Dermatology path Flashcards
A 2 month old boy was taken to the physician to discuss the following birth mark. His mother wanted to know if besides disfiguring, there was any harm in leaving the mark on her son’s leg. What, if any, risks are associated with such large nevi?
Large congenital nevi:
“Bathing trunk nevi”
~10% risk of developing melanoma
A woman comes into the dermatologist concerned about the following mark on her arm. She has heard that it could be melanoma. What types of features would the physician look for to be concerned about melanoma?
Atypical nevus:
Rate of conversion to melanoma: < 1 in 200,000 for people < 40, 1 in 33,000 for people > 60 years
Risk factors:
UV exposure–> blistering lesions (history of multiple burns in early life)
- One blistering sunburn–> doubles risk
- Intermittent exposure hypothesis (infrequent, heavy sun exposure)
Skin phenotypes:
- light skin
- Blond/red hair
- Blue/green eyes
- Prominent freckling
Clark/dysplastic/atypical melanocytic nevi
- Larger than 5 mm with irregular borders
Family history:
- 10-15% melanoma patients have positive family history
- Younger first-degree relative ex: 40 year old brother (not 85-year old grandmother)
ABCDE of Melanoma:
A: Asymmetry – one half is not identical to the other half
B: Border – irregular, notched, scalloped, ill-defined
C: Color – Varying shades from one area to the next
D: Diameter – > 6 mm or pencil eraser
E: Evolving
* Other reasons for changes in mole:
- Inflammation
- Folliculitis
- Trauma
- Hormonal influence
- Natural evolution
Below: Melanoma
Below is a histologic specimen from an atypical colored patch on a woman’s arm. What types of changes have occured and what would be visible on the surface?
Melanoma: Atypical distribution of epidermal cells, nuclear and cellular atypia, hyperplastic growth
Identification:
Light source, magnification, polarization (dermatoscopy- below)
Immunohistochemistry:
Useful adjunct to H&E diagnosis of melanoma
- Poorly differentiated tumors
- Little or no pigment
- Spindle cell tumors
- + pagetoid spread –> not clearly melanoma
Stains:
MART-1 (Melan-A)
- Most sensitive and specific
HMB-45
S-100
Histo:
Cytologic atypia:
- Cellular enlargement
- Nuclear enlargement
- Nuclear pleomorphism
- Hyperchromasia of nuclei
- Nucleolar variability
- Mitoses
Architectural disorder:
- Asymmetry
- Poor circumscription
- Variation in size of nests of melanocytes in the lower epidermis and dermis
- Lack of maturation of nests with descent into the dermis
- Pagetoid spread
A 67 year old woman with a history of repeated sunburns as a child and adolescent comes to her physician because of changes in a mark on her cheek. What is her diagnosis and what caused these changes?
Lentigo maligna melanoma:
Represents up to 15% of cutaneous melanomas
- Diagnosed most frequently in the 7th-8th decade of life
- Arises in a precursor lesion termed lentigo maligna
- 5% of lentigo malignas progress to invasive melanoma
Pathogenesis: cumulative sun exposure
- Found on chronically sun-damaged skin
- Head and neck
- Preference for the nose and cheek
- Slow growing
Appearance: Ill-defined, asymmetric, brown to black macule with color variegation and an irregular border
* Both LM and LMM more difficult to excise because of ill-defined margins
Least association with nevi
- *Histo**:
- Background: solar elastosis, melanophages, atrophic epidermis with effaced rete-ridges, uneven pigmentation (foci of solar lentigo or solar keratosis frequent), and melanocytic hyperplasia
- Uneven distribution and increase in number of melanocytes in the lower 1/3 epidermis (significant scatter infrequent); at the periphery solitary melanocytes (multinucleation common) frequently predominate over nests making it difficult to assess the boundaries of the neoplasm
- Lentigo maligna melanoma: if melanocytes are found in the dermis
- Atypia ranges from subtle to marked
A man came in for an annual physical and his physician noted a mark on his back (below). The physician asked if he had always had this mark and he denied seeing it before, though he didn’t spend much time examining the skin on his back. Why is the physician concerned and what could it be?
Superficial spreading melanoma:
Most common subtype:
- Account for 70% of all melanomas
- Diagnosed most often between the ages of 30 and 50 years
Occurs at any site, most frequently:
- Trunk of men
- Legs of women
Pathogenesis:
- Asymptomatic
- Slowly changing from months-years
- Brown to black macule with color variegation and irregular, notched borders
- Best fits the ABCD criteria
- When enters radial growth phase–> papule or nodule
** Can arise de novo or in a pre-existing nevus
Histo:
Melanocytes present at all levels of the epidermis:
- “pagetoid” cells in “pagetoid” spread (AKA scatter or buckshot effect)
intraepidermal component is prominent
- “radial horizontal growth phase” neoplastic cells confined to epidermis and papillary dermis
A 68 year old man of Chinese descent comes to his physician for plantar warts on his feet that won’t go away. On exam the physician notes the atypical discoloration of the warts and suspects it may be something else. A biopsy is taken. What would you expect to see in the lesion?
Acral lentiginous melanoma:
5-10% of all melanomas:
- Most common subtype in darker-pigmented individuals
- 60-72% in African Americans
- 29-46% in Asians
Median age of onset being 65 years old
- Most common site is the sole
- Not all palmar or plantar melanomas are ALMs (minority are SSMs or NMs)
Appearance:
- Variegation in color and irregular borders
- May be mistaken for plantar wart or hematoma
More advanced lesion upon diagnosis associated with poorer outcomes
** ALM is not thought to be associated with sun exposure
- *Histo**:
- within the epidermis, there is marked increase in solitary melanocytes lacking a well-nested pattern with foci of effaced rete-ridges
- there is significant scatter of melanocytes as there are melanocytes at all levels of the epidermis including the cornified layer*
A 58 year old man comes to his physician for what he believes is a bad case of nail fungus. His thumbnail has been cracking and peeling and recently there is some bruising that has developed at the base of the nail, though he can’t remember injuring his thumb. What is his possible diagnosis and prognosis?
