Path Final SDL Questions

Soon Jae is a 45 year old Korean American and an avid golfer. Being in good health, he is surprised to find his legs feeling weak (rubbery) and quickly develops tingling in his feet. Over the next few hours, the weakness extends to the trunk and hands. He leaves work and goes to the ER for a diagnosis and treatment. A lumbar puncture shows moderate elevation of CSF protein but essentially no pleocytosis. Physical exam initially showed normal deep tendon reflexes. However, the medical student working him up two hours later reports no deep tendon reflexes in the legs. Which of the following is the most likely diagnosis?

Acute demyelinating inflammatory polyneuropathy (ADIP)

A 57 year old woman is admitted with a chief complaint of right r=breast mass. Primary right breast cancer with axillary metastases was confirmed. A right mastectomy was performed with axillary lymph node sampling and plastic reconstruction of the breast. Histopathologic examination of the resected specimens revealed invasive ductal carcinoma. About 16 months later, multiple lung metastases were detected. At that time imminohistochemical staining of the erbB gene product was carried out on the surgical specimens and resulted strongly positive on the surface of carcinoma cells. The patient was treated with Matuzumab (IgG monoclonal antibody targeting erbB) intravenously. The metastatic lesions in the lung decreased in size and finally disappeared. Two years after the initial administration of Matuzuman, pulmonary tissue from both upper lobes which mimicked the scars on the chest X-ray were excised. The histopathologic examination revealed no tumor cells. After the surgery, the Matuzumab treatment was stopped. The relapse-free state continued for 3 years. erbB gene product in normal cells is a:

Cell membrane growth factor receptor

A 5-month-old girl was brought to the hospital emergency room by her parents who noted that she had been lethargic and not eating for a period of 24 hours. On taking the history from the infants' parents, the emergency room physician suspected a bacterial infection since the child was given foods including honey over the past 24 hours. On physical examination, the emergency room physician documents profound flaccid tone in the baby. Which one of the following is the most likely causative organism for this infant's disease?

Clostridium botulinum

A 5-year-old boy has been experiencing difficulty with ambulation noticed by his parents for the past 6 months. On examination, it was demonstrated that he had difficulty arising from a seated position on the floor of the exam room. The pediatrician is concerned that the patient may have genetic abnormality involving which of the following structural proteins?

Dystrophin

A 22 year old woman complained of sudden vision loss in the left eye for the previous 2 months. During the same time a relative has noted a bright reflex in the eye. Ophtalmoscopic examination showed a whiteish, elevated retinal mass at the temporal position in the left eye./ The right eye showed no signs of extraocular extension. There was no family history of intraocular neoplasia. The eye was surgically removed. Histopathologic examinatino of the retinal tumor revealed retinoblastoma. Which of the following mechanisms most likely explains the occurrence of the ocular malignancy in this patient?

A mutation of a protooncogene occurred in a single retinocyte during patient's adoecence and transformed the cell, whose progeny then formed the tumor.

Mr. Corbin is a 77-year-old retired police officer. He presented in a wheelchair to ER with severe, constant pain and progressive swelling of the left knee. His symptoms had suddenly occurred two days before at night after he had gone to bed feeling well. He could not recall any injury to the knee. The patient recalled that 1 month before the visit he had an episode of acute pain and swelling in his right big toe that lasted about 3 days. He smoked five cigarettes a day and drank two glasses of wine a day. On examination, the patient did not have a fever and had a heart rate of 82 beats/min and a blood pressure of 130/75 mm Hg. His body mass index was within normal limits. His left knee was red, hot, swollen, and tender with minimal range of motion. His right big toe was normal. No other joint involvement was detected and there were no extra-articular findings. The knee was aspirated, and approximately 25 mL of whitish cloudy fluid was removed and showed a cell count of 40,000 WBC/mm3 (reference range <200). Examination of the synovial fluid under compensated polarised light microscopy revealed numerous intracellular and extracellular negatively birefringent crystals. Blood tests showed an erythrocyte sedimentation rate of 55 mm/h (normal <20), C reactive protein level of 1.2 mg/dL (normal <0.5), and uric acid level of 8.5 mg/dL (reference range 3.6 - 8.5). Peripheral white blood cell count, platelet count, and hemoglobin concentration were within normal limits. Kidney and liver function parameters, and electrolytes were normal. Which of the following diseases can best explain these clinical, and laboratory findings in this patient? Chemical analysis of negatively birefringent crystals found in Mr. Corbin's synovial fluid showed that these crystals are composed of which of the following compounds?

Acute gouty arthritis Monosodium urate

A 21-year-old man presented with a two year history of low back pain radiating down both buttocks and down the posterior aspect of his thighs. The pain and stiffness is eased with movement and exercise, but is much worse at night and with prolonged inactivity. Examination revealed a reduced forward flexion of the spine. The patient also had reduced chest expansion of 2 cm across the fourth rib space. The routine laboratory studies were normal but the inflammatory markers were elevated with ESR of 41 mm/hr (normal: <20) and C-reactive protein of 21 mg/L (normal: 10). X-rays of the lumbar sacral spine revealed early syndesmophyte formation. Three years later he developed proteinuria with no apparent precipitating cause or significant previous history. A renal biopsy showed glomerular deposits of amyloidosis. Which of the following is the most likely explanation of this patient's renal condition?

Ankylosing spondylitis

The 23-year-old Mr. Blum complains of stiffness and pain in his lower back that is sufficiently severe to cause him to awaken at night. He first noticed morning stiffness in his lower back during his college years, but it seems to be getting progressively worse, and between his lack of sleep and his stiffness, he is beginning to have difficulty performing his new job as a tax accountant. He also describes occasional pain in his right eye and sensitivity to light. An X-ray of the sacroiliac regions shows fusion of the joint spaces and ossification of the intervertebral discs in the lumbar spine. Serologic tests for rheumatoid factor and antinuclear antibodies are negative. Which of the following is the most likely diagnosis? The prevalence of the condition Mr. Blum suffers from closely correlates with the prevalence of which of the following HLA antigens in a given population? Mr. Blum is more susceptible to developing which of the following extra-articular manifestations of his spine disease?

Ankylosing spondylitis B27 Uveitis

The 25-year-old Ms. Carrington presented with complaints of spinal pain in the cervical, lower thoracic and upper lumbar areas, sacroiliac joint pain that alternated between the right and left sides, and pain in both feet at the plantar fascia attachment to the calcaneus. Although she rarely awoke during the night because of pain, she had constant spinal pain and early-morning stiffness. She usually felt better during the day, but the pain often appeared or worsened in the evening and at night with bed rest. Despite management with anti-inflammatory doses of diclofenac and naproxen, as well as prednisone 10 mg/day, her condition progressively worsened. Physical examination at presentation revealed presence of sacroiliac joint tenderness, limited painful motion of both lumbar and thoracic spine in all directions. The thoracic excursion was limited to 80/83 cm. The sacroiliac provocation tests were strongly positive on both sides. Laboratory screening showed an ESR of 64 mm/hr (normal: <20), a C-reactive protein of 42 mg/L (normal: <10). On radiographs of the spine, bony bridges extending from T12 to L1 were seen. Lateral radiographs of the feet disclosed ossification of the plantar calcaneocuboid ligament. Which of the following is most likely to explain Ms. Carrington's clinical, laboratory and radiologic findings? Which of the following joint structures is the site of primary pathologic change in Ms. Carrington's disorder?

