Skin Pathology
Disease
Cause/Risk Factors
Ichthyosis
Genetic (X-Linked)
Acquired
Symptoms
Lack of normal skin shedding
Steroid Sulfatase Deficiency
Urticaria
Edematous plaque (wheal); Pruritis
Lesions disappear in 24 hours
Angioedema of lips and eyelids
Minimal inflammatory cell infiltrate
Acute Dermatitis
Erythema, Blisters, Pruritis
Subacute Dermatitis
Erythema, Oozing, Crusting & Pruritis
(Early Scale)
Chronic Dermatitis
Erythema, Scaling, Pruritis
Buzzwords
Acquired = Paraneoplastic
Other
X-Linked = Due to steroid sulfatase deficiency
Acquired = Part of paraneoplastic syndrome
Allergic = Type I (IgE) Hypersensitivity
All wheals are not urticartia
Allergic Contact Dermatitis = Type IV (CMI) Hypersensitivity
Drug Related Dermatitis = Eosinophils (Penicillin)
Photeczematous Dermatitis = UV Light – Deep Infiltrate
Atopic Dermatitis = Family History
Acute Eczematous Dermatitis
Erythema Multiforme Minor
HSV
Wheals, Target Lesions, Blisters
Limited
Associated with HSV
Erythema Multiforme Major
(Stevens Johnson Syndrome)
Drugs
Mycoplasma
Wheals, Target Lesions, Blisters
Widespread-Severe
Confluent Target Lesions
Target Lesions
Almost always associated with drugs (Dilantin, Sulfa, etc)
Minimal Lymphocyte Infiltrate
Vacuolar alteration along BM
Dead Keratinocytes in epidermis
Erythema Multiforme Major
(Toxic Epidermal Necrolysis)
Drugs
Mycoplasma
Wheals, Target Lesions, Blisters
Explosive Skin and Mucous Membrane Damage
Target Lesions
Like a burn
Occurs within 24 hours – treated like burn
Minimal Lymphocyte Infiltrate
Vacuolar alteration along BM
Dead Keratinocytes in epidermis
Classic Psoriasis
AD
Arthritis
Flat Silvery Plaques
Nail Dystrophies (30%)
Auspitz Sign = Pinpoint Bleeding
Flat Plaques
Munro’s Anscesses
Arthritis
Koebner Phenomenon
Acanthosis without spongiosis
Parakeratotic Scale, PMNs in epidermal layer
Stratum Corneum Microabscesses (Munro’s)
Guttate Psoriasis
AD
Arthritis
Eruptive small scaly Papules
Nail Dystrophies (30%)
Auspitz Sign = Pinpoint Bleeding
Small Scaly Papules
Munro’s (Micro) Abscesses
Arthritis
Koebner Phenomenon
Acanthosis without spongiosis
Parakeratotic Scale, PMNs in epidermal layer
Stratum Corneum Microabscesses (Munro’s)
AD
Arthritis
Gerneralized Red Scaly Skin
Nail Dystrophies (30%)
Auspitz Sign = Pinpoint Bleeding
Red Scaly Skin
Munro’s (Micro) Abscesses
Arthritis
Koebner Phenomenon
Acanthosis without spongiosis
Parakeratotic Scale, PMNs in epidermal layer
Stratum Corneum Microabscesses (Munro’s)
Erythrodermic Psoriasis
Target Lesions
Minimal Lymphocyte Infiltrate
Vacuolar alteration along BM
Dead Keratinocytes in epidermis
Skin Pathology (Contd)
Disease
Pustular Psoriasis
Cause/Risk Factors
AD
Symptoms
Localized = Palms & Soles, Painful
Gernearlized = (Von Zumbush), Fatal
Nail Dystrophies (30%)
Auspitz Sign = Pinpoint Bleeding
Buzzwords
Other
Von Zumbrush (fatal)
Munro’s (Micro) Abscesses
Arthritis
Koebner Phenomenon
Acanthosis without spongiosis
Parakeratotic Scale, PMNs in epidermal layer
Stratum Corneum Microabscesses (Munro’s)
Koebner Phenomenon
Civatte Bodies (Colloid Bodies)
Wickham Stria
Band like lymphocytic infiltrate in dermal-epidermal junction
Saw-tooth rete ridges, Dead Keratocysts (Civatte Bodies) in DEJ
Orthokeratotic Hyperkaratosis
SCC may develop in mucous lesions
Lichen Planus
Hepatitis C?
Limited &Pruritic
Lesions on skin and mucous membrane
Violaceous Papules with Wickham Stria
Lacy, white mucous membrane lesions
Localized Lupus Erythematosus
Autoimmune
Hyperkeratotic lesions/rash on sun exposed areas
Immunoglobulin DEJ band
Periappendageal and perivascular lymphocytic infiltrate
Vacuolar alteration along DEJ with BMZ thickening
Necrotic keratinocytes in epidermis, Mucin in dermis
Immunoglobulin and complement in lesions
Systemic Lupus Erythematosus
Autoimmune
Hyperkeratotic lesions/rash on sun exposed areas
Immunoglobulin DEJ band
Periappendageal and perivascular lymphocytic infiltrate
Vacuolar alteration along DEJ with BMZ thickening
Necrotic keratinocytes in epidermis, Mucin in dermis
Immunoglobulin and complement in ALL of skin
Autoimmune (Desmoglein 3 Ab)
Suprabasal Blisters
Mucous Membrane lesions precede skin
Trunk, Face, Extremities
Net Wire Fence on IF
Suprabasal
May be lethal
Intraepidermal Blisters-Suprabasal
Positive Direct Immunofluorescence (Net Wire Fence)
Acantholytic keratinocytes floating in blisters
Pemphigus Foliaceous
Subcorneal blisters
Crust more common than blisters
Mucous membrane not involved
Trunk, Face, Extremities
Subcorneal
Corn Flakes
No mucous membrane
Endemic (S. America) or Sporadic
Intraepidermal Blisters – Subcorneal (Superficial)
Positive Direct Immunofluorescence (Net Wire Fence)
Acantholytic keratinocytes floating in blisters
Pemphigus vegetans
Hyperplastic lesions in intertriginous areas
Oozing & crusting (no blisters)
Often axilla or groin
Pemphigus Erythematosus
Localized form of P. Foliaceous
Face only
Pemphigus Vulgaris
No blisters
Warty plaques
Positive Direct Immunofluorescence (Net Wire Fence)
Acantholytic keratinocytes floating in blisters
Intraepidermal Blisters
Positive Direct Immunofluorescence (Net Wire Fence)
Acantholytic keratinocytes floating in blisters
Bullous Pemphigoid
Autoimmune (BMZ element Ab)
Sub-epidermal (tense) blisters – don’t rupture
Older Patients
Mucous Membrane Rare
Bullous Pemphigoid antigen
Sub-epidermal
Mucous Membrane only involved in
Mucous Membrane & Scarring Types
Blisters contain eosinophils
BMZ line of compliment (& less frequently immunoglobulin)
Dermatitis Hepetiformis
Gluten Sensitivity
HLA-B8 & HLA-DR3
Grouped vesicles on erythematous base
Very pruritic
On extensor surfaces
Celiac Disease
Micro Abscesses
Extensor Surfaces
Micro abscesses of PMNs destroy dermal papillae
Direct Immunofluorecense shows granular deposits
of IgA in dermal papillae
May have some bowel overlap (celiac sprue)
Friction Blister
High heat & moisture
Subcorneal split
Melanobullous Disorders
(Epidermolysis bullosa)
Genetic
Blister with minimal frictional trauma
Group of disorders: All w/ defect in elements holding skin together
Skin Pathology (Contd 2)
Disease
Porphyria
Cause/Risk Factors
Genetic
Acquired
Symptoms
Buzzwords
Blistering & Scarring
Milial Cyst formation in sun exposed areas
Hypertrichosis of temples
Hemachromatosis
Group of disorders (Porphyria Cutanea Tarda most common)
Uroporphyrinogen Decarboxylase Deficiency
Non-inflammatory Comedones at first
Papules, pustules, nodules & cysts later
Significant scarring
Acne Vulgaris
Other
Disease of Epidermal Appendages
Inflammatory Disease of Sebaceous Follicles
Erythema Nodosum
Unknown
Birth Control Pills
Sarcoid
Strep Infection, TB
Anterior surface of legs
Painful lesions
Rarely drains to skin surface
Erythema Induratum
Unknown
TB
Posterior surface of legs
May ulcerate
More of a Panniculitis – Inflammation of fat lobules
Human Papilloma Virus
All body surfaces
Verrucous Papules/Nodules
Grow Rapidly
Bleed easily
Filliform epidermal projections with parakeratosis
Dilated paipllary capillaries
Keratohyaline granules
Some koilocytes
Commonly on legs and face
Slightly Raised
Hyperpigmented
Spread by scratching
Obvious koilocytosis
Minimal keratinocyte proliferation
Common Wart
Flat Wart
Really more of a septitis
Plantar Wart
Keratohyaline like granules
Moist Wart
Proliferation of keratinocytes with kocloyctosis
Molluscum Contagiosum
Pox Virus
Bullous Impetigo
Staph aureus
(Group A Strep?)
Actinic Keratosis
UV Radiation
Squamous Cell Carcinoma
Actinic Keratosis
Carcinogens, Ulcers, Scars, Arsenic
HPV
Ionizing Radiation
Papules with a hair follicle opening
May become large in immunosuppressed
Cytoplasmic inclusions (35 microns)
Spread worsened by topical steroids
Sub-corneal blister with acantholytic epidermal cells, staph & PMNs
Rough (sandpaper like)
Red with indistinct borders
Epithelial Dysplasia in lower epidermis
Can become Squamous cell carcinoma
May regress, but all should be treated
Fleshy to erythematous with scaly nodules
CIS = Bowen’s Diease; epidermis replaced by atypical keratinocytes
Infiltrates to dermis; Nodular proliferation of dysplastic keratinocytes
UV induced rarely metastasizes to nodes
Mucous Membrane is more likely to metastasize
Bowen’s Disease
Skin Pathology (Contd 3)
Disease
Cause/Risk Factors
Squamous Cell Carcinoma
Actinic Keratosis
Carcinogens, Ulcers, Scars, Arsenic
HPV
Ionizing Radiation
Symptoms
Fleshy to erythematous with scaly nodules
Basal Cell Carcinoma
Sun Exposure?
