Free USMLE Step 1 Musculoskeletal and Skin practice questions

The face forms in weeks 4 to 8 from neural crest rich prominences around the stomodeum. The two medial nasal prominences merge in the midline to form the intermaxillary segment, which gives the philtrum, the premaxilla carrying the four incisors, and the primary palate in front of the incisive foramen. Each maxillary prominence must then fuse with this merged segment to complete the lateral upper lip and alveolus. Failure of that fusion produces a cleft lip lateral to the philtrum, anterior to the incisive foramen, often through the alveolus (where the lateral incisor is frequently disturbed). Cleft lip, with or without cleft palate, is more common in males, is usually unilateral and more often left sided, and is linked to maternal smoking.

B. Failed fusion of the palatine shelves causes cleft palate posterior to the incisive foramen; this patient's palate is intact. Isolated cleft palate is more common in females and more often syndromic.

C. Failure of the medial nasal prominences to merge gives a rare median cleft lip through the philtrum, associated with holoprosencephaly. This patient's philtrum is intact.

D. Failed maxillary and mandibular fusion widens the mouth (macrostomia) at the angle, not through the upper lip.

E. A persistent groove between the lateral nasal and maxillary prominences produces an oblique facial cleft along the nasolacrimal groove toward the eye.

Long-standing, steroid-resistant scaly patches on sun-protected skin (buttocks, trunk) that progress to plaques, with a clonal CD4+ T-cell population that has lost the pan-T antigen CD7, indicate mycosis fungoides, the most common primary cutaneous lymphoma. The neoplastic cells are skin-homing CD4+ helper T cells with convoluted, cerebriform nuclei. They show epidermotropism, migrating into the epidermis with little accompanying spongiosis, and their intraepidermal clusters are Pautrier microabscesses. Despite the name, these collections consist of malignant lymphocytes, not neutrophils, and the disease has nothing to do with fungi. Mycosis fungoides evolves over years from patch to plaque to tumor stage. When the same cerebriform cells circulate with generalized erythroderma and lymphadenopathy, the disease is Sezary syndrome.

A. Neutrophil collections in a parakeratotic stratum corneum are Munro microabscesses of psoriasis. B. Marked spongiosis with eosinophils suggests eczematous or allergic contact dermatitis, which should not contain a clonal CD7-negative T-cell population. D. Large CD30+ hallmark cells with horseshoe nuclei characterize anaplastic large cell lymphoma, including primary cutaneous ALCL. E. An angiocentric, angiodestructive infiltrate with necrosis is the pattern of extranodal NK/T-cell lymphoma, nasal type.

This child has acute hematogenous osteomyelitis of the distal femoral metaphysis, most likely from Staphylococcus aureus (gram-positive cocci in clusters), the most common cause at every age. In growing long bones, the nutrient artery branches end in capillary loops at the metaphysis that turn back sharply toward large venous sinusoids. Blood flow slows in these loops and phagocytic cells are sparse, so bacteria circulating during a transient bacteremia settle there, attach to bone matrix through collagen-binding adhesins and multiply. Pus under pressure then strips the periosteum, compresses vessels and kills bone, producing a sequestrum that is later walled off by an involucrum. The distal femur and proximal tibia, the fastest growing metaphyses, are the favorite sites.

B. Transphyseal vessels persist only in infants younger than about 18 months; they let metaphyseal infection spread into the epiphysis and joint, but they do not explain why bacteria settle in the metaphysis, and this 7-year-old has no joint involvement. C. Cortical density does not determine where hematogenous bacteria lodge; the problem with antibiotics is dead bone (sequestrum), which develops later. D. Joint lymphatics do not seed bone; spread is usually from bone to joint, not the reverse. E. End-artery supply to the epiphysis underlies osteonecrosis, such as Legg-Calvé-Perthes disease, not infection of the metaphysis.

Forceful upward traction on the abducted arm, as when grabbing a bar or branch during a fall, stretches the lowest elements of the plexus, producing Klumpke palsy of the lower trunk (C8 and T1). C8 and T1 supply all the intrinsic hand muscles through the ulnar and median nerves, including all lumbricals and interossei, so the hand shows a total claw (MCP hyperextension and IP flexion) with loss of finger abduction, adduction and grip. Sensory loss over the little finger (C8) and medial forearm (T1) matches the dermatomes. The ptosis and miosis are Horner syndrome: preganglionic sympathetic fibers to the head leave the cord with the T1 root and enter the sympathetic chain through its white ramus, so a lesion involving T1 close to the spine interrupts them. Preserved shoulder abduction and elbow flexion exclude upper plexus injury.

