Chapter 26: Soft Tissue Flashcards
Sarcomas with complex karyotypes which are pleomorphic and genetically heterogenous and carry a poor prognosis are most often seen in whom?
Adults
Most soft tissue tumors are sporadic, but there is a minority that is associated with germline mutations such as what?
Tumor Suppressor gene: NF1, Gardner, Li-Fraumeni, Osler-Weber-Rendu
Environmental exposure: radiation, burns, toxins
what is the cytogenic abnormality associated with ewing sarcoma family tumors?
t(11;22)(q24;q12)
A well-encapsulated mass of mature adipocytes that is soft, mobile, and painless arising most commonly in adults is known as what?
Lipoma
what is lipomatosis?
when multifocal lipomas involve a limb
what is the histology of a lipoma?
encapsulated mass of normal appearing adipose tissue
Liposarcoma most often arises in whom and in which locations?
- 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
what are the 3 different histologic variants of a liposarcoma?
well differentiated, myxoid, and pleomorphic
Which genetic abberations is associated with the myxoid type of liposarcomas?
t(12;16) –> 12q encodes MDM2 a potent inhibitor of p53
Which genetic abberation is associated with the well-differentiated type of liposarcoma?
12q13-q15 –> 12q encodes MDM2 a potent inhibitor of p53
What is the morphology of the well-differentiated type of liposarcoma?
Contains mature adipocytes with scattered atypical spindle cells
What is the morphology of the myxoid type of liposarcoma?
abundant Basophilic myxoid matrix, arborizing capillaries (“chicken-wire”) + primitive cells at various stages of adipocyte differentiation
Which age group is the myxoid type of liposarcoma most common in and where in the body do they arise?
30 y/o arising in the thigh and leg
Which translocation is associated with nodular fasciitis?
t(17;22) –> MYH9-USP6 fusion gene
What is the histology associated with the pleomorphic complex karyotype of liposarcoma?
sheets of anaplastic cells with bizarre nuclei admixed with variable numbers of immature adipocytes= lipoblasts
What are the 3 classes of fibrous tumors?
nodular fasciitis, superficial fibromatoses, and deep fibromatosis (desmoid tumors)
What is a self-limited fibroblastic and myofibroblastic proliferation usually seen in young adults in the upper extremity?
nodular fasciitis
A history of what is seen in some cases of nodular fasciitis?
Trauma
Whom does nodular fasciitis arise in and in which locations; describe its typical presentation.
- Appear in UE’s (arms, forearm) of young adults (20-30 yo)
- Grow rapidly over several weeks or months; typically no larger than 5cm
what is the translocation associated with nodular fasciitis?
t(17;22) → MYH9-USP6 fusion gene = clonal, self-limited, proliferation
What is the prognosis and tx of nodular fasciitis?
Often spontaneously regress and if excised, rarely recurs
What occurs in the palmar (dupuytren contracture) subtype of superficial fibromatosis?
- Irregular or nodular thickening of the palmar fascia; unilateral or bilaterally
- Slow progression to flexion contracture, mainly affecting 4th and 5th fingers of hand
Which fibrous soft tissue tumors are large, infiltrative masses that frequently recur, but do not metastasize?
Deep Fibromatosis (Desmoid Tumors)
Patients with what germline mutation and syndrome are predisposed to developing deep fibromatosis (desmoid tumors)?
APC mutations –> familial adenomatous polyposis (FAP) - Gardner syndrome
Which age group and sex most often develop Deep Fibromatosis (desmoid tumors); where do they arise?
- Women in teens to 30’s
- Arise in anterior abdominal wall but may also be seen in limb girdles or the mesentery
Mutations in which 2 genes are associated with Deep Fibromatosis (desmoid tumors)?
