Appendix cancer differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Soroush Seifirad, M.D.[2]

Overview

Appendix cancer must be differentiated from benign appendix lesions (Mucocele, acute appendicitis), adenexal masses, and carcinoid tumors of other organs.

Differentiating appendix cancer from other Diseases

appendix cancer must be differentiated from other diseases that cause [clinical feature 1], [clinical feature 2], and [clinical feature 3], such as [differential dx1], [differential dx2], and [differential dx3].

OR

appendix cancer must be differentiated from [differential dx1], [differential dx2], and [differential dx3].

OR

As appendix cancer manifests in a variety of clinical forms, differentiation must be established in accordance with the particular subtype. [Subtype name 1] must be differentiated from other diseases that cause [clinical feature 1], such as [differential dx1] and [differential dx2]. In contrast, [subtype name 2] must be differentiated from other diseases that cause [clinical feature 2], such as [differential dx3] and [differential dx4].

Differentiating appendix cancer from other diseases on the basis of [symptom 1], [symptom 2], and [symptom 3]

On the basis [symptom 1], [symptom 2], and [symptom 3], appendix cancer must be differentiated from [disease 1], [disease 2], [disease 3], [disease 4], [disease 5], and [disease 6].

Diseases		Clinical manifestations							Para-clinical findings							Gold standard
		Symptoms				Physical examination
									Lab Findings		Imaging				Histopathology
		Abdominal pain	Change in girdle size	Change in bowel habits	Other symptoms	Abdominal mass	abdominal tenderness	Other physical examination findings	Urinary 5-hydroxyindoleacetic acid (5-HIAA) and/or Serum Chromogranin A (CgA)	Other lab findings	CT scan	MRI	Utrasounography	Other diagnostic studies and imaging modalities
Appendix cancer	Adenocarcinoma1	+/-	-/+	Constipation	Generally asymptomatic Appendicitis symptoms Nausea & vomiting,decreased appetite (anorexia) No gas or stool pass (intestinal obstruction) Bone pain (bone metastasis) Bloating (ascites)	-	-	Ascites Shifting dullness	-	CEA CA 19-9	Soft tissue thickening Wall irregularity Presence of pseudomyxoma peritonei Calcification Internal septations Periappendiceal fat stranding and intraperitoneal free fluid which is a nonspecific finding Cystic lesion	Diffusion weighted MRI has been shown to be the modality of choice for peritoneal carcinomatosis Increased fluid signal on T2 weighted sequence Soft tissue mass in the appendix Invasion to other structures	Dilated appendix Periappendiceal fluid collection Distinct appendix wall layers	Positron emission tomography (PET)	Gross pathology: Gray/yellowi color Cystic structures with angiolymphatic invasion Microscopic pathology:????????????????????????????	Biopsy
	Carcinoid tumor2	+/-	-	Diarrhea	Generally asymptomatic Flushing Palpitation Dyspnea	-	-	Tricuspid regurgitation murmur Wheezing	+	Ki67: a reliable marker of cell proliferation				Somatostatin scintigraphy with 111-indium-octreotide Bone scintigraphy with 99mTc-methylene diphosphonate (99mTcMDP) Positron emission tomography (PET)	Gross pathology: Gray/yellowi color Cystic structures with angiolymphatic invasion Microscopic pathology:???????????????	Biopsy
	Goblet cell carcinoid
	Lymphoma
Appendix Mucocele	Mucosal hyperlasia	-	-	-	Generally asymptomatic Benign even after rupture	-	+/-	N/A	-	N/A	low attenuation well defined mass in RLQ near cecum Inflammation is the key to distinguish between appendicitis and mucocele Wall thickness does not distinguish between malignant and benign mucocele Intramural nodule is a sign of neoplastic lesions Imaging is not a reliable method to distinguish between neoplastic and nonneoplastic lesions, hence every patient should undergo surgery, appendectomy and histopathologic evaluation of the lesion	|Rounded right iliac fossa mass T1: the signal depends on the mucin concentration, may be from hypointense to isointense T2: hyperintense	Histologically benign Dilated fluid filled appendix in the right lower quadrant. Thin appendiceal wall A focus of hyperechogenicity Since generally there is no inflammation Surrounding fat is normal. No peri-appendiceal fluid or collection	N/A	Similar to hyperplastic colon polyp	Biopsy
	Simple or retention cyst	-	-	-		-	+/-	-	-	N/A					Degenerative epithelial changes because of obstruction	Biopsy
	Mucinous cystadenomas	+/-	+/-	+/-Diarrhea +/-Constipation	Generally asymptomatic Rupture may lead to Pseudomyxoma peritonei	+/-	+/-	If develop pseudomyxoma peritonei: Ascites Shifting dullness	-	CEA CA 19-9					Histologically benign Similar to colon adenomatous polyps or villous adnomas	Biopsy
	Mucinous cystadenocarcinomas	+/-	+/-	+/-Diarrhea +/-Constipation	+/-	+/-	-		-	CEA CA 19-9					Glandular invasion into the stoma Pseudomyxoma peritonei	Biopsy