Ankylosing spondylitis Enthesis

A 56-year-old woman presented to her family practitioner complaining of 3 months worsening fatigue. She complains that she has difficulty climbing stairs and raising her hands above her head. The patient further relates that she is a 40 pack-year smoker of cigarettes. Your review of her chart reminds you that you are currently treating this patient for hypercholesterolemia and hypertension. Which of the following laboratory serologic studies may be helpful in your work-up of this patient?

Anti-Jo 1 antibodies

A 44-year-old woman who presented to her primary care physician complaining of chest discomfort, fatigue and increasing difficulty with her normal daily activities was found to have a poorly defined 3.5 cm anterior mediastinal mass on chest CT. Which of the following studies would be most helpful in the diagnosis of this patient?

Anti-striated muscle antibody test

Genetic testing was able to document the presence of numerous CTG trinucleotide repeats in a patient who had a strong family history of a musculoskeletal disease. Family members related that the severity of disease has appeared to worsen over the generations. This phenomenon is called:

Anticipation

A 67-year-old woman presented with a mass on her right breast. Physical examination revealed a 3-cm mass palpable on the upper medial quadrant of her right breast. A hard lymph node was also palpable in the right axilla. An open surgical biopsy of the breast mass was performed. The result of the biopsy was invasive ductal carcinoma of the breast. Two months later the patient was admitted with difficulty in swallowing, muscle weakness with activities such as climbing stairs, a violaceous rash over her eyelids, an erythema in a V-shaped distribution over the anterior neck and upper chest, and erythema distributed over her upper back. A muscle biopsy reveals lymphocytic perivascular infiltrates and perifascicular atrophy of muscle fibers. Which of the following serum myositis specific autoantibodies is most likely to be present in this patient?

Anti Mi-2 antibodies

A 28 year-old Caucasian man presents to your office with elevated erythrocyte sedimentation rate, elevated C-reactive protein, and mild symmetrical subchondral bony sclerosis and calcification at the sacroiliac joint. If this condition were to progress in severity, what would be a long-term chronic manifestation of this disorder?

Bamboo spine

A 14-year-old boy was originally diagnosed with progressive muscle weakness thought to represent a dystrophinopathy at the age of 7 years. The patient has a maternal uncle who died of heart disease at the age of 18 years, presumed to represent cardiomyopathy. A muscle biopsy was performed and demonstrated partial immunostaining for the dystrophin protein and little to no fatty or fibrous replacement of the skeletal muscle tissue. Which of the following combinations of diagnosis and genetic transmission best characterizes this patient?

Becker muscular dystrophy; X-linked recessive

A 44-year-old man with no significant past medical history presented with bilateral lower extremity paralysis noted that he relates was at first more severe in his distal extremities. He now notes that he has difficulty standing from a seated position and walking. He has recently experienced "an upset stomach with diarrhea". The most likely infectious agent leading to this constellation of symptoms is

Campylobacter jejuni

Mrs. Wright presents with painful proximal phalangeal joints (PIP) in both hands. Past medical history is positive for a 10-year history of arthritis that is treated with NSAIDs. On clinical exam, both hands present with firm enlargements of the PIPs that are not warm or red but are tender to palpation. This condition is called:

Bouchard nodes

The 70-year-old Mr. Marlowe presented with progressive weakness in all extremities, dementia and incontinence. He had no family history of neurological disease. He was alert, mental function was preserved on orientation, attention, judgment, immediate and recent memory but was impaired on delayed recall memory and calculation. Cranial nerve examination was normal. Moderate motor weakness was noted in all extremities. Sensation was intact in all extremities. Deep tendon reflex was decreased. Nerve conduction tests and electromyography showed sensorimotor polyneuropathy. A brain MRI showed diffuse white matter and ischemic changes in bilateral deep parietal area and a focal signal intensity increase in the left dentate nucleus of cerebellum. Hematological tests were normal. Serum creatine kinase (CK) level was 1,337 U/L (normal: 55-170), myoglobin was 144 μg/L (normal: 0-60). Biopsy of the left vastus lateralis muscle revealed the presence of PAS-positive amylase-resistant polyglycosan bodies in small peripheral nerves of the perimysium. Which of the following is the most likely diagnosis? The structure of the Mr. Marlowe's muscle glycogen was evaluated by determining the absorption spectrum of its iodine complex and showed a polymer of glucose with less branching points but longer outer chains. This abnormal glycogen is also known as:

Branching enzyme deficiency Amylopectin

The 57-year-old Mr. Connor presented with a 3-year history of chronic severe persistent pain of his right shoulder. Pain was present at rest, aggravated on motion and awakened him from sleep when he rolled over onto his right shoulder. Symptoms increased with rainy weather. Subacromial steroid injections performed twice relieved symptoms only temporarily. Inspection of the right shoulder was unremarkable. The patient was tender to palpation over the greater and lesser tuberosities. Plain radiographs and MRI studies of the shoulder joint showed dense calcific deposits within the upper part subscapularis tendon and in the anterior part of the supraspinatus tendon. Which of the following is the most likely diagnosis? Mr. Connor underwent shoulder arthroscopy under general anesthesia. A 5 mm incision was made in the upper border of the subscapularis tendon along its longitudinal axis. The main portion of calcific content was squezzed out of the tendon due to the arthroscopic lavage effect. The remnants were removed with a curette. Spectral analysis revealed that the calcified deposits were composed of which of the following compounds?

Calcific periarthritis Basic calcium phosphate

A 17-year-old boy was admitted with peripheral edema, elevated blood pressure, and reduced urine volume. Laboratory studies revealed blood urea nitrogen (BUN) of 45 mg/dL (normal: 10-20), serum creatinine of 2.5 mg/dL (normal: 0.5-1.0), and serum potassium of 6.2 mEq/L (normal: 3.5-5.0). He noted proximal weakness, fatigue, muscle pain and muscular cramps after physical activities and exercise at school. Accordingly, a muscular disease leading to rhabdomyolysis was suspected. Serum creatine phosphokinase (CK) and urine myoglobin were found to be elevated. Hydration and administration of alkaline diuretics were considered, immediately, and thereafter, urine output increased and serum creatinine level decreased to 1.1 mg/dL. Which of the following muscle disorders is the patient most likely to have?

Glycogen Storage Disease

Which of the following joints is spared in rheumatoid arthritis but is most frequently involved in osteoarthritis?

DIP

A 17-year-old boy has a painless mass in the back of her knee. He has felt a mass over 6 months ago. He has restricted angle of motion in the knee and is now having difficulty when he walks. A radiograph reveals a mass in the distal femoral metaphysis that erodes his bone cortex, lifting up the periosteum. The mass does not extend into the epiphyseal region. The biopsy is obtained and the microscopic examination reveals malignant looking cells producing anastomosing osteoid trabeculae on a sarcomatous stroma. The bone tumor described in this patient has a predilection for which of the following bones?

