Chapter 26: Soft Tissue

Question 1

Sarcomas with complex karyotypes which are pleomorphic and genetically heterogenous and carry a poor prognosis are most often seen in whom?

Answer 1

Adults

Question 2

Most soft tissue tumors are sporadic, but there is a minority that is associated with germline mutations such as what?

Answer 2

Tumor Suppressor gene: NF1, Gardner, Li-Fraumeni, Osler-Weber-Rendu

Environmental exposure: radiation, burns, toxins

Question 3

what is the cytogenic abnormality associated with ewing sarcoma family tumors?

Answer 3

t(11;22)(q24;q12)

Question 4

A well-encapsulated mass of mature adipocytes that is soft, mobile, and painless arising most commonly in adults is known as what?

Answer 4

Lipoma

Question 5

what is lipomatosis?

Answer 5

when multifocal lipomas involve a limb

Question 6

what is the histology of a lipoma?

Answer 6

encapsulated mass of normal appearing adipose tissue

Question 7

Liposarcoma most often arises in whom and in which locations?

Answer 7

• Common malignant ST tumor, adults (50-60 y/o)
• Arise in deep ST of prox. extremities and retroperitoneum

-They recur locally repeatedly, unless completely excised

Question 8

what are the 3 different histologic variants of a liposarcoma?

Answer 8

well differentiated, myxoid, and pleomorphic

Question 9

Which genetic abberations is associated with the myxoid type of liposarcomas?

Answer 9

t(12;16) –> 12q encodes MDM2 a potent inhibitor of p53

Question 10

Which genetic abberation is associated with the well-differentiated type of liposarcoma?

Answer 10

12q13-q15 –> 12q encodes MDM2 a potent inhibitor of p53

Question 11

What is the morphology of the well-differentiated type of liposarcoma?

Answer 11

Contains mature adipocytes with scattered atypical spindle cells

Question 12

What is the morphology of the myxoid type of liposarcoma?

Answer 12

abundant Basophilic myxoid matrix, arborizing capillaries (“chicken-wire”) + primitive cells at various stages of adipocyte differentiation

Question 13

Which age group is the myxoid type of liposarcoma most common in and where in the body do they arise?

Answer 13

30 y/o arising in the thigh and leg

Question 14

Which translocation is associated with nodular fasciitis?

Answer 14

t(17;22) –> MYH9-USP6 fusion gene

Question 15

What is the histology associated with the pleomorphic complex karyotype of liposarcoma?

Answer 15

sheets of anaplastic cells with bizarre nuclei admixed with variable numbers of immature adipocytes= lipoblasts

Question 16

What are the 3 classes of fibrous tumors?

Answer 16

nodular fasciitis, superficial fibromatoses, and deep fibromatosis (desmoid tumors)

Question 17

What is a self-limited fibroblastic and myofibroblastic proliferation usually seen in young adults in the upper extremity?

Answer 17

nodular fasciitis

Question 18

A history of what is seen in some cases of nodular fasciitis?

Answer 18

Trauma

Question 19

Whom does nodular fasciitis arise in and in which locations; describe its typical presentation.

Answer 19

• Appear in UE’s (arms, forearm) of young adults (20-30 yo)
• Grow rapidly over several weeks or months; typically no larger than 5cm

Question 20

what is the translocation associated with nodular fasciitis?

Answer 20

t(17;22) → MYH9-USP6 fusion gene = clonal, self-limited, proliferation

Question 21

What is the prognosis and tx of nodular fasciitis?

Answer 21

Often spontaneously regress and if excised, rarely recurs

Question 22

What occurs in the palmar (dupuytren contracture) subtype of superficial fibromatosis?

Answer 22

• Irregular or nodular thickening of the palmar fascia; unilateral or bilaterally
• Slow progression to flexion contracture, mainly affecting 4th and 5th fingers of hand

Question 23

Which fibrous soft tissue tumors are large, infiltrative masses that frequently recur, but do not metastasize?

Answer 23

Deep Fibromatosis (Desmoid Tumors)

Question 24

Patients with what germline mutation and syndrome are predisposed to developing deep fibromatosis (desmoid tumors)?

Answer 24

APC mutations –> familial adenomatous polyposis (FAP) - Gardner syndrome

Question 25

Which age group and sex most often develop Deep Fibromatosis (desmoid tumors); where do they arise?

Answer 25

• Women in teens to 30’s
• Arise in anterior abdominal wall but may also be seen in limb girdles or the mesentery

Question 26

Mutations in which 2 genes are associated with Deep Fibromatosis (desmoid tumors)?

Answer 26

APC or CTNNB1 (β-catenin) —> ↑ Wnt signaling

Question 27

What is the gross appearance of a deep fibromatosis (desmoid tumor)?

Answer 27

gray-white, firm, poorly demarcated masses, 1-15 cm in diameter

-they are rubbery and tough and infiltrate surrounding muscle, nerve, and fat

Question 28

What is the characteristic histologic pattern of Deep Fibromatosis (Desmoid Tumors)?

