A 72-year-old man comes to the office due to progressive weakness, fatigue, anorexia, and a 10-kg (22-lb) weight loss over the past 4 months.  He says that food doesn’t taste as good as it once did, and he feels full after eating only a small amount.  The patient has had a morning cough for the past several years and had streaks of blood in his sputum 2 weeks ago.  He has a 50-pack-year smoking history.  On examination, the patient appears frail with a sunken face and bitemporal wasting.  His arms are thin with notable muscle wasting.  Lung examination reveals wheezing on the right side.  Chest x-ray reveals an irregular right perihilar mass.  Which of the following is most likely contributing to this patient’s muscle wasting?

A 62-year-old woman comes to the physician after finding a lump in her breast.  Physical examination reveals a firm, immovable, irregularly shaped mass.  Mammography is performed and shows a spiculated, calcified lesion that was not seen on prior studies.  A tissue biopsy is diagnostic for infiltrating ductal carcinoma.  Malignant tumors such as infiltrating ductal carcinoma are typically associated with varying degrees of disordered differentiation and maturation.  Which of the following findings is most characteristic of an anaplastic tumor?

A 32-year-old woman comes to the office for evaluation of a breast lump.  She noticed the lump a few months ago but thinks it might be getting larger.  The patient has a history of right lower limb amputation at age 17 due to osteosarcoma.  The patient’s mother died of an adrenal tumor, and her younger sister died of leukemia.  Examination of the left breast shows a 5-cm, firm immobile mass with irregular borders.  Which of the following gene mutations is the most likely etiology for this patient’s condition?

A 54-year-old man comes to the office due to a neck mass that has been slowly growing over the past 3 months.  The mass is not painful.  The patient has had no associated fever or chills but has lost weight.  He has no chronic medical conditions and takes no daily medications.  He has smoked a pack of cigarettes per day for the last 30 years and has used alcohol occasionally.  Physical examination reveals a 2-cm, hard, left-sided supraclavicular lymph node.  Biopsy of the lymph node reveals anaplastic cells that are diffusely positive for cytokeratin immunohistochemical stain.  Which of the following is the most likely origin of the cells detected on the biopsy?

Rats subjected to chronic inhalation exposure of formaldehyde develop nasal squamous cell carcinomas.  Decreased activity of which of the following genes is likely to be found on cytogenetic studies of the tumor cells?

A 45-year-old woman comes to the office due to 2 weeks of persistent back pain.  She has also had excessive fatigue, anorexia, and unintentional weight loss over the past several months.  The patient has no prior medical problems but has a history of cancer in the family.  An imaging study reveals a lytic lesion in the T10 vertebral body.  Analysis of the biopsy sample shows cell lineage with abnormally high replicative potential.  A genetic study reveals a single nucleotide substitution causing an activating mutation.  Which of the following genes is most likely involved in this patient’s disease?

A 65-year-old man comes to the emergency department due to acute-onset, severe right flank pain; nausea; and vomiting for the past hour.  His medical conditions include prostate cancer and membranous nephropathy.  Blood pressure is 148/60 mm Hg and pulse is 95/min.  On physical examination, the patient appears to be in moderate distress due to pain and is diaphoretic.  There is right costovertebral angle tenderness.  Urinalysis shows hematuria.  Contrast-enhanced CT scan reveals a wedge-shaped perfusion defect in the right kidney.  The affected renal tissue is most likely to develop which of the following histologic changes over the next several days?

A 17-year-old girl with a history of depression is brought to the emergency department after attempting suicide.  Her parents report that she consumed 2 bottles of insecticide after having an argument with her sister approximately 2 hours prior to presentation.  The patient’s symptoms include nausea, vomiting, abdominal pain, and copious watery diarrhea.  She has a known history of self-cutting and suicidal ideations but no prior suicide attempts.  Blood pressure is 86/42 mm Hg and pulse is 120/min.  Her breath has a faint garlic odor, and she has numerous healing linear scars on her forearms.  Which of the following medications should be administered immediately?

Researchers are conducting a study to determine the effectiveness of a novel humanized monoclonal antibody in patients with metastatic colorectal cancer.  This medication works by binding to the programmed cell death-1 receptor on T cells to block its ligands from binding.  They find this therapy is most effective in patients with a high degree of microsatellite instability or defects in DNA mismatch repairs.  Which of the following best explains the favorable drug effect in this subset of patients?

A 25-year-old previously healthy man comes to the office due to penile lesions.  The patient first noticed a nontender papule on his penis a month ago, and it has progressively increased in size and number.  He reports no fever, dysuria, or penile discharge.  The patient is sexually active with multiple partners and uses condoms inconsistently.  Physical examination reveals 3 soft, flesh-colored, papillary lesions measuring <1 cm on the dorsum of the penis.  There are no enlarged inguinal lymph nodes, and the remainder of the examination is normal.  Treatment is started with a topical agent that acts as a toll-like receptor agonist to increase antiviral cytokine production.  Which of the following medications was most likely prescribed to this patient?

