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| Case of the Week Thursday 20/9/2005 |
Presented by Dr. Mahmoud Abdo
Familial Adenomatous Polyposis
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Personal history
• Eman shokry saleh , 27 years old .
• Mother of 3 ,youngest is 7 months .
• Housewife.
• Borne and living in Beni swif .
• No history of contact with canal water .
• Menarche at 11 years ,cycles were regular average in amount and duration .
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Complaint
Right hypochondrial and epigastric pain.
Bleeding per rectum .
Present history
• The condition started 5 years ago with a gradual onset and progressive course of bleeding per rectum that was not related to defecation . It was not associated with fever or tenesmus . The patient attributed this bleeding to piles .
• 5 months ago, the patient started to develop dull aching right hypochondrial and epigastric pain with no special precipitating or relieving factors and irrespective of the bleeding episodes.
• There was no significant weight loss , anorexia or bleeding from other body orifices.
• There was no change in the bowel habits.
• The patient sought medical advice, abdominal ultrasound was done and revealed enlarged liver with multiple focal lesions , then she was referred to our department for further work-up
• There was no symptoms suggestive of liver cell failure like abdominal distention , lower limb swelling or jaundice.
• On systemic inquiry , no other abnormality detected .
Past history
• History of appendicectomy 10 years ago
• No previous history of blood transfusion
• The patient is not known to be diabetic or hypertensive.
• No history of specific drug intake in the last 6 months.
Family history
Her mother died from colon cancer while she was 35 years old.
General examination
• The patient is fully conscious , of average intelligence , lying comfortably on bed .
• Comlexion : pale .
• Pulse : 100 bpm , regular .
• Temperature : 36.5- 37.2 °C all through the hospital stay .
• Blood pressure : 110/70 .
• The rest of the general examination revealed no significant abnormality .
Chest , cardiovascular , neurological and fundus examination revealed no abnormality .
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• Shape : distended .
• Recti : divaricated .
• Scar of previous appendicectomy 3 cm in length , healed by primary intention .
• No dilated or visible abdominal wall veins .
• No hernias or abnormal pigmentation .
• Size :
• Upper border : is detected in the 5 th space midclavicular line .
• Lower border :
• Right lobe : 5cm below costal margin in the M.C.L .
• Left lobe :10cm below xiphisternum in the midline .
• Edge : rounded .
• Surface : irregular .
• Consistency : soft to firm .
• Spleen is not felt.
• No ascites is detected clinically .
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• Proteins : +++
• Pus cells : 6 - 8 /H.P.F
• R.B.C : 1-2 /H.P.F
Urinary proteins
• Urine volume : 1500.000 ml /24hours
• Urine proteins : 0.005 g/dl
• Urine proteins : 0.08 g /24 hrs
Urine culture
Stool analysis
R.B.Cs: many .
C.B.C
• W.B.Cs : 12.800 / µl
• B : 0
• M :5
• E :1
• St :3
• Seg : 83
• L :8
• RBCs: 2800 000 / µl
• HGB : 6.5 gm /dl
• HCT : 19.8 %
• MCV : 70.4 fl
• MCH : 23.3 pg
• MCHC : 33.0 g/dl
• PLT : 376 000/micro litre.
• Comment :
• marked microcytic hypochromic anemia .
• mild PMN leucocytosis.
Iron study
• Serum iron: 21 µg/dl.(N : 37-157)
• TIBC: 405 µg/dl.(N : 250-380)
E.S.R
• First hour : 100 mm
• Second hour : 127 mm
Corrected E.S.R :
• First hour : 50 mm
• Second hour : 63.5 mm
Liver biochemical profile
• Bil (total): 0.46 mg/dl
• ALT : 38 u / l
• AST : 34 u / l
• ALP : 200 U/L
• T.Proteins : 7.5 g / dl
• S.Albumin : 4.2 g/dl
top of the page Prothrombin time and conc.
• Prothrombin time : 12.2 sec
• Prothrombin conc. : 96 %
• I.N.R : 1
Kidney function
• Urea : 15 mg/dl
• Creatinine : 0.8 mg/dl
Abdominal ultrasound
• Liver : enlarged in size ,homogenous echopattern ,irregular surface and normal hepatic veins.There are multiple hepatic focal lesions ,the largest is 13x7 cm at the posterior segment of the right lobe ,hyperechoic with central necrosis. P.v measures 9mm in diameter and is patent. No I.H.B.R dilatation.