Answer 28

Cytologically bland fibroblasts arranged in broad sweeping fascicles amid dense collagen; histology resembles scar

Question 29

What is the clinical course of Deep Fibromatosis (Desmoid Tumors) and how are they dealt with?

Answer 29

• May be disfiguring and disabling; may be painful
• Because of extensive infiltration, may be difficult to resect

Question 30

What are the most common soft tissue sarcomas of childhood and adolescence?

Answer 30

Embryonal and alveolar type of rhabdomyosarcoma

Question 31

what are the 4 subtypes of rhabdomyosarcoma?

Answer 31

alveolar. embryonal, pleomorphic, and spindle cell/sclerosing

Question 32

Where do the pediatric forms of rhabdomyosarcomas most often arise?

Answer 32

Sinuses, head and neck, and GU tract

Question 33

Which genetic aberrations and translocations are associated with alveolar rhabdomyosarcomas?

Answer 33

Fusion of FOXO1 with either PAX3 = (2;13) or PAX7 = (1;13)

Question 34

What is the morphology of alveolar rhabdomyosarcomas?

Answer 34

• Networks of fibrous septae dividing cells into clusters and aggregates; centers are dischohesive
• Resemblance to pulmonary alveoli
• Cross striations are not a common feature

Question 35

What is a subtype of an embryonal rhabdomyosarcoma variant that develops in the walls of hollow, mucosal-lined structures, such as the naso-pharynx, common bile duct, bladder, and vagina?

Answer 35

sarcoma botryoides

***grape like mass***

Question 36

In sarcoma botryoides, where the tumor cells abut the mucosa of an organ, they form a submucosal zone of hypercellularity called what?

Answer 36

Cambium layer

Question 37

Where does embryonal rhabdomyosarcoma most often arise, characteristic morphology, and age group?

Answer 37

• Arise in genitourinary tract
• Patients 1-5 y/o
• Primitive spindle cells, “strap cells“

Question 38

What is tx for rhabdomyosarcoma; which variant has the best and which has the worst prognosis?

Answer 38

• Tx is surgery + chemotherapy, with or without radiation
• Botryoid variant = best prognosis
• Pleomorphic variant = worse prognosis

Question 39

Phenotype of multiple cutaneous leiomyomas may be transmitted as an autosomal dominant trait associated with what?

Answer 39

Uterine leiomyomas + renal cell carcinoma –> hereditary leiomyomatosis and renal cell cancer syndorme

Question 40

Hereditary leiomyomatosis and renal cell cancer syndorme is due to what mutation and loss of what?

Answer 40

Germline loss-of-function mutation in fumarate hydratase gene on 1q42.3

Question 41

Soft tissue leiomyomas are usually 1-2 cm and are composed of what?

Answer 41

Fascicles of densely eosinophilic spindle cells that tend to intersect each other at right angles

Question 42

Leiomyosarcomas most often develop in which age group, sex, and structures; common presentation?

Answer 42

• Present as painless firm masses, most often in women who are 40-60 y/o
• Arise in deep ST’s of the extremities and retroperitoneum

Question 43

Morphology of Leiomyosarcomas?

Answer 43

Pleomorphic eosinophilic spindle cells w/ blunt-ended, hyperchromatic nuclei arranged in interweaving fascicles

Question 44

Leiomyosarcomas arising where are particularly deadly?

Answer 44

Those arising from great vessels, especially the IVC

Question 45

Leiomyosarcomas will stain positive for what?

Answer 45

Antibodies to smooth muscle actin and desmin and caldesmon

Question 46

How does Synovial Sarcoma typically present and in which age group?

Answer 46

Pt’s in their 20s-40s presenting with deep-seated mass in thigh, leg, chest wall or head and neck that has been present for several years
NOT associated with the synovium

Question 47

Which characteristic chromosomal translocation is associated with Synovial Sarcomas?

Answer 47

t(x;18) producing SS18-SSX1, -SSX2, or -SSX4

Question 48

Synovial sarcomas, especially the biphasic type can be differentiated from other sarcoma by (+) immunohistochemical staining for what?

Answer 48

Epithelial markers (i.e., keratin)

Question 49

Characteristic morphology of Synovial Sarcoma and how do the monophasic vs. biphasic types differ?

Answer 49

• Tight fascicles of uniform basophilic spindle cells
• Biphasic type also contains gland-like structures

Question 50

What is the prognosis of Synovial Sarcomas and where do they metastasize?

Answer 50

• 5-year of 25% to 62% related to stage** and **patient age
• Commonly metz to lung and regional LN’s

Question 51

What is a malignant mesenchymal tumor with high-grade, pleomorphic cells that cannot be classified into another category by histomorphology, immunophenotype, and genetics?

Answer 51

undifferentiated pleomorphic sarcoma