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Disease/Syndrome

Parathytroid Primary Hyperparathyroidism Secondary Hyperparathyroidism Tertiary Hyperparathyroidism

Manifestation
excess PTH, Adenoma causes 80% of 1 hypocalcemic stim of PTH; cell proliferation Autonomous 1 hyperparathyroidism c preexisting hyperparathyroidism v rare, neck mass; c bone dz; 30% metastases; carcinoma invades normal structures

Lab Tests

PTH PTH; Ca++

PTH

Carcinoma

High Ca++

Adrenal
Cortex Hypoadrenalism Addison's Dz (Primary Chronic insufficiency) Elevated ACTH; elevated eosinophils; autoimmune; HA, nausea, vomiting, low Na+; high K+, Ca++; Cosyntropin abdominal pain, diarrhea, fever, Stimulation Test (0.25mg synthetic hypotension, hypoglycemia; anorexia ACTH, 30 mins then draw blood, c weight loss; unusually tan skin; serum cortisol should rise to Primary Acute insufficiency "crave salt" 20mcg/dl); (usually Addison's "crisis") Lack of ACTH; Still able to secrete gluccocorticoids, but no Secondary Adrenal mineralcorticoids;hypotension; Insufficiency hyponatremia; weight loss Cosyntropin Stimulation Test Hyperadrenalism low plasma renin, hypokalemia, hypernatremia, alkalosis, Hyperaldosteronism hypertension, muscle weakness, Ratio of Aldosterone: Renin; K+, (Conn's Syndrome) poluuria, polydipsia HCO3-

Central obesity, "moon" face, buffalo Hypercortisolism (Cushing's hump, supraclavicular fat pads, thin Dz or Syndrome) extremities. Adrenal virilisation; adrenal feminization (rare); hirsutism; Hypersecretion of sex menstral irregularities; hypertension steroids (rare); May secrete aldosterone, cortisol, or Adenoma sex steroids

Elevated or low ACTH; High Cortisol; low K+; Cosyntropin Stim Test Serum adrogen; testosterone levels; FSH; LH; Cosyntopin Stimulation Test; Aldosterone; cortisol; testosterone; estrogen

Carcinoma

functional or not; poor prognosis

cortisol

Medulla 5 Ps: Pallor, Palpitations (Epi & NE), Perspiration(epi & NE); Pain (Abd cramping); Pressure (HTN); Rule of 10's: 10% Familial; 10% malignant: 10 bilateral; 10% ectopic; 10% metastasize (vasoconstriction) Usually seen in children, rare in adults, usually arises in adrenals

Pheochromocytoma

Neuroblastoma

T3, T4, TSH, epi, NE UA, increased urinary homovanillic acid, vanillylmandelic acid, DA, metanephrine

Pancreas
Insulinoma: B-cell insulin producing tumor Gastrinoma: ZollingerEllison Syndrome Neoplasia Syndromes neoplasias or hyperplasias of Parathyroid, cortex, pituitary, MEN-I pancreas c peptic ulcers Pheochomocytomas, medullary carcinoma of thyroid, parathyroid MEN-Iia (Sipple Syndrome) hyperplasia or adenoma MENIIb Same as Iia s parathyroid abnormality most common, produces insulin gastrin-secreting pancreatic tumor, may be in duodenum; present c multiple peptic ulcers C-peptide & pro-insulin will be elevated; FPG

Gross

Microscopic

Adenoma> 100g; hyperplasia=all 4 glands; adenoma=1 gland; reddish brown solitary mass

encapsulated proliferation of chief cells; sheets of neoplastic cief cells

invasive, lobulated, firm, hard tannish, unencapsulated masses

Trabecular pattern, fibrosous bands, mitotic figs, blood vessel invasion

small adrenals c decreased cortex

bilateral, diffuse (75%; cortex is grossly visible, yellow, inner brown layer) or nodular (25%; visible nodules>2.5cm) hyperplasia of the adrenal glands.

packed with lipids

solitary, small, bright yellow, encapsulated

large, soft tumor with variegated cut surface c hemorrhage & necrosis, invasive

abundant eosinophilic or clear cytoplasm; well-diff or pleomorphic

solid ovoid mass < 5cm

sheets of clusters of pleomorphic cells sheets of small cells resembling neuroblasts, dense nuclei, scant cyto

soft, friable tumor, calcification

vary in size, some v small, grow slowly

Tx

Notes

Remonve only enough so pt is euparathyroid

Frequently the result of chronic renal failure

en bloc resection; poor prognosis; death from high Ca++

Acute: hydrocortisone and saline immediately; ABX to prevent bacterial infection; Chronic: Hydrocotisone, daily; Fludrocortisone acetate, daily; DHEA;

1Adrenal Insufficency - gluccocorticoids affected>mineralcorticoids; 2Adrenal Insufficency - mineral>glucco. Addison's "crisis"; rapid withdrawal of hormones; massive hemorrhagic destruction; Waterhouse-Friderichsen

Mineralcorticoids

adrenalectomy

good prognosis, esp if detected early

Transphenoidal surgery to remove pit tumor c hydrocortisone or prednisone therapy to compensate for loss; radiosurgery for Nelson's syndrome; 65% from pituitary Cushing's; 20% from laproscopic for adrenals; ectopics are adrenal Cushing's; 10% ectopic ptorduction; surgically resected; iatrogenic Cushing's OCPs, if appropriate; bilateral adrenalextromy; spironolactone; metformin;

Surgical removal - but micrometastases usually occurs.

