Please enable JavaScript.

Coggle requires JavaScript to display documents.

EXOCRINE PANCREAS - Coggle Diagram

- - - - affected more commonly by the most relevant malignant tumor of the pancreas
      - ductal adenocarcinoma
        
        intraductal papillary neoplasm
        
        giant cell adenocarcinoma
    - - affected by aggressive tumors
        
        cystic serous tumor
        
        cystic mucinous tumor
        
        endocrine tumor
        
        they can cause peripancreatic invasion and metastases
  - - - M:F = 2:1
        
        age ranges from 55 to 85
    - - smoke
        
        chronic alcohol consumption
        
        high fat diet
        
        chronic pancreatitis
        
        idiopathic familial pancreatitis
        hereditary syndromes
    - - KRAS
        
        mutated in 90% of cases
        
        not used for diagnosis, since it is found in healthy individuals as well
      - BRCA2
        
        relevant to be identified both for hereditary predisposition and treatment; high malignancy
    - - pre-invasive stages affecting the ducts, i.e. intraepithelial pancreatic neoplasia
        
        observed either in samples with chronic pancreatitis or close to the invasive tumor
        
        definition:
        non-invasive lesion affecting small ducts, <0,5 cm, either flat, papillary or micropapillary in architecture
      - many steps are required for lesions to become neoplastic and then eventually invasive
        
        low-grade
        
        increased height of the cells, increased mucinous content
        
        leading mutation: KRAS
        
        high-grade
        
        in situ intraductal carcinoma
        
        it is necessary exclude the presence of adenocarcinoma in the surrounding tissue
        
        this lesion is the main precursor of ductal invasive adenocarcinoma
        
        leading mutation: p63, SMAD4, BRCA2
    - - similar to those of chronic pancreatitis
      - whitish, sclerotic mass, irregular margins, hard texture
        
        dilation of the main duct, detectable at US
        
        upstream pancreatitis
        
        possible extension to
        
        papilla of Vater, causing jaundice due to impaired bile drainage
        
        celiac tripod, posterior to the pancreas, causing pain
        
        superior mesenteric vessels
        
        the first to be affected is the vein, then eventually the artery
    - - sclerotic deposition and intense desmoplastic reaction, accounting for the hard consistency of the lesion
      - ducts of small or medium size, with atypias of vaious degrees, which may resemble chronic pancreatitis when low-grade
      - perineural invasion: peculiar feature of PDAC, whicih is exploited for DD
    - - associated with Lynch syndrome
        
        due to microsatellite instabillity due to mutations in MMR gene (MSH2 and MLH1), which can be sporadic or germline
        
        the pathologist should suspect this syndrome when seeing an undifferentiated lesion with abundant lymphocytic infiltration and possible colloid
        
        the next step is IHC to evaluate MSI/MMR status. In doubtful cases, MSI-PCR is used
    - - based on glandular differentiation, mucin production, mitoses/HPF, nuclear atypias
        
        G1
        
        well-differentiated glands, intensive mucin production, <5 mitoses/HPF, low-grade atypias
        
        G2
        
        moderately differentiated glands, irregular mucin production, 6-10 mitoses/HPF, moderate polymorphism
        
        G3
        
        poorly differentiated glands, abortive mucin production, >10 mitoses/HPF, marked polymorphism
    - - the most important parameter determining prognosis
      - T
        
        evaluation of the margins, the posterior lamina (looking for vessel's involvement), peripancreatic adipose tissue, spleen and duodenum
        
        if none of these extrapancreatic sites is involved, the tumor is staged as pT1 or pT2 according to its size (< or > 2cm)
        
        pT3: extrapancreatic extension to the duodenum, ampulla of Vater, biliary tract, peripancreatic tissue
        
        extension to extrapancreatic structures is frequent and a cause of tumor unresectability
        
        neoadjuvant therapy with folfirinox (ct), losartan and chemoradiotherapy
        
        pT4: extension to stomach, spleen, colon, adjacent large vessels
      - N
        
        LNs involvement
        
        pN1: metastasis in regional lymph nodes
      - M
        
        M0: no metastases
        
        M1: distant metastases
    - - in the pancreas, BRCA2 mutations are associated with a 5-10% lifetime risk of developing pancreatic cancer
        
        relevant to be detected to guide therapeutic decisions (if present, PARP inhibitors are used)
  - - - main duct
        
        branch duct-type
        
        mixed duct-type
        
        main difference with PAN-IN: it affects the main duct, >0,5 cm
        
        histology is similar being either micropapillary or papillary
    - - frequency of 1%
        
