FPP/MSS Flashcards
Pemphigus vulgaris
Autoimmune blistering disease. Acquires. Rare. Effects the elderly. Caused by autoantibodies against desmosal proteins specifically desmoglein 1 and 3. This weakens the desmosomes and results in intraepidermal blistering. Flaccid blisters that quickly turn into erosions. Affects mucosal and cutaneous sites. Nikolsky sign is positive.
Ichthyosis vulgaris
“Fish scale” Common AD genetic condition. Caused by mutations in the profilaggrin gene that leads to a defective cornified envelop. Extremities, primarily the shin, are affected. Presents with dry skin, hyperlinear palms.
UV
Known to promote the development of skin cancers like basal cell carcinoma, squamous cell carcinoma, and melanoma.
UVC
200-280 nm. Absorbed by the ozone. Very little reaches earths surface.
UVB
280-320 nm. Penetrates the epidermis and superficial dermis. Causes erythema and sunburn.
UVA
320-400 nm. Penetrates the dermis. Causes tanning and photo aging.
SPF
A measure of the protection against UVB. SPF= MED(protected)/MED(unprotected).
Sunscreen (physical blockers)
zinc oxide, titanium oxide. Reflects and scatters light.
Sunscreen (chemical blockers)
PABA, oxybenzene, avobenzene. Absorbs UV light and converts it to heat.
Collagen in the skin
Primarily type 1 and type 3. During embryogenesis and wound healing there is an increase in type 3. Produced by fibroblasts.
Marfans syndrome
Caused by a mutation in the fibrillin gene. AD. MS: tall and thin body type, long limbs and fingers, scoliosis, flexible joints. Eye: myopia, ectopia lentis. Skin: striae. CV: Aortic aneurysms/dilations, mitral valve prolapse.
Ehlers Danlos syndrome
Caused by a variety of mutations that disrupt collagen production. Results in fragile skin, prone to scarring, flexible joints, arthritis, severe scoliosis, rupture of the blood vessels, intestines, and the uterus.
Morphea
Localized scleroderma. Acquired autoimmune disease characterized by sclerosis (thickening of collagen). Appears erythematous and as indurated plaques that slowly expand. Can leave behind fibrotic and atrophic scars and can cause some joint and neurological complications.
Systemic sclerosis
Acquired autoimmune disease. More common in middle aged women. CREST: calcinosis cutis, Raynauds, Esophageal dysmotility, Sclerodactyly, Telangiectasia. Diffuse systemic sclerosis: Widespread sclerosis, pulmonary fibrosis, renal failure, GI disease, cardiac disease.
Erythema nodosum
Inflammation of the subcutis layer. Presents as tender, red nodules that arise in the shins. Reactive panniculitis means EN was caused by wither strep pharyngitis, oral contraceptives, IBD, or a malignancy.
Bullous pemphigoid
Antibodies are directed towards the BP antigens 1 and 2 (BP230 and BP180). Results in subepidural blistering. Niklosky sign is negative.
Generalized atrophic benign epidermolysis bullosa (GABEB)
Due to an absent or decreased expression of type 17 collagen (BP180).
Laminin 332
Binds to hemidesmosomes on the basal keratinocyte and to type 7 collagen in the dermis providing adhesion between the two structures. Within the lamina densa.
Mucous membrane pemphigoid
Antibodies against laminin 332, BP 180, and integrins. Results in the development of scars, strictures, synechiae, and blindness.
Epidermal bullosa acquisita
Antibodies against type 7 collagen. Even slight trauma elicits blistering. Erosions and healing leaves behind atrophy, milia, scars, and pigmentation defects.
Inherited epidermolysis bullosa
EB simplex is due to keratin 5, 14. Junctional EB is due to laminin 332, BP180, integrins. Dystrophic EB is due to collagen type 7. Kindler syndrome is due to Kindlin 1.
Hair follicle
Hair bulb, isthmus, infundibulum.
Hair cycle
Growth phase: anagen. Transition phase: catogen. Resting phase: telogen.
