Mucinous cystadenocarcinoma

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Qurrat-ul-ain Abid, M.D.[2], Ammu Susheela, M.D. [3]

Mucinous cystadenocarcinoma of the renal pelvis was first described in 1960 by Hasebe et al. Mucinous cystadenocarcinoma is one of the most aggressive forms of cancer. KRAS mutations are found in mucinous carcinomas. The organs involved in pathogenesis of mucinous cystadenocarcinoma are ovary, appendix, pancreas, colon, rectum, retroperitoneal organs, testes, salivary gland, lung, bladder, and breast. On gross pathology, multiloculated, smooth grey surface, and multilocular mass with thin walls and mucinous material are characteristic findings of mucinous cystadenocarcinoma. On microscopic histopathological analysis, mucinous differentiation, nuclear atypia, and necrosis are characteristic findings of mucinous cystadenocarcinoma. Mucinous cystadenocarcinoma commonly affects individuals older than forty years of age. Females are more commonly affected with mucinous cystadenocarcinoma of pancreas than males. Common risk factors in the development of mucinous cystadenocarcinoma are obesity and post-menopausal women on hormone replacement therapy. According to the American Joint Committee on Cancer (AJCC), there are 4 stages of mucinous cystadenocarcinoma based on the clinical features and findings on imaging. Each stage is assigned a letter and a number that designate the tumor size, number of involved lymph node regions, and metastasis. Findings on CT suggestive of mucinous cystadenocarcinoma include rounded or ovoid tumor, internal septations, and calcification. The main mode of treatment of mucinous cystadenocarcinoma is chemotherapy and radiation. The most effective treatment for mucinous cystadenocarcinoma is surgical resection.

Mucinous adenocarcinoma of the renal pelvis was first described in 1960 by Hasebe et al.

Mucinous adenocarcinoma is one of the most aggressive forms of cancer. KRAS mutations are found in mucinous cystadenocarcinomas. The organs involved in pathogenesis of mucinous cystadenoma are ovary, appendix, pancreas, colon, rectum, retroperitoneal organs, testes, salivary gland, lung, bladder, and breast. On gross pathology, multiloculated, smooth grey surface, and multilocular mass with thin walls and mucinous material are characteristic findings of mucinous adenocarcinoma. On microscopic histopathological analysis, mucinous differentiation, nuclear atypia, and necrosis are characteristic findings of mucinous adenocarcinoma.

Mutations in the KRAS gene cause mucinous cystadenocarcinoma.

Mucinous cystadenocarcinoma must be differentiated from mucinous cystadenoma, serous cystadenoma, and pseudocyst.

Mucinous cystadenocarcinoma commonly affects individuals older than forty years of age. Females are more commonly affected with mucinous cystadenocarcinoma of pancreas than males.

Common risk factors in the development of mucinous cystadenocarcinoma are obesity and post menopausal women on hormone replacement therapy.

If left untreated, most of the patients with mucinous cystadenocarcinomas may be confined to the organ itself. Common complications of mucinous cystadenocarcinoma include metastasis and inguinal hernia. The presence of metastasis is associated with a particularly poor prognosis among patients with mucinous cystadenocarcinoma.

According to the American Joint Committee on Cancer (AJCC) there are 4 stages of mucinous cystadenocarcinoma based on the clinical features (pattern recongnition) and findings on imaging. Each stage is assigned a letter and a number that designate the tumor size, number of involved lymph node regions, and metastasis.

According to the American Joint Committee on Cancer (AJCC), there are 4 stages of mucinous cystadenocarcinoma based on the clinical features and findings on imaging. Each stage is assigned a letter and a number that designate the tumor size, number of involved lymph node regions, and metastasis.

Symptoms of mucinous cystadenocarcinoma of ovary include mass in the abdomen, increase in abdominal size, bloating, weight loss, shortness of breath, and pain abdomen.

Patients with mucinous cystadenocarcinoma usually appear normal. Physical examination of patients with mucinous cystadenocarcinoma is usually remarkable for abdominal distention, shifting dullness, a palpable abdominal mass, and coarse crackles upon auscultation of the lung bases.

Electrocardiogram findings in patients with mucinous cystadenocarcinoma are within normal limits.