Distinguishing from adenoma - larger, pleomorphism, high mitotic rate, atypical mitosis, venous invasion, necrosis, capsular invasion; poor prognosis c 1-3 y survival.

surgical removal May differentiate into gangliobeuroblastoma or ganglioneuroma

removal

10% malignant

65% malignant

Disease/Syndrome

Manifestation

Lab Tests

Grave's Dz (Hyperthyroidism)

Hypothyroidism/Myxedma Thryoiditis

Autoimmune (IgG abx) & may be assoc c other immune disorders; weight loss c increased appetite, exopthalmos, tremor, anxiety, sweating, tachycardia. Young>Old; Females>Males TSH; Serum T3, T4; TSH-R Ab; low energy, weight gain, pathological depression, constipation, lethargy, dry cool skin, dulled reflexes TSH; Serum T3, T4; TSH-R Ab;

Hashimoto's Thyroiditis

Abx from T-cells and B-cells to microsomal peroxidase, TGB, or TSH TSH; Serum T3, T4; TPO-Ab, receptors; hypothyroid symptoms, TGB-Ab, TSH-R Ab; trauma, or secondary to hematogenous

Acute/Subacute Thyroiditis Neoplasias

TSH; Serum T3, T4; TSH-R Ab;

Papillary Carcinoma

most common malignancy (70-90%)

Follicular Adenoma

most common neoplasm seen, usually B9, 4th-5th decade of life uncommon, <15% of malignancies, spreads along blood supply and not lymph 10% of malignancies, large and aggressive 5% of malignancies, sporadic, 20% familial; MEN2A or 2B <2% of malignancies

Follicular Carcinoma Anaplastic Carcinoma Medullary Carcinoma Lymphoma

biopsy dx via calcitonin levels

Gross

Microscopic

Tx
Propanolol for immediate symptom relief; Thiourea drugs (mehimazole, PTU) to prepare for irradiation; radioactive I; Surgical removal

diffusely enlarged, firm thryoid diffusely enlarged, somewhat nodular

hyperplastic c tall, columnar cells; scalloping and tufting lymphoplastic infiltrate; atrophic follicles, fibrosis, oxiphilic metaplasia

L-thyroxine

diffusely enlarged, somewhat nodular; years later = atrophy

lymphocyctic infiltration, atrophic follicles, fibrosis, metaplasia L-thyroxine lymphocytes, giant cells, and granulomas surround damaged Propanolol for symptoms until follicles euthyroid again.

single thyroid mass, can be multifocal, white, firm, gritty mass

papillae c fibrovascular cores, psammoma bodies, defined by nuclear features: overlap, central clearing, nuc enlargement uniformly sized follicles, no vascular invasion or extracapsular sim to follicular adenomas, papillary features (i.e. nuclear) sheets of bizarre cells, atypia, hard to identify amyloid

single, well defined mass, encapsulated, widely/minimally invasive; infiltrative, blood vessels and/or extra-capsular extension aggressive, infiltrative, large superior thyroid, multicentric, grey/white somewhat circumscribed

Notes

Good prognosis

Prognosis: widely invasive (50% metastases) minimally invasive (3%) Fatal: 6 months after dx Prognosis: 50% @ 5ys

Genes
Ras (H, K variants) c-src

Normal Function
A GTPase in transduction pathway A tyrosine kinase that conveys growth stim signals

Mutations/Mechanisms
usually missense mutation in codon 12, 13, or 61 C-terminal mutation gene is translocated from chrm 18 to chrm 14 (t14; 18) near IgG enhancer region translocation (t8; 14), (t2; 8), or (t8; 22)

bcl-2

inhibits apoptosis activates genes involved in cell replication

Ig-myc, c-myc, N-myc

BCR-ABL

encodes a tyrosine kinase

translocation (t9; 22)

her2/neu/c-erb-B2

encodes a growth factor receptor Encode cell regulatory proteins (transcription factors); tumor suppresor; forms dimers then tetramers which bind to DNA, induce genes for apoptosis or repair. Low DNA damage = repair; High DNA damage = apoptosis.

gene amplification of receptor

p53 "guardian of the genome"

pRB

Encode cell regulatory proteins; tumor suppresor tumor suppressor protein expressed in retina; regulates cell cycle cyclin dependent kinase, prevents ~P of RB protein. Blocks cell progression in cell cycle "caretaker genes" blocks cell progression

inactivated in a number of ways: ~HPV E6 inactivates p53 ~Point mutation ~Gene deletion ~Epigenetic silencing inactivated in a number of ways: ~HPV E7 inactivates RB ~Intragenic mutation ~Gene deletion ~Epigenetic silencing hereditary mutation or nonhereditary mutation inactivated in many carcinomas and melanoma inactivation mutations lead to missense mutations during DNA replication = oncogene activation & tumor suppresor inactivation Failure leads to microstelite instability (MSI)

RB1 (Retinoblastoma)

CDKN2 p16

Nucleotide excision repair of UV damage; DNA base dimers; multiNER Genes (7 groups) step pathway MMR Gene Family (MLH1, MSH2, Mismatch repair of DNA damage; MSH6, PMS1, PMS2) replaces correct base pair

APC

MEN2a/MEN2b/RET

hereditary (auto dom) and de tumor suppressor gene on chrom 5 novo mutations = inactivation menin tumor suppressor gene; RET TKR gene; a group of disorders; Multiple Endocrine Neoplasias; B9 auto dom inheritance; point and malignant mutation on RET oncogene

BRCA1/BRCA2

tumor suppressor genes on chrm 17 unable to repair and 13, involved in DNA repair mutations/damage to DNA

Viruses
HPV EBV HTLV causes condylomas, verrucae in humans Virus integrates into DNA

Result
RAS-GTPase remains active and MAP kinase goes unregulated increased cell proliferation Highly active, un-inhibited, kinase overexpression of bcl-2 and prevention of apoptosis lymphoma high transcription levels of myc & cell replication; Burkitt's Lymphoma Translocation results in a fusion protein (BCR & ABL) and deregulation of ABL kinase activity; activation of many signal trans pathways; cell proliferation; Chronic myeloid leukemia (CML), Acute myeloid leukemia (AML)

Notes
mutation seen in many cancers Kinases are druggable, so many new drug tx usually mimc ATP

double minute chromosomes appear in karyotypes: 100s of copies of N-myc gene = overexpression = cell proliferation

"Philadelphia Chromosome"; imatinib (Gleevec) helps "blast crisis" howev relapse is common in CML (result of 2 mutation); Diff bt CML & AML is breakage point before translocation `~Double minute chromatin bodies; seen in 20% od Breast CA; ~Tx: anti-Her2 monoclonal Ab (Herceptin), 15% increase clinical response, longer survival increased cell replication and tumorigenicity rate Most commonly mutated gene in human CA. Normal cells contain 2 copies of regulatory gene. Both need to be inactivated = cancer phenotype. Not usually detected in a ~HPV E6: dysreg of cell cycle checkpoints, cell bc short half life. Inactive p53 = longer increased cell replication half life = CA & present on stains.