• Gall bladder : average-sized with thickened wall ,no stones or mud inside , C.B.D is not dilated
• Spleen : mildly enlarged (longest axis 13.5 cm),homogenous echopattern
• Conclusion :
• Multiple hepatic focal lesions (1ry Vs metastatic )
• Chronic noncalcular cholecystitis
• Mild splenomegaly
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Gross : liver core needle biopsy specimens, fragmented together measuring 1.2x0.2 cm
Microscopic examination : examination of several serial sections from the received specimen revealed the presence of a neoplastic growth involving all the core portions and composed of solid and irregular acini lined with atypical epithelial cells with enlarged hyperchromatic dark nuclei , increased N/C ratio, and rather eosinophilic cytoplasm,their lumens show occasional R.B.Cs.there are focal areas of dense fibrosis but thin fibrotic areas focally seen between the malignant acini .the solid areas were arranged focally in a trabecular pattern and are composed of the same atypical cells. No normal hepatic tissue is included in this specimen
Conclusion: liver needle biopsy specimen from a case with multiple hepatic focal lesions {?metastatic} revealed: Adenocarcinoma grade 2 , likely H.C.C with a predominant acinar pattern Vs metastatic from a 1ry tumour in GIT ,pancreas or ovaries for further investigations:imaging profile and seromarkers.
Tumor markers
Colonoscopy
Colonoscopic examination was done till the caecum and revealed :
Multiple variable-sized sessile and pedunculated polyps involving the whole colon with normal mucosa inbetween.Multiple biopsies were taken for histopathological examination.
Histopathology of colonic polypi
Examination of the specimen received revealed :
Mixed hyperplastic and adenomatous (mainly tubular)colonic polypi.The lamina propria was edematous and infiltrated by inflammatory cells with occasional lymphoid aggregates .No evidence of specific infection ,dysplastic or malignant changes in all sections examined.
? Diagnosis : multiple hyperplastic and adenomatous (mainly tubular)colonic polypi
? N.B: the probability of familial adenomatous polyposis is highly considered.
Upper G.I Endoscopy
Normal upper endoscopic findings.
X-ray studies
• Skull : Normal
• Mandible : Unerupted tooth is seen ; most posteriorly ; on the right aspect of the alveolar margin of the mandible, with a thin sclerotic enclosing rim, yet with no definite cysts related to it .
• Chest: Normal apart from :
• Elevated right diaphragmatic copula.
• Bilateral mainly right-sided accentuation of bronchovascular markings.
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Classification of large bowel polyps
• Epithelial
• Adenomas - tubular, villous, tubulovillous
• Metaplastic polyps
• Mesodermal
• Lipoma
• Leiomyoma
• Haemangioma
• Hamartoma
• Juvenile polyps
• Peutz-Jeghers syndrome
Adenomas
• Benign epithelial neoplasm
• They are pre-malignant
• Risk of malignancy increases with size
• Malignancy more common in villous rather than tubular lesions
• Most adenomas are asymptomatic
• 10% of population over 45 years have adenomatous polyps
• If do become symptomatic usually present with bleeding, mucous discharge or prolapse
• Villous adenomas may produce hypokalaemia but this is rare
• Diagnosis is often by sigmoidoscopy or colonoscopy
• Full colonoscopy essential to exclude other lesions
• Treatment is by transanal excision or colonoscopic snaring
• Patients require regular colonoscopic surveillance
Adenocarcinoma arising in the head of the tubular adenoma
Microscopically : early adenocarcinoma infiltrating the head and stalk region of this tubular adenoma
Adenocarcinoma arising in a villous adenoma
Metaplastic polyps
• Small plaques approximately 2 mm in diameter
• Pathogenesis unknown
• Not pre-malignant
Hyperplastic polyp
The most frequent polyp of the colon and rarely progresses to malignancy.
