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MSK Final > Pathology > Flashcards

Pathology Flashcards

1
Q

What is the most common benign soft tissue tumor in adults?

A

Lipoma

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2
Q

Lipoma: define

A
  • A benign tumor of fat
  • the most common soft tissue tumor of adulthood
  • most frequently during middle adulthood
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3
Q

Lipoma: gross features

A
  • soft, mobile, and painless (except angiolipoma)
  • Cured by simple excision, rarely recur
  • well-encapsulated mass of mature adipocytes
  • Superficial tissues; proximal extremities and trunk
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4
Q

What is the most common soft tissue sarcoma in adults?

A

Liposarcoma

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5
Q

What are the 3 subtypes of liposarcoma, in order of worsening prognosis?

A
  • well-differentiated
  • myxoid
  • pleomorphic
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6
Q

Where are lipomas vs liposarcomas typically found?

A

Lipoma: superficial (palpatable)
Liposarcoma: deep tissue (can’t palpate)

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7
Q

A 12;16 translocation is associated with what diagnosis?

A

Myxoid Liposarcoma

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8
Q

What is tuberous sclerosis, and what diagnosis is it associated with?

A

Development of multiple benign tumors throughout the body
cardiac rhabdomyoma
- Note: tumors are benign (no uncontrolled growth), but there are serious side effects)

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9
Q

Are skeletal muscle tumors usually benign or malignant?

A

Malignant

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10
Q

What are the 2 types of synovial sarcoma, and how do you distinguish them?

A
  • monophasic: spindle cells in waves, no gland involvement

- biphasic: PLUS gland involvement

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11
Q

What are the subtypes of rhabdomyosarcoma, from best to worst prognosis? (4)

A
  • botryoid
  • embryonal
  • alveolar
  • pleomorphic
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12
Q

What soft tissue tumor is associated with trauma?

A

Nodular fasciitis

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13
Q

Contrast infantile and adult subtype fibrosarcoma.

A
  • 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
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14
Q

What soft tissue tumor classically presents on the palm?

A

superficial fibromatosis

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15
Q

Contrast clinical presentation of dermatomyositis vs. polymyositis.

A

Both are characterized by proximal muscle weakness (travels distal over time), but dermatomyositis invovles skin lesions while polymyositis does not

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16
Q

Contrast the presentation sites of superficial vs. deep fibromatosis.

A
  • superficial: palmar, plantar, penile

- deep: abdominal cavity, limb, girdle

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17
Q

Gottron papules are associated with what diagnosis?

A

Dermatomyositis

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18
Q

What is the gender incidence of Duchenne’s and Becker’s?

A

Both are more common in males (dystrophin gene is X-linked)

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19
Q

Contrast the age of presentation with Duchenne vs Becker’s.

A
  • Duchenne will present in childhood (usually by 5 yrs old).

- Becker will be much later

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20
Q

What do people with ALS typically die from?

A

Respiratory failure (loss of control of the diaphragm)

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21
Q

Tongue involvement is classic for what diagnosis?

A

Amyotrophic lateral sclerosis (ALS)

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22
Q

Autoantibodies against post-synaptic Ach receptors are characteristic of what diagnosis?

A

Myasthenia Gravis

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23
Q

Contrast clinical presentation of Myasthenia Gravis vs Eaton-Lambert.

A
  • Myasthania Gravis: gets worse with exercise, better with rest
  • Eaton-Lambert: gets better with exercise (rapid repetitive stimulation), worse with rest
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24
Q

Autoantibodies against presynaptic calcium channels are characteristic of what diagnosis?

A

Eaton-Lambert syndrome

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25
Q

Diplopia and ptosis are associated with what diagnosis?

A

Mysthenia Gravis

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26
Q

Myasthenia Gravis is often associated with what underlying condition?

A

Thymoma

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27
Q

Eaton-Lambert is often associated with what underlying condition?

A

Small cell carcinoma of the lung

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28
Q

What is the characteristic cell of a rhabdomyosarcoma?

A

Rhabdomyoblast

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29
Q

What are “tadpole cells” and when do they appear?