Anorexia
Characterized by an abnormal increase in lanugo hair types.
Hirsutism
Characterized by an abnormal increase in terminal hair types.
Telogen effluvium
No patches. Stressor results in an increase in the number of hairs in the resting phase. Thus, more hairs are in growth arrest and are shedding. Occurs 3 months after the stressor and eventually returns to normal after the stressor is no longer present.
Alopecia areata
Autoimmune condition characterized by the sudden development of round, smooth patches of hair loss. Nail pits may also be seen. Alopecia totalis and alopecia universalis. Lack of erythema distinguishes it from tinea capitis.
Anagen effluvium
Characterized by hair loss due to medication- chemotherapy.
Acne vulgaris
Peaks in adolescence. Initially acne develops as a result of an increase in sebum production in combination with impaired shedding of the conreocytes results in plugging of the hair follicle- formation of a comedone. A plugged hair follicle can rupture (under the influence of p. acnes) resulting in inflammation.
Topical retinoids
Targets the comedone. Normalizes follicular keratinization. Causes expulsion of existing keratinaceous plugs and prevents the formation of new lesions.
Topical and oral antibiotics
Targets p. acnes preventing inflammation.
Oral contraceptives
Blocks the production of androgens.
Acne rosacea
Related to vascular hyperactivity. Presents with easy blushing developing into a reddened complexion triggered by an external stimuli like alcohol. Also characterized by erythematous papules and pustules. No comedones.
Tinea versicolor
Malassezia furfur. Warm/humid climate. Oval to round scaly patches with fine overlying scale. Hyper or hypo pigmented skin.
Vitiligo
Autoimmune T cell mediated disorder. Results in the destruction of melanocytes and depigmented patches. In affected skin the number of melanocytes is markedly diminished and even absent. Symmetric involvement, unpredictable course, and spontaneous repigmentation.
Oculocutaneous albinism
Inherited disorder that results in congenital absence or marked reduction of pigment in the skin, hair, eyes. Occurs as a result of defects in melanin production due to a defective tyrosinase. Patients are at an increased risk for skin cancers.
Melanocytic nevi
Due to benign proliferations of melanocytes. Junctional nevi: nests in the DEJ; flat. Compound nevi: nest in the DEJ and within the dermis. Intradermal nevi: nests within the dermis; raised.
Congenital melanocytic nevi (CMN)
Larger than acquired. Malignancy depends on ABCDE: Asymmetry, border, color, diameter, evolution.
Ephelides
Freckles. Occurs on sun exposed areas of the body and darkens with sun exposure.
Cafe au lait macules (CALM)
Well circumscribed uniformly light to dark brown macules or patches which typically appear in infancy. Flat, pigmented birthmarks. Caused by a collection of pigmented-producing melanocytes in the epidermis of the skin.
Solar lentigines
Tan to dark brown or black macule due to exposure to UV radiation. Seen later an life and are bigger, which distinguishes them from ephelides.
Dermal melanocytosis
Blue to gray patch over the lumbrosacral region.
Neurofibromatosis Type 1
AD. Caused by mutations in the NF1 gene encoding neurofibromin. Develop mutiple CALMs, axillary and inguinal freckling. Neurofibromas can develop within skin appearing as soft rubbery papules. Plexiform neurofibroma- “bag of worms”.
Tuberous sclerosis
AD. Results in benign tumor formation in multiple organs. Caused by mutations in TSC1 and TSC2, encoding hamartin and tuberin. Skin involvement is manifest as facial angiofibromas (telangiectactic papules. Periungual macules (ash leaf macules). Majority are new and spontaneous mutations.
Piebaldism
AD. Characterized by congenital patch of white hair (poliosis) and white areas on the skin due to an absence of melanocytes within the sites. Areas are stable, in contrast to vitiligo, which is typically progressive.
Waardenburg syndrome
AD/AR. Characterized by achromia (white color) of hair, skin, or both. Congenital deafness, partial or total heterochromia irides, medial eyebrow hyperplasia (unibrow), broad nasal root, dystopia canthorum. Can be associated with mutations in the Pax 3 gene.
