Pathology Flashcards
What is the most common benign soft tissue tumor in adults?
Lipoma
Lipoma: define
- A benign tumor of fat
- the most common soft tissue tumor of adulthood
- most frequently during middle adulthood
Lipoma: gross features
- soft, mobile, and painless (except angiolipoma)
- Cured by simple excision, rarely recur
- well-encapsulated mass of mature adipocytes
- Superficial tissues; proximal extremities and trunk
What is the most common soft tissue sarcoma in adults?
Liposarcoma
What are the 3 subtypes of liposarcoma, in order of worsening prognosis?
- well-differentiated
- myxoid
- pleomorphic
Where are lipomas vs liposarcomas typically found?
Lipoma: superficial (palpatable)
Liposarcoma: deep tissue (can’t palpate)
A 12;16 translocation is associated with what diagnosis?
Myxoid Liposarcoma
What is tuberous sclerosis, and what diagnosis is it associated with?
Development of multiple benign tumors throughout the body
cardiac rhabdomyoma
- Note: tumors are benign (no uncontrolled growth), but there are serious side effects)
Are skeletal muscle tumors usually benign or malignant?
Malignant
What are the 2 types of synovial sarcoma, and how do you distinguish them?
- monophasic: spindle cells in waves, no gland involvement
- biphasic: PLUS gland involvement
What are the subtypes of rhabdomyosarcoma, from best to worst prognosis? (4)
- botryoid
- embryonal
- alveolar
- pleomorphic
What soft tissue tumor is associated with trauma?
Nodular fasciitis
Contrast infantile and adult subtype fibrosarcoma.
- infantile: high mitotic rate with hemorrhage/necrosis; tends to present on axial or extremities; better prognosis
- adult: herringbone pattern; tends to present on lower extremities and trunk
What soft tissue tumor classically presents on the palm?
superficial fibromatosis
Contrast clinical presentation of dermatomyositis vs. polymyositis.
Both are characterized by proximal muscle weakness (travels distal over time), but dermatomyositis invovles skin lesions while polymyositis does not
Contrast the presentation sites of superficial vs. deep fibromatosis.
- superficial: palmar, plantar, penile
- deep: abdominal cavity, limb, girdle
Gottron papules are associated with what diagnosis?
Dermatomyositis
What is the gender incidence of Duchenne’s and Becker’s?
Both are more common in males (dystrophin gene is X-linked)
Contrast the age of presentation with Duchenne vs Becker’s.
- Duchenne will present in childhood (usually by 5 yrs old).
- Becker will be much later
What do people with ALS typically die from?
Respiratory failure (loss of control of the diaphragm)
Tongue involvement is classic for what diagnosis?
Amyotrophic lateral sclerosis (ALS)
Autoantibodies against post-synaptic Ach receptors are characteristic of what diagnosis?
Myasthenia Gravis
Contrast clinical presentation of Myasthenia Gravis vs Eaton-Lambert.
- Myasthania Gravis: gets worse with exercise, better with rest
- Eaton-Lambert: gets better with exercise (rapid repetitive stimulation), worse with rest
Autoantibodies against presynaptic calcium channels are characteristic of what diagnosis?
Eaton-Lambert syndrome
Diplopia and ptosis are associated with what diagnosis?
Mysthenia Gravis
Myasthenia Gravis is often associated with what underlying condition?
Thymoma
Eaton-Lambert is often associated with what underlying condition?
Small cell carcinoma of the lung
What is the characteristic cell of a rhabdomyosarcoma?
Rhabdomyoblast
What are “tadpole cells” and when do they appear?
