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Benign & Malignant Soft Tissue Neoplasms

Orthopedics
by

Jonathan Hancock

on 11 September 2013

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Transcript of Benign & Malignant Soft Tissue Neoplasms

Benign & Malignant Soft Tissue Neoplasms
Benign and Malignant Soft Tissue Neoplasms
One of the greatest predictors for resident success on the Orthopaedic In-Training
Examination (OITE) is reviewing previous OITE questions. However, no studies have
examined which review sources contain the most answers to previously asked OITE
questions. The goal of this study was to determine which review source contains the
most answers to previously asked OITE questions.
Each question from the 2006 to 2010 OITEs was examined. The questions were placed
into 1 of 13 categories based on their topic. The publication date of the recommended
readings associated with each question was recorded. The answer to each question was
then searched for in 3 commonly used review sources: Miller’s Review of Orthopaedics,
5th edition (MRO), American Academy of Orthopaedic Surgeons Comprehensive
Orthopaedic Review (COR), and www.orthobullets.com (OB). Searchable electronic
versions of each textbook were used, and each question had a 12-minute time limit.
Of 1358 questions, 665 (49%) were found in all 3 sources. Significantly more answers
were found on OB (99.4%) compared with MRO (60%) and COR (62%) (P<.0001).
Significantly more answers to questions in each question category were found on OB
compared with MRO or COR (P<.0001). More than 50% of all recommended readings
for OITE questions were published within 5 years of the OITE.
Residents using OB to review for the OITE will be exposed to significantly more answers of previously asked OITE questions than residents using MRO or COR (P<.0001). www.healio.com/sept.2012
Muscle Tumors
Peripheral Nerve Tumors
Fibrogenic Tumors
Fibromatosis
Calcifying aponeurotic fibroma
Nodular fasciitis
Malignant fibrous histiocytoma
Fibrosarcoma
Desmoid Tumor
Desmoid Tumor
-fibrogenic lesion that is benign and very invasive
-Females > Males
- Shoulder, chest wall, back, thigh
- Associated with Familial adenomatous polyposis, Chromosome 8, 20
-associated w/ Dupuytren contractures, Ledderhose disease
-Usually enlarging painless mass
-Low on T1, low to medium on T2
-100% positive for estrogen receptor-beta
-Wide resection with radiotherapy
Malignant Fibrous Histiocytoma & Fibrosarcoma
Similar clinical and radiographic features
-Generally ages 30-80
-Enlarging, painless mass > 5 cm
-MRI low on T1, high on T2
-Similar on histology
-Distinctive: MFH spindle cells arranged in storiform (cartwheel pattern)
Fibrosarcoma has fasciculated growth pattern with fusiform or spindle-shaped cells separated by interwoven collagen fibers.
-Wide-margin local excision with radiotherapy
Prevalence of Answers to Orthopaedic
In-Training Examination Questions in 3
Commonly Used Orthopedic Review Sources
-Normally presents in the metaphyseal region of long bones
-Originates as smooth muscles cells likely from blood vessels
-Usually presents in the 6th-7th decades of life
-spindle cell neoplasm w/ cigar-shaped cells
-cells aligned in fascicles
-Treatment w/ wide resection +/- chemotherapy
Leiomyosarcoma
Appears like Muscle on T1
(OBQ08.8) A 35-year-old female presents to your office after incidental finding of a aggressive looking lytic lesion in her pelvis. She has no pain, is not pregnant, but states she has been losing weight over the last 6 months for an unknown reason. Bone scan shows significant uptake in the area of her pelvis. Immunohistochemistry stains positive for smooth muscle actin. Which of the following slides correlates to your expected findings on histology? Topic Review Topic
FIGURES: A B C D E
QID: 394

1. Figure A
2. Figure B
3. Figure C
4. Figure D
5. Figure E
PREFERRED RESPONSE: D
DISCUSSION: Based on the patients history (unexplained weight loss) and bone scan, she has an aggressive lesion in her pelvis. Immunohistochemisty staining for smooth muscle actin suggests a tumor of smooth muscle origin - or a leiomyosarcoma. The prefix - "leio-" designates smooth muscle tumors. The histopathology presented in Figure A shows interlacing bundles of smooth muscle cells with variable uniformity, high nuclear/cytoplasmic ratio, and mitotic figures - consistent with leiomyosarcoma. The other histopathology slides are: Figure B - Giant cell tumor, Figure C - Myeloma, Figure D - Osteosarcoma, Figure E - hyaline cartilage. The two cited review articles by Berlin et al and Antonescu et al describe the clinical, radiographic, and histology of this disease as described above.



REFERENCES:

1. Berlin O, Angervall L, Kindblom LG, Berlin IC, Stener B. Primary leiomyosarcoma of bone. A clinical, radiographic, pathologic-anatomic, and prognostic study of 16 cases. Skeletal Radiol. 1987;16(5):364-76. Review. PMID:3306938 (Link to Abstract)

2. Antonescu CR, Erlandson RA, Huvos AG. Primary leiomyosarcoma of bone: a clinicopathologic, immunohistochemical, and ultrastructural study of 33 patients and a literature review. Am J Surg Pathol. 1997 Nov;21(11):1281-94. Review. PMID:9351566 (Link to Abstract)
-Most common soft tissue sarcoma under 15 years old.

-Three main types: Embryonal, Alveolar and Pleomorphic (adult).

-Small round blue cell tumor

-Head/neck, GU & extremities involved

-May have lymph involvement

-Treatment w/ wide resection and chemo +/- Radiation therapy

Rhabdomyosarcoma
-Dark on T1, Bright on T2
Rhabdomyosarcoma
Rhabdomyosarcoma
-few striations may be seen
-not many mitoses
(OBQ07.104) The fusion gene resulting from the chromosomal translocation t(X;18)(p11;q11) is chararcteristically found in which malignancy?

