Hertz Joints and Soft Tissue

Question 1

Osteoarthritis

Answer 1

called degenerative joint disease, is characterized by degeneration of cartilage that results in structural and functional failure of synovial joints

lesions of osteoarthritis (OA) stem from degeneration of the articular cartilage and its disordered repair

Question 2

Clinical Course

of osteoarthritis

Answer 2

insidious disease. Patients with primary disease are usually asymptomatic until they are in their 50s.

If a * young person has significant manifestations of osteoarthritis, a search for some underlying cause should be made. Characteristic symptoms include deep, achy pain that worsens with use, morning stiffness, crepitus, and limitation of range of movement. Impingement on spinal foramina by osteophytes results in cervical and lumbar nerve root compression and radicular pain, muscle spasms, muscle atrophy, and neurologic deficits.

Typically, only one or a few joints are involved except in the uncommon generalized variant. The joints commonly involved include the hips, knees, lower lumbar and cervical vertebrae, proximal and distal interphalangeal joints of the fingers, first carpometacarpal joints, and first tarsometatarsal joints. * Heberden nodes, prominent osteophytes at the distal interphalangeal joints*, are common in women (but not men)

Question 3

Rheumatoid Arthritis

Answer 3

• chronic inflammatory disorder of autoimmune origin that may affect many tissues and organs but principally attacks the joints, producing a nonsuppurative proliferative and inflammatory synovitis

ulnar deviation of fingers

T and B cell process

CD4+ T helper (TH) cells may initiate response by reacting with an arthritogenic agent, perhaps microbial or a self-antigen

TNF - firmly implicated; TNF * antagonists = effective therapies

The synovium of RA contains * germinal centers with secondary follicles and abundant plasma cells which produce antibodies, some of which are against self-antigens

Find pannus growing in joint space

Question 4

Rheumatoid Arthritis

and skin

Answer 4

• Rheumatoid subcutaneous nodules - most common cutaneous lesions.
• usually in those with severe disease,
• arise in regions of the skin subjected to pressure, including the ulnar aspect of the forearm, elbows, occiput, and lumbosacral area.
• Less commonly they form in the lungs, spleen, pericardium, myocardium, heart valves, aorta, and other viscera.
• Rheumatoid nodules are firm, nontender, and round to oval, and in the skin arise in the subcutaneous tissue. Microscopically they * resemble necrotizing granulomas with a central zone of fibrinoid necrosis surrounded by a prominent rim activated macrophages and numerous lymphocytes and plasma cells.

Question 5

Rheumatoid arthritis and blood vessels

Answer 5

• high titers of rheumatoid factor –> vasculitis.

The acute necrotizing vasculitis involves * small and large arteries.

It may involve the pleura, pericardium or lung evolving into chronic fibrosing processes.

Frequently, segments of small arteries such as vasa nervorum and the digital arteries are obstructed by an obliterating endarteritis resulting in peripheral neuropathy, ulcers, and gangrene.

Leukocytoclastic vasculitis produces purpura, cutaneous ulcers, and nail bed infarction.

Ocular changes such as uveitis and keratoconjunctivitis (similar to Sjögren syndrome, may be prominent.

Question 6

clinical course of RA

Answer 6

may begin *slowly and insidiously with malaise, fatigue, and generalized musculoskeletal pain, likely mediated by IL-1 and TNF. After several weeks to months the joints become involved.

The pattern of joint involvement varies, but it is * generally symmetrical and the small joints are affected before the larger ones.

Symptoms usually develop in the hands (metacarpophalangeal and proximal interphalangeal joints) and feet, followed by the wrists, ankles, elbows, and knees. Uncommonly the upper spine is involved, but the lumbosacral region and hips are usually spared

Question 7

dx of RA

Answer 7

The presence of multisystem involvement must be distinguished from other forms of chronic arthritis (* lupus, scleroderma, Lyme disease).

The diagnosis of RA is supported by:

Characteristic *radiographic findings,
Sterile, turbid synovial fluid with decreased viscosity, poor mucin clot formation, and inclusion-bearing neutrophils, and
The combination of rheumatoid factor and anti-CCP antibody (80% of patients).

