Path Exam 2- GI disease & lymphomas Flashcards
Cholera
- sites: SI
- symptoms: severe watery diarrhea “rice water”
- complications: dehydration, electrolyte imbalances
A subunits catalyzes ADP-ribosylation of GTP-binding proteins causing persistant activation of adeylate cyclase wwhich increases cAMP and Cl- secretion
Campylobacter spp.
- sites: colon
- symptoms: watery or bloody diarrhea
- complications: Guillain-Barre, arthritis
- -looks like UC
Shiegellosis
- sites: left colon, Ileum
- symptoms: bloody diarrhea
- complications: Reiter syndrome, HUS
- looks like UC
Salmonellosis
- sites: colon and SI
- symptoms: watery or bloody diarrhea
- complications: sepsis, abscess
- looks like UC
Enteric (typhoid) fever
- sites: SI
- symptoms: bloody diarrhea, fever
- complications: chronic infection, carrier state, encephalopathy, myocarditis; *perforation
Fecal mononuclear leukocytes
Yersinia spp.
- sites: ileum, appendix, right colon
- symptoms: abdominal pain, fever, diarrhea
- complications: Autoimmune e.g. reiter syndrome of reactive arthritis
E. coli (EnteroToxigenicEC)
- sites: SI
- symptoms: severe watery diarrhea
- complications: dehydration, electrolyte imbalance
Enterohemorrhagic (EHEC)
- sites: colon
- symptoms: bloody diarrhea
- complications: HUS
Pseudomembranous Colitis
C. difficile
- sites: colon
- symptoms: watery diarrhea, fever
- complications: relapse, toxic megacolon, mushroom cloud/ volcanic erruption
Whipple disease
- sites: SI
- symptoms: diarrhea/malabsorption (lymphatic transport)
- complications: arthritis*, CNS dis, PAS + macrophages in lamina propria
-male farmers 30-50yrs
-symptoms may last YEARS
Tropheryma whippelii
Follicular lymphoma
- B cell
- Indolent; median survival 7 yrs
- CD 20, 19, 10
- t(14:18) overexpress BCL2 (blocks apoptosis, chemo res.)
- nodal
- follicles that are BCL2 +
- adults; middle yrs
- poor response to chemo, can transform into large B cell
Large B cell lymphoma
- B cell
- Aggressive; months, good response to chemo
- CD 19, 20
- BCL6 (↑ growth ↓ differentiation ↓ apoptosis)
- often extranodal: CNS in HIV, Waldeyer ring (destructive mass in liver or spleen)
- diffuse large lymphs
- any age, HIV and transplant, HIV assoc.
- some arise form other B lymphoma
Burkitt
- B cell
- Aggressive; most rapid growing human malignancy
- CD 19, 20, 10 (surface IgM and BCL6)
- t(8;14) MYC aerobic glycolysis
- starry sky (intermediate lymphocytes, abundant mitosis, apoptic bodies)
- usually extra: kidney, ovary, adrenals
- responsive to chemo
African: facial, mandible 100% EBV
HIV: node/extra nodal 25% EBV
Sporadic: all ages, youth-ileocecal mass, kidney, ovaries (1/3) 15-20% EBV
MALT/marginal
- B cell
- Indolent
- CD 19, 20; post germinal center, memory B cells
- t(11;18) BCL10 or MALT1
- H. pyloryi, Sjogren, Thyroiditis
- diffuse lymphs, B cells at diff stages of differentiation including plasma cells
- reactive polyclonal prolif initially → monoclonal transformation (B-cell clone that is still dependent on T cells)
- remain localized for prolonged periods, late systemic spread
- regression may still occur
- may regress w/ antibiotics
Anaplastic Large cell
-T cell
-aggressive; curable w/ chemo
-CD8. CD30
-ALK (2p23) rearrangement- defining
-Soft tissues of children
-Horseshoe shape nucleus
-curable
(immunoperoxidase stain for ALK)
Adult T cell leuk/lymphoma
- T cell
- subacute 1 yr
- CD 4
- Skin, nodes, bone marrow
- convoluted nuclei (clover shaped)
- hypercalcemia (demylination may occur), *peripheral lymphocytosis
-HTLV-1 infection (Japan, w africa, carrib)
Mycosis fungoides
- T cell
- Indolent, years
- CD4 Sezary cell (CLA, CCR4, CCR10)
- starts in skin, RASH patch phase → plaque → tumor → LN → bone marrow
- cerebriform nuclei, *pautrier absc
- topical treatment of “fungus” for years, not curable
Sezary cell leukemia
- T cell
- Aggressive
- CD4 Sezary cell
- Erythroderm (exfoliative) BM: leukemia
- Cerebriform nuclei
HL: Nodular sclerosis type
- most common type
- lacunar and some diagnostic RS cell CD15+, CD30+, *EBV-
- young adults or adolescents
- M=F
- collagenous bands
- mediastinum (cough & dyspnea), lower cervical and supraclavicular nodes
- very good prognosis (stage I or II when diagnosed)
