Pathology Flashcards
Mutation in sickle cell anemia
Glutamic acid to valine at amino acid 6 of beta chain
Most common salivary gland neoplasm
Pleomorphic adenoma
What is the composition of Hb Barts?
4 gamma chains
Mole with greatest malignant potential
Junctional nevus
child presents with an array of macules, papules, vesicles, and bullae, reddish, with pale eroded center involving the extremities, lips and oral mucosa in a symmetric pattern. There was intake of penicillin and sulfonamides for urinary tract infection. The patient most likely has:
Erythema multiforme
- target lesions described
- associated with drug intake of sulfonamides and penicillins
Differentiation of pemphigus and bullous pemphigoid
Pemphigus has positive nikolsky sign (due to dissolution of intercellular attachments by autoantibodies).
Patient came in due to urticaria and you also noted the presence of grouped vesicles. Further examination revealed granular deposits of IgA at the tips of dermal papillae. The patient most likely has..
Celiac disease - case described findings in dermatitis herpetiformis associated with celiac disease
- tx gluten free diet
Patient presented with honey colored crusts. What would you expect on microscopic examination?
Accumulation of neutrophils beneath the stratum corneum (Subcorneal pustule)
Pterygium vs Pingueculum
Pingueculum does not invade the cornea, unlike pterygium
Leading cause of irreversible blindness in the developed world
Age related macular degeneration
- oxidative stress -> degeneration of retinal pigment epith
Most common primary intra-ocular malignancy of children
Retinoblastoma
- presents usually as leukocoria
- characteristic: Flexner Wintersteiner rosettes
Most common breast mass in women younger than 35 y.o
Fibroadenoma
Most common cause of bloody nipple discharge in women younger than 50 y.o
Intraductal papilloma
Most common type of breast cancer
Invasive ductal carcinoma
- characteristic grating sound due to small central foci or streaks of chalky white elastotic stroma
Most common cause of bilateral breast cancer
Invasive lobular carcinoma
- signet ring cells in indian file pattern
Most common cause of hydronephrosis in infants and children
Ureteropelvic junction obstruction
- usually at the left ureter
- usually bilateral in infants, unilateral in adults
Explanation behind ureteral obstruction in pregnancy
- relaxation of ureteral smooth muscle due to progesterone
- enlarging fundus causes pressure on ureters at the pelvic brim ( one area of constriction)
Histopathologic hallmark of primary sclerosing cholangitis
Onion skin fibrosis
Most common cause of bladder adenocarcinoma
Patent urachus
- failure of obliteration of fetal allantois
- presents as drainage of urine from the umbilicus in newborn
Clinical triad of acute cystitis
Dysuria, suprapubic pain, frequency
Causative agent of condyloma acuminata
HPV 6 and 11
Characteristic morphology seen in Bowen disease
Erythroplasia of Qeyrat: multiple shiny, red, sometimes velvety plaque
Intact basement membrane
*associated with visceral malignancies
Type of penile carcinoma in situ that can progress to invasive carcinoma
Bowen disease
Protective factor against squamous cell CA of penis
Circumcision
True or False
Neonatal testicular torsion is associated with an anatomic defect
False
Adult testicular torsion is the one associated with bilateral defects (BELL-CLAPPER deformity)
Most common benign paratesticular tumor
Adenomatoid tumor
- nodules at upper pole of epididymis
True or False
Malignant paratesticular tumors are usually due to rhabdomyosarcoma in children
True
In adults, due to liposarcomas.
Malignant paratesticular tumors located at the distal end of the spermatic cord (proximal usually benign lipomas)
Patient with testicular tumor, mass was homogenous, yellow white and mucinous. Histopath exam revealed the presence of structures resembling endodermal sinuses, the tumor is most likely a :
Yolk sac tumor
- structures resembling endodermal sinuses are schiller duval bodies
- tumor is also associated with markers: AFP, and alpha 1 antitrypsin
True or False
In the postpubertal male, all teratomas are regarded as malignant unless proven otherwise
True
- in children usually benign
- presents with painless enlargement of the testis
Testicular mass was excised in a patient with precocious puberty and gynecomastia, and was noted to grossly be golden brown with a homogenous surface. What would be the morphologic finding upon HP?