Question 8

Juvenile Idiopathic Arthritis

Answer 8

Juvenile idiopathic arthritis (JIA) is a heterogeneous group of disorders of unknown cause that present with arthritis before age 16 and persist for at least 6 weeks.

Compared to RA, in JIA:
Oligoarthritis is more common,
Systemic disease is more frequent
Large joints are affected more often than small joints
Rheumatoid nodules and rheumatoid factor are usually absent
Antinuclear antibody (ANA) seropositivity is common

Question 9

Seronegative Spondyloarthropathies

Answer 9

Pathologic changes in the ligamentous attachments rather than synovium
Involvement of sacroiliac joints, with or without other joints
Absence of rheumatoid factor
Association with HLA-B27

Question 10

Ankylosing Spondylitis

Answer 10

Ankylosing spondylitis causes destruction of articular cartilage and bony ankylosis, especially of the * sacroiliac and apophyseal joints (between tuberosities and processes)

Disease involving the sacroiliac joints and vertebrae becomes symptomatic in the * second and third decades of life as lower back pain and spinal immobility. Involvement of peripheral joints, such as the hips, knees, and shoulders, occurs in at least one third of affected individuals.

Approximately *90% of patients are HLA-B27 positive

Question 11

Reactive Arthritis

Answer 11

(= Reiter’s Syndrome)

Reactive arthritis is defined by a triad of * arthritis, nongonococcal urethritis or cervicitis, and conjunctivitis**

Most affected individuals are men in their 20s or 30s, and more than 80% are HLA-B27 positive. This form of arthritis also affects individuals infected with the human immunodeficiency virus (HIV).

The disease is probably caused by an autoimmune reaction initiated by prior infection of the genitourinary system * (Chlamydia) or the gastrointestinal tract (Shigella, Salmonella, Yersinia, Campylobacter).*

**“Can’t see, can’t pee, can’t climb a tree”

Question 12

Enteritis Associated Arthritis

Answer 12

Enteritis-associated arthritis is caused by gastrointestinal infection by Yersinia, Salmonella, Shigella, and Campylobacter

The arthritis appears abruptly and tends to involve the knees and ankles but sometimes also the wrists, fingers, and toes. Unlike reactive arthritis, it * lasts for about a year, then generally clears and only rarely is accompanied by ankylosing spondylitis.

Question 13

Psoriatic Arthritis

Answer 13

Psoriatic arthritis is a chronic inflammatory arthropathy associated with psoriasis that affects peripheral and axial joints and entheses (ligaments and tendons)

Symptoms manifest between the ages of 30 and 50. It develops in more than 10% of the psoriatic population, * usually concurrently or following the onset of skin disease.

SI joints are involved in 20% of patients, but predominantly a peripheral arthritis of the hands and feet. The * distal interphalangeal joints of the hands and feet are first affected in an ** asymmetric distribution –> “pencil in cup” deformity

Question 14

Infectious Arthritis

Answer 14

= Suppurative Arthritis

Bacterial infections that cause acute suppurative arthritis usually enter the joints from distant sites by hematogenous spread

The classic presentation is the sudden development of an acutely painful and swollen joint that has a restricted range of motion. Systemic findings of * fever, leukocytosis, and elevated sedimentation rate are common. In disseminated gonococcal infection the symptoms are more subacute.

In 90% of * nongonococcal cases, the infection involves only a single joint, most commonly the knee followed in frequency by the hip, shoulder, elbow, wrist, and sternoclavicular joints. The axial joints are more often involved in drug users.

Joint aspiration is diagnostic if it yields * purulent fluid in which the causal agent can be identified. Prompt recognition and effective antimicrobial therapy can prevent joint destruction.

Question 15

Lyme Arthritis

Answer 15

• Borrelia burgdorferi,
• transmitted by deer ticks of the **Ixodes ricinus complex.
• leading arthropod borne disease in the United States. I
• progressively involves multiple organ systems.
• initial infection of the skin is followed within several days or weeks by dissemination of the organism to other sites, especially the joints.
• *60% to 80% of untreated individuals with the disease develop arthritis during the late stage. –> large joints, esp. knees, shoulders, elbows, and ankles in descending order of frequency.
• Usually one or two joints are affected at a time, and the attacks last for a few weeks to months, migrating to new sites.