Subungual melanoma:
Variant of ALM:
- Generally arises from the nail matrix
- Most commonly on the great toe or thumb
- A widening, dark, or irregularly pigmented longitudinal nail streak (melanonychia striata)
+/- Nail dystrophy
- *Hutchinson sign=**
- _Pigmentation of the proximal nail fold
- Poor prognosis,_ associated with advanced subungual melanoma
A 55 year old man comes to his physician for an annual physical and a skin check. The doctor notes a nodule on the man’s shoulder blade (below). What is the physician concerned this could be? What are poor prognostic indicators?
Nodular melanoma:
Second most common type of cutaneous melanoma:
- Accounts for 15-30% of all melanomas
- Believed to arise as a de novo vertical growth phase tumor without the pre-existing horizontal growth phase
Epi:
- Mean age of onset is 53 years
- More common in men
Appearance:
- Occurs most frequently on the trunk
- Blue to black, or pink to red-colored, nodule
+/- ulceration
* Tend to be diagnosed at a thicker, more advanced stage with an associated poorer prognosis
Histo:
Neoplastic cells are present in the papillary and reticular dermis with a “vertical growth phase”
“vertical growth phase” defined as aggregations of neoplastic cells in the dermis are larger than those in the epidermis
A 70 year old woman comes to the dermatologist because of a cyst on her forehead that has gotten larger and she wants to have removed. She states it has actually started to hurt as well. What is the dermatologist concerned about and what histologic features may be visible?
Desmoplastic melanoma:
Indurated papule, plaque, nodule
Pigmentation absent in at least 40% of cases (i.e. amelanotic)
Typical locations:
- Head and neck (53.2%)
- Extremities (26.2%)
- Trunk (20.6%)
Mean age 63 years old
Diagnosis is delayed due to non-specific clinical features
Histopathologically, it may simulate fibrosis/scar or a neural neoplasm leading to misdiagnosis and inappropriate treatment
Histo:
Architecture:
- intraepidermal component may or may not be present
- interstitial fibrosis and collagenization
- thick lesion usually: mean Breslow depth at dx is 2-6.5mm (red arrow)
- lymphocytic infiltrates often as nodular aggregates (blue arrow)
Cytology:
- elongated, usually basophilic cells, tapered nuclei (black arrow)
- S100+ but other melanocytic markers often negative (HMB45, Melan A/Mart 1, MITF)
- Neurotropism is common
A 14 year old girl is admitted to the hospital with a skin eruption over a large area of her body. A skin biopsy reveals no bacteria. What is a possible diagnosis?
Toxic Epidermal Necrolysis: (could also be staph exfolatoxin, but that only involves subcorneal splitting- this is necrotic)
Involves at least 2 mucous membranes
Eruption involves greater than 30% of a patient’s body surface area
Diagnosis supported by skin biopsy
Poor prognosis, supportive care
Histo: extensive necrosis of epidermis
A 35 year old African American man visits a dermatologist after being unsuccesfully treated with topical antibiotics for a suspected case of folliculitis. What is his diagnosis based on the appearance of his skin and the inability to cure with antibiotics?
Acne keloidalis nuchae: seen in AA
Bands of thick collagen
Chronic inflammatory cells
Hair follicle destruction
A 32 year old woman comes to your office complaining of long-standing painful abscesses in her armpits and along her buttocks and thighs. Her previous physician told her it was due to an infection and lack of proper hygeine. She has been thoroughly cleaning the affected areas and taking antibiotics but the abscesses don’t seem to get any better. In fact, they seem to get worse around her menstrual cycle. What is her diagnosis?
Hidradenitis Suppurativa:
Primarily an inflammatory process
Multi-focal and symmetric involving 2 or more locations
Treatment is difficult, significant scar results
* Often confused with infection like Staph abscess or folliculitis
Histo:
Suppurative, granulomatous inflammation
Sinus tracts
Fragments of hair shafts
A 50 year old man comes to the physician with a suspected abscess on his chest. He did not cut the skin but the cyst is swelling and red. Antibiotics have helped in the past with the swelling and redness but he wants to get rid of it. What is the diagnosis and treatment?
Epidermal cyst:
Firm, mobile nodules, originate from plugged hair follicles
Confused with abscess when inflamed
Antibiotics reduce inflammation, treatment is excision
Histo:
Cyst lining with granular layer
Lamellated keratin
A man comes into the physician for a new rash all over his body. He states he was feeling fine until about 2 days ago when he developed a sore throat. What is his likely diagnosis, what else may develop on his skin, and what is his treatment?
Scarlet fever:
Caused by Group A Streptococci, erythrogenic exotoxin
Begins 24-48 hours after sore throat
Sandpaper-like papules
Below: Pastia lines and subsequent desquamation of palms and soles can occur
Diagnosis is strep culture or ASO
Treat with antibiotics
An older man comes to your clinic for a red firm rash that developed on his face after shaving. He had a sore throat for the past two days prior to developing the rash. What is his diagnosis and treatment?
Erysipelas:
Caused by Group A streptococcus
Infection of superficial dermal lymphatics often from lacerations
Erythematous, brawny plaque on face or legs
Diagnosis is clinical
Treat with oral antibiotics
A 75 year old woman is being treated for arthritis by her physician who notes the following on her skin. She feels fine except for her knee pain which prevents her from walking very much (she is largely confined to a chair within her home. What is her diagnosis, what caused it, and what is the treatment?
Stasis dermatitis: can be confused by staph or s. pyogenes cellulitis.
Caused by v_enous stasis_
Erythema or even yellow-brown plaques with lichenification
Often bilateral
Diagnosis is often clinical
Treatment is compression and topical steroids
A 25 year old woman returns from a hiking trip in the Adirondaks with the following on her arm. What is her diagnosis and what changes are seen in her skin?
Erythema migrans:
Caused by Borrelia burgdorferi
Begins 3-32 days after bite as a papule and becomes annular
25-50% of patients develop multiple lesions
EM fades on its own
Diagnosis is clinical
Treatment is with doxycycline
Histo:
Superficial and deep perivascular mixed cells infiltrated
Plasma cells are often present
A 50 year old man, recently returned from a trip to Morrocco, comes to his physician for treatment of a foul-smelling ulcer on his penis. There is no lymphadenopathy. What is his diagnosis?