X-ray is not used in the diagnosis of mucinous cystadenocarcinoma. Instead, ultrasound, CT scan and MRI are used in the diagnosis and staging of the tumor.

Findings on CT suggestive of mucinous cystadenocarcinoma include rounded or ovoid tumor, internal septations, and calcification.

Findings on MRI suggestive of mucinous cystadenocarcinoma include lower signal intensity for loculi with watery mucin on T1-weighted images.

Ultrasound may be helpful in the diagnosis of mucinous cystadenocarcinoma. Findings on ultrasound suggestive of mucinous cystadenocarcinoma include mural thickening and solid components.

On microscopic histopathological analysis, mucinous differentiation, nuclear atypia, and necrosis are characteristic findings of mucinous cystadenocarcinoma.

There are no other imaging findings associated with mucinous cystadenocarcinoma.

There are no other diagnostic studies associated with mucinous cystadenocarcinoma.

The main mode of treatment of mucinous cystadenocarcinoma is chemotherapy and radiation.

The most effective treatment for mucinous cystadenocarcinoma is surgical resection.

There are no established methods for primary prevention of mucinous cystadenocarcinoma.

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For patient information, click here

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Qurrat-ul-ain Abid, M.D.[2], Ammu Susheela, M.D. [3]

T DeJulio and other pathologists studying the development of colitis-induced mucinous carcinoma described the association of PTEN mutation with the development of invasive mucinous cystadenocarcinoma. Mucinous cystadenocarcinoma of the renal pelvis was first described as a separate entity in 1960 by Hasebe et al.

• In 1886, T DeJulio and other pathologists, studying the development of colitis-induced mucinous carcinoma, described the association of PTEN mutation with the development of invasive mucinous cystadenocarcinoma.^[1]
• Mucinous cystadenocarcinoma of the renal pelvis was first described in 1960 by Hasebe et al.^[2]
• Cystic lesions of the pancreas were first described by Becourt in 1824.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Qurrat-ul-ain Abid, M.D.[2], Ammu Susheela, M.D. [3]

Mucinous cystadenocarcinoma is one of the most aggressive forms of cancer. KRAS mutations are found in mucinous carcinomas. The organs involved in the pathogenesis of mucinous cystadenocarcinoma are ovary, appendix, pancreas, colon, rectum, retroperitoneal organs, testes, salivary gland, lung, bladder, and breast. On gross pathology, multiloculated, smooth gray surface, and multilocular mass with thin walls and mucinous material are characteristic findings of mucinous cystadenocarcinoma. On microscopic histopathological analysis, mucinous differentiation, nuclear atypia, and necrosis are characteristic findings of mucinous cystadenocarcinoma.

• Mucinous cytsadenocarcinoma is one of the most aggressive forms of cancer.

• Mucinous cystadenocarcinoma of the ovary is a rare malignant ovarian mucinous tumor that originates from the ovarian epithelium.
• 3 – 4% of primary ovarian cancers account for mucinous cystadenocarcinoma.^{[1] [2][3]}
• Women are affected in their late 40s to early 50s in the perimenopausal stage.^[4]
• Approximately 80% are mucinous cystadenomas, the majority are borderline and the rest are malignant tumors.^[1][5][6][7]
• Majority of mucinous carcinomas of the ovary are metastasized from another site, often from the gastrointestinal tract.^[2]
• Primary ovarian mucinous carcinomas usually evolve from mucinous borderline neoplasms of the ovary.^[1][4][6]
• KRAS mutations are found in mucinous carcinomas^[8]

• Mucinous cystadenocarcinoma of the pancreas largely occur in the body or tail of pancreas, and less commonly in the head of the pancreas.^[9]
• WHO have classified mucinous cystadenocarcinoma into three categories depending on the epithelial dysplasia:^[10][11]
  • Low grade
  • Intermediate
  • High grade^[12]
    • Non-invasive
    • Invasive^[13]

• It is the most common tumor of appendix.
• The tumor produces mucus and can spread to the organs.
• Excess spread of the tumor to the abdomen is called peritoneal mucinous carcinomatosis (PMCA).^[14][15]
• There are two types:^[16]
  • Non-neoplastic appendiceal mucinous lesions
  • Neoplastic appendiceal mucinous lesions
• Chronic obstruction can lead to mucinous cysts known as retention cysts.
• Neoplastic appendiceal mucinous lesions contain serrated polyps.
• Cysts are formed due to obstruction of the lumen by a fecalith, endometriosis involving the appendix, local process leading to focal scarring.