Ovarian cancer		+/-	+/-	+/-Constipation	Pelvic/abdominal pain or pressure Vaginal bleeding/discharge Dyspnea GI disturbance	+	+/-	Ascites Shifting dullness Fever Pleural effusion	-	Depends on the underlying etiology Iron HCG LDH Calcium Estrogen progestron Testosterone AFP CA 125 Ki 67	Adnexal mass Adenexal Cyst (simple or complex) Fluid accumulation Endometrial thickening calcification Pleural effusion Peritoneal involvement Lymphandenopathy	Adnexal mass Adenexal Cyst (simple or complex) Except for Thecoma, ovarian masses are generally hyperintense on T1 and hypo or isointense on T2 imaging Fluid accumulation Endometrial thickening calcification Pleural effusion Peritoneal involvement Lymphandenopathy	Adnexal mass Adenexal Cyst (simple or complex) Fluid accumulation Increased Doppler flow Endometrial thickening calcification	N/A	Depends on the tumor type. You may find the details here.	Biopsy
Colorectal cancer		+/-	+/-	+/-Diarrhea + Constipation	Weight loss Fatigue Low caliber of stools Nausea and vomiting Mucus in stools Rectal prolapse In Carcinoids : Weight loss Weakness Flushing Wheezing Shortness of breath Palpitations Leg edema	+	+/-	???????	-/+(Carcinoid tumors)	Anemia Positive Fecal occult blood test High levels of CEA and CA 19-9	luminal narrowing, intestinal wall thickening,intussusception, bowel obstruction, hepatic metastases, intestinal perforation,enlarged lymph nodes	Tumor mass and the extension of tumor to other structures liver, lung and brain Metastasis	Generally not recommended: may evaluate liver metastasis or presence of fluid in abdominal cavity, but it is neither sensitive nor specific.	PET scan, Endoscopy, Colonoscopy, Barium enema	Depends on the tumor type.. You will find more information here	Biopsy
Pseudomyxoma peritonei		+	+	+/-Diarrhea +/-Constipation	Bloating	-	+	Ascites Shifting dullness	-	Non specific Depends on the etiology of the disease	Low-attenuation Scalloping of the visceral surfaces differentiates pseudomyxoma from other causes of peritnoitis. Typically does not invade visceral organs or spread by lymphatic or hematogenous routes unlike mucinous carcinomatosis	Characterized by a mass which is hypointense on T1-weighted MRI and hyperintense on T2-weighted MRI. MRI has better sensitivity in detecting ascites fluid and mucocele.	The echoes within pseudomyxoma peritonei are not mobile. Echogenic septations within the gelatinous ascites. Scalloping of the hepatic and splenic margins	18F-FDG PET scan	Depending on WHOclassification, whether it's low or high grade with cellular atypia or acellular mucin. ( DPAM, PMCA) Gelatinous ascites in peritoneum and visceralorgans,usually underneath the right hemidiaphragm, liver. Omental cake Immunohistochemisty CK 20 CDX2 MUC2 MUC5AC	Diagnostic laparascopy/laparatomy
Carcinoid syndrome		-/+	-	Diarrhea	Flushing Palpitation Dyspnea	-	-	Tricuspid regurgitation murmur Wheezing	+	Depends on the tumor type: Ki67 N-terminal pro–B-type natriuretic peptide Substance P Neurotensin Bradykinin Human chorionic gonadotropin Neuropeptide L Pancreatic polypeptide	Depends on the primary tumor location and type	Depends on the primary tumor location and type	Depends on the primary tumor location and type	Somatostatin scintigraphy with 111-indium-octreotide Bone scintigraphy with 99mTc-methylene diphosphonate (99mTcMDP) Positron emission tomography (PET) 123I-MIBG scintigraphy Capsule endoscopy (CE) Enteroscopy Angiography MRI Angiography Endoscopic ultrasonography (EUS)	Salt and pepper nuclei Cellular uniformity Central ovoid nucleus Presence of ribbons, trabeculae, nesting, glands, gyriform, pseudorosettes Insulinoma (Amyloid deposition) Somatostatinom (Psammoma bodies) Hyaline globules IHC Synaptophysin (almost always, strongly and diffusely expressed ) Chromogranin A CD56 and PGP ( less specific) PDX1 and ISL1	Biopsy from the tumor is the gold standard method of diagnosis, meanwhile 5-HIAA (5-hydroxyindoleacetic acid) is the most specific marker of carcinoid tumors
Appendicitis 3		LLQ / RRQ	-	+/- Diarrhea Intermittent Secretory type + Constipation	Nausea & vomiting,decreased appetite Anorexia	+/-	+	Rebound tenderness Abdominal guarding Rovsing's sign Psoas sign Obturator sign TR exam might reveal tenderness in the rectovesical pouch Tachypnea Tachycardia Hypotension Diaphoresis Pallor	-	Leukocytosis Left shift	Appendiceal wall thickening /perforation peri-appendiceal inflammation, fluid accumulation,fat stranding	Increased fluid signal on T2 weighted sequence	Evidences of inflammation Dilated appendix Periappendiceal fluid collection Distinct appendix wall layers	Tc-99m labeled anti-CD15 antibodies	Evidences of inflammation	A combination of Imaging (ultrasonography or CT scan, while CT scan is more sensitive), physical exam and history Alvarado Score

¹ Adenocarcinomas usually present with appendicitis, barely they might present with Pseudomyxoma peritonei; meanwhile Pseudomyxoma peritonei is more prevalent in perforated mucocele, goblet cell tumor or high stages of adenocarcinoma.

² Generally appendix carcinoids are asymptomatic, they were only become symptomatic if they metastasize to the liver, or in rare cases make an obstruction and present with appendicitis which is quit uncommon in appendiceal carcinoids compared to appendiceal adenocarcinoma. Any patient with carcinoid syndrome should be evaluated for appendix carcinoids.

³ Every patient with appendicitis should be evaluated for appendix cancer, 0.5 in 100 appendicitis cases are because of appendix cancer.