Front: Granuloma inguinale:
K. granulomatis
2-3 weeks post infection
beefy red, foul-smelling ulcer without lymphadenopathy
Below: Lymphogranuloma venereum (LGV):
Chlamydia trachomatis
3-30 days post-infection
Begins as a painless erosion
Erosion heals, leading to massive, fluctuant LAD
The following histological specimen was obtained from the fingertip of a 12 year old girl. What is her diagnosis?
HPV Verruca
Papillomatosis
Hyperkeratosis
Hypergranulosis
Dilated blood vessels
Viral changes
What is the diagnosis of the rash on the face of this man? IS it viral or bacterial?
HSV: herpetic sycosis (front), herpes gladiatorum (below)
The following is a skin biopsy from a vesicle on the face of an 18 year old boy 3 days after acquiring an upper respiratory tract infection. Based on the histology, what infection does he have?
Herpes simplex virus:
Epidermal necrosis with vesicle
Below:
Enlarged, multinucleated keratinocytes with margination, and steel-grey nuclei
A 25 year old man comes to the physician with an itchy rash on his body that resembles chicken pox, but he’s sure he had chicken pox when he was 5 years old. What might his diagnosis be?
Pityriasis lichenoides et verioliformis (PLEVA):
Appears very similar to varicella
Much longer time frame
Diagnose with skin biopsy
No great treatment, light therapy, antibiotics, or immune-suppressants
Histo:
Ulceration of epidermis
Dense interface dermatitis
Extravasated RBCs
A 22 year old man is checked into the hospital after developing the following rash. He had a URI and sinus infection a couple of weeks ago that was treated with amoxicillin. Based on his appearance, what might be going on?
HHV4 EBV eruption (morbilliform)
Occurs 7-10 days after treatment with amoxicillin, ampicillin
A baby was born with severe eye problems and the following marks on his skin. What is his diagnosis?
HHV5 CMV baby:
In adults, infection similar to EBV
TORCH syndrome
“Blueberry muffin baby”
In AIDS can be devastating
Can also co-infect with HSV
Treatment is gangciclovir
What HHV infection is apparent on the skin of this baby? What is the disease commonly known as?
HHV6: Roseola
A 25 year old man comes into the physician with a papery, scaly rash all over his body. He has been feeling a bit feverish and sore recently but didn’t seek medical attention until this rash appeared. What is his diagnosis?
Pityriasis Rosea HHV 6 and 7:
Viral exanthem
20% have mild flu-like symptoms
Begins with 2-10cm oval, scaling patch
Followed by smaller oval patches with cigarette-paper scale along skin tension lines on trunk
Diagnosis is clinical
Treatment with topical steroids
Histo:
Focal parakeratosis and spongiosis
Perivascular lymphocytes
A mother brings her newborn son into the physician because of some little pimples around his chest and underarm. What is his diagnosis and treatment?
Molluscum contagiosum:
Common in kids, resolve on their own
Can be STD in adults; giant molluscum seen in AIDS
Histo: Henderson-Patterson bodies
A man comes into the physician freaking out that he has a flesh-eating bacteria. Based on the appearance of his arm below, what might his diagnosis be?
Majocchi’s granuloma:
Dermatophyte invades and ruptures the hair follicle
Most commonly T. rubrum
Treat with oral antifungals
A 60 year old man is concerned he may have a fungal infection (based on the appearance below) but his histologic exam reveals no organisms. What is his likely diagnosis and treatment?
Nummular dermatitis:
Commonly found on the extremities
Round, erythematous plaques with scale
Pathology shows spongiotic dermatitis
Treat with topical steroids
A 24 year old woman has been using topical antifungals in an effort to treat what she thought was a foot fungus (tinea pedis) but she hasn’t been able to make it go away. What is her diagnosis based on the gross appearance and the excessive keratinization seen on histology?
Palmar-plantar psoriasis:
Multiple presentations: dry, scaling patches, verrucous plaques, or pustules
Diagnosis by skin biopsy
Treatment with topical steroids, PUVA, immune supressants
A 45 year old woman comes to her doctor with a horrible scabbing infection on her arm. She scraped her arm a few weeks ago and the wound won’t heal with neosporin. What is her diagnosis and what type of organism is probably involved?
Deep fungal infection
Term for subcutaneous mycoses, usually chromoblastomycosis
Common etiologic agent is Fonasacea pedrosoi
Verrucous plaques and nodules
Diagnose by sclerotic bodies on H&E
Treat with oral antifungals
A 15 year old girl is brought to the dermatologist for a rash/lesion on his arm. A culture reveals bacterial infection. She went to a nail salon recently before this infection started. What might be causing these marks?
Atypical mycobacterium:
Most common etiologic agents are M. fortuitum, M. chelonei, M. abscessus
Infections linked to surgical procedures and nail salon baths
Diagnose by culture
Treat with debridement and combination antibiotics
A 55 year old AIDS patient is being treated for recurrent psoriasis outbreaks on his arms but there seems to be no recession of his symptoms. Based on the pathophysiology of AIDS, his psoriasis should actually be slightly improved with decreased T-cell function. What might his issue actually be?
Norweigan crusted scabies:
Immune-compromised, debilitated patients
HUGE mite load
- Hyperkeratotic lesions
BOTH topical or oral therapy needed
A 67 year old woman who has been treated for DVT in the past presents to her physician with the following purpuric discoloration of her legs (both sides) accompanied by an aching, tingling sensation. What is her likely diagnosis and what are the treatments?
Venous insufficiency:
Incompetent one-way bicuspid valves in veins of legs prevent backflow–> chronic inflammation, fibrosis, etc.