Distal femoral metaphysis and proximal tibial metaphysis

An 80-year-old man experienced bilateral hip pain, most severe following ambulation, but occurring also at night. The patient was able to get about using a cane. After osteoarthritis was diagnosed he underwent bilateral hip joint replacement. The removed femoral heads in connection with hip joint arthroplasty were examined for gross and microscopic markers of wear-and-tear. Both femoral heads were deformed and the articular cartilage was completely eroded. This abnormality is called:

Eburnation

A 51-year-old female presented with progressive muscle weakness in the lower extremities. She had a generalized eythroderma and demonstrated features suggestive of a heliotrope rash on her face. No Gottron's papules were seen on examination. She has no history of skeletal muscle disease in her family. To make the diagnosis, the clinician requested a punch biopsy of the patient's skin on her lower extremity. The morphologic findings one would expect to see are_________________. Based on this patient's diagnosis of dermatomyositis, she is at increased risk for developing __________________.

Epidermal atrophy and lymphocytic perivascular inflammatory infiltrate; visceral cancer

The 10-year-old Owen presented to your clinic with increasing pain in the left upper arm of approximately 3 months' duration and a recent onset of low-grade fever. On physical examination, you notice some local tenderness and soft tissue swelling over the proximal and mid thirds of the left humerus. Plain radiograph showed a large ill-defined, destructive, diaphyseal intramedullary lesion with permeative pattern of bone destruction and perpendicular spiculated periosteal reaction. The lesion was associated with an extraosseous soft tissue involvement. Biopsy material showed a highly cellular, infiltrative neoplasm consisting of sheets of tightly packed, round cells with very scant cytoplasm ("round blue cell tumor"). Other fields showed extensive necrosis. Your diagnosis is: Owen's bone neoplasm has most likely originated from which of the following cell types? Molecular studies of Owen's bone neoplasm would most likely reveal abnormalities in which of the following genes or chromosomes?

Ewing sarcoma Neuroectodermal cell T(11;22)

A 48-year-old woman was referred for evaluation of myalgias. She had muscle problems dating to childhood. She tired easily and was unable to keep up with her peers in athletic events. Shortly after beginning to exercise, she experienced weakness and a burning sensation in her muscles. She could not complete assigned running tasks in the allotted time and frequently became nauseated and sometimes vomited after running. She was labeled as a "slacker" because of this behavior. No cola-colored urine was noted during these events. Symptoms improved with rest. On examination, mental status, cranial nerves, sensation, and tendon reflexes were normal. Muscle strength was reduced in the deltoids, biceps brachii, wrist extensors and flexors, and iliopsoas but muscle contraction could still move joint against resistance. She had difficulty arising from a squat. There was no organomegaly. Laboratory studies disclosed serum CK levels of 670 U/L (normal: 55-170). An electromyogram (EMG) of limb muscles was normal. A deltoid muscle biopsy specimen disclosed numerous fibers that contained subsarcolemmal accumulations of PAS positive material that was completely digested with amylase. Forearm ischemic exercise test failed to produce lactate and staining for glycogen phosphorylase was negative. The most likely diagnosis is:

Glycogen storage disease type V

An 11-year-old boy was referred to a neurologist after several months of difficulties with daily activities including baseball practice. He has been experiencing weakness of the upper extremities and has had difficulty swinging the baseball bat. Physical examination revealed weakness of the upper extremities but no significant weakness was identified elsewhere. Which of the following diagnostic and genetic loci/abnormality combinations best identify the diagnosis in this patient?

Fascioscapulohumeral dystrophy, chromosome 4

A 56-year-old woman presents complaining that her hands and feet are stiff and sore. She states that this discomfort is most severe first in the morning. She has dealt with this pain for 8 months, and she now reports that it is more difficult to knit and sew, which are two of her favorite pass-times. She also recalls that her mother and grandmother suffered similar afflictions after they reached middle age. On physical examination, her finger joints appear to have a doughy swelling and are warm; the proximal interphalangeal and metacarpophalangeal joints are most severely affected. An X-ray examination of the hands shows narrowing of the joint spaces of the metacarpophalangeal joints, and a moderate ulnar deviation of the digits. Adjacent bones show localized osteopenia. Laboratory studies conducted on a blood sample will most likely show antibodies directed against which of the following proteins?

Fc portion of IgG

A 40-year-old woman was referred with joint pain, neutropenia, splenomegaly and scabies which resulted in an admission to hospital. She reported a 20-year history of joint disease. At the time of admission, physical examination revealed deformities of the bilateral joints of hands, wrists, elbows and feet. Swan-neck, boutonniere deformity and ulnar deviation of the digits were noted in both hands. Subcutaneous nodules were absent. The spleen was palpable about 5 cm below the left costal margins. Laboratory studies showed a WBC count of 3,730 cells/mm3(normal: 4,000-10,000), with 30% neutrophils on the differential count (normal: 40-73), hemoglobin of 6.9 g/L (normal: 10-16), hematocrit of 17.5% (normal: 36-46) and platelets of 75,000 (normal: 150,000-400,000). ESR was 140 mm/h, (normal: <20) and rheumatoid factor was 165 IU/mL (normal: <15). Which of the following is the most likely diagnosis?

Felty syndrome

A 53-year-old man presented with multiple subcutaneous nodules. Seven years ago nodules had first appeared around his distal interphalangeal joints. Since then, many more had developed and he now had 15 nodules over his hands and elbows, varying from a few millimeters to a few centimeters in size. The largest nodules were over his elbows. There were no lesions over the ears or elsewhere. The subcutaneous nodules resembled rheumatoid nodules; they were very firm, skin-colored and non-tender. The patient reported a 10-year history of bouts of pain accompanied by swelling, redness, and functional impairment of wrist joint. Physical examination revealed mobile and tender cutaneous nodules and swollen wrist joint. Routine laboratory studies were normal. Rheumatoid factor and all other autoantibodies tested were unremarkable. An excisional biopsy of a subcutaneous nodule overlying the right olecranon was carried out. Which of the following histopathologic findings would be consistent with rheumatoid nodules?

Fibrinoid necrosis surrounded by a palisade of macrophages

A skeletal muscle biopsy from a 6-year-old male child who was diagnosed with Duchenne muscular dystrophy would most likely show which of the following morphologic abnormalities?

Fibroadipose tissue replacement of skeletal muscle

A 40-year-old woman complained of pain and tumefaction in the upper portion of her right arm. She did not have fever, or trauma. Physical examination, showed a raised mass in the proximal portion of the right arm; with no clinical signs of neurovascular damage. There was no local erythema or skin lesions, and no palpable lymphadenopathy. Plain radiograph and MRI scan showed a soft tissue mass of the right forearm. A biopsy was performed. Microscopic examination showed fascicles of spindle cells with areas of collagen fibers, arranged in fascicles with herringbone appearance. The mitotic index was elevated. Which of the following is the most likely diagnosis?

Fibrosarcoma

All of the following classes of regulatory genes are targets of genetic damage during carcinogenesis except:

Genes that regulate free-radical scavenging system (Targets: tumor suppressor genes, prooncogenes, telomerase)

Mr. Rivera is a 24-year-old collegiate football player who suffered a forearm injury when he slipped and fell during a match. The patient presented with a painful swelling at the wrist dorsal ulnar side, about 2.5 cm, in the absence of any skin discoloration. Wrist examination showed a limited range of motion (ROM): pronation, supination and circumduction were painful. A radiographic examination of the left wrist was performed. No fracture was seen, but an osteolytic area was found in the ulnar meta-epiphysis. Contralateral wrist ROM was normal. An incisional biopsy was performed and the microscopic appearance is shown. Which of the following is the most likely diagnosis? The neoplastic component of Mr. Rivera's bone tumor has most likely originated from which of the following cell types? Molecular studies of Mr. Rivera's bone tumor would most likely reveal abnormalities in which of the following genes or chromosomes?