1. Synovial sarcoma

2. Chronic myelogenous leukemia (CML)

3. Ewings sarcoma

4. Alveolar rhabdomyosarcoma

5. Clear cell sarcoma


PREFERRED RESPONSE 1

DISCUSSION: The SYT-SSX1 and SYT-SSX2 fusion genes resulting from the chromosomal translocation t(X;18)(p11;q11) are chararcteristically found in synovial sarcoma.


Synovial sarcoma occurs most commonly in patients 15 to 40 years of age and affects males greater than females. It is a slow growing tumor that has a propensity for the juxta-articular regions around the knee, shoulder, arm, elbow, and foot. The treatment for synovial sarcoma is wide resection and radiation +/- chemotherapy with a 10 year survival of approximately 25%.


Incorrect Answers:
2-BCR-ABL is an oncogene associated with chronic myelogenous leukemia (CML), the result of a reciprocal translocation between chromosome 9 and 22.


3-The EWS (EWSR1) gene is involved in translocations in Ewing's sarcoma, clear cell sarcoma, desmoplastic small round cell tumor and myxoid liposarcoma. The Ewing sarcoma family of tumors is characterized by recurrent translocations that fuse EWS to one of the following genes FLI1 (>90% of cases), ERG, ETV1, E1AF and FEV.


4-PAX3-FKHR is a gene fusion seen in Alveolar Rhabdomyosarcoma and is specific for the high risk metastatic subgroup.


5-In clear cell sarcoma, DSRCT and myxoid liposarcoma EWS is fused to ATF1, WT1 and CHOP respectively.


REFERENCES:

1. Fletcher J: Cytogenic analysis of soft tissue tumors, in Soft Tissue Tumors, 2001; Kawai et al, N Engl J Med, 1998

Question Authors:

Greg Galano MD, Derek Moore, Michael Hughes MD,
Neurilemoma
aka: Schwannoma
-Benign and usually painless
-Occurs mainly in adults 20-50 y/o, NF2 patients
-Very + S100 antibody staining
-Encapsulate the nerve
Neurilemoma (Schwannoma)
Antoni A: spindle cells w/ twisted nuclei
-Verocay bodies, nuclear palisading, whorling cells

Antoni B: less orderly & less cellular, vessels are large and irregular
Neurilemoma (Schwannoma)
MRI: lower than muscle on T1, Higher than fat on T2
(OBQ06.248) Which treatment factor has shown to be most important for five-year disease-free survival in patients with subcutaneous sarcomas?

1. dose of chemotherapy
2. addition of adjuvant radiation
3. size of operative margin
4. length of chemotherapy course
5. addition of radiofrequency ablation
PREFERRED RESPONSE 3

DISCUSSION: Basically, there are studies which show microscopic residual tumor when a marginal resection is done. The size of the operative margin is the most important treatment-related factor. If the proper treatment was not done initially for a subcutaneous high-grade sarcoma the patient should be taken back to provide adequate margins. The authors also concluded that size is the most important tumor-related factor.

REFERENCES:
1. Gibbs CP, Peabody TD, Mundt AJ, Montag AG, Simon MA. Oncological outcomes of operative treatment of subcutaneous soft-tissue sarcomas of the extremities. J Bone Joint Surg Am. 1997 Jun;79(6):888-97 PMID:9199387 (Link to Abstract)
Question Authors:
Greg Galano MD,
Neurofibroma
-solitary or multiple (neurofibromatosis)
-multiple cell types (fibroblast are most common)
-arise in non-myelinic schwann cells after losing NF1 tumor suppressor gene
-Unable to produce neurofibromin which regulates RAS mediated pathway
-Physical exam: Need 2 or more for dx
Cafe-au-lait spots (6+)
optic glioma
axillary freckles (crowe's sign)
2+ neurofibromas
1st degree relative
anterolateral bowing of tibia
lisch nodules (iris)

5-25% risk of developing into Peripheral Malignant Nerve Sheath Tumor or Neurofibrosarcoma
Desmoid Tumor
-well differentiated fibroblasts
-Uniform spindle cells w/ elongated nuclei
-100% positive for Estrogen receptor-beta
(OBQ09.225) A 20-year-old female presents with a "rock-hard" mass in the calf shown in Figure A. MRI, gross pathology, and histology images are shown in Figure B-D, respectively. Immunohistochemical studies of the mass were strongly positive for Estrogen receptor-beta expression. What is the most likely diagnosis? FIGURES: A B C D

1. Osteosarcoma
2. Leiomyosarcoma
3. Extraabdominal fibromatoses (desmoid tumor)
4. Angiosarcoma
5. Chondroblastoma

(OBQ10.149) Estrogen receptor blockade has been moderately successful treating which of the following tumors, while reducing the morbidity of side-effects associated with previous treatments?

1. Desmoid tumor
2. Ewing’s sarcoma
3. Synovial sarcoma
4. Multiple myeloma
5. Giant cell tumor

PREFERRED RESPONSE 1

DISCUSSION: Moderate, short-term success has been accomplished by treating desmoid tumors, also known as aggressive fibromatosis, with tamoxifen. These tumors can be found throughout the body and are benign, but can be locally aggressive. Among the soft-tissue tumors, they have the highest rate of local recurrence after wide resection when adjuvant therapies are not used. Various chemotherapy and radiation regimens have been used to successfully treat these tumors. However, tamoxifen is the preferred choice for patients who cannot tolerate the side-effects of traditional chemotherapy and radiation. Some studies have found that 100% of desmoid tumors express estrogen receptor-beta. Hosalkar et al provide an excellent review of musculoskeletal desmoid tumors, and express the conclusions above.

REFERENCES:
1. Hosalkar HS, Torbert JT, Fox EJ, Delaney TF, Aboulafia AJ, Lackman RD. Musculoskeletal desmoid tumors. J Am Acad Orthop Surg. 2008 Apr;16(4):188-98. Review. PMID:18390481 (Link to Abstract)
2. Weiss S, Goldblum J. Fibromatoses. In: Weiss S, Goldblum J, eds. Soft Tissue Tumors, 4th ed. St Louis, MO: Mosby; 2001:309-346.
Question Authors:
Aaron Bott MD,
PREFERRED RESPONSE 3

DISCUSSION: The clinical presentation and imaging studies are consistent with extraabdominal fibromatoses, also known as a desmoid tumor.