Noduloulcerative = translucent telangiectasia
Superficial = scaly red patch
Sclerosing = scar like plaque
Basal Cell Nevus Syndrome
PTC gene mutation
Hundreds of basal cell carcinomas
Frontal losing jaw
Cysts
Bifid ribs
Buzzwords
Bowen’s Disease
Other
CIS = Bowen’s Diease; epidermis replaced by atypical keratinocytes
Infiltrates to dermis; Nodular proliferation of dysplastic keratinocytes
UV induced rarely metastasizes (if it does = to nodes)
Mucous Membrane is more likely to metastasize
Most common cancer, rarely metastasizes (if it does = blood)
1) Noduloulcerative = basaloid cells in fibromucinous stroma
2) Superficial = Buds of basaloid cells in dermal epidermal junction
3)Sclerosing = strands of basaloid cells in fibrous stroma
Merkel Cell Carcinoma
Similar to BCC under microscope
Cutaneous neuroendocrine carcinoma
Melanoma
Assymetric
Border Notching
Color Irregularity
Diameter > 6 mm
Pagetoid Growth – Radial, larger cells, buckshot scatter
Lentiginous Growth – Radial, singly & nests, dermal-epidermal jxn
Vertical Growht – Metastatic, grows into dermis
Dermatofibrosarcoma Protuberans
Nodule or plaque
Storiform pattern
Infiltrates fat
Poor margins, CD34 +
Destructive but rarely Metastatic
Histiocytosis X
(Langerhans Histiocytosis)
(Letterer-Siwe Disease)
Similar to seborrheic dermatitis w/ hemangiomas
Cutaneous T Cell Lymphoma
(Mycosis Fungoides)
Red Scaly Patches, Plaques or nodules
Pruritic
With or without leukemia
Sezary Syndrome
Erythriderma + Leukemia
Vitiligo
Melanocyte loss or damage
Patchy Hypopigmentation
May become generalized
Albinism
Genetic (lack tyrosinose)
Inability to produce pigment
Freckle
(Ephelis)
Tan-brown macules
Darker in summer/lighter in winter
Birbeck Granules
Several patterns exist, but all have histiocytes present
Also eosinophils and lymphocytes
Cells contain Birbeck Granules, S-100 + & CD1a +
Due to clonal proliferation of CD4 cells (Sezary-Lutzner Cells)
Cell Clusters = Pautrier micro-abscesses
Hyperpigmentation of rete
No proliferation of melanocytes
Skin Pathology (Contd 4)
Disease
Cause/Risk Factors
Symptoms
Buzzwords
Melasma
Facial & neck (mask like) hyperpigmentation
Mask of Prenancy
Seborrheic Keratosis
Benign keratinocyte proliferation in elderly
Rough (warty); Most common on trunk
Fleshy colored (brown to black)
“Stuck on look”
Dermatosis Papulosa Nigra
Tiny dark popular seborrheic keratoses
On Mongoloid or Negroid populations
Acanthosis Nigricans
Obese young to middle age
Hyperinsulinism/Type II DM Predisposition
Folded skin (not thickened)
Seen on extensor surfaces (hard to see on neck)
Other
Epidermal = hyperpigmented basal layer keratinocytes
Dermal = incontinent melanin pigment in papillary dermis
Occurs in pregnancy
Proliferation of basaloid keratinocytes (may be more squamoid)
Often hyperkeratotic
Cystic foci of lamellated keratin
Leser Trelat Sign = rapid occurrence fue to internal malignancy
Fibroepithelial Polyp
(Skin Tag or Acrochordon)
(Squamous Papilloma)
Acanthosis Nigrans?
Diabetes?
Epithelioid Cysts
Acne? (Epidermoid)
Injury? (Epidermal Inclusion)
Dome shaped nodule
Poral opening
Fixed to epidermis
Wall and cyst keratin look like normal skin
90% of all cutaneous cysts
Most from follicular infundibulum
Trichilemmal (Pilar) Cysts
Genetic (AD-multiple in women)
Dome shaped papule
Fixed to epidermis - No pore
Firmer than epidermoid cyst
Mainly on scalp
Lining like middle of hair follicle
Pink homogenous keratin
About 10% of cysts
Dermoid Cysts
Most common cyst on face of infant (Rare)
Lined like epidermoid cysts
Hair follicle elements (sebaceous glands) in wall
Occur in developmental fusion planes
Steatocystoma
Oily Center
Wall lined by sebaceous glands
Usually on trunk (teens or older)
Keratocanthoma
Rapidly growing module with keratin filled crater
Self healing Squamous Cell Carcinoma
Appendage Tumor
Flesh colored papules and nodules
Nevocellular Nevi
(Melanocytic Nevi)
UV Light Exposure
Thick Seborrheic Keratosis like epithelium or fibrous core
Lentigo Simplex (1-2mm)
Junctional Nevus (2-3mm) = Distal Extremities
Compound Nevus (3-5mm) = Body
Intradermal Nevus (3-5mm, flesh colored) = Face
Benign Tumor of Melanocytes; Develop before age 40
Junctional = ↑ # melanocytes at rete ridges
Compound = clusters at rete & crests, sheets & strands at dermis
Intradermal = junctional disappears leaving dermal component
Skin Pathology (Contd 5)
Disease
Dysplastic Nevi
Cause/Risk Factors
Genetic (AD)
Sporadic (benign)
Hyperlipidemia?
Buzzwords
Other
Aberrant Differentiation of common nevi
Junctional or compound
Lentiginous proliferation singly/in nests w/ lateral bridging
Concentric & Lamellar Fibrosis; Patchy lymphatic infiltrate
Trunk or proximal extremities
Larger than common nevi & border irregularity
+/- Cytologic atypia
Firm Dermal Papule; Indents when pressed
Reddish tan to black; Multiple
Usually on women’s legs
Assymptomatic
Benign Fibrous Histiocytoma
(Dermatofibroma)
Xanthoma
Symptoms
Dimple Sign
Women’s Legs
Circumscribed proliferation of spindled fibroblasts
Trap collagen bundles at periphery; Foamy macrophages; CD34May not be a true neoplasm
Not neoplasms, but collections of foamy macrophages
Tuberous & Tendinous = yellow nodules
Plane = yellow streaks in skin folds (palmar areas)
Xanthelasma = yellow plaques on eyelids (not from Hyperlipidemia)
Flesh colored to yellow papules
On butt, posterior thighs, knees & elbows
Cherry Angioma
2-3mm hemangiomas in adults
No internal disease implications
Strawberry Angioma
Rapidly growing
In infants
Usually involutes
If multiple, internal lesions are likely
Mastocytoma
Few lesions
Urticate, blister when rubbed (Darier Sign)
Involutes after months to years
Urticaria pigmentosa
Slightly smaller than mastocytomas & numerous
Rubbing →histamine release (diarrhea & ↑ HR)
Histamine release from mast cell granules
Diffuse Intracutaneous
Mastocytosis
Diffusely infiltrated with mast cells
Diffuse edema causes “pigskin look”
Concern for Mast Cell Leukemia & Internal Organ Involvement
Telangiectasia Macularis
Eruptiva Perstons
No Darrier sign
Tan macules with telangiectasias
Mainly on trunk
Disease of middle age
Darier Sign
Middle Age
Localized dermal nodule of mast cell infiltration
Minimal Increase in mast cells around dermal vessels
Cells stain melachromatically with several stains
Soft Tissue Pathology
Disease
Cause/Risk Factors
Symptoms
Buzzwords
Lipoma
(BenignFatty Tumor)
On back, shoulders, abdomen & extremities
Slow growing, freely mobile, painless
Painless
Most common soft tissue tumor in adults; More common in ♂
Liposarcoma
(Malignant Fatty Tumor)
Proximal extremities & retroperitoneum
Slow growing, deep seeded mass
Lipoblast is diagnostic
Mets (esp to lungs) & recurrence are common
Lipoblast
T(12:16)
Chicker Wire
Most common sarcoma in adults; More common in ♂
5 Types: Well differentiated, Myxoid, Round Cell (rare, very
aggressive), Dedifferentiated, Pleomorphic (Bizarre giant cells)
Myxoid = chicken wire; Round Cell & Pleomorphic = bad prognosis
Rapid growth
Cell culture appearance
Men = Women
Nodular fasciitis
(Benign Fibrous Tumor)
Trauma?
Volar aspect of forearm; Grows rapidly & tender
Cell Culture Appearance with hemorrhage
Dupuytren’s Conracture
Palmar Fibromatosis
(Borderline Fibrous Tumor)
Alcoholism
Diabetes
Epilepsy
Volar surface of hand
Self-limited or Progressive; Doesn’t metastasize
Estrogen Sensitive
Other
Increasing frequency with age
More common in men
Peyronie’s Disease
Penile Fibromatosis
(Borderline Fibrous Tumor)
Penile Fibromatosis
Self-limited or Progressive; Doesn’t metastasize
Estrogen Sensitive
Extra-Abdominal Fibromatosis
(Borderline Fibrous Tumor)
Shoulder & Chest Wall
Self-limited or Progressive; Doesn’t metastasize
Estrogen Sensitive
Women
More common in women
Treat with radiation or Tamoxifen
Infiltrative with 50% recurrence
Women
Childbirth
Women of childbearing age following childbirth
25% Recurrance
Herringbone
Usually 30-55 yo males
39-54% survival with recurrence > 50% & mets > 25%
Mets to lung, vertebral body & skull
Frequent mitoses, pleomorphism & necrosis
Abdominal Fibromatosis
(Borderline Fibrous Tumor)
Childbirth?
Abdominal Wall
Self-limited or Progressive; Doesn’t metastasize
Estrogen Sensitive
Intra-Abdominal Fibromatosis
(Borderline Fibrous Tumor)
FAP (Gardner’s Syndrome)
Mesentery or Pelvic Wall
Self-limited or Progressive; Doesn’t metastasize
Estrogen Sensitive
Retroperitoneal Fibromatosis
(Borderline Fibrous Tumor)
Compress aorta or ureters
Self-limited or Progressive; Doesn’t metastasize
Estrogen Sensitive
Fibrosarcoma
(Malignant Fibrous Tumor)
Retroperitoneum or lower extremities
Slow growing & painless; Hypoglycemia
Fasiculated growth of spindle cells
Fibrous Histiocytoma
(Benign Fibrohistiocytic Tumor)
Extremities, Solitary, Slow growing nodule
Can look like Basal Cell Carcinoma
Early to mid adult life
Cured by excision; Deep lesions may recur
Intradermal or SubQ proliferation of bland spindle cells
Doesn’t invade epidermis, may cause hyperplasia
Dermatofibrosarcoma protuberans
(Borderline Fibrohistiocytic Tumor)
Trunk & Proximal Extremities
Soriform or cartwheel pattern?
