd M, Modlin I
Systemic therapeutic options for carcinoid.
Semin Oncol. 2013; 40(1):84-99 [PubMed]

"Carcinoids" are mostly slow-growing neuroendocrine neoplasms (NENs) with low proliferative activity. A wide range of therapeutic options with variable efficacy exist, including locoregional ablative strategies. Thereafter, some patients may not require medical therapy for years depending on the rate of progression or recurrence. However, the majority of patients require systemic treatment and therein lies the dilemma, since no antiproliferative agent is currently approved for carcinoids. Somatostatin analogs (SSAs), and to a lesser extent interferon-alpha, are standard therapy for carcinoids associated with the carcinoid syndrome. These drugs have some antiproliferative efficacy. SSAs rarely lead to tumor remission but may modestly prolong time to tumor progression. Chemotherapy is of limited value in carcinoids with low proliferation indices but may be useful in higher grade tumors. Peptide receptor-targeted radionuclide therapy may be of benefit and is mostly used after medical therapies fail. However, it is considered an investigational modality. More recently, targeted drugs such as mammalian target of rapamycin (mTOR) inhibitors and anti-angiogenics have been investigated. Objective remissions are rare. Their value remains to be rigorously elucidated. Increased efficacy requires a better understanding of the underlying tumor biology and identification of molecular pathological criteria to allow appropriate preselection of candidates for targeted therapies.

Valeriani M, Agolli L, Falco T, et al.
A case report of metastatic atypical thymic carcinoid with ectopic ACTH production: locoregional control after adaptive radiation treatment.
Tumori. 2012; 98(6):172e-5e [PubMed]

Thymic carcinoid is an extremely rare malignancy. This tumor is often associated with endocrine disorders such as Cushing's syndrome, multiple endocrine neoplasia type 1 and superior vena cava syndrome. We describe the case of a 44-year-old Italian woman with metastatic atypical thymic carcinoid secreting ectopic adrenocorticotropic hormone who was treated with adaptive radiation therapy with a curative dose schedule for a symptomatic mediastinal tumor. After 22 months, the patient was in good clinical condition, presenting stable disease without any evidence of local or systemic progression. To our knowledge there are no previously reported data regarding radical radiotherapy in the treatment of thymic carcinoids.

Hurtado-Cordovi J, Lipka S, Avezbakiyev B, Multz AS
Budd-Chiari syndrome induced by stage IV rectal carcinoid.
Am J Med Sci. 2013; 345(3):246-7 [PubMed]

Budd-Chiari syndrome (BCS) is defined as an obstruction of the hepatic venous outflow anywhere from the small hepatic veins to the suprahepatic inferior vena cava. In this study, a rare case of BCS induced by a metastatic rectal carcinoid is presented. A 57-year-old African American woman with stage IV rectal carcinoid presented with right upper quadrant pain, associated with decreased appetite and weight loss >13 kg over 2 months. Computed tomography scan with contrast enhancement revealed filling defects in the left and middle hepatic veins extending into the suprahepatic inferior vena cava to the junction of the right atrium, suggesting BCS. Thrombophilia workup was negative, and no signs of liver cirrhosis or portal hypertension were found. A hepatitis profile workup yielded negative results. This is the first reported case of BCS that is associated with a metastatic rectal carcinoid. More research is needed to identify the mechanism leading to thrombogenesis in carcinoid tumors.

Fukami Y, Kurumiya Y, Mizuno K, et al.
A 12-mm carcinoid tumor of the minor duodenal papilla with lymph node metastases.
Jpn J Clin Oncol. 2013; 43(1):74-7 [PubMed]

Carcinoid tumors located in the minor duodenal papilla are extremely rare, with only a few cases reported in the literature. Herein, we report the case of a 71-year-old man with a 12-mm carcinoid tumor at the minor duodenal papilla with lymph node metastases. Multidetector-row computed tomography with contrast enhancement revealed a 12-mm well-enhanced tumor in the duodenum. Upper gastrointestinal endoscopy showed a 12-mm submucosal tumor at the minor papilla of the duodenum. Biopsy specimens revealed a carcinoid tumor, and a subtotal stomach-preserving pancreatoduodenectomy was performed. Carcinoid tumors at the minor duodenal papilla have a high prevalence of nodal disease, even for tumors <2 cm in diameter. Therefore, we believe that radical resection with tumor-free margins (i.e. pancreatoduodenectomy) is the treatment of choice.