Capillary malformations
Flat lesions composed of dilated capillaries. Port-wine stain: always present at birth. Tend to darken and thicken over time. Associated with increased levels of VEGF.
Sturge Weber syndrome
Capillary malformation (port wine stain) in the V1 distribution plus neuro defects. Results in seizures, developmental delay, migraines, glaucoma, and increased choroidal vascularity.
Hemangiomas
Relatively common benign vascular tumors. Composed of epithelial cells that line the blood and lymph vessels. They go through a growth phase and then involute. In contrast, capillary malformations remain flat.
PHACE syndrome
Posterior fossa brain malformations. Hemangiomas of the face. Arterial cerebrovascular anomalies. CV anomalies. Eye anomalies.
Congenital ectodermal dysplasia (ED)
X-linked. Characterized by developmental defects of the hair, teeth, nails, sweat glands, lens of the eyes.
Hypohidrotic ectodermal dysplasia
One type of ED caused by mutations in the ectodysplasin signaling pathway- EDA, EDAR, EDARADD- which provide instructions for making proteins that work together during embryonic development. Present with an impaired ability to sweat, peg teeth, sparse hair, thin skin, low-lying ears, flattened nasal bridge, square forehead.
Seborrheic keratosis
Benign and common lesion of the epithelium. Develop in the middle to elderly. Appear as brown to black waxy papules or plaques. Most common on the face, trunk, upper extremities.
Leser-trelat sign
Sudden onset of multiple seborrheic keratosis which can be associated with internal malignancy. Most commonly associated with adenocarcinoma of the stomach.
Actinic keratosis
Solar keratosis. Common lesion that develops as a result of chronic sun exposure. Represents a dysplastic condition. Presents as rough, erythematous, yellow/brown, scaly lesions in the middle to elderly. Remain stable or regress or 0.1-10% can become malignant- squamous cell carcinoma.
Squamous cell carcinoma
Common in older individuals. 20% of all skin cancers. UV radiation is the most common cause, but can also be caused by chronic ulcers, old burn scars, HPV, radiation, arsenic, immunosuppression. SCC in situ presents as a red scaly plaque. Invasive lesions tend to be nodular an may ulcerate. 5% of SCC develop an invasive component and of these 30% have metastatic potential. The likelihood of metastatic potential is related to the degree of invasion and the thickness of the lesion.
Keratoacanthoma
Variant of SCC believed to originate from the hair follicle. Pink papule or nodule with a central keratin plug. Grows rapidly over a period of 2-10 weeks. Occurs mainly on sun damaged skin. Some lesions resolve spontaneously while others can cause extensive local destruction. Proliferating epithelium is well-differentiated.
Basal cell carcinoma
Most common human cancer. Secondary to chronic cun exposure. Can be locally destructive. Slow growing tumore that rarely metastasizes. Associated with dysregulation of the shh and PTCH pathways. Presents as pink, pearly, papules with prominent arborizing subepidermal blood vessels (telangiectasia). Ulceration and erosion are common.
Melanocytic nevi (acquired vs congenital)
Melanocytes are normally present in the basal layer of the epidermis. They can increase with sun exposure (acquired nevi) or there can be an increased number from birth (congenital nevi).
Dysplastic nevi
May occur sporadically or in a familial form. Are typically larger than acquired nevi. Multiple dysplastic nevi can, but not always, predispose someone to melanoma.
Dysplastic nevus syndrome
Multiple dysplastic nevi (>80). Familial variant is AD with mutations in the CDKN2A gene. Patients have an increased risk of developing other neoplasms- pancreatic cancer.
Melanoma
Most serious form of skin cancer. Risk factors include: excessive exposure to UV, fair complexion, childhood sunburns, many dysplastic nevi, family hx, or old age. Most important clinical sign is a change in an existing nevus. ABDCE changes. Radial growth is not as concerning as vertical growth. Superficial type (back/extremities). Nodular type (vertical growth, poor prognosis). Lentigo maligna (head and neck). Acral lentiginous (palm, soles, nails, AA).
