Hot Topics Exam 3 Flashcards
Autoimmune
Females, 4th-5th decades
Dry mouth (xerostomia), dry eyes (xerophthalmia, kerato-conjunctivitis sicca)
Intense lymphocytic infiltrate in salivary glands
Increased risk for lymphoma (40x)
Parotid enlargement; uni/bilateral
Can be primary
Can be secondary occurs in setting of other autoimmune diseases
Sjogren’s Disease
Most common neoplasm, 60% occur in parotid Lobulated, firm on palpation Variably encapsulated Epithelial and myoepithelial components 10% recurrences May undergo malignant transformation
Pleomorphic adenoma (benign)
Primarily affects parotid gland
Cystic neoplasm with papillary infoldings and lymphoid tissue
10% bilateral
Warthin tumor (papillary cystadenoma lyphomatosum, benign)
Squamous and mucous cells
Most common SG malignancy
Parotid and minor glands
May note bluish color due to mucin and cystic growth pattern
Mucoepidermoid carcinoma (malignant)
inability of lower esophageal sphincter to relax
difficulty in swallowing
Achalasia
Arise due to portal hypertension
Seen in 90% of cirrhotic patients
Often asymptomatic, but rupture can result in massive hemorrhage/death
Esophageal varices
Extrinsic agents: Acids, Alkalis, Pill lodging, Chemical, Trauma, Heavy Smoking
Iatrogenic causes: Chemotherapy, Radiation, Graft versus host disease
Infectious agents: More common in immune-suppressed patients, include fungal and viral (CMV, HSV)
Intrinsic: reflux of gastric juices-central to GERD (gastroesophageal reflux disorder) associated mucosal injury
-Symptoms: dysphagia, heartburn, regurgitation gastric contents. Odynophagia
Oral manifestations of GI Reflux:
a. Gastric acid enamel erosion may be seen in patients with chronic gastric reflux (e.g. GERD, hiatal hernia, chronic alcoholism and bulimia)
b. Enamel loss often affects lingual/palatal surfaces
c. Extent of loss may reflect reflux duration or frequency
Esophagitis
Intestinal metaplasia within the esophagus squamous mucosa
Complication of GERD with increased risk of adenocarcinoma.
NOTE: despite risk, most persons with ______do not develop esophageal tumors.
Diagnostic features for _____: 1) extension abnormal mucosa above gastro-esophageal junction, 2) demonstration of squamous metaplasia (intestinal metaplasia)
Barrett Esophagus
Leiomyomas (tumors of smooth muscle), mucosal polyps, squamous papillomas, Lipomas (tumor of fat)
Esophagus benign lesions
Worldwide rate < SCCa or esophagus
Usually affect the distal third of the esophagus
Associated with long-standing GERD or Barrett change
Increased in Caucasians
Increased in males over females (7:1)
Dysphagia, “Chest Pain”, weight loss
Often detected at late stage: 25% 5yr survival.
Esophageal adenocarcinoma
Adults
> 45 yo
Males > females (4:1)
Esp. African-American males (6:1 vs white men)
Risk factors: EtOH, tobacco use, very hot beverages, caustic esophageal injury, vitamin/trace metal deficiencies, fungal contamination of food, nitrates and nitrosamines
Occurs primarily in the middle third of the esophagus
Most common esophageal malignancy worldwide, but regional variation recognized (Diet, environment, genetics, most common variant in China, Brazil, South Africa)
Plummer Vinson, Achalasia, Esophagitis
Very poor prognosis (9% 5 yr survival)
Squamous Cell Carcinoma of the Esophagus
Abrupt, transient
Pathogenesis: Cigarettes, Alcohol, Stress, Ischemia, NSAID’s, aspirin, infection
May range from asymptomatic to pain, nausea and vomiting. May develop erosion and/or hemorrhage.
Pathology: Punctate hemorrhage, erosion, edema, acute inflammation
Acute gastritis (stomach-reactive lesion)
Primarily caused by infection with Helicobacter pylori in patients with H. pylori (spiral or curved bacilli): 90% of cases.
Often acquire the infection in childhood.
Helicobacter pylori present in 65 % of gastric ulcers, 85-100 % of duodenal ulcers
Treatment with antibiotics and proton pump inhibitors.
