Desmoid tumors

Question 1

What are desmoid tumors (DT)?

Answer 1

DTs are rare, benign, slow-growing fibroblastic neoplasms that arise from musculoaponeurotic stromal elements, and tend to recur locally.

Question 2

What is another commonly used name for DT?

Answer 2

DT is also known as aggressive fibromatosis; musculoaponeurotic fibromatosis; or desmoid-like fibromatosis (previously called fibrosarcoma grade I of desmoids type).

Question 3

DT appears histologically similar to what tumors?

Answer 3

DT appears histologically similar to well-differentiated fibrosarcoma.

Question 4

Any histopathologic features to differentiate DT from these tumors?

Answer 4

Most neoplasms resembling DT have specific histologic diagnostic features and lack nuclear β-catenin immunoreactivity. 70%–75% of DTs express
nuclear a-catenin. (WHO 4th edition, 2013)

Question 5

What is the approximate incidence of DT?

Answer 5

2.4–4.3 cases/million population; this risk increases 1,000-fold in pts with FAP.

Question 6

What genetic abnormality is associated with DT?

Answer 6

5%–15% of DTs are associated with mutations to the APC gene, resulting in FAP.

Question 7

What is the clinical syndrome associated with DT?

Answer 7

Gardner syndrome is associated with DT, and 10%–20% of pts with this syndrome will develop DT.
Sebaceous cysts, Osteomas, and Desmoid tumors.
(Mnemonic: Gardner SOD)

Question 8

What genetic mutation presents in DT sporadic cases?

Answer 8

Activating Wnt/a-catenin (CTNNB1) pathway, identified in appx 85% of cases of sporadic DT.

Question 9

Is there a sex or age predilection for DT?

Answer 9

Yes, DTs typically present in women during childbearing yrs. There is no racial or ethnic predilection.

Question 10

What 2 environmental conditions are associated with DT?

Answer 10

DTs have been associated with high estrogen states (such as pregnancy) and trauma per retrospective and anecdotal reports

Question 11

What is the typical presentation of an extremity DT?

Answer 11

Most DTs of the extremity present as a deep-seated, painless mass with a Hx of slow growth.

Question 12

What % of DTs are intra-abdominal, and with what clinical syndrome are intra-abdominal DTs associated?

Answer 12

10%–30% of DTs are intra-abdominal, and they are associated with Gardner syndrome. Intra-abdominal DTs are often a source of significant morbidity and mortality.

Question 13

What is the typical presentation of an intra-abdominal DT?

Answer 13

An intra-abdominal DT can present with bowel ischemia, obstruction, or complications with ileoanal anastomosis after colectomy for FAP.

Question 14

What is the natural Hx of untreated DTs?

Answer 14

DTs can regress spontaneously or remain stable, however, ∼50% will continue to grow slowly and invade into surrounding structures.

Question 15

Do DTs have metastatic potential?

Answer 15

No. DTs do not have metastatic potential but are locally aggressive with a predilection for LR.

Question 16

After a careful H&P, what imaging should be done to evaluate for a DT?

Answer 16

An MRI of the extremity is recommended to evaluate the extent of an extremity DT. A CT or MRI of the abdomen may be helpful to evaluate an intra-abdominal or abdominal wall mass.

Question 17

How do DTs display on MRI imaging?

Answer 17

On T1, DTs are near homogeneous and isointense to muscle; on T2 they are more heterogeneous. After initial growth, spontaneous evolution of desmoids is characterized by shrinking and an increase in low-signal areas on T2

Question 18

What is the metastatic workup for DTs?

Answer 18

DTs are benign and do not have metastatic potential. Consequently, no systemic imaging is needed outside of the primary tumor.

Question 19

Can DT be distinguished from malignant ST tumors on the basis of imaging?

Answer 19

No. DT cannot be distinguished from malignant ST tumors on the basis of imaging

Question 20

Define the staging system for DT.

Answer 20

DTs are NOT included in AJCC 8th edition. There is no defined staging system for DT. Important features to guide the management include location, size, and the ability to resect with a wide margin

Question 21

What type of Bx should be done to evaluate a mass suspected of being a DT?

