Carcinoid tumors are rare, neuroendocrine malignancies with a reported incidence of 1 to 2 cases per 100,000 individuals.1,2 Carcinoids typically arise in the intestine, with the appendix most frequently involved, or more rarely from the thymus, bronchus, stomach, or pancreas. Primary ovarian carcinoid tumors are so very rare, accounting for only 0.3% to 1% of all carcinoid tumors,2,3 that a clinician may not encounter even one during his/her entire career. Furthermore, because these tumors account for <0.1% of all ovarian neoplasms,4 they may not be suspected by the gynecologic surgeon and remain undiagnosed until the time of surgery.
Consistent with their low incidence, case reports or series describing primary ovarian carcinoid are sparse in the literature.3,5–10 The anesthesia literature is especially exiguous, with only a few case reports over the last 2 decades.11–13 We present a case of undiagnosed primary ovarian carcinoid, discuss the preoperative clues that could have led to suspicion of this tumor, and describe management strategies that can be used. The patient provided written consent for the publication of this report.
A 115-kg, 39-year-old woman with a medical history of hypothyroidism, previous cesarean delivery, and multiple subsequent vaginal births presented for bilateral laparoscopic ovarian cystectomy for several large ovarian cysts, believed to be dermoid in origin. Her preoperative examination was notable for a distinctive, violaceous malar rash with teleangiectasia and skin thickening. The rash had been present for 2 years. A dermatologist had diagnosed the condition as rosacea and had given her a steroid cream, which did not work. She also had a loud, blowing, high-pitched, midsystolic heart murmur heard loudest along her left lower sternal border, which had never been brought to her attention. The patient stated that she had no limitations on her activity, was able to care for her children, and could easily climb 2 flights of stairs. She reported that she no longer drank alcohol because in the past few years it had begun to cause her to become markedly “flushed.”
Because of her high level of functional activity without symptoms, the decision was made to proceed to surgery despite the newly diagnosed murmur.14 Preoperatively, her arterial blood pressure was 135/67 mm Hg and her heart rate was 78 beats per minute. General anesthesia was uneventfully induced with propofol, and vecuronium was used for muscle relaxation. The trachea was intubated and anesthesia was maintained with sevoflurane and intermittent boluses of fentanyl. Upon insertion of the laparoscope into the abdominal cavity, a large amount of blood was noted, along with a puncture site on the right ovarian mass, consistent with injury from the Veress needle. The bleeding was controlled with bipolar cautery. The left ovarian cyst was removed without difficulty; however, resection of the right ovarian mass was complicated by its large size and highly vascular nature. This led to profuse bleeding, noted by the surgeon to be unusual for a dermoid.
Soon after resection of the right cyst, the patient became hypotensive to 70/40 mm Hg, bradycardic, and a large amount of blood was noted in the abdomen. A vascular surgery consult was requested and the procedure was converted to a laparotomy. A second large-bore IV cannula and an arterial line were placed. The hypotension was treated with a rapid 1-L bolus of crystalloid, phenylephrine, ephedrine, and vasopressin, and 2 U of packed red blood cells was transfused. No vascular source of bleeding was found and it was concluded that the blood was from the original Veress needle injury. Shortly thereafter, the patient's hemodynamic status stabilized.
Intraoperative frozen section examination revealed the left cyst to be a dermoid tumor containing a large piece of skull; however, the right ovarian tumor had features consistent with primary ovarian carcinoid. After obtaining consent from the patient's husband, the patient's entire right ovary and fallopian tube were removed. Because of concern that the ovarian mass might be a metastatic lesion from an intestinal primary, the bowel was examined and found to be benign. The surgery was completed, the trachea was extubated, and the patient was brought to the recovery room without further complications. The remainder of her hospital stay was uneventful. Final pathology confirmed the right ovarian tumor to be a primary ovarian carcinoid.
Upon telephone follow-up with the patient 2 months later, she reported that the all of her clinical symptoms, including the facial rash, had completely resolved. An outpatient echocardiogram revealed trace tricuspid and mitral regurgitation with no evidence of valvular lesions.