Spirochetes can only be identified in about 25% of joints with arthritis but the diagnosis can be *confirmed by serologic testing for anti-Borrelia anti­bodies.

• most respond to antibiotic therapy.

Question 16

Crystal-Induced Arthritis

Answer 16

Articular crystal deposits are associated with a variety of acute and chronic joint disorders. Endogenous crystals shown to be pathogenic include * monosodium urate (gout), calcium pyrophosphate dehydrate (pseudogout)*, and basic calcium phosphate

Question 17

Gout

Answer 17

Hyperuricemia *(plasma urate level above 6.8 mg/dL) is necessary, but not sufficient, for the development of gout

Hyperuricemia can result from either * overproduction or reduced excretion

The *inflammation in gout is triggered by precipitation of monosodium urate (MSU) crystals into the joints, which result in the production of cytokines that recruit leukocytes

Question 18

factors in gout

Answer 18

Hyperuricemia does not necessarily lead to gouty arthritis. Many factors contribute to the conversion of asymptomatic hyperuricemia into primary gout, including the following

Age of the individual and duration of the hyperuricemia. Gout usually appears after 20 to 30 years of hyperuricemia.
Genetic predisposition. In addition to the well-defined X-linked abnormalities of HGPRT, primary gout follows multifactorial inheritance and runs in families. Polymorphisms in genes involved in urate transport and homeostasis (URAT1 and GLUT9) are also associated with gout.
Heavy alcohol consumption
Obesity
Drugs (e.g., thiazides) that reduce excretion of urate
Lead toxicity (so-called saturnine gout)

Question 19

Clinical Course

of gout

Answer 19

• more common in men and >30. Patients with obesity, metabolic syndrome, excess alcohol intake and renal failure are at increased risk
• Asymptomatic hyperuricemia appears around puberty in males and after menopause in females.
• Acute arthritis presents after several years as sudden onset of excruciating joint pain associated with localized hyperemia, warmth. Constitutional symptoms are uncommon except for occasional mild fever. Most first attacks are monoarticular; 50% occur in the first metatarsophalangeal joint. Eventually, about 90% of affected individuals experience acute attacks in the following locations (in descending order of frequency): insteps, ankles, heels, knees, wrists, fingers, and elbows. Un­treated, acute gouty arthritis may last for hours to weeks, but gradually there is complete resolution.
• Asymptomatic intercritical period: Resolution of the acute arthritis leads to a symptom free interval. Although some patients never have another attack, most experience a second acute episode within months to a few years. In the absence of appropriate therapy, the attacks recur at shorter intervals and frequently become polyarticular.
• Chronic tophaceous gout develops on average about 12 years after the initial acute attack and the appearance of chronic tophaceous arthritis. At this stage, radiographs show characteristic juxta-articular bone erosion caused by osteoclastic bone resorption and loss of the joint space. Progression leads to severe crippling disease

Question 20

Calcium Pyrophosphate Crystal Deposition Disease (Pseudo-Gout)

Answer 20

Calcium pyrophosphate crystal deposition disease (CPPD), also known as *pseudo-gout and chondrocalcinosis, usu­ally occurs in individuals older than 50 years of age and becomes more common with increasing age, rising to a prevalence of 30% to 60% in those 85 years or older

CPPD is frequently asymptomatic. However, it may produce acute, subacute, or chronic arthritis that can be confused with osteoarthritis or rheumatoid arthritis.

The joint involvement may last from several days to weeks and may be monoarticular or polyarticular; the knees, followed by the wrists, elbows, shoulders, and ankles, are most commonly affected. Ultimately, approximately 50% of affected individuals experience significant joint damage.