Autoimmune-gastritis: 10 % of cases (E.g. Pernicious Anemia)
Pathology: Atrophic epithelium, chronic inflammation, intestinal metaplasia
Clinical course: Ulceration, cancer risk 2-4% (intestinal metaplasia)
Chronic Gastritis (stomach-reactive lesion)
H. pylori, NSAID use
Gastric hyperacidity, recurrent ulcers with intermittent healing
98 % duodenum or stomach
Lifetime risk about 10 % for males, 4 % females
Peptic ulcer complications: Intractable pain, hemorrhage, perforation (5 %), obstruction-edema, fibrosis (2 %)
Peptic ulcer disease
Hyperplastic, fundic gland polyps, adenomas & inflammatory polyps
Approximately 75% of gastric polyps are inflammatory or hyperplastic.
Leiomyomas
Benign stomach neoplasias
90-95 % of gastric cancers these
Other malignant tumors of the stomach include: Lymphoma (4 %), Carcinoid (3 %), Spindle cell tumors (2 %)
3 % of all cancer deaths
Overall marked decrease in U.S. due to reduced use of smoked and salt-cured meat. There is an association with GERD-due to increased rates for cancer of gastric cardia. Linitis plastica, aggressive form of stomach cancer.
Risk factors for development of gastric adenocarcinomas: Hereditary factors, consumption of smoked and salt cured meat (Nitrites), GERD, Pernicious anemia (B12deficiency), atrophic gastritis (intestinal metaplasia), Chronic gastritis (H. pylori), A pre-existing adenomatous polyp
5 year survival < 10 % (advanced)
Prognosis: Dependent on depth of invasion, metastasis
Metastasis: Liver, lung, ovaries, supraclavicular lymph node (Virchow’s node)
Gastric Adenocarcinoma (stomach neoplasia)
“leather bottle appearance” markedly thickened stomach wall, reactive to diffusely-infiltrative
Linitis plastica
Celiac disease (Gluten allergen), Tropical sprue (Aerobic bacteria), Lactase (disaccharidase) deficiency, Abetalipoproteinemia (Transepithelial transport defect, mono- and triglycerides)
Small intestine malabsorptive diarrhea
Gluten-sensitive enteropathy
Caucasians; 1:100-200
Hypersensitivity to gliadin
Morphology: Blunted villi, Inflammatory infiltrate
Dramatically improves with withdrawal of wheat gliadin and related grain proteins from the diet
Celiac disease
Vibrio cholerae, Campylobacter jejuni-acute, self-limited colitis “traveler’s diarrhea”
Infectious enterocolitis
Malabsorption of Iron, Pyridoxine, Folate, or B12 deficiency, bleeding from Vitamin K deficiency
Anemia
Defective Ca, Mg, Vitamin D and protein absorption leads to
Osteopenia, tetany
Generalized malnutrition can lead to these 3 things
Amenorrhea, impotence and infertility
Peripheral neuropathy and nyctalopia can be due to deficiencies in these two vitamins
A and B12
initial oral sign can be atrophic glossitis (bald, reddish tongue). Patchy or involvement of entire dorsum surface of tongue. Overt tongue lesions are usually tender. Burning sensation (glossopyrosis) is a common complaint.
oral manifestations of malabsorption (B12 and anemia)
Accounts for less than 6% of all GI tumors
Benign: Adenoma, leiomyoma
Malignant: Adenocarcinomas, carcinoid tumors (often associated with hormone production), lymphoma, sarcoma.
Tumors of Small Intestine
Most common malignancy of the GI tract.
Dietary factors are implicated-especially low intake of unabsorbable vegetable fiber and high intake of refined carbohydrates and fat.
Genetic component: increased incidence in FAP patients.
Other risk factors: Age > 50 years, family history of colorectal carcinoma, inflammatory bowel disease, personal history of adenoma/colorectal carcinoma
Most important prognostic indicators: Depth of invasion and lymph node metastases
Adenocarcinoma of the Colon
In the US this cancer is responsible for causing 15% of all CA deaths
Adenocarcinoma of the colon
Entails mutations of APC gene. Most common polyposis syndrome of the gastrointestinal tract
Estimated penetrance for adenomas > 90 %: Adenomas throughout colorectum (average onset 16 yo)
Risk of extracolonic tumors (upper GI, desmoid, osteoma, thyroid, brain, other)
Risk of affected patients developing colon cancer approaches 100%
Require > or equal to 100 polyps to diagnose FAP
Familial Adenomatous Polyposis
FAP + Extraintestinal lesions
Oral manifestions of ______: Unerupted teeth, supernumerary teeth, dentigerous and mandibular cysts, increased risk for odontomas, delayed tooth eruption. Also develop benign skin lesions. Congenital hypertrophy of retinal pigment epithelium (CHRPE).