• Mucinous cystadenocarcinoma is associated with mature cystic teratoma.

Mucinous Cystadenocarcinoma of Ovary

• 8 – 20 cm in size.^[3]
• Cystic or solid.
• Unilateral and confined to the ovary.
• Smooth external surface.
• Intact surface of the ovary without external implants.^[1]
• Involvement of surface of ovary in case of metastasized tumor.^[17][18]
• Rarely, mucinous cystadenocarcinoma can lead to pseudomyxoma peritonei which can have the following features:^[4][19][20]

• Multiloculated
• Sticky, gelatinous fluid (glycoprotein)
• Necrosis
• Typically unilateral
• Smooth gray surface
• Internal surface comprised of multilocular mass with thin walls
• Mucinous material and solid nodules on the wall

• Mucin-producing intraductal neoplasm
• Sharply demarcated
• Cystic masses with a thick fibrous covering
• No contact with the pancreatic duct system^[21]

• Non-neoplastic appendiceal mucinous lesions: retention cysts or mucoceles.^[22][23]
• Neoplastic appendiceal mucinous lesions: polypoid lesions

Microscopic features:

Following features are common to mucinous cystadenocarcinoma of all regions:

• Mucinous differentiation
• Tall columnar cells with apical mucin
• Endocervical or intestinal-like appearance
• Back-to-back cribriform glands with confluent growth pattern
• Invasive morphology
• Desmoplastic stromal response
• Infiltration of the tumor capsule

Malignant characteristics on microscopy:

• Nuclear atypia
• Necrosis
• Absent cilia

• Complex glandular structure^[4]
• Stromal invasion^[24]
• Expanding pattern of growth (back to back glands with minimal intervening stroma) ^[3]
• Infiltration of stroma in the form clusters of glands and nest
• Columnar epithelium of glands with the eosinophilic lake of mucin inside
• Desmoplastic stromal reaction

Immunophenotype:

• Gastrointestinal markers CK20 and CDX2 positive.^[25]
• CK7 expression.^{[26][27][28][29]}
• p16 expression.^[30]

Molecular biology:

• KRAS mutation in 75 percent of cases.^[31][32][33]
• Mucin genes (MUC2, MUC3, and MUC17) positivity.^[34][35][36]

• Tumor is composed of:^[21]
  • Columnar epithelium
  • Ovarian-type stroma
  • Luminal mucin

• Epithelium may form a single layer or papillary folds.
• May show mitoses
• Stroma is composed of small spindle-shaped cells

Immunohistochemistry^[21]

Stroma is usually positive for:

• Estrogen and progesterone
• Inhibin
• Calretinin

• Can be non-neoplastic or neoplastic depending on the features.

• Non-neoplastic appendiceal mucinous lesions:
  • Mucin filled simple mucoceles
  • Epithelial flattening
  • Mucin expulsion
• Neoplastic appendiceal mucinous lesions:^{[37][38][39][40][41]}
  • Mixed histopathological characteristics
  • Serrated polypoid form
  • Dysplastic lesions
  • Hyperplasia
  • Proteoglycan-rich extracellular matrix
  • Desmoplastic reaction
  • stromal invasion

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Qurrat-ul-ain Abid, M.D.[2]; Ammu Susheela, M.D. [3]

Mutations in the KRAS gene cause mucinous cystadenocarcinoma.

• KRAS mutations are found in mucinous carcinomas of ovary.^[1][2][3][4]
• Chronic luminal obstruction of the appendix may lead to cyst formation and due to continued mucin secretion by the mucosal epithelium, may lead to mucous cyst adenoma formation.
• Hyperplastic lesions of epithelium with dysplasia may progress to mucin secreting cystadenocarcinomas.^[5][6]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Qurrat-ul-ain Abid, M.D.[2]; Ammu Susheela, M.D. [3]

Mucinous cystadenocarcinoma must be differentiated from mucinous cystadenoma, serous cystadenoma, and pseudocyst.