- background infiltrate: T-lymph, eosinophils, macrophages, plasma cells
HL: Mixed cellularity
- mononuclear & diagnostic RS cells CD15+, CD30+, *EBV+
- Biphasic: young adults and older adults 55+
- M > Fe
- poorer prognosis (stage III or IV)
- likely to have B symptoms (*cyclic fever, night sweats, weight loss)
- background infiltrate: T-lymph, eosinophils, macrophages, plasma cells
HL: Lymphocyte predominance
- more common in young males
- frequent L&H (popcorn cell)
- -CD 15-. CD30-. *CD20+. *BCL6+
- cervical/axillary lymphadenopathy, mediastinum
- background: variants of follicular dendritic cells and reactive B cells
- tend to recur
- excellent prognosis
Familial adenomatous polyposis (70% of FAP)
- molecular defect:
- genes:
- transmission:
- sites:
- histology:
-molecular defect: APC/WNT pathway
-genes: APC
-transmission: *autosomal dominant
-sites: none
-histology: NUMEROUS tubular, villous; typical
adeonocarcinoma (need 100 to make diagnosis)
- colorectal carcinoma 100% of untreated pts
- congenital hypertrophy of retinal pigment epi
- numerous colorectal adenomas as teenagers (30yrs)
Familial adenomatous polyposis (<10% of FAP)
- molecular defect:
- genes:
- transmission:
- sites:
- histology:
- molecular defect: DNA mismatch repair
- genes: MUTYH
- transmission: *none, recessive
- sites: none
- histology: sessile serrated adenoma; adenoma; mucinous adenocarcinoma
- colorectal carcinoma 100% of untreated pts
- congenital hypertrophy of retinal pigment epi
- numerous colorectal adenomas as teenagers (<30yrs)
Hereditary nonpolyposis colorectal cancer (Lynch syndrome)
- molecular defect:
- genes:
- transmission:
- sites:
- histology:
- molecular defect: DNA mismatch repair (results in microsatellite instability)
- genes: MSH2, MLH1 (inherit one mutant DNA repair gene)
- transmission: autosomal
- sites: right side
- histology: sessile serrated adenoma; mucinous adenocarcinoma
-increased risk of colorectal & extraintestinal cancer
Sporadic colon cancer (80%)
- molecular defect:
- genes:
- transmission:
- sites:
- histology:
- molecular defect: APC/WNT pathway
- genes: APC
- transmission: none
- sites: left side
- histology: tubular, villous; typical adenocarcinoma
Sporadic colon cancer (10-15%)
- molecular defect:
- genes:
- transmission:
- sites:
- histology:
- molecular defect: DNA mismatch repair
- genes: MSH2, MLH1
- transmission: none
- sites: right side
- histology: sessile serrated adenoma; mucinous adenocarcinoma
Peutz-Jeghers syndrome
- age:
- gene:
- GI lesions:
- extra-GI symptoms:
Hamartomatous polyps syndrome
- age: 10-15 yrs
- gene: KHB1/STK11; autosomal dominant
-GI lesions: arborizing polyps (CT, **SM, lamina propria and glands) (intussusception) ;
SI > colon > stomach; *colonic adenocarcinoma
-extra-GI symptoms: skin macules (around eye, mouth, nostrils, buccal mucosa, genitalia, perianal)
–INCREASED RISK of thyroid, breast, lung, pancreas, gonadal, and bladder cancer
Juvenile polyposis
- age:
- gene:
- GI lesions:
- extra-GI symptoms:
Hamartomatous polyps syndrome
- age: <5 yrs
- gene: autosomal dominant (SMAD4, BMPR1A)
- GI lesions: juvenile polyps in RECTUM (3-100);
–INCREASED RISK of gastric, SI, colonic, and pancreatic adenocarcinoma (GI cancers)
-extra-GI symptoms: pulmonary arteriovenous malformations, digital clubbing
Gardner syndrome
- variation of FAP (10-15 yrs, APC, MUTYH, multi adeomas)
- plus osteomas, desmoids, skin cysts
Turncot syndrome
- variation of FAP (10-15 yrs, APC, MUTYH, multi adeomas)
- plus CNS tumors (gliomas)
Oligohydramnios (Potter’s) sequence
decreased amniotic fluid leads to fetal compression
- flattened facies
- positional abnormalities of hands and feet
- compromised growth of chest wall (pulmonary hypoplasia)
- nodules in amnion (amnion nodosum)
Pentad of premature infants
- RDS (hyaline membrane disease): deficiency of pulmonary surfactant (most produced after 35 wks)
- retinolental fibroplasia: O2 toxicity- changes in expression of VEGF
- bronchopulmonary dysplasia: O2 toxicity- arrested development of alveolar septation at saccular stage, dependent on oxygen after 28 days
- necrotizing enterocolitis: inversely related to gestational age, symptoms dont appear until 1st feeding, intestinal ischemia prereq.