APC or CTNNB1 (β-catenin) —> ↑ Wnt signaling
What is the gross appearance of a deep fibromatosis (desmoid tumor)?
gray-white, firm, poorly demarcated masses, 1-15 cm in diameter
-they are rubbery and tough and infiltrate surrounding muscle, nerve, and fat
What is the characteristic histologic pattern of Deep Fibromatosis (Desmoid Tumors)?
Cytologically bland fibroblasts arranged in broad sweeping fascicles amid dense collagen; histology resembles scar
What is the clinical course of Deep Fibromatosis (Desmoid Tumors) and how are they dealt with?
- May be disfiguring and disabling; may be painful
- Because of extensive infiltration, may be difficult to resect
What are the most common soft tissue sarcomas of childhood and adolescence?
Embryonal and alveolar type of rhabdomyosarcoma
what are the 4 subtypes of rhabdomyosarcoma?
alveolar. embryonal, pleomorphic, and spindle cell/sclerosing
Where do the pediatric forms of rhabdomyosarcomas most often arise?
Sinuses, head and neck, and GU tract
Which genetic aberrations and translocations are associated with alveolar rhabdomyosarcomas?
Fusion of FOXO1 with either PAX3 = (2;13) or PAX7 = (1;13)
What is the morphology of alveolar rhabdomyosarcomas?
- Networks of fibrous septae dividing cells into clusters and aggregates; centers are dischohesive
- Resemblance to pulmonary alveoli
- Cross striations are not a common feature
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?
sarcoma botryoides
***grape like mass***
In sarcoma botryoides, where the tumor cells abut the mucosa of an organ, they form a submucosal zone of hypercellularity called what?
Cambium layer
Where does embryonal rhabdomyosarcoma most often arise, characteristic morphology, and age group?
- Arise in genitourinary tract
- Patients 1-5 y/o
- Primitive spindle cells, “strap cells“
What is tx for rhabdomyosarcoma; which variant has the best and which has the worst prognosis?
- Tx is surgery + chemotherapy, with or without radiation
- Botryoid variant = best prognosis
- Pleomorphic variant = worse prognosis
Phenotype of multiple cutaneous leiomyomas may be transmitted as an autosomal dominant trait associated with what?
Uterine leiomyomas + renal cell carcinoma –> hereditary leiomyomatosis and renal cell cancer syndorme
Hereditary leiomyomatosis and renal cell cancer syndorme is due to what mutation and loss of what?
Germline loss-of-function mutation in fumarate hydratase gene on 1q42.3
Soft tissue leiomyomas are usually 1-2 cm and are composed of what?
Fascicles of densely eosinophilic spindle cells that tend to intersect each other at right angles
Leiomyosarcomas most often develop in which age group, sex, and structures; common presentation?
- 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
Morphology of Leiomyosarcomas?
Pleomorphic eosinophilic spindle cells w/ blunt-ended, hyperchromatic nuclei arranged in interweaving fascicles
Leiomyosarcomas arising where are particularly deadly?
Those arising from great vessels, especially the IVC
Leiomyosarcomas will stain positive for what?
Antibodies to smooth muscle actin and desmin and caldesmon
How does Synovial Sarcoma typically present and in which age group?
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
Which characteristic chromosomal translocation is associated with Synovial Sarcomas?
t(x;18) producing SS18-SSX1, -SSX2, or -SSX4
Synovial sarcomas, especially the biphasic type can be differentiated from other sarcoma by (+) immunohistochemical staining for what?
Epithelial markers (i.e., keratin)
Characteristic morphology of Synovial Sarcoma and how do the monophasic vs. biphasic types differ?
- Tight fascicles of uniform basophilic spindle cells
- Biphasic type also contains gland-like structures
What is the prognosis of Synovial Sarcomas and where do they metastasize?
- 5-year of 25% to 62% related to stage** and **patient age
- Commonly metz to lung and regional LN’s
What is a malignant mesenchymal tumor with high-grade, pleomorphic cells that cannot be classified into another category by histomorphology, immunophenotype, and genetics?
undifferentiated pleomorphic sarcoma