~HPV E7: dysreg of cell cycle checkpoints, increased cell replication tumor growth during replication phase of retinal cells; occurs before 5ys of age "caretaker genes" inactivated and allows other mutations to accum = CA "caretaker genes" inactivated and allows other mutations to accum = CA "Two-hit" Model: if inherited mutation then greater susceptibility for tumor growth

often involved in hereditary CA

UV damage is not corrected = increased risk of skin CA & melanomas 10-15% of all tumors have MSI; 95% of HNPCC tumors have MSI

Xeroderma pigmentosum (XP); Familial inheritance of CA HNPCC - hereditary non-polyposis colon cancer

increased polyp fomration in colon, with increased risk of extra-colic tumors; 100% risk of CA if untreated

Familal Adenomatous Polyposis (FAP)

Medullary thyroid cancer, pheochromocytoma, increased risk of developing breast cancer at early age; also increased risk of ovarian, fallopian, colon, pancrease and (in men) prophylactic oophoroectomy and prostate cancer salpingectomy should be discussed

Low grade dysplasia - Additional genetic hits - high grade dysplasia - additional genetic hits - carcinoma

HPV 6 & 11 are low risk for CA; HPV 16 & 18 are strongly assoc w SCC of the cervix

Gross Appearance
Penis
Congenital Abnormalities Hypospadias Epispadias Phimosis Urethra open on ventral side urethra open on dorsal side Foreskin cannot be retracted Medical emergency; foreskin retracted but unable to return to normal position; can result in infarct and tissue damage B9 fibrosis tissue results in curvature of penis; pain during sex Persistent erection

Paraphimosis Peyronie's Disease Pripism Neoplasms

Condyloma accumination wart-like growths Carcinoma in situ (a.k.a. Bowen's Dz or erythroplasia of Queyrat) pink-red velvety plaques

Squamous Cell Carcinoma

slowly growing, redish cauliflower-like growths

Testis
Congenital Abnormalities failure of the testis to descend; 4% of newborn boys; testis twist on it's cord causing venous occlusion; excruciating pain

Cryptorchidism Testicular torsion

Vaicocele Hydrocele Hernia Spermatocele Neoplasms Germ cell tumors

enlargement of venous vascular plexus fluid accum bt visceral and parietal layers; scrotal mass; often B9; abdominal contents in inguinal canal; painful; bowel infarct possible; cystic dilation of epididymis

B9; in situ; late adolescence, ealry adulthood; usually midline locations

Seminoma

yellow to tan tumors w little necrosis

Embryonal carcinoma

Yolk sac tumor

hemorrhagic or necrotic resembles fetal yolk sac (Schiller-Duval bodies look like glomerulus) mixed with other germ cell tumors two or more germ cell layers (ex mesoderm, endoderm, ectoderm)

Teratomas

Choriocarcinomas

placental like appearance mixtures of germ cells often seen in primary tumor

Mixed germ cell tumors

Prostate
Congenital abnormalities Stenotic urethral valve child only dribbles urine - no forceful stream

Nodular hyperplasia

affects central portion of prostate w acute presentation of urine retention

Adenocarcinoma

develops in the peripheral zone; firm nodule palpated rectally;

Histo

Tx

complete disorganization of the epithelium w enlarged hyperchromatic nuclei and atypical mitotc figures

full thickness squamous epithelial atypia, but no stromal invasion

Histo determines the type of tumor

uniform sheets of udifferentiated germ cells surrounded by lympoid infiltrate Radiation is not as effective; pleomorphic; form glands, tubules, and even chemotherapeutic agents are more primitive embryo-like structures effective

cells may mimic adult tissues (Mature) or fetal tissues (Immature) cytotrophoblasts and syncytotrophoblasts must be present

newer forms of chemo are effective respond v well to chemotheraopy when caught early; but still a high mortality rate

hyperplasia of cells

treated with drugs that inhibit 5alphareductase

histological presentation determines grading no good therapy bc many pts level of the cancer present too late

Notes

HPV 6 & 11 causes B9 lesions; HPV 16 &18 are higher risk for developing CA almost all are uncircumsized; bacteria proliferate and their waste is carcinogenic; HPV 16 & 18 carcinogenic virus; accumulated detritis beneath foreskin = carcinogenic; 90-95% 5 year survival; drops to 50% if there is lymph node involvement; 20% have lymph node involvement

failure of spermatogenesis and increased risk for germ cell testicular tumors

assoc w infertility bc increase blood flow = increase temp = decreased spermatogenesis

usually 4th or 5th decade of life; highly sensitive to radiation; 9095% 5 year survival; scattered syncytiotrophoblastic cells may secrete hCG. 95+% cure rate; metastasize via lymph and vessels; more aggressive than seminoma & often presents at a later stage produce alpha-fetoprotein and used as a marker for dz progression in children = B9; in postpubertal males = treated as having malignant potential secretes large amounts of hCG; usually fatal. prognosis depends on the cells present (ex choriocarcinoma = fatal, seminoma = 95% survival)

can lead to hydronephrosis and renal failure "normal" phenomena; seen in 95% of males over the age of 70; due to an imbalance bt estrogen and testosterone; PSA is a good marker & Prostatic acid phosphatase is typically elevated; detection has gotten better, but survival rates have not.

Gross Appearance
Benign Epidermal Tumors Seborrheic Keratosis Skin Tags Epidermal Cyst "stuck on" scaly brown/tan papules of varying sizes small, soft, flesh colored papules bumps, sometimes painful, underneath the epidermis elevated, dome-shaped nodule with a central keratin crater. Fast growing, slowly heals and leaves a scar wide variety of tumors involving: sweat glands, sebaceous glands, and follicular origins flat brown to black pigmented spots; mostly in older indiciduals in sun-damaged skin lightly pigmented look like large freckles; normal skin texture rarely present at birth, macules, papules, or dome-shaped tumors anywhere on skin; small size, circumscription, and uniform color

Keratoacanthoma

Adnexal Tumors

Lentigo Freckle (ephelis) Caf Au Lait

Melanocytic Nevi Junctional Nevi Compound Nevi Intradermal Nevi Spindle (Spitz) Nevi