There are 3 features of this case that are of interest. First, what clinical signs and symptoms suspicious for primary ovarian carcinoid can be elicited on clinical examination? Second, what is the significance of the newly diagnosed murmur? Finally, does the suspicion of an ovarian carcinoid change the anesthetic plan, and what are the options for management?
Carcinoid tumors secrete a wide variety of neurohumoral substances such as serotonin, histamine, tachykinin, bradykinin, kallikrein, corticotropin, substance P, motilin, and prostaglandins.15 Persistent systemic exposure to large quantities of these hormones and biogenic amines can result in carcinoid syndrome, the classic triad of flushing of the upper extremities and face, wheezing, and diarrhea (Table 1). Normally, systemic exposure does not occur with an intestinal carcinoid until it has metastasized, because of efficient hepatic metabolism of the secreted substances. However, primary ovarian carcinoids can cause these symptoms directly, because their venous drainage bypasses the portal system. Our patient presented with an unusual, distinctive facial rash that had been misdiagnosed as rosacea, and a recently developed intolerance to alcohol because of severe cutaneous flushing. Particularly in the context of no prior workup for malignancy and a known ovarian mass, these were the first 2 important clues to our patient's underlying condition.
Our patient also had a newly diagnosed and clinically impressive murmur. Should this have led to further workup? A large prospective Dutch study found that the positive predictive value for detecting valvular heart disease using cardiac auscultation was only 70%, and that murmurs never reflected valvular heart disease in patients younger than 40 years.14 However, although there are only a few case reports of cardiac lesions due to primary ovarian carcinoid, cardiac involvement may affect up to 50% of patients with carcinoid syndrome. The typical finding is tricuspid valve stenosis and/or regurgitation secondary to fibroproliferative endomyocardial changes. These changes are thought to be the result of chronic exposure to elevated levels of serotonin. The left-sided heart valves are protected by pulmonary metabolism of tumor products. Mild-to-moderate tricuspid regurgitation or stenosis is usually benign and clinically well tolerated; however, in more severe cases, right heart failure with resulting pulmonary hypertension can occur. The murmur appreciated on examination was probably indicative of some degree of tricuspid involvement in our patient, but she lacked any symptoms indicative of right heart failure. Therefore, preoperative echocardiogram was likely unnecessary because it would not have altered the anesthetic management. Yet, combined with the facial rash and cutaneous flushing, the murmur completed a compelling picture of carcinoid disease.
Anesthetic management of patients with carcinoid disease can be challenging, because they can exhibit extreme hemodynamic lability and exaggerated physiologic responses to seemingly innocuous stimuli. A titrated induction of anesthesia is advisable to avoid excessive hemodynamic changes, as is avoidance of catecholamines and sympathomimetic drugs, because drugs such as norepinephrine, epinephrine,16 dopamine, and β-agonists (e.g., albuterol) have been reported to trigger a carcinoid crisis. Use of histamine-releasing drugs (e.g., morphine, succinylcholine, and atracurium) should also be avoided, because of the risk of bronchospasm. Ondansetron, a serotonin antagonist, is the first choice as an antiemetic drug and may also provide additional symptom control.17
Carcinoid crisis refers to the sudden and dramatic release of excessive amounts of mediator substances, which can result in shock and circulatory collapse. It is usually the result of tumor manipulation and is undoubtedly what happened in this case. Treatment is to stop manipulation of the tumor and to treat the hypotension and other mediator-induced effects17 through intravascular volume expansion18 and careful administration of vasopressors. If conventional treatment does not work, octreotide, a synthetic somatostatin analog, can be used to effectively suppress the release of mediator substances and to antagonize secretory and vasomotor effects. Octreotide has a half-life of 1.5 hours, versus the short half-life of somatostatin of 1 to 3 minutes. Notably, octreotide inhibits insulin secretion in response to hyperglycemia, which complicates glucose management, especially if steroids are being concurrently administered.