Rod shaped crystalloids of Reinke - seen in Leydig cell tumor
Patient came in due to testicular mass, no other signs or symptoms noted. Mass showed distinct trabeculae that formed cordlike structures and tubules, what other findings do you expect on examination?
Presence of crystalloids of Charcot-Bottcher (Sertoli cell tumor)
Most common form of testicular neoplasm in men over 60 y.o
Testicular lymphoma
- aggressive non hodgkins lymphoma
Most common form of prostatitis
Chronic abacterial prostatitis
- clinically indist from chronic bacterial prostatis, but with no history of recurrent UTI
Hormone responsible for hyperplasia in BPH
Dihydrotestosterone
Hallmark finding in BPH
Nodular hyperplasia
*originates from periurethral transition zone
The presence of ____________ are virtually diagnostic for prostate adenoCA
Osteoblastic metastases
- since its usually asymptomatic and detected late
- mets to axial skeleton (LUMBAR > prox femur > pelvis > thoracic spine > ribs)
Complication of PID leading to adhesions between small bowel and pelvic organs (violin string adhesions)
Fitz Hugh Curtis syndrome
True or False
Chronic atrophic vulvitis can progress to carcinoma
True
AKA Lichen sclerosus
- Atrophy of epidermis, Hydropic degen of basal cells, Collagenous fibrous dermis, lymphocytic bandlike infiltrate (cardinal feats)
- carcinoma is complication
Greatest risk factor for vaginal cancer
Previous carcinoma of cervix or vulva
Most common pathogen in placental infections
Group B streptococcus (from ascending bact infection in PROM)
Most common sites of metastasis of choriocarcinoma
Lungs and vagina
CSF finding in Guillain Barre syndrome
Albuminocytologic dissociation : increased CSF protein with no associated increase in WBC
Gene mutation in Spinal muscular atrophy (infantile motor neuron disease)
SMN 1
*also associated with destruction of anterior horn cells
Genetic mutation in disease characterized by the presence of ring fiber (subsarcolemmal band of cytoplasm) and sarcoplasmic mass
Described is Myotonic dystrophy- results from CTG trinucleotide repeats
Most common primary malignant bone tumor
Osteosarcoma
- usually in metaphysis of long bones
- on xray: Codman triangles and sunburst appearance
This tumor of the bone affects the epiphyses of long bones and usually occurs in 10-20 y.o
Chondroblastoma
- chicken wire of mineralization is seen
Patient presents with polyostotic fibrous dysplasia and endocrinopathies. On P.E cafe au lait spots are seen. this disease commonly presents as..
Precocious puberty
- disease is McCune-Albright syndrome
- chinese character trabeculae
Onion skin appearance on radiographs
Ewing sarcoma
- mutation in EWS gene on ch 22
- affects diaphysis of long bones
- micro char: homer wright rosettes
Most common form of skeletal malignancy
Metastatic disease
Radiographic hallmarks in rheumatoid arthritis
Joint effusions and juxta-articular osteopenia with erosions
Radiographic deformity seen in psoriatic arthritis
Pencil in cup deformity (erosive joint disease)
This type of brain herniation may lead to compression of branches of the anterior cerebral artery
Subfalcine (Cingulate) herniation
- cingulate gyrus herniates under falx cerebri
Mechanism of injury in epidural hematoma
Fracture of temporoparietal bone (pterion) leading to severance of the middle meningeal artery
Patient came was brought into the ER with fluctuating levels of consciousness. History of trauma reported. What is your expected finding on CT scan?
A crescent shaped lesion
- patient most likely has subdural hematoma caused by tearing of bridging veins
- usually have delayed presentation with fluctuating levels of consciousness
Most common cause of intraparenchymal hemorrhage
Hypertension
- development of minute aneurysms in basal ganglia : Charcot-Bouchard microaneurysms
Location of predilection of herpes encephalitis
Temporal lobes
- acute hemorrhagic, necrotizing enceph
- with cowdry type A intranuclear inclusions
Most common area for CMV encephalitis
Paraventricular subependymal regions
Sites usually devoid of inflammation in rabies encephalitis
Pyramidal neurons of the hippocampus
Purkinje cells of cerebellum
Most frequent presentation of multiple sclerosis
Unilateral visual impairment
- due to optic neuritis or retrobulbar neuritis
Most common cause of dementia
Alzheimers disease
Genetic alteration in Huntington’s disease
CAG trinucleotide repeats
What part of the brain is affected in Huntington’s disease?