Mycosis fungoides
T cell lymphoma. Late adulthood and male predominance. Presents as red or pink scaly patches.
Sezery syndrome
Blood involvement of T cell lymphoma. Erythroderma- skin is diffusely red and scaly. Poor prognosis.
Impetigo
Common superficial bacterial infection. Contagious. S. aureus. Small vesicles that rupture and are replaced by thick yellow crust. Mouth, nose and extremities are most commonly affected.
Staphyloccocal scalded skin syndrome (SSSS)
Toxin mediated exfoliative dermatitis. Usually caused by toxigenic strains of s. aureus. Two toxins cause intraepidermal splitting through the granular layer by targeting desmogelin 1. There is a sudden onset of skin tenderness, macular eruption, and development of large easily ruptured, flaccid bullae.
Cellulitis
Deep pyogenic infection. Diffuse inflammation of the connective tissue most commonly on the legs. Expanding area of erythema. Erysipelas- elevated border / spreads rapidly. More common in males and in lower extremities.
Verrucae
Warts caused by HPV (DNA). Vulgaris, plantar, or anogenital. Most are caused by low risk HPV and are self limiting. Show papillomatous hyperplasia of the epidermis , vacuolization, keratohyaline granules, intracytoplasmic aggregates.
Condyloma accuminatum
Caused by HPV 6/11. STD. High risk HPV (16, 18, 31, 33) may increase the risk for cancer. Single or multiple papular lesions that are pearly, filiform, fungating, cauliflower, or plaque-like.
Herpes simplex virus
DNA virus. HSV1 causes herpes labialis while HSV2 causes herpes genitalis. Virus can travel along sensory nerves. Apidermal acantholysis (loss of intercellular connections) with several multinucleated keratinocytes with glassy intranuclear inclusions and ballooning degeneration.
Varicella/ Herpes Zoster
Varicella is caused by VZV and is highly contagious and is spread through the respiratory route. Incubation time is 11-20 days. Herpes Zoster or shingles results from reactivation of latent VZV. Causes girdle like vesicular eruption in the thoracic/lumbar region or with facial lesions as a result of trigeminal nerve involvement.
Molluscum contagiosum
Caused by a pox virus. Direct skin to skin transmission. Solitary or multiple waxy papules. Inverted nodule “crater like”. Eosinophilic cytoplasmic bodies.
Scabies
Caused by the mite sarcoptes scabiei and it transmitted by prolonged direct human contact. Extremely pruritic papulovesicular eruption.
Dermatophytoses
Tineae. Invade and colonize keratinized tissues. Scaly, erythematous plaques, often annular. Capitis- scalp. Corporis- trunk/back. Barbae- beard. Cruris- jock itch. Pedis- foot.
Acanthosis nigricans
DM. Manifestation of insulin resistance. Brown, velvety plaques present on the posterior neck, axillae and occasionally the groin.
Diabetic dermopathy
DM. Characterized by brown, atrophic macules on the shins- possibly trauma related. Marker for poor diabetes control.
Bullous diabeticorum
DM. Rare. Male>female. More common in those with long standing diabetes. Acral in location.
Necrobiosis lipoidica
DM. re. Yellow atrophic plaques. Multiple, bilateral, usually shins. Likely to ulcerate in males.
Pretibial myxedema
Occurs in some with Graves disease (hyperthyroidism). Cutaneous infiltration of the skin of shins with mucin. Peau d’orange, skin colored to brown red, firm. Represents deposition to hyaluronic acid in the skin.
Addison’s disease
Primary adrenocortical insifficiency. Hyperpigmentation (MSH like effect from the increased ACTH). Diffuse, sun-exposed sites of trauma/scars, axillae, perineum, nipples, palmer creases, nevi, mucous membranes, hair, nails, striate. Loss of ambisexula hair. Fibrosis and calcification of cartilage.
Cushing’s disease
Overproduction of cortisol. Moon facies, dosicervical fat pad, truncal obesity, spindly limbs, striae distensae, easy bruisability, slow wound healing, acne, hirsutism.