        M:F = 3:1
        
        pts are usually around 80
    - - related to Peutz-Jaghers syndrome
        
        main sign: brown maculae in the mouth
      - associated with genomic alterations, e.g. KRAS and GNAS
    - - he main duct appears dilated, filled by the neoplastic growth and mucus produced by the tumor
    - - different histotypes, e.g. gastric-type, intestinal-type and pancreatobiliary-type
    - - low-grade
      - high-grade
        
        associated with a reduced survival and possible invasion; diagnosis relies on cytological structures
  - - - mainly localized in the tail
        
        more frequent in the females
        
        90% of pts are affected by VHL syndrome
        
        low malignancy, benign in 90% of cases
    - - cystic serous tumor
        
        easily recognized by the radiologist at US examination thanks to the central area of sclerosis and the multiloculated cystic aspect, looking like a sponge at macroscopy
        
        usually solitary and well-demarcated
      - cystic mucinous tumor
        
        solitary, well-circumscribed, mostly unilocular with gelatinous content and possibly containing papillary formations
        
        no relation with the main ductal system
    - - cystic serous tumor
        
        serous cystadenoma
        
        cystic spaces (spongy-like), lined by cuboidal cells, containing glycogen (PAS+, PAS-d-), no atypia nor mitoses
        
        serous cystadenocarcinoma
        
        rare, similar to cystadenoma in appearance, major atypias but poorly marked; LN or hepatic metastases
      - mucinous cystic neoplasm
        
        distinctive ovarian-type stroma consists of densely packed spindle-shaped clls with round or elongated nuceli and sparse cytoplasm and its presence is required for the diagnosis
        
        low-grade
        
        cells arranged on one line, mucus content (PAS+ and PAS-d+), nucleus located at the base
        
        high-grade
        
        marked architecture disarray (cell stratification, nuclear polarity and mitoses)
    - - serous cystic adenoma
        
        resection only in case of disabling symptoms and when the cyst diagnosis is uncertain
      - mucinous cystic tumors
        
        surgical resection is indicated and curative only for non-invasive MCNs
- - - - absence of the pancreas, frequently associated with other malformations
    - - due to a defect in embryonic development causing the dorsal and ventral pancreatic ducts not to fuse together
      - bile ducts drain into the major duodenal papilla and the dorsal pancreatic duct into the minor duodenal papilla (Santorini duct)
        
        predisposition to pancreatitis development
    - - the pancreas is placed over and envelops the duodenum, like a ring
      - it can cause duodenal obstruction, various papillary anomalies and paraductal pancreatitis
  - - - LUNGS: thick mucus causes small airways obstruction, leading to recurrent respiratory exacerbations
        
        LIVER: biliary cirrhosis, gallstones and steatosis
        
        INTESTINE: meconium ileus, distal intestinal obstruction syndrome, fibrosing colonopathy
        
        KIDNEYS
        
        SWEAT GLANDS: salty sweat
        
        PANCREAS: exocrine insufficiency, fat soluble vitamin malabsorption, CF-related diabetes
        
        BONES: osteoporosis, arthritis, hypertrophyc pulmonary osteoarthropathy
        
        PANCREATIC DISEASE
        
        highest penetrance, earlist manifestations
        
        in physiological conditions, CFTR encodes for a protein expressed on the apical membrane of epithelial cells in the small pancreatic ducts
        
        lower pH, reduced volume and higher protein content of the pancreatic secretions account for the increased thickness of the mucus produced by the epithelial cells of the ducts eventually leading to obstruction
        
        at microscopy
        
        dilation of the ducts
        
        dense mucus within ducts
        
        possible calcifications in the mucus
        
        atrophy of acinar cells leading to reduction in digestive enzymes production and secretion
        
        exocrine cells are replaced by adipose tissue (lipomatous atrophy)
        
        in advanced diseases, only residual endocrine islets are seen in the adipose tissue
    - - main ones
        
        inadequate peak bone mass during puberty
        
        increased bone losses in adults
      - additional ones
        
        BMI, male sex, advanced pulmonary disease, malnutrition and chronic therapies
  - - - epidemiology
        