A. Upper trunk (Erb) injury follows lateral neck traction and gives the waiter's tip posture with weak deltoid, rotator cuff and biceps; the hand is spared.

B. Middle trunk (C7) injury weakens triceps and wrist extension with middle finger numbness; it does not cause total claw hand or Horner syndrome.

D. Posterior cord injury affects axillary and radial nerves: weak deltoid and extensors (wrist drop) without intrinsic hand paralysis.

E. Lateral cord injury weakens the musculocutaneous nerve and the lateral root of the median nerve (elbow flexion, forearm pronation and flexors) and spares the intrinsic hand muscles and sympathetics.

The drug is hydroxychloroquine, recommended for essentially every patient with SLE and continued through pregnancy. It is a lipophilic weak base that diffuses into acidic endosomes and lysosomes, becomes protonated and trapped, and raises their pH. Endosomal TLR7 and TLR9 require an acidic compartment and proteolytic processing to sense the RNA and DNA within internalized immune complexes, so hydroxychloroquine blunts the TLR-driven type I interferon response of plasmacytoid dendritic cells. Higher lysosomal pH also impairs antigen processing and loading of peptides onto MHC class II, which reduces presentation of self-antigens to T cells. Clinically the drug lowers flare rates, organ damage, thrombosis and mortality. Because it accumulates in the retinal pigment epithelium, it can cause bull's-eye maculopathy, so baseline and then yearly eye screening after 5 years is needed.

A. Calcineurin inhibition is the mechanism of cyclosporine and tacrolimus (and voclosporin in lupus nephritis), not of an antimalarial. B. Dihydroorotate dehydrogenase, a pyrimidine synthesis enzyme, is inhibited by leflunomide in rheumatoid arthritis. C. DNA cross-linking describes cyclophosphamide, an alkylating agent reserved for severe nephritis or CNS lupus and not used indefinitely or in pregnancy. E. Complement-mediated B-cell depletion describes rituximab, an intravenous anti-CD20 antibody, not an oral weak base.

The oral anti-MRSA drug given for weeks, with myelosuppression (anemia and thrombocytopenia) and a warned interaction with an SSRI (risk of serotonin syndrome from weak MAO inhibition), is linezolid. Linezolid is an oxazolidinone that binds the 23S rRNA of the bacterial 50S subunit and prevents formation of the 70S initiation complex, so translation cannot begin. It is active against MRSA and vancomycin-resistant enterococci.

Bacterial 70S ribosomes differ from human cytoplasmic 80S ribosomes, which is the basis of selective toxicity. Human mitochondrial ribosomes, however, resemble bacterial ones. Prolonged linezolid exposure (usually more than 2 weeks) inhibits mitochondrial protein synthesis in marrow precursors, which helps explain the dose- and duration-dependent thrombocytopenia and anemia, as well as lactic acidosis and optic and peripheral neuropathy with long courses.

A. Causing misreading through the 30S subunit is the action of aminoglycosides, which are bactericidal and cause nephrotoxicity and ototoxicity rather than cytopenias.

B. Blocking aminoacyl-tRNA entry at the A site is the action of tetracyclines, associated with photosensitivity and tooth discoloration.

C. Blocking translocation through 23S rRNA is the action of macrolides such as erythromycin, known for GI dysmotility and QT prolongation.

E. Inhibiting peptidyl transferase is the action of chloramphenicol, which also causes marrow toxicity (dose-related suppression and idiosyncratic aplastic anemia) but is not an oral anti-MRSA option that interacts with SSRIs.

Crops of palpable purpura on the lower legs about 7 to 10 days after starting a new drug, with no systemic involvement, is cutaneous (hypersensitivity) small-vessel vasculitis. The biopsy shows the classic leukocytoclastic vasculitis: neutrophils around postcapillary venules, fibrinoid necrosis, nuclear dust from fragmented neutrophils (leukocytoclasis) and extravasated red cells, which make the purpura palpable. The 7- to 10-day lag is the time needed to make antibodies against the drug (here a sulfonamide), which then form immune complexes with circulating drug antigen. These deposit in venule walls, where hemodynamic factors favor deposition in dependent areas. Complement activation generates C5a and recruits neutrophils, which release enzymes that destroy the vessel wall. This is a type III hypersensitivity reaction, confirmed by the granular immunoglobulin and complement. Stopping the drug usually clears the rash within weeks, but a urinalysis is always checked because identical skin histology occurs in systemic vasculitis.