Extraabdominal fibromatoses (desmoid tumor) is an infiltrative tumor composed of fibroblasts and myofibroblasts that, despite high incidence of local recurrence, does not metastasize. It occurs in individuals 15-40 years of age and is 10,000 times more likely to develop in patients with familial adenomatous polyposis (FAP) syndrome. Treatment is typically wide resection much like soft tissue sarcoma.

Deyrup et al reviewed 40 cases of extraabdominal fibromatosis and found that 100% of the patients were positive for estrogen receptor-beta expression and 100% of the cases were negative for estrogen receptor-alpha expression.

Illustration A details the histopathology of the desmoid tumor in this case.

Illustrations: A


REFERENCES:
1. Deyrup AT, Tretiakova M, Montag AG. Estrogen receptor-beta expression in extraabdominal fibromatoses: an analysis of 40 cases. Cancer. 2006 Jan 1;106(1):208-13 PMID:16333857 (Link to Abstract)
2. Weiss SW, Goldblum JR: Enzinger and Weiss’ Soft Tissue Tumors, ed 5. Philadelphia, PA, Mosby Elsevier, 2008, pp 237-246
Question Authors:
Michael Hughes MD, Ben Taylor MD,
(OBQ09.258) Which inherited condition shows a strong association with extra-abdominal desmoid tumors? Review Topic

1. Familial adenomatous polyposis
2. Sinding-Larsen-Johansson syndrome
3. Ollier's disease
4. Fanconi anemia
5. McCune-Albright syndrome

PREFERRED RESPONSE 1

DISCUSSION: Patients with Familial adenomatous polyposis (FAP) have a 10,000 times increased risk of developing extra-abdominal desmoid tumors.

Familial adenomatous polyposis (FAP) is an inherited condition due to mutation in the tumor suppressor gene APC that manifests with multiple benign polyps in the epithelium of the large intestine, with risk for malignant polyp transformation over time. The mutation in the APC tumor suppressor gene predisposes these patients to other neoplasms, including extra-abdominal desmoid tumors.

The review by Hosalker discusses the genetics, diagnosis, and management of patients with desmoid tumors. They report that desmoid tumors, also known as aggressive fibromatosis, are rare fibroblastic tumors that exhibit a wide range of local aggressiveness.

Incorrect Answers: Sinding-Larsen-Johansson syndrome, Ollier's disease, Fanconi anemia, and McCune-Albright syndrome show no association with extra-abdominal desmoid tumors.

REFERENCES:
1. Hosalkar HS, Fox EJ, Delaney T, Torbert JT, Ogilvie CM, Lackman RD. Desmoid tumors and current status of management. Orthop Clin North Am. 2006 Jan;37(1):53-63. Review. PMID:16311111 (Link to Abstract)
2. Menendez LR (ed): Orthopaedic Knowledge Update: Musculoskeletal Tumors. Rosemont, IL, American Academy of Orthopaedic Surgeons, 2002, pp 243-253
Question Authors:
Patrick O'Donnell MD/PhD,
Pigmented Villonodular Synovitis
-Monoarticular reactive synovitis with proliferation of synovial villi and nodules
-Most common in adults 30-50 years old
-Knee 80%, hip, shoulder and ankle
-Can be extra-articular (giant cell tumor of tendon sheath)
-Chromosome 5q33 rearrangement
-Cystic lesions on both sides of joint
-Mechanical pain and limited ROM
*Recurrent atraumatic hemarthroses
-Local recurrence is 30-50%, lower w/ RT

Hemosiderin-stained, multi-nucleated giant cells w/ inflammatory cells
Cystic erosions on both sides of the joint w/ sclerotic margins
MRI: low signal on T1 & T2
Treatments for PVN
Observation or.....

Total synovectomy
-Arthroscopic synovectomy
-Arthroscopic w/ posterior open synovectomy
- Synovectomy w/Total joint Arthoplasty
-Synovectomy w/ joint arthrodesis
(SBQ07.5) A 45-year-old male presents with a 6-month history of recurrent knee effusions and pain. There is no history of trauma. Exam shows a large joint effusion, decreased range of motion, and a nodularity surrounding the knee. MRI and arthroscopic intra-articular picture are shown. What is the most likely diagnosis?
FIGURES: A B

1. Synovial sarcoma
2. Rheumatoid nodule
3. Septic arthritis
4. Synovial chondromatosis
5. Pigmented villonodular synovitis
PREFERRED RESPONSE 5

DISCUSSION: The history, examination, MRI, and arthroscopic intra-articular image are most consistent with a diagnosis of pigmented villonodular synovitis. PVNS is a benign condition which can predispose patients to early arthritis. It should be noted that the MRI shows nodular findings in both the anterior and posterior portions of the knee. Arthroscopic image shows the deep red fronds classic for PVNS secondary to hemosiderin deposition in the synovium. These findings are specifically reviewed in the article by Bhimani et al where they focus on the history, presentation, imaging appearance, and treatment modalities for PVNS and focus on the MRI appearance of these lesions.

Treatment for symptomatic PVNS includes synovectomy. Often this can be accomplished arthroscopically in the anterior portion of the knee, but the synovial nodules in the posterior knee often require a formal posterior arthrotomy to remove.

True intra-articular malignancies are quite rare, and despite the misnomer, synovial sarcoma is NOT an inter-articular process. Rather, synovial sarcoma tends to occur around, but not within, joint. While rheumatoid nodules, synovial chondromatosis, and lipoma arborescens are all frequent intra-articular lesions, PVNS is the most likely diagnosis based on the MRI and arthrotomy image.