Slow growing followed by rapid progression
Locally aggressive with 50% recurrence
May rarely metastasize
Diffusely infiltrates dermis & subcutis; can invade epidermis
Malignant Fibrous Histiocytoma
(Malignant Fibrohistiocytic Tumor)
Lower extremity
Most common sarcoma of late adult life
Storiform: Cartwheel w/spindle histiocytes & giant cells
Myxoid: Tumor cells & inflammatory cells around vessels
Giant Cell: Histiocytes, Fibroblasts & Osteocyte like cells
Inflammatory: Only in retroperitoneum (histiocytes & inflammatory)
Soft Tissue Pathology (contd)
Disease
Cause/Risk Factors
Symptoms
Buzzwords
Other
Myxoid w/ Round & Spindle cells
Rhabdomyoblast (eosinophillic tadpole cell)
Head, Neck, GU Tract & Retroperitoneum
Most common soft tissue tumor of kids
Most common type of rhabdomyosarcoma
Metrs to bone marrow (20%)
Treat with surgery, radiation & Chemo
Botryoid
Malignant Rhabdomyosarcoma
(Skeletal Muscle Tumor)
Myxoid below epithelium
Rhabdomyoblast (eosinophillic tadpole cell)
GU tumor of young girls
Nasopharynx, Bladder, Vagina, Bile Duct
Variant of embryonal arising in hollow vscera
“Bunch of Grapes”
Metrs to bone marrow (20%)
Treat with surgery, radiation & Chemo
Alveolar
Malignant Rhabdomyosarcoma
(Skeletal Muscle Tumor)
Extremities
Rhabdomyoblast (eosinophillic tadpole cell)
Round to oval cells with loss of cohesion
Pleomorphic
Malignant Rhabdomyosarcoma
(Skeletal Muscle Tumor)
Large, bizarre, multinucleate cells
Extremities
Few Rhabdomyoblasts
Uncommon
Appears in older patients
Metrs to bone marrow (20%)
Treat with surgery, radiation & Chemo
Multiple & Painful
Pilar arrector, genitalia, blood vessel, soft tissue & organ origin
Solitary lesions cured by excision
Smooth Muscle Tumor of
Undetermined Malignant Potential
STUMP (Intermediate)
Bland spindle cells with elongated nuclei
Atypia & Mitoses rare
Hemorrhage & necrosis
Uterine leiomyoma (fibroid) most common
Leiomyosarcoma
(Malignant SM tumor)
Non-Specific: Weight loss, mass, N&V
Elongate spindle cells with cigar nuclei
Frequent mitoses & atypia
Necrosis & Hemorrhage
Females
More common in females
Arise from retroperitoneum or abdominal cavity
Retroperitoneum: 29% 5 year survival
Deep soft tissue: 64% 5 year survival
Synovial Sarcoma
(Malignant Synovial Tumor)
Large joints (esp. knee)
Palpable mass & pain; Focal calcification
Biphasic: spindle fasicles & Cuboidal glands
Almost herring-bone; Epithelial Antigen (EMA)
t(X:18)
Focal Calcification
EMA & Cytokeratin
Most common in adolescents & young adults
t(X:18)
Aggressive & recurrence: 28-36%; Mets: 50%
May not arise from synovium! Tumor must arrive “fresh”
Hemangioma
(Benign Vascular Tumor)
Looks like malformation/hamartoma
Capillary, cavernous
Embryonal
Malignant Rhabdomyosarcoma
(Skeletal Muscle Tumor)
Leiomyoma
(Beinign Smooth Muscle Tumor)
Genetic? (AD)
Girls
t(2:13) & t(1:13)
t(2:13) & t(1:13)
Aggressive
Metrs to bone marrow (20%)
Treat with surgery, radiation & Chemo
Infants & Children
Hemangiopericytoma
Benign & Malignant
Angiosarcoma & Hemangiosarcoma
(Malignant Vascular Tumor)
Hepatic: Arsenic, PVC, Thorotrast
Lymphan
Kaposi’s Sarcoma
Transplant
AIDS-HSV8
European: Chronic
Variable Clinical Course
Ashkanazi Jews: Indolent
Africans: Fatal
Breast Pathology
Disease
Cause/Risk Factors
Symptoms
Buzzwords
Other
Acute Mastitis
Nursing
Cracks or Fissures in nipple
Inflammation of duct, lobules or both
Most Common Inflammation
Acute Mastitis is most common
Insipissation of secretions
Chronic periductal inflammation
Duct dilation with inflammatory cells
Plugged ducts
Older Women
Duct Ectasia
Mostly 5th and 67th decades
Poorly defined ropy area
Subareolar Abscess
(Periductal Mastitis)
Smoking?
Painful red subareolar mass
Recurrent with scarring
Fat Necrosis
Trauma
Surgery
Radiation
Seatbelts, Underwire bras
Hemorrhagic or grey-white necrotic area
Signs of inflammation/repair
Non-Proliferative
Fibrocystic Change Syndrome
Hormones?
Single or multiple painful lumps; Calcification
Changes in size with menstruation
Brown to blue w/ Semi-transparent fluid
Proliferative (without atypia)
Fibrocystic Change Syndrome
(Epithelial Hyperplasia)
Hormones?
Single or multiple painful lumps; Calcification
Changes in size with menstruation
Ductal & Lobular Hyperplasia
Most common condition of female breast, no clinical significance
20-59 yo; Fibroadenomatosis: many small areas like fibroadenomas
Risk of breast cancer = 1.5-2X that of non-proliferative change
Proliferative (with atypia)
Fibrocystic Change Syndrome
(Epithelial Hyperplasia)
Hormones?
Single or multiple painful lumps; Calcification
Changes in size with menstruation
Ductal Hyperplasia & Atypia
Lobular Hyperplasia (proliferation <1/2 acini)
Most common condition of female breast, no clinical significance
20-59 yo; Fibroadenomatosis: many small areas like fibroadenomas
Risk of breast cancer = 5X that of non-proliferative change
10X risk if family history
Sclerosing Adenosis
Hormones?
Single or multiple painful lumps; Calcification
Changes in size with menstruation
Intralobular fibrosis (radial scar) & necrosis
Small distorted acini
Central Scar/Surround Ducts
Most common condition of female breast, no clinical significance
20-59 yo; Fibroadenomatosis: many small areas like fibroadenomas
Firm & confused with cancer
Risk of breast cancer = 1.5-2X that of non-proliferative change
Fibroadenoma
Circumscribed, variable size; Calcification
Myxoid to Hyalinized glands & stroma
Most Common Benign Tumor
Most common benign tumor of breast; young women
Slight increased risk of cancer (esp w/ proliferative change)
Phyllodes Tumor
(Cystosarcoma Phylooides)
Stroma more cellular than fibroadenoma
Mitotic activity
Highly Cellular
Rare tumor resembling fibroadenoma
May become malignant
Tends to recur locally
Smoking
Trauma
Best seen by FNA
May mimic carcinoma
Granulomatous Mastitis
Silicone Reaction
Most Common Overall
Most common condition of female breast, no clinical significance
20-59 yo; Fibroadenomatosis: many small areas like fibroadenomas
Epithelial lining with + change
Fibrosis & Adenosis (↑ acinar units)
Breast Pathology (contd)
Disease
Cause/Risk Factors
Intraductal Papilloma
Symptoms
Buzzwords
Other
Papillary Polypoid growth in major duct
Nipple discharge, bleeding, nipple changesa
Subareolar nodule
Bleeding!
Discharge
If solitary, not associated with cancer
If Multiple, 1.5-2X risk of cancer
Hard to distinguish from papillary carcinoma
Intraductal Carcinoma
Estrogen Excess
BRCA1 & 2
P53
Geography & Diet
Spreads throughout ducts; Can be multifocal
Comedocarcinoma: high grade w/ necrosis
Noncomedo: variable grades
Infiltrating Duct Carcinoma
Estrogen Excess
P53
Geography & Diet
BRCA1 (Medullary type)
most common form
hard with variable morphology
Ductal Carcinoma In Situ
(With Microinvasion)
Estrogen Excess
BRCA1 & 2
P53
Geography & Diet
Rarely palpable
Presents with calcification
Lobular Carcinoma in Situ
Estrogen Excess
BRCA1 & 2
P53
Geography & Diet
Non-invassive
Monomorphic cells fill lobules
Multifocal or bilateral
Often Bilateral
9X risk of ductal or lobular invasive cancer
Incidental finding
Lobular Carcinoma
Estrogen Excess
BRCA1 & 2
P53
Geography & Diet
Infiltrating
“Indian File” Pattern
Poorly circumscribed
Often Bilateral
Hard to detect
Paget’s Disease of the Breast
Estrogen Excess
BRCA1 & 2
P53
Geography & Diet
Tumor cells in Squamous epithelium of nipple
Red and ulcerated nipple
May be non-palpable
Gynecomastia
↑ Estrogens or Gonadotropins
Drugs (pot, HT meds, H2 blockers)
Liver Disease
Abnormal Overgrowth of ducts & surround tissue
Non-Invasive; 1/3 of mammogram detected cacncers (increasing)
Noncomedo: cribriform, solid, papillary, micropapillary
Medullary = Good Prognosis
Mucinous = Cells in Pools
Medullary: pleomorphic sheets with lymph infiltrade, good prognosis
Mucinous(Colloid): soft with pools of mucin, good prognosis
Tubular: well differentiated & small, very good prognosis
Papillary: rare but good prognosis
Not progressive, but a risk for cancer
Always associated with underlying carcinoma
May be invasive or in-situ
Ovary Pathology
Disease
Serous Cystadenoma
(Surface Epithelial Ovarian Tumor)
Cause/Risk Factors
Symptoms
Buzzwords
Ciliated epithelium (Fallopian tube)
Peg Cells
Unilocular or Paucilocular cyst
Cuboidal/Columnar
Other
Most common ovarian tumor, frequently bilateral
Borderline Serous Tumor
(Surface Epithelial Ovarian Tumor)
Ciliated epithelium (Fallopian tube)
Atypia; Cuboidal/Columnar
Psammoma bodies
No stromal invastion
Psammoma Bodies
Complex Papillary Growth Pattern
Prognosis related to peritoneal implants
Serous Cystadenocarcinoma
(Surface Epithelial Ovarian Tumor)
Ciliated epithelium (Fallopian tube)
Atypia; Cuboidal/Columnar
Psammoma bodies
Stromal invastion
Stromal Invasion
Psammoma Bodies
Commonest Malignant Tumor
Complex Papillary Growth Pattern (Serous Papillary)
Prognosis related to peritoneal implants
Mucinous Cystadenoma
(Surface Epithelial Ovarian Tumor)
Intestinal or endocervical epithelium; large
Mucinous Columnar
Borderline Mucinous Tumor
(Surface Epithelial Ovarian Tumor)
Intestinal or endocervical epithelium; large
Glandular & Papillary growth
Atypia; Stratification of cells
Mucinous Columnar
Mucinous Cystadenocarcinoma
(Surface Epithelial Ovarian Tumor)
Intestinal or endocervical epithelium; large
Very complex
Looks like colonic adenoma with Dysplasia/CIS
Mucinous Columnar
Endometrioid Adenofibroma
(Surface Epithelial Ovarian Tumor)
Endometrial gland epithelium
Squamous metaplasia
Non-mucinous columnar
Rare
Borderline Endometrioid Tumor
(Surface Epithelial Ovarian Tumor)
Endometrial gland epithelium