Blue Nevi

Congenital Nevi Premalignant & Malignant Tumors

most occur in children, but some occur in adults deep blue or black lesion, most commonly seen on the bum, dorsum of the hands, feet, face rarely, at birth, small to "giant" brown to black nevi involveing a large segment of the body

Actinic Keratosis

small, scaly papules or patches on sunexposed surfaces well defined scaly plaque anywhere on the skin (sun exposed or not) Scaly,crusted papules or nodules

Bowen's Dz Squamous Cell Carcinoma

Basal Cell Carcinoma

pearly, translucent papule or nodule with surface telangectasia and often a central ulceration

anywhere on skin; rare in prepubertal children, infrequent in teens; 20s-50s increased incidence; large than nevi; irregular borders; variations in color (black, brown, blue, tan, pink, red, white); usu Malignant Melanoma accomp by changes in appearance 70% of all MM; flat pigmented patchy, Superficial spreading malignant assortment of colors & if verticle growth = melanoma nodular slowly growing, flat, tan-brown lesion, often Lentigo maliga melanoma sev cm in size, sun-exposed areas

Nodular malignant melanoma 10-15% of MM least common of all MM; most common MM in darker skinned pts; usually on palms, soles, subungually, or mucous membranes; macules w irregular borders Acral lentiginous melanoma and varying color

Tumors of the Dermis Dermatofibroma common on extremities: firm, intradermal nodules flesh colored mass of variably size; capillaries open and blood russhes in turning the mass red or purple rapidly evolving, pedunculated, red-purple tumor that occurs on skin or mucous membranes; bleeds easily one or multiple red to purple papules and patches

Infantile capillary hemangioma Lobular capillary hemangioma (Pyogenic Granuloma) Kaposi's Sarcoma

Lymphoid Infiltrates

B9 reactive processes that produce papules, nodules, or plaques

Mycosis Fungoides Inflammatory Skin Dz Dermatitis Allergic Contact Dermatitis

subtle erythematous patches that resemble dermatitis

eczema, erythema, scaling of the skin erythema, blistering, extremely pruritic, persists for 3 weeks

Atopic Dermatitis

spongiotic dermatits, erythemous open and closed comedones; inflammation of hair follicules usually due to infection palpable purpura sometimes w plaques or nodules; often lower extremities eruption of macules, papules, vessicles or bullae and my be triggered by virus (i.e. Herpes), infection or drugs superficial bacterial infection caused by staph. Aureus or strepto. Pyogenes; erythemous papules progress to blisters and pustules; then "honey-colored" crusts STD (Treponema pallidum); three stages: 1. Primary lesion (chancre): painless, elevated border, resolves on its own. 2. Secondary stage: wart-like lesions on genitals w maculopapular eruption on palms and soles; 3. Tertiary syphilis: endarteritis, ischemia which cause disorders of the CNS and aorta; gumma = nodular or ulcerative lesion at this stage. HPV, papules w irregular, papillated surfaces; single or multiple; verrucae vulgaris: commonest, hand warts; verrucae plantaris: flattened, callous-like warts on soles; verrucae plana: flattened warts, anywhere; condyloma acumination: warts in the anogenital region; flesh-colored, dome-shaped papules found in multiples caused by the poxvirus family blisters, sometimes grouped, on an erythemous base; "fever blisters" around mouth; anogenital lesions; Zoster - lesions along a dermatome Tinea capitis (head), cruris (groin), pedis (foot): red, scaly, arcuate patches; capitis may include hair loss; Tinea versicolor: white, scaly patches on trunk; Candida albicans: similar to cruris, but w papules and pustules; Candida: diaper dermatitis; Sarcoptes scabiei: arthropod burrows into stratum corneum, lays eggs

Folliculits

Vasculitis

Erythema Multiforme

Impetigo

Syphilis

Wart (Verrucae)

Molluscum

Herpes

Superficial Fungal Infections

Scabies

Histo

Tx

papillomatosus or plaque-like proliferation of orderly, mature epidermal cells. Excision or LN2 core of reticular dermal collagen covered by normal (or sometimes papillomatous, SK-like) epidermis Snipped off lined by epidermis and filled with keratin florid downgrowth of squamous epithelium that forms a cup, which fills with keratin

depends on origin

increased number of melanocytes in basal layer normal number of melanocytes in basal layer w increased function or melanin production

unifrom small, cyto bland, rounded melanocytes arranged in discrete nests and strands melanocytes between the dermal-epidermal junction occupy the junction as well as the dermis limited to dermis nests of lare spindle epitheliod melanocytes collections of pigmented dendritic melanocytes in dermis

if atypical = excise/bx monitor for changes, Bx when they occur monitor for changes, Bx when they occur monitor for changes, Bx when they occur

monitor for changes, nodules, etc

epidermal proliferation and cytologic atypicality of keratinocytes, especially those near the basilar layer; thickened keratin layer; dermis - basophilic fibers = sun damage; LN2

full thickness epidermal atypia proliferation of atypical, eosinophilic, squamoid epithelium with varying degrees of keratin

Complete excision complete sxcision

nodular proliferation of atypical basal cells with peripheral palisading and retaction from the adjacent dermis

Complete excision

Onset: abnormal proliferation of melanocytes, may extend to the dermis - host usually keeps it contained to dermis initially; Radial growth phase: small groups of cells form aggregate nodules in dermis w net growth in radial direction; Vertical growth phase: expands and fills the dermis = ultimately invading deeper; Fully developed MM: nests & atypical melanocytes at dermal-epidermal jxn, variable sizes, extend into dermis Removed in toto; Excision, & form nests, nodules, and sheets, mitotic figs; punch biopsy long radial growth phase before entering vertical growth phase radial growth phase lasts 10-40 years before vertical phase develops very short radial growth phase; extensive vertical growth phase = nodular; very little lateral spread, so small epidermis component

radial growth phase > nodular MM; vertical growth phase = nodular component of lesion

proliferation of fibroblasts and histiocytes (macrophages) = scar sheets of closely packed capillaries that form large nodules with "pushing margins

local excision nothing - usually disapper by mid-childhood

lobular arrangement of capillaries that can be obscured by ulceration, edema, or inflammation removal/excision erythrocytes occupy distinct narrow slits bt individual spindle cells irradiation; excision