Oral manifestations can contribute to early recognition of the condition and allow for appropriate screening for bowel disease and other neoplasms
Garner’s Syndrome
Second most common polyposis syndrome
Gastrointestinal hamartomatous polyps (Intussusception) and pigmented macules of mucous membranes and skin.
Melanin deposits around nose, lips, buccal mucosa, hands and feet, genitalia and perianal region. Develop in early childhood
Non-sun dependant freckling of the skin around the lips and the vermilion zone of the lips – Common feature.
Average age at diagnosis: 23 -26 yo
Gastrointestinal and non gastrointestinal cancer more common after 45 yo.
Peutz Jegher Syndrome
Clinical manifestations- Chronic intermittent diarrhea +/- blood, colicky abdominal pain; Presents in young adulthood
Pathology- Segmental transmural inflammation of bowel, particularly ileum (distal small bowel) and colon. Any portion of the GI tract → Oral involvement frequently seen; Frequently spares the rectum; Ulcerations, granulomas, thickened bowel wall, stenotic, with fat wrapping, fissure and fistula formation, Noncaseating granulomas; Distribution: Often note “skip lesions”
Crohn disease
Oral manifestations of this disease:
a. Multifocal, linear, nodular, polypoid or diffuse mucosal thickening with predilection for labial and buccal mucosa and mucosal folds –Can be confused with aphthous ulcers.
b. Mucosal ulcer “cobblestone” Diseased tissue lower than normal tissue
c. Subepithelial, noncaseating granulomatous inflammation identical to those seen in the bowel. Infections (fungal, TB) should be ruled out.
d. Typically persistent and remit and relapse over the years
Crohn disease
Clinical: Diarrhea, tenesmus, colicky lower abdominal pain; Risk for development of carcinoma
Pathology: Begins in rectosigmoid area and extends proximally. Not transmural
Continuous (diffuse) involvement (pseudo-polyps), not patchy
Small to large ulcerations, crypt abscesses
Greater risk of dysplasia and adenocarcinoma
Association with primary sclerosing cholangitis (PSC)
Ulcerative colitis
Oral manifestations of this disease:
Rare, less common
a. Scattered, clumped or linearly oriented arc-shaped pustules on an erythematous mucosa at multiple oral sites with variable severity, “snail-track” (Pyostomatitis Vegetans), but may also be seen in Crohn patients
b. Long-standing lesions may become granular, polypoid or fissured and mimic Crohn disease
c. 10% of patients develop arthritis of temporo-mandibular joints.
d. Lesions mimic the crypt abscesses of colonic lesions with no evidence of granulomas. Rule out candidiasis, benign migratory glossitis, and pemphigus vegetans.
Ulcerative colitis
Among top 10 most common causes of death in the U.S and the primary route for liver-related deaths.
Etiologies include: Alcohol (EtOH) abuse (toxicity, nutritional deprivation), viral hepatitis, non-EtOH steatohepatitis, biliary disease, obesity, DM, medications, iron overload.
Iron overload can lead to hepatocyte death and inflammation. Complications include reduced liver function, portal hypertension and increased risk for hepatocellular Ca
Morphologic changes are: 1) bridging fibrous septa, 2) parenchymal nodules, 3) changes in architecture, with parenchymal injury and scarring as the end result. A fibrotic liver has a markedly compromised blood supply and decreased function.
Clinical manifestations:
oNonspecific symptoms e.g. weight loss, weakness. Reserve may mask symptoms.
oLiver failure
oPortal hypertension– Ascites; Collateral venous channels; Splenomegaly
Cirrhosis
Increased pressure of portal blood flow can occur: prehepatic (obstructive thrombi), intrahepatic (cirrhosis), and post hepatic (right sided heart failure).
Consequences of ______: 1) ascites (excess fluid in peritoneal cavity-fluid is generally serous in nature), 2) esophageal varices, 3) splenomegaly, 4) hepatic encephalopathy, 5) hypogonadism.
portal hypertension
1.Excess bilirubin. 2.0 mg/dl
•Unconjugated: Insoluble, toxic
•Conjugated: Soluble, nontoxic
2.Causes of jaundice: hemolytic anemias (#1), bilirubin overproduction, hepatitis, obstruction of bile flow.
3.Function of hepatic bile: 1) emulsification of fats with bile salts, 2) elimination of bilirubin, excess cholesterol, xenobiotics, etc.
