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Monthly Archives: April 2010
Familial Adenomatous Polyposis Syndrome
Familial Adenomatous Polyposis (FAP) Syndrome
Familial Adenomatous Polyposis Syndrome Inheritance pattern
- autosomal dominant inheritance
- APC gene is on chromosome 5q21
- APC gene plays a role in the WNT pathway in the degradation of the beta-catenin
- beta-catenin role is to turn on transcription factors in the nucleus that lead to cell cycle progression
-mutations in the APC leads to absence of b-catenin degradation and signal independent tranlocation into the nucleus where it turns on the cell cycl
Familial Adenomatous Polyposis Syndrome Clinical Presentation
- two types of clinical presentations:
Classic Familial Adenomatous Polyposis
- minimum of 100 colonic polyps
- polyps in ampulla of Vater – this leads to a prophylactic colectomy in siblings and first-degree relatives which are at risk
Attenuated Familial Adenomatous Polyposis
- patients tend to develop fewer polyps (average 30), and most of the polyps are located in the proximal colon
- lifetime risk of cancer development is usually around 50%
Gardner syndrome
- polyps identical to those in classic FAP
- multiple osteomas (particularly of the mandible, skull, and long bones)
- epidermal cysts
- fibromatosis – desmoid tumors
- less frequent are abnormalities of dentition, such as unerupted and supernumerary teeth
- higher frequency of duodenal and thyroid cancer
Turcot syndrome
- combination of adenomatous colonic polyposis and tumors of the CNS
2/3 have have APC gene mutations and develop brain medulloblastomas
- 1/3 have mutations in one of the genes associated with HNPCC and develop brain glioblastomas
Gross Features of Familial Adenomatous Polyposis
-hundreds to thousands of adenomas evenly distributed through colorectum and appendix
- adenomas range from microscopic to 1cm in diameter with larger adenomas found in the rectosigmoid
- rectum occasionally spared, especially in the attenuated FAP
- colorectal carcinomas may be multifocal
Microscopic Features of Familial Adenomatous Polyposis
- histologically identical to sporadic adenomas
- normal intervening mucosa
- adenomas evolve from single adenomatous crypts
Symptoms and Management
- patients may be asymptomatic before puberty
- initial symptoms are rectal bleeding and diarrhea
- carcinomas start about 6 years after first symptoms
- 100% colon cancer without intervention
- treatment is prophylactic total colectomy
- following colectomy, the most common cause of death is periampullary cancer in 20%
Posted in Colon, GI, Syndrome
Tagged , adenoma, apc, apc gene, b-catenin, Cancer, carcinoma, Colon, colorectal, Familial Adenomatous Polyposis, gardner, periampullary cancer, polyps, Syndrome, turcot
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Hereditary Nonpolyposis Colorectal Cancer Syndrome
Hereditary Nonpolyposis Colorectal Cancer (HNPCC) Syndrome
Hereditary Nonpolyposis Colorectal Cancer (HNPCC) Syndrome, also known as Lynch syndrome, is a rare colorectal syndrome that can lead to cancer of the colon.
Hereditary Nonpolyposis Colorectal Cancer Syndrome Inheritance pattern
- autosomal dominant
- syndromal patients have only one functional allele and cancer occurs through loss of heterozygosity (LOH)
- mutations occur in mismatch repair genes (MLH1, MSH 2, MSH6, PMS 1, PMS 2)
- mutations lead to microsatellite instability which are mostly repeats in intronic regions
What to look for?
- you can look for the loss of the genes themselves
- you can look at particular microsatellite loci and see how many have instability
- 0/5 – stable
- 1/5 – low frequency instability
- 2 or greater/5 – high frequency of instability – MSI-H
- microsatellite instability is NOT specific to HNPCC, as it is seen in 10-15 % of sporadic colorectal carcinomas. Sporadic tumors arise in older patients who lack a family history. The activity of the mismatch repair genes in sporadic tumors is lost through hypermethylation
Diagnostic criteria is through the Amsterdam II criteria
Clinical presentation
- development of multiple cancers at an early age, including cancer of the colon, endometrium, renal pelvis and ureter, small bowel, ovary, brain, hepatobiliary tract and sebaceous tumors
Muir -Torre Syndrome
- sebaceous tumors along with HNPCC type of internal malignancy
Turcot Syndrome
- tumors of the CNS (usually gliobalstomas) and multiple colorectal tumors
Gross Appearance
- predilection for right colon and cecum all the way to the transverse colon
- usually polypoid in appearnace rather than diffuse
Microscopic Appearance
- sporadic tumors have the same features as tumors associated with HNPCC
- proximally located mucinous type of colorectal adenocarcinomas +/- tumor infiltrating lymphocytes
- proximally located, poorly differentiated medullary or undifferentiated colorectal adenocarcinomas – these are well circumscribed and lacking abundant desmoplastic stroma and may contain tumor infiltrating lymphocytes
- adenomas – many have a villous morphology and high grade dysplasia, with rapid progression to carcinoma
Posted in Colon, GI, Syndrome
Tagged , gross, Hereditary Nonpolyposis Colorectal Cancer Syndrome, hnpcc, loss of heterozygosity, lynch syndrome, medullary adenocarcinoma, microsatellite instability, microscopic, mismatch repair genes, mlh, mucinous adenocarcinoma, muir-torre syndrome, multiple cancers, mutations, right colon, Syndrome, turcot syndrome
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Carcinoid syndrome
Carcinoid syndrome
Symptoms of Carcinoid Syndrome
- skin flushing
- diarrhea
- right sided heart disease due to fibrosis of the tricuspid valve and stenosis of the pulmonary valve
- bronchoconstriction
Detection of Carcinoid Syndrome
Serotonin secretion is confirmed by measuring the 24 hour urine levels of 5-HIAA (5-hydroxyindoleacetic acid), which is a breakdown product of the hormone, serotonin.