A. IgE-mediated mast cell degranulation (type I) causes urticaria or anaphylaxis within minutes to hours. C. ANCA vasculitis is pauci-immune, with few or no deposits. D. Cytotoxic T-cell killing of keratinocytes is the mechanism of Stevens-Johnson syndrome and toxic epidermal necrolysis. E. Antibodies against basement membrane proteins cause linear deposits, as in bullous pemphigoid or anti-GBM disease.

The protein is transforming growth factor-beta (TGF-beta), the master driver of fibrosis. In a wound it is released from platelet granules and secreted by macrophages, the key cells of repair, during the inflammatory and proliferative phases. TGF-beta stimulates fibroblasts to make collagen (especially type I) and fibronectin, drives their differentiation into myofibroblasts that contract the wound, and inhibits matrix metalloproteinases while increasing tissue inhibitors of metalloproteinases, so matrix accumulates. It is also anti-inflammatory, suppressing lymphocyte proliferation and helping resolve inflammation. Its receptors are serine/threonine kinases that signal through SMAD transcription factors, a feature that distinguishes it from the receptor tyrosine kinase growth factors. Excess TGF-beta activity underlies keloids, systemic sclerosis, pulmonary fibrosis and cirrhosis.

A. PDGF, also released by platelets and macrophages, is chemotactic and mitogenic for fibroblasts and smooth muscle cells, but it signals through a receptor tyrosine kinase and is not immunosuppressive. B. VEGF drives angiogenesis in granulation tissue through receptor tyrosine kinases on endothelial cells. D. EGF, also acting through a receptor tyrosine kinase, stimulates keratinocyte migration and proliferation during re-epithelialization. E. FGF-2 promotes angiogenesis and fibroblast proliferation through receptor tyrosine kinases but is not the main inhibitor of collagen breakdown or of lymphocytes.

The pruritic, purple, polygonal, planar papules with Wickham striae, a Koebner line along a scratch and reticular white oral lesions are lichen planus. The remote injection drug use and raised ALT suggest chronic hepatitis C, its classic association. Lichen planus is the prototype interface (lichenoid) dermatitis: a dense band of CD8+ T cells hugs the dermal-epidermal junction and kills basal keratinocytes, causing vacuolar change and apoptotic keratinocytes (Civatte bodies). Above the band there is compact orthokeratosis, wedge-shaped hypergranulosis (the microscopic correlate of Wickham striae) and pointed, sawtooth rete ridges. Melanin dropped into the dermis from the damaged basal layer explains the hyperpigmentation left after lesions heal.

A and B describe psoriasis, the mirror image of lichen planus: IL-23 and Th17 signaling drive parakeratosis with neutrophil collections in the stratum corneum (Munro microabscesses), a thin or absent granular layer and dilated capillaries in elongated dermal papillae that bleed when scale is lifted (Auspitz sign). Psoriasis forms silvery plaques on the extensor surfaces, not purple flexor papules. C. Spongiosis with scale at follicular openings fits seborrheic dermatitis, with greasy yellow scale in sebum-rich areas. D. Atypical lymphocytes clustered in the epidermis (Pautrier microabscesses) define mycosis fungoides, which forms patches and plaques in sun-protected skin.

Numerous large, irregular, variegated nevi with histologic architectural disorder (bridging junctional nests), cytologic atypia and lamellar fibroplasia are dysplastic nevi. In a family with melanoma across generations, this is familial atypical multiple mole melanoma (FAMMM) syndrome, inherited in an autosomal dominant manner. The usual cause is a germline mutation in CDKN2A, which encodes p16INK4a, an inhibitor of CDK4 and CDK6. Without p16, cyclin D-CDK4/6 phosphorylates Rb freely, releasing E2F and pushing cells through the G1 to S checkpoint. In nevi, p16 normally enforces oncogene-induced senescence after a BRAF-driven burst of growth, so its loss lets melanocytic clones keep progressing.

CDKN2A is also inactivated in most sporadic pancreatic ductal adenocarcinomas, and germline carriers have a markedly increased lifetime risk of pancreatic cancer. Families with this mutation are therefore offered pancreatic surveillance in addition to frequent skin examinations.

A. Medullary thyroid carcinoma is associated with germline RET mutations in multiple endocrine neoplasia type 2, which has no relationship to nevi. B. Hepatocellular carcinoma is driven mainly by chronic hepatitis B or C, cirrhosis and aflatoxin, not by CDKN2A. C. Clear cell renal cell carcinoma is the signature tumor of von Hippel-Lindau syndrome (VHL loss). E. Colorectal adenocarcinoma is associated with APC (familial adenomatous polyposis) and mismatch repair genes (Lynch syndrome, including the Muir-Torre variant with sebaceous tumors and keratoacanthomas).