Thomas D, Tsolakis AV, Grozinsky-Glasberg S, et al.
Long-term follow-up of a large series of patients with type 1 gastric carcinoid tumors: data from a multicenter study.
Eur J Endocrinol. 2013; 168(2):185-93 [PubMed]

OBJECTIVE: To study the clinical presentation, diagnostic approach, response to treatment, and the presence of other pathologies in patients with gastric carcinoid type 1 (GC 1) tumors.
DESIGN AND METHODS: Retrospective analysis of 111 patients from four institutions and a mean follow-up of 76 months.
RESULTS: The main indications for gastroscopy were upper gastrointestinal tract symptoms. The mean number of lesions, maximum tumoral diameter, and percentage of cells expressing Ki-67 labeling index were 3.6±3.8, 8±12.1 mm and 1.9±2.4% respectively. Serum gastrin and chromogranin A (CgA) levels were elevated in 100/101 and 85/90 patients respectively. Conventional imaging studies demonstrated pathology in 9/111 patients. Scintigraphy with radiolabeled octreotide was positive in 6/60 without revealing any additional lesions. From the 59 patients who had been followed-up without any intervention, five developed tumor progression. Thirty-two patients were treated with long-acting somatostatin analogs (SSAs), leading to a significant reduction of gastrin and CgA levels, number of visible tumors, and CgA immune-reactive tumor cells in 28, 19, 27, and 23 treated patients respectively. Antrectomy and/or gastrectomy were initially performed in 20 patients and a complete response was achieved in 13 patients. The most common comorbidities were vitamin B12 deficiency, thyroiditis, and parathyroid adenomas.
CONCLUSIONS: Most GCs1 are grade 1 (82.7%) tumors presenting with stage I (73.9%) disease with no mortality after prolonged follow-up. Ocreoscan did not provide further information compared with conventional imaging techniques. Treatment with SSAs proved to be effective for the duration of administration.

Singla S, Gupta S, Reddy RM, et al.
68Ga-DOTA-NOC PET and peptide receptor radionuclide therapy in management of bilateral ovarian metastases from gastrointestinal carcinoid.
Jpn J Clin Oncol. 2012; 42(12):1202-6 [PubMed]

The management of neuroendocrine tumours is challenging when curative surgery is ruled out because of distant metastases. We report a case of gastrointestinal carcinoid with bilateral ovarian metastases in a 50-year-old female who received octreotide therapy followed by peptide receptor radionuclide therapy and surgery thereafter. Somatostatin receptor expression on neuroendocrine tumours has implications in diagnosis and therapy. (68)Ga-DOTA-NOC PET is a recent advancement in the field of somatostatin receptor imaging. The lesions which demonstrate tracer uptake on positron emission tomographic studies can be further planned for treatment with octreotide and (177)Lu-DOTA-TATE. The case in discussion responded well to non-invasive treatment options before proceeding to definitive surgical management.

Kaplan AL, Margolis DJ, Said J, Chin AI
Primary carcinoid tumor of urinary bladder discovered on pelvic magnetic resonance imaging.
Urology. 2012; 80(5):e55-7 [PubMed]

Pure primary carcinoid tumor of the urinary bladder is an exceedingly rare lesion with less than twenty cases reported in the English language literature. These tumors are typically small and rarely invade past the lamina propria. Amenable to transurethral resection alone, they are associated with a favorable prognosis. We present a case of pure primary carcinoid tumor of the bladder discovered on T2-weighted pelvic magnetic resonance imaging.