• Mucinous borderline tumor of the ovary
• Metastatic mucinous carcinoma^[1]

• Mucinous cystadenoma of pancreas
• Pancreatic pseudocyst
• Serous cystadenoma of pancreas

• Appendicitis
• Mesenteric cyst^[2][3]

Mucinous cystadenocarcinoma of ovary	Clinical manifestations		Para-clinical findings					Gold standard
	Sign and symptoms	Physical examination
			Lab Findings	Imaging			Histopathology
				US	CT	MRI
Mucinous borderline tumor of the ovary	Asymptomatic initially Vaginal bleeding Abdominal mass	Increased abdominal girth Abdominal mass	Decreased Hb Raised CEA	Localizes tumor	Demarcates the cancer	To visulaize the extent of the tumor	Large multiloculated cystic masses mucus-containing cysts	Image guided biopsy and histopathological analysis
Metastatic mucinous carcinoma[4][5]	Ascities Abdominal mass Abdominal fullness Early satiety Fatigue Bowel obstruction Pleural effusion Pelvic or abdominal pain Venous thromboembolism Bloating Urinary frequency	Increased abdominal girth Abdominal mass Ascities Pallor Lymphadenopathy	Incresed CA-125 Decreased-Hb Raised CEA	For the assessment for ascites and to the extent of cancer	Shows intra-abdominal spread	Shows distant metastasis and extent of the tumor	Mucinous differentiation Tall columnar cells with apical mucin Endocervical or intestinal-like appearance Back-to-back cribriform glands with confluent growth pattern Invasive morphology	Image-guided biopsy of patients with peritoneal metastasis and histopathological analysis
Mucinous cystadenocarcinoma of pancreas	Symptoms	Physical examination	Lab Findings	US	CT	MRI	Histopathology	Gold standard
Mucinous cystadenoma of pancreas[6][7][8][9][10]	Asymptomatic Epigastric fullness Abdominal mass Nausea and vomiting Back pain	Epigastric mass Abdominal fullness Ascities Pallor Lymphadenopathy	CEA CA 19-9 Hb	EUS for evaluation of the cyst wall, may show nodules within the cyst To obtain aspiration of the cyst material To perform biopsy	CT is important for differentiating MCN from other tumors Shape is smooth Main pancreatic duct is not dilated	MRI cross-sectional images may show unilocular or multilocular cyst with a solid component peripheral calcification wall thickening Papillary structures Hypervascular pattern	Solitary, multilocular or unilocular cysts with a fibrotic wall and containing mucin Columnar epithelium lined mucin-producing cysts with different level of dysplasia	Biopsy and histopathology
Pancreatic pseudocyst	Abdominal pain Abdominal mass Bloating	Abdominal mass	Amylase levels raised (plasma or serum) Lipase levels raised (plasma)	US may not be a good modality of diagnoses as pancreas lies behind the stomach (and so a gas-filled stomach will obscure the pancreas	CT scan is the gold standard for initial assessment and follow-up	To establish the relationship of the pseudocyst to the pancreatic ducts	collection of fluid containing pancreatic enzymes, hemolysed blood and necrotic debris around the pancreas	FNA and cytology
Serous cystadenocarcinoma of pancreas[11][12][13]	Abdominal/flank pain Weight loss Per-rectal bleeding	Palpable mass	Amylase levels raised (plasma or serum) Lipase levels raised (plasma)	US localizes the mass and shows its extent	CT shows well-circumscribed, multilocular masses Macrocysts appear well-circumscribed with lobulations Microcysts are not very visible on CT and MRI is used to locate them	Too see features of the primary tumor Local invasion Metastatic lesions Microcyts appear hyperintense	Multiple cysts Cuboidal epithelium Glycogen-rich cells Serous fluid	Biopsy and histopathology
Mucinous cystadenocarcinoma of appendix	Symptoms	Physical examination	Lab Findings	US	CT	MRI	Histopathology	Gold standard
Appendicitis	Abdominal pain Fever Nausea or vomiting Atypical symptoms include: Constant pain in the right iliac fossa Prolonged diarrhea	Fever Tachycardia Hypotension Tachypnea Rebound tenderness Abdominal guarding Rovsing’s sign Psoas sign Obturator sign	Leukocytosis shift to the left in the segmented neutrophils	Ultrasound may be helpful in the diagnosis of appendicitis Findings include: Noncompressible, dilated appendix Appendicolith Echogenic prominent Pericaecal fat and periappeniceal fluid collection	CT scans are preferred over ultrasounds for diagnosing appendicitis Increase in appendiceal lumen with the outer-wall-to-outer-wall transverse diameter greater than 6 mm Appendiceal wall thickening (wall ≥ 3mm) Appendiceal wall hyperenhancement Mural stratification of the appendiceal wall	Magnetic resonance imaging has become the common technique for diagnosing appendicitis in children and pregnant patients periappendiceal stranding appears as an increased fluid signal on the T2 weighted sequence (while it is reflected by fat stranding on a CT scan)	Inflammation of the appendiceal wall can result in perforation and development of a contained abscess or generalized peritonitis. The wall of the appendix can become ischemic as vascular and lymphatic occlusion progress.[14]	Histopathological analysis
Mesenteric cyst[2]	Asymptomatic Acute or chronic abdominal pain	Smooth, round and mobile abdominal mass	–	Shows echogenic mass in appendix	CT scan are the best diagnostic tool	Provides significant information of the size and localization Cystic masses associated with areas of fat necrosis and hemorrhage	Lymphangioma: endothelial lining Enteric duplication cyst: Enteric lining and double-muscle lining with neural elements; Enteric cyst: Enteric lining (mucosa with no muscle layer Mesothelial cyst: mesothelial lining Nonpancreatic pseudocyst has no lining, with a fibrous wall.	Enucleation and Histopathological analysis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Qurrat-ul-ain Abid, M.D.[2], Ammu Susheela, M.D. [3]