Myocytes (eosinophilic, side nucleus), appear in better differentiated rhabdomyosarcomas (embryonal)
Lipoma: histology
- Normal fat
- Clear cytoplasm
- Few vessels
- Low mitoses- small nuclei
Liposarcoma: define
- Malignant tumor of adipose tissue
* One of the most common sarcomas of adulthood (50s to 60s)
general Liposarcoma: gross features
- Deep
- fixed
- Large
- not well circumscribed
- soft tissues of the proximal extremities and in the retroperitoneum
Liposarcoma characteristic cell
lipoblast
Liposarcoma: mutation
• Amplification of 12q13-q15 and t(12;16) are characteristic of well-differentiated and myxoid liposarcomas, respectively
○ One of the key genes in the amplified region of chromosome 12q is MDM2
○ MDM2 encodes a potent inhibitor of p53
liposarcoma: 3 subtypes
- well-differentiated
- myxoid
- pleomorphic
liposarcoma: 1. well-differentiated morphology
a. Normal adipocytes with few atypical spindle cells
○ Inactive/slow
Good prognosis
liposarcoma: 2. myxoid morphology
a. abundant basophilic extracellular matrix, arborizing capillaries and primitive cells at various stages of adipocyte differentiation reminiscent of fetal fat
b. Hyperchromatic nuclei
○ Malignant behavior
liposarcoma: 3. pleomorphic morphology
a. sheets of anaplastic cells, bizarre nuclei and variable amounts of immature adipocytes (lipoblasts)
○ Aggressive and frequently metastasizes
○ Rapid growth
○ Poor prognosis
Nodular Fasciitis:define
fibrous tumor
• A self-limited fibroblastic and myofibroblastic proliferation
Nodular Fasciitis: characteristics
- young adults
- upper extremity
- A history of trauma is present in ~25% of cases
- tumors grow rapidly over a period of several weeks or months
- Typically spontaneously regresses and if excised, it rarely recurs
- Arises in the deep dermis, subcutis, or muscle
- less than 5 cm, circumscribed, or slightly infiltrative
Nodular Fasciitis: mutation
• t(17;22) that produces a MYH9-USP6 fusion gene indicates that it is a clonal, but self-limited, proliferation
Nodular Fasciitis: histology
- Richly cellular and contains plump, immature-appearing fibroblasts and myofibroblasts arranges randomly
- A gradient of maturation
- Lymphocytes and extravasated RBCs are common
- Neutrophils are unusual
- Zonal patterns
Fibromatosis: histology
· Nodular or poorly defined broad fascicles of fibroblasts
· long, sweeping fascicles
· surrounded by abundant dense collagen
· resembles a scar
· No atypia
· Low mitotic activity
Superficial Fibromatosis: define
• An infiltrative fibroblastic proliferation that can cause local deformity but has an innocuous clinical course
All forms affect males more frequently than females
Superficial Fibromatosis: subtypes (3)
- Palmar (Dupuytren contracture)
- Plantar
- Penile (Peyronie disease)
A mutation of the FGFR3 gene is associated with what diagnosis?
Achondroplasia
A mutation of the COL1A1 gene is associated with what diagnosis?
Osteogenesis imperfecta
Osteopetrosis is usually due to a defect in what protein?