Niimi K, Goto O, Fujishiro M, et al.
Endoscopic mucosal resection with a ligation device or endoscopic submucosal dissection for rectal carcinoid tumors: an analysis of 24 consecutive cases.
Dig Endosc. 2012; 24(6):443-7 [PubMed]

AIMS: Endoscopic submucosal dissection (ESD) has several advantages over conventional endoscopic mucosal resection, including a higher en bloc resection rate and more accurate pathological estimation. However, ESD is a complex procedure that requires advanced endoscopic skills. The aim of our study is to evaluate the efficacy of endoscopic mucosal resection with a ligation device (EMR-L) compared to ESD for rectal carcinoid tumors.
METHODS: Between September 2003 and April 2011, 24 rectal carcinoid tumors in 24 patients treated by ESD or EMR-L were retrospectively analyzed. The indications for endoscopic treatment were node-negative rectal carcinoid tumors. We compared the therapeutic outcomes of the ESD group (n = 13) and the EMR-L group (n = 11).
RESULTS: Both groups had similar mean tumor sizes (ESD: 5.5 ± 2.1 mm; EMR-L: 4.4 ± 2.2 mm). The rates of en bloc and complete resection were, respectively, 100% and 92.3% for ESD, and 100% and 100% for EMR-L. Perforations did not occur in either group. Postoperative bleeding occurred in one EMR-L case, and it was endoscopically managed. However, there were no differences in therapeutic outcomes between the two groups. The mean procedure time was longer in the ESD group (28.8 ± 16.2 min) than in the EMR-L group (17.4 ± 4.4 min), without a significant difference. The mean hospitalization period was significantly shorter in the EMR-L group (1.8 ± 3.1 day) than in the ESD group (6.2 ± 2.1 day), and eight EMR-L cases were treated in an outpatient setting.
CONCLUSIONS: EMR-L is a simple and effective procedure that compares favorably to ESD for small rectal carcinoid tumors.

Fossmark R, Sørdal Ø, Jianu CS, et al.
Treatment of gastric carcinoids type 1 with the gastrin receptor antagonist netazepide (YF476) results in regression of tumours and normalisation of serum chromogranin A.
Aliment Pharmacol Ther. 2012; 36(11-12):1067-75 [PubMed]

BACKGROUND: Patients with chronic atrophic gastritis have long-term gastric hypoacidity, and secondary hypergastrinaemia. Some also develop gastric ECL cells carcinoids (type 1 GC). Most type 1 GC remain indolent, but some metastasise. Patients undergo surveillance, and some are treated with somatostatin analogues, endoscopic resection or surgery. Netazepide (YF476) is a highly selective, potent and orally active gastrin receptor antagonist, which has anti-tumour activity in various rodent models of gastric neoplasia driven by hypergastrinaemia. Netazepide has been studied in healthy volunteers.
AIM: To assess the effect of netazepide on type 1 GC.
METHODS: Eight patients with multiple type 1 GC received oral netazepide once daily for 12 weeks, with follow-up at 12 weeks in an open-label, pilot trial. Upper endoscopy was performed at 0, 6, 12 and 24 weeks, and carcinoids were counted and measured. Fasting serum gastrin and chromogranin A (CgA) and safety and tolerability were assessed at 0, 3, 6, 9, 12 and 24 weeks.
RESULTS: Netazepide was well tolerated. All patients had a reduction in the number and size of their largest carcinoid. CgA was reduced to normal levels at 3 weeks and remained so until 12 weeks, but had returned to pre-treatment levels at 24 weeks. Gastrin remained unchanged throughout treatment.
CONCLUSIONS: The gastrin receptor antagonist netazepide is a promising new medical treatment for type 1 gastric carcinoids, which appear to be gastrin-dependent. Controlled studies and long-term treatment are justified to find out whether netazepide treatment can eradicate type 1 gastric carcinoids.