Giant cell tumor Fibroblast Telomeric associations

A 39-year-old woman presents with a palpable nodular mass located in the soft tissue of the right forearm. MRI scanning showed that the lesion was located between the flexor muscle tendons and the radial diaphysis and was strictly adherent to the median nerve and ulnar artery. The nodule was excised. Grossly, a rubbery tan-gray soft-tissue tumor was encountered. Microscopic examination revealed a spindle cell tumor with vesicular nuclei and moderate cytoplasm. In addition, a number of giant cells were scattered throughout. No mitotic activity or atypia was noted. Which of the following is the most likely diagnosis?

Giant cell tumor of tendon sheath

Noah was a 6-pound, 6-ounce boy, born to a 26-year-old mother by normal spontaneous delivery after a normal gestation. During the first month of life the baby apparently was in good health, but failed to gain sufficient weight. In the second month, the legs swelled intermittently, and frequent bouts of abdominal distention and projectile vomiting occurred, usually 10 to 15 minutes following milk ingestion. On hospitalization at the age of 3 months the infant appeared rather ill, hypoactive, dehydrated, and poorly nourished. Enlargement of the tongue was striking. The heart was considerably enlarged and tachycardia was present. The abdomen was distended and the liver palpable 3 cm below the right costal margin. Bilateral grade-II pitting edema of the legs was noted. Chest X-rays showed extreme globular enlargement of the heart. The presence of a congenital cardiac anomaly was suspected but cardiac catheterization revealed normal right atrial and ventricular pressures and oxygen saturations. In view of the clinical and radiologic findings the possibility of myocardial storage disease was entertained, and a calf muscle biopsy was performed. Microscopic examination revealed coarse vacuolization of the cytoplasm of skeletal muscle fibers. All these vacuoles were filled with a PAS-positive material that was completely digested by amylase, and stained strongly for acid phosphatase. These staining characteristics reveal that __________is accumulated in________________.

Glycogen, lysosomes

Which of the following findings would you not expect to see in a patient with polymyositis?

Gotttron's papules and heliotrope rash

Mrs. Lamar presents with painful distal phalangeal joints (DIP) in both hands. Past medical history is positive for a 10-year history of arthritis that is treated with NSAIDs. On clinical exam, both hands present with enlargement of the DIPs that are not warm or red but are tender to palpation. This condition is called: What do you expect to see in Mrs. Lamar's hand radiograph?

Heberden nodes Joint space narrowing with osteophytes

Clinical manifestations of botulinum toxin exposure include all of the following except:

High fever (You WOULD see normal BP, brachycardia, symmetric neurologic defects, blurred vision)

A 47 year old woman preented with epigastral pain. A gastric tumor was detected by an upper gastrointestinal endoscopy. She was therefore admitted to the National Cancer Center Hospital East for further examinatin. THe patient's past history revealed that she has undergone operations for endometrial cancer at age 35 and for colon cancer at age 45. Her pedigree included three patients with advanced cancer of the colon, two patients with uterine cancer and one patient with hepatocellular carcinoma. The patient underwent total gastrectomy. Histopathologic examination revealed a well-differentiated adenocarcinoma. Genetic testing on the biopsied tissue indicated the presence mutation that affected the MSH2 gene. Which of the following events best explains the mechanism of carcinogenesis in this patient?

Inability to repair errors in DNA replication

A skeletal muscle biopsy was performed and demonstrated so-called "cracks" in the myofibers with associated myofiber vacuolization. Based on these morphologic findings, you would expect a diagnosis of:

Inclusion Body Myositis

The most common inflammatory myopathy diagnosed in a 70-year-old man most likely is:

Inclusion body myositis

Impairment of the acetylcholine receptor at the neuromuscular junction in patients with myasthenia gravis is mediated by which of the following?

Increased destruction of the Ach receptor

A 61 yr old man with a long-standing history of alcohol abuse is admitted to your clinic in April 2010, complaining of abdominal pain and abdominal fullness with elevated serum amylase. He was treated for pancreatitis and was released in May. However, he presents again in June 2010 with recurrence of symptoms. You suspect pancreatic carcinoma. MRI scans did not detect any tumor in the pancreas. The pancreatic juice was collected through a catheter placed in the pancreatic duct. The exfoliated cells in the pancreatic juice were submitted to cytological analysis. Which of the following findings in the pancreatic juice and/or exfoliated pancreatic cells would most likely support the diagnosis of cancer?

Increased telomerase activity in exfoliated pancreatic cells

A 20-year-old male college student presented on November 1st to the student health department with bilateral thigh pain and swelling of 3 weeks' duration. He admitted to having been the victim of a hazing incident. On September 15th he was struck repeatedly on both of his thighs for a prolonged period of time while standing at attention. He had been so badly bruised he was unable to walk for the ensuing 2 days. The patient did not seek medical attention at that time, hoping his symptoms would resolve. On physical examination there was a 14-cm fixed palpable mass in the right thigh and another 8-cm fixed palpable mass in his left thigh. Radiographs showed extensive new bone located adjacent to the anterior and lateral aspects of the femur bilaterally. An MRI revealed a 13 x 2.5 x 3.5 cm ossification in the right vastus lateralis muscle and a 7.8 x 3.2 x 1.7 cm ossification in the vastus intermedius muscle. Which of the following is the most likely diagnosis?

Myositis ossificans

According to CDC it is estimated that 33 to 35% of men and women in the United States are obese. Obesity is a clear risk factor for developing osteoarthritis. Obese persons are at a higher risk of osteoarthritis of which of the following joints?

Knee

A 5-year-old boy was admitted to the pediatric ward with a history of progressive enlargement of the abdomen and muscle weakness since birth. A family history of similar symptoms during childhood in adult relatives of the patient was obtained. Clinical examination revealed massive hepatomegaly, and muscle weakness. Intellectual development and growth rate were normal and no kidney enlargement was demonstrated on radiological investigation. Routine biochemical tests revealed grossly elevated serum aspartate (AST) and alanine aminotransferase (ALT) activities; the bilirubin concentration was normal. Acid-base status and serum glucose, lactate, triglyceride, urate and ketone body concentrations were normal. Chemical quantitation of glycogen in the liver and erythrocytes confirmed increased concentrations in both (14.69 g/l00 g wet weight and 453 μg/mg Hb respectively). The structure of the erythrocyte glycogen was evaluated by determining the absorption spectrum of its iodine complex and showed a polymer of glucose with a highly-branched core but very short peripheral chains. This glycogen structure is known as:

Limit dextrin

A 35-year-old woman presented with a 6-year history of a slowly progressive, painless left cheek swelling. Physical examination revealed a 6 x 6 cm non-tender doughy mass in the left cheek with no overlying skin changes. The intra-oral mucosa over the mass appeared normal. Ultrasonography revealed a fairly well circumscribed echogenic mass in the left cheek. Other investigations performed included full blood count, serum urea and electrolyte, and urinalysis which were all within normal limits. The mass was excised under general anesthesia and the wound closed using a chromic 3/0 suture. Grossly, the surgical specimen was an irregular yellowish mass. Microscopic examination revealed sheets of mature adipocytes, containing large clear cytoplasm and eccentric nucleus with inconspicuous vascularity and no evidence of cellular atypia. These clinical and pathological features are consistent with a diagnosis of:

Lipoma

Genetically engineered mice were produced in the Centre for Gene Therapy by introducing the FUS-CHOP transgene into the mouse genome. The expression of the transgene was successfully driven by the elongation factor 1α promoter to all tissues. Cohorts of transgenic mice were generated to analyze the effects of the FUS-CHOP fusion gene. Uniformly, male and female FUS-CHOP transgenic mice showed the same symptoms beginning as early as 8 weeks of age with increasing signs over time leading to death in 100% of the mice by 12 months of age. At the time of autopsy, these animals had developed palpable masses of which of the following tumors?

