Carcinoid Tumor

Victor Ghobrial, MD Temple University Conemaugh Memorial Hospital

Temple University/Conemaugh Memorial Hospital Carcinoid

HPI
80 yrs WF admitted to hospital C/O abdominal pain and weakness Pain started 12 months ago and was at max on admission Located mid abdomen but radiates to lower quadrants bilaterally Pain is colicky, waxes and wanes over the course of days Pain associated with nausea and diarrhea
Temple University/Conemaugh Memorial Hospital Carcinoid

PMH
No significant history Pt is non smoker, non drinker, widow and has three children Cholecystectomy Appendectomy

Temple University/Conemaugh Memorial Hospital Carcinoid

History
Social Hx: worked in multiple jobs, retired 25 yrs ago ROS : abdominal pain, nausea and vomiting, hot flashes, night sweats No other symptoms

Temple University/Conemaugh Memorial Hospital Carcinoid

Physical Exam
Vitals WNL HEENT: unremarkable Neck: supple, no lymphadenopathy Ht: RRR, no murmurs Lungs: CTAs B/L Abdomen: soft, moderate tenderness to palpation, no masses Exter: no E,C,C Neuro: no focal deficits
Temple University/Conemaugh Memorial Hospital Carcinoid

Labs
Hgb Hct WBC Plat 9.5 29 11.1 301 Na K Cr BUN Cl 127 3.9 0.4 13 93 Alka Phos 149

CO2 29

Temple University/Conemaugh Memorial Hospital Carcinoid

Our Patient
80 yrs c/o colicky abd pain for one yr Admitted with increasing discomfort and weakness with inability to eat Diffusely tender abdomen Hyponatremic

Temple University/Conemaugh Memorial Hospital Carcinoid

Hospital Course
Upper GI small-bowel follow through: sliding hiatal hernia EGD: antral gastritis Colonoscopy: sever diverticulosis with stricture of sigmoid colon Sigmoid colectomy did not relieve abd pain Mesinteric angiography was negative
Temple University/Conemaugh Memorial Hospital Carcinoid

Colonic Bx
Diverticulosis and tumour nests in the wall including serosa and muscularis propria Cells strongly +ve for NSE and Cytokeratin highly suggestive of neuroendocrine tumour such as carcinoid tumour

Temple University/Conemaugh Memorial Hospital Carcinoid

Hospital Course
CT of chest: small nodules non diagnostic 5-HIAA in urine was 14 (Normal 6) PIC line inserted for TPN Primary of a carcinoid tumour was not found Pt placed on Sandostatin, Kytril and Diludid Eventually pt expired two months later.
Temple University/Conemaugh Memorial Hospital Carcinoid

Carcinoid tumors
Rare, but are the most common gastrointestinal neuroendocrine tumors. Symptoms of the carcinoid syndrome are infrequent occurring in approximately 10% of patients with small bowel carcinoid.

Temple University/Conemaugh Memorial Hospital Carcinoid

Temple University/Conemaugh Memorial Hospital Carcinoid

Age
the age distribution of carcinoid tumors ranges from the 2nd to the 9th decade peak incidence occur between the ages of 50 and 70
Temple University/Conemaugh Memorial Hospital Carcinoid

PATHOLOGY
Carcinoid tumors were so named because they seemed morphologically different and clinically less aggressive than the more common intestinal adenocarcinoma Carcinoids arise from enterochromaffin cells of the gastrointestinal tract. The term enterochromaffin refers to the ability to stain with potassium chromate (chromaffin), a feature of cells that contain serotonin
Temple University/Conemaugh Memorial Hospital Carcinoid

ORGAN-RELATED FEATURES
The clinical characteristics of carcinoid tumors vary with the location of the tumor.

Temple University/Conemaugh Memorial Hospital Carcinoid

Appendix
Carcinoid tumors are the most common neoplasms in the appendix. Approximately 1 in 300 appendixes contain a carcinoid tumor. They arise from endocrine cells in the lamina propria and submucosa. And are detected most commonly in the patients in their 40s or 50s.

Temple University/Conemaugh Memorial Hospital Carcinoid

Prognosis of appendiceal carcinoids

It is best predicted by the size of the tumor. Tumors 2 cm in size (found in approximately 95% of patients) are unlikely to have metastasized when diagnosed In contrast, up to 30% of larger tumors have already metastasized at diagnosis Five year survival in patients with distant metastasis is approximately 30%

Temple University/Conemaugh Memorial Hospital Carcinoid

Small intestine
Carcinoid tumors of the small intestine represent approximately one-third of small intestine neoplasms . The tumors are felt to arise from intraepithelial endocrine cell, in contrast to appendiceal carcinoids, which arise from subepithelial endocrine cells. Small intestinal carcinoid tumors are most commonly located in the ileum within 60 cm of ileocecal valve. Multiple tumors are present in up to 30 percent of patients
Temple University/Conemaugh Memorial Hospital Carcinoid

Clinical Presentation
Patients usually present in their 60s or 70s with abdominal pain or small bowel obstruction, and often with metastases to lymph nodes or the liver
Bowel obstruction or abdominal pain may be due to intussusception, the mechanical effect of the tumor, or mesenteric ischemia due to local fibrosis or angiopathy

Temple University/Conemaugh Memorial Hospital Carcinoid

Colon
Colonic carcinoids are usually detected in patients who are in their 70s during evaluation for abdominal pain, anorexia, or weight loss. The majority of tumors are located in the right colon, particularly the cecum Because of the high capacitance of the right colon, most patients do not become symptomatic until the tumors are large.
Temple University/Conemaugh Memorial Hospital Carcinoid