Kandil E, Noureldine SI, Koffron A, et al.
Outcomes of laparoscopic and open resection for neuroendocrine liver metastases.
Surgery. 2012; 152(6):1225-31 [PubMed]

BACKGROUND: We sought to compare the outcomes in patients with hepatic carcinoid tumor metastases treated with open versus laparoscopic liver resection.
METHODS: A retrospective analysis of our liver surgery database was performed. All patients who underwent liver resection for hepatic carcinoid tumor metastases were included. Patients were divided into 2 groups depending on the surgical approach. Patients with concomitant primary and metastatic liver lesions underwent open resection.
RESULTS: Thirty-six patients underwent resection over a 10-year period (21 open and 15 laparoscopic). Both groups were similar in terms of gender, body mass index, tumor size, incidence of carcinoid syndrome, and extent of resection (P > .05). The laparoscopic group had less mean operative time (2.7 vs 5.4 hours), less mean blood loss (158.3 vs 538.9 mL), and a shorter hospital stay (3.2 vs 7.5 days; P < .05 for all). Complications were similar in both groups (20% vs 33%; P = .21). Two laparoscopic cases required conversion. The 3-year disease-free survival for the laparoscopic group was 73.3% compared to 47.6% for the open group (P = .2).
CONCLUSION: To our knowledge, this is the first reported study comparing laparoscopic versus open liver resection in the treatment of liver metastases from carcinoid tumors. Our series confirms that selective cases can safely be managed laparoscopically.

Fox M, Van Berkel V, Bousamra M, et al.
Surgical management of pulmonary carcinoid tumors: sublobar resection versus lobectomy.
Am J Surg. 2013; 205(2):200-8 [PubMed]

BACKGROUND: Surgical resection of bronchopulmonary carcinoid tumors can be curative and remains the primary treatment modality. There are limited data to delineate the optimal extent of resection for this disease.
METHODS: A retrospective review of the 3,270 patients diagnosed with typical and atypical carcinoid tumors between 2000 and 2007 in the Surveillance Epidemiology and End Results registry was performed.
RESULTS: The mean follow-up period was 46 months (range, 1-95 mo). Overall survival (OS) and disease-specific survival at 5 years was 80% and 90%, respectively. The mean OS was slightly better in the lobectomy group compared with those undergoing sublobar resection (86 vs 83 mo; P = .008). After adjusting for age, this finding was no longer present (P = .513). By using multivariate analysis, sublobar resection was noninferior to lobectomy with regard to disease-specific survival and OS (P < .05).
CONCLUSIONS: Compared with lobectomy, sublobar resection is associated with noninferior survival in patients with typical carcinoid of the lung.

Poiana C, Carsote M, Trifanescu R, et al.
Case study of appendiceal carcinoid during pregnancy.
J Med Life. 2012; 5(3):325-8 [PubMed] Free Access to Full Article

The carcinoid tumor of the appendix is one of the most common tumors of the appendix, but one of the rarest anatomic locations of carcinoids. The prognosis is very good, as most tumors are incidentally discovered during surgery for acute or sub-acute appendicitis. The diagnosis is exceptional when combined with pregnancy. We present such a case of a 27-year-old female patient. An emergency appendectomy was performed, and soon after, pregnancy was confirmed. The patient had a tumor smaller than 1 cm in diameter, at the tip of the appendix. The immunochemistry revealed the neuroendocrine profile by positive reaction for chromogranin A and synaptophysin, with a ki-67 profile at an undetectable level. After surgery, the neuroendocrine markers and the octreoscan were negative, consequently indicating a favorable prognosis. Further follow-up is necessary, even though not all the authors recommend it (considering the low index to the associated metastases, especially for small appendiceal tumors). A short review of the literature is presented, starting with this case report.