- bloody stools, abdominal distention, circulatory collapse (sepsis and shock)
-subependymal hemorrhage: 2ry bleeding into ventricles, always causes brain damage
Menetrier Disease
Hypoproteinemic Hypertrophic gastropathy
-excessive secretion of TGF-a →
-causes massive foveolar (surface MUCINOUS epi) hyperplasia of the fundus and body
-lots of mucus produced and not much acid:
*protein-losing enteropathy → hypoproteinemia
increased risk for adenocarcinoma
Zollinger-Ellison syndrome
- Gastrin secreting tumor → parietal cell proliferation (hyperplasia) → enlarged rugal folds
- Gastrin secreting tumor → ECL release H2 → increased acid → duodenal ulcers or chronic diarrhea (Rx PPI)
- Gastrinomas (duodenum, pancreas, antrum) may be sporadic or occur in MEN I pateints
- over half act malignant
- may be multiple and exceedingly small
Reed Sternberg Cell
Malignant cell of Hodgkin lympoma
-binucleated, bilobed giant cells
Classic RS:
- CD 15+, CD 30+
- IL5 → eosinophillia
- IL10 → ↓ Th1 & CTL response
- TNFa & bFGF → fibrosis
- M-CSF → monocyte/macrophage infiltration/ activation
- various chemokines → increase Th2 response
Non-Classic RS:
-CD15-, CD30-, CD20 +
Multiple Myeloma pathogenesis & morphology
- tumor cells & BM stromal cells → IL-6 GF for MM
- Plasma cells → MIP1a activates osteoclasts and causes bone lesions & hypercalcemia
- increased risk of infection
excess Ig predisposes for:
- serum hyperviscosity
- proteinuria w/ renal damage
- risk of infection
MORPHOLOGY:
- Increased/abnormal plasma cells in BM
- normal plasma cells
- plasmablasts; mulitnucleated cells
- Ig inclusions- Russell bodies
- Mott cell- lots of russell bodies
- Dutcher body: Ig in nucleus
Multiple Myeloma clinical features & labs
- Bone pain: lower back
- Hypercalcemia (MIP1a): confusion, weakness
- recurrent bacterial infections
- renal insufficieny
- symptoms of amyloidosis: racoon eyes, kindey problems (light chains?)
- hyperviscosity syndrome
LABS
- M protein
- IgG, A, D, light chain (immunofixation)** or
- Bence-Jones protein in urine (kappa or lambda light chain)**
- peripheral cytopenia (↓ WNC, RBC, platelets)
- bone marrow plasmacytosis (>30%)**
- increased BUN & creatinine
- increased uric acid & LDH
- low albumin w/ high total protein
- ROULEAUX
** + end organ damage & 1+ CRAB for diagnosis
Cryptosporidium
- sodium malabsorption & chloride secrtetion
- tight junction permeability
- attach to enterocyte brush border and form vacuole
- persists in AIDS
location: throughout GI most numerous terminal ileum
- nonbloody watery diarrhea
Tuberous sclerosis
- age:
- gene: TSC1, TSC2
- GI lesions: hammartomatous polyps (rectal)
- extra-GI symptoms: facial angiofibroma, cortical tubers, renal angiomyolipoma
Lymphoplasmacytic lymphoma
- indolent B-cell neoplasm
- older adults >50+
- portion of neoplastic B cells -> plasma cells
- only IgM
- no free light chains (no renal failure) or amyloidosis
- bone marrow w/ russell and dutcher bodies
- involves lymph nodes* live* and spleen*
- hepatospenomegaly, lymphadenopathy
- anemia
- -BM replaced
- -AI hemolytic anemia due to cold agglutinins (IgM)
- Hyperviscosity syndrome (headache, dizzy, stupor, deaf, visual impairment)
Achalasia
LES fails to relax
- symptom onset in YOUNG ADULTHOOD
- risk of regurg and aspiration
- risk for squamous cell carcinoma
shared systemic features of Crohns and UC
- erythema nodosum
- pyoderma gangrenosum (UC)
- migratory polyarthritis
- ankylosing spondylitis
- uveitis
- primary sclerosing chonalgitis (UC 10x)
- occur in developed countries
- mainly females, white, ashkenazi jews
- begins in teens/late 20s
- precipitated by stress