Liposarcoma

A 55-year-old patient presented with ascending paralysis following a bought of gastroenteritis. The presumed diagnosis is Guillain-Barre syndrome. On the work-up of the patient, a lumbar puncture was requested to evaluate cerebrospinal fluid. Which of the following findings would you expect to see in this patient's cerebrospinal fluid?

No lymphocyte pleocytosis, elevated protein

Patients with Emery-Dreifuss muscular dystrophy have mutations in EMD and LMNA genes. These genes encode emerin and lamin A proteins which are localized to the:

Nuclear membrane

The primary means of prevention of the development of peripheral neuropathy in diabetic patients is:

Maintenance of a normal blood glucose

Which of the following joints is most commonly involved in patients with rheumatoid arthritis?

Metacarpophalangeal joint

A 56-year-old woman presented with what appeared to represent Guillain-Barre syndrome after experiencing a viral-like illness. Which of the following muscle groups would expect to be affected by paralysis first?

Muscles of fine motor movements of the hands

A 13-year-old girl with Graves' disease and hyperthyroidism underwent antithyroid treatment with propylthiouracil. Two weeks following the initiation of antithyroid treatment she developed left blepharoptosis, diplopia, and dysphagia, which responded promptly to edrophonium administration. A chest CT showed a large soft tissue mass in front of the ascending aorta, which was proven histopathologically as thymic hyperplasia. Which of the following is most likely to explain this patient's muscle weakness symptoms?

Myasthenia gravis

A 57-year-old female with no significant past medical history presents to her primary care physician complaining of increasing difficulty maneuvering her hands and lower extremities. On examination, she has difficulty flexing her hands as well as flexing her knees. Her family history is significant for having a mother, grandmother, and great-grandfather who experienced similar symptoms. A skeletal muscle biopsy demonstrated morphologic features suggesting inclusion body myositis. Based upon the patient's clinical findings, family history and muscle biopsy results, which of the following genetic abnormalities would you suspect?

Myosin heavy chain mutation

Mr. Scott is a 55-year-old man with a 3-year history of progressively increasing bilateral knee pain, left worse than right. During the past 3 months he was in a sedentary job, his weight increased by more than 10 kg (22 pounds), and his symptoms increased significantly. Mr. Scott reported left knee pain as being 6 out of 10 on the visual analog scale, and he was using a walking stick to walk any distance. He had minimal symptoms at night, stiffness that resolved after about 15 minutes in the morning, and symptoms that worsened as the day went on. His pain was exacerbated by walking more than 15 minutes or on hills and by long periods of sitting. Mr. Scott found relief by using a walking stick, moving his knees when sitting, and taking regular doses of a nonsteroidal anti-inflammatory drug and paracetamol, Mr. Scott's radiographic films showed a decreased medial knee joint height with osteophyte formation. Which of the following is most likely to explain Scott's clinical findings? Which of the following structures is the site of primary morphologic change in Scott's joint disease?

Osteoarthritis Articular cartilage

The 43-year-old Mrs. Jones presented with a chief complaint of pain in both wrists and knees. She reported a slow developing joint pain that started in the groin and on the outside of the hips. She mentioned that her pain radiates sometimes to buttocks and knee. Her lower limb symptoms have been present for 6 months resulting in the patient walking with a limp. The wrist pain is a new presentation. Upon physical exam, there is no joint swelling or erythema of the wrists or knees. Some crepitus is noted with range of motion of both knees (right more than left). What is the most likely diagnosis? Mrs. Jones undergoes arthrocentesis of the left knee which yielded 5 mL of synovial fluid. A synovial fluid analysis was carried out. Which of the following sets of results would most likely be present in this patient?

Osteoarthritis Translucent straw colored fluid with a WBC count of 1500 cells/mm3 and 10% neutrophils on the differential count

A 16-year-old boy has a painful, slowly growing mass in the back of his right knee. He has felt a mass over 6 months ago. He has restricted angle of motion in the knee and is now having difficulty when he walks. A radiograph reveals a mass in the distal femoral metaphysis that erodes his bone cortex, lifting up the periosteum. The mass does not extend into the epiphyseal region. The biopsy is obtained and the microscopic examination reveals malignant looking cells producing anastomosing osteoid trabeculae on a sarcomatous stroma. Based upon the history, physical, radiographic and biopsy findings the most likely diagnosis is:

Osteosarcoma

In June 2010, Mr. Clemson consulted a local physician with a 6-month history of right knee pain and was treated with a non-steroidal anti-inflammatory drug. In December 2010, he consulted another local clinic since the knee pain had increased and was referred to your out-patient clinic. On physical examinations, redness and swelling of the anterior aspect of the knee were noted, and flexion of the knee joint was restricted to 120°C. He could not raise her lower leg against gravity because of muscle atrophy around the right thigh. On radiographs, osteolytic and osteoblastic lesions were irregularly distributed in the tibial metaphysis which was enlarged, and the cortical layer was irregularly discontinuous. MR imaging also demonstrated an intraosseous lesion. A biopsy is obtained and the microscopic examination reveals malignant looking cells producing anastomosing osteoid trabeculae on a sarcomatous stroma. Which of the following is the most likely diagnosis? Molecular studies of Mr. Clemson's tibial tumor would most likely reveal abnormalities in which of the following genes or chromosomes?

Osteosarcoma Genes encoding proteins of Wnt signaling pathway

A 23-year-old male patient was diagnosed with neuropathy after EMG and nerve conduction studies. Clinical examination revealed distal lower extremity skeletal muscle atrophy. Genetic testing documented a duplication of a segment of the short arm of chromosome 17. The __________ gene is duplicated in this disease and the most common form of genetic transmission is ___________. The disease is best characterized as ___________.

PMP22, autosomal dominant, CMT type I

The 42-year-old Mrs. Gates presents complaining of neck pain. She was involved in a motor vehicle accident ten years ago. Since then, her neck has never felt "right." She has frequent neck pain, which cause her to miss many days of work as an assembly line worker. Mrs. P states her neck pain frequently radiates to the base of her head and down into her shoulder blades. She has no arm or leg pain, no bowel or bladder complaints, and no problems with coordination of her hands or feet. On physical examination, her neck is stiff with a markedly decreased range of motion. A neurological exam shows no abnormalities of nerve function. A plain film cervical radiograph shows decreased disk heights from C3 to C6. There is marked bony proliferation of the anterior bodies with development of marginal osteophytes at the endplates. Which of the following terms is most likely to explain Mrs. Gates' radiological findings?