Yellow color of skin and sclera
Jaundice and cholestasis
yellow color of sclera
icterus
a benign, self-limiting disease. ___viremia is transient-rarely screen donor blood for ____
- Fecal-oral route of transmission, seen with overcrowding/unsanitary conditions. Ingestion of contaminated water and food
- Incubation 2-6 weeks
- NO carrier state. No chronic disease
Hep A
a.acute hepatitis with recovery and clearance (Self-limited in 90% cases)
b.nonprogressive chronic hepatitis
c.progressive disease ending in cirrhosis
d.asymptomatic carrier state. ___induced liver disease is an important precursor for hepatocellular carcinoma.
•DNA virus
•Parenteral contact/sexual spread
•Incubation 4-26 weeks
•Host immune response determines the ultimate outcome. Hepatocyte damage-likely reflects CD8+ cytotoxic T cell damage to ______infected hepatocytes. Optimal outcome is to obtain viral clearance without a lot of collateral damage to liver tissues.
Serology: Remains in blood
Vaccine: 95 % protective Ab response
Increased risk of hepatocellular response
Hep B
- a major cause of liver disease worldwide. With ____ infection the progression to chronic disease occurs in the majority of patients and cirrhosis develops in 20-30% of infected individuals. With ___note persistent infection, chronic hepatitis.
•RNA virus
•Parenteral contact/sexual spread
•Incubation 7-8 weeks, acute phase is asymptomatic
•No vaccine because of genomic instability
•Cirrhosis occurs in approximately 80-85%, and may develop 5 to 20 years later.
•Risk factor for hepatocellular carcinoma.
•Most frequent viral infection associated with the need for liver transplantation. Previously treated with interferon and ribavirin. Treatment with protease and nucleoside inhibitors now considered curative.
oCombination drugs: Harvoni (2014, sofosbuvir & ledipasvir). 12 week course, several others since 2014; often given with ribavirin
oCurative in most patients. Side effects fatigue and headache.
Very expensive (Harvoni $95K, Mavyret [2017] 12 weeks $40K)
Hep C
(requires presence of Hepatitis B for infection) occurs as a co-infection. Co-infection presents like Hepatitis B-usually transient and self-limited
Hep D
(similar to A) is an enterically transmitted, water-borne infection-high mortality rate in pregnant women. Not associated with chronic liver disease
Hep E
(some similarity to C but is not hepatotropic) infection does not increase liver enzymes such as serum aminotransferases. Replicates in bone marrow and spleen
Hep G
is a chronic, progressive, hepatitis variant with an unknown etiology. Pathology is associated with T-cell mediated autoimmunity
Autoimmune Hepatitis
o3 overlapping forms: 1) hepatic steatosis, 2) EtOH hepatitis, 3) cirrhosis (only develops in a minority of patients).
o60 % of chronic liver disease associated with overuse of alcohol
40-50 % of deaths due to cirrhosis
Alcoholic Liver Disease
little fibrosis at onset, increased deposition with EtOH consumption. ____change is reversible if discontinue EtOH consumption. Mallory or Mallory-Denk bodies: clumps of cytokeratins, eosinophilic cytoplasmic inclusions.
Fatty liver from EtOH
the liver resembles from both macro and micro cirrhosis developing from hepatitis.
Final stage of cirrhosis
chronic disorder, steatosis, hepatitis, progressive fibrosis, cirrhosis, marked perturbations of vascular perfusion. Only develop cirrhosis in a small fraction of alcoholics
EtOH liver disease
Patients develop hepatocyte injury, and 10-20% progress to cirrhosis (seen primarily in obese patients).
•Approximately 70% obese persons have some form of fatty liver disease
•Liver biopsy necessary to establish the diagnosis, note increased liver enzymes in 90% of affected patients.
Nonalcoholic steatohepatitis (NASH)
Excessive accumulation of body iron. Most is deposited in liver, pancreas and heart. 4 hereditary forms (autosomal recessive, chromosome 6) and acquired form with excess iron intake.
•Liver features: Micronodular cirrhosis with hemosiderin, Hepatosplenomegaly, diabetes mellitus, skin pigmentation
•Lifetime accumulation of Fe-symptoms generally slow onset and notice around 5th or 6th decade of life.
•Males to females: 5 to 7:1
•Associated with abnormal regulation of intestinal absorption of Fe
•Clinical and microscopic features of hereditary hemochromatosis: increased in males, hepatomegaly, abdominal pain, increased skin pigmentation (especially after UV light), deranged glucose metabolism, cardiac arrhythmias, atypical arthritis.