Rectum
The vast majority of rectal carcinoids are found incidentally by rectal examination or endoscopy. They are most commonly diagnosed in patients in their 60s.
The size of rectal carcinoids correlates closely with the likelihood of metastases. Tumors smaller than 2 cm are rarely metastatic, while 10 percent of larger tumors metastasize, most often to local lymph nodes or the liver
Temple University/Conemaugh Memorial Hospital Carcinoid

Stomach
Gastric carcinoids are relatively uncommon. They are grouped into three categories Type 1: gastric carcinoids are associated with chronic atrophic gastritis and often pernicious anemia they account for 70 to 80 percent of all gastric carcinoids.
Temple University/Conemaugh Memorial Hospital Carcinoid

Type 2
Type 2 gastric carcinoids occur in association with gastrinomas (Zollinger-Ellison syndrome) or multiple endocrine neoplasia (MEN) type 1. They account for less than 5 percent of gastric carcinoids. Similar to carcinoids in atrophic gastritis, the tumors are thought to arise from ECL cells.
Temple University/Conemaugh Memorial Hospital Carcinoid

Type 3
Type 3 gastric carcinoids are known as sporadic carcinoids because they occur in the absence of atrophic gastritis or the Zollinger-Ellison or MEN-1 syndromes. They account for 20 percent of gastric carcinoids, and are the most aggressive; local or hepatic metastases are present in up to 65 percent of patients who come to resection
Temple University/Conemaugh Memorial Hospital Carcinoid

Lung
Pulmonary carcinoids are classified among other pulmonary neuroendocrine tumors such as small cell lung cancer. The tumors are thought to arise from Kulchitsky's cells within the bronchial mucosa Most tumors are perihilar.
Temple University/Conemaugh Memorial Hospital Carcinoid

Clinical Presentation
Patients usually present in their 50s with recurrent pneumonia, cough, hemoptysis or chest pain The tumors are capable of secreting several different hormones, which can produce a number of paraneoplastic syndromes including Cushing's syndrome, acromegaly, and the carcinoid syndrome, which occurs in less than 5% of patients
Temple University/Conemaugh Memorial Hospital Carcinoid

Ovary
Rare carcinoids arising in ovarian teratomas are noteworthy because they can produce the carcinoid syndrome without hepatic metastases due to their direct drainage into the systemic circulation

Temple University/Conemaugh Memorial Hospital Carcinoid

CLINICAL FEATURES
The majority of patients with carcinoid tumors are asymptomatic, and the tumor is diagnosed incidentally at endoscopy, surgery, or autopsy. The initial symptoms of carcinoid may be nonspecific. When present, symptoms correlate with the location and extent of the tumor

Temple University/Conemaugh Memorial Hospital Carcinoid

Temple University/Conemaugh Memorial Hospital Carcinoid

Carcinoid Syndrome
This is the term applied to a constellation of symptoms mediated by various humoral factors elaborated by some carcinoid tumors. These tumors synthesize, store, and release a variety of polypeptides, biogenic amines, and prostaglandins
Temple University/Conemaugh Memorial Hospital Carcinoid

Tryptophan metabolism
In normal subjects, one percent of dietary tryptophan is converted to serotonin; however, this value may increase to 70 percent or more in patients with the carcinoid syndrome . Serotonin is then metabolized to 5hydroxyindoleacetic acid (HIAA)
Temple University/Conemaugh Memorial Hospital Carcinoid

Amine products
Histamine responsible for the atypical flushing associated with these tumors Kallikrein a protein that cleaves kinin from plasma kininogens, vasodilator, stimulates intestinal motility and increases vascular permeability. Prostaglandins Prostaglandins E and F stimulate intestinal motility and fluid secretion in the normal gastrointestinal tract Polypeptides insulin, corticotropin (ACTH), gastrin, vasoactive intestinal peptide, or somatostatin,
Temple University/Conemaugh Memorial Hospital Carcinoid

CLINICAL FEATURES
Cutaneous flushing Episodic flushing is the clinical hallmark of the carcinoid syndrome, and occurs in 85 percent of patients. Diarrhea Secretory diarrhea occurs in 80 percent of patients and is often the most debilitating component of the syndrome.
Temple University/Conemaugh Memorial Hospital Carcinoid

CLINICAL FEATURES
Bronchospasm Ten to twenty percent of patients with the carcinoid syndrome have wheezing and dyspnea, often during flushing episodes Cardiac valvular lesions Pathognomonic plaque-like deposits of fibrous tissue develop in the heart in approximately 3 to 4 percent of all patients with carcinoid tumors
Temple University/Conemaugh Memorial Hospital Carcinoid

Temple University/Conemaugh Memorial Hospital Carcinoid

BIOCHEMICAL TESTING
Urinary excretion of 5-HIAA The most useful initial diagnostic test for the carcinoid syndrome is to measure 24-hour urinary excretion of 5-hydroxyindoleacetic acid (HIAA), which is the end product of serotonin metabolism This test has a sensitivity of 75 percent and specificity of up to 100 percent
Temple University/Conemaugh Memorial Hospital Carcinoid

Medical Rx
.Somatostatin analog Octerotide Flushing and diarrhea are initially relieved in 75 to 80 percent of patients treated with 50 g three times daily subcutaneously . A longer acting somatostatin analogue (Sandostatin LAR Depot) is easier to use than the short acting preparation. Patients with diarrhea could be treated with cyproheptadine, a serotonin antagonist, while those with gastric carcinoids that elaborate histamine would be treated a histamine blocker.
Temple University/Conemaugh Memorial Hospital Carcinoid