Spondylosis

A 40-year-old male was diagnosed with an inflammatory myopathy based upon review of history, physical examination and a variety of laboratory studies. Based upon these findings, a diagnosis of dermatomyositis is made. Which of the following descriptions of the muscle biopsy findings would you most likely expect to see in this patient?

Perifascicular atrophy with evidence of vasculitis

The 20-year-old Ms. Gibbs presented with a 4-year history of progressively intermittent pain and swelling of both knees. There was no history of trauma. A physical examination revealed swollen and tender knees with a limited range of flexion movement. Joint aspiration recovered hemorrhagic joint fluid. Plain radiographs were normal, but MRI scan showed a joint effusion with synovial hyperplasia and hyposignal seen on both T1- and T2-weighted images was consistent with the hemosiderin deposits on both of knees. An open synovectomy of the left knee was carried out. Histological analysis revealed papillary hypervascular synovial tissue remained by chronic inflammatory infiltrate including foamy histiocytes, mononuclear cells, giant cells, with numerous deposits of hemosiderin. This constellation of findings is consistent with: Molecular studies of Ms. Gibs' synovectomy specimen would most likely reveal abnormalities in which of the following genes or chromosomes?

Pigmented villonodular synovitis T(1;2)(p13;q37)

Emma was a 4 month old female child with two-month history of breathlessness, sweating over forehead and difficulty in feeding. On admission, she weighed 2.5 kg, had marked tachycardia and severe respiratory distress. Blood pressure was normal. Examination revealed cardiomegaly and hepatomegaly, the spleen was not palpable. Respiratory system was normal. Laboratory studies disclosed a normal hemogram, blood sugar, electrolytes and renal parameters. Acid maltase levels estimated from peripheral blood leukocytes were found to be reduced to 200 nmoles/mg protein/hour (normal: 300-700). Which of the following is the most likely diagnosis? On screening for acid maltase activity both Emma's parents were carriers. Elder sibling had normal levels of the enzyme. The child was treated with supportive measures but showed no significant improvement and died 3 weeks later. What do you expect the postmortem examination of her skeletal muscles to reveal?

Pompe disease Enlarged secondary lysosomes filled with glycogen

An 80-year-old man presented with a three month history of painful swelling of the right first toe. No other complaint was elicited. He had a history of alcohol abuse for more than 40 years Family history of hyperuricemia was present in his mother and brother. Physical examination was normal except for marked erythema and gross swelling in the area of the right first metatarsophalangeal joint. Laboratory data were normal except for a serum uric acid level of 8.6 mg/dL (normal: 4-8.5) and a peripheral blood WBC count of 11,400 cells/mm3 (normal: 4,000-10,000). An arthrocentesis of the right first metatarsophalangeal joint was performed, yielding 0.2 cm3 of thick and whitish fluid. Examination of the synovial fluid revealed a WBC count of 25,000 cells/mm3 (normal: 0-200) and the presence of monosodium urate crystals and under polarizing microscope indicated the presence of negatively birefringent crystals. A diagnosis of acute gouty arthritis was made and the patient was started on colchicine, and allopurinol. Which of the following findings played the most decisive role in reaching the definitive diagnosis?

Presence of negatively birefrnigement crystals in the synovial fluid

Mr. Wallace was a healthy 56-year-old fireman and professional squash coach. He was referred with a three year history of intermittent right knee pain of progressively increasing severity, exacerbated by exercise. There was no history of trauma. His sporting activities had become restricted by pain, and he had been obliged to retire as a professional sportsman. On physical examination, diffuse swelling in the anterior knee was observed. He was afebrile and had no joint erythema or warmth. Knee films demonstrated a small effusion. Robert underwent arthroscopy of the right knee, at which time a diffuse, white speckled appearance of the meniscus was noted, consistent with crystal deposition. Biopsies of the meniscal cartilage were sent for histological examination. Histological examination showed fibroconnective tissue containing rhomboid shaped crystalline deposits which demonstrated weakly positive birefringence. Which of the following diseases can best explain these clinical, and laboratory findings in this patient? Chemical analysis of positively birefringent crystals found in Mr. Wallace's meniscal cartilage showed that these crystals are composed of which of the following compounds?

Pseudogout Calcium pyrophosphate dehydrate

A 40-year-old alcoholic man presented with gradually increasing multiple subcutaneous nodules on both the lateral malleoli, lateral parts of bilateral feet and toes, left palm, right elbow, helix of left ear ranging in size from 1-1.5 cm diameter since last one and half year. These nodules were firm and non-tender. Few of them had broken into the skin discharging whitish chalky particulate material. He had intermittent mild pain in the great toes since last six months. He did not receive any major medication except painkillers in the past. Systemic examination was normal. Radiographs of both the feet and the hands showed soft tissue swellings with no involvement of bones. Fine needle aspiration cytology was performed from subcutaneous nodules on the left leg using a 21-gauge needle. Polarizing microscopy of the smears demonstrated scattered stacks of negatively birefringent, slender, needle-shaped crystals, associated with chronic inflammatory infiltrate. These crystals are the final degradation product of which of the following biomolecules?

Purines

Many patients with diabetes mellitus eventually experience symptoms of peripheral neuropathy. The classic sensory deficit in these patients is described as ___________, and the pathogenic mechanism in this disease is considered primarily:

Stocking glove; ischemic

Hester is a 6 month old girl that is referred to your hospital for white reflex in both eyes for 5 months. The mother first noticed white reflex on the right eye when the child was one month old and since then it has been progressively increasing and has involved the left eye within the span of 3 to 4 months. Review of systems is negative. On ophthalmologic examination, sligth exophthalmos (proptosis) is noted in both eyes with eyeball and cornea appearing relatively enlarged. Yellowish-white opacity is seen on both the eyes behind the cornea. On CT scan of the orbits, a solid retinal tumor that involved the vitreous on both sides is seen. There are no signs of extraglobe extension. The clinical and imaging findings are consistent with the diagnosis of bilateral retinoblastoma. Both eyes are removed. Histopatholigc examination reveals a retinal tumor composed of malignant cells with large hyperchromatic nuclei and numerous mitotic figures. Homer-Wright rosettes, which are highy characterisitic for retinoblastoma, were present. Molecular anazlysis of the neoplastic cells will most likely reveal which of the following genes? Which of the following mechanisms has most likely initiated the neoplastic transformation in Hester's retinal cells?

Rd Loss of inhibition to cell proliferation

A 28-year-old man complains of burning pain on urination, as well as pain in his fingers and his left eye. He also relates a recent episode of bacillary diarrhea contracted during a visit to Mexico. Physical examination confirms arthritis and conjunctivitis. An x-ray of the sacroiliac regions shows pseudo widening of the joint spaces. The patient responds well to treatment with NSAIDs such as ibuprofen. Which of the following is the most likely diagnosis?

Reiter syndrome

An 8-month-old boy was noted to have a bilobed mass arising from the right anterolateral chest wall measuring 5.8 cm in the longest dimension on CT scan. The patient otherwise appeared healthy. After an initial diagnostic biopsy, the patient underwent a wide local excision of the tumor. The resection included chest and abdominal wall muscle, chondral cartilage, and portion of the right diaphragm. No evidence of tumor metastasis was found on radiological assessment or examination of the patient's bone marrow. The biopsy and the resection specimens both showed proliferation of small blue tumor cells with scant cytoplasm on a myxoid stroma. There was evidence of differentiation at the periphery of the tumor, with larger tumor cells that showed eosinophilic cytoplasm with eccentric nucleus. A few of them were "tadpole-shaped" cells and very few of them had cross striations. Which of the following is the most likely diagnosis?