Cutaneous Acute Lupus
Malar cheek rash. Discoid lesions. oral ulcers. Photosensitivity.
Chronic Lupus (DLE)
Usually ears, face, scalp, arms. Mucosal involvement in some. Atrophic (thin) scarring with telangiectasias, follicular scales, hypo and hyper pigmentation. Leaves scars.
Dermatomyositis
Autoimmune disease with inflammation of skin ans muscles. Heliotrope rash of the eyelids. Poikiloderma. Gottrons’s papules: pink to purple, flat topped papules seen on elbows, knees, and dorsal surfaces of the hands. Positice ANA. Elevated CRP/ESR.
Sarcoidosis
Caused by noncaseating granulomas in multiple organ systems. Red to brown macules on the face typically on the eyes and nose.
Lofgren’s syndrome
Sarcoidosis syndrome. Hilar adenopathy, erythema nodosum, fever, iritis, arthritis.
Porphyria cutanea tarda
Caused by a defect in uroporphyrin decarboxylase which breaks down heme proteins. Enzyme system is stressed by chronic hepatitis c infection of the liver, but PCT can also be caused by some drugs, alcohol, and iron overload in the liver. Causes fragile blisters from trauma and sun exposure.
IBD specific
Crohn’s disease with granulomas in the skin. Involvement of oral mucosa with granulomatous inflammation. FIstulas to skin.
IBD non-specific
Erythema nodosum. Pyoderma gangrenosum- sterile and rapid ulceration of the skin caused by neutrophillic infiltration. Dusky border.
Dermatitis herpetiformis
Consequence of gluten insensitivity. An immune reaction in the small bowel leads to antibody formation which can enter the blood and eventually attach to skin causing dermatitis herpetiformis. Very pruritic. Dapsone can relieve the itching.
Inorganic matrix of bone
70%. Composed of calcium and phosphate. Called hydroxyapatite.
Organic matrix of bone
30%. The osteoid. Composed of type 1 collagen, proteoglycans and glycoproteins- promotes clacification.
Osteopetrosis
Characterized by the growth of dense, heavy bone, which is caused by immature osteoclasts that lack a ruffled border. This is a pure osteoclast disease. Severe cases result in the marrow space not being formed, thus hematopoeisis is severely impaired. Thus, patients are supplemented with vit D3 and severe cases need a bone marrow transplant. Though bones are dense and massive, they are also weak because there are unable to assume their lamellar structure that remodeling produces.
Osteoporosis
Osteoclast mediated resorption of the bone matrix occurs faster than osteogenesis, resulting in hollow, fragile bones. Every 10% loss of bone mass doubles the risk of fracture. Obesity (leptin) induces the CNS to inhibit bone formation- inhibits osteoblasts.
Osteoclast development
M-CSF induces monocyte proliferation. RANKL induces osteoclast differentiation. OPG inhibits this process by binding to RANKK receptor.
Clinical management of osteoporosis
PTH 1-34. Spikes of PTH favor osteoblast formation, whereas a constant level of PTH favors osteoclast activity. Anti-resorptive drugs, which encourage osteoclast apoptosis (SERMS, bisphosphonates, mABs). Anabolic agents like RunX2.
Lipoma
Most common soft tissue of adulthood. Benign, solitary lesions. Multiple lipomas usually suggest the presence of hereditary syndromes. Most are mobile, slowly enlarging, painless masses. Complete excision is usually curative.
Liposarcoma
One of the most common sarcomas of adulthood. Deep soft tissues of proximal extremities and retroperitoneum. May develop into large tumors. Well differentiated is a slow growing tumor usually caused by amplification of the 12q region which contains the MDM2 gene (product of which binds to and degrades P53). A myxoid/round cell tumore is more aggressive and is usually caused by a t(12,16) translocation resulting in a fusion gene encoding an abnormal TF that may interfere with adipocyte differentiation.
Lipoblastoma
Children, usually composed of lipoblasts. PLAG1.
Hibernoma
Children. Brown fat tumor.