- With aging, valves compromised (incompetent)–> dilated veins
Seen in 6-7% population > 50 years:
- Superficial veins (most common): saphenous veins, tributaries
- Deep veins: anterior and posterior tibial, peroneal, popliteal, deep femoral, superficial femoral, iliac veins
- Perforating veins
Causes:
- Congenital, abnormal valves
- Age-related
- Trauma (injury, vein stripping)
- Venous thrombosis
Symptoms:
- Throbbing, burning, aching, heaviness, restless legs, leg fatigue
Clinical manifestations:
- Spider veins
- Varicose veins
- Stasis dermatitis (often confused with bilateral cellulitis)
- Acroangiodermatitis of Mali (tumor-like veins)- below
- Stasis ulcers
- Lipodermatosclerosis (loss of hair, shiny scar-like skin)
- *Treatment:**
- Compression
- Sclerotherapy
- Vein stripping with ligation
- Valvuloplasty
A 32 year old woman comes to her physician with a new onset of red bumps on her skin. She doesn’t remember having any contact with any irritative substances and only states that she has been having intermittent diarrhea. On further questioning, she does that the diarrhea seems to have some correlation with her diet and she’s been avoiding bread products more recently which seems to help. What is her diagnosis and treatment?
Dermatitis herpetiformis:
Blistering disease of skin due to immune-complex deposition in papillary dermis
- More common in N. Europeans
- Age of onset= 2nd-3rd decade
- 20% of patients have celiac disease, over 90% have GI findings on endoscopy
Clinical findings:
- Herpetiform (grouped) vesicles symmetrically distributed on knees, elbows, forearms, buttock, scalp (rare)
- May have crusted lesions with non-specific pruritis (like atopic dermatitis, scabies, drug eruption)
Pathogenesis:
-
Circulating antibodies including IgA to:
- Gliadin (antigen= wheat protein)
- Reticulum
- Smooth muscle endomysium
- Tissue transglutaminase - Deposition of immune-complexes in mucosa of:
- Small intestine (malabsorption symptoms)
- Papillary dermis of skin (blistering)
Diagnosis:
- Antigens in skin:
- epidermal transglutaminase
- antigen-antibody complex deposits in skin
- NON-circulating - Skin biopsy
- lesional skin forhisto: subepidermal bulla with neutrophils
* *- Peri-lesional skin for immunofluorescence study (granular IgA deposition)** - Tissue transglutaminase Ab in serum
- DQ2/DQ8 HLA testing
- high prevalence in normal population (low positive predictive value)
- High negative predictive value
Treatment:
- Gluten-free diet (slow improvement)
- Dapsone (anti-neutrophilic for skin symptoms)
- Monitor for enteropathy-associated T-cell lymphoma (due to constant antigenic stimulation); DQ2 homozygotes at high risk
A 62 year old man with a history of ethanol abuse comes to the physician following a trip to Florida after he developed a rash on his hands. The rash has some fluid-filled blisters. What might his diagnosis be given his underlying condition and apparent photosensitivity?
Porphyria cutanea tarda:
PCT= most common cause of all porphyria
2 forms:
- Sporadic (80-90%):
- Decreased activity of uroporphyrinogen decarboxylase in liver secondary to underlying liver disease - Familial (10-20%):
- Decreased activity of uroporphyrinogen decarboxylase in all tissues, including erythrocytes
** Most gene carriers asymptomatic until sufficient liver damage occurs
Preciptiators:
- *- Male, over 40, alcohol**
- EtOH, estrogen, hexachlorobenzene, iron overload
- Iron overload (in PCT)-_> decreased uroporphyrinogen decarboxylase activity
Pathogenesis:
- Uroporphyrinogen decarboxylase deficiency–> accumulation of photoactive molecules that absorb visible violet light
- Photo-excited porphyrins in skin–> oxidative damage–> photosensitivity reactions
Clinical manifestations:
- Photosensitivity
- Blisters and skin fragility on sun-exposed sites, dorsa of hands and feet, face
- Shiny skin
- Hypertrichosis (Hairy face)
Associated disease:
- Hep B, C
- HIV
- Beta-thal
- Hemachromatosis
- Hepatocellular carinoma
- EtOH
Diagnosis:
- Skin biopsy (pauci-inflammatory subepidermal bulla= epidermal lifting with no inflammation, necrosis)
- Fresh urine (pink to orange-red with Wood’s lamp)
- Porphyrin analysis (24 hr urine, plasma, stool)
Treatment:
- Phlebotomy (decrease Fe overload)
- Hydroxycholorquine (anti-malarial)
- Block sun exposure
A 40 year old woman comes to her doctor because of new onset of joint pain in her knees and ankles. Additionally she has developed nodular rashes on her skin. She takes birth control pills but is in otherwise excellent health. She read online that this might be a manifestation of Lyme disease but she hasn’t been outdoors in months (it’s March). What is another possible diagnosis?
Erythema nodosum:
Occurs at any age, generally young, healthy adult women
- Tender erythematous nodular eruption (pre-tibial)
- May be accompanied by arthralgia (ankles, knees, wrists)
- Septal panniculitis
Hypersensitivity reaction associated with other diseases, but 1/2 idiopathic
- Infections (strep, viral, fungal)
- IBD
- Drugs (OCP, sulfonamides, penicillin)
Usually self-limited
- *Treatment:**
- Oral corticosteroids, SSKI (super-saturated potassium iodide)
- *Histo**:
- Septal
- Mostly chronic inflammation
- Granulomas
- Fibrosis
- Mimicry: Infection, Factitia
A 35 year old diabetic man comes to the physician after developing a plaque-like rash on his shin he can’t remember any injury to his shin. Based on the appearance and his health, what might it be?
Necrobiosis Lipoidica:
Unknown pathogenesis
Morphology:
- Plaques with violaceous brown border, atrophic center
- Histiocytes, lymphocytes, plasma cell around blood vessels
Epidemiology:
- *- 0.3% diabetic patients have NLD**
- 22-65% with NLD have diabetes
- Avg age= 30 years
No effective treatment:
- intralesional steroids
- doxycycline (anti-granulomatous)
A 47 year old woman with a 20 year history of SLE comes to the hospital after she developed some bruising on her toes that has gotten progressively worse. She doesn’t remember hurting her feet, but the brusing has gotten worse and the skin is breaking down. What is occuring and what might you expect to see histologically?