Classic triad: cirrhosis with hepatomegaly, diabetes mellitus, and skin pigmentation.
•Diagnosis obtained by assessing serum Fe.
Treatment: Phlebotomy, Fe chelators
Hemochromatosis
Results from a failure to incorporate copper (Cu) into ceruloplasmin-consequently get accumulation of toxic Cu levels in liver, brain and eye.
•Usually presents between 6 to 40 years of age.
•Autosomal recessive
•Morphology: Acute/chronic, steatosis, necrosis, cirrhosis
•Presentation: acute or chronic liver disease. May present with tremor or behavioral changes.
•Screening test-NOT serum (as levels may actually be low), instead use Cu levels in urine (good for screening) or Cu levels in liver (definitive diagnosis).
•Chelation: D-Penicillamine
Wilson’s Disease
Develop pulmonary emphysema from protein degrading enzymes. Also develop liver disease, formation of Mallory bodies and PAS positive granules within hepatocytes
Alpha-1-antitrypsin deficiency
results from obstruction extrahepatic duct
a. Biliary tree obstruction-the primary cause is cholelithiasis (gall stones), then malignancies of biliary tree or head of pancreas.
b. Develop secondary inflammation-then fibrosis, hepatic scarring
Secondary Biliary cirrhosis
a.Inflammatory autoimmune disease-affects intrahepatic bile ducts.
b.Primary feature-nonsuppurative inflammatory destruction of medium sized intrahepatic ducts-also get portal inflammation, scarring and eventually cirrhosis.
Thought to be an autoimmune etiology
Primary biliary cirrhosis
a. Fibrosing cholangitis of bile ducts-develop luminal obliteration
b. Liver eventually develops biliary cirrhosis
c. NOTE: same common endpoint i.e. biliary cirrhosis as primary and secondary biliary cirrhosis
d. Note an increase in chronic pancreatitis and hepatocellular carcinoma (HCC) in PCS patients
Primary sclerosis cholagitis
single or multiple nodules may develop
a. In a non-cirrhotic liver “focal nodular hyperplasia” or “nodular regenerative hyperplasia”
b. Common factor-focal or diffuse alteration in hepatic blood supply, resulting in obliteration of the portal veins and a compensatory increase in arterial supply
Nodular hyperplasia
Cavernous hemangioma
Hepatic adenoma-increase in young women using oral contraceptives
Concerns with these: 1) mimic HCC, 2) subcapsular hemorrhage-from a rupture and bleed, 3) may transform to HCC.
Are associated with hormonal stimulation
Benign liver neoplasms
- Cancer of biliary tree-most are adeno CAs
- Very desmoplastic tumor-tumors are firm and gritty
- Can get collision tumor with HCC
- Asymptomatic until late stage
- Generally fatal within 6 months
Cholangiocarcinoma
•Most common liver tumor in young pediatric patients
•Epithelioid type
•Mixed epithelial-mesenchymal
•Treatment-chemotherapy then surgical resection
Is rapidly fatal (within months) if not treated
Hepatoblastoma
- Benign
- Association with oral contraceptives, if discontinued, may regress
- Presentation
- Acute abdomen
- Intra-abdominal bleed
- Histology: bland hepatocytes and no bile ducts
Hepatocellular adenoma
- Worldwide- 3rd most common cause of cancer deaths; 3:1 males
- Etiologic factors-cirrhosis (90%), due to chronic viral infection (HBV, HCV) or chronic alcoholism, NASH (nonalcoholic steatohepatitis), food contaminants (primarily aflatoxins).
- All HCC variants-strong propensity for vascular invasion
Hepatocellular Carcinoma
Variant of HCC oYoung males and females (20-40 yo) oDistinct from HCC oNo known risk factors o“Scirrhous tumor” oPatients generally do NOT have underlying liver disease-better prognosis. oTreatment: Surgery Better prognosis (32 % 5 yr survival)
Fibrolamellar Variant
- ______- primary soft tissue sites for metastases to occur. Metastatic tumors are more common than primary tumors
- Most common primary cancers are colon, breast, lung and pancreas
- Liver weight may exceed several kilograms. Often multiple nodules
- Often only sign is hepatomegaly-liver has tremendous functional reserve
Liver and lungs
10-20% of adults. Increased risk with increasing age and obesity, Caucasian women over men (2:1), cholesterol (80 %) and pigment/bilirubin stones (20 %).