Reactive proliferation (Nodular faciitis)
Self limited and not a true tumor. Rarely occurs after excision. Deep dermis, subcutis or muscle. Several cms with poorly defined margins.
Myositis ossificans
Presence of metalplastic bone. Usually develops in the proximal muscles. Eventually entire lesion ossifies and intratrabecular spaces become filled with bone marrow.
Superficial fibromatoses
Locally aggressive, but do not metastasize. Palmar- dupuytren contracture. Plantar. Penile- peyronie disease. May stabilize and resolve spontaneously.
Deep fibromatoses
Desmoid tumors. Behavior lies between benign fibrous tumors and low-grade fibrosarcomas. Frequently recurs. Some associated with Gardner’s syndrome- AD including colonic polyps. Mutations in the APC or beta-catenin gene.
Fibrosarcoma
Malignant tumors composed of fibroblasts. Deep tissues of the thigh, knee, retroperitoneum. Aggressive tumors.
Uterine leiomyomas
Fibroid. Most common neoplasm in women. May also arise in the skin or deep soft tissue.
Leiomyosarcoma
Skin and deep tissues of the extremities and retroperitoneum. Superficial- usually small and have a good prognosis. Deep/retroperitoneum- large and cannot excise. There is local extension and metastatic spread.
Rhabdomyosarcoma
Most common soft tissue sarcoma of childhood. Embryonal RMS- head, neck, orbital, parameningeal, GU tract. Sarcoma botryoides (grape-like masses). Alveolar RMS- deep soft tissues of the extremities. Translocation of the PAX3/7.
Synovial sarcoma
Young adults more commonly males. Mostly occurs in deep soft tissues of the extremities, esp around the knee. Shows a translocation creating a fusion gene encoding a chimeric TF. Treated aggressively. Common metastatic sites are the lungs, bone, and regional lymph nodes.
Gout
Arthritis stemming from a metabolic disorder resulting in elevation of uric acid and inflammatory microcrystals in the joint spaces.
Gout incidence in women
Increases after menopause. Estrogen promotes urate excretion.
Acute gout attack
Probably due to a release of crystals from preformed deposits. Changes in temp, pH, fluid status may initiate attack.
Clinical presentation of gout
Abrupt onset of severe pain. Lightening attacks. Typically monoarticular and in the lower extremities. Exam shows synovitis with redness and swelling and extreme tenderness. Self limited and usually resolves within 8-10 days.
Tophi
Deposits of crystalline uric acid surrounded by an inflammatory reaction attempting to engulf the crystals.
Chronic topaceous arthritis
Repetitive episodes of gout. Urate encrusts articular surfaces and forms deposits that destroy cartilage.
Gout: Allopurinol
Block formation of uric acid
Gout: Uricase
Breaks down uric acid
Gout: Probenecid
Increases excretion of uric acid
Gout: NSAIDs, cholchicine, steroids
Reduces degree of inflammation
Rheumatoid arthritis
Inflammatory symmetric polyarthritis (chronic) affecting large and small joints. Genetic predisposition- HLA-DR. Women>men. There is a proliferation of synovium with characteristics of benign, locally invasive tumor.
History features of RA
Gradual onset of joint pain, swelling and inflammation present for more than 6 weeks in 3 or more joints. Symmetrical in nature. Morning stiffness lasting greater than an hour and present for more than 6 weeks.
Chronic papillary synovitis
Chronic inflammation of the synovium: CD4 T cells, plasma cells, macrophages, and giant cells frequently form lymphoid follicles. Accompanied by synovial cell hyperplasia which results in a pannus formation filling the joint space and articular damage. Increased osteoclast activity can lead to the erosion of the underlying bone and sometimes even ankylosis (fusion) due to fibrosis and ossification.
Rheumatoid nodules
Develop most commonly on the skin and in areas exposed to pressure. Non-tendor, firm. Central zone of fibrinoid necrosis surrounded by a rim of epitheliod histiocytes. Necrosis is secondary to vascular damage and possible secondary to vasculitis associated with RA. Most commonly occur in patients who are RF or CCP positive.