Hui CK
Collision adenoma-carcinoid tumour of the colon complicated by carcinoid syndrome.
Singapore Med J. 2012; 53(9):e195-7 [PubMed]

Tumours consisting of a glandular component, either an adenoma or adenocarcinoma, and a carcinoid component are uncommon. These tumours can be differentiated into collision, composite or amphicrine tumours. Most cases reported in the literature were mixed adenocarcinoma-carcinoid tumours. To date, only four cases of mixed adenoma carcinoid tumours have been reported in the literature. This case report describes a unique case of collision adenoma-carcinoid tumour in the colon complicated by carcinoid syndrome in a 45-year-old woman who presented with a one-month history of diarrhoea and weight loss. She developed recurrence of the carcinoid component of the tumour four months after endoscopic resection. We conclude that carcinoid syndrome can occur in an adenoma-carcinoid tumour; however, the prognosis of this condition is uncertain.

Loaiza-Bonilla A, Rossi F, Alkhalil B
Tracheal carcinoid presenting as refractory cervicalgia in a postpartum patient: correlation versus epiphenomenon.
Ear Nose Throat J. 2012; 91(9):E11-4 [PubMed]

Primary tracheal carcinoid tumor is an extremely rare disorder that has been reported only occasionally in the medical literature. We report a case of a 36-year-old African American woman who presented to the emergency department complaining of persistent neck pain for the preceding week. She was 2 weeks postpartum and had no significant medical history. Laboratory workup was unremarkable. Computed tomography and magnetic resonance imaging showed a polypoid mass in the trachea. After bronchoscopy and laser ablation of the mass were performed, the final diagnosis of carcinoid tumor was made. To our knowledge this is the first reported case of this tumor in a postpartum patient. Further studies regarding the interactions between the natural history of carcinoid tumors and pregnancy are warranted. Their infrequency, clinical features, and pathophysiology make tracheal carcinoid tumors a formidable and interesting diagnostic challenge.

Mazza E, Abdulcadir D, Raspanti C, Acquafresca M
A challenging case of epigastric pain: diagnosis and mini-invasive treatment of a large gastroduodenal artery pseudoaneurysm.
BMJ Case Rep. 2012; 2012 [PubMed]

The authors present a case of a gastroduodenal artery pseudoaneurysm in a patient with a medical history of pancreatic surgery. The lesion was found and evaluated by ultrasound, CT-angiography and then treated with trans-catheter embolisation. This mini-invasive approach led to a complete resolution of the lesion.

Boddaert G, Grand B, Le Pimpec-Barthes F, et al.
Bronchial carcinoid tumors causing Cushing's syndrome: more aggressive behavior and the need for early diagnosis.
Ann Thorac Surg. 2012; 94(6):1823-9 [PubMed]

BACKGROUND: The aim of this study was to revisit the characteristics and outcomes of adrenocorticotropin-secreting bronchial carcinoid tumor (BCT) responsible for Cushing's syndrome (CS).
METHODS: We conducted a single-institution retrospective review of 14 patients who underwent pulmonary resection for BCT that presented as CS from October 1993 to November 2011.
RESULTS: The group consisted of 8 male patients (57%) and 6 female patients. The mean age was 40 years (range, 16-63 years). Three patients (21%) underwent unnecessary adrenalectomy or hypophysectomy, or both, before diagnosis of the main cause. The mean interval between clinical presentation and the chest operation was 33 months (range, 3-136 months). Operations included 12 lobectomies (86%), 1 segmentectomy, and 1 wedge excision. All patients underwent radical lymph node dissection. Histologic examination showed 11 typical carcinoids (79%) and 3 atypical carcinoids. Twelve patients were classified pT1 (86%) and 2 patients were classified pT3 because of the presence of 2 tumors in the same lobe. Lymph node metastases were found in 7 patients (50%) (3 pN1 and 4 pN2). The mean follow-up was 59 months (range, 3-174 months). No recurrence was observed.
CONCLUSIONS: Early detection of adrenocorticotropin-secreting BCTs is challenging. However, it avoids adrenalectomy and unnecessary hypophysectomy, limits the deleterious effects of chronic hypercortisolism, and reduces the risk of metastasis. The high prevalence of lymph node involvement confirms the aggressiveness of these tumors and justifies anatomic resection and radical lymph node dissection. Under these circumstances, the prognosis remains favorable, even in cases of N2 disease.