Squamous metaplasia
Non-mucinous columnar
Rare
Endometrioid Adenocarcinoma
(Surface Epithelial Ovarian Tumor)
Endometrial gland epithelium
Squamous metaplasia
Non-mucinous columnar
20% of ovarian cancers
15% coexist with endometriosis
15-30% associated with carcinoma of endometrium
40% bilateral
Clear Cell Adenocarcinoma
(Surface Epithelial Ovarian Tumor)
Endometrial pg 
Hobnail morphology
Glycogen Rich
Hobnail
Poor Prognosis
Considered a variant of endometrioid
High grade, aggressive, rarely survive 5 years
40% bilateral
Brenner Tumor
(Surface Epithelial Ovarian Tumor)
Bladder epithelium
Mesothelial, Cuboidal, Stratified
Unilateral
Benign
Most common transitional cell tumor
Benign; May be associated with mucinous tumor
90% unilateral
Borderline Brenner Tumor
(Surface Epithelial Ovarian Tumor)
Bladder epithelium
Mesothelial, Cuboidal, Stratified
Most common type of mucinous tumor
May resemble adenoma of colon
Malignant Ascites
Pseudomyxoma peritonei (malignant mucinous ascites)
Rare
Ovary Pathology (contd)
Disease
Cause/Risk Factors
Symptoms
Buzzwords
Other
Transitional Cell Carcinoma
(Surface Epithelial Ovarian Tumor)
Bladder epithelium
Mesothelial, Cuboidal, Stratified
Granulosa Cell Tumor
(Sex Cord-Stromal Tumor)
Estrogenic (post menopausal bleeding)
Coffee Bean Nuclei
Microfollicles (Call-Exner Bodies)
Coffee Bean
Call-Exner Follicles
Estrogen
Usually post-menopausal; Risk of endometrial carcinoma
Unilateral; May present with rupture (hemoperitoneum)
Malignant but indolent course in 5-25%
Intraabdominal recurrences after 10-20 years
Thecoma-Fibroma
(Sex Cord-Stromal Tumor)
Estrogenic (uterine bleeding)
Solid tumor of plump spindle cells
Cytoplasmic lipid droplets
Benign
Unilateral
Oil-Red-O Positive
Estrogen
Mixed granulose-theca tumor
Risk for endometrial carcinoma
Sertoli-Leydig Androblastoma
(Sex Cord-Stromal Tumor)
Tubules & Cords of sertoli & leydig cells
Resemble immature testis
50% androgenic & virilizing
Crystals
Virilizing
Stage I: well differentiated – benign
All poorly differentiated or > Stage II: malignant
Dysgerminoma
(Germ Cell Tumor)
Sheets of large primitive germ cells
Stroma contains lymphocytes
Some giant cells
HCG
Like Seminoma
Endodermal Sinus Tumor
(Germ Cell Tumor)
Schiller-Duval Bodies
Hyaline Globules
AFP & AAT
Schiller-Duval Bodies
Choriocarcinoma
(Germ Cell Tumor)
Malignant syncitiotrophoblast capping malignant
cytotrophoblast
Rare in ovary, usually with other germ cell tumors
Benign Cystic Teratoma (Dermoid)
(Mature Teratoma)
Peutz-Jeghers
Pregnancy
Rare
HCG & HPL
Skin with hair, sebaceous glands, muscle, bone,
cartilage, neural tissue
Infants-Children
Radiosensitivity: good results
Tumor Markers: HCG
Usually in children
Embryonal Yolk Sac Differentiation
Tumor Markers: AFP & AAT
Related to pregnancy in younger patients
Must be distinguished from origin:uterine, tubular or ovarian
Tumor Markers: HCG, HPL
May spread to solid organs (unusual for most ovarian cancer)
Derived from endoderm, ectoderm or mesoderm
Most common ovarian tumor in 2nd-3rd decade
Monodermal (Specialized)
(Mature Teratoma)
ex. Thyroid (Struma ovarii)
Immature (Malignant) Teratoma
CEA
Can become Squamous Cell Ca
Composed of fetal or embryonic tissue
Behavior & Prognosis depends on grade (I-III)
Malignant Degeneration of Mature Teratoma in older women
Tumor Marker: CEA
Embryonal Carcinoma
AFP
HCG
HPL
Rare in ovary (not rare in testis)
Primitive, anaplastic tumor
Tumor Markers: AFP, HCG, HPL in some
Metastatic Carcinoma
Krukenberg (GI)
Usually from GI or breast
Krukenberg tumor = bilateral mets (signet ring) from GI
Tumor may stimulate stromal hyperplasia w/ ↑ E2 & AUB
Ovary Pathology (contd 2)
Disease
Cause/Risk Factors
Symptoms
Buzzwords
Follicular Cyst
(Functional Cyst)
Granulosa Cells secrete fluid high in Estrogen
Estrogen
Size < 5 cm
Origin is follicles undergoing atresia
Luteinized Follicular Cyst: stromal lining becomes luteinized
Corpus Luteum Cyst
(Functional Cyst)
Fluid high in progesterone
Lipid turns gelatinous; hemorrhagic
Progesterone
Follicle post-ovulation has delayed resolution of cavity
Fibroblastic layer of CT with shell of luteinized theca
Non-functional Cyst
Predominantly serous
Smooth
Lined by Cuboidal
“Simple Cyst”
Inclusion of coelomic epithelium
Para-Ovarian
Similar to paratubal
Chocolate Cyst
Polycystic Ovary Disease
Other
Darkly Colored
Obesity, 2 Amenorrhea, Hirsutism
Anovulatory & Dismenorrhea; Infertility
Bilateral ovarian enlargement, ↑ LH & E2, ↓ FSH
Cysts w/ luteinized theca interna & fibrotic cortex
Estrogen
Obesity
Amenorrhea
Hirsutism
Not a true cyst
Chronic Anovulatory Syndrome (Stein Levinthal is a variant)
3.5-7% of women (3rd decade)
Due to increased Estrogen
Menometrorrhagia, Endometrial Hyperplasia & Adenocarcinoma
Uterus Pathology
Disease
Cause/Risk Factors
Symptoms
Buzzwords
Other
Acute Endometritis
Strep/Staph
Post-Partum
Post-Abortion
Acute Inflammation + Necrosis
Birth or Abortion
Usually an ascending infection
Chronic Endometritis
PID
Retained POC
IUD
Actinomyces/TB
Plasma Cells
Endometrial glands & stroma in myometrium
Menorrhagia, Colicky dysmenorrheal,
Dyspareunia & Pelvic Pain
Adenomyosis
Endometriosis
Regurgitation?
Metaplastic?
Vascular or Lymphatic Dissemination
Endometrial glands & stroma outside uterus
Ovaries>Ligaments>Rectovaginal Septum>
Pelvic Peritoneum>Scars
Dysfunctional Uterine Bleeding
No Corpus Luteum Production
↑ Estrogen
Endometrial Hyperplasia
Prolonged Estrogen stimulation
Abnormal Uterine Bleeding
Endometrial Polyp
Hyperplasias?
Tamoxifen
Benign Proliferation of endometrial glands
Abnormal Uterine Bleeding
Infertility
Causes Infertility, dysmenorrheal & Pelvic Pain
Affects women in 3rd & 4th decade
More common at beginning of menstrual life
Excess Estrogen: Endocrine, Tumor, Obesity, Malnutrition
Endocrine dependent – affects mitotic index
Profuse bleeding, pain, impaired fertility
Sharply circumscribed mass in myometrium
Mitotic Index < 20, No necrosis, No/Mild atypia
Leiomyoma
(Fibroid)
Endometrium in Myometrium
Uterine Elnargement
Simple Hyperplasia: Lowest risk for carcinoma
Complex Hyperplasia: Less than 5% risk for carcinoma
Atypical Hyperplasia: 25% associated with development of cancer
Whorling Bundles
Common (1 in 4 women); Esp common in black women
Whorling bundles of smooth muscle
Subtypes: Mitotically active, Cellular, Atypical, Myxoid,
Neurilemoma-like & lipoleiomyoma
Adenocarcinoma
(Endometrial Carcinoma)
Obesity, DM, ↑BP, Nulliparity,
E2 Therapy, Anovulatory Cycles
Atypical Hyperplasia
Early Menarche/Late menopause
Irregular bleeding
Malignant glands
Most common invasive GYN cancer
75% in post menopausal women
Adenoacanthoma
(Endometrial Carcinoma)
Obesity, DM, ↑BP, Nulliparity,
E2 Therapy, Anovulatory Cycles
Atypical Hyperplasia
Early Menarche/Late menopause
Irregular bleeding
Malignant glands, Benign Epithelium
Younger women, related to hormones, better prognosis
Adenosquamous Carcinoma
(Endometrial Carcinoma)
Obesity, DM, ↑BP, Nulliparity,
E2 Therapy, Anovulatory Cycles
Atypical Hyperplasia
Early Menarche/Late menopause
Irregular bleeding
Malignant glands & Squamous epithelium
Same or Worse prognosis than adenoacanthoma
Clear Cell Carcinoma
Grade III?
Poor Prognosis
Poor Prognosis
Occur in older women without history of Estrogen Therapy
Uterus Pathology (contd)
Disease
Papillary Serous Carcinoma
Cause/Risk Factors
Symptoms
Buzzwords
Grade III?
Poor Prognosis
Mucinous Carcinoma
Other
Poor Prognosis
Occur in older women without history of Estrogen Therapy
Occur in older women without history of Estrogen Therapy
Grade I Endometrial Carcinoma
Well Differentiated
Easily Recognized Glandular Pattern
Grade II Endometrial Carcinoma
Moderately Differentiated
Tumor in glands/solid sheets
Grade III Endometrial Carcinoma
Poorly Differentiated
Mostly solid sheets
Ex. Papillary Serous or Clear Cell Carcinoma
Stage IA/B Endometrial Carcinoma
Confined to Corpus
Length of uterine cavity < 8 cm (A)
Length of uterine cavity > 8 cm (B)
90% 5 year survival
Stage II Endometrial Carcinoma
Involves corpus & cervix
30-50% 5 year survival
Stage III Endometrial Carcinoma
Outside uterus but not outside true pelvis
< 20% 5 year survival
Stage IV Endometrial Carcinoma
Outside true pelvis
Involves mucosa of bladder ot rectum
< 20% 5 year survival
Malignant Mixed
Mesodermal Tumors (MMMT)
Malignant glands & stroma
No necrosis?
Poor Prognosis
Postmenopausal women; Poor prognosis
From stromal cells of mullerian mesoderm
Homologous (tissue of origin native to uterus)
Heterologous (Tissue of origin is foreign to uterus)
Leiomyosarcoma
Any Mitotic Index, coagulative necrosis, atypia
Uterine Enlargement
Most common uterine sarcoma; 40-60 yo
From myometrium (malignant smooth muscle)
Recur & Metastasize (hematogenously)
Poor prognosis w/ 40% 5-year survival
Endometrial Stromal Sarcoma
Margin between tumor & myometrium
Stromal Nodule (benign counterpart)
Best prognosis
From endometrial stromal cells; Mean age < 50 yo
High grade: indistinct borders; Low grade: pushing borders
5 year survival is 50%
Endolymphatic stromal myosis: penetrates lymph (50% recur)
Fallopian Tube Pathology
Disease
Cause/Risk Factors
Symptoms
Buzzwords
Usually unilateral
Unicornuate uterus
Aplasia
Hypoplasia
Other
DES (a contraceptive)
DES
Rare
Accessory orifices more common (failed tubal ligation)
Duplication
Acute Salpingitis (PID)
1º STD(Gonococcus-60%,Chlamydia)
2º Invasion due to local organisms
(Strep, Staph, Coliforms, Anaerobes,
post D&C/abortion, postpartum, IUD)
Subacute Salpingitis (PID)
Granulomatous
TB
Mycoplasma
Viral
Chronic Salpingitis (PID)
Chlamydia?