DePonti et al report their 10 year experience with arthroscopic treatment of PVNS of the knee. They found that localized PVNS responded well to lesional excision but that diffuse PVNS required an extended synovectomy to accomplish stable local control of the lesion.

Chin et al report their results on 40 patients with diffuse PVNS. They divided their treatment into surgery alone, surgery and intra-articular radiation, and surgery with external beam radiation. They found the knee scores and range of motion improved post-operatively in all groups, and there was suggestion that intra-articular adjuvant radiation improved the rates of local control.

REFERENCES:
1. De Ponti A, Sansone V, Malcherè M. Result of arthroscopic treatment of pigmented villonodular synovitis of the knee. Arthroscopy. 2003 Jul-Aug;19(6):602-7. Review. PMID:12861198 (Link to Abstract)
2. Chin KR, Barr SJ, Winalski C, Zurakowski D, Brick GW. Treatment of advanced primary and recurrent diffuse pigmented villonodular synovitis of the knee. J Bone Joint Surg Am. 2002 Dec;84-A(12):2192-202. PMID:12473708 (Link to Abstract)
3. Bhimani MA, Wenz JF, Frassica FJ. Pigmented villonodular synovitis: keys to early diagnosis. Clin Orthop Relat Res. 2001 May;(386):197-202. PMID:11347835 (Link to Abstract)
Question Authors:
Patrick O'Donnell MD/PhD, Michael Hughes MD, John Badylak MD,

(OBQ09.221) A 24-year-old man presents with pain and a mass in the anterior ankle. Plain radiographs are normal, MRI is shown in Figure A (arrrows indicate the mass), and biopsy is shown in Figure B. What is the most likely diagnosis? Topic Review Topic
FIGURES: A B
QID: 3034

1. Aneurysmal bone cyst
2. Periosteal osteosarcoma
3. Chondroblastoma
4. Myositis ossificans
5. Pigmented villonodular synovitis (PVNS)
DISCUSSION: The MRI and biopsy are diagnostic for pigmented villonodular synovitis (PVNS), a tumor like condition that is locally aggressive but without risk for metastatic spread. The MRI demonstrates an intra-articular mass without bone destruction. The biopsy shows a nodular pattern of giant cells, diffuse proliferation of mononuclear cells of synovial- or histiocytic-type, and hemosiderin. These components of the biopsy make the diagnosis of PVNS. Treatment is complete excision (synovectomy) of the lesion.

Bickels et al describe their experience with 7 patients with PVNS and the success of adjuvant therapy. They found a high rate of complications following intra-articular injection of yttrium 90 in the ankle joint. As such, they do not recommend this treatment and like many continue to support synovectomy for symptomatic lesions.

Sharma et al describe 14 cases of PVNS of the foot and ankle evaluating the clinical, radiographic, and histopathology factors which influence local recurrence. They found a 14.3% recurrence rate with standard therapy including amputation for appropriate cases and more importantly identified incomplete synovectomy as a possible contributor towards local recurrence.

Incorrect answers:
1) Aneurysmal bone cyst - this lesion is extra-osseous. ABCs occur within the bone.
2) Periosteal osteosarcoma - the pathological section shows no signs of osteoid or malignant cells
3) Chondroblastoma - again, this lesion is extra-osseous. Chondroblastoma occurs within the bone.
4) Myositis ossificans - typically doesn't occur this close to the joint and would appear different on pathological section.

REFERENCES:
1. Bickels J, Isaakov J, Kollender Y, Meller I. Unacceptable complications following intra-articular injection of yttrium 90 in the ankle joint for diffuse pigmented villonodular synovitis. J Bone Joint Surg Am. 2008 Feb;90(2):326-8. PMID:18245592 (Link to Abstract)
2. Sharma H, Jane MJ, Reid R: Pigmented villonodular synovitis of the foot and ankle: Forty years of experience from the Scottish bone tumor registry. J Foot Ankle Surg 2006;45:329- 336 PMID:16949531 (Link to Abstract)
Question Authors:
Patrick O'Donnell MD/PhD, Derek Moore, Ben Taylor MD,
Synovial Sarcoma
Malignant sarcoma that arises near but not usually in a joint
-"Synovial" sarcoma is a misnomer
-Generally arises in 15-40 y/o M > F
-Most common malignant sarcoma of foot
-Chromosomal translocation t(X:18) in >90% of cases
-Associated with SYT-SSX fusion protein production
-Usually high histological grade w/ mets to lungs
-Slow growing mass with regional lymphadenopathy
Synovial Chondromatosis
-Proliferative disease of the synovium related to chondrocytes metaplasia
-Usually affects ages 30-50
-Male > female 2:1
-Knee is most common
-Insidious onset, pain with activity, decreased ROM
-X-rays vary on stage, stippling of calcification late
-MRI show cartilage nodules then calcifications
-Histo: discrete hyaline cartilage with varying stages of calcification
(OBQ04.197) A 47-year-old man presents with right groin pain. Hip radiograph, CT, arthroscopy, and histology slide are shown in Figures A through D. Which of the following statements is true regarding this condition? FIGURES: A B C D
QID: 1302

1. This is a benign metaplastic process which requires wide excision due to the risk of malignant transformation
2. This is a benign metaplastic process which requires symptomatic treatment
3. This is a benign neoplastic process which requires marginal excision
4. This is a benign neoplastic process which requires intralesional excision and adjuvant chemotherapy
5. This is a malignant neoplastic process which requires hip disarticulation and coverage

PREFERRED RESPONSE 2
DISCUSSION: The history, images, and histology slide are all consistent with synovial chondromatosis, a benign metaplastic process which requires symptomatic treatment only. Metaplasia, in contrast to neoplasia, is a process where one cellular phenotype transforms into another cellular phenotype, each non-cancerous. Two examples are the synovial transformation to chondroid tissue in synovial chondromatosis and Barrett's esophagus where normal squamous epithelium is replaced with metaplastic columnar epithelium. While synovial chondromatosis has a low risk of malignant transformation, Barrett's metaplasia has a high risk of malignant transformation and therefore requires more aggressive treatment.