- *Leukocytoclastic vasculitis**:
- *Immune-complex deposition mediated destruction of post-capillary venules**
Skin= most common involved organ
- Purpuric papules (palpable purpura)
- Urticarial papules, purpuric macules, vesicles/bullae, pustules, ulcers
- Distal areas, classically bilateral legs
Skin lesions my have systemic signs/symptoms:
- Fever, joint pain, abdominal pain, bloody urine
- may indicate internal organ involvement
- *Manifestation of diseases/meds:
- Connective tissue diseases**
- Viral, bacterial infections
- Malignancies, lymphomas/leukemias
50% cases are idiopathic
Workup: CBC, BUN, Cr, LFT, ESR, RF, ANA, Antistreptolysin, cryocrit, serum protein electrophoresis, hepatitis serologies
- *Histo**:
- Neutrophils
- Extravasated RBCs
- Fibrin deposition around vessels
Treatment:
NSAIDs, antihistamines
Colchicine
Antibiotics (Dapsone)
Corticosteroids
A 45 year old man comes to the doctor because of a new patchy bruise on his legs that he can’t explain. Titers are ordered which test positive for HBsAg. Based on his underlying illness and presentation, what might his diagnosis be?
Polyarteritis nodosa: skin manifestations:
Necrotizing neutrophilic vasculitis of small to med-sized vessels with predilection for GI tract, liver, kidneys, skin
Symptoms:
- Fevers, arthralgia, myalgia, abdominal pain, mononeuritis multiplex, renovascular HTN, microaneurysms, NO pulmonary involvment
- Skin involved in 50% cases, livedo reticularis, plaques, nodules, ulcerations
- 10% skin-limited
Associated with:
- Hep B (7%)
- Hep C, HIV, strep, CMV, parvo B19
- Most cases idiopathic
Presentation:
- ulceration
- dispigmentation: retiform purpura on legs- worrisome vasculitis/vasculopathy (non-blanching)
- nodules
A 37 year old woman comes to her physician with the following purpura on her legs. In her chart, you see that she has had 2 miscarriages and one premature delivery in the last 5 years. You perform a dilute venom viper test to test for what pathologic condition? How would you treat her?
Antiphospholipid syndrome:
APL syndrome seen in women (80%) ~42 years old
1-5% young, health people have Antiphospholipid antibodies without consequences
- Occur with other conditions; IgM are present at low levels (infections, cancer, drugs, hemodialysis)
Group of heterogeneous antibodies:
- *1. Lupus anticoagulant
- dilute Russell’s viper venom time (PTT prolongation)
- Corrects with addition of excess phospholipid/platelets**
2. Anticardiolipin - ELISA on cardiolipin-coated platelet in presence of bovine serum
3. anti-beta2 glycoprotein antibodies (phospholipid binding proteins) - ELISA for coated platelets
Diagnostic criteria:
- Anticardiolipin or lupus anticoagulant antibodies 2+ times, 6 weeks apart
- Clinical: vascular thrombosis +/- pregnancy complications
Clinical classfication:
- Primary: no associated disease (90%)
- Secondary: SLE, RA
Presentation:
1. Thrombosis of large and small vessels of both arteries and veins of any organs
- deep venous thrombosis= most common
- arterial thrombosis= strokes and TIA
2. Complications
- pulmonary emboli
- emboli of vegetation of cardiac valves
- gynecologic: miscarriages usually during fetal period, premature delivery
3. Acute involvement of small vessels= similar to HUS, TTP
- results in loss of organ function
- Catastrophic antiphospholipid syndrome
Cutaneous manifestations:
- superficial thrombophlebitis
- ulcers
- livedo reticularis
- *- acrocyanosis**
- *Treatment:**
- High intensity warfarin therapy (INR: 3.1-4.0)
- Plasmapheresis and/or IVIG for refractory and “catastrophic” cases
A 56 year old man with a history of ulcerative colitis comes to the physician because of an infection on his legs that won’t go away. He treated it with neosporin and Hydrogen peroxide but the lesion hasn’t improved. After a culture of the wound reveals no abundant bacteria, what is his likely diagnosis?
Pyoderma gangrenosum:
Diagnosis of exclusion
Chronic suppurative inflammation resulting in tissue destruction
Size and depth of the ulcers vary
Associated diseases:
- inflammatory bowel disease, especially ulcerative colitis
- IgA monoclonal gammopathy
- leukemia
A 49 year old woman awaiting kidney transplant is on dialysis when she develops lesions in her skin. She is worried she has an infection. What is likely to be her diagnosis, what caused it, and is there a treatment?
Calciphylaxis
Almost exclusively seen in patients with end-stage renal disease
- Progressive calcification of small arteries result in ischemic necrosis of the skin
- No effective treatment
- High mortality rate-60 to 80% due to sepsis
Histo: fractured blood vessel lining= calcification
Treatment: difficult (already sick with dialysis)
A 68 year old man comes to the office for a huge bruise that apparently formed around his eye over the past two days. He claims there was no inciting trauma but is clearly worried about what it might mean. A blood draw is performed that reveals elevated WBC count and a plasma electrophoresis demonstrates elevated Ig. What might be seen on skin biopsy and what caused the purpura seen?
Amyloidosis:
Underlying causes: Multiple myeloma and Waldenstrom’s macroglobulinemia
- Amyloid consists of immunoglobulin light chains
- Deposition may occur in any organs
Skin and mucosal lesions
- deposits in vessels result in purpuras (leaky vessels)
- pink translucent papules and nodules
macroglossia
Classic sign: carpal tunnel syndrome and purpura (e.g. raccoon eye sign, pinch purpura)
Diagnosis:
_1. Skin biopsy
- amorphous pink homogeneous material
- stains with Congo red, which turns bright green_fluorescence upon polarization
2. Rectal mucosal biopsy
3. Abdominal subcutaneous fat aspirate
A 25 year old man comes to the dermatologist because he thinks he is developing acne or a rash on his back that his girlfriend said he should have treated. The “rash” is clearly not acne and does not follow a pattern for dermatitis. A blood panel reveals severely elevated triglycerides (500) and a punch biopsy is performed. What would the punch biopsy reveal and what is his diagnosis?