Rhabdomyosarcoma

A 33-year-old woman presented complaining of pain and swelling in multiple joints since November 2009. She also complained of significant morning stiffness that last for more than one hour. On physical examination, you notice that the fourth and fifth metacarpophalangeal, second, and third proximal interphalangeal joints are swollen and warm. The distal interphalangeal joints are spared. Laboratory findings initially include an ESR of 64 mm/hr (normal: <20), C-reactive protein (CRP) of 13 mg/dL (normal: <1). Her basic chemistry, liver function tests, hemogram, and complement levels are essentially within normal limits. Serological tests are positive for antinuclear antibody, rheumatoid factor, and anti-citrullinated protein antibodies. Her radiological findings are negative for any joint effusion or destruction. What is your diagnosis?

Rheumatoid arthritis

A 35-year-old woman had suffered from recurrent swellings and pain of both knee joints for 3 years. The symptoms used to be relieved with salicylate medication and aspiration of joint fluid, but the symptoms recurred soon after stopping medication. Her laboratory studies including hemogram and blood chemistries were all within the normal range. The serum levels of rheumatoid factor and antinuclear antibodies were negative. X-ray films of joint did not show any abnormality. For the diagnostic purpose a small amount of synovial fluid was aspirated. The aspirated fluid was turbid yellow. Microscopically, there were many polymorphonuclear leukocytes (70-120 per high power field) in clear background. Approximately one third of polymorphonuclear leukocytes showed multiple small dense intracytoplasmic inclusions. Based on the clinical, laboratory and cytologic findings the most likely diagnosis is:

Rheumatoid arthritis

Which of the following treatments would not be potentially helpful in the treatment of myasthenia gravis?

Systemic chemotherapy for malignant lung tumor

A 64-year-old woman presented with pain and swelling in her left knee joint. The patient had had knee pain for many years and was diagnosed with osteoarthritis of the knee, at a private clinic 5 years ago. She was prescribed and treated with hyaluronic acid and steroid injection, but the symptoms repeatedly got better then worse in a cyclical way. She was not obese, her body mass index was 23 kg/m2 (normal: 18-25). On physical examination you notice that her left knee was swollen and sore. Extension and flexion range of motion in the left knee was 120° (normal range: 0-135°). Full knee flexion was impossible. A simple radiograph on her left knee joint revealed marked tissue edema and narrowing of the femorotibial compartment. MRI studies showed severe synovial hypertrophy. Laboratory studies revealed an ESR of 38 mm/hr (normal: <20), C-reactive protein of 1.8 mg/dL (normal: <0.1), rheumatoid factor of 169 IU/mL (normal: 0-15), anti-citrullinated protein antibodies of 217 IU/mL (normal: 0-25) and negative ANCA. For diagnostic purposes, open synovial biopsy was performed from the left knee joint. Microscopic examination of the synovial tissue showed exuberant diffuse proliferation of synovial lining cells and a highly vascularized fibrous tissue with infiltrations of lymphocytes, macrophages and occasional neutrophils. No granulomas were seen. What is your diagnosis?

Rheumatoid arthritis

A 59-year-old woman with a 3 year history of rheumatoid arthritis and small hand joint involvement complains of dyspnea. She is referred to the local hospital for evaluation. A chest X-ray shows a large left-size pleural effusion. Thoracentesis produces 500 mL of turbid fluid. Pleural fluid laboratory testing reveals a WBC count of 2000/mm3(normal <300), with predomination of lymphocytes in the differential count, and a total protein of 4.6 g/dL (normal<3). The Gram stain, acid fast bacilli stain and fungal stains of the pleural fluid were all negative. The patient's dyspnea improves after thoracentesis. On hospital day 3, a chest CT scan shows two 1 x1 cm-diameter lung nodules at the right posterior base. A transthoracic biopsy of one lung nodule is performed. Microscopic examination shows a central area of fibrinoid necrosis surrounded by palisading macrophageal cells. Special stains for mycotic and acid fast organisms are negative. Most of the lung sample showed interstitial fibrosis and chronic inflammation. Which of the following is the most likely cause of this patient's pulmonary condition?

Rheumatoid lung disease

A 69-year-old man with a diagnosis of chronic myeloid leukemia is treated with intensive chemotherapy. He goes into remission, but develops pain in the left wrist. On physical examination, there is swelling and warmth on palpation of the wrist. Polarized light microscopy of fluid aspirated from the wrist joint shows needle-shaped crystals that display negative birefringence. A diagnosis of acute gouty arthritis was made. Which of the following types of gout is this patient most likely to have?

Secondary gout

A 21-year-old woman is referred to your clinic with the diagnosis of McArdle disease and elevated serum CK level. Which of the following clinical syndromes do you expect to see in this patient?

Severe exercise induced myalgia, cramps and myoglobinuria

A 5-year-old boy was brought to his pediatrician by his parents who noted that he has had increasing difficulty climbing stairs and is not able to run and play with his friends. On physical examination, the pediatrician describes pseudohypertrophy of the calf muscles and is able to document a positive Gower sign. Which of the following would you least expect to see in association with this patient's disease process?

Skeletal muscle biopsy documents prominent myofiber inclusions

A 50-year-old woman presents to her physician complaining of significant lower extremity weakness. A history and physical examination is conducted. Laboratories demonstrated that she had a serum creatine kinase of 3200 U/L (normal: 55-170). The most likely site of pathology in this patient is:

Skeletal muscle tissue

A 66-year old man with a long history of tobacco smoking presented to the emergency room with hemoptysis and lethargy. Family members related that the patient had been experiencing increasing difficulty walking around his house. Physical exam revealed a man appearing his stated age with cachexia and significant bilateral muscle weakness. CT examination revealed a large pulmonary hilar mass. The most likely diagnosis in this patient is:

Small cell carcinoma of the lung

You are examining a dorsoventral radiograph from a patient with ankylosing spondylitis, and notice bony growths originating inside the ligaments of the intervertebral joints, that appear to be contributing to fusion of the vertebrae. What are these calcified growths referred to?

Syndesmophytes

Which of the following is a manifestation of enthesitis?

Syndesmophytes and achielles tendon calcification

A 38-year-old woman presents to your clinic for evaluation of pain, warmth and swelling in the left knee. She reports that her knee problems started 6 years ago when she developed severe pain and swelling in the left knee. On examination you notice a thin, afebrile woman in no acute distress. The patient complains of morning stiffness lasting 2 hours, pain and swelling in the wrists, small joints of her hands and feet. On physical examination, both knees, wrists, metacarpophalangeal and interphalangeal joints of her both hands are warm, swollen and tender to palpation. Laboratory studies revealed normal blood chemistries, WBC count was 11,100 cells/mm3 (normal: 4,000-10,000), hematocrit 42% (normal: 35-45), and ESR 30 mm/hr (normal <20). The test for rheumatoid factor was positive, and antinuclear antibody was negative. Which of the following joint structures is the site of primary morphologic change in this patient's joint disorder?