Gilbert and Shpitzer each report on their case series of synovial chondromatosis treated with synovectomy and loose body removal showing good long term results.

REFERENCES:
1. Diseases of the synovial membrane, in McCarthy EF, Frassica FJ (eds): Pathology of Bone and Joint Disorders. Philadelphia PA. WB Saunders, 1998, pp 307-310
2. Gilbert SR, Lachiewicz PF. Primary synovial osteochondromatosis of the hip: report of two cases with long-term follow-up after synovectomy and a review of the literature. Am J Orthop (Belle Mead NJ). 1997 Aug;26(8):555-60. Review. PMID:9267556 (Link to Abstract)
3. Shpitzer T, Ganel A, Engelberg S. Surgery for synovial chondromatosis. 26 cases followed up for 6 years. Acta Orthop Scand. 1990 Dec;61(6):567-9. PMID:2281768 (Link to Abstract)
Question Authors:
Patrick O'Donnell MD/PhD, Michael Hughes MD
-X-rays show calcification
-MRI show low on T1 and high on T2
-Histo: reveals spindle cells which are sheets of fibrous cells with small nuclei and whirling patterns and epithelial cells that are gland, nest or cyst like
(OBQ11.98) Which of the following fusion proteins is associated with synovial sarcoma?
QID: 3521

1. BCR-ABL
2. SYT-SSX
3. EWS-FLI1
4. FUS-CHOP
5. COL1A1-PDGFB
PREFERRED RESPONSE 2
DISCUSSION: The t(X;18) chromosomal translocation is commonly associated with synovial sarcoma. This chromosomal translocation forms a common fusion protein seen in synovial sarcoma, the SYT-SSX protein. There are several different forms of the SYT-SSX fusion protein seen in synovial sarcoma - where either the SSX1, SSX2, or SSX4 genes combine with the SYT gene product.

Tornkvist et al describe the molecular analysis used in the pathological diagnosis of synovial sarcoma. Using specific PCR primers directed against the fusion protein seen in synovial sarcoma, they have increased both the sensitivity and specificity of this molecular diagnosis.

The incorrect answers are associated with the following disease conditions:
BCR-ABL: the Philadelphia chromosome is seen in CML
EWS-FLI1: Ewing's sarcoma
FUS-CHOP: Myxoid liposarcoma
COL1A1-PDGFB: Dermatofibrosarcoma protuberans
(OBQ05.253) The chromosomal translocation t(X;18)is found in which of the following conditions?
QID: 1139

1. Myxoid liposarcoma
2. Synovial Sarcoma
3. Osteosarcoma
4. Ewing's Sarcoma
5. Clear cell sarcoma

PREFERRED RESPONSE 2
DISCUSSION: Synovial sarcoma is a rare soft tissue sarcoma with biphasic features of both spindle cell and epithelial differentiation. Synovial sarcoma is a rare high-grade tumor that spreads along fascial planes and, thus, can be much more widespread than apparent on initial evaluation. Males are more commonly affected than females with a ratio of 1.1:1. Synovial sarcoma is characterized by a specific chromosomal translocation t(X;18)(p11;q11) that is observed in more than 90% of cases. The t(X;18)(p11;q11) translocation fuses the SYT gene from chromosome 18 to either of 2 homologous genes at Xp11, either SSX1 or SSX2. The fusion proteins SYT-SSX1 and SYT-SSX2 function as aberrant transcriptional regulators, resulting in either activation of protooncogenes or inhibition of tumor suppressor genes.

Kawai et al found that SYT-SSX fusion transcripts are a defining diagnostic marker of synovial sarcomas. These fusion transcripts may yield important independent prognostic information and provide important information for different types of treatment.

Incorrect Answers
Answer 1: Myxoid liposarcoma is associated with chromosomal translocation t(12;16)
Answer 4: Ewing's sarcoma with t(11;22)
Answer 5: Clear cell sarcoma with (12;22), Myxoid Chondrosarcoma with t(9;22),

(OBQ08.15) A 22-year-old female has a painful foot mass. Clinical photo, MRI, and histology slide are shown in Figures A through C. What is the most likely diagnosis?
FIGURES: A B C
QID: 401

1. Osteosarcoma
2. Morton's neuroma
3. Synovial sarcoma
4. Fibrous dysplasia
5. Desmoid tumor
PREFERRED RESPONSE 3
DISCUSSION: The clinical photo, MRI, and histology slide are consistent with a diagnosis of synovial sarcoma, one of the most common soft tissue sarcomas of the foot/ankle. Despite the name "synovial sarcoma," these tumors do not occur inside joints or in relation to the synovial tissue. Rather, they occur in peri-articular locations of the lower extremity over 60% of the time. The pathology section shows the classic epithelial cells in gland like structures with associated elongated spindle cells, classic for synovial sarcoma. The common translocation X:18 is associated with synovial sarcoma and the fusion of the SYT and SSX gene products.

Lewis et al evaluated prognostic factors in 112 patients with synovial sarcoma treated at their institution. They found that tumor size greater than 5cm or bone/neurovascular invasion were all independent adverse predictors of distant recurrence and mortality.

In a related study, Thompson et al retrospectively evaluated 38 patients with biopsy proven synovial sarcoma. In their cohort, they too found a strong association between tumor size and patient survival.