Osteoarthritis
Most common cause of arthritic in adults. Progressive joint disorder caused by the gradual loss of cartilage. Results in the development of bony spurs at the margins of the joints and subchondral cysts.
Clinical presentation of osteoarthritis
Non inflammatory joint pain. Fusiform swelling of the joints. Spares the MCPs. Heberden nodes at the DIPs and Bouchard nodes at the PIPs.
Osteophytes
Bony outgrowths associated with the degeneration of cartilage and joints.
Geode
Subchondral cyst formed by break in cartilage allowing synovial fluid to be forced into space.
Osteomyelitis: hematogenous
Results from seeding of bone related to previous bacteremia. More common in children. Staph aureus, strep, TB, salmonella.
Osteomyelitis: direct implantation
Resulting from penetrating activity. Pseudomonas.
Osteomyelitis: contiguous
Resulting from direct spread of bacteria from an overlying wound or pressure ulcer. Staph aureus, gram neg., strep, anaerobes, candida.
Osteomyelitis: infection of prosthetic device
Results from infection of prosthesis, with spread of organisms into the adjacent bone. Coagulase neg., staph, gram neg., strep.
Characteristics of osteomyelitis
Damage to the periosteum may result in pieces of dead bone (sequestrum) or new bone formation (involucrum). Localized abscesses may also form (brodie’s abscess). X-rays are not always sensitive enough. MRI is more effective. Cultures of open ulcers are unreliable.
Biofilms
Aggregations of microorganisms adherent to a surface like bones or teeth or prostheses. Adherent organisms are embedded in a matrix that they produce- called slime/polymeric substance/glycocalyx. Are likely to become resistant to antibiotics.
Osteoid osteoma
Benign bone forming tumor. Long bones: femur or tibia. Less than 2 cm. Causes night pain. Responds to aspirin. There is a radiolucent lesion within a sclerotic cortex. Typically appears in teenage years with male predominance. Local excision is the treatment of choice.
Osteoblastoma
Benign bone forming tumor. Vertebrae or long bone metaphysis. Greater than 2 cm. Painful and not responsive to aspirin. Expansive radiolucency with mottling.
Osteosarcoma
Malignant mesenchymal tumor in which malignant cells produce osteoid or bone. Most common sarcoma of bone. Bimodal age distribution. Metaphysis of bone. Hematogenous spread to lungs is common. Sites of bone growth or disease are more susceptible to develop OS- Pagets disease.
Risk factors of osteosarcoma
Inherited mutant allele of RB gene. Mutation of P53 suppressor gene (Li-Fraumeni- bone and soft tissue sarcomas). Overexpression of MDM2. Prior irradiation.
Imaging of OS
Pooly delineated. Bone destruction. Cortical disruption. Bone matrix. Soft tissue extension. Codman’s triangle- triangular shadow between the raised periosteum and the cortex.
Treatment of OS
Non-adjuvant chemotherapy and surgical resection.
Osteochondroma
Most common benign tumor of the bone. Metaphysis of long bone. Malignant transformation is rare, but there is an increased risk with multiple osteochondromas. Is AD and most commonly secondary to mutation in EXT-1 (8q24).
Enchondroma
Benign hyaline cartilage lesion. Intramedullary chondroma is an enchondroma. (Juxtacortical chondroma is a periosteal chondroma). Usually asymptomatic and incidental finding. Appendicular skeleton. X ray shows lytic, lobulated, cortical thickening. Treatment is none unless lesion shows changes.
Multiple chondromatosis
Frequent point mutations in IDH1 and IDH2. Ollier’s disease: multiple enchondromata, tend to have regional distribution, severe skeletal malformation. Maffucci’s syndrome: multiple enchondromata + angiomata, severe skeletal malformation, higher incidence of malignant transformation.
Chondrosarcoma
Malignant tumor in which neoplastic cells produce purely cartilaginous matrix. Second most common bone sarcoma. Usually affects the pelvis, ribs, femur, and humerus. Imaging shows medullary location. “popcorn-like” lesion. Generally are more cellular and more pleomorphic than enchondromas.