Baig S, Patil N, Considine N
Carcinoid tumour of the middle ear.
J Coll Physicians Surg Pak. 2012; 22(9):604-6 [PubMed]

A case of middle ear mass in a young female from Ireland is described, who presented with left ear hearing loss and intermittent bloody discharge from the same ear. Examination under microscope revealed occlusive polyp in the left ear and a biopsy had been taken under general anaesthesia. Histopathology report described an adenoma / carcinoid tumour of the middle ear confirmed by positive immunohistochemical staining. CT temporal bones revealed the extension of the disease. The patient underwent left tympanotomy and excision of the tumour. In general, these tumours are regarded as benign but may be mistaken for adenocarcinomas because of their histological heterogenecity.

Kidd M, Gustafsson BI
Management of gastric carcinoids (neuroendocrine neoplasms).
Curr Gastroenterol Rep. 2012; 14(6):467-72 [PubMed]

Gastric neuroendocrine neoplasms of the stomach can be divided into the usually well-differentiated, hypergastrinemia-dependent type I and II lesions and the more aggressively behaving gastrin-independent type III lesions. Mainly due to better diagnostics and awareness of this tumor, the observed incidence has increased more than tenfold over the last 30 years. Small (<15-20 mm) localized type I and II lesions that are slowly proliferating (Ki67<2%) can usually be managed conservatively with endoscopic surveillance. Reducing hypergastrinemia by surgical removal of an underlying gastrinoma is important in inhibiting growth and induce reduction of type II lesions, while the specific gastrin receptor antagonist YF476 or gastrin antibodies may become useful for both type I and II lesions. Infiltrating and metastasized tumors and type III lesions require a more aggressive approach with surgical resection and consideration of modalities such as somatostatin analogs, cytotoxics, and peptide receptor targeted treatment.

Capurso G, Rinzivillo M, Bettini R, et al.
Systematic review of resection of primary midgut carcinoid tumour in patients with unresectable liver metastases.
Br J Surg. 2012; 99(11):1480-6 [PubMed]

BACKGROUND: Surgery for small intestinal neuroendocrine tumours (SI-NETs) is limited by metastatic disease in most patients. However, resection of the primary lesion alone has been advocated in patients with unresectable liver metastases. The present systematic review investigated the value of surgical resection of the primary lesion in patients with unresectable metastatic disease.
METHODS: MEDLINE was searched for studies reporting the outcome of patients with SI-NETs and unresectable liver metastases where there was an explicit comparison between resection of the primary lesion alone and no resection. The primary outcome was overall survival. Secondary outcomes were progression-free survival, treatment-related mortality and relief of symptoms.
RESULTS: Meta-analysis was not possible, but six studies were analysed qualitatively to highlight useful information. Possible confounders in these studies were the inclusion of patients with other primary tumour sites, unknown primary tumour or non-metastatic disease. Bearing in mind these limitations, there was a clear trend towards longer survival in patients who underwent surgical resection in all studies; their median overall survival ranged from 75 to 139 months compared with 50-88 months in patients who did not have resection. The difference between the two groups was statistically significant in three studies. Data on symptomatic improvement were scarce and did not suggest a clear benefit of surgery. Surgery-related mortality seemed low.
CONCLUSION: Available data suggest a possible benefit of resection of the primary lesion in patients with unresectable liver metastases, but the studies have several limitations and the results should therefore be considered with caution.