        50-60y
        
        M:F = 2:1
        (gallstones-related obstruction is more common in females)
      - clinics
        
        acute abdominal pain, which may radiate to the back, giving rise to a stabbing sensation
        
        elevation of serum amylase or lipase, which may reach 3-4x the upper limit of normal
      - causes
        
        toxic: alcohol, pesticides, drugs
        
        obstructive: gallstones, worms, congenital defects
        
        metabolic: hyperlipidemia, hypercalcemia and acidosis
        
        infectious: parasitic, viral and bacterial
        
        genetic: mutations in CFTR, PSTI1, SPINK1, PRSS1
      - etiopathogenesis
        
        DUCT OBSTRUCTION
        
        cholelithiasis, causing ampullary obstruction or alcoholism causing ductal concretions
        
        blockade in the secretion leading to edema, which impairs blood flow resulting in ischemia
        
        necrosis, acinar cell injury and release of activated enzymes
        
        activated enzymes cause interstitial inflammation and edema, proteolysis (by proteases), fat necrosis (by lipases and phospholipases) and hemorrhages (by elastase)
        
        DIRECT ACINAR CELL INJURY
        
        alcohol, drugs, trauma, ischemia, viruses
        
        DEFECTIVE INTRACELLULAR TRANSPORT
        
        due to alcohol or duct obstruction
        
        all these mechanisms lead to acute necrosis and possible involvement of vessels by elastase action
        
        result: acute necrotic hemorrhagic pancreatitis
      - classification
        
        serous: during the first stages of edema and congestion
        
        suppurative: rare finding, due tobacterial superinfection
        
        necrotic hemorrhage: frequent finding
      - pathology
        
        micro
        
        coagulative necrosis: cell destruction
        
        mild inflammation with few PMNs
        
        vascular damage with bleeding
        
        steatonecrosis: calcium deposits may be observed
        
        macro
        
        edematous parenchyma looking bright
        
        necrosis
        
        soft tissue at touch
        
        hemorrhages due to action of enzymes on vessels
        
        steatonecrosis due to lipase release
      - evolution
        
        95% survival with restitutio ad integrum and/or pseudocyst or sterile abscess formation
        
        5% death from shock within a week
    - - it results from repeated episodes of mild/moderate inflammation
        
        pathological changes of the parenchyma are sclerotic-regressive lesions with exocrine and later endocrine cell destruction
      - clinics
        
        pain, steatorrhea, malabsorption, weight loss and late diabetes
        
        diabetes arises later in the course of the disease because endocrine islets respond better to inflammation and stress
      - etiology
        
        biliary tract disease, less relevant than alcoholism
        
        alcoholism (in 80% of patients)
        
        CFTR mutations
        
        non-alcoholic forms include various causes of obstruction (stones, tumors, cysts)
        
        idiopathic (20%)
        
        non-alcoholic forms associated conditions
        
        malnutrition, hereditary defects (SPINK1, PRSS1), smoke, autoimmune forms, hypercalcemia rarely reported, pancreas divisum
      - pathogenesis
        
        dilation of the ducts (duct ectasia) and protein plugs, due to massive fibrotic reaction occluding the duct
        
        destruction and replacement of the acinar parenchyma: the exocrine portion of the pancreas is disrupted, while some endocrine islets are usually still observable
        
        diffuse fibrosis
      - pathology
        
        macro
        
        increase in volume and consistency, dilation and distortion of the duct's lumen
        
        histology
        
        stroma and sclerotic bands replace the necrotic parenchyma
        
        ductular reaction in chronic pancreatitis may resemble a pancreatic ductal carcinoma
        
        endocrine islets and a few distorted acini
    - - lymphoplasmacytic sclerosing pancreatitis (LPSP)
        
        no granulocytes epithelial lesions (GELs)
        
        comparison of the two
        
        epidemiologically, the frequency is increasing in both cases; they affect males more than females and middle-aged pts
        