Non-ossifying fibroma
Common in developmental cortical defect. It is the most common space occupying lesion of bone. Usually found on the metaphysis of tibia or femur in the 1st-3rd decades. Eccentric, lytic, peripheral sclerosis. Incidental finding or pathologic fracture.
Fibrous dysplasia
Abnormal bone growth where normal bone is replaced with fibrous tissue. Usually involves the ribs, mandible, or femur. Polyostotic (involvement of multiple bones) results in a crippling deformity with craniofacial involvement. Imaging shows expansile, circumscribed, thinned cortex. “Chinese characters” pathology. Treatment is conservative except for polyostotic FD.
McCune-Albright syndrome
Polyostotic FD with endocrinopathies and CALMs. F>M. Sexual precocity, acromegaly, Cushing’s syndrome. Activating germline mutations of GTP binding proteins. Result is excess cAMP leading to endocrine gland hyperfunction.
Ewing Sarcoma
Second most common malignant bone tumor in childhood. Presents as painful, enlarging mass. Diaphysis of long tubular bones, ribs, and pelvis. Destructive moth-eaten, permeative, medullary lesion with a large soft tissue mass. Onion-skin pattern of periosteal reaction in response to rapid growth. Caused by a t(11:22) translocation. Treatment is chemotherapy and surgery with possible radiation. CD99 present on membranes.
Giant cell tumor
Young adults; f>m. Epiphyseal location, usually the knee, proximal humerus, and radius. Most are benign, but locally aggressive. May destroy cortex of bone and extend into the soft tissue.
Metastatic bone tumors
Most common malignant bone tumor especially in adults. Solitary lesions mimic a primary bone tumor and precedes discovery of its source. 70% go to the axial skeleton. Mostly lytic. May be blastic (bone forming). *0% come from breast, lung, thyroid, kidney.
Bone remodeling signal pathway
WNT signaling via beta catenin promotes osteoblast proliferation and matrix synthesis. Mature osteocytes, when unloaded, secrete SOST, which inhibits WNT signaling. Mechanical loading inhibits SOST expression by osteocytes, thereby allowing for WNT signaling.
Type 1 collagen
Primary protein component in bone. It is a large triple helical protein that self assembles into fibrils with an offset of 1/4 the molecule length, leading to a regular striped appearance on electron microscopy, with a periodicity of 6.7nm. Adjacent molecules of collagen are covalently cross-linked initially yielding aliphatic bonds, but mature to aromatic bonds which have a higher bond energy and are thus, harder to break.
Osteogenesis imperfecta
A group of diseases that result from mutations in the genes encoding type 1 collagen. This results in deficient production or improper assembly of the ECM resulting in a high susceptibility to fracture. Results in pure sclera. This is a pure osteoblast disease.
Osteomalacia
Inadequate mineralization of the bone matrix due to malabsorptive disorders, vit D deficiency, phosphate wasting disorders, and a low calcium diet. Results in weak bone.
Rickets
Osteomalacia in a growing adolescent. Long bones assum a bow shape. Bone function is normal, but the lack of appropriate mineral substrates leads to abnormal bone function.
Sclerosteosis/ Van Buchem’s Disease
Skeletal mass is abnormally high due to mutations of the protein SOST (which normally blocks WNT signaling and osteoblast proliferation). Disrupts the mechanosensory system, resulting in bones perceiving that they are being loaded even when they are not. This is a pure osteocyte disease. Nerve entrapment can lead to facial palsy and deafness. Some mutations can also lead to syndactyly.
Paget’s Disease
Focally excessive breakdown and formation of bone leading to disorganized bone remodeling. Can result in pain, nerve entrapment, weakening of the affected areas bc of the presence of woven as opposed to lamellar bone and bone deformity arising as a result of aberrant modeling in this setting. There is osseous bowing and enlargement. Serum alkaline phosphate is increased during the blastic phase and urinary hydroxyproline is increased during the lytic phase. Predisposition to OS.