Eruptive xanthoma:
Usually widespread eruption of yellowish papules
- High triglcyeride level due to lipoprotein lipase deficiency, less often seen in patients with diabetes and patients on retinoids (accutaine, isotretinoins)
- Skin biopsy shows lipid laden foamy histiocytes and interstitial deposition
- Complications include pancreatitis and atherosclerosis
A 55 year old woman comes to the dermatologist in tears, complaining that her psoraisis will not go away even though she’s been treating it as directed. On exam, she states that the plaques she has have never gone into remission, but have remained fairly stable for the past few months. Based on her presentation, what might her diagnosis be? What would be seen on blood smear?
Mycosis fungoides:
The most common form of T-cell lymphoma of the skin (NOT fungus!)
Clinical stages include patch, plaque, nodular, tumor, and erythrodermic stages
- Unlike psoriasis, which has flares and remission, this is continuous
Most patients have patches for a lifetime and a few will have progressive disease resulting in death
Pathogenesis:
- Neoplastic proliferation of T-helper cells (CD4+)
- Sézary cells (CD4+ cells with convoluted nuclei) are found in the blood in the erythrodermic stages
Treatment will depend on the clinical manifestation, but the disease is incurable
A 55 year old man comes to the physician for a rash on his arm that he thinks might be shingles- he’s been feverish and feeling ill for several weeks. On exam, it is noted that he has lost 18 pounds since his last visit three months ago. Additionally the rash is not confined to one dermatiome. What else might the physician be concerned about?
**Sweet's syndrome**: _Paraneoplastic syndrome_ (remote effect from primary neoplasm- paraneoplastic pemphigus, necrolytic migratory erythema, erythema gyratum repens)
- Acute febrile neutrophilic dermatosis
Characterized by:
- **tender edematous erythematous papules and plaques
- accompanied by fever and peripheral neutrophilia**
Skin biopsy:
- band like infiltrate of neutrophils in the dermis with edema of the papillary dermis
- no leukocytoclasis of neutrophils (no dust)
Associated with:
- *- acute myeloid leukemia**
- drugs-GMCSF (neutrophil maturation)
- pregnancy
- inflammatory bowel diseases
- upper respiratory infections
Treatment:
- Corticosteroids (treat infection/ malignancy first)
A 22 year old woman with a peanut allergy came to home after a flight with an extremely itchy rash on her legs. What changes have occured histologically and what is her diagnosis?
Urticaria:
Angiocentric skin changes
Often young adults
- Transient, lasts < 24 hrs
- Non-purpuric wheals: Edematous, erythematous papule or plaque
- Intensely pruritic (itchy)
- Angioedema (deep)
- Chronic forms: Urticarial vasculitis, Underlying disease
Pressure
- Dermatographism
Type I hypersensitivity reaction
- Immunologic (IgE-mediated): Mast cell degranulation, Release of histamine, prostaglandins
- Non-immunologic: Mechanical (dermatographism), Temperature
Pathophys:
- Mast cells degranulate: release Histamine, prostaglandins, cytokines
- -> Vascular dilation, Dermal edema, Endothelial activation
- E-selectin/CLA binding
- Angiocentric inflammation: Lymphocytes, neutrophils, eosinophils
- No epidermal changes
An 8 year old boy is brought to the physician by his mother after a palpable rash forms on his leg and he complains of abdominal pain and brown urine. 1 week earlier he had an upper respiratory infection that has resolved. A skin biopsy is performed which reveals the following. What changes have occured and what is his diagnosis?
Necrotizing vasculitis:
Angiocentric skin changes
Seen on Lower extremities
- Palpable purpura= Red macules and papules with dot-like hemorrhage
- Diascopy
Limited to skin or systemic
- Drugs, infection, connective tissue disease, underlying malignancy (Idiopathic in 50%)
Henoch-Schönlein Purpura: seen after strep, viral illness (hematuria, abdominal pain, vasculitis mediated by IgA)
Pathophys:
- Infiltrate of neutrophils with fragmentation (nuclear “dust”)
- Neutrophils chew thru fibrin in vessel walls and lumen (fibrinoid necrosis)
- Hemorrhage due to vessel wall destruction (extravasation–> no blanching)
- Positive DIF (direct immunofluorescence)
A 50 year old man comes to his doctor after developing a blistering, itchy rash on his arms. Yesterday he was pulling weeds in his backyard. What types of histologic changes have occured on histology? What is his diagnosis?
Allergic contact dermatitis:
Form of Spongiotic dermatosis
Pruritic, well-demarcated, erythematous, edematous papules and plaques with vesicle formation
- Blisters in 1-2 days (Often linear lesions)
- *- Epicutaneous contact (Poison ivy)**
- Scaly with chronicity
Pathophys:
- Type IV reaction= cell-mediated or delayed hypersensitivity
- Antigen taken up by LC; LC to draining LN; present to T helper cells (MHC class II); becomes sensitized
- Sensitization/challenge
Histo:
- Intercellular edema between keratinocytes: May form vesicles (front)
- Langerhans (APCs) cells in vesicles
- Perivascular infiltrate of lymphocytes, histiocytes, and eosinophils
A 30 year old woman comes to the physician with a silvery, scaly patch on both of her elbows. She has scratched some of it off and there are erythematous lines around the plaques. A biopsy of the site reveals the following changes in her skin. What is her diagnosis and what types of pathological changes have led to her symptoms?
Psoriasis:
Acanthotic process: hyperplasia of epidermis
Erythematous plaques with silvery scale
- Pustules (early)
- Silvery scale (late)
- Often symmetric, B/L: Elbow, knees, scalp, intertriginous, or generalized
- *- Koebner phenomenon (damage–> lesion)**
- Auspitz sign (scale lifted–> bleeding)
- HLA types : Cw6, B13, B17, Bw57
Psoriatic arthritis: seen in 5-8% of psoriasis patients
- higher association with nail bed changes
Histo:
- “Regular” acanthosis
- Parakeratosis
- Neutrophils in scale
- Loss of granular layer
- Thin suprapapillary dermal plate
- Prominent, dilated capillaries
- *Pathogenesis:**
- Lymphocytes
- Autoreactive T cell
- Keratinocytes
- Shortened epidermal cell cycle (28x nl production)
- Vessel alterations: abnormal post-capillary vessels (dilated)
A 30 year old woman comes to her physician because of a new onset of hair loss on her scalp. At the site of hair loss there is scaling and erythema, which led her to believe she had tinea capitis, but topical antifungals have not changed the course of her disease. A biopsy is performed that reveals the following changes in the interface between the dermis and epidermis. What is her diagnosis?