Synovial membrane

A 58-year-old woman was referred to your clinic because of swelling and pain of the right knee for 6 months. Physical examinations were unremarkable except for a swollen right knee with local tenderness. The range of motion of the right knee was moderately limited in all directions. Laboratory examinations revealed a WBC count of 4,510 cells/mm3(normal: 4,000-10,000) and C-reactive protein of 4.75 mg/dL (normal: <0.8). MR imaging of the right knee showed moderate amount of effusion and marked synovial proliferation. Aspiration of joint effusion yielded 3 mL of yellow fluid. No crystals were found on microscopic examination. Synovial fluid analysis revealed a WBC count of 48,000 cells/mm3. The Gram stain and acid-fast stain of the aspirated synovial fluid were negative, and the routine aerobic and anaerobic bacterial cultures were also negative. You suspect the patient has monoarticular rheumatoid arthritis. For diagnostic purposes, you perform an open synovial biopsy from the right knee joint. Which of the following histopathologic findings would most likely confirm your suspicion?

Synovial pannus

The 55-year-old Mr. Bodine presented with a six months history of a painless growing nodule in his left leg. During the last two months the mass had enlarged more rapidly. Past medical history was not significant. Physical examination revealed a large subcutaneous mass, covered by dystrophic and thinned skin. On palpation, the tumor was firm, with clinical distinct margins. No popliteal and inguinal lymphadenopathy was found, and peripheral pulses of the left leg were present and valid. MRI studies revealed an inhomogeneous tumor measuring 6 × 5 × 23 cm in the antero-lateral compartment of left leg, within the tibialis anterior and the extensor digitorum longus muscles. A percutaneous core-cut biopsy was performed. Histologically the tumor was constituted of numerous glands. These were lined by one layer of cuboidal to columnar cells showing eosinophilic cytoplasm and round nuclei with a single small nucleolus. Lumina were round to irregular and their caliber varied from small to medium large. Their content was composed of mucinous, PAS-positive material. Glands were immersed within tightly packed monotonous proliferation of spindle-shaped cells arranged in lose fascicles. Atypical mitoses were frequently seen. Which of the following is the most likely diagnosis? Molecular studies of Mr. Bodine's leg neoplasm would most likely reveal abnormalities in which of the following genes or chromosomes?

Synovial sarcoma T(X;18) leading to the formation of the XYT and SSX1 gene fusions

A 72-year-old female patient with a 25 year history of diabetes mellitus type II, hypertension and hypercholesterolemia presents to her primary care physician complaining of severe foot and ankle pain. She relates that the pain is relentless, but does improve mildly after she takes over-the-counter acetaminophen. Examination demonstrates bilateral sensory deficits within the feet and diminished ankle reflexes. A measurement of her blood glucose by point-of-care device showed it to be 365 mg/dl. Her hemoglobin A1c was later returned at 8. Which of the following statement is not true concerning this patient's diagnosis?

The patient will have specific genetic abnormalities making her susceptible to the illness

The gower sign describes:

The process by which a child with Duchenne muscular dystrophy moves to standing position

A 57-year-old man with a history of hypercholesterolemia and alcohol abuse presented with a six-month history of increasing numbers of gradually enlarging nodules of the auricle. The largest lesion was becoming more painful with pressure while sleeping. The patient denied previous trauma but had been diagnosed with gouty arthritis 10 years earlier. The arthritis involved only the proximal first metatarsal joint of the left foot. Because of recurrent attacks, the joint was mildly deformed. The patient did not control hyperuricemia regularly and only took medication during acute attacks. The concentration of serum uric acid was 10.4 mg/dL (normal: 3.8-7.0). Family history of hyperuricemia, but without gouty arthritis, was present in his mother and brother. On physical examination there were several pale, nontender nodules measuring 2 to 10 mm in diameter over the left auricle (shown). Which of the following terms most accuratedly indicates the nature of the auricular lesions in this patient?

Tophus

A 7 year old boy was admitted with severe anemia, fatigue and abdominal pain. On physical examination, there was a large palpable mass in the gastric region. Laboratory studies revealed hemoglobin 5.6 g/dL (normal: 10-15); WBC count of 3600 cells/mm3 (normal 4000-10000); and platelet 313900 cells/mm3 (normal 150000-400000). Abdominal ultrasound revelaed a 7 x 6-cm mass at the anterior wall of the stomach. Histopathologc examination of the endoscopic biopsy showed diffuse infiltration of an atypical lmphomatous cell population with scanty basophilic cytoplasm. Immunohistochemical tumor markers were consistent with Burkitt lymphoma. Genetic screening identified a dysregulation of expression of myc protein. Which of the following events best explains the mechanism of carcinogenesis in this patient?

Translocation of the gene resulting in persistent expression

A 71 year old man presented in 2010 with chest pain and ECG signs of myocardial ischemia. He had a positve stress echocardiogram and underwent coronary bypass surgery. In 2011, a CBC test gave the following results: hemoglobin 13.1 g/dL (normal 12-18), WBC count of 55,500 cells/mm3 (normalL 4000-10000) with 58% neutrophils, 6.8% lymphocytes, 5.9% monocytes, 2% eosinophills, 5.9% monocytes, 2% eosinophil, 3.5% basophils, 8.2% metamyelocyes., 16% myelocytes and platelet count of 534400cells/mm3 (normal: 140000-400000). Bone marrow aspiration and biopsy studies revealed hypercellular marrow with marked granulocytic and megakaryocytic hyperplasia. Genetic analysis revealed the presence of the philadelphia chromosome. Which of the following events best explains the mechanism of carcinogenesis in this patient?

Translocation of the gene resulting in persistent expression

A 39-year-old woman presented to her primary care provider complaining of severe muscle weakness in both lower extremities as well as the upper extremities. A physical examination documented a facial rash and papules on the interphalangeal joints of the hands. You make a diagnosis of dermatomyositis and remember than this patient is at increased risk of developing:

Visceral malignancies

A genetic counselor elicits a genetic history from a family affected by a muscular dystrophy. On questioning, the family recalls that the disease has been in the family for at least 3 generations. Some sons appear to be affected, but no disease is apparent in the mothers of these children. The most likely mode of inheritance in this family is:

X-linked recessive

A 38-year-old underwent an elective cesarean operation at 35 + 3 weeks of pregnancy. A lively male infant (weight: 3120 g) was born. The mother developed a respiratory insufficiency on the second postpartum day. Laboratory studies showed an elevated anti-acetylcholine receptor antibody titer of 54.5 nmol/L (normal: <0.4). The interdisciplinary therapeutic approach included ventilatory assistance via endotracheal intubation, pyridostigmine, azathioprine, and corticosteroids. The patient was stabilized and was dismissed in good clinical condition. Which of the following is the clinical diagnosis?

myasthenia gravis

A 28 year old man referred to a clinic with a diagnosis of gastric carcinoma with mulitple liver metastases. There was no previous history of malignant disorders but his 11 year old son suffered from a liver tumor diagnosed as a hepatocellular carcinoma and underwent surgical resection followed by systemic chemotherapy. The father received systemic chemotherapy. However, the disease was progressive during the course and he died 3 months after admission. The family history of pediatric cancer and the young onset of the gastric carcinoma prompted genetic analysis with suspicion of a genetic abnormality. The final diagnosis was Li-Fraumeni syndrome. The genetic analysis in this patient did reveal germline mutations of which of the following genes?

p53