•Cholesterol cholelithiasis (mostly radiolucent) vs bilirubin cholelithiasis (mostly radiopaque)
•Pigment stones → Hemolysis, GI disorders, Biliary infections
Increased with estrogen (pregnancy and oral contraceptives)
Increased with gall bladder stasis
Hereditary contribution
80% of patients with stones remain asymptomatic
If symptomatic, develop colicky biliary pain, inflammation, may eventually note perforation, obstruction of gall bladder or erode into ileum with GI obstruction.
Cholelithiasis (gall stones)
1.May be acute or chronic, 4th – 6th decades, F > M
2.Almost always occurs in association with gallstones
3.Note upper right quadrant pain, may note low level fever, anorexia, tachycardia, nausea, vomiting. Acute symptoms-can arise very abruptly.
4.Chronic-not as dramatic a presentation. Note recurrent bouts of colicky epigastric or right quadrant pain.
•Vague symptoms, Stones (90 %), Fibrosis & Inflammation
Cholecystitis
1.Increased frequency in women in their seventh decade of life.
2.Whites > Blacks
3.5th among GI malignancies
4.Mean five year survival is 5%
Risk factors include _____(95 % associated with ____) or infectious agents within the ______
Cancer of the gall bladder (adenocarcinoma)
…include gallstones…with stones…the gallbladder
•Reversible parenchymal injury associated with inflammation,
80% of cases related to biliary tract disease or alcoholism; infections e.g. mumps, trauma, metabolic diseases (e.g. hypercalcemic states), medications (e.g. estrogens, chemotherapy), idiopathic
•Release of lipases, inflammation, proteolysis. Necrosis of vessels with hemorrhage. Fat necrosis.
•Symptoms are ABDOMINAL PAIN. This is the cardinal manifestation. “upper back intense pain”. Full blown acute pancreatitis is a medical emergency due to the potential to release toxic enzymes.
Elevated enzymes (Amylase, Lipase), Organ failure, Abscess, Mortality (8 %)
Acute Pancreatitis
•Develop irreversible destruction exocrine pancreas, with ensuing fibrosis and eventual destruction of the endocrine parenchyma.
•Etiology unclear: Alcoholism, biliary disease, hypercalcemia, hyperlipidemia, oxidative stress, idiopathic? genetic?
•Morphology: Reduced acini, chronic inflammation, fibrosis, obstruction ducts, spare islets
•Symptoms range from severe abdominal pain to silent (only detected once the patient develops diabetes mellitus).
Diagnosis-requires a high degree of suspicion-may have already destroyed acinar cells, so may not see an increase in serum amylase
Chronic Pancreatitis
serous cystadenomas, females over males, 2:1, usually seventh decade
•Close to 95% of mucinous cystic neoplasms arise in women. Can be associated with invasive cancer.
Intraductal papillary mucinous neoplasms increased males over females
cystic pancreatic neoplasms
•Fourth leading cause of cancer death in the US (lung, colon, breast, pancreas)
•Precursor lesion is PanINS (pancreatic intraepithelial neoplasias)
•Primarily a disease of the elderly, 80% of the cases between 60-80 years
•Environmental influence-primarily cigarette smoking (Doubles risk)
•Also increased risk with diabetes mellitus & chronic pancreatitis
•New onset diabetes mellitus in older patient-raises concern re: Pancreatic Cancer
•Often remain silent until invade into adjacent structures. Pain is usually the first sign, but typically too late. Obstructive jaundice is associated with tumors at the pancreatic head.
•Trousseau sign: Migratory thrombophlebitis-formation of platelet aggregation factors and procoagulants from tumor or its necrotic products.
Clinical course is very brief and very aggressive. Rapidly fatal. Most patients die within 6 months
Pancreatic cancers (infiltrating ductal carcinomas of the pancreas)
refers to an abnormal opening of the urethra along the ventral aspect of the penis, and occurs in 1/300 live male births. The opening may be restricted and lead to an increased risk of urinary tract infections
hypospadias
refers to the urethral opening on the dorsal aspect of the penis. This abnormality is less common, but also exhibits an increased prevalence of urinary tract infections in addition to predisposition to urinary incontinence
epispadias
is a synonym for carcinoma in situ of the penis. ____disease is not specific to the penis but may occur on other cutaneous or mucosal surfaces. Its major clinical importance lies in the potential progression to invasive squamous cell carcinoma
Bowen disease
- accounts for about 0.4% of cancer in males.
- most common penile neoplasms.
- extremely rare among men who are circumcised early in life.
- Human papillomavirus (HPV 16/18) may be involved with development of ____ cancer, and circumcision may improve hygiene and lessen exposure to oncogenic viruses.