In conclusion, carcinoid tumors are rare entities, and the diagnosis is often not made until after the patient has been anesthetized and an intraoperative histopathologic sample has been taken. Tumor manipulation during the course of resection can cause extreme hemodynamic instability. In clinical situations with preoperative findings leading to suspicion for an undiagnosed ovarian carcinoid tumor, steps can be taken to optimize perioperative management. These strategies include delaying surgery until further diagnostic tests can be performed, or if performed, ensuring the availability of octreotide, a smooth controlled induction with minimal hemodynamic changes, invasive arterial blood pressure monitoring, and ready access to blood products.
Name: Matthew Levin, MD.
Contribution: This author helped write the manuscript and participated in the case.
Attestation: Matthew Levin approved the final manuscript.
Name: Brigid C. Flynn, MD.
Contribution: This author helped write the manuscript and participated in the case.
Attestation: Brigid C. Flynn approved the final manuscript.
1. Crocetti E, Paci E. Malignant carcinoids in the USA, SEER 1992–1999: an epidemiological study with 6830 cases. Eur J Cancer Prev 2003;12:191–4
2. Maggard MA, O'Connell JB, Ko CY. Updated population-based review of carcinoid tumors. Ann Surg 2004;240:117–22
3. Somak R, Shramana M, Vijay S, Nita K. Primary carcinoid tumor of the ovary: a case report. Arch Gynecol Obstet 2008;277:79–82
4. Modlin IM, Shapiro MD, Kidd M. An analysis of rare carcinoid tumors: clarifying these clinical conundrums. World J Surg 2005;29:92–101
5. De la Torre J, Garcia A, Castellvi J, Lopez M, Gil A. Primary ovarian trabecular carcinoid tumour: a case report with an immunohistochemical study and a review of the literature. Arch Gynecol Obstet 2004;270:274–7
6. Davis KP, Hartmann LK, Keeney GL, Shapiro H. Primary ovarian carcinoid tumors. Gynecol Oncol 1996;61:259–65
7. Robboy SJ, Norris HJ, Scully RE. Insular carcinoid primary in the ovary: a clinicopathologic analysis of 48 cases. Cancer 1975;36:404–18
8. Robboy SJ, Scully RE, Norris HJ. Primary trabecular carcinoid of the ovary. Obstet Gynecol 1977;49:202–7
9. Baker PM, Oliva E, Young RH, Talerman A, Scully RE. Ovarian mucinous carcinoids including some with a carcinomatous component: a report of 17 cases. Am J Surg Pathol 2001;25:557–68
10. Kopf B, Rosti G, Lanzanova G, Marangolo M. Locally advanced ovarian carcinoid. J Exp Clin Cancer Res 2005;24:313–6
11. Botero M, Fuchs R, Paulus DA, Lind DS. Carcinoid heart disease: a case report and literature review. J Clin Anesth 2002;14:57–63
12. Watson JT, Badner NH, Ali MJ. The prophylactic use of octreotide in a patient with ovarian carcinoid and valvular heart disease. Can J Anaesth 1990;37:798–800
13. Farling P, Durairaju A. Remifentanil and anaesthesia for carcinoid syndrome. Br JAnaesth 2004;92:893
14. van Klei WA, Kalkman CJ, Tolsma M, Rutten CL, Moons KG. Pre-operative detection of valvular heart disease by anaesthetists. Anaesthesia 2006;61:127–32
15. Sporrong B, Falkmer S, Robboy SJ, Alumets J, Hakanson R, Ljungberg O, Sundler F. Neurohormonal peptides in ovarian carcinoids: an immunohistochemical study of 81 primary carcinoids and of intraovarian metastases from six mid-gut carcinoids. Cancer 1982;49:68–74
16. Peart WS, Robertson JI, Andrews TM. Facial flushing produced in patients with carcinoid syndrome by intravenous adrenaline and noradrenaline. Lancet 1959;2:715–6
17. Graham GW, Unger BP, Coursin DB. Perioperative management of selected endocrine disorders. Int Anesthesiol Clin 2000;38:31–67
18. Anesthesia for patients with endocrine disease. In: Morgan GE, Mikhail MS, Murray MJ, eds. Clinical Anesthesiology. 4th ed. New York: McGraw-Hill, 2005:802–16