Soft tissue tumors

Question 1

What is a mesenchymal tumor? How are the classified?

Answer 1

• also called a soft tissue tumor
  
  • nonepithelial extraskeletal tumors (excluding reticuloendothelial system, glia, and supporting tissue of parenchymal organs)
• classified according to the tissue they recapitulate (muscle, fat, fibrous tissue, vessels, or nerves)
• bengin= -omas
• malignant= -sarcomas

Question 2

What are the incidences of benign and malignant soft tissue tumors?

Answer 2

• sarcomas are rare (1% of all cancers; ~12,000 cases/yr in US)
• benign tumors outnumber sarcomas 100:1 (mostly lipomas and hemangiomas)

Question 3

What is the pathogenesis of soft tissue tumors?

Answer 3

• majority occur sporadically, but an important minority are associated with genetic syndromes
  
  • Neurofibromas= mutation in NF1
  • Gardner syndrome (fibromatosis)= mutation in APC
  • Li-Fraumeni syndrome (soft tissue sarcomas)= mutation in P53
  • Osler-Weber-Rendu syndrome= multiple genes
• the cause of most soft tissue tumors is unknown

Question 4

What is the age distribution of sarcomas?

Answer 4

• overall incidence increases with age (15% arise in children)
• rhabdomyosarcoma= common in children
• synovial sarcoma= common in young adulthood
• liposarcoma and pleomorphic/undifferentiated sarcomas later in life

Question 5

What is the anatomic distribution of sarcomas?

Answer 5

Majority in the extremities (40% in lower extremities, especially the thigh)

Question 6

What are the factors that determine the prognosis of a tumor?

Answer 6

**the tumor grade is an important factor predicting its behavior

• I-III grading (low/intermediate/high) based on
  
  • degree of differentiation/pleomorphism
  • average number of mitoses per high powered field
  • extent of necrosis (presumably a reflection of rate of growth)
• Size (>/< 5cm), depth, and stage (I-IV) also provide important diagnostic and prognostic info

**small, low grade= surgical resection
**large, high grade= resection + chemo and radiation

Question 7

How do you commonly treat soft tissue sarcomas?

Answer 7

Wide surgical excision

Can be followed by radiation and chemotherapy (for large and/or high grade tumors)

Question 8

Describe a lipoma (gross/histologic characteristics)

Answer 8

• most common (benign) soft tissue tumor of adulthood
• bengin (-oma)
• most are solitary lesions (multiple seen in rare hereditary syndromes)
  
  • soft, yellow, well-encapsulated mass
  • mature white fat cells on histological exam with no pleomorphism
• most are mobile, slowly enlarging, painless masses
• complete excision usually is curative

Question 9

Describe a liposarcoma (gross/histologic characteristics)

Answer 9

“LPS”

• the most common sarcoma of adulthood
• common in the deep soft tissues of proximal extremities and retroperitoneum; may develop into large tumors
• histological variants; all recur unless adequately excised
  
  • well-differentiated (relatively indolent; “lazy”)
  • myxoid/round cell (intermediate)
  • pleomorphic (usually aggressive and may metastasize)

Question 10

What are two other notable adipose tissue tumors?

Answer 10

1. lipoblastoma
   **children, primarily composed of lipoblasts
   **PLAG1
2. hibernoma
   **children, brown fat (versus white fat in lipoma)

Question 11

Describe fibromatoses

Answer 11

• superficial (benign but annoying)
  
  • palmar, plantar, penile
  • may stabilize and resolve spontaneously, some recur
• deep-seated “desmoid tumors”
  
  • behavior lies between benign fibrous tumors and low-grade fibrosarcomas
  • frequently recur after incomplete excision
  • some associated with Gardner syndrome (an APC mutation) or beta-catenin gene mutations

Question 12

Describe a fibrosarcoma

Answer 12

• malignant tumor composed of fibroblasts
• mostly in adults
• common in deep tissue of the thigh, knee, and retroperitoneum
• aggressive tumors (recur in >50% of cases, metastasize in >25%)
• marked by vimentin stain

Question 13

Describe a leiomyoma

Answer 13

• uterine leiomyomas= most common neoplasm in women
  
  • may also arise in skin and deep soft tissues
• usually <1-2 cm
• solitary lesions easily cured, but multiple tumors may be difficult to remove

Question 14

Describe a leiomyosarcoma

Answer 14

• 10-20% of soft tissue sarcomas
• adults, F>M
• skin and deep soft tissues of the extremities and retroperitoneum
  
  • superficial leiomyosarcomas usually small and have good prognosis
  • those in retroperitoneum are large, cannot be entirely excised -> local extension and metastatic spread

Question 15

Describe a rhabdomyosarcoma (RMS)

Answer 15

KNOW this

• most common soft tissue sarcoma of childhood and adolescence, usually <20 yo
• most commonly in head and neck or genitourinary tract
• subtypes;
  
  • embryonal
  • alveolar
  • pleomorphic

Question 16

Describe embryonal RMS

Answer 16

KNOW this

• 49% of RMS
• more frequent <10 yo
  
  • head and neck (esp orbital and parameningeal)
  • genitourinary tract **infant girls with protruberant vaginal lesions; “bunch of grapes”
  • deep soft tissues of the extremities, pelvis and retroperitoneum
• variants;
  
  • sarcoma botryoides
  • spindle cell
  • anaplastic
• ERMS often has loss of 11p15 and extra copies of 8, 12, 13 and/or 20

Question 17

Describe alveolar RMS

Answer 17

KNOW this

• 31% of RMS
• more frequent between 10 and 25 yo
• deep soft tissues of the extremities (less frequent in head/neck, perineum, pelvis, retroperitoneum)
• pathogenic translocations specific to ARMS;
  
  • t(2;13)/PAX3-FOXO1 (FKHR)
  • t(1;13)/PAX7-FOXO1 (FKHR)

Question 18

Describe a synovial sarcoma

Answer 18

• 5-10% of all soft tissue sarcomas
• young adults, more commonly males
• over 80% in deep soft tissue of extremities, especially around knees
• histologically biphasic (looks like 2 tissues) or monophasic
• characteristic t(X;18)(p11;q11) with SYT-SSX1 or SYT-SSX2
• common metastasis to lung, bone, and regional lymph nodes (5 year survival 25-60%, 10 year survival 25%)
  
  • treat aggressively with surgery/chemo

Question 19

What is a pseudosarcomatous proliferation?

Answer 19

• reactive non-neoplastic lesion that develops in response to some form of local trauma (or is idiopathic)
• develop suddenly and grow rapidly
• hypercellularity, mitotic activity, and primitive appearance mimic sarcoma
• e.g. nodular fasciitis or myositis ossificans

Question 20

Describe nodular fasciitis

Answer 20

• “self limited” or “transient neoplasia”; presudosarcomatous prolifertion in respons to trauma
• deep dermis, subcutis, or muscle
• several centimeters with poorly defined margins
• MYH9-USP6 translocation from t(17;22)
• “tissue culture” appearance and extravesated RBCs on histology

Question 21

Describe myositis ossificans

Answer 21

• pseudosarcomatous proliferation; antecedent trauma in >50% of cases
• on proximal extremities, especially in young adults
• presence of metaplastic bone; eventually the entire lesion ossifies and the intertrabecular spaces become filled with bone marrow
• must be distinguished from extraskeletal osteosarcoma