mixed cell population of small and large lymphocytes; germinal centers, eosinophils, plasma cells, giant cells band-like infiltrate in the superficial dermis composed of atypical lymphoid cells with hyperchromatic nuclei showing folded nuclear contours evolves over years, no tx

superficial dermis: infiltration of lymphocytes epidermis: widening of spaces bt keratinocytes due to edema; if severe, corticosteroid lotion exudation of plasma proteins

superficial dermis: infiltration of lymphocytes epidermis: widening of spaces bt keratinocytes due to edema; if severe, corticosteroid lotion exudation of plasma proteins superficial portion of follicle is dilated. Neutrophils may infiltrate the follicular lumen; walls may rupture neutrophils infiltrate vessel walls, enodthelial swelling, erythrocyte extravasion, sometimes thrombitic occlutsion of the vessel, and fibrin deposit Three major micro findings: 1. vacular degeneration of basilar layer; 2. formation of eosinophilic/apoptotic bodies @ epidermis/dermal border; 3. perivascular lymphocytic infiltrate aggregates of neutrophils at the epidermal surface; subcorneal pustules (bt stratum corneum and epidermis)

Acne meds, Abx

varying degrees of inflammation involving dermis; plasma cells in the infiltrate; endarteritis obliterans turning more granulomatous. Spriochetes in primary and secondary.

hyperkeratosis, papillomatosis, acanthosis (epidermal hyperplasia); koilocytes, keratinocytes w pyknotic nuclei & surrounding clear halos LN2, excision flask-shaped invagination of epidermis; molluscum bodies: eosinophilic globules w vacuolization intraepidermal blistering; infected keratinocytes = multinucleated; nuclei have a "gun metal" gray appearance

removal

sim to spongiotic dermatitis; hyphae and pseudohyphae KOH to diagnose; -azoles to identifiable in the stratum corneum treat adult mites, eggs, fecal material in stratum corneum; dermis: perivascular and interstitial infiltration of lymphocytes and eosinophils

Notes
Sometimes Bx to R/O Malignancy aka: fibroepithelial polps or acrochordons aka: sebacous cyst

DiffDx: SCC syringoma: sweat gland tumor; trichoepithelioma: follicular origin Peutz-Jeghers syndrome = multiple lentigos on hands and feet.

> 6 @ 1.5cm or more is indicative of Neurofibromatosis (esp Type I)

can be misdiagnosed as malign melanoma

risk for developing malign melanoma; may even be present at birth

Most SCC arise from Aks precancerous dermatosis; once invasive (5% of cases) metastic rate is ~ 40%; possibly related to HPV (16 & 18) Aks = precursor for SCC; 10-40% metastases rate, conditionally;

Most common skin malignancy; Grows relentlessly if not excised completely; v low risk of metastases;

In US: 1 in 90; 80% 5-year survival rate; increasing lattitude = decreasing risk of skin CA; thickness = indicator of prognosis; MM < 0.75mm almost never metastasize; MM > 4.0mm = 60% metastasize; In bt = intermediate risk for metastasis; women have better survival rate than men; MM on extremities have better prognosis than other sites

usually middle aged or elderly pts

rarely recur

treated if they compromise another fxn (ex sight)

Assoc w AIDS pts; Red patch that Tom Hanks had in Philadelphia Leukemias and lymphomas produce monomorphic, cytologically atypical dermalsubcutaneous infiltrates with diffuse, destructuve patterns

linear blisters or erythema are indicitive of plant allergen contact

Ex: acne vulgaris

neutrophil accum = pustules; TEN (toxic epidermal necrolysis) can occur in severe cases = full thickness loss of the epidermis; pt treated in burn unit.

Possible Complication: poststreptococcal glomerulonephritis

relationship bt HPV & cervical cancer

common in children, may also be STD

HSV Types 1 & 2 and Varicella-zoster

highly transmissable from person to person; itching is intense

Gross/Clinical Appearance
Inflammatory & Infections Dz

Non-infectious Cervicitis

Chlamydia trachomatis

chemical or mechanical irritationa mucopurulent discharge, partner may have urethritis; Complications: endometritis, salpingitis, PID, tubal infertility, neonate pneumonia

Herpes Simplex Virus 2 (HSV2) Vulvar Lesions Vulvar Cysts

non-painful vesicles and painful shallow ulcerations on the anus, urethra, bladder, vagina, vulva, cervix

hard palpatable mass post-menopausal white, scaly changes of the Lichen sclerosis et atrophicus vulva; painful; wax paper appearance

Padget's Dz

post-menopausal red, eczematous w irregular borders, slowly progressive dz

Melanoma Vaginal Lesions Clear cell carcinoma Embyronal Rhabdomyosarcoma Cervical Lesions

women in 60s - 70s pigmented or nonpigmented plaque or mass

adolescents clear, cyst like appearance children: Botryoides (grape-like), several protruding from the vagina, could also be in bladder

Endocervical polyp

polypoid growth projecting from external cervix os

Adenocarcinoma in situ For SCC & HPV - see class notes. Uterus Corpus

arise in the transformation zone

Acute Endometritis Chronic Endometritis

fever, chills, pelvic pain irregular bleeding,possible fever, chills, pelvic pain

Endometrial polyps

irregular bleeding Perimenopausal women; proliferation of glands, irregular bleeding

Endometrial hyperplasia Endometrial Adenocarcinoma

Endometroid = hyperplasia; 75% postmenopausal (ave age:63); obese + chronic anovulation = excess estrogen; Endometrioid irregular bleeding; UPSC tends to occur in eldery women and in the setting of atrophy; UPSC present at a higher stage and are much more aggressive Uterine Papillary Serous than Endometrioid CA; present w abnormal Carcinoma (UPSC) bleeding

Leiomyomas

25% Premenopausal; irregular bleeding, pelvic, pain, infertility; can get extremely large rare, malignant, sim to leiomyomas but with foci of hemorrhage and necrosis

Leiomyosarcomas

Malignant Mixed Mullerian Tumor (MMMT) Molar Pregnancy

Characteristic presentation: Elderly women, polypoid mass, prtoruding through cervical canal

empty egg fertilized by two sperm; abnormal Complete hydatidiform mole villi, no fetal tissue one egg fertilized by two sperm; abnormal and Incomplete hydatidiform mole normal villi, some fetal tissue Fallopian Tube Acute alpingitis (PID) Ectopic Pregnancies result of infection (gonorrhea, chlamydia, mycoplasma, E.coli); abcess and scarring zygote implants in tube instead of endometrium;