Therapy is supportive. There is no known treatment that prevents or slows crystal formation

Question 21

telling real gout from pseudogout

Answer 21

real gout is YIPA- yellow in parallel (yellow/blue with 90 degree rotation)

(pseudo is yellow in perpendicular)

Question 22

Robbins key concepts for arthritis

Answer 22

osteoarthritis- most common disease of joints, degenerative process of articular cartilage in which matrix breakdown exceeds synthesis. Inflammation is minimal and typically secondary. Local production of inflammatory cytokines may contribute to the progression of joint degeneration

RA- chronic autoimmune inflammatory disease that affects mainly small joints, but can be systemic. RA is caused by a cellular and humoral imune response against self-antigens, particularly citrullinated proteins. TNF plays a central role and antagonists against TNF are of clinical benefit.

Seronegative spondloarthropathis- heterogeneous group of likely autoimmune arthritides that preferentially involve the SI and vertebral joints and are associated with HLA-B27.

Suppurative arthritis- direct infection of a joint space by bacterial organisms.

Lyme disease- systemic infection by Borrelia burgdorferi which manifests, in part, as an infectious arthritis, possibly with an autoimmune component in chronic stages.

Gout and pseudogout result from inflammatory responses triggered by precipitation of urate or calcium pyrophosphate, respectively.

Question 23

Joint Tumors and Tumor-Like Conditions

in general

Answer 23

Reactive tumor-like lesions, such as ganglions, synovial cysts, and osteochondral loose bodies commonly involve joints and tendon sheaths.

They usually result from trauma or degenerative processes and are much more common than neoplasms

Question 24

Ganglion and Synovial Cysts

Answer 24

• ganglion- small (1 to 1.5 cm) cyst, almost always located near a joint capsule or tendon sheath. Common around joints of the wrist- firm, fluctuant, pea-sized translucent nodule. result of cystic or myxoid degeneration of connective tissue; hence the cyst wall lacks a cell lining.

The lesion may be multilocular and enlarges through coalescence of adjacent areas of myxoid change. The fluid that fills the cyst is similar to synovial fluid; however, there is no communication with the joint space

Herniation of synovium through a joint capsule or massive enlargement of a bursa may –> synovial cyst. A well-recognized example is the synovial cyst that forms in the popliteal space in the setting of rheumatoid arthritis * (Baker cyst). The synovial lining may be hyperplastic and contain inflammatory cells and fibrin

Question 25

Diffuse tenosynovial giant cell tumor

Answer 25

presents in the ** knee in 80% of cases, followed in frequency by the hip, ankle, and calcaneocuboid joints. Affected individuals typically complain of pain, locking, and recurrent swelling similar to monoarticular arthritis.

Tumor progression limits the range of movement of the joint and causes it to become stiff and firm. Sometimes a palpable mass is appreciated. Aggressive tumors erode into adjacent bones and soft tissues, causing confusion with other types of neoplasms. In contrast, the localized variant manifests as a solitary, slow-growing, painless mass that frequently involves the tendon sheaths along the wrists and fingers; it is the most common mesenchymal neoplasm of the hand. Cortical erosion of adjacent bone occurs in approximately 15% of cases.

Both types are amenable to surgical excision, but recurrence is common. Clinical trials using antagonists of M-CSF signaling have produced encouraging responses.

Question 26

Soft Tissue

tumors

Answer 26

non-epithelial tissue excluding the skeleton, joints, central nervous system, hematopoietic and lymphoid tissues.

Benign outnumber the malignant by 100x.

Most soft tissue sarcomas (very aggressive) arise in the extremities, esp. thigh

Question 27

tumor deep to the fascial plane or retroperitoneal is

Answer 27

bad

Question 28

diagnosing soft-tissue tumors and tumor-like lesions

Answer 28

Multiple modalities required for diagnosis

Question 29

Fascicles of eosinophilic spindle cells intersecting at right angles. Tumor type?

Answer 29

Smooth muscle

Question 30

Short fascicles of spindle cells radiating from a central point like spokes on a whieel- storiform. Tumor type?

Answer 30

Fibrohistiocytic

Question 31

Nuclei arranged in columns- palisading. Tumor type?

Answer 31

Schwann cell

Question 32

Herringbone. Tumor type?