REFERENCES:
1. Lewis JJ, Antonescu CR, Leung DH, Blumberg D, Healey JH, Woodruff JM, Brennan MF. Synovial sarcoma: a multivariate analysis of prognostic factors in 112 patients with primary localized tumors of the extremity. J Clin Oncol. 2000 May;18(10):2087-94. PMID:10811674 (Link to Abstract)
2. Thompson RC Jr, Garg A, Goswitz J, Cheng EY, Clohisy DR, Dusenbery K. Synovial sarcoma. Large size predicts poor outcome. Clin Orthop Relat Res. 2000 Apr;(373):18-24. PMID:10810458 (Link to Abstract)
Question Authors:
Patrick O'Donnell MD/PhD, Guillem Lomas MD, Derek Moore,
Hemangiomas
-Benign vascular neoplasms
-They can be deep (cavernous) or superficial (capillary)
-< 30 y/o are most common
-Cavernous are found in lower extremities primarily
-The hand is a common place for capillary
-Most infantile hemangiomas will involute by age 7
-20% are caused by trauma
-No incidence of malignant transformation
-Pain is variable, size is variable due to activity
-X-rays may show phleboliths
-MRI is high on T1 & T2 w/ "bag of worms" appearance of heterogeneity
Treatment of Hemangiomas
Non-Operative:
-Observe, NSAIDs, Vascular stockings, Activity modification for smaller lesions, non-painful or childhood lesions
-Sclerotherapy or Embolization by IR for large, painful lesions that failed NSAIDs and vascular stockings
Operative:
-Marginal resection for lesions of the hand
-Wide excision for lesions on the limb
-Recurrence is High
(OBQ06.119) A 17-year-old male presents to your office with hand swelling and intermittent pain. His pain occurs when his hand is held in a dependent position or when he is swimming. While he was born with a birthmark on his hand, he has noticed it is progressively getting bigger. Clinical photograph, radiographs, and histology are shown. What is the most likely diagnosis? FIGURES: A B C D
QID: 305

1. Synovial sarcoma
2. Epitheliod sarcoma
3. Angiosarcoma
4. Benign hemangioma
5. Giant cell tumor of tendon sheath

PREFERRED RESPONSE 4

DISCUSSION: The clinical history, photograph, radiographs, and histology are all consistent with a benign hemangioma. Hemangiomas are very common benign tumors which can become painful when engorged with blood secondary to dependent positions or physical activity. The clinical photograph shows the associated skin changes which occur when hemangiomas are located in subcutaneous locations. The radiographs show classic phleboliths (calcifications within blood vessels) on the ulnar side of the radiograph. The histology photograph shows no cellular atypia or malignant features. Rather, multiple large endothelial-lined vascular dilations are seen each filled with erythrocytes.

REFERENCES:
1. Menendez LR 9ed): Orthopaedic Knowledge Update: Musculoskeletal Tumors. Rosemont, IL, American Academy of Orthopedic Surgeons, 2002, pp243-253
2. Weiss SW, Goldblum JR: Benign tumors and tumor-like lesions of blood vessels, in Enxinger FM, Weiss SW 9eds): Soft Tissue Tumors. St. Louis, MO, Mosby, 2001, pp837-890.
Question Authors:
Patrick O'Donnell MD/PhD,
Angiosarcoma
Rare and aggressive endothelial-derived tumor from blood vessels
-Male > female
-Venous stasis and trauma
-Poor prognosis, tend to metastasize to lungs and lymph nodes
-Insidious onset of pain w/ skin changes are hallmark
-Usually doesn't involve bone but can
-MRI: Low on T1, High on T2
-Histo: malignant cells associated with vascular structures. Anaplasia.
(OBQ12.25) A 75-year-old male presents with a slowly enlarging, painless thigh mass. Physical exam demonstrates a mass measuring approximately 7 cm in size. Figure A and B demonstrate a T1-weighted MRI and T2-weighted MRI respectively. The histologic findings from a biopsy are shown in Figure C. Which of the following is the most likely diagnosis. FIGURES: A B C


1. Liposarcoma
2. Desmoid Tumor
3. Undifferentiated Pleomorphic Sarcoma
4. Synovial sarcoma
5. Schwanoma
PREFERRED RESPONSE 3
DISCUSSION: The clinical history and figures shown are consistent with a diagnosis of undifferentiated pleomorphic sarcoma.

Previously referred to as malignant fibrous histiocytoma, undifferentiated pleomorphic sarcoma (UPS) most often presents as a painless, slowly enlarging mass. On an MRI scan, the mass appears with dark on T1 and bright on T2. These findings may be suggestive of UPS, but histologic evaluation is needed to help confirm the diagnosis. The mainstay of treatment includes radiation and wide surgical resection.

Schuetze presents a review article that describes the utility of PET scans in evaluation of sarcomas. The authors report that PET scans are a useful tool in conjunction with MRI and histologic analysis. Additionally, they discuss that a decrease in the uptake of glucose has been found to be an early predictor of therapy response in patients with osteosarcoma, Ewing’s, and gastrointestinal stromal tumors.

Randal et al. review the controversy surrounding whether malignant fibrous histiocytoma (MFH) is a unique clinicopathologic entity or a subtype of pleomorphic sarcoma. They report that the World Health Organization classification no longer includes MFH as a distinct diagnostic category but rather as a subtype of undifferentiated pleomorphic sarcoma.

Figure A and B demonstrates the MRI appearance of a pleomorphic sarcoma. Figure C shows the histologic examination of undifferentiated pleomorphic sarcoma. This hisotology is characterized by storiform pattern (cells emanate from a central focus), irregular fascicles, and variable cellularity. Pleomorphic and bizarre tumor cells with foamy cytoplasm and marked atypia appear on a background of inflamed collagenous stroma. There are numerous mitotic figures, including atypical forms. Multinucleated giant cells may be seen.

Incorrect Answers:
Answers 1: Liposarcomas will demonstrate lipoblasts and mature adipose tissue on histology. Signet ring cells are seen at the edges of the tumor.
Answer 2: Desmoid tumors often present in the upper torso, affecting the shoulder, chest wall, and back. They may occasionally affect the lower extremities. They enhance on MRI with gadolinium, but desmoid tumors are typically dark on T1 and T2 imaging. Diagnosis is made by histology, which will show fibroblasts with abundant collagen.
Answer 4: Synovial sarcomas are usually seen in peri-articular regions (shoulder, back, knee, elbow). Joint involvement is rare. MRI findings are non-specific with increased signal seen on T2 images. On histologic analysis, the more common biphasic pattern with epitheliod type cells forming glandular structures mixed with spindle shape cells is seen. They are often associated with the X;18 translocation and the SYS-SSX fusion protein.
Answers 5: Schwannoma will typically be more homogenous, often have a target sign on MRI imaging and will have Antoni A and B cells on pathologic analysis.