Management of Carcinoid Tumors
Low risk Carcinoid
Local excision for small lesions < 2 cm, with no mesoappendix invasion and no lymphovascular invasion.
Uncertain behavior if > 2 cm or lymphovascular invasion, no mesoappendix invasion.
High risk lesions have at least a cecal resection. These high risk tumors are found at the base of the appendix with caecal margin involvement.
Higher risk lesions require hemicolectomy. These include carcinoid lesions above 2 cm or with invasion of mesoappendix.
Pseudoinvasion
Pseudoinvasion
Pseudoinvasion is basically herniated glands. It is important for a pathologist to recognize pseudoinvasion in order to not call it cancer and to avoid overtreatment.
-glands are cystically dilated and surrounded by normal lamina propria, with NO desmoplastic response
-there are dilated vessels, hemorrhage and hemosiderin-laden macrophages
- there may be a visible connection to the surface mucosa from the pseudoinvaded glands
Posted in Colon, GI
Tagged , Colon, colorectal cancer, not cancer, pseudoinvasion, rectal
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Colon Cancer arising in an Adenoma
Colorectal Cancer in an Adenoma
Features of a Cancer arising in an adenoma, what to look for?
Colon cancer in lamina propria is staged as Tis and is treated by somple polypectomy during scoping.
Colon cancer arising in an colonic adenomatous polyp, which breaches the muscularis mucosa is staged T1) and can be treated with polypectomy, unless there is:
-high grade dysplasia
-lymphovascular invasion
-positive stalk margin (e.g. remaining tumor which the surgeon was unable to completely remove)
- the adenoma is large, >2cm
If any of the above, then the patient needs a hemicolectomy.
Anal Cancer
Anal Cancer
- mainly consists of squamous cell carcinoma within the anal canal and anorectal junction.
Anal cancer squamous cell carcinoma variants:
-Basaloid (cloacogenic) type
-large cell keratinizing type
-large cell non-keratinizing type
The above is the old classification. Not used anymore as many of the tumors show a mixture of morphologies. Types that are worth remembering are:
-squamous cell carcinoma with mucinous microcysts
-small cell ( anaplastic ) carcinoma - not small cell neuroendocrine carcinoma
BOTH of the above carcinomas, have a less favorable prognosis
-veruccous carcinoma - behaves better than regular squamous cell carcinoma and only invades locally without metastasizing
Posted in Anus, GI
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Gastrointestinal Diseases in HIV
Gastrointestinal Diseases in HIV
Infections
-adenovirus
-CMV
-coccidiosis
-cryptosporidiosis
-intestinal spirochetosis
-anorectal syphilis
Cancer: Dysplasia and Malignancy
-anal condylomata
-anal intraepithelial neoplasia
-squamous cell carcinoma of the anus
-lymphoid neoplasms
-Kaposi s sarcoma
AIDS Enterocolopathy
- consists of Graft versus Host like changes associated with chronic diarrhea in AIDS patients, in the absence of demonstrable infections
-increased apoptotic enterocytes and decreased number of mitotic figures that would be appropriate for the extent of mucosal injury seen
Posted in GI, Infections
Tagged , AIDS enterocolopathy, diseases, gastrointestinal, GI
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Salivary Gland Cancers
World Health Organization Classification of Tumors of the Salivary Glands.
Benign Salivary Gland Tumors:
1. Plemorphic adenoma
2. Myoepithelioma
3. Basal cell adenoma
4. Warthin tumour
5. Oncocytoma
6. Canalicular adenoma
7. Sebaceous adenoma
8. Lymphadenoma – 1) sebaceous, 2) non-sebaceous
9. Ductal papilloma – 1) inverted ductal papilloma, 2) intraductal papilloma, 3) sialadenoma papilliferum
10. Cystadenoma
Malignant Salivary Gland Tumors:
1. Acinic cell carcinoma
2. Mucoepidermoid carcinoma
3. Adenoid cystic carcinoma
4. Polymorphous low-grade adenocarcinoma
5. Epithelial-myoepithelial carcinoma
6. Clear cell carcinoma, NOS
7. Basal cell adenocarcinoma
8. Sebaceous carcinoma
9. Sebaceous lymphadenocarcinoma
10. Cystadenocarcinoma
11. Low-grade cribiform cystadenocarcinoma
12. Mucinous adneocarcinoma
13. Oncocytic carcinoma
14. Salivary duct carcinoma
15. Adenocarcinoma, NOS
16. Myoepithelial carcinoma
17. Carcinoma ex pleomorphic adenoma
18. Carcinosarcoma
19. Metastasizing pleomorphic adenoma
20. Squamous cell carcinoma
21. Small cell carcinoma
22. Large cell carcinoma
23. Lymphoepithelial carcinoma
24. Sialoblastoma
References:
Robbins Basic Pathology 7th ed, edited by Vinay Kumar, Ramzi S. Cotran, and Stanley J. Robbins, 873 pp, Philadelphia, Pa, Sounders, 2003.
Posted in Salivary Gland
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