Mycoplasma?
May be assymptomatic
Open conduit/tubal damage by prior infection makes it succeptable
Mural scarring with adhesions and occlusions
Complication: Tubo-ovarian abscess (TOA), pyosalpinx,
hydrosalpinx, infertility, ectopic pregnancy
Ectopic Pregnancy
PID
Endometriosis
Gestation outside endometrial cavity
Pelvic/Abdominal Pain; Missed Menses
↑ HCG, Absent uterine gestational sac, mass
95% tubal, 2% maternal mortality
Complications: Rupture, pregnancy loss, hemoperitoneum
Fallopian Tube Cysts
Para/Mesonephric remnants
Trauma
Surgery
Fimbrial (hydatids of Morgagni), Ligamentous,
Tubal Body
Fallopian Tube Neoplasms
Suppurative Infection of fallopian tube
Pelvic Pain, Fever, Mucopurulent Discharge
Chandelier Sign
Mimics appendicitis
Mimics Appendicitis
Chandelier Sign
Hydatids of Morgagni
Repeat Infections cause scarring
Complication: Sepsis (Arthritis, Meningitis Endocarditis, Peritonitis)
Hydrosalpinx (healed acute)
Common; < 4 cm in size
Rare: Leiomyoma, Adenomatoid Tumor, Nerve sheath tumor
Malignant: 1º Rare, 95% serous papillary adenocarcinoma from
serous epithelium (poor prognosis)
Mets: common; from GU, GI, pancreas & breast
Placenta Pathology
Disease
Cause/Risk Factors
Symptoms
Buzzwords
Other
Succenturiate Lobe
(Accessory Lobe)
Vessel Rupture during delivery→Fetal blood loss
Retention of lobe→postpartum bleeding/infection
Bipartite
Two equal lobes
Placenta previa
Placenta over cervical os
Bleeding
Associated with placenta acreta
Placenta acreta
Abnormally adherent to myometrium
Placenta increta
Villi grow into myometrium
Complications: failure of separation, postpartum bleeding, rupture
Placenta percreta
Villi grow through uterine wall
Complications: failure of separation, postpartum bleeding, rupture
Velamentous Insertion
Vessel compression or thrombosis
Rupture during delivery→Fetal blood loss
Single Uterine Artery
Fetal Malformations
Increased risk of fetal mortality
Meconium Stain
Pigmented macrophages in amnion/chorion
Pigmented macrophages
May be related to intrauterine fetal distress
Large amounts can cause intrauterine asphyxia
Amnion nodosum
Amnion studded with nodules of cellular debris
“Epithelial Plaques”
with oligohydramnios
cellular debris
Associated with oligohydramnios (renal agenesis & immature lungs)
Amniotic Band Syndrome
Strings of amnion entangle limbs or digits
Infarction
Pregnancy-induced Hypertension
Arterial supply unsupported across fetal membranes
No Decidua
Due to lack of deciduas
Must be removed
Complications: failure of separation, postpartum bleeding, rupture
Difficult to distinguish from some chromosome abnormalities
Interruption of blood supply from uterine arteries to placenta
Placenta Pathology (contd)
Disease
Cause/Risk Factors
Symptoms
Abruptio placentae
Pre-eclampsia
Cocaine/Crack
Abdominal Trauma
Decreased blood to baby & increased pressure
Low SES?
Prolonged Rupture of Membranes
Group B Strep (most common) Gram – Enterics,
Staph, Anaerobes, Mycoplasma, Viruses, Candida
Inflammation of membranes, chorionic plate,
Cord(funisitis) & fetus; Evidence of aspiration
Most common type of placental infection
May result in abortion, stillbirth, malformations or neonatal infection
High frequency of negative cultures
Hematogenous Infection
(transplacental)
(T)oxoplasmosis
(O)ther
(R)ubella
(C)ytomegalovirus (H)erpes
Fever, Encephalitis, Chorioretinitis,
Hepatosplenomegaly, Pneumonitis, Myocarditis,
Hemolytic Anemia, Skin Lesions, Retardation
Cataracts, Heart & Bone defects
May result in abortion, stillbirth, malformations or neonatal infection
Etiologic agent usually unknown
Most parasitic, viral & a few bacterial infections enter via placenta
Changes involve villi!
Toxemia of Pregnancy
Placental Ischemia (trophoblast failure)
Vasoconstriction (Angiotensin, etc)
DIC (Thromobxane)
Small placenta
Many large infarcts
Retroplacental hematoma
Organ Damage (liver, kidney, brain)
Pre-eclampsia: Hypertension, Edema, Proteinuria (6% of pregnancy)
Eclampsia: Seizures & Coma
Treatment: Bedrest, diet, BP drugs, induction of delivery
Dizygous Pregnancy
Hereditary
Release & Fertilization of 2 ova
Dichorionic & Diamniotic
+ Fused Placenta
Ascending (transcervical) Infection
Acute Chorioamnionitis
Buzzwords
Other
Premature seperation of placenta
Partial or complete
Usually occurs late
Monozygous Pregnancy
Single fertilized ovum
Monochorionic/Diamniotic or
Monochorioinic/Monoamniotic
Vascular Anastomoses
Occur with all monochorionic placentas
Complete Hydatidaform Mole
Gestational Trophoblastic Disease)
1st trimester bleeding, Hyperthyroidism
Toxemia (25%), Hyperemesis gravidarum
Hydropic villi, 46XX/Y (solely paternal)
↑ Uterus, trophoblastic proliferation & atypia
Partial Hydatidaform Mole
Gestational Trophoblastic Disease)
Missed abortion, 69 XXX/Y, Embryo present
↓ uterus
18-20 weeks
Treatment: D&C, follow HCG, physical exam, CXR
Persistant GTD
Either Metastatic or non-metastatic
Risks: Initial HCG >100K, Uterus > 16 weeks, Ovaries > 6 cn,
age > 50, Hyperthyroidism, Pre-eclampsia, DIC, pulmonary
insufficiency & hyperemesis
Non-metastatic & Good Prognosis: single chemotherapy 100% remit
Unbalanced A→V shunt results in twin-twin transfusion syndrome
70% fatality
↑HCG
Solely Paternal
High risk of Permanent GTD
Most common form of persistant or Metastatic GTD following mole
Hydropic villi invade myometrium & metastasize to lung & vagina
Risk of uterine perforation & hemorrhage
Invasive Mole
Choriocarcinoma
Placental Site Trophoblastic Tumor
16-18 weeks
High risk of persistant GTD
Treatment: D&C, follow HCG, physical exam, CXR
Pregnancy
Hydatidaform mole
Spontaneous abortion
Ectopic pregnancy or teratoma
Malignant neoplasm of trophoblast
Persistantly elevated or rising HCG
Abnormal Uterine Bleeding
Symptoms related to mets
Proliferation of intermediate trophoblast
Abnormal uterine bleeding & enlargement
HCG low, HPL high
Mimics pregancy
Most Serious
HCG
Hemorrhagic, necrotic nodules; no villi
Made of plexiform masses of cytotrophoblast & syncitiotrophoblast
Aggressive (invade blood vessels)
Responsive to chemotherapy
HPL
Nodular mass of intermediate trophoblast
Infiltrates endometrium & myometrium
Resembles implantation site
90& benign, don’t to chemotherapy; hysterectomy is preferred
Cervical & Vulvar Pathology
Disease
Cause/Risk Factors
Symptoms
Cervical Carcinoma
HPV; Early age at first intercourse
Many sexual partners; Immune Status
High risk male partners; Inflammation
Tobacco, Low Folate, OCPs; p53
Unexplained bleeding (esp. post coitus)
Eye, mouth, larynx, tracheobronchial tree,
esophagus, bladder, anus, genital tract lesions
Koilocytosis, Multinucleate, Hyperkeratosis
Human Papilloma Virus
Condyloma acuminatum
(HPV Lesion)
HPV
Verrucous lesion
Multiple
Perineal, Perianal, Vulva, Vagina or Cervix
Flat Lesions
(HPV Lesion)
HPV
Cervix
Squamous Metaplasia
HPV
Replacement of glandular epithelium by
Squamous
Buzzwords
Other
E6 & E7 (from HPV) interact with p53 & RB genes
Koilocytosis
Infection always precedes cancer, but not sufficient to cause it
Most women exposed to HPV at some time; Most regress
Persistant infection is necessary for development of cancer
HPV 16, 18, 31 & 45: high risk, integrate into DNA
Usually just on Cervix
Not Premalignant
Not Premalignant
Protective
Low-Grade Squamous
Intraepithelial Lesion (LSIL)
Dysplasia in lower 1/3 of epithelium
Same as Cervical Intraepithelial Neoplasia (CIN1)
HPV cytologic change
Treatment: Colposcopy
High Grade Squamous
Intraepithelial Lesion (HSIL)
Dysplasia in lower 2/3 of epithelium (CIN 2)
Dysplasia in most of epithelium (CIN 3)
Dysplasia throughout epithelium (CIS)
Basement membrane intact
CIN 3 = Only most superficial layer is spared
Treatment: Colposcopy, Biopsy, Endocervical Sampling
Cone biopsy is done for persistant unexplained abnormality
Atypical Squamous Cells
Changes suggestive of SIL
ASC of Undetermined Significance: HPV Triage or Colposcopy
ASC can’t exclude HSIL: Colposcopy
More difficult & harder to diagnose
Treatment: Colposcopy & endocervical sampling; Endometrial