REFERENCES:
1. Schuetze SM. Utility of positron emission tomography in sarcomas. Curr Opin Oncol. 2006 Jul;18(4):369- 73. PMID:16721133 (Link to Abstract)
2. Randall RL, Albritton KH, Ferney BJ, Layfield L. Malignant fibrous histiocytoma of soft tissue: an abandoned diagnosis. Am J Orthop (Belle Mead NJ). 2004 Dec;33(12):602-8. Review. PubMed PMID: 15641745. PMID:15641745 (Link to Abstract)
Question Authors:
Amiethab Aiyer, Patrick O'Donnell MD/PhD, Michael Hughes MD,
(OBQ05.34) A 34-year-old male with an eleven-year history of hand exposure to polyvinyl chloride presents with hand pain, but no constitutional symptoms. Physical exam shows lesions involving the nail-folds of the thumb, long, and ring finger as well as several soft-tissue masses in the palm. A radiograph is shown in Figure A and an axial T2 MRI is shown in Figure B. Angiography shows diffuse involvement of multiple lesions in the hand. A CT scan of the chest shows metastasis to the lungs. He undergoes an open biopsy and a representative histology image is shown in Figure C. The biopsy specimen stains positive for CD31 endothelial marker. What is the most likely diagnosis?
FIGURES: A B C

1. Epithelioid sarcoma
2. Chondrosarcoma
3. Angiosarcoma
4. Osteosarcoma
5. Synovial sarcoma


PREFERRED RESPONSE 3
DISCUSSION: The clinical presentation, imaging, and histology are consistent with angiosarcoma, which is a rare, aggressive malignancy that grows insidiously.

The clinical appearance of the tumor in the hand often has central necrosis that is manifested with overlying skin changes. Radiographs often reveal eccentric, purely lytic, metaphyseal and diaphyseal lesions, with no visible matrix mineralization. The histology often shows vascular channels with neoplastic cells that have abundant eosinophilic cytoplasm and large nuclei with mitotic figures. CD31 is a sensitive marker for angiosarcoma. A wide range of treatments have been proposed including resection, forequarter amputation, adjunctive radiation, and chemotherapy depending on the extent, metastasis, and aggressiveness of the lesion.

Vandevender et al offer a Level 5 evidence review on vascular hand tumors. They state that "angiography helps determine the extent of the lesion and may show metastasis" and MR imaging is valuable for evaluating the size and extent of the lesion.

Walsh et al provided an overview of vascular tumors, classifying them into benign, congenital and malignant. Angiosarcomas can arise following irradiation and poly-vinyl chloride exposure.


REFERENCES:
1. Vandevender DK, Daley RA. Benign and malignant vascular tumors of the upper extremity. Hand Clin. 1995 May;11(2):161-81. Review. PMID:7635879 (Link to Abstract)
2. Walsh JJ 4th, Eady JL. Vascular tumors. Hand Clin. 2004 Aug;20(3):261-8, v-vi PMID:15275685 (Link to Abstract)
Glomus Tumor
Benign soft tissue tumor of the glomus body tissue. (paravascular temperature regulating structure)
-It is usually subungal
-frequently delayed diagnosis
-A.k.a paraganglioma
-Usually 20-40 y/o
-Can involve the bone and cause erosions
- Paroxysmal pain, super tender to touch, intolerance to cold
-Nail ridging & discoloration are common
-Can show cortical deformity on x-ray.
-Low on T1 and high on T2
-Not many atypical cells but organized in gland like or nest cells. May have vascular structures close by
-Marginal excision is curative


(OBQ11.113) A 20-year-old male presents with 3 months of pain and swelling in his ring finger. Clinical photo, radiograph, and histology slide are shown in Figures A through C. What is the most likely diagnosis?
FIGURES: A B C
QID: 3536

1. Melanoma
2. Squamous cell carcinoma
3. Synovial sarcoma
4. Epithelioid sarcoma
5. Glomus tumor
PREFERRED RESPONSE 5

DISCUSSION: The history, clinical photograph, radiograph, and histology section are all consistent with a diagnosis of glomus tumor, a benign tumor often found in the hand and under the fingernails. Developing from the glomus body, they were previously called paragangliomas and characteristically, they are often quite painful. Placing the finger in cold water can exacerbate the pain. Even though they are benign tumors, they are locally aggressive, and this coupled with the significant pain leads many to suggest amputation, particularly for tumors as aggressive as this case (Illustration A).

The clinical photograph here shows an ecchymotic fingertip without identification of a specific mass. Given the intraosseous location of this patient's tumor, the bone has become very cystic and shows significant erosive changes. The histological slide shows the bland appearing stroma with the neoplastic tumor cells showing their classic dark nuclei and pink cytoplasm.

McDermott and Weiss review the history, diagnosis, and treatment of glomus tumors. As these tumors can often be small and difficult to visualize, patients often go undiagnosed or misdiagnosed for years. Advanced imaging like MRI can help support the diagnosis. While surgical excision typically provides complete pain relief, locally aggressive glomus tumors sometimes require aggressive surgical resection.

Incorrect answers:
1, 2, 3, 4) While melanoma, squamous cell carcinoma, synovial sarcoma, and epithelioid sarcoma are all very common in the hands, none have the same histopathological appearance as the glomus tumor seen here.