Endometriosis Fallopian Tube Carcinoma Ovary Non-neoplastic cysts "Functional cysts"

endometrial glands and stroma outside of the endometrium; commonly on the fallopian tubes, ovaries, pelvic/abd cavity. resemble serous papillary carcinoma of ovary

Exaggerated follicle; large enough to secrete estrogen; endometrial hyperplasia and Follicular cysts abnormal bleeding a corpus leuteum that does not regress to a corpus albicans; result = cyst that secretes progesterone = menstrual abnormalities +/Leuteal cysts mass Neoplasms Surface Epithelial **Serous papillary

Most common; Range from B9 cystadenomas - borderline - malignant/carcinoma; 5 subtypes: S

single or multiple smooth walled cysts; 15-20% Serous cystadenomas bilateral multicystic, lined by papillary excrescences; 30Serous papillary borderline 40% bilateral

more cystic and solid than borderline tumors; Serous Carcinoma 70% bilateral **Mucinous Columnar cells filled w mucin - viscous, Mucinous cystadenoma Mucinous Borderline gelatinous fluid; less frequently seen and less Mucinous Carcinoma often bilateral; Can become extremely large;

Endometrioid presence of endometrial glands Brenner islands or urothelial/transitional cells Clear Cell extremely rare Account for 15% of ovarian tumors; most Germ Cell common in children & adolescents B9; all age groups; cysts filled w hair, sebum, Mature Teratomas teeth Immature Teratomas Malignant; solid component Dysgerminoma 20s and 30s; unilateral

adolescents, young women; aggressive & Yolk sac Tumor malignant Embryonal carcinoma malignant, aggressive, young women Malignant; most occur in uterus, but some in Chroiocarcinoma ovaries Sex-cord stromal <10% of ovarian tumors; peri- and post-menopausal women; unilateral secretes hormones: p

80% of SCST; B9; irregular or postmenopausal bleeding; well cirumscribed Fibroma masses w solid, whit cut surface Granulosa cell tumor Malignant

Histo
non-specific inflam infiltrate: acute (neutrophils) or chronic (plasma cells, lymphocytes)

Tx

follucular cervicitis; Dx confirmed by IMF or IHC Three Stages: 1. glassy nuclei, chromatin pushed to periphery; 2. Prominent nuclear inclusion; 3. 3M's (multinucleation, margination of chromatin, and molding of nuclei); anti-virals

Bartholin's gland clogged, and still producing mucus = cyst Bx thin epithelium w stromal band; older lesions have sig fibrosis intraepithelial proliferation of malignant glandular-like cells; bt squamous cellsand stroma - but rarely invade stromal cells nests of cells infiltrating the dermis and single cells percolatin gup through the dermis Excision

glands composed of clear cells that "hobnail" or nuclei are point outward round nucleus and a belly of eosinophilic cyto.

Chemo if metastases

overgrowth of stroma, covered by thinner layer of endocervical epithelium loss of cyto mucin, nuclear enlargement, hyperchromatic and mitotically active nuclei

focal aggregates of neutrophils in stroma (microabscesses) and neutrophils disrupting and filling gland lumens infiltrate of plasma cells and lymphocytes cystically dilated glands, fibrotic stroma, and thick-walled blood vessels simple or complex, with or without cytological atypia

High N:C ratio; Tumor grade and stage based on depth of myometrial invasion and number of lymph node involvement

Hysterectomy

well-circumscribed, spherical mass, dense, whorled, tan-white; interlacing bundles of smooth muscle cytological atypia, mitotic activity, and necrosis mix of adenocarcinoma, malignant mesenchymal (such as leiomyosarcoma, rhabdomyosarcoma, osteosracoma, stromal sarcoma)

46XY or 46XX; villi are markedly enlarged, trophoblastic proliferation 69XY or 69XX;

secretes B-hCG

etiology: "backwash" from endometrium up & out of tubes; B9 metastasis spread of endometrium; metaplastic transformation of epithelial surfaces; "powder burns" on ovaries

tadenomas - borderline - malignant/carcinoma; 5 subtypes: Serous papillary, Mucinous, Endometrioid, Brenner, Clear Cell ciliated columnar cells single layer of simple ciliated columnar cells complex papillae lined by more atypical cells than cystadenoma

often resembles borderline but also + stromal invasion cysts lined by simple layer of mucinous cells complex and proliferative stromal invasion

gland fusion and cytologic atypia nests of cells w oval, bland nuclei clear cytoplasm, papillare are lined by "hobnail" nuclei; stromal invasion

adult tissue from germ layers some or all fetal tissure - usually neural secrete B-hCG (marker)

Schiller Duvall bodies, resemble yolk sac secrete a-fetal protein atypical, mitotically active cells cytotrophoblasts and syncytiotrophoblasts Produce B-hCG post-menopausal women; unilateral secretes hormones: progesterone & estrogen

bland spindle cells nuclear grooves, resemble coffee beans

may secrete estrogen 75% secrete estrogen (= abnormal, post-menopausal bleeding)

Notes
Chemicals: douche, spermacide; Mechanical: sex, tampons; Often asymptomatic

Most common STD in W. Hemisphere

risk of mother to baby transmission if mother has active lesions; C-section preferred

Can mimic malignancy <5% risk for developing SCC

15% have an assoc malignancy in another part of the body (breast, colon) survival is determined by depth of lesion. <1.5mm = excellent prognosis. If metastases, <5% make it 5 years

Grow rapidly, metastasize to lymph nodes; 50% 5 year survival rate

usually asymptomatic, but may ulcerate and bleed (i.e. post-coital bleeding)

HPV related.