sampling on women > 35
Atypical Endocervical cells: Cone biopsy
Atypical Glandular Cells
Microinvasive
(Invasive Cervical Cancer)
Squamous Cell Carcinoma
(Invasive Cervical Cancer)
Small Cell Carcinoma
(Invasive Cervical Cancer)
Invasive no more than 3 mm (IA1) or 3-5 mm (IA2) beneath BM
Horizontal spread < 7mm
No vascular space invasion
Most Common
Most common type (80%)
1) Large Cell nonkeratinizing (most common)
2) Large cell keratinizing
Cervical & Vulvar Pathology (contd)
Disease
Cause/Risk Factors
Symptoms
Adenocarcinoma
(Invasive Cervical Cancer)
Buzzwords
Other
Increasing Incidence
Increasing Incidence; HPV 18 most common
Harder to detect (lower sensitivity on PAP)
Adenosquamous Carcinoma
(Invasive Cervical Cancer)
Lichen Sclerosus
(Vulvar Dystrophy)
Grossly white & scaly plaque
Discomfort & Pruritis
Thinned epithelium with atrophy & fibrosis
Squamous Cell Hyperplasia
(Vulvar Dystrophy)
Epithelial Thickening & Hyperkeratosis
Grossly white & scaly plaque
Discomfort & Pruritis
White Plaque - Thickening
Dyskeratosis, Atypia, Disturbed maturation
Abnormal mitoses, No invasion
Bowen’s Disease (CIS-VIN)
Vulvar Intraepithelial Neoplasia
HPV
Vulvar Dystrophy
Cervical & Vaginal Carcinoma
Squamous Carcinoma of Vulva
Keratinizing
White Plaque - Thinning
Elderly
Collagen Layer
Common in elderly
Younger Women
VIN I-III: Mild severe dysplasia (similar to cervix)
CIS (or VIN III): Also known as Bowen’s Disease
Mets to inguinal nodes
Malignant Melanoma of Vulva
Paget’s Disease of Vulva
Intraepithelial or invasive
Nabothian Cyst
Inflammation
Squamous Metaplasia (over glands)
Cystically dilated endocervical glands
Mucous filled cysts plugged by Squamous epithelium
Endocervical Polyps
Inflammation
May cause bleeding
Inflammation & Metaplasia
Common
Vulva, Vagina & Cervix
Multinucleate cells with viral inclusions
Risk to newborn babies
Herpes Simplex II
Yeast Infection
Candida albicans
Diabetes, Pregnancy, OCPs
Cervical & Vulvar Pathology (contd 2)
Disease
Trichomonas vaginalis
Chlamydia trachomatis
Bacterial Infection
Cause/Risk Factors
Symptoms
Buzzwords
Other
Small, pear or oval shaped with small nucleus
Most Common
Very frequent
May spread to other gyn organs
Cocci = abnormal
Rods = normal
Male GU Pathology
Disease
Cause/Risk Factors
Symptoms
Vesico-Ureteral Reflux
Short intra-vesical portion of ureter
Bladder Enlargement
Abnormal Patency of Valve
Incompetent Vesico-Ureteral Valve
Regurgitation of urine into distal ureter
Infection (pyelonephritis); Hydronephrosis;
Chronic Renal Failure (Reflux Nephropathy)
Non-Infectious Cystitis
Cytotoxic Drugs (Cyclophosphamide)
Ionizing Radiation
Idiopathic (Interstitial Cystitis)
Frequency, Lower Abdominal Pain, Dysuria,
Hematuria, Urgency; No exudate/ulceration
Inflammation, edema, hyperemia, hemorrhage
Inflammatory cells on mucosa in lamina propria
Infectious Cystitis
Young ♀ (short urethra,hormonal, etc)
Elderly ♂ (obstruction, catheters)
Urinary Tract Abnormalities
Diabetics
Frequency, Lower Abdominal Pain, Dysuria,
Hematuria, Urgency
Calculi
(Nephrolithiasis)
Stasis (Obstruction, Diverticuli)
Infection, Foreign Body,
Metabolic Disease
Urothelial Carcinoma
Smoking, Industrial Dyes
Analgesics, Cyclophosphamide
Schistosoma haematobium
Bladder>Renal Pelvis>Ureter>Urethra
Papillary, Sessile, Flat (CIS)
Painless Hematuria
Increasing Incidence, Decreasing Mortality; Males>Females
Urothelial in origin; Radiation Therapy is useless
TCC (most) Squamous & Adenocarcinoma (rare); Mets to lymph
Flat CIS tends to progress; Muscularis Propria Invasion is critical
Acute Bacterial Prostatitis
Pyogenic bacteria
Intraprostatic Reflux of Urine
Catheter, Biopsy, Hematogenous
Diffuse suppurative inflammation
Fever, Chils & Dysuria
Necrotizing Inflammation with PMNs
Microabscesses centering on glands and ducts
Chronic Bacterial Prostatitis
Pyogenic bacteria
Intraprostatic Reflux of Urine
Catheter, Biopsy, Hematogenous
Indolent or Recurring Infection
Insidious onset, recurring infection
Dysuria, Perineal/Low Back Pain
Antibiotics penetrate prostate poorly
Lymphoplasmacytic infiltrate in stroma with macrophages
Lymphocytes in stroma with age
Chronic Abacterial Prostatitis
Unknown
Chlamydia/Mycoplasma
Low Back Pain
Absense of pyuria
Presence of 10 PMNs/HPF
Buzzwords
No exudate/ulceration
Cyclophosphamide
Other
Chronic: Thickening of wall with plasma cells from vessel damage
Fungal & TB = granulomatous
Hemorrhagic Cystitis: Cyclophosphamide
Complications: Pyelonephritis, VUR, Calculi, CRF & fistulas
Caused by: Bacteria (Coliforms, TB), Fungi (Candida, Torulopsis),
Parasites (Schisto), Viruses (Adeno), Chlamydia & Mycoplasma
Hemorrhagic Cystitis: bacterial & adeno infxn
Arise in urinary bladder or renal pelvis, lodge at outflow narrowing
Cpmplications: Hydronephrosis, Infection, Chronic Renal Failure
Hard to distinguish from chronic bacterial prostatitis
Granulomatous Prostatitis
Non-infectious
Induration of prostate (resembles cancer)
Rare
Due to immune response to secretions from prior bacterial infxn,
massage, biopsy or instrumentation
Palisading granulomas
Nodular Hyperplasia (BPH)
DHT
Estrogens (Estradiol?)
Proliferation of stroma & glands in mid-prostate
Obstructed urinary tract (hesitancy & frequency)
Lack prominent nucleoli
Have prominent double layered lining
No malignant potential; Disease of the elderly
Nodules in transitional zone: yellow-pink, soft, milky exudate
Nodules in periurethral zone: firm & rubbery
Bladder Distended, ↑ Resid. Volume, Infection, Incontinence, VUR
Prostatic Adenocarcinoma
Age, Race, Family Hx
Hormonal
Diet
90% asymptomatic at diagnosis
Back pain from vertebral mets
Crystal Inclusions; High Free PSA
No basal layer; Prominent nucleoli
Most common cancer in males/2nd most common cancer death
Peripheral>>Central>Transitional
Grading is prognostic; Staging determines treatment
Yellow, rubbery indurated nodules
Prostatic Intra-epithelial Neoplasia
Intraglandular malignant cells
Basal Layer present
No basal layer
Precursor lesion to prostatic carcinoma
Male GU Pathology (contd)
Disease
Cause/Risk Factors
Cryptorchidism
Symptoms
Buzzwords
Undescended Testicle
Other
Predisposes to infertility & testicular tumors
Inflammation of Epididymis
UTI
Gonorrhea
Chlamydia
Congenital Defects/Obstruction
Initially an acute inflammation with PMNs & edema, later abscess
If chronic can cuse scarring and infertlility
Inflammation of Testis
UTI
Syphilis
Congenital Defects/Obstruction
Less common than inflammation of epididymis
Initially an acute inflammation with PMNs & edema, later abscess
If chronic can cuse scarring and infertlility
Torsion
Violent movement
Trauma
Twisting of spermatic cord
Cuts of f veins/arteries
Vascular engorgement & veinous infarction
Assymptomatic or painless enlargement
Primitive germ cells with stromal lymphocytes
Syncitial Giant Cells (produce HCG)
Seminoma
(Pure Germ Cell Tumor)
Best Prognosis
HCG – no AFP
Most common Pure GCT
Best prognosis
Older patients (30s)
Older age group (60s)
Benign unless associated with a sarcoma
Spermatocytic Seminoma
Choriocarcinoma
Hemorrhage & Necrosis
HCG
Aggressive - Metastatic
HCG
Embryonal Carcinoma
Abortive gland formation
Mixed GCT
Hemorrhagic
Yolk Sac Tumor
(Endodermal Sinuys Tumor)
Lace-Like Pattern
AFP
Yonger Patients
AFP
Embryonic-Placental line tumor
Proliferation of primitive placental cells
Most aggressive
Rare in pure form
Embryonal Line
Anaplastic cohesive nest of cells
Frequent component of mixed GCT
Embryonal-Allantoic Line
Most common tumor of infancts & children
Good prognosis in children
Usually associated with embryonal carcinoma in adults
Embryonal-Somatic Line
Cystic & Sclerotic Foci
Components of all three germ layers
In children: Pure & Benign; In adults: mixed & malignant
Teratoma
Hydrocele
Neighboring infections/tumors
Idiopathic
Accumuation of serous fluid in tunica vaginalis
Hematocele
Trauma
Torsion
Bleeding Disorders
Blood within tunica vaginalis
Male GU Pathology (contd 2)
Disease
Cause/Risk Factors
Trauma>?