Discoid Lupus:
Interface changes in epidermis/dermis:
Acute Form:
- Facial erythema (malar rash)
- Generalized erythema: Face, arms, neck, dorsal hands
- Bullae
Subacute Form
- Psoriasiform
- Annular vesicular
- *Chronic Forms**
- Discoid lesions (5-10% have systemic disease)
- Scaling, atrophic plaque
- Hypo/hyperpigmentation
- Follicular plugging
- Alopecia
- Panniculitis (50% have systemic disease)
Discoid lupus (confined to skin, may develop systemic disease in 5-10%):
- Localized to skin
- Scaling atrophic plaques
- Pigmentary changes
- Telangiectasia
- Alopecia
- Follicular plugging
Discoid lupus histology:
- Hyperkeratosis (scale)
- Epidermal atrophy= Lymphocytes attacking DEJ (interface)
1. Basal cell vacuolization due to interface
2. Necrotic keratinocytes (attacked by lymphocytes- pyknotic keratinocytes)
3. Pigment incontinence: dump melanin
- Superficial & deep perivascular & perifollicular: Follicular destruction
- Dilated vessels
- Positive ‘Lupus Band’= Granular IgG & C3 along thickened BM
A 50 year old man comes to the physician with a scaly purple plaque on his leg. Histology reveals the following. What type of pathological changes have occured and what is his diagnosis?
Lichen planus:
Interface process
Scaly, flat-topped, violaceous papules and plaques
The 5 Ps:
- Pink to purple
- Pruritic
- Polygonal
- Papules
- Plaques
- Often wrists and ankles; Can occur anywhere including oral mucosa
- Most cases idiopathic
- *Histo: interface process=**
- _Superficial band-like lymphocytic infiltrate (DEJ)
- Necrotic keratinocytes_
- Hyperkeratosis
- Hypergranulosis (wedge-shaped)
- Irregular acanthosis
- Saw-toothing of rete edge
A 45 year old man comes to the physician with a group of large, flaccid blisters (some of which have ruptured) and is worried he has an infection. A skin biopsy reveals the following changes. What is his likely diagnosis and what indicates this is more likely autoimmune that infectious?
Pemphigus vulgaris
Vesiculobullous process
- Flaccid blisters; Easily ruptured
- Erosions
- Scalp, mucosa, intertriginous sites
- Nikolsky sign: press lateral edge of blister, it will spread
- Genetic predisposition
- Commonly 40s-50s
- Autoimmune disease
Histo:
- Blistering is Supra-basal (Tombstone pattern where basal keratinocytes still attached to dermis)
- Acantholysis
- Autoantibodies to Desmoglein 3–> destruction of Desmosomes
** vs Bullous pemphigoid= entire epidermal layer lifts from dermis (no keratinocytes still resting on basement membrane= sub-basal)
- Sub-epidermal blistering also seen in dermatitis herpetiformis
What type of procress has occured in the skin biopsy below?
Bullous pemphigoid:
Bullous pemphigoid: vesicullobullous disease in which there is a subepidermal blister, seen here with an inflammatory infiltrate containing many eosinophils.
Autoantibodies against epidermal basement membrane (vs pemphigus vulgaris= desmoglein 3 antibodies against adhesion molecules)
What type of changes have occured in the skin biopsy from this patient with a history of ulcerative colitis?
Dermatitis herpetiform histo:
vesiculobullous process where the split is subepidermal and associated with collections of neutrophils at the tips of the dermal papillae. This disease is associated with celiac sprue/gluten sensitive enteropathy.
A 65 year old man comes to his doctor with concerns that he has developed a melanoma based on his long-standing history of sun exposure. The physician biopsies the lesion and the following changes are noted on histology. What is present in the lesion that indicates it as malignant or benign? What is his diagnosis?
Seborrhaic Keratosis:
Benign Epidermal neoplasia
- Middle age and older
- Oval or round “stuck on” papule or plaque
- Flesh-colored to brown or black
- Rough surface
- Symmetrical, sharp margins
- Sign of Leser-Trélat: multiple developed over short period of time–> underlying malignancy (release of growth factors)
- Cause???- genetics, sun exposure, viral
Histo:
- Basaloid keratinocytes (follicular infundibulum): can grow up or invaginate
- “Horn cysts”= invagination, gives rough appearance
- No melanocytic derivation (keratinocytes!)
A 75 year old man is sent to the dermatologist for concerns about a spot on his forehead that is scaly and slightly nodular. A biopsy reveals the following. Based on the histology and presentation, what is his diagnosis?
Squamous cell carcinoma:
Malignant epidermal neoplasia
- Scaling, erythematous to flesh-colored plaque or nodule
- May be scaly, ulcerated or crusted
- Occurs most often on sun-exposed skin (75% on head and neck)
- Also on mucous membranes and sites of chronic injury (burn scars, irradiated sites, sinus tracts)
2nd most common skin cancer
- UV radiation induced immunosuppression
- Locally invasive
Potential to metastasize
- 2-5% of SCCs related to sun exposure
- Up to 20% of SCCs arising in sites of chronic injury (draining sinuses, burn scars) and mucous membranes
Histo:
- Atypical keratinocytes
- Growth into underlying dermis
- Keratin pearls (altered, denser homogenous keratin formation)
- Hyperkeratosis
- Parakeratosis
An 8 year old girl is brought to the dermatologist for an unsightly wart on her hand. Based on the histology, what caused this wart and what type of changes are seen?
HPV Verrucae:
Benign epidermal neoplasia; Also, an infection (HPV)!