- over 40 and may be preceded by Bowen’s disease.
- begins as a crusted plaque or nodule with irregular margins that usually develops a central ulceration.
- Less frequently, it forms a papillary mass. Treatment - surgical excision.
- 5-year survival is 66%.
- Widespread metastasis is rare;
- local metastasis to inguinal lymph nodes reduces 5-yr survival to 27%
Squamous cell carcinoma of the penis
- Inflammatory processes, fungal infections, dermatoses
- Rare neoplasms; most squamous cell carcinoma
- 1st human cancer associated with occupational (environmental) factors (chimney sweeps)
Disorders of the scrotum
- failure of testicular descent from the abdomen to the scrotum.
- diagnosis cannot be confirmed until 1 year of age because the timing of completion of the descent is variable.
- present in 1% of the male population and may be unilateral or bilateral (10%).
- Untreated bilateral ____ results in sterility.
- In unilateral cases, the contralateral descended testis may undergo atrophy, also leading to sterility.
- Failure of descent also is associated with a 3-5 times increased risk of testicular malignancy manifesting as intratubular germ cell neoplasia developing within the atrophic tubules.
- Surgical placement of the testes into the scrotum (orchiopexy) before puberty reduces but does not eliminate the risk of cancer and infertility
Cryptorchidism
- inflammation of the testes.
- the inflammation begins as a primary urinary tract infection
- secondary ascending infection of the testes.
- Epididymitis is more common than ___.
- Swelling and tenderness are common signs in affected patients.
- Frequently the origin is a STD
- other common causes including nonspecific ___, mumps, and tuberculosis.
- complicates mumps in 20% of infected adult males but rarely in children. In severe cases, mumps-associated ___ can result in sterility
Orchitis
Cancers of the testes typically are divided into
seminomas or nonseminomatous germ cell tumors
2 markers for staging, diagnosis and follow-up for cancers of testis
- a-fetoprotein
- HCG
arise from the epithelium of the seminiferous tubules and remain localized for long periods. However, spread occurs via lymphatics. They respond well to chemotherapy and are extremely radiosensitive. Therefore, they are one of the most curable cancers
seminomas
spread earlier, are less radiosensitive and utilize the hematogenous and lymphatic routes, with the lungs and liver often involved at the time of diagnosis. As Lance Armstrong can attest, treatment of testicular neoplasms is a modern medical success story. Of the 8K cases each year in the US, only about 400 die of their disease
nonseminomatous tumors
small gland associated with pathoses that vary from benign and significantly symptomatic to silent but deadly
prostate
- clinically apparent inflammation of the __ which may be acute or chronic. The __ will be enlarged and tender.
- Bacterial __ may be acute or chronic and is caused by the same organisms which commonly produce urinary tract infections (E. coli).
- Chronic nonbacterial ___ (90-95 % of cases), also known as chronic pelvic pain syndrome, is of unknown etiology and doesn’t respond to antibiotics.
- Both acute and chronic __ present with dysuria, urinary frequency, lower back pain and poorly localized suprapubic or pelvic pain.
- Antibiotics penetrate the __ poorly, and the most common cause of recurrent urinary tract infections is the surviving bacteria
prostatitis
- refers to hyperplastic enlargement of the prostate, often associated with urinary symptoms.
- Benign prostatic hypertrophy is a time-honored synonym, which is a misnomer and has been replaced with benign prostatic hyperplasia.
- The alteration is a common pathosis that begins during the forties (20 % of men) and increases with age; 90% are affected by the eighth decade.
- Stromal and glandular proliferation result in enlargement. The central portions of the gland adjacent to the urethra (Inner periurethral zone) are involved most frequently; impingement on the prostatic urethra leads to dysuria
- No more than 10% of men require surgical relief of the obstruction (TURP – Transurethral resection of the prostate) secondary to prostatic hyperplasia.
- Medical management with drug therapy may also be considered.
- Although the cause is unknown, androgens appear to have a central role in its development
Nodular hyperplasia of the prostate
- most common cancer of men over 50 years of age, with the peak prevalence between 65-75
- significant evidence suggests androgens contribute significantly to the development of this cancer.
- Hereditary and environmental contributions also have been suggested.
- clinically evident carcinomas invade adjacent structures and metastasize via both the lymphatics and the bloodstream. Regional node involvement occurs early.