A

Myocytes (eosinophilic, side nucleus), appear in better differentiated rhabdomyosarcomas (embryonal)

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30
Q

Lipoma: histology

A
  • Normal fat
    • Clear cytoplasm
    • Few vessels
    • Low mitoses- small nuclei
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31
Q

Liposarcoma: define

A
  • Malignant tumor of adipose tissue

* One of the most common sarcomas of adulthood (50s to 60s)

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32
Q

general Liposarcoma: gross features

A
  • Deep
  • fixed
  • Large
  • not well circumscribed
  • soft tissues of the proximal extremities and in the retroperitoneum
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33
Q

Liposarcoma characteristic cell

A

lipoblast

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34
Q

Liposarcoma: mutation

A

• 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

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35
Q

liposarcoma: 3 subtypes

A
  1. well-differentiated
  2. myxoid
  3. pleomorphic
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36
Q

liposarcoma: 1. well-differentiated morphology

A

a. Normal adipocytes with few atypical spindle cells
○ Inactive/slow
Good prognosis

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37
Q

liposarcoma: 2. myxoid morphology

A

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

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38
Q

liposarcoma: 3. pleomorphic morphology

A

a. sheets of anaplastic cells, bizarre nuclei and variable amounts of immature adipocytes (lipoblasts)
○ Aggressive and frequently metastasizes
○ Rapid growth
○ Poor prognosis

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39
Q

Nodular Fasciitis:define

A

fibrous tumor

• A self-limited fibroblastic and myofibroblastic proliferation

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40
Q

Nodular Fasciitis: characteristics

A
  • 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
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41
Q

Nodular Fasciitis: mutation

A

• t(17;22) that produces a MYH9-USP6 fusion gene indicates that it is a clonal, but self-limited, proliferation

42
Q

Nodular Fasciitis: histology

A
  • 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
43
Q

Fibromatosis: histology

A

· Nodular or poorly defined broad fascicles of fibroblasts
· long, sweeping fascicles
· surrounded by abundant dense collagen
· resembles a scar
· No atypia
· Low mitotic activity

44
Q

Superficial Fibromatosis: define

A

• An infiltrative fibroblastic proliferation that can cause local deformity but has an innocuous clinical course

All forms affect males more frequently than females

45
Q

Superficial Fibromatosis: subtypes (3)

A
  1. Palmar (Dupuytren contracture)
    1. Plantar
    2. Penile (Peyronie disease)
46
Q

A mutation of the FGFR3 gene is associated with what diagnosis?

A

Achondroplasia

47
Q

A mutation of the COL1A1 gene is associated with what diagnosis?

A

Osteogenesis imperfecta

48
Q

Osteopetrosis is usually due to a defect in what protein?

A

Carbonic anhydrase II (catalyzes synthesis of H2CO3 from H2O and CO2)
- can’t create the acidic microenvironment necessary for osteoclast function

49
Q

Describe Superficial Fibromatosis subtype: Palmar (Dupuytren contracture)

A

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

50
Q

Deep Fibromatosis: gross

A

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

51
Q

Deep Fibromatosis: mutation

A

APC or β-catenin genes
increased Wnt signaling
majority are sporadic

52
Q

Dx predisposed for Fibromatosis

A

familial adenomatous polyposis (Gardner syndrome)

germline APC mutations are predisposed

53
Q

Fibrosarcoma: define

A

malignant mesenchymal tumor derived from fibrous connective tissue

54
Q

Fibrosarcoma: histo

A

immature proliferating fibroblasts or undifferentiated anaplastic spindle cells in a storiform pattern
“Herringbone pattern”

55
Q

Rhabdomyoma: define

A

Benign tumor of skeletal muscle

56
Q

Rhabdomyoma: associated dx

A

Cardiac rhabdomyoma~ tuberous sclerosis (multi-system benign tumors)

57
Q

Rhabdomyoma: histo

A

Eosinophilic spider-cells (“legs”)
Low mitotic activity
Well formed

58
Q

Rhabdomyosarcoma: define

A

A malignant tumor of skeletal muscle

59
Q

Rhabdomyosarcoma: common age group/site

A

Most common malignant soft tissue tumor in children

Common site: head/neck and vagina in young girls

60
Q

Rhabdomyosarcoma: histo

A

Characteristic cell: rhabdomyoblast

Round Blue to eosinophillic skeletal muscle cells

61
Q

Rhabdomyosarcoma: immunostain

A

(+) Desmin and Myo D1 immunostain

62
Q

Rhabdomyosarcoma: (4) subtypes and prognosis

A

Botryoid (best prognosis)
Embryonal (good)
Alveolar (intermediate)
Pleomorphic (poor)

63
Q

Rhabdomyosarcoma: mutation

A

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

64
Q

Leiomyoma: define

A

A benign tumor of smooth muscle

65
Q

Leiomyoma: common site

A

often arises in the uterus (most common neoplasm in women)

erector pili muscles (pilar leiomyomas)

66
Q

Leiomyoma: mutation

A

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

67
Q

Leiomyoma: histo

A

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

68
Q

uterine Leiomyoma: Dx associated

A

renal cell carcinoma

69
Q

Leiomyosarcoma: define

A

A malignant tumor of smooth muscle

70
Q

Leiomyosarcoma: associated dx

A

Mets to lungs

71
Q

Leiomyosarcoma: common sites

A

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

72
Q

Leiomyosarcoma: histo

A

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

73
Q

Leiomyosarcoma: antibody stain

A

mmunohistochemically, they stain with antibodies to smooth muscle actin and desmin

