CIS - Dobson, Putthoff

Question 1

24 yo female, multiple skin lesions. Over 100 tan-brown macules and papules over her body, in sun-exposed and non-sun-exposed surfaces, 2-8mm. Single and clustered atypical melanocytes at DE junctions, linear fibrosis of superficial dermis, sparse inflammatory infiltrate in dermis.

Most likely molecular change?

Answer 1

Dysplastic nevus

Inherited loss of function of CDNK2A gene

Question 2

FGFR3 RTK mutation

Answer 2

SKs, acanthosis nigricans, achondroplasia

Question 3

DNA MMR genes MSH/MLH1

Answer 3

HNPCC, Muir-Torre

Question 4

Unbridled SHH signaling

Answer 4

BCC

Question 5

34 yo caucasian, moles have been getting larger, darker, and more numerous. Chloasma and linea nigra present. 15 pigmented macules, all under 3-4mm, symmetric w/ regular borders and uniform color. Scattered tan-brown polypoid lesions attached by slender stalk on neck and exilla. These have increased as well. The latter ones are…?

What is going on?

Answer 5

Fibroepithelial polyps/acrochordons/skin tags

Pregnancy –> causing increase in these

Question 6

Lipomas, liposarcomas - LOOK UP

Answer 6

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Question 7

Pilar cysts (wen) - LOOK UP

Answer 7

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Question 8

69 farmer male pattern baldness, new lesion on top of head over 4 months. Prior scalp biopsies on head. Red-tan nodular and centrally ulcerated lesion on scalp. Also scattered red-ten hyperkeratotic lesions on scalp, face, and arms. Nodular mass shows atypical polygonal cells with intercellular bridges extending into the dermis and involving lymphatics

The benign lesions?

Genetics?

Answer 8

Squamous cell carcinoma

Actinic keratoses??

TP53 mutations at pyrimidine dimers (xeroderma pigmentosum = risk)

Question 9

19 female w/ multiple maculopapular skin lesions. PMH of Meigs syndrome. Multiple pearly papules, some appear pigmented. Vascular telangiectasia. Some erythematous and ulcerated. Multifocal islands of basophilic cells in mucinous matrix. Cells at periphery are palisading. No hair follicules.

Genetics? Result?

Common associated tumors?

Answer 9

Nevoid BCC syndrome (Gorlin syndrome)

Germ-line mutation in one PTCH allele
—> SHH pathway activation

Ovarian fibroma, medulloblastomas, odontogenic…

Question 10

FGFR3 – 3 things

Answer 10

• Thanatophoric dysplasia (achondroplasia)
• Acanthosis nigricans
• Seborrheic keratosis

Question 11

Osteosarcoma - 2 genes

Answer 11

RB

TP53 - Li Fraumeni syndrome

Question 12

11 male, new arm fracture after falling out of bed. Had other fractures, some form of bone disease. Small for age. Slight hearing impairment bilaterally and small deformed blueish teeth. Complete fracture of mid humerus w/o bone deformities.

Genetics?

Answer 12

Osteogenesis imperfecta

Mutation in genes encoding alpha-1 and alpha-2 chains (COL1A1 and COL1A2)

Question 13

11 male, new arm fracture after falling out of bed. Had other fractures, some form of bone disease. Small for age. Slight hearing impairment bilaterally and small deformed blueish teeth. Complete fracture of mid humerus w/o bone deformities. What slow growing locally aggressive tumor w/ pinwheel fibroblasts is associated with the same molecular abnormality?

Genetics? (2)

Other description for the “pinwheel” fibroblasts?

What bone deformities would you be looking to rule out? (examples)

Answer 13

Dermatofibrosarcoma protuberans

COL1A1, PDGF-beta (LOOK UP)

Storiform (swirling)

Erlenmeyer flask, Codman triangle, onion skin, etc

Question 14

Kids w/ bone disease

Answer 14

• OI
• Osteopetrosis
• Rickets
• Renal osteodystrophy
• ## Osteonecrosis

Question 15

Sequestrum

Answer 15

Dead bone in osteomyelitis

Question 16

Involucrum

Answer 16

Newly deposited shell of bone around devitalized dead bone in osteomyelitis

Question 17

Ollier disease, Maffucci syndrome – what lesions?

Answer 17

Enchondromas

Question 18

GNAS1 gain of function mutation

If combined w/ soft tissue (intramuscular) myxomas?

If combined w/ precocious puberty and brown skin spots?

Answer 18

Fibrous dysplasia

Mazabraud’s syndrome

McCune-Albright syndrome

Question 19

t(X;18)

Made up of? (2)

Answer 19

Synovial sarcoma

BIPHASIC – Malignant spindle-shaped cells + malignant epithelioid cells of gland-like structures

Question 20

HLA-DRB1

Answer 20

Rheumatoid arthritis

Question 21

Increasing clumsiness for several days following atypical pneumonia and mononucleosis. Numbness in LEs and decreased DTRs bilaterally. Progresses to respiratory failure.

Described as what type of disease?

Time frame to be considered a chronic inflammatory demyelinating polyneuropathy? What else differentiates the 2?

Answer 21

Guillan-Barré

Acute, inflammatory demyelinating polyneuropathy

2+ months, responds to steroids (if chronic)

Question 22

Increasing clumsiness for several days following atypical pneumonia and mononucleosis. Numbness in LEs and decreased DTRs bilaterally. Progresses to respiratory failure. CSF is most likely to show what?

Answer 22

Increased protein, scant white cells

Question 23

Gram (+) rods, non-spore forming

Gram (+) rods, spore-forming

Answer 23

Diphtheria, Listeria

Anthrax, Clostridium

Question 24

Distal, symmetric sensorimotor neuropathy w/ autonomic components

Answer 24

Diabetic neuropathy

Question 25

Mexican lady, leonine thickening facies, pins and needles of LEs, increased difficulty walking. Type 2 DM on oral hypoglycemic medication. Shallow erythematous ulcerations on shin regions and features consistent w/ bilateral sensorimotor neuropathy to approximately the mid-calf bilaterally. Normal HbA1C. High PGL-1 antibodies.

Answer 25

Leprosy – Infectious neuropathy

Question 26

27 white female, blurry vision and malaise. Weakness and fatigue several months ago especially while walking or with prolonged standing. Drooping eyelids and some nystagmus upon exam. Repetitive physical exercises w/ generalize rapid muscle fatigue.

If muscle fatigue got better w/ physical exercises?

Answer 26

Myasthenia Gravis

Lambert-Eaton Myasthenic Syndrome

Question 27

27 white female, blurry vision and malaise. Weakness and fatigue several months ago especially while walking or with prolonged standing. Drooping eyelids and some nystagmus upon exam. Repetitive physical exercises w/ generalize rapid muscle fatigue. Chest X-Ray shows anterior-superior mediastinal mass of 5.2 cm in diameter.

Answer 27

Thymic tumor

Question 28

67 white female, fatigue and lethargy. Profound lack of energy for months and wants to know about iron supplementation. Obese, glucose elevated. Weakness localized to proximal leg extensors and hand/wrist muscles. Norma H/H. Worried about inflammatory myopathy, order muscle biopsy antibody studies and TSH.

Answer 28

Inclusion body myositis