        LPSP features a high percentage of pts with high levels of serum IgG4 as well as IgG4 detectable in the tissue, while IDCP does not
        
        clinically, extra-èamcreatic involvement can b present in LPSP (proximal biliary stenosis, sialadenitis, retroperitoneal fibrosis, interstitial nephritis)
        
        IBD can be associated with both forms (IDCP>>>)
        
        LPSP is more prone to give relapses
        
        histopathological diagnosis
        
        LPSP
        
        morphology
        
        infiltratioin of plasma cells and lymphocytes
        
        storiform fibrosis
        
        damage of exocrine cells, phlebitis obliterans and arterial involvement
        
        IgG4 IHC
        
        abundantinfiltration of IgG4+ plasma cells localizing around ducts, i.e. >10 plasma cells IgG4+/HPF
        
        IDCP
        
        morphology
        
        ductocentric (periductal) inflammation
        
        direct damage of the pancreatic epithelium of the ducts by granulocytes with ductal microabscesses
        
        suggested GEL
        
        infiltration and microabscess in intralobular ducts
      - idiopathic ducto-centric pancreatitis (IDIP)
        
        it features GELs and possibly ductal abscesses
  - - - underlying pathogenetic mechanism:
        
        lack of production or action on insulin targets
    - - I
        
        juvenile
        
        acute onset with early metabolic acidosis
        
        viral etiology is suspected, then possibly sustained by Ab anti-insulin
        
        therapy is insulin-dependent
      - II
        
        adult
        
        insidious onset
        
        less aggressive
        
        insulin-independent
        
        association with obesity
    - - type I
        
        marked insulitis, i.e. lymphocytic infiltrate within islets
      - type II
        
        islet hyalinization (vanishing of islets' beta cells and replacement by hyaline deposits
        
        amyloidosis
        
        fibrosis
        
        atrophy
        
        beta cells glycogenosis
    - - macrovascular
        
        due to atherosclerosis of the aorta, coronaries, renal arteries, limb arteries
      - microvascular
        
        due to increased thickness of the capillary's basal membrane with paradoxical increase in capillaries' permeability
      - organs involved
        
        EYES
        
        retinopathy, cataracts and glaucoma due to retinal artery involvement
        
        KIDNEYS
        
        the high blood pressure damages small blood vessels and the glomerulus is affected by the increased blood glucose resulting in diabetic nephropathy
        
        glomerular damage
        
        clinical signs of increasing severity over time:
        
        isolated proteinuria
        
        nephrotic syndrome
        
        chronic renal failure
        
        it consists of
        
        BM thickening
        
        damage of podocytes' pedicels
        
        increased number of mesangial cells
        
        increased mesangial matrix production
        
        hyalinosis of afferent and efferent arterioles
        
        histological picture
        
        obliteration of capillaries' lumen due to mesangial hyperplasia and increased matrix production
        
        membrane thickening
        
        vessels hyalinosis
        
        1 more item...
        
        tubules involvement
        (diabetic tubulopathy)
        
        thickening of the BM
        
        intratubular protein deposits (pinkish in histological images, resembling colloif found in thyroid follicles (thyroidization of the kidneys)
        
        pyelonephritis, due to increased glucose content in the urine and ascending infection from the bladder
        
        renal papillae
        (diabetic microangiopathy)
        
        there is the development of ischemia and the papillary necrosis
        
        necrosis may cause detachment of a portion of the papilla, which ends up obstructing the tubules
        
        1 more item...
        
        NERVES
        
        NEUROPATHY due to demyelinating changes with predominant axonal damage in the PNS
        
        NUMBNESS
        
        BRAIN
        
        same process of hyalinosis of vessels and macrovascular complications
        
        increased risk of stroke and cerebrovascular disease
        
        transient ischemic attack
        
        cognitive impairment
        
        HEART
        
        high blood pressure and insulin resistance
        --> increase in the risk for CAD
- - - - acinar cells produce digestive enzymes, ingluding trypsinogen, chymotrypsinogen, elastase, lipase, amylase, phospholipase, nuclease