Carbonic anhydrase II (catalyzes synthesis of H2CO3 from H2O and CO2)
- can’t create the acidic microenvironment necessary for osteoclast function
Describe Superficial Fibromatosis subtype: Palmar (Dupuytren contracture)
Irregular or nodular thickening of the palmar fascia
Attachment to the overlying skin causes puckering and dimpling
Slowly progressive flexion contracture
fourth and fifth fingers of the hand
Deep Fibromatosis: gross
Abdominal cavity, limb girdle
Large, infiltrative masses that frequently recur but do not metastasize
Gray-white, firm, poorly demarcated masses varying from 1 to 15 cm in greatest diameter
Rubbery and tough, with marked infiltration of surrounding βmuscle, nerve and fat
Deep Fibromatosis: mutation
APC or β-catenin genes
increased Wnt signaling
majority are sporadic
Dx predisposed for Fibromatosis
familial adenomatous polyposis (Gardner syndrome)
germline APC mutations are predisposed
Fibrosarcoma: define
malignant mesenchymal tumor derived from fibrous connective tissue
Fibrosarcoma: histo
immature proliferating fibroblasts or undifferentiated anaplastic spindle cells in a storiform pattern
“Herringbone pattern”
Rhabdomyoma: define
Benign tumor of skeletal muscle
Rhabdomyoma: associated dx
Cardiac rhabdomyoma~ tuberous sclerosis (multi-system benign tumors)
Rhabdomyoma: histo
Eosinophilic spider-cells (“legs”)
Low mitotic activity
Well formed
Rhabdomyosarcoma: define
A malignant tumor of skeletal muscle
Rhabdomyosarcoma: common age group/site
Most common malignant soft tissue tumor in children
Common site: head/neck and vagina in young girls
Rhabdomyosarcoma: histo
Characteristic cell: rhabdomyoblast
Round Blue to eosinophillic skeletal muscle cells
Rhabdomyosarcoma: immunostain
(+) Desmin and Myo D1 immunostain
Rhabdomyosarcoma: (4) subtypes and prognosis
Botryoid (best prognosis)
Embryonal (good)
Alveolar (intermediate)
Pleomorphic (poor)
Rhabdomyosarcoma: mutation
genetically heterogenous:
Fusions of FOXO1 or FKHR to either PAX3 gene (alveolar)
PAX3 initiates skeletal muscle differentiation
Fusion interferes with the gene expression program that drives differentiation
t(2;13) translocation= chimeric proteins
Leiomyoma: define
A benign tumor of smooth muscle
Leiomyoma: common site
often arises in the uterus (most common neoplasm in women)
erector pili muscles (pilar leiomyomas)
Leiomyoma: mutation
autosomal dominant trait that is also Germline loss-of-function mutation in the fumarate hydratase gene located on chromosome 1q42.3
Enzyme participates in the Krebs cycle
Leiomyoma: histo
fascicles of densely eosinophilic spindle cells that tend to intersect each other at right angles
blunt-ended, tapered, elongated nuclei
minimal atypia and few mitotic figures
uterine Leiomyoma: Dx associated
renal cell carcinoma
Leiomyosarcoma: define
A malignant tumor of smooth muscle
Leiomyosarcoma: associated dx
Mets to lungs
Leiomyosarcoma: common sites
develop in the deep soft tissues of the extremities and retroperitoneum
Present as painless firm masses
Retroperitoneal tumors may be large and bulky and cause abdominal symptoms
Leiomyosarcoma: histo
eosinophilic spindle cells with blunt-ended/round, hyperchromatic nuclei
High mitotic activity
arranged in interweaving fascicles
Tumor cells contain bundles of thin filaments with dense bodies and pinocytic vesicles
Individual cells are surrounded by basal lamina
Leiomyosarcoma: antibody stain
mmunohistochemically, they stain with antibodies to smooth muscle actin and desmin
Synovial Sarcoma: define
soft tissues near the knee joint MISNOMER (NOT from synoviocytes)
Synovial Sarcoma: common clinical sx/sites
Sites: head, neck, chest wall
Well circumscribed
Patients present with a deep-seated mass that has been present for several years
Synovial Sarcoma: mutation
chromosomal translocation t(x;18)(p11;q11) producing SS18-SSX1, -SSX2, -SSX4 fusion genes that encode chimeric transcription factors
Synovial Sarcoma: histo: 2subtypes
1 Monophasic- uniform spindle cells with scant cytoplasm and dense chromatin growing in short, tightly packed fascicles
2 Biphasic- spindle cells, gland-like structures composed of cuboidal to columnar epithelioid cells