A 13-year-old boy is admitted to the hospital due to fever and fatigue for the past week.  The patient recently received a cadaveric renal transplant for glomerulonephritis, and his immunosuppressive medication regimen was increased a month ago due to early evidence of rejection.  Temperature is 37.7 C (99.9 F).  Heart and lung examinations are unremarkable.  The liver is mildly enlarged, and the spleen tip is palpable.  There is notable adenopathy of the bilateral inguinal and axillary regions.  A complete blood count shows mild leukopenia.  Histopathology findings from biopsy of one of the enlarged lymph nodes are shown in the image below.

Which of the following is the most likely cause of this patient’s presentation?

A 72-year-old man is evaluated due to a scaly lesion behind his right ear.  A diagnosis of squamous cell carcinoma is confirmed on biopsy, and the patient undergoes excision of the lesion with clear margins.  The wound is left to heal by secondary intention.  Three weeks later, the patient returns to the office with a 2.5-cm raised, soft, granular lesion at the excision site.  Biopsy of a representative lesion is shown in the image below:

A 15-year-old boy is brought to the emergency department due to worsening rash and profuse sweating for the past week.  Symptoms began gradually, and the patient first noticed the sweating on a cold day, which he thought was unusual.  He has also felt generally unwell, with difficulty sleeping and sensitivity to light.  Physical examination shows an anxious-appearing boy with obvious hyperhidrosis.  Temperature is 36.7 C (98.1 F), blood pressure is 170/96 mm Hg, pulse is 112/min, and respirations are 16/min.  Skin examination is significant for an erythematous maculopapular rash over the torso, thighs, and upper arms, as well as pink macules over the palms and soles with associated desquamation.  Neurologic examination shows a slight tremor.  Excessive exposure to which of the following is most likely responsible for this patient’s presentation?

A 68-year-old man with a long history of using chewing tobacco comes to the office for follow up of squamous cell carcinoma (SCC) of the oral cavity.  A month ago, the patient was diagnosed with SCC of the left lateral tongue.  He underwent resection, the surgical specimen showed clear margins, and he started additional treatment.  The patient recently noticed a second ulcerative lesion on the right lateral tongue.  Biopsy is performed and it also shows SCC.  The second tumor most likely arose from which of the following mechanisms?

A 3-year-old boy is brought to clinic by his mother due to fevers.  Three weeks ago, the patient developed a fever, cough, and runny nose.  He attends day care, where several children have had viral upper respiratory infections.  Symptoms had briefly resolved 10 days ago, but the fever recurred last week after the patient returned to day care.  Since then, he has been home due to fever occurring almost daily despite acetaminophen administration.  Temperature is 38.3 C (100.9 F).  Examination shows enlarged lymph nodes in the neck region.  Lymphadenopathy at which of the following locations is most concerning for malignancy rather than infection in this patient?

A 64-year-old man comes to the office due to generalized edema, fatigue, and dyspnea on exertion for 2 months.  The patient has a 25-year history of poorly controlled rheumatoid arthritis.  Temperature is 36.9 C (98.4 F), blood pressure is 108/70 mm Hg, and pulse is 90/min.  The patient is thin and appears chronically ill but is in no acute distress.  There is no lymphadenopathy.  Breath sounds are decreased at the lung bases.  Musculoskeletal examination shows severe deformities of the hands and feet related to rheumatoid arthritis.  There is pitting edema of both legs up to the knees.  Peripheral pulses are normal.  Urinalysis shows 4+ protein but is otherwise normal.  A renal biopsy is performed.  Which of the following histologic abnormalities is most likely to be seen in this patient’s glomeruli?

A 32-year-old chef accidentally slices into the tip of her thumb while hurriedly trimming ribeye steaks with a knife.  The laceration extends through the skin into the subcutaneous pulp.  Which of the following sequences is most likely to occur in the subsequent wound healing process?

An 81-year-old woman reports progressively increasing bilateral shoulder pain for 2 months.  Over the past 2 weeks, she has developed burning pain in her right thumb, index, and middle fingers.  Medical history is significant for type 2 diabetes mellitus and end-stage renal disease due to diabetic nephropathy.  The patient has received hemodialysis for the past 10 years.  Vital signs are normal.  Examination reveals normal heart and lung sounds.  There is no organomegaly.  Both shoulders are hypertrophied.  There is thenar atrophy on the right hand and soft tissue fullness at the right wrist.  Which of the following is most likely responsible for this patient’s current condition?

A 65-year-old man is evaluated for progressive shortness of breath.  He has had exertional dyspnea for the past year and has been experiencing weight gain and peripheral edema for the last several weeks.  He has no previous history of cardiac or pulmonary disease.  Cardiac biopsy of the left ventricle shows the histopathologic findings on the slide below.

Which of the following are the most likely echocardiographic findings in this patient?