Atrophy of caudate nucleus
Wernicke encephalopathy versus Korsakoff syndrome
Both are thiamine (vit B1) deficiencies, wernicke’s is reversible and involves the mamillary bodies while korsakoff syndrome is irreversible and involves the dorsomedial nucleus of the thalamus
Presence of Homer wright rosettes
Medulloblastoma
Most common benign brain tumor in adults
Meningioma
- usually parasaggital
- psammoma bodies also seen
Most common brain malignancy
Brain metastasis
Bilateral schwannoma association
Neurofibromatosis type 2
*Neurofibromatosis type 1 is associated with plexiform neurofibromas (shredded carrot appearance)
Most common cause of hyperpituitarism
Adenoma in anterior pituitary
Most frequent type of hyperfunctioning pituitary adenoma
Prolactinoma
- tend to undergo dystrophic calcification-> psammoma bodies or pituitary stones
Sudden hemorrhage into the pituitary gland clinically presenting with a triad of headache, diplopia, and hypopituarism
Pituitary apoplexy
- neurosurg emergency
Most common cause of syndrome of inappropriate ADH secretion
Small cell carcinoma of the lung
Most common cause of hypopituitarism in chuldren
Craniopharyngioma
- from rathke’s pouch remnants
- adamantinomatous type most often in children
Hypothyroidism developing in older child or adult
Myxedema (Gull disease)
- fatique, apathy, mental sluggishness, non pitting edema
Implicated auto antibodies in Hashimoto thyroiditis
Anti-thyroglobulin and anti TPO
Most common cause of painful thyroid gland
Subacute thyroiditis
- triggered by viral infection (Coxsackie)
Complication wherein an autonomous nodule develops within a long standing goiter and produces hyperthyroidism
Plummer syndrome
Most common primary thyroid cancer in adults and children
Papillary thyroid carcinoma
- associated with radiation exposure
Most diagnostic finding in papillary thyroid carcinoma
Orphan annie nuclei
True or False
Follicular thyroid carcinoma has frequent lymphatic invasion
False
Papillary thyroid carcinoma has frequent lymphatic invasion, follicular undergoes hematogenous spread and usually metastasizes to bone
Characteristic feature seen in neuroendocrine neoplasm derived from parafollicular/C cells
Acellular amyloid deposits
- seen in medullary thyroid carcinoma
Most common cause of secondary hyperparathyroidism
Renal failure
Complication in type 2 DM
Hyperosmolar hyperglycemic state
*in Type 1 DM: DKA
Most common cause of death in diabetics
Myocardial infarction
Most common pancreatic endocrine neoplasm
Insulinoma
- 80% have MEN1
Whipple triad in insulinoma
Symptoms of hypoglycemia
Low plasma glucose at time of symptoms
Symptom relief when glucose is raised to normal
Most common manifestation of primary hyperaldosteronism
Hypertension
*remember aldosterone acts to reabsorb Na :)
Most common enzyme deficiency in congenital adrenal hyperplasia
21-hydroxylase deficiency
- presents as ambiguous genitalia in females, precocious puberty in males, and hypotension
Pathogenesis of cystic fibrosis
Deletion of 3 nucleotides coding for phenylalanine aa508
Definitive diagnosis of Barrett esophagus
Demonstration of intestinal goblet cells
Most useful diagnostic marker in GIST
C-Kit
*GIST is the most common mesenchymal tumor of the abdomen
Mechanism of diarrhea in Whipple’s disease
Malabsorptive diarrhea due to impaired lymphatic transport
*whipples disease clinical triad: diarrea, malabsorption, weight loss
Earliest Chrohn’s disease lesion
Aphthous ulcer
Juvenile polyps are mostly located in the ____________
Rectum
- mostly present as rectal bleeding
Clinical triad in hepatopulmonary syndrome
Chronic liver disease
Hypoxemia
Intra pulmonary vascular dilations (mediated by NO)
*dec arterial oxygen sat (orthodeoxia) and increased dyspnea from supine to upright also seen (platypneg)
Clinical triad in hemochromatosis
Hepatomegaly, DM, bronze skin pigmentation
Strongest environmental influence in pancreatic adenocarcinoma
Cigarette smoking
*60% are found in the head of the pancreas– painLESS obstructive jaundice
Extrinsic compression of the common hepatic duct that can be mistaken for pancreatic CA
Mirizzi syndrome
Most frequent pre-existing histologic lesion in aortic dissection
Cystic medial degeneration/necrosis
Earliest manifestation of hypertensive heart disease
Increase in the transverse diameter of myocytes
54 yr old female came in due to unilateral temporal headache, with blindness on the ipsilateral side. She also complained of muscle and joint pains, upon lab exam serum CK was normal. What are the most common arteries involved?