- Osseous metastasis is the most common form of hematogenous spread
carcinoma of the prostate
- represents a useful marker in the management of prostate cancer,
- is elevated in both normal prostate and those affected by cancer, prostatitis, or nodular hyperplasia. ___ is of limited value when used as an isolated screening test
- value is enhanced considerably when combined with other tests
PSA
- most common tumor is _____, which represents 90% of neoplasms of the bladder. This typically occurs in men between the ages of 50 and 80 years and the dominant presenting manifestation is painless hematuria.
- Predisposing factors include cigarette smoking, chronic cystitis, infection with Schistosomiasis, and exposures to various carcinogens
- The tumor is preceded by a premalignant precursor lesion which often has a papillary growth pattern, but can also be flat. Tumor cells generally lack cohesion and are shed into the urine
urothelial cell carcinoma
- venereal disease that is produced by a spirochete, Treponema pallidum.
- Greater than 24,000 cases reported in the U.S. in 2015.
- African Americans affected 30X more often than whites. The peak of incidence is between 20-24 years old, followed by 15-19 years old
- infection produces two types of antibodies
syphilis
two types of antibodies produced by sphylis
- syphilitic reagin
- treponemal antibody
simple screening tests for syphilis
- VDRL
- RPR
- FTA- expensive (more specific)
•painless chancre which arises at the site of entry 9-90 days (mean of 21 days) after exposure.
•Glans penis in the male and the
•vulva or cervix in females are common sites. Lips, fingers, oropharynx and anus are also possible sites.
•. Serologic tests begin to become positive after 1-2 weeks of infection and are positive in the vast majority by 4-6 weeks. Because of the early negativity of the screening tests,
•dark-field examination of the exudate is extremely important in the diagnosis of early ___ ___.
•____spirochetes can be found within the normal oral flora and this makes the dark-field method of limited use for primary oral lesions.
-Spirochetemia occurs during this stage. 50% of the females and 30% of the males either never develop or do not detect the chancre. Chancres heal in 4-6 weeks
primary syphilis
•25% of untreated patients, healing of the chancre is followed within 2 months
•presenting with generalized lymph node enlargement combined with widespread mucocutaneous lesions that are maculopapular, scaly or pustular and even involve the palms and soles.
-Oral and vaginal areas of localized spongiotic mucositis are called mucous patches.
-Elevated large broad plaques (condyloma lata) can form in moist skin areas such as the axillae, inner thighs and anogenital area.
-Mucosal condyloma lata are not rare and often noted in the oral cavity, pharynx and external genitalia.
-All sites are infectious. The rash can be extremely subtle and may be ignored. All serologic tests are positive
secondary syphilis
•arises in 30% of untreated patients usually after a latent period of 5-20 years.
•It may affect any part of the body, but it shows a predilection for the cardiovascular system (80%) and the CNS (10%). The aorta may develop scarring, weakening and dilation secondary to obliterative endarteritis. Brain atrophy produces dementia.
•Rubbery gray-white areas of total necrosis (gumma) may be seen most frequently in mucocutaneous tissue and bone. Nasal and palatal bones are not uncommon sites. The gumma is due to hypersensitivity to products of the spirochete and to ischemia from obliterative endarteritis.
-Treponemes are difficult to find in ___ ___ and this stage is much less infectious. With treatment, gummas will become areas of scar; the cardiovascular and neural damage is irreversible.
-The nonspecific serologic screening tests typically are negative. Once exposed the highly sensitive specific treponemal antibody tests are positive for life
tertiary syphilis
can be divided into three patterns: stillbirth, infantile and late
congenital syphilis
refers to liveborn infants that at birth or within the first few months of life present with clinical lesions similar to those seen in secondary syphilis
infantile syphilis
refers to cases of untreated congenital syphilis of more than 2 years duration. Classic manifestations of this chronic infection include interstitial keratitis of the eyes, saber shins, saddle nose, Hutchinson’s incisors, mulberry molars, eighth nerve deafness, gummas and neurosyphilis
late congenital syphilis
- Interstitial keratitis
- Hutchinson’s teeth
- Eighth nerve deafness
Hutchinson’s Triad
frequent sexually transmitted disease caused by Neisseria gonorrhoeae, a gram-negative diplococcus. An estimated 800K cases occur annually in the U.S., and this is complicated by the emergence of strains which are resistant to multiple antibiotics. Humans are the only natural reservoir, and spread requires direct contact with the mucosa of an infected person
- 80% of the females and 40% of the males are asymptomatic
- ascending infection in males results in acute prostatitis, epididymitis or orchitis
Gonorrhea
Ascending infection involving the uterus, fallopian tubes, and ovaries results in
acute salpingitis