- Seen at Sites of inoculation
- Malignant transformation with immunosuppression
- “Black dots” when peeled away
Types:
- Verruca vulgaris
- Verruca palmaris/plantaris
- Verruca plana
- Condyloma acuminatum
HIsto:
- Benign squamoid proliferation
- Crown-like with vascularized spires; irritation–> bleeding–> black hemorrhagic spots
- Koilocytosis: nucleus with glassy appearance (intranuclear virus)–> crinkled with halo
- Keratohyaline granules within keratinocytes
- HPV genome (typing): immunohistochem, FISH (high or low risk)
- Cell-mediated immune response–> resolution (unless immune suppressed)
A 75 year old man comes to the doctor after his wife notices a rough, scaly horn on his forehead. He has a history of chronic sun exposure. A biopsy is performed to rule out what and what is his actual diagnosis based on the histology?
Actinic Keratosis
Pre-malignant epidermal changes:
- Rough, scaling, reddish, ill-defined patch or plaque (can see cutaneous horn; may also be wart, carcinoma–> biopsy!)
- Occurs on sun-exposed skin
- UV-radiation induced keratinocyte DNA damage
- Can spontaneously regress (up to 25%)
- May progress to squamous cell carcinoma
Histo:
- Variable atypia; Less than full epidermal thickness
- Hyperkeratosis
- Parakeratosis
- Solar elastosis
- Chronic dermal inflammation
A 55 year old woman is sent to the dermatologist for analysis of a pearly papule on her shoulder. She is fair-skinned and has a history of repeated burns as a child. Based on the histology, what is her diagnosis and prognosis?
Basal cell carcinoma:
Malignant epidermal neoplasia
- Erythematous patch with central erosion/ulceration and rolled, pearly border OR a pearly papule or nodule
- Telangiectasia
- Seen on sun-exposed skin, most common on face
- Most common skin cancer; most common human malignancy
- Rarely metastasizes but may be locally aggressive
Histo:
- Enlarged basaloid keratinocytes (increased mitoses)
- Individual cell necrosis= malignancy
- Bud and extend into dermis
- Peripheral palisading
- Separation artifact on histologic preparation: due to mucinous stroma- washed away after processing
The following is a biopsy from a nevus on the shoulder of a 32 year old woman. What type of nevus formation is present?
Benign melanocytic neoplasia: junctional (front), compound (below)
Benign melanocytic neoplasia
- Most acquired after age 6 months and before age 35
Variable (but uniform) appearance:
- Macular or papular
- Brown to flesh-colored
- Usually <5 mm in diameter
Junctional: present as nest in epidermal-dermal junction
Compound: involves dermis and epidermis
Dermal: neval cells only seen in dermis
Histo:
- Derived from neural crest origin
- Maturation with descent into dermis
Below was a biopsy sample from a nevus on a 25 year old man. What type of nevus is present?
Intradermal melanocytic nevus:
Benign melanocytic neoplasia
- Most acquired after age 6 months and before age 35
Variable (but uniform) appearance:
- Macular or papular
- Brown to flesh-colored
- Usually <5 mm in diameter
Junctional: present as nest in epidermal-dermal junction
Compound: involves dermis and epidermis
Dermal: neval cells only seen in dermis
Histo:
- Derived from neural crest origin
- Maturation with descent into dermis
Below: Melanocytic nevus
A 64 year old man with a family history of malignant nevi has a nevus biopsied after his physician notices some abnormalities in their color and shape. Based on the histology, what type of nevus does he have, and what risks does this carry?
Dysplastic nevus:
Melanocytic dysplasia
- Controversial entitiy
Abnormal: clinical appearance, architecture, cytology, stroma
Isolated vs dysplastic nevi syndrome
- Clinical phenotype
- Personal and family history
- 100% lifetime risk
Premalignant potential, markers for increased melanoma risk
Histo:
- Irregular nests: bridging (nests coalesce), shoulder (epidermal component descends beyond dermis)
- Cytologic atypia
- Stromal fibrosis, lamellar fibroplasia (collagen, onion-skin layering around rete ridges)
The following was excised from the arm of a 57 year old woman. What are the prognostic indicators for the progression of this lesion?
Melanoma progression:
Melanoma progression: grows throughout epidermis into dermis
Radial growth phase (RGP): melanoma in epidermis with small nests in dermis (upper right)
Vertical growth phase (VGP): melanoma extends deeper into dermis (lower left)- poorer prognosis with deeper penetration
Prognosis:
TNM stage:
1. Measured Depth (mm)= thickness (#1 prognostic feature)
2. Ulceration (bad sign)
3. Mitotic rate (more mitoses, worse prognosis)
- Clark level (obsolete finding- how deep)
- TIL Response (tumor-infiltrating lymphocyte response= good prognosis)
- Regression (bad prognosis: body eradicates part of melanoma)
- Vascular Invasion (mets)
- Microscopic Satellites (bad)
- Gender (F fare better than M)
- Site (extremities except hand and feet do better)
- Stage (metastasized= prognostic indicator)
The following biopsy was taken from a lesion on the hand of a patient who was recently diagnosed with AIDS. What caused this lesion, what is visible within the histology (cell types) and how can he be cured?
**Kaposi's Sarcoma**: Virally induced (HHV8) vascular hyperplasia rather than a neoplasia - Metastatic vs multifocal - AIDS defining disease (HHV8 infection accompanied by immune suppression to manifest)
In immunocompromised individuals, it can be found in the skin and in any visceral organs, especially:
- GI bleeding, pulmonary hemorrhage, lymph nodes
4 types:
- Epidemic AIDS related
- Usually related to low CD 4 count - Classic/ sporadic
- Elderly Mediterranean/ Eastern European men
- Seen in lower extremity
- NOT immune compromised - Immunocompromised
- Transplantation
- Sirolimus (mTOR inhibitor- can cause OR treat in transplant patients), anti-VEGF, antiangiogenesis - Endemic/ African
- Indolent or aggressive
- Lymphadenopathic form in children
Manifestations:
Patch, plaque, nodular, exophytic, infiltrative, lymphadenopathic
Histology
- Spindle cell proliferation of endothelial cells with slit-like vascular spaces, extravasated RBCs
- May be more lymphatic in origin than vascular by staining patterns