Illustrations: A


REFERENCES:
1. Campanacci M. Glomus tumor. In: Campanacci M, Enneking WF, eds. Bone and Soft Tissue Tumors: Clinical Features, Imaging, Pathology and Treatment. 2nd ed. New York, NY: Springer-Verlag; 1999:1083-1087.
2. McDermott EM, Weiss AP. Glomus tumors. J Hand Surg Am. 2006 Oct;31(8):1397-400. Review. PMID:17027805 (Link to Abstract)
Question Authors:
Patrick O'Donnell MD/PhD, Ben Taylor MD, John Badylak MD,
Lipomas
Common benign tumor of mature adipocytes
-Can be subcutaneous, extramuscular or intramuscular
-Multiple variants i.e. Hibernoma is brown fat tumor (vascular) that occurs in 20-40 y/o
-Usually painless masses except angiolipoma
-Homogenous signal of fat throughout MRI, High on T1 and Low on T2
-Observe or marginally resect
(OBQ09.27) After months of right shoulder pain, a 70-year-old man undergoes work up of a right arm mass with a MRI and also has a CT of his chest/abdomen/pelvis. A representative MRI image is shown in Figure A. He has difficulty using his arm because of the increasing size of the mass. The CT scans shows no evidence of metastatic disease. What is the next step in management?

FIGURES: A

QID: 2840



1. Core biopsy

2. Radiation therapy

3. Chemotherapy followed by surgery

4. Observation

5. Surgical excision


PREFERRED RESPONSE ▼ 5

DISCUSSION: The T-1 weighted MRI shows a soft tissue homogeneous mass that has the same signal intensity as fat, and is intramuscular. Based on the history in the stem, and the imaging provided, the patient has an intramuscular lipoma. These are slow growing and painless. Biopsy of these lesions is not necessary because the diagnosis can usually be made on MRI. Dalal et al provide a review of lipomatous masses, commenting that lipomas are very common and comprise 50% of soft tissue neoplasms, and that marginal surgical excision is the treatment and recurrence rates range from 15-60%.



REFERENCES:

1. Schwartz HS (ed): Orthopaedic Knowledge Update: Musculoskeletal Tumors 2. Rosemont, IL, American Academy of Orthopaedic Surgeons, 2007, pp 277-287

2. Dalal KM, Antonescu CR, Singer S. Diagnosis and management of lipomatous tumors. J Surg Oncol. 2008 Mar 15;97(4):298-313. PMID:18286473 (Link to Abstract)
Liposarcomas
Heterogenous class of with differentiation towards adipose tissue
Lipoblast is (signet ring sign) classic for liposarcomas
-Occur in older adults 50-80 years old
-Males > females
-Lower extremities, retroparitoneal > upper extremities
Many different types: Well-differentiated, myxoid, round cell, pleomorphic, and dedifferntiated
Well-differntiated Liposarcomas
-Low grade, well defined pattern of adipocytes.
-Low malignant potential
-Bright on T1 and Dark on T2
-Tx: Marginal resection w/o RT
Myxoid Liposarcomas
-Translocation (12;16)
-Most common liposarcoma 50%
-Low to intermediate grade
-Intermediate risk of mets 10-30%
-Tx: Wide resection and RT
Round Cell Liposarcoma
-Small round cells on histology
-Dark on T1 and Bright on T2
-Wide resection w/ RT
Pleomorphic Liposarcomas
-High grade pleomorphic cells
-Large adipocytes w/ abnormal nuclei
-Dark on T1 and Bright on T2
-Wide surgical resection with RT
Dedifferentiated Liposarcomas
These are the worst of liposarcomas
-high grade sarcomas
-Low on T1 & High on T2
-Wide surgical resection with RT
(OBQ07.70) A 40-year-old female presents with a painless enlarging left thigh mass. Radiograph, T1, and T2 MRI images are shown in Figures A through C. Biopsy specimen is shown in Figure D. What is the most likely diagnosis? Topic Review Topic
FIGURES: A B C D
QID: 731

1. Lipoma
2. Liposarcoma
3. Hemangioma
4. Chondrosarcoma
5. Leiomyosarcoma
PREFERRED RESPONSE 2
DISCUSSION: Liposarcomas are a heterogenous group of soft tissue sarcomas. The common histological cell is the lipoblast (signet ring cell). The plain radiograph shows the large lesion with increased soft tissue density but no overlying bone changes. MRI shows a large lesion in the posterior thigh that is heterogeneous, dark on T1 and bright on T2). Multiple different sub-types of liposarcoma exist including well-differentiated, round cell, myxoid, etc. Treatment of liposarcomas includes radiotherapy and surgical excision.

Kilpatrick et al evaluated 95 patients retrospectively and found on multivariate analysis that age over 45years, greater than 25% round cell differentiation, and tumor necrosis were all poor prognosticators in liposarcoma.

Sundaram et al evaluated the MRI characteristics of myxoid liposarcomas (the most common subtype of liposarcoma). They found that myxoid liposarcomas contain less than 10% mature fat accounting for their T1 signaling characteristics (dark on T1).

Schwartz et al present a case report regarding liposarcoma of the extremities and provide a valuable review of the imaging characteristics, treatment options, and local and distant recurrence outcomes of liposarcomas.



REFERENCES:
1. Kilpatrick SE, Doyon J, Choong PF, Sim FH, Nascimento AG. The clinicopathologic spectrum of myxoid and round cell liposarcoma: A study of 95 cases. Cancer 1996;77:1450-1458 PMID:8608528 (Link to Abstract)
2. Sundaram M, Baran G, Merenda G, McDonald DJ. Myxoid liprosarcoma: Magnetic resonance imaging appearances with clinical and histological correlation. Skeletal Radiol 1990;19:359-362 PMID:2377902 (Link to Abstract)
3. Schwartz HS, Weiss SW, Sim FH, Beabout JW. Liposarcoma of the soft tissues. Orthopedics 1987;10:1065-1068 PMID:3615295 (Link to Abstract)
Question Authors:
Patrick O'Donnell MD/PhD, Ben Taylor MD, John Badylak MD,
Jonathan Hancock DO, MSA
September 9th, 2013

References
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