Juvenile polyps
• Commonest form of polyp in children
• Can occur throughout large bowel but are most common in the rectum
• Usually present before 12 years
• Present with Prolapsing lump or rectal bleeding
• Not pre-malignant
• Treated by local endoscopic resection
Juvenile polyp
Juvenile polyps consist of an expansion of normal cellular elements including the lamina propria, gastric glands, and inflammatory cells
Peutz-Jeghers syndrome
• Rare familial disorder
• Circumoral pigmentation and intestinal polyps
• Polyps found throughout gut but most common in the small intestine
• Presents in childhood with bleeding, anaemia or intussusception
• Polyps can become malignant
Inflammatory pseudopolyps
• Occur as a complication of ulcerative colitis or Crohn's disease of the colon. They are completely harmless and carry no risk of cancer but they can be confused with adenomatous polyps on examination.
Definition
Autosomal dominant inherited disorder characterized by the presence of hundreds to thousands of adenomatous polyps throughout the colon.
Incidence
• Age :
• The average age of onset of plyposis is 16 years.
• The average age of onset of colo-rectal cancer is 39 years.
• In attenuated F.A.P, the average age of onset of polyposis is 36 years and the averge age of onset of cancer is 54 years.
• Sex :
Male to female ratio 1:1
• Race:
F.A.P is described in all races
Pathophysiology • APC gene is a tumor suppressor gene
• Its inactivation is the initial step of the for the formation of an adenomatous polyp
• The APC gene mutation leads to loss of the normal APC protein which normally promotes apoptosis
• Rapid uncontrolled growth of cells that lack APC gene activity leads to accumulation of multiple genetic events that ultimately leads to cancer on top of the formed polyps
History
• Family history.
• Unexplained rectal bleeding,diarrhoea or abdominal pain .
• Most patients with F.A.P are asymptomatic till they develop cancer.
Examination
• Congenital hypertrophy of the retinal pigment epithelium (C.H.R.P.E)
• Osteomas of the skull and the mandible.
• Dental abnormality.
• Epidermoid cysts.
• Fibromas.
• Palpable abdominal mass.
• Palpable mass on rectal examination.
Investigations
? Lab studies:
• C.B.C
? Imaging studies:
• Sigmoidoscopy.
• Colonoscopy.
• Dental and skull x-rays.
• O.G.D
• Barium studies.
• CT scanning.
? Other tests:
• In vitro protein synthesis.
Multiple fundic polyps in a patient with familial adenomatous polyposis
Procedures
• Endoscopic polypectomy using a diathermy snare for histopathological confirmation.
• The characteristic histology of a polyp from a patient with F.A.P is: tubular adenoma.
• After the patient is diagnosed..
1- Medical care.
2- Surgery.
3- Family member screening.
1-Medical care
• Colonoscopic surveillance every 3:6 months and removal of large polyps.
• After the diagnosis , O.G.D should be performed every 1:3 years.
• Examination of the ampulla by a side-viewing duodenoscope.
• Sulindac and celecoxib have no primary role in patients who did not have an operation .They decrease the number and the size of polyps in upper G.I.T , rectum and ileal pouch.
• Postoperative sigmoidoscopic surveillance and ablation of any polyp should be done every 3:6 months.
• Desmoid tumors may respond to anti-estrogen therapy (tamoxifen) and Sulindac since estrogen appears to stimulate their growth.
• Chemotherapy with doxorubicin and dacarbasine may be attempted .
2-Surgery
• Colectomy with mucosal proctectomy and ileo-anal pouch pull-through is the procedure of choice in most centers
• Subtotal colectomy and ileo-anal anastomosis.
• Panproctocolectomy with terminal ileostomy.
3- Screening
• Screening of family members of patients with F.A.P should start at the age of 12 years . Flexible sigmoidoscopy should be done every 1:2 years until age of 35 then very 3 years.
• Genetic testing may eliminate the need for screening in some members of the family.
Complications
• Colorectal cancer: (100%)
• Duodenal or periampullary adenocarcinoma : (4-12%)
• Desmoid formation: (20% typically post-colectomy)
• Other cancers :
• Medulloblastoma.
• Hepatoblastoma.
• Thyroid and adrenal cancers.
• Rectal cancer: (retained rectum)
Prognosis
• Median life expectancy of cases with untreated FAP is 42 years.
• Median life expectancy is increased after colectomy.
• Post-colectomy, upper GI malignancies and desmoid are the most common causes of death.
Patient education
• After colectomy cancer surveillance
• Family members screening.
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