Temporal and ophthalmic artery
- Temporal (giant cell) arteritis - occurs in those >50, presents with polymyalgia rheumatica
- morphology: nodular intimal thickening, multi nucleate giant cells
Most common acquired heart disease in children
Kawasaki disease
Indications for giving Aspirin in children
Juvenile RA
Kawasaki disease
RF
*JK Rowling
Most common benign tumor of the liver and spleen
Cavernous hemangioma
Gross changes in M.I
Mottling in 4 hrs
Bright yellow appearance in 1 wk
Red granulation tissue 2 wks
Gray white scar 2 months
Irrevrsible cell injury in M.I
20-40 minutes
Coagulation necrosis in M.I
4-12 hrs
*presence of wavy fibers and myoctolysis at periphery
At what day post M.I is the heart most prone to rupture?
3rd day (heart is softest)
Macrophages seen in M.I
Days 3-7
Granulation tissue most prominent in M.I
1-2 wks
Electron microscopy finding in post strep glomerulonephritis
Subepithelial humps
Electron microscopy finding in post strep glomerulonephritis
Subepithelial humps
The first manifestation of almost all forms of injury to cells due to influx of ions and failure of energy dependent ion pumps
Cellular swelling
Type of reversible injury characterized by appearance of lipid vacuoles in the cytoplasm, often seen in cells participating in fat,etabolism(liver, heart)
Fatty change (steatosis)
Irreversible condensation of chromatin in the nucleus of a cell undergoing necrosis or apoptosis; nuclear shrinkage with increased basophilia
Pyknosis
Destructive fragmentation of the nucleus of a dying cell
Karyorrhexis
Complete dissolution of the chromatin of a dying cell
Karyolysis
Pathway of apoptosis triggered by loss of survival signals, DNA damage, and accumulation of misfolded proteins; inhibited by anti apoptotic members of the Bcl family
Mitochondria I/Intrinsic pway
Initiator caspase for intrinsic pathway of apoptosis
Caspase 9
Pathway of apoptosis responsible for elimination of self reactive lymphocytes and damageby cytotoxicT lympo, initiated by TNF receptors
Death receptor/Extrinsic pathway
Initiator caspases for extrinsic pathway of apoptosis
Caspases 8,10
Executioner caspases
Caspase 3,6
Regulated cell death that results in necrosis (morphologically), caspase independent, activated R1P1 and R1P3 complexes leading to increased ROS and decreased ATP prodn in mitochondria
Necroptosis
Type of apoptosis often seen in microbe infected cells; caspase I releases IL-1 and with caspase 11 causes injury
Pyroptosis
Marker for autophagy, involved in formation of autophagosome
LC3
*autophagy: sequestration of cellular organellesinto cytoplasmic autophagic vacuoles; survival mech under stress conditions
Effect pf caloric restriction on longevity
Increased due to decreased IGF 1 signaling
Proteins produced in response to food deprivation with actions that lead to prolonged longevity (anti apoptotic, anti ROS)
Sirtuins
General steps of an inflammatory response
Recruitment of leukocytes Regulation of response Recognition of injurious agent Removal of agent Resolution
Morphologic hallmarks of acute inflammation
Vasodilation and accumulation of WBCs and fluid in extravascular tissue
Most notable mediator that produces vasodilation
Histamine
Most common mechanism of increased microvascular permeability
Endothelial cell contraction
Initial vascular response to injury
Vasoconstriction
Process of leukocyte accumulation at the periphery of blood vessels
Margination
Molecules in endothelium and wbc responsible for rolling
P and E selectins on endothelium with Sialyl Lewis X on wbc
glycam 1, CD34 on endothelium with L selectin on leukocyte
Molecules responsible for adhesion
ICAM 1 on endothelium with CD 11/18 integrins in wbc
VCAM1 on endothelium with VLA 4 on wbc
Molecules in the endothelium responsible for transmigration (diapedesis)
PECAM 1/CD 31
What are the different chemoattractants?