Culprit: bacterial infection (ex. Streptococcus, staphylococcus, gonorrhoeae) or postpartum/postabortal (ex placental remnants) Infection (chlamydia, gonorrhoeae) or trauma

common and B9 if cytologic atypia is present = premalignant, and risk increases for endometrial cancer

Endometrioid CA is curable if caught early enough; Much worse prognosis for UPSC

Metastasize to lung, liver, and brain within 2 years of diagnosis; 5 year survival rate is 12-25%

aggressive, poor prognosis (30% 5 year survival) 5% develop into choriocarcinoma characterized by infiltrating trophoblasts; invades vessels and metastasizes to lung, brain & liver

Can cause narrowing of tubes = infertility and ectopic pregnancies life threatening: rupture and hemorrhage

hemorrhage, scarring, and pain <1% of all gynecologic malignancies

cinous, Endometrioid, Brenner, Clear Cell

Stromal invasion classifies this as a carcinoma = treatment; most common malignancy of the ovary; 5 year survival rate <50%; depends on Stage at Dx Pseudomyxoma peritoneii "jelly belly": mucin filled abdomen secondary to disseminated mucin from an appendex or ovarian problem. <50% 5 year survival bc intestinal adhesions and 15-20% of ovarian endometrioid carcinomas are assoc w uterine endometrial endometrioid carcinomas B9 for the most part

Rarely teratoma cells produce SCC or melanoma if ruptures, teratoma pieces may implant and continue to grow

Spread hematogenously Meig's syndrome: 1. ascites; 2. pleural effusions; 3. ovarian mass; Meig's can sometimes be mistaken for CA, but syndrome fades once tumor is removed fab prognosis; recur or metastasize 1015 years after Dx

ogen

Disease/Syndrome
Inflammatory Conditions Acute Mastitis

Manifestation / Gross
Usually occurs c breast feeding Foreign material (ie. Silicone leakage), mycobacterial infection, sarcoidosis, mass inflammation and mass, usually the result of trauma or ruptured fibrocystic cyst, fibrosis, microcalcification

Microscopic
S. aureus granulomatous inflammation: macrophages, giant cells, lymphocytes

Granulomatous Mastits

Fat Necrosis B9 Proliferative Breast Dz

fat necrosis - yellow, white nodules

Fibrocystic changes

mass, asymmetry, age: 20 - 50yo, dilation of terminal ducts Often accompanies fibrocystic changes central fibroelastotic core w radiated ducts and lobules, superimposed proliferative chanves

Ductal Hyperplasia

metaplasia, increased fibrosis, superimposed ductal epithelial hyperplasia increased epithelial cells within ducts, some show atypical ductal hyperplasia

Radial scar B9 Neoplasms

Fibroadenoma

Intraductal papilloma

Nipple Papilloma

Common, Age: 20-35, enlarge during pregn, Age: 50, Large ductal involvement = nipple discharge; small ductal involvement = usually, younger patient Age: 4th & 5th decades, ducts in nipples are affected, nipple discharge or erosion, subareolar mass

elongated ducts embedded in loose fibromyxoid stroma, smooth round contour

papillary architecture, lined by epithelial-myoepithelial cells

papillary architecture, lined by epithelial-myoepithelial cells

Carcinoma In Situ (CIS)

malignant neoplastic epithelial cells within the basement membrane, microcalcifications are also present malignant neoplastic, ductal-type cells confined within the basement membrane; variable cytologic atypia may form a mass lesion; unifocal dz and architectural patterns, +/- comedo process necrosis Usually found incidnetally on a bx for another lesion, multifocal dz nipple ulcerations, or eczema type changes malignant neoplastic lobular-type cells within the basement membrane tumor cells confined to nipple epithelium

Ductal Carcinoma in situ (DCIS) Lobular Carcinoma in situ (LCIS) Paget's Dz

Invasive Carcinoma Invasive Ductal CA Invasive Lobular CA

Inflammatory CA

Phylloides Tumor Male Breast Path

most common malign in women; Age: 50s, Risk Factors: FamHx, Genetics (BRCA1 or 2), hormonal status, radiation, proliferative breast Tumor cells breached basement dz. membrane malign ductal cells arranged in cords, 50-70% of Breast CA; mass nests, or tubules 2nd most common CA (5-10%); small malignant cells arranged in often does not present w a mass cords "single file" erythematous dermal changes; "peau d'orange"; extensice dermal lyphatic spread of tumor to overlying skin no distinct histo stromal hypercellularity, bland ductal elements, usually classified as lowgrade tumor :leaf-like"; Age: 45, mass

Gynecomastia

Male Breast CA

hypertrophy & hyperplasia of both glandular and stromal tissue 1% of all Breast CA; esp seen in Klienfelter's, nipple discharge, elderly men

Tx
Abx to avoid abcess

Notes

may sim CA on mammogram and clinical presentation

excision

may sim CA

Reg mammogram

may sim CA, limits mammogram interpretation

increased risk of CA

B9 but may sim CA

Increased risk of DCIS

B9 but may sim Paget's Dz

precursor to invasive CA, but not all progress

"Comedocarcinoma" = high grade cytology + comedo necrosis; assoc w increased risk of invasive CA in ipsilateral breast; Increased risk of invasive CA for ipsilateral and contralateral breast assoc w underlying in situ or invasive CA

Spreads hematogenous or lymphatically; skin and chest wall; will first metastasize to axillary lymph nodes, internal mam nodes, supraclavicular nodes; Prognosis related to TNM of CA

10% develop CA in ipsilateral or contralateral breast

poor prognosis; <2years

High grade tumors are prone to metastasis

Usually due to increased estrogen (obesity) and/or decreased androgenic activity; Klienfelter's

Prognosis depends on stage at presentation

Disease/Syndrome
Placenta Previa Placenta Accreta Placenta Increta Placenta Percreta

Manifestation / Gross
Painless vag bleeding; placenta implants in the lower uterine segment; Total/Complete; Partial or Marginal; Vaginal bleeding; Post-partum bleeding can cause morbidity; Anchoring villi implant in superficial myometrium; Vaginal bleeding w cramping; placenta prematurely detaches from uterine wall 1 artery instead of 2 (carry deoxy blood from fetus to placenta)

Placenta Abruption Single Umbilical Artery (SUA)

Umbilical cord knot Velamentous insertion

Fetuses move and can knot up cord; "true knot" in ~ 5% of pregn; false knots cord inserts into fetal tissue instead of placental disc; Inlamm of placental membranes; may cause premature rupture; ascending infection; fluid is opaque w greenish hue stips of amnion wrap around and amputate fetal structures; early to late pregn; lg abd, cranial defects; amputation of digits mom is normotensive, but pregn BP > 140/90; usu after 20 wks; 2 readings, 6 hours apart 3 characteristic signs: 1. BP > 160/110; 2. Proteinuria; 3. Edema, esp face; Results: reduced perfusion of uterus = hypoxia of placenta & possbl fetus Preeclampsia + siezure = eclampsia