Dumaswala B, Bicer EI, Dumaswala K, et al.
Live/Real time three-dimensional transthoracic echocardiographic assessment of the involvement of cardiac valves and chambers in carcinoid disease.
[PubMed]

We present an adult with metastatic carcinoid disease affecting the heart, in whom live/real time three-dimensional transthoracic echocardiography (3DTTE) provided incremental value over two-dimensional transthoracic echocardiography (2DTTE). Initial 2DTTE was able to demonstrate severe pulmonic and tricuspid regurgitation, but was unable to visualize the posterior leaflet of the tricuspid valve or the right (right anterior) leaflet of the pulmonic valve. Further analysis with 3DTTE demonstrated thickening, restricted mobility, and noncoaptation of all three leaflets of both the tricuspid and the pulmonary valves. En face viewing of tricuspid and pulmonary regurgitation vena contractas permitted more reliable quantification of regurgitation severity. In addition, localized, linear, echogenic areas consistent with carcinoid deposits were noted along the inner walls of the right atrium, atrial septum, and inferior vena cava. To the best of our knowledge, endocardial carcinoid deposits have never been reported by 2D or 3D echocardiography. En face viewing of these deposits by 3DTTE enabled measurement of their dimensions and areas. Subcostal examination also identified large circumscribed hepatic lesions consistent with metastatic disease. Neither the carcinoid deposits nor the metastatic lesions were detected by 2DTTE. This case demonstrates the usefulness of 3DTTE as a supplement to 2DTTE in more comprehensively assessing carcinoid involvement of the heart.

Salzman R, Stárek I, Tichá V, et al.
Metastasizing middle ear carcinoid: an unusual case report, with focus on ultrastructural and immunohistochemical findings.
Otol Neurotol. 2012; 33(8):1418-21 [PubMed]

BACKGROUND: There are only 4 unequivocal cases of metastasizing middle ear carcinoid previously reported.
OBJECTIVE: To present a case of metastasizing middle ear carcinoid, to review previously reported cases, and to discuss the clinical nature of this tumor, which is similar to "orthotopic" carcinoids bearing definite metastatic potential.
STUDY DESIGN: Case report. PATIENT, INTERVENTION, RESULTS: We present a 72-year-old woman who developed ipsilateral parotid gland and cervical lymph node metastases 8 and 11 months after surgical removal of a primary middle ear lesion. She subsequently required 2 revision procedures and radiotherapy for local recurrences. Her case was complicated by nonsurgically induced permanent facial nerve paralysis, the cause of which remains obscure. At the end of the 8-year follow-up, the patient was alive with locally, recurrent tumor eroding the cranial base and invading the posterior intracranial fossa but with no signs of metastases.
MAIN OUTCOME MEASURES: Light microscopy and immunohistochemical analysis.
CONCLUSION: Considering the reported high rate of recurrence and their consequent metastases, a middle ear carcinoid should be classified as a neuroendocrine low-grade carcinoma.

Zhong CX, Yao F, Zhao H, et al.
Long-term outcomes of surgical treatment for pulmonary carcinoid tumors: 20 years' experience with 131 patients.
Chin Med J (Engl). 2012; 125(17):3022-6 [PubMed]

BACKGROUND: Bronchial carcinoids are rare malignant neuroendocrine neoplasms. Some issues regarding surgical treatment of bronchial carcinoids remain controversial, including the role of bronchoplastic surgery and necessity of systematic lymphadenectomy.
METHODS: This retrospective study involved 131 consecutive patients surgically treated for carcinoid tumors at Shanghai Chest Hospital between March 1990 and August 2010.
RESULTS: Eighty-nine (67.9%) of the patients were male, and the mean age was 46 years, ranging from 17 to 81 years. Preoperative fiberoptic bronchoscopy was performed in all patients. Endoscopic biopsy was performed in 100 patients with central tumors, and 70 (70%) patients were diagnosed as bronchial carcinoid. The resections performed consisted of 31 pneumonectomie, 32 lobectomies, 26 bilobectomies, 34 sleeve lobectomies, six bronchoplastic procedures without lung resection, and two segmentectomies. During a median of 87 months follow-up, there were nine recurrences including three local recurrences and 6 distant recurrences. No bronchial recurrences were observed. The 3-, 5- and 10-year overall survival rates of pneumonectom and bronchoplastic surgery (including sleeve lobectomy and bronchoplastic procedure without lung resection) were 93.2%, 81.0% and 69.4%, 97.5%, 91.9% and 70.0%, respectively. Multivariate Cox regression indicated that histology and nodal status were significant independent prognostic factors.
CONCLUSIONS: Bronchoplastic surgery should be considered whenever possible for central carcinoids. Systematic lymphadenectomy is recommended for bronchial carcinoid patients. Histology and nodal status were significant independent prognostic factors of overall survival of patients with bronchial carcinoid.