Exogenous: bacterial products (N-formylmethionine, lipids)
Endogenous: IL 8, C5a, LTB4
Vasoactive amine that results in vasoconstriction; sources include platelets and neuroendocrine cells
Serotonin
Most abundant complement
C3
Anaphylatoxins
C3a, C4a, C5a
Anti inflammatory cytokines for regulation of the inflammatory response
Lipoxin, TGF beta, IL 10
Two kinds of cells seen in granulomas
Epithelioid cells (activated macrophages with pink, granular cytoplasm resembling epithelial cell) and giant cells
Tissue whose cells can readily regenerate as long as stem cells are preserved (bone marrow, vaginal epith)
Labile tissues
Cells are quiescent and have minimal replicative activity nirmally; capable of proliferating in response to injury or loss of tissue mass (smooth ms, endothelium, liver parenchyma)
Stable tissues
Cells of these tissues considered to be terminally differentiated and non proliferative in post natal life (neurons, cardiac muscle)
Permanent tissue
Type of repair in labile and stable tissues; influenced by growth factors
Regeneration
Type of repair in chronic, severe inflammation and in permanent tissues
Connective tissue deposition
Steps in healing by connective tissue deposition
Angiogenesis
Formation of granulation tissue
Remodeling of scar
Most notable growth factor in angiogenesis
VEGF
Most important cytokine for synthesis and deposition of connective tissue
TGF- beta
Pink, soft, granular tissue seen beneath the scab of a skin wound;HALLMARK of tissue healing, appears by 3-5 days
Granulation tissue
Histologic findings of granulation tissue
Proliferation of fibroblasts and new thin walled delicate capillaries in loose ECM, often with admixed inflammatory cells mainly macrophages
General morphologic appearance of edema
Clearing and separation of ECM, and subtle cell swelling
Characterized by alveolar capillaries engorged with blood with associated alveolar septal edema or focal minute intra alveolar hemorrhage
Acute pulmonary congestion
Pulmonary septa are thickened and fibrotic eith hemosiderin laden macrophages in alveolar spaces
Chronic pulmonary congestion
The central vein and sinusoids of the liver are distended with blood, with central hepatocyte degeneration; periportal hepatocytes are better oxygenated
Afute hepatic congestion
Central regions of the hepatic lobules are grossly red brown, sltly depressed and are accentuated against the surrounding zones of uncongested tan, sometimes fatty liver. (+) centrilobular necrosis with hepatocyte drop out, hge, and hemosiderin laden macrophages
Chronic hepatic congestion
Pathologic form of hemostasis
Thrombosis
Major contributor to the development of arterial thrombi
Turbulence or endothelial injury
Major contributor to development of venous thrombi
Stasis
Laminations composed of pale platelet and fibrin deposits alternating with darker red cell rich layers; Signifies formation of thrombus in flowing blood
Present in antemortem thrombus
Lines of zahn
Most common site of arterial thrombosis
Coronary > cerebral > femoral
Most common site of venous thrombosis
Superficial or deep veins of the leg
*thrombi in superficial leg veins rarely embolize
Deep leg thrombi are most common source of venous emboli
Most common and most dreaded sequelae of deep venous thrombosis
Pulmonary embolism
Embolus occluding a bifurcation in the pulmonary tree; associated with sudden death due to acute right sided heart failure
Saddle embolus
A venous embolus which entered the systemic circulation through an interartedial or interventricular defect
Paradoxical embolus
Microscopic fat globules found in circulation after fractures of long bones or after soft tissue trauma; can lead to pulmo insufficiency, neuro symptoms, anemia, and thrombocytopenia
Fat embolism
Gas bubbles within the circulation obstructing vascular flow and causes distal ischemic injury (decompression sickness- bends, chokes)
Air embolism
Most common lysosomal storage disorder; most common form is chronic. Type II (non neuropathic) is most severe
Microscopically: distended phagocytic cells in liver, spleen, BM, LN, tonsils, thymus and peyer patches, with fibrillary cytoplasm “crumpled tissue paper appearance”
Gaucher disease
Prominent occiput, mental retardation, micrognathia, low set ears, short neck, overlapping fingers, CHDs, renal malformation, limited hip abduction, rocker bottom feet
Trisomy 18 (Edward syndrome)
Microcephaly, microphthalmia, mental retardation, polydactyly, cardiac and renal defects, umbilical hernias, rocker bottom feet
Trisomy 13 (Patau syndrome)
Chromosome 22q11.2 deletion syndrome
DiGeorge syndrome (CATCH22) and velocardiofacial syndrome
Ch 22q11.2 deletion syndrome are at high risk for these disorders:
Schizophrenia and bipolar disorder
2 or more X chr, 1 or more Y chromosomes. Important cause of reduced spermatogenesis and male infertility.