Answer 32

Fibrosarcoma

Question 33

Mixture of fascicles of spindle cells and groups of epithelioid cells- biphasic. Tumor type?

Answer 33

Synovial sarcoma

Question 34

Classification of soft tissue tumors continues to evolve as new molecular genetic abnormalities are identified

Answer 34

Clinically, soft tissue tumors range from benign, self-limited lesions that require minimal treatment to intermediate grade, locally aggressive tumors with minimal metastatic risk to highly aggressive malignancies with significant metastatic risk and mortality.

The term sarcoma is applied somewhat inconsistently such that some, but not all, locally aggressive tumors fall into this category. Tumors with significant metastatic potential are, of course, con­sidered sarcomas.

Pathologic classification integrates morphology (e.g., muscle differentiation), immunohistochemistry and molecular diagnostics. In addition to accurate diagnosis, grade (degree of differentiation) and stage (size and depth) are important prognostic indicators.

Question 35

Tumors of Adipose Tissue- lipoma

Answer 35

Lipoma, a benign tumor of fat, is the most common soft tissue tumor of adulthood

Question 36

Liposarcoma

Answer 36

one of the most common sarcomas of adulthood.

It occurs mainly in people in their 50s to 60s in the deep soft tissues of the proximal extremities and in the retroperitoneum

Question 37

Nodular fasciitis

Answer 37

trauma-induced tumor coming off the fascial plane

Question 38

Superficial Fibromatosis

Answer 38

infiltrative fibroblastic proliferation that can cause local deformity but has an innocuous clinical course. All forms of superficial fibromatosis affect males more frequently than females. They are characterized by nodular or poorly defined broad fascicles of fibroblasts in long, sweeping fascicles, surrounded by abundant dense collagen. Several clinical subtypes have been identified:

Palmar (dupuytren contracture), Plantar, Penile (Peyronie disease)

Question 39

Palmar Superficial Fibromatosis (Dupuytren contracture):

Answer 39

Irregular or nodular thickening of the palmar fascia either unilaterally or bilaterally (50%). Over a span of years, attachment to the overlying skin causes puckering and dimpling. At the same time a slowly progressive flexion contracture develops that mainly affects the fourth and fifth fingers of the hand.

Question 40

Plantar Superficial Fibromatosis

Answer 40

Common in young patients, unilateral and without contractures.

Question 41

Penile Superficial Fibromatosis

Peyronie disease

Answer 41

): Palpable induration or mass on the dorsolateral aspect of the penis. Eventually, it may cause abnormal curvature of the shaft, constriction of the urethra, or both.

Question 42

Deep Fibromatosis (Desmoid Tumors)

Answer 42

large, infiltrative masses that frequently recur but do not metastasize.

They are most frequent in the teens to 30s, predominantly in women.

Abdominal fibromatosis generally arises in the musculoaponeurotic structures of the anterior abdominal wall but tumors can arise in the limb girdles or the mesentery.

Question 43

Deep-Seated Fibromatosis (Desmoid Tumors)- Types

Answer 43

Deep-seated fibromatosis is divided into extra-abdominal, abdominal, and intra-abdominal types, but all have similar gross and microscopic features.

Extra-abdominal fibromatosis occurs in men and women with equal frequency and arises principally in the musculature of the shoulder, chest wall, back, and thigh.

Abdominal fibromatosis generally arises in the musculoaponeurotic structures of the anterior abdominal wall in women during or after pregnancy.

Intra-abdominal fibromatosis tends to occur in the mesentery or pelvic walls, often in individuals having familial adenomatous polyposis

Question 44

Skeletal Muscle Tumors

Answer 44

Skeletal muscle neoplasms, in contrast to other mesenchymal histotypes, are almost all malignant.

The benign variant, rhabdomyoma, is frequent in individuals with tuberous sclerosis

Question 45

Rhabdomyosarcoma

Answer 45

a malignant mesenchymal tumor with skeletal muscle differentiation.

Three subtypes are recognized: *alveolar (20%), * embryonal (60%) and * pleomorphic (20%). Rhabdomyosarcoma (alveolar and embryonal) is the most common soft tissue sarcoma of childhood and adolescence, usually appearing before age 20.