Ohara I, Ogata S, Okusa Y, et al.
Serotonin- and somatostatin-positive goblet cell carcinoid of the duodenum.
Acta Med Okayama. 2012; 66(4):351-6 [PubMed]

In the duodenum, mixed exocrine-endocrine tumors exhibiting both neuroendocrine and glandular differentiations [cf. appendiceal goblet cell carcinoids (GCCs)] are rare. We present a Japanese case with a duodenal GCC that was found during pathologic examination of a gastrectomy specimen removed for gastric mucosal cancer. The tumor was widely distributed within both the first portion of the duodenum and the gastric antrum, although mucosal involvement was observed only in the duodenum. The tumor cells formed solid nests, trabeculae, or tubules, and some displayed a goblet cell appearance. They were immunoreactive against antibodies for both serotonin and somatostatin, and showed an argentaffin reaction (similar to a "midgut" enterochromaffin cell carcinoid). Ultra-structurally, the tumor cells had an amphicrine nature. Physicians encounter GCC in the duodenum only rarely, and its discovery may be incidental. Its diagnosis will be challenging and will require careful clinical and pathologic examinations.

Hammel P, Hentic O, Neuzillet C, et al.
New treatment options with cytotoxic agents in neuroendocrine tumours.
Target Oncol. 2012; 7(3):169-72 [PubMed]

There are numerous treatment options for patients with advanced digestive neuroendocrine tumours (NETs). Medical treatment includes systemic chemotherapies, targeted therapies, somatostatin analogs, liver-directed therapies such as (chemo)embolization or thermoablation, and peptide receptor radionuclide therapy. Cytotoxic chemotherapies can help control tumour progression in patients with non-resectable tumours and may improve symptoms by reducing tumour bulk. In addition, tumour response is usually greater than that obtained with targeted therapies. This should be taken into consideration in neoadjuvant strategies. Efficacy of temozolomide depends on the O(6) methylguanine DNA methyl transferase status, and thus, this drug will likely have to be considered in the future in patients with a favourable enzyme profile. Because numerous treatment options are available for patients with advanced digestive NETs, and thanks to their long survival, successive drugs should be used. Careful attention should be paid to the adverse events in order to maintain the quality of life in these patients who have with a long life expectancy.

Srivastava SA, Wang Y, Vallone J, Felix JC
Primary clear cell carcinoid tumors of the vulva.
Am J Surg Pathol. 2012; 36(9):1371-5 [PubMed]

Neuroendocrine tumors are uncommon in the female genital tract and have been described in the ovary, uterus, cervix, and vagina. Primary carcinoid tumors have not been described in the vulva. We report 3 cases in 3 middle-aged women who presented with a solitary vulvar nodule without any other associated symptoms. All were treated with simple local excision. Two tumors were composed exclusively of clear cells arranged in nests separated by fibrovascular septae. The third tumor predominantly exhibited nests of eosinophilic granular cells with scattered areas of cells showing clear cytoplasm. Immunohistochemical staining for chromogranin and neuron-specific enolase confirmed neuroendocrine differentiation in all cases. Follow-up of 5.5 to 16 years showed no evidence of recurrence or metastasis. Primary clear cell carcinoid tumors of the vulva need to be considered in the differential diagnosis of vulvar masses with clear cell features. Immunohistochemistry plays an important role in the diagnosis of these lesions.