Clinical feats: eunuchoid body, testicular atrophy, micropenis, absence of secondary sex characteristics etc
Klinefelter syndrome (most common 47XXY)
Complete or partial monosomy of X chromosome. Female hypogonadism in phenotypic females. Single most impt cause of primary amenorrhea
Clinical feats: ovarian streaks, absence of secondary sex characteristics, short, cystic hygroma of head and neck, preductal CoA
Turner syndrome
Property of trinucleotide repeat disorders where disease worsens with each successive generation
Anticipation
Most common cause of MR after downs syndrome. CGG expansion in FMR1 gene in X chromosome. Most distinctive feature is macro-orchidism
Fragile X syndrome
Autosomal dominant neurodegenerative disorder. CAG expansion on HTT gene on ch4p16.3. Relentlessly progressive and uniformly fatal
Huntington disease
Diseases featuring maternal inheritance, usually a fundamental defect is abnormality in the electron transport chain
Mitochondrial disorders
Ex. MELAS, leber hereditary optic neuropathy
Deletion in paternally derived ch 15q11.2q13. Clinical feats include MR, hypotonia, profound hyperphagia, obesity, small hands and feet, hypogonadism
Prader-Willi syndrome
Deletion in maternal ch15q12. Clinical feats include MR, ataxic gait, seizure, and inappropriate laughter “happy puppet”
Angelman syndrome
Autoantibodies associated with congenital heart block in neonatal lupus
Anti-Ro, anti-La
Histopath finding in SLE with skin involvement
LM: liquefactive degeneration of basal layer, edema at DEJ, mononuclear infiltrates around bld vessels and skin appendages
IF: deposition of Ig and complement in DEJ
Clinicopathologic entity with a triad of dry eyes, dry mouth and other manifestations such as arthritis
Sjogren syndrome
Triad of chronic inflammation, widespread damage to small blood vessels, and progressive interstitial and perivascular fibrosis in the skin and multiple organs
Systemic sclerosis
Most common autoantibody associated with diffuse cutaneous systemic sclerosis
Anti-DNA topoisomerase I (anti-Scl 70)
Common autoantibody associated with limited scleroderma
Anti-centromere antibodies
Most common antibody associated with scleroderma renal crisis
Anti-RNA pol III
Most common extracutaneous manifestation of systemic sclerosis
Raynauds phenomena
Most common cause of death in patients with systemic sclerosis
Interstitial lung disease and pulmonary arterial hypertension
Complication of hematopoietic stem cell transplantation where immunologically competent cells attack the tissues of immunocompromised host
Graft vs host disease
Primary immune deficiency characterized by absent or markedly decreased number of B cells in circulation. Depressed serum levels of all immunoglobulin
X-linked agammaglobulinemia (Bruton disease)
Cardinal features of thymic hypoplasia
CATCH22 Cardiac defect (TOF) Abnormal facies Thymic aplasia Cleft palate Hypocalcemia
Disorder of lymphocyte activation. Absence of CD40L (CD145) resulting in lack of class switching. Increase in IgM and decrease in IgA, IgG, and IgE
Hyper IgM syndrome
X linked recessive disease characterized by thrombocytopenia, eczema, and marked vulnerability to recurrent infection resulting in early death
Wiskott-Aldrich syndrome
Hereditary angioedema
C1 inhibitor deficiency
Deficiency of this causes increased susceptibility to pyogenic bact inf
C3
Deficiency increases susceptibility to immune complex mediated disease
C1q, C2, and C4
Deficiency increases susceptibility to Neisseria infections
C5-C9