Lymphatic Obstruction
Hypospadias
Malformationo of urethral groove & canal
Opening on ventral surface
Epispadias
Malformationo of urethral groove & canal
Opening on dorsal surface
Phimosis
Prepucial orifice is too small to allow retraction
Secondary infections/carcinoma
Balanoposthitis
Non-specific inflammation of shaft & foreskin
HPV
Benign tumorous growth
Pedunculated Papillary growth
Arund prepuce & coronal sulcus
Koilocytic change & raisinoid nucleus
Carcinoma in Situ
HPV (16,17,etc)
Squamous Malignancy confined to epithelium
Full thickness Dysplasia
High mitotic index
Invasive Squamous Carcinoma
Poor Hygeine; Lack of circumcision
HPV infection
Smegma
Infiltrating nests of Squamous epithelia
Atypia & mitotic figures
Keratin pearls
Bleeding & infection
Verrucous Squamous Carcinoma
Other
Cystic accumulation of semen in spermatic cord
Chylocele
Condyloma acuminatum
Buzzwords
Dilated veins within spermatic cord
Painful
Varicocele
Spermatocele
Symptoms
Opening may be constricted & cause obstruction/UTI
Ejaculation may be hampered & cause infertility
Forcible retraction may cause urethral constriction/urine retention
Villous branching projections with fibrovascular cores
Lined by Squamous epithelium with hyperkeratosis
Squamous cells reveal perinuclear vacuolization
Bowen’s Disease
Bowen’s Disease: white/opaque plaques of shaft
Erythroplasia of Queyrat: red velvety plaques on glans/prepuce
Bowenoid Papulosis: multiple pigmented papules on younger pts
Bowenoid = not progressive
Papillary, Exophytic or verrucous (condyloma-like)
Slow progression with local mets to inguinal nodes
Special type of Squamous carcinoma
Broad bulbous pushing margins with underlying tissue
Good prognosis
Although locally invasive, rarely metastasizes
Bone & Joint Pathology
Disease
Osteoarthritis
Rheumatoid Arthritis
Cause/Risk Factors
Symptoms
Buzzwords
Other
Age
Mechanical
Trauma
Weight Bearing Joints
Hip, Knees, Lumbar & Cervical, PIP/DIP fingers
Pain, Stiffness, ↓ ROM
Osteophytes & Cysts
PIP/DIP
Most Common
Progressive Erosion/Remodeling of Bone & Cartilage
Autoimmune
Juvenile Rheumatoid Arthritis
Chronic Systemic Inflammatory Disease of Joints
Women>Men, Younger age of onset
IgM to IgG (RF)
Skin (Nodules), Vessels, Heart, Lungs, Etc
Proliferative, non-suppurative synovitis; Joint ankylosis
Metacarpophalangeal
Systemic Polyarthritis, Rheumatoid Factor
Fibrinoid Necrosis with inflammatory collar
Nodules on extensor surface/viscera
Pain, Stiffness, Swelling, MCP Joints
Rx: NSAIDS, Analgesics, DMARDS, Immunosuppresion, anti-TNF
Systemic Presentation precedes Joints
Fever, Hepatic & Lymph Node Enlargement
Seronegative for RF
ANA
Large Joints
Fewer Joints than RA
Called “Still’s Disease” in adults
Ankylosing Spondyloarthritis
(Marie-Strumpell Disease)
(Seronegative Spondyloarthopathy)
HLA-B27
Infection
Axial Joints (Sacroiliac)
Low Back Pain; Bamboo Spine
Aortic Insufficiency
Lung Fibrosis & Uveitis
Adolescent Boys
Reactive Arthritis
(Reiter Syndrome)
(Seronegative Spondyloarthopathy)
HLA-B27
Infection (GI & GU Bacteria)
Arthritis, Urethritis & Conjunctivitis
Arthritis waxes & wanes
Enteropathic Arthritis
Bowel Infection
HLA-B27
Abruptly appearing arthritis
Knees & Ankles
Arthritis lasts ~ 1 year
Psoriatic Arthritis
Sausage Digits
Iritis & Conjunctivitis
Less Severe & More Remitting
5% of Psoriatic Population
Acute Arthritis: PMNs in synovium
Chronic Tophaceous: Fibrotic synovium & cartilage destruction
Gouty Nephropathy: uric acid stones in renal interstitium
Rx: NSAIDS, allopurinol, colchicine
Gout
Primary
Secondary (Malignancy or Metabolic)
Familial, Male, Age, Purines, Alcohol
Obesity, Thiazides, Lead, ↑ BP
Hyperuricemia
Tophi (urate crystals & inflammatory cells)
Secondary Pyelonephritis
Bone erosion & loss of joint space
Chondrocalcinosis
(Pseudogout)
Age
Sporadic (trauma)
Heriditary (8q)
Hyperparathyroid
Calcium Pyrophosphate
Inflammtory infiltrate (PMNs) causes damage
Staph, Strep, Gonococci,
H. influenzae, Gram - rods
Fever, Pain, Swelling
↑ WBC, ESR, CRP
Sudden swollen, painful w/ ↓ ROM
Usually a single joint
Corticosteroid Arthopathy
Hemochromatosis/Hemosiderosis
(Pigmentary Arthropathy)
Bacterial Arthritis
H. influenzae in children
Staph in older children/adults
Gonococcus in young adults
Bone & Joint Pathology (contd)
Disease
Cause/Risk Factors
Symptoms
Tuberculous Arthritis
TB
Usually weight bearing joints
Synovium grows as pannus
Viral Arthritis
Parvo B19
Rubella
HCV
HIV
Variable
Lyme Disease
Borrelia burgdorferi
Symptoms within weeks to years of disease onset
Usually one or two large joints
Buzzwords
Other
Hematogenous from viscera or adjacent osteomyelitis
Ganglion
Small cyst near joint capsule or tendon sheath
Wrist
Synovial-like Fluid
Cystic or myxoid degeneration of connective tissue
Synovial Cyst
Herniation of synovium through capsule
Baker’s Cyst in RA
Pigmented Villonodular Synovitis
Giant Cell Tumor of Tendon Sheath
Pain, locking, recurrent swelling
Benign proliferation of joints, tendon sheats, bursa
Most common mesenchymal neoplasm of hand
Synovial Sarcoma
Large joints (knee)
Palpable mass & pain in 50%
t(x:18)
Focal calcification
Less than 10% are intraarticular
More common in adolescent males
Mets in 50%; Aggressive in 1/3
Biphasic: Spindle Cells in Fascicles, Columnar/Cuboidal in glands
Pathologic Fracture: Diseased Bone
Compund Fracture: Broken Skin
Stress Fracture: Repetative Minimal Injury
Comminuted Fracture: Bone Fragmented
Most common bone disorder
Hematoma, Fibrosis, Callus, Woven Bone,
Remodeling
Bone Fractures
Jagged edges
Lacks nuclei
Necrotic Bone
Osteoporosis
Adolescents
Age
Genetics
↓Vit D, Calcium, Estrogen
Decreased bone mass, Fracture, Pain
Vertebral Column, Femoral Neck, Wrist
Osteomalacia/Rickets
Vitamin D Deficiency
Defective Mineralization
Osteopenia
Fractures
Renal Osteodystrophy
Skeletal Changes
Chronic Renal Disease
Loss of transverse trabeculae
↑ Osteoclast, ↓Osteoblast activity
Rx: SERMs, Diphosphonates, Calcitonin
↑ Serum: Alk Phos & PTH
↓ Urine: Ca
↓ Serum: Ca, P, Vit D
↑ Urine: P
Phosphate Retention, Hypocalcemia, abnormal Vit D metabolism
Metabolic Acidosis, Aluminum Deposition
Bone & Joint Pathology (contd 2)
Disease
Cause/Risk Factors
Symptoms
Buzzwords
Osteitis Deformans
(Paget’s)
Viral? (Paramyxo, Measles)
Abnormal Remodeling of Bone
Mosaic Pattern & Cement Lines
PAIN! – due to nerve compression
High cardiac output
Mosaic Pattern & Cement Lines
Osteomyelitis
Pyogenic, TB, Viral, Dungal
Parasitic
Trauma or Hematogenous spread
Immunosuppression & DM
Fever, Malaise, Pain, ↑ WBC, ESR, CRP
Acute purulent inflammation & necrosis
Repair by fibrosis & new bone
Squamous Cell Carcinoma in sinus tract
Bacterial Osteomyelitis
Staph (all ages); Gram- (drug abusers)
H influenze/Group B Strep (neonates)
Salmonella (Sickle Cell)
Group G Strep (alcoholics, diabetics)
Mostly polyostotic
Pelvis, Long Bones, Spine, Skull; Older Males
Phases: Osteolytic, Mixed, Osteosclerotic
Acute or Chronic
Not HIV/AIDS
Metaphysis common
Sequestrum (old necrotic) Involucrum (new bone sleeve)
Salmonella = Sickle Cell
Tuberculous Osteomyelitis
TB
Chronic-Occult (from lung or viscera)
Monostic (usually spine)
Inguinal Mass (iliopsoas or psoas abscess)
Pain, fever, malaise, weight loss
Avascular Necrosis
(Septic or Idiopathic Osteonecrosis)
Corticosteroid, Alcohol, Radiation
Hemoglobinopathies, Coagulopathy
Vasculitis, Pancreatitis,
Caisson Disease, Gaucher’s Disease
Femoral Head
Pain & Secere secondary osteoarthitis
Chronic Corticosteroids
Osteochondroma
Heriditary?
Exophytic, Painless
Metaphysis of long bones
Pedunculated or broad base
Cartilage Cap, Echondral ossification
Painless
Pott’s Disease = TB in spine
Malignancy rare
Most common neoplasm of cartilage
Children, Adolescents, Young adults
Malignancy rare
Multiple Chondromatosis = Ollier Disease
Hands & Feet
Radiolucent nodules of cartilage
Echondroma-Echondromatosis
Other
Osteoid Osteoma
Nocturnal Pain – responds to Asprin/NSAIDs
Appendicular – arms & legs
Nocturnal Pain
Benign tumor of children & young adults
Radiolucent osteid nidus surrounded by dense reactive bone
Osteoblastoma
Like osteoid osteoma
Usually in vertebrae
Adults
Larger mass in adults
Malignant potential; Recurs
Finrous Dysplasia of Bone
Bone replaced by fibrous tissue/woven bone
Painless
Limb Distortion & Fracture
No osteolblasts
No osteoblasts
Usually monostotic (ribs, skull, long bones)
Adolescents
McCune-Albright Syndrome
Café-au-lait spots
Endocrinopathy
Polyostotic
Metastatic
Breast, Prostate, Lung, Thyroid
Kidney
Multifocal (Thyroid & Kidney solitary)
Pain, Fracture, ↑ Calcium & Alk Phos
Spine, Pelvis, Ribs, Skull, Humerus, Femur
Lytic or blastic (prostate): most mixed
Rare
Most Common
Myelophthisis = marrow infiltration
Bone & Joint Pathology (contd 3)
Disease
Cause/Risk Factors
Symptoms
Buzzwords
Other
Pain, Mass, ↑ Alk Phos
Mets to lungs
Metaphysis, periosteum long bones (knee)
Most common primary bone forming tumor
Young or elderly
Malignant bone & osteoid
Treatment: Surgery & Chemotherapy
Chondrosarcoma
Pain, Mass, Slow Growing
Wide Distrubution: Pelvis, Shoulder, Ribs, Legs
Mets to lungs
Older patients with osteosarcoma
Malignancy hard to assess
Ewing’s Sarcoma
Mass, pain, fever, ↑ WBC, ESR, anemia
Small Round Blue Cell Tumor
Anemia
Multiple Myeloma
Spine, Ribs, Pelvis, Skull
Monoclonal Gammopathy (M Protein)
Pain, Lysis, Fracture, Anemia, ↑ Calcium
Fever, Weight Loss, Amyloid
M-Protein
Bone Resorption (Osteitis fibrosa cytica)
Cortical Bone
Brown Tumor
Brown Tumor
Von Recklinghausen’s
Osteosarcoma
Hyperparathyroidism
Hypoparathyroidism
Rb
P53
Paget’s, Infarcts, Radiation
Adenoma, Hyperplasia
Hypocalcemia
Children (most with translocation)
Medullary cafvity of femur & pelvis
Lytic destruction & periosteal reaction
Treatment: chemo, radiation, surgery
Widespread prolideration of plasma cells
↑ Serum: Ca, Alk Phos, PTH, Vit D
↑ Urine: Ca & P
↓ Serum P
↑ Serum: P
↓ Urine: Ca & P
↓ Serum: Ca, PTH, Vit D
No Change: Alk Phos
Genetic Pathology
Disease
Cause/Risk Factors
Symptoms
Buzzwords
Down Syndrome