A 64-year-old man develops diarrhea, abdominal pain, nausea, vomiting, and anorexia 3 weeks after starting radiation therapy for prostate cancer.  Physical examination shows abdominal tenderness.  Sigmoidoscopy reveals hyperemia, edema, erosion, and ulceration of the intestinal mucosa.  Stool and serum chemistries are normal.  Radiation enteritis is suspected.  Which of the following is most likely the primary mechanism responsible for this patient’s intestinal changes?

A 44-year-old woman comes to the office due to a breast mass.  Physical examination reveals a hard, fixed mass in the right breast with palpable ipsilateral axillary lymphadenopathy.  Mammography demonstrates a spiculated right-sided breast lesion.  The patient undergoes mass resection and axillary lymph node dissection.  Histopathologic examination shows ductal adenocarcinoma with local spread to the axillary nodes.  The ability of the tumor to reach draining lymph nodes is facilitated by which of the following changes at the primary tumor site?

A 48-year-old woman comes to the office due to a sore throat for the past 3 months.  On examination, she is found to have an enlarged, ulcerated left tonsil and a firm, nontender, nonmobile left neck mass.  The patient undergoes biopsy of the tonsil.  Pathology is consistent with squamous cell carcinoma.  Further analysis of the biopsy specimen shows expression of viral genome proteins.  Which of the following most likely predisposed the patient to the development of this malignancy?

A 48-year-old woman comes to the office 10 days after undergoing breast reduction surgery.  She feels well overall and is taking acetaminophen as needed for pain control.  Vital signs are normal.  Examination of the breasts reveals intact surgical incisions without drainage; the incisions are pink, shiny, and slightly warm.  The surrounding skin has mild edema but no erythema.  Which of the following wound healing processes is most likely occurring at this time?

A 65-year-old man comes to the office for evaluation of a 2.5-cm nodular skin lesion on the right lower forearm.  The mass has been present for 3 months and recently became painful.  Vital signs are normal.  Examination demonstrates no regional lymphadenopathy.  Biopsy of the mass shows atypical keratinocytes within the epidermis that are seen extending into the dermis.  The atypical keratinocytes have enlarged nuclei with scant amounts of cytoplasm; keratinization is absent.  The neoplastic cells touch the local neural tissue.  PET/CT scans show no evidence of bone, pulmonary, or hepatic metastases.  These findings are most consistent with which of the following?

A 73-year-old woman comes to the emergency department with a 3-day history of worsening breathlessness and cough productive of thick, rust-colored sputum.  The patient has a longstanding history of hypertension.  Temperature is 38.3 C (101 F), blood pressure is 130/68 mm Hg, pulse is 102/min, and respirations are 24/min.  BMI is 27 kg/m².  Jugular venous pressure is normal and there is no lower extremity edema.  Heart sounds are normal with no murmur.  Lung auscultation reveals left lower lobe crackles and bronchial breath sounds.  Leukocyte count is 14,000/mm³ with 80% neutrophils and 7% bands, hemoglobin is 13.6 g/dL, and platelets are 400,000/mm³.  Serum levels of which of the following are most likely to be elevated in this patient?

A 67-year-old man comes to the office after he noticed several nodules in his left axilla.  He has a history of malignant melanoma on his upper back, which was treated with wide surgical excision 4 years ago.  The patient undergoes biopsy of an axillary lesion, and histopathology reveals melanoma recurrence.  Subsequent whole-body positron emission scan shows diffuse metastatic disease involving the lungs, liver, and left axillary nodes.  Checkpoint inhibitor therapy with pembrolizumab is initiated, which leads to significant reduction in the size of the axillary nodules and metastatic lesions.  Which of the following best correlates with the treatment response in this patient?

A 58-year-old woman comes to the emergency department due to abdominal discomfort and bloating.  Physical examination reveals ascites.  Abdominal ultrasonography shows a mass in the left ovary, and subsequent paracentesis reveals malignant cells.  Surgical excision of the mass is performed.  Histopathology shows high-grade serous carcinoma composed of atypical cells with pleomorphic nuclei and mitotic figures.  Large numbers of T cells are present in the tumor stroma; further evaluation shows the tumor expresses PD-1 ligands that interact with the PD-1 receptor on the infiltrating T cells.  Which of the following is most likely occurring in the tumor microenvironment as a result of this interaction?

A 55-year-old man is evaluated due to a nonhealing left forearm wound.  The patient had an excisional biopsy of a suspicious skin lesion at the site of the wound several weeks ago.  He has a history of uncontrolled type 2 diabetes mellitus and hypertension.  Vital signs are within normal limits.  Physical examination shows a 2.5-cm wound surrounded by erythema on the left forearm.  Upregulation of which of the following would most likely improve fibroblast proliferation and reepithelization in this nonhealing wound?

A 15-year-old boy is brought to the clinic for a wound check.  Three weeks ago, the patient fell while skateboarding and sustained a large abrasion to the right flank.  Since his last visit, he has been showering daily and applying topical antibiotic ointment to the affected area.  Examination of the right flank shows a clean, healed wound covered in pearly pink epithelium.  The cells responsible for repopulation of this patient’s epithelium are most likely to demonstrate which of the following features?