Acute Chorioamnionitis

Amniotic Band Syndrome

Pregn Induced HTN (PIH)

Preeclampsia Eclampsia

Microscopic

Tx
C-section Detected by ultrasound; MRI for characterization; If severe post-partum bleeding = hysterectomy

hematoma will show layering & entrapped deciduas Ultrasound to detect; could be indicative of chromosomal abnormality; Exam fetal anatomy "true knots" : usually ok, but if pulled tight can cause fetal mortality in 5-10% & thrombosis; "false knot" : circuitous course of vessels within cord causes C-section; if fetal distress or decreased bunching = ok. fetal mvmnt

neutrophil exudate

Placenta small w infarcts (pale tan or gray firm wedges); accum of lipid laden macrophages; fibrinoid necrosis & thrombosis

Delivery IV: MgSO4

Notes
Risk factors: multiparity, advanced maternal age; prior C-sec. A = @ endometrium; In = in myometrium; Perc = perfed ~1% of pregn; Risk factors: HTN, hypercoagulable state, smoking, prior abruption, chorioamnionitis

1% of cords

Monochorionic twins & longer cords have greater risk vulnerable to compression and rupture; not protected in Wharton's jelly

leading cause of 2nd trimester fetal mortality & preterm labor; strep B

May be accom by HELLP (Hemolytic anemia; Elavated Liver enzymes; Low Platelets);

Disease/Syndrome

Manifestation / Gross

Usually preterm babies (24-28wks) tachypnea, grunting, chest retactions and cyanosis; Lungs: Respiratory Distress Syndrome heavy, boggy consolidated; Type II (RDS) pneumocytes not producing srufactant Necrosis of the intestinal tract; abnormal blood flow & infection; presents after initial feeding; Necrotizing enterocolitis (NEC) Bowels: dusky to black appearance low birth weight babies & inability to autoregulate flow of vasculature, esp brain; capillary rupture leads to hemorrhage; first 3 Intraventricular Hemorrhage (IVH) days of life Profound fetal edema: pleural, pericardial, & abdm spaces; accomp by polyhydramnios & a lg Fetal Hydrops placenta Edema resulting from Rh- mom carrying Rh+ baby; Mom's IgG AB cross placenta & attack fetal RBCs = profound fetal anemia & edema; result: cardiac failure, massive fluid accum. caused by cardiac failure, anemia, and hypoproteinemia; result in fluid shift;

Inmmune Hydrops

Non-immune hydrops

Microscopic

Tx

atelectasis alternating w expanded alveoli full thickness ischemic necrosis; ++ inflamm

mechanical ventilation & surfactant replacement

Bowel resecting

Monitor w head ultrasounds

Rhogam (anti-D gammaglobulin) Intrauterine blood transfusions;

Notes

risk for developing bronchopulmonary dysplasia

Grade (I-IV): I = subependymal/germinal matrix; II = ext to lateral ventricles; III = lateral ventricles enlarge; IV = intraparenchymal hemorrhage;

Caused by placental chorangioma (B9 vascular tumor); parvovirus infections (parvo B19); Down's syndrome;

Disease/Syndrome

Manifestation / Gross
Thrombosis leading to: vessel occlusion (MI, stroke, gangrene), vessel narrowing (progressive/chronic ischmeia), embolism, aneurysm (weak vessel walls).

Microscopic
Fatty streaks fibrofatty plaques (atheroma: collagen, macrophages, "foam cells") w intact epithelium advanced fibrofatty plaque (ulceration, necrosis, calcification of core, neovascularization, thinning of tunica media)

Atherosclerosis Aneurysms

localized dilation of vessels due to weakening of tunic media Fusiform or saccular distension; common in the aorta or iliac Atherosclerotic Aneurysms arteries; HTN result of atherosclerotic plaques Blood dissects inner 2/3s of media away from outer 1/3 along length of vessel "double-barreled" aorta uncommon; ascending aorta and arch; "tree bark" appearance all three are immune mediated

Dissecting Aneurysms Syphilitic Aneurysms Vasculitis

Necrotizing vasculitis; upper & lower resp tract & kidneys; mid Wegener Granulomatosis age & older adults; men>women older adults; large & small arteries in the head and neck; Sx: Giant Cell (Temporal) H/A, visual disturbances, facial Arteritis pain small & med muscular arteries; mid age & older; Sx: fatigue, fever, weakness, depend on organ involved (skin, GI, kidney, Polyarteritis Nodosa (PAN) heart, etc) Dz of veins & lymphatics

1. Tissue Necrosis; 2. Vasculitis; 3. Granulomatous inflammation

vessels are nodular; lymphocystic infiltrate in media; giant cells;

segmental involvment, mixed inflammatory infiltrate; no granulomas,

Varicose Veins Deep Vein Thrombosis (DVT) Lymphangitis Tumors of Blood Vessels Hemangioma Kaposi Sarcoma

large, distended ropy veins in the lower extremities; can be painful incompetent valves stasis or inflamm in deep veins = thrombi that can embolize = pulmonary or sudden death inflamm of lymph vessels, esp if prev trauma B-hemolytic streptococci

B9, red papule; "birthmarks" AIDS, malig endothelial tumor, red, skin, GI, lungs

assoc w AAV8 (Human Herpesvirus 8)

Angiosarcoma

rar, malign, skin and soft tissue, liver

Tx

Notes

TPA, blood thinners

~Risk Factors: age, male, genetics, hyperlipidemia, smoking, DM, Type A, obesity, homocysteine or CRP

excision, replacement with prosthetic graft

Prone to rupture hemorrhage into extravascular space; common in HTN, Marfans, Ehlers-Danlos; Cystic Medial Necrosis (degen of collagen)

Anti-neutrophilic Cytoplasmic Antibody (ANCA) = dx marker;

T-cell mediated

seen more in Hep B, and certain types of leukemia

hemorrhoids = varicose veins of the bum

long flights, car rides, bed rest

Large = port wine stain

envmtl carcinogen: arsenic & vinyl chloride