Trisomy 21 (47, XX, +21)
Mosaicism (46,XX/47,XX+21)
Unbalanced Translocation
Flattened back of head & facial profile,
upslanted eyes, epicanthal folds, flat nasal bridge,
Small ears, protruding tongue, short neck, single
palmar crease, short stature, gap between toes
Palmar Crease
Protruding Tongue
Upslanted Eyes
Trisomy 18
Trisomy 18 (47,XX,+18)
Mosaicism (46,XX/47,XX+18)
Low Birth Weight, Failure to Thrive
Hypertonia, Weak Cry, Poor Suck, Apnea
Microcephaly, Low set ears, overlapping fingers
Rocker Bottom Feet
Rocker Bottom Feet
Low Birth Weight
Trisomy 13
Trisomy 21 (47, XX, +13)
Mosaicism (46,XX/47,XX+13)
Unbalanced Translocation
Normal Birth Weight, Failure to Thrive
Holoprosencephaly, Hypotonia, apnea, Seizures,
Hearing Loss, Microcephaly, Close eyes,
Cleft Lip/Palate, Polydactyly
Turner Syndrome
45X; 46X,i(X)(q10); 46Xdel(X)(p)
46Xdel(X)(q); 46Xr(X)
45X/46XX; 45X/46XY
Short at birth, webbed neck,
lymphedema over dorsum of hands/feet
Shield Chest, Pigmented nevi, Minimal breasts
↑ FSH & LH, ↓ E2; Infertility
47, XXX
XXX
Tall
↑ risk for chromosome abnormalities in offspring
Slightly lower IQ – need special education
Behavior Problems
Kleinfelter Syndrome
47, XXY
Mosaicism
Small testes, Infertility
Tall stature, long legs, Behavior Problems
Gynecomastia; Lower IQ – special ed
Low DHT, High FSH & E2
47, XYY
XYY
Tall, cystic acne, large teeth
↑ risk for chromosome abnormalities in offspring
↑Distractability ↓ Impulse Control
Fragile X Syndrome
Fra X (q27.3)
Full Mutation = > 200 CGG repeats
Large Head, Large Ears, Strong Jaw, High Palate
Lax Eustachian Tubes, Hyperflexible Joints
Mitral Prolapse, Macroorchidism
ADHD, Repetitive Speech, Autistic-like
Inherited Mental Retardation
Most Common Inherited Cause of Mental Retardation
Less severe in females
Sherman Paradox: Assymptomatic carriers have problems w/ age
Neurofibromatosis Type I
(Von Recklinghausen Disease)
NF-1
Neurofibromas with button-hole effect
Pigmented Skin Lesions (Café au-lait)
Lisch Nodules (iris hamartomas)
Button-hole effect
NF-1 = tumor suppressor gene
Marfan’s Syndrome
FBN1
Skeletal Changes
Ocular Changes (ectopia lentis)
Cardiovascular Changes (Mitral Valve Prolapse)
Defective fibrillin
Tay-Sachs Disease
(Sphingolipidosis)
Hexosaminidase A Deficiency
(Splice site or frameshift mutation)
GM2 Ganglioside Accumulation
Motor/Mental Deterioration - Death at age 2-3
Cherry Red spots on macula
Neurons have lisosomes filled with gangliosides
-1,40Glucosidase Deficiency
Glycogen Accumulation
Cardiomegaly
Hepatomegaly (mild)
Muscle hypotonia
Pompe Disease Type 2
(Glycogenosis)
Polydactyly
Other
VSD, ASD & AV Canal; Duodenal Atresia, Leukemia,
Hypothyroidism, Poor immunity, Hearing loss, Strabismus, Myopia,
Mosaicism = Milder
VSD, ASD, Polyvalvular Dysplasia, Esophageal Atresia,
Imperforate Anus, Cryptorchidism
High mortality
ASD,VSD,PDA, Dextrocardia, Omphalocele, Intestinal Malrotation
Cystic Kidneys, Scalp Defects & Hemangiomas
Common; 99% of 45X spontaneously abort;
45X/46XY = risk for gonadoblastoma
Coarctation of aorta, bicuspid aortic valve, aortic stenosis
Hypertension, Hypothyroidism, DM
No tendency for criminal behavior
Genetic Pathology (contd)
Disease
Cause/Risk Factors
Symptoms
Buzzwords
Gaucher Disease
(Sulfatidosis)
Glucocerebrosidase Deficiency
Glucocerebroside Accumulation
Type I: Splenomegaly & Bone
Type II: Infants (early death)
Type III: Juveniles, CNS
Most Common
Metachromatic Leukodystrophy
(Sulfatidosis)
Arylsulfatase A Deficiency
Sulfatide Accumulation
Motor defecits (death in 10 years)
Demyelination causes gliosis
MPS I (Hurler Syndrome)
(Mucopolysaccharidosis)
a-L-iduronidase Deficiency
Heparan & Dermatan Sulfate Accumulation
Skeletal Deformities & Corneal Clouding
Mental Retardation, Joint Stiffness, HSmegaly
Umbilical Herniation, Heart Problems
Corneal Clouding
MPS II (Hunter Syndrome)
(Mucopolysaccharidosis)
a-L-iduronidase Deficiency
No corneal clouding
X-Linked
Milder
X-Linked
I-Cell Disease (ML-II)
(Mucolipidosis)
N-acetylglucosamine-1-P-transferase
Hurler-like
↑ Hexosaminidase B & Iduronate Sulfatase
Inclusion bodies in fibroblasts
Von Gierke Disease
Glucose-6-Phosphatase Deficiency
Glycogen Accumulation
Hypoglycemia, Hepatomegaly
Hyperlipidemia, Hyperuricemia
Hepatic Glycogen Storage Disease
McArdle Disease
Glucose-6-Phosphatase Deficiency
Muscle Cramps after exercise
Failure to raise lactate levels
Muscle Glycogen Storage Disease
Lesch-Nyhan Syndrome
(X-Linked Recessive)
HGPRT Deficiency
CNS Problems – Mental Retardation
Self Mutilating
Hyperuricemia, Gout, Renal Stones
Orange Sand in diaper
Xeroderma Pigmentosum
Defective Nucleotide Excision Repair
XPA, XPB, XPC, XPD,
XPE, XPF, XPG
Also XPV (DNA Synthesis)
Hypo/Hyperpigmentation of the Skin
Neurological Abnormalities
↑ BCC, SCC & Melanoma & internal cancer
Clouding of cornea, atrophy of eyelid
Cockayne Syndrome
Transcription Coupled Repair Defect
CSA or CSB
Sunlight Sensitivity, Progeria, Growth Failure
Neurological Defects, Dental Defects, Cataracts
Typical Facies & Dwarfed
Long arms & Legs, Sunken Eyes
XP/CS
Defective Excision Repair &
Transcription
XPB, XPD or XPG
Sun Sensitivity of XP
Growth Abnormalities of CS
HNPCC
Inheritance of Colon Tumors
hMSH2, hMSH3, hMSH6 (mutS)
hMLH1, hPMS1, hPMS2 (mutL)
Microsatellite Instability-Mismatch Repair Defect
Spontaneous Mutations
Endometrial, Gastric, UT, Ovarian & Colon
Tumors
Other
Most Common Lysosome Storage Disease
Problem in macrophages
Treatment: Enzyme replacement, Bone Marrow Transplant
Late infantile form is most common type
Detected with dyes
Self Mutilation
Orange Sand
Normal at birth, rapid deterioration at 6 mos
6-10 year life expectancy without BM transplant
Remove all teeth
UV Light Induced Pyrimidine DImers cause damage
Skin cancer within first decade
Autosomal Recessive
No cancer
Growth Abnormalities
Typical Facies
No cancer predisposition
Early Death (12 years)
Autosomal Recessive
Sunlight sensitivity due to defective excision repair
XPB & XPD are part of Transcription Factor TFIIH
Autosomal Recessive
AD
Autosomal Dominant – early loss of remainig good allele
Cancer Genetics Pathology
Disease
Cause/Risk Factors
Symptoms
Buzzwords
Other
Sis Protooncogene
Encodes PDGF
Inappropriately expressed by Carcinomas causing cell growth
HER2/neu
Encodes EGF Receptor
Overexpressed in Breast & Ovarian Cancer
(Can be treated with Herceptin)
Ret Oncogene
c-abl Oncogene
Constiutively signals in Thyroid Carcinoma in absence of GF
Encodes a Tyrosine Kinase
Abnormal cell localization in CML t(9:22)
A fusion gene with bcr/c-abl
Required for signal transduction by growth factor receptors
Mutated at codons 12 & 13
Most mutated oncogenes
Ras Oncogene
NF1
A GTPase activating Protein (GAP)
(turns of Ras)
Missing in melanoma and Neurofibromatosis
APC
Regulates -Catenin
(cell contact signaling)
Defective in colorectal cancer & benign intestinal polyps
In Familial Intestinal Polyposis
C-Myc
A transcription factor
Placed next to immunoglobulin heacy chain in Burkitt’s Lymphoma
T(8:14)
L-Myc
A transcription factor
In Lung Tumors
N-myc
A transcription factor
In Neuroblastomas
Rb
Master regulatory protein
Controls entry into cell cycle
Unphosphrylated form binds (inactivates) E2F transcription factor
Phosphorylated by Cyclin/CDK; Controlled by CDK Inhibitors
Inactivated in Retinoblastoma, Osteosarcoma & by HPV E7 protein
Bcl-1
Cyclin D1 gene
Overexpression causes Rb inactivation
Inactivated in Mantle Cell Lymphoma by t(11:14)
Cancer Genetics Pathology (contd)
Disease
hMSH1, hMSH2
Caspases 3,6 & 7
Cause/Risk Factors
Symptoms
DNA Repair genes
Buzzwords
Other
Defective in Heriditary Nonpolyposis Colorectal Cancer
(Rapid cancer progression)
Cause apoptosis
Fas
A death receptor in the extrinsic apoptosis pathway
Tumor Necrosis Factor
A death receptor in the extrinsic apoptosis pathway
Bcl
A pro-apoptotic protein in the intrinsic apoptosis pathway
Opens mitochondrial membrane pores
Cytochrome C
A pro-apoptotic molecule in the intrinsic apoptosis pathway
Released from mitochondria
Activates Apaf-1
Apaf-1
A pro-apoptotic molecule in the intrinsic apoptosis pathway
Activates initiator caspases to cleave effector caspases
Translpant Pathology
Disease
Cause/Risk Factors
Symptoms
Buzzwords
Other
Immediate (seconds to minutes)
Clot formation and occlusion
Rare
Due to preformed HLA antibodies directed against HLA class I
Results from pregnancies, transfusions or previous transplants
Activated complement attracts PMNs and damages endothelium
Acute Rejection
Weeks to months
Most common type of rejection
Cellular: Mediated by cytotoxic T cells
Humoral: Antibodies made against HLA Type I antigens
Treatment: Immunosuppression or Plasmapheresis
Chronic Rejection
Lungs: Obliterative Bronchilitis
Liver: Bile Duct Disappearance
Kidney: Scarring
All patients have chronic rejection, but few get organ failure
Damage primarily against arteries
Circumferential intimal fibrosis & lumen narrowing
Graft Versus Host Disease
Fibrosis of skin
Cholestasis of liver
Strictures in GI
Infection
Caused by Contaminating Donr Lymphocytes
Balanced required: Too few donor T cells = no engraft
Hyperacute Rejection
Usually occurs < 6 months after transplant
First month = endogenous flora
After first month = opportunistic flora
Infection
Cytomegalovirus
Lung: Interstitial Pneumonia
Liver: Acute Hepatitis
GI: Esophagitis, Gastritis, Diarrhea
Most common viral infection in transplant patients
Cellular enlargement, basophilic intranuclear inclusions, halo,
eosinophilic cytoplasmic inclusions
Aspergillus
Branching septate hyphae
Silver Stain
Blood Vessel Occlusion
Most commonly in neutropenic BM transplant patients
Hard to treat
Squamous Cell Carcinoma
Herpes Simplex Virus I
Skin and Lip
Squamous Cell Carcinoma
HPV
Cervix
Kaposi’s Sarcoma
HHV 8
Post Transplant
Lymphoproliferative Disorders
EBV
OKT3
Highest incidence in Lung & Heart
B Lymphocyte Infection
Plasmacytic Hyperplasia: Polycolonal; Oropharync & Lymph
Polymorphic B Cell: Monoclonal; Lymph or Extradnodal
Lymphoma & Multiple Myeloma: Monoclonal (malignant)