Mucinous cystadenocarcinoma commonly affects individuals older than forty years of age. Females are more commonly affected with mucinous cystadenoma of pancreas than males.

• 3 to 4 percent of primary ovarian cancers is mucinous cancers of the ovary.^[1][2][3]
• With predominance in perimenopausal women late 40s to early 50s.
• Account for 10 to 15% of all ovarian tumors.^[1][4][5][6]
• Benign mucinous cystadenomas make 80 percent of these.

• Mostly in perimenopausal women in late 40s to early 50s.^[7]
• More common in females than males.

• Appendiceal mucinous neoplasms are rare.
• 1000 to 2000 cases are diagnosed annually in the United States.^[8]
• More common in females.^[9]
• Age of diagnosis 50s and 60s.^[10]

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Qurrat-ul-ain Abid, M.D.[2]; Ammu Susheela, M.D. [3]

Common risk factors in the development of mucinous cystadenocarcinoma are obesity and post menopausal women on hormone replacement therapy and genetic predilection.

Common risk factors of mucinous cystadenocarcinoma include the following:^[1]

• Obesity

• Post menopausal women on hormone replacement therapy
• Perimenopausal or post-menopausal state
• Smoking
• KRAS mutation

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Qurrat-ul-ain Abid, M.D.[2], Ammu Susheela, M.D. [3]

If left untreated, most of the patients with mucinous cystadenocarcinoma may be confined to the organ itself. Common complications of mucinous cystadenocarcinoma include metastasis and inguinal hernia. The presence of metastasis is associated with a particularly poor prognosis among patients with mucinous cystadenocarcinoma.

• If left untreated, most of the patients with mucinous cystadenocarcinoma may be confined to the organ itself.
• Some of them may develop metastasis to the gastrointestinal tract.^[1]

• Common complications of mucinous cystandenocarcinoma are:

• Metastasis
• Inguinal hernia

• Mucinous cystadenocarcinoma has a much more favorable prognosis than most other forms of adenocarcinoma.
• Advanced stages of mucinous cystadenocarcinoma have an inferior prognosis.
• 5-year survival has been stated to be approximately 50% when treated with cytoreduction (debulking) surgery to remove all of the tumors in the abdomen which is combined with hyperthermic intraoperative peritoneal chemotherapy (HIPEC).

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