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Tumors Masquerading as Hematomas

William G. Ward, Sr., MD

*

; Bruce Rougraff, MD

; Robert Quinn, MD

;

Timothy Damron, MD

§

; Mary I. O’Connor, MD

; Robert E. Turcotte, MD

;

and Matthew Cline, MS

*

Suboptimal patient management can occur when malignant soft tissue tumors with internal hemorrhage masquerade as simple hematomas. We retrospectively reviewed 31 patients with malignancies who had diagnostic delays averaging 6.7 months (range, 1.0–49.3 months). The diagnoses included soft tissue sarcomas (27), metastatic cancers (three), and lymphoma (one). History of subcutaneous ecchymosis was positive in only five patients (three of whom had trauma), negative in 18, and unknown in eight. Ecchymosis was pres-ent in two patipres-ents, abspres-ent in 20, and unknown in nine. Pre-vious treatments included observation and reassurance (21), aspiration (11), incision and drainage (10), unplanned resec-tions (seven), physical therapy (seven), medication adminis-tration (six), and arthroscopy (one). Interpretations of initial MRI (21) and ultrasound (four) did not raise suspicion of underlying cancers. Traumatic hemorrhage usually causes subcutaneous ecchymosis. However, intratumoral hemor-rhage often is contained by a pseudocapsule, which prevents fascial plane tracking and subcutaneous ecchymosis, thus providing a diagnostic clue. Magnetic resonance imaging and ultrasound studies may not accurately diagnose questionable lesions. Diagnostic delay or inappropriate treatment may re-sult if patients do not receive appropriate followup, biopsy

(usually open), or referral whenever the diagnosis is in doubt.

Level of Evidence: Level IV, diagnostic study. See the Guide-lines for Authors for a complete description of levels of evi-dence.

Several case reports have described malignant tumors ini-tially diagnosed as hematomas. McIver et al4 reported a case of metastatic hepatocellular carcinoma that presented as an epidural hematoma in the cranium. van der Wall et al7 and Kelm et al3 reported cases of occult sarcomas initially diagnosed as sports-related injuries with hemato-mas. Such diagnoses can delay or alter treatment and worsen the prognosis. Ogose et al6

reported a patient with Ewing’s sarcoma that mimicked a traumatic hematoma. After repeated aspirations of the thigh, the diagnosis of Ewing’s sarcoma was established. The patient died of his disease several weeks after being correctly diagnosed.6

Few large studies have focused on tumors that masquer-ade as hematomas. Most reports are isolated case studies. The only reported series of sarcomas that mimicked trau-matic hematomas was reported by Imaizumi et al.2 They described six rapidly growing large lesions. Aspiration bi-opsy specimens of five of the six patients were reported as negative for a neoplastic lesion. Correct diagnosis was made by open biopsy after MRI. Imaizumi et al recom-mended a prompt open biopsy for any soft tissue mass that is clinically and radiographically indistinguishable from a chronic hematoma.2

Three of us (WGW, BR, TD) at course lectures pre-sented several cases of soft tissue sarcomas initially diag-nosed as hematomas. Consequently, we collected this se-ries of cases in which malignant soft