Answer 21

A core needle or open incisional Bx is the preferred method for any tumor that may be a malignant STS.

Question 22

What is considered the primary modality for Tx of DT?

Answer 22

Surgical resection used to be the gold standard. However, based on recent data describing a high rate of PFS (50%) and spontaneous regression (28%) a “watch and wait” policy is a reasonable option.

Question 23

What are the indications for Sg in pts with DT?

Answer 23

Features to identify pts at low risk of progression, whom would most benefit from a “watch and wait” policy, have not yet been established. Sg is still a valuable option when the expected morbidity is low (function-preserving
Sg) with wide (2 cm) –SMs.

Question 24

For what type of pts is nonoperative initial management of DT always entertained?

Answer 24

For pts with DTs that are large, slow-growing, involve the mesentery; encase vessels or joints or when anesthesia or Sg carries morbidity

Question 25

What is the recurrence rate after margin– Sg vs. margin+ Sg for primary DT?

Answer 25

In primary DT Tx with Sg, LR is 15% for –margin resection, and LR is 33% for +margin resection. (Janssen et al., BJS 2017)

Question 26

What is the recurrence rate after Sg (with +ve/indeterminate margin) for primary DT with or without adj RT?

Answer 26

In DT Tx with Sg (+ve/indeterminate margin), LR is 23% after RT, and LR is 40% without RT. (Janssen et al., BJS 2017)

Question 27

What factors should be considered when determining whether or not to offer adj RT for DT?

Answer 27

Factors to be considered when considering adj RT for DT:
1. Margin status. Margin– pts are unlikely to benefit.
2. Location. Adj RT for resected retroperitoneal/intra-abdominal DTs is
associated with significant Tx risks.
3. Salvage options. Lesions that may undergo repeat resections may be
appropriately observed.
4. Pt age. There should be a high threshold for using adj RT in children.

Question 28

What is the response rate (complete or partial) for inoperable DT treated with RT alone?

Answer 28

For inoperable DT treated with RT alone 50% showed complete or partial response. (EORTC 62991-22998, Ann Oncol 2013)

Question 29

What dose of RT is needed to control DT with RT alone?

Answer 29

A dose >50 Gy is needed to treat DT with RT alone. The recommended dose for gross Dz is 56 Gy.

Question 30

What dose of RT is recommended after an R1 resection of DT in a pt who cannot be salvaged with repeat resection?

Answer 30

A pt treated with adj RT after an R1 resection should be treated to a dose of 50 Gy in 1.8–2 Gy/fx.

Question 31

Define the CTV for RT in the management of DT.

Answer 31

The CTV to include when treating DT with RT includes the tumor bed (and/or gross tumor), a portion of the muscle compartment to cover fascial planes, or neurovascular structures along which tumor may track with a 3–5 cm CTV margin longitudinally and 2 cm in all other directions respecting bony, facial and compartmental boundaries.

Question 32

What are potential medical approaches to treat DT?

Answer 32

ER modulators (tamoxifen), NSAIDs, low-dose cytotoxic chemo (Mtx, vinblastine or doxorubicin based), interferon, TKI.

Question 33

What are recent projections for the trajectory of systemic medical Tx in DT?

Answer 33

Lev et al. from MDACC, showed a significant increase in systemic medical Tx in recent yrs with decreased reliance on Sg alone and suggested neoadj
Tx may be associated with improved outcomes.
De Camargo et al. (Cancer 2010) observed greatest radiological response with antiestrogens and anthracycline regimens than other agents

Question 34

What are the potential late complications associated with RT Tx to the extremity?

Answer 34

Late complications associated with RT to the extremities:

1. Fibrosis
2. Edema
3. Fracture
4. 2nd malignancy
5. Joint stiffness
6. Neuropathy

Question 35

How did IMRT affect RT complications?

Answer 35

IMRT and IGRT resulted in decrease of RT side effects. Reports on extremity sarcoma treated with IMRT from MSKCC and PMH showed edema 7.9%, 11.1% and stiffness 14.5%, 5.6% respectively.