74
Q

Synovial Sarcoma: define

A

soft tissues near the knee joint MISNOMER (NOT from synoviocytes)

75
Q

Synovial Sarcoma: common clinical sx/sites

A

Sites: head, neck, chest wall
Well circumscribed
Patients present with a deep-seated mass that has been present for several years

76
Q

Synovial Sarcoma: mutation

A

chromosomal translocation t(x;18)(p11;q11) producing SS18-SSX1, -SSX2, -SSX4 fusion genes that encode chimeric transcription factors

77
Q

Synovial Sarcoma: histo: 2subtypes

A

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

78
Q

Undifferentiated Pleomorphic Sarcoma (UPS): define

A

General diagnosis of exclusion

Includes malignant mesenchymal tumors with high-grade, pleomorphic cells that cannot be classified into another category

79
Q

Undifferentiated Pleomorphic Sarcoma (UPS): prognosis

A

Prognosis is poor with metastases arising in 30-50% of cases

Very aggressive

80
Q

Undifferentiated Pleomorphic Sarcoma (UPS): histo

A

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

81
Q

Antibody Mediated DISEASES OF THE NEUROMUSCULAR JUNCTION (2)

A

Myasthenia Gravis

and Lambert-Eaton Myasthenic Syndrome

82
Q

Myasthenia Gravis: mechanism

A

autoantibodies directed against postsynaptic ACh receptors

aggregation and degradation of the receptors, and damage of the postsynaptic membrane through complement fixation

83
Q

Myasthenia Gravis: associated Dx

A

strong association with thymic abnormalities
thymoma (tumor of thymic epithelial cells)
thymic hyperplasia
Appearance of B-cell follicles in the thymus

84
Q

Myasthenia Gravis: Clinical Features

A

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

85
Q

Myasthenia Gravis: Tx

A

Acetylcholinesterase inhibitors that increase the half-life of ACh are the first line of treatment
immunosuppressive drugs (glucocorticoids, cyclosporine, rituximab)
Thymectomy

86
Q

Lambert-Eaton Myasthenic Syndrome: mechanism

A

antibodies that block ACh release by inhibiting a presynaptic calcium channel

87
Q

Lambert-Eaton Myasthenic Syndrome: clinical Sx

A

rapid repetitive stimulation increases muscle response
Patients typically present with weakness of their extremities
Proximal weakness

88
Q

Lambert-Eaton Myasthenic Syndrome: associated Dx

A 
underlying malignancy (paraneoplastic syndrome)
Small cell carcinoma of the lung
89
Q

Lambert-Eaton Myasthenic Syndrome: can you treat with Acetylcholinesterase inhibitors?

A

No response

Treatment: immunosuppressive agents and glucocorticoids

90
Q

Congenital DISEASES OF THE NEUROMUSCULAR JUNCTION

A

AR Myasthenic Syndromes

91
Q

AR Myasthenic Syndromes: mutation

A

Autosomal recessive mode of inheritance

loss-of-function mutations in the gene encoding the ε-subunit of the AChR

92
Q

AR Myasthenic Syndromes: age and Sx

A 
marked by varying degrees of muscle weakness
perinatal period (congenital)
poor muscle tone, external eye muscle weakness, and breathing difficulties
93
Q

Botulism: mechanism

A

caused by exposure to a neurotoxin that is produced by the anaerobic Gram (+) organism Clostridium botulinum
Blocks the release of ACh from presynaptic neurons

94
Q

Autoimmune Inflammatory Myopathies OF SKELETAL MUSCLE

A

Dermatomyositis and Polymyositis

95
Q

Dermatomyositis: sx

A

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

96
Q

Dermatomyositis: mechanism

A

Deposition of the complement membrane attack complex (C5b-9)

humoral immune injury: infiltrate rich in B cells and CD4+ T cells

97
Q

Dermatomyositis: labs

A

High creatine kinase

(+) ANA and anti-Jo-1 antibody

98
Q

Dermatomyositis: histo

A

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

99
Q

Polymyositis:histo

A

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

100
Q

greatest risk for osteomyelitis

A

1) hematogenous spread

2) trauma, surgery, diabetes, vascular insufficiency, implants/prostheses

101
Q

lab value: 25-hydroxyvitamin D is LOW (<20)

Dx?

A

vitamin D deficiency

rickets/osteomalacia

102
Q

Duchenne muscular dystrophy: mechanism

A

mutations that cause deletion of dystrophin (loss of function)

MSK Final (15 decks)

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