Pleomorphic rhabdomyosarcoma is seen predominantly in adults. The pediatric forms often arise in the sinuses, head and neck and genitourinary tract, locations that do not normally contain much skeletal muscle, underscoring the notion that sarcomas do not arise from mature, terminally differentiated muscle cells

Question 46

rhabdomyosarcoma treatment and prognosis

Answer 46

Rhabdomyosarcomas are aggressive neoplasms that are usually treated with surgery and chemotherapy, with or without radiation therapy.

The histologic type and location of the tumor influence survival. The botryoid variant of embryonal rhabdomyosarcoma has the best prognosis, while the pleomorphic subtype is often fatal

Question 47

Leiomyoma

Answer 47

benign tumor of smooth muscle, often arises in the uterus; in fact, uterine leiomyomas are the most common neoplasm in women.

They develop in 77% of women and, depending on their number, size, and location, may cause a variety of symptoms including infertility.

Leiomyomas may also arise from the erector pili muscles (pilar leiomyomas) found in the skin, nipples, scrotum, and labia and rarely in the deep soft tissues and the muscularis of the gut. Pilar leiomyomas may be * multiple and painful

Question 48

Leiomyosarcoma

epidemiology

Answer 48

Leiomyosarcoma accounts for 10% to 20% of soft tissue sarcomas.

They occur in adults and afflict women more frequently than men.

Most develop in the deep soft tissues of the extremities and retroperitoneum

Treatment depends on tumor size, location, and grade.

Superficial or cutaneous leiomyosarcomas are usually small and have a good prognosis, whereas those of the retroperitoneum are large, cannot be entirely excised, and cause death by both local extension and metastatic spread, especially to the ** lungs

Question 49

Synovial Sarcoma

Answer 49

Synovial sarcoma was so-named because the first described cases arose in the soft tissues near the knee joint and a morphologic relationship to synovium was postulated. However, this name is a misnomer, as these tumors can present in locations (chest wall, head and neck) that lack synovium and their morphologic features are inconsistent with an origin from synoviocytes.

• 10% of all soft tissue sarcomas

Most occur in people in their 20s to 40s. Patients usually present with a deep-seated mass that has been present for several years

treated aggressively with limb-sparing surgery and frequently chemotherapy.

The 5-year survival varies from 25% to 62%, related to stage and patient age.

Common sites of metastases are the lung and occasionally the regional lymph nodes

Question 50

Undifferentiated Pleomorphic Sarcoma

Answer 50

includes malignant mesenchymal tumors with high-grade, pleomorphic cells that cannot be classified into another category by a combination of histomorphology, immunophenotype, ultrastructure or molecular genetics.

Despite advances in molecular characterization of sarcomas, UPS represents the largest category of adult sarcomas. Most arise in the deep soft tissues of the extremity, especially the thigh of middle aged or older adults.

The diagnosis of malignant fibrous histiocytoma (MFH), sometimes used interchangeably with UPS, has fallen out of usage because (1) the category included both undifferentiated tumors and others that were reclassified with immunohistochemistry or molecular methods, and (2) no consensus exists for the morphologic definition of fibrohistiocytic

Question 51

Robbins Key Concepts- Soft Tissue Tumors

Answer 51

those that don’t fall into categories of epithelial, skeletal, CNS, hematopoietic or lymphoid tissues. A sarcoma= malignant mesenchymal tumor.

Although all soft tissue tumors probably arise from pluripotent esenchymal stem cells, rather than mature cells, tumors can be classified into:

• those that recapitulate a mature mesenchymal tissue- further subdivided into benign and malignant
• those composed of cells for which there is no normal counterpart (e.g. synovial sarcoma, undifferentiated pleomorphic sarcoma)

Sarcomas with simple karyotypes demonstrate reproducible, chromosomal and molecular abnormalities which contribute to pathogenesis and are sufficiently specific to have diagnostic utitily.
Most adult sarcomas have complex karyotypes, tend to be pleomorphic and genetically heterogeneous with a poor prognosis.