Undifferentiated Pleomorphic Sarcoma (UPS): define
General diagnosis of exclusion
Includes malignant mesenchymal tumors with high-grade, pleomorphic cells that cannot be classified into another category
Undifferentiated Pleomorphic Sarcoma (UPS): prognosis
Prognosis is poor with metastases arising in 30-50% of cases
Very aggressive
Undifferentiated Pleomorphic Sarcoma (UPS): histo
Large, anaplastic spindled to polygonal cells
Storiform/ pin-wheel pattern/ whirling
hyperchromatic irregular, bizarre nuclei
High mitotic rate
Sheets
Lesions contain myxoid areas (gelatinous)
Inflammation and giant cells
Antibody Mediated DISEASES OF THE NEUROMUSCULAR JUNCTION (2)
Myasthenia Gravis
and Lambert-Eaton Myasthenic Syndrome
Myasthenia Gravis: mechanism
autoantibodies directed against postsynaptic ACh receptors
aggregation and degradation of the receptors, and damage of the postsynaptic membrane through complement fixation
Myasthenia Gravis: associated Dx
strong association with thymic abnormalities
thymoma (tumor of thymic epithelial cells)
thymic hyperplasia
Appearance of B-cell follicles in the thymus
Myasthenia Gravis: Clinical Features
Fluctuating weakness that worsens with exertion and often over the course of a day
Diplopia and ptosis due to involvement of extraocular muscles are common
Decrement in muscle response with repeated stimulation
Myasthenia Gravis: Tx
Acetylcholinesterase inhibitors that increase the half-life of ACh are the first line of treatment
immunosuppressive drugs (glucocorticoids, cyclosporine, rituximab)
Thymectomy
Lambert-Eaton Myasthenic Syndrome: mechanism
antibodies that block ACh release by inhibiting a presynaptic calcium channel
Lambert-Eaton Myasthenic Syndrome: clinical Sx
rapid repetitive stimulation increases muscle response
Patients typically present with weakness of their extremities
Proximal weakness
Lambert-Eaton Myasthenic Syndrome: associated Dx
underlying malignancy (paraneoplastic syndrome) Small cell carcinoma of the lung
Lambert-Eaton Myasthenic Syndrome: can you treat with Acetylcholinesterase inhibitors?
No response
Treatment: immunosuppressive agents and glucocorticoids
Congenital DISEASES OF THE NEUROMUSCULAR JUNCTION
AR Myasthenic Syndromes
AR Myasthenic Syndromes: mutation
Autosomal recessive mode of inheritance
loss-of-function mutations in the gene encoding the ε-subunit of the AChR
AR Myasthenic Syndromes: age and Sx
marked by varying degrees of muscle weakness perinatal period (congenital) poor muscle tone, external eye muscle weakness, and breathing difficulties
Botulism: mechanism
caused by exposure to a neurotoxin that is produced by the anaerobic Gram (+) organism Clostridium botulinum
Blocks the release of ACh from presynaptic neurons
Autoimmune Inflammatory Myopathies OF SKELETAL MUSCLE
Dermatomyositis and Polymyositis
Dermatomyositis: sx
symmetric proximal muscle weakness and skin changes
slow in onset, symmetric, and often accompanied by myalgias
Lilac colored discoloration of the upper eyelids (heliotrope rash) and periorbital edema
Rash with scaling on flexors
Gottron papules
Telangiectasias
Dermatomyositis: mechanism
Deposition of the complement membrane attack complex (C5b-9)
humoral immune injury: infiltrate rich in B cells and CD4+ T cells
Dermatomyositis: labs
High creatine kinase
(+) ANA and anti-Jo-1 antibody
Dermatomyositis: histo
infiltrates of mononuclear inflammatory cells in the perimysial connective tissue and around blood vessels
atrophy at periphery of fascicle (perifascular)
EM may show tubuloreticular endothelial cell inclusions that are linked to a type I interferon response
Polymyositis:histo
Mononuclear inflammatory cells (macrophages)
endomysial in location
Degeneration necrotic, regenerating, and atrophic myofibers are typically found in a random or patchy distribution
Perifascicular pattern of atrophy is absent
greatest risk for osteomyelitis
1) hematogenous spread
2) trauma, surgery, diabetes, vascular insufficiency, implants/prostheses
lab value: 25-hydroxyvitamin D is LOW (<20)
Dx?
vitamin D deficiency
rickets/osteomalacia
Duchenne muscular dystrophy: mechanism
mutations that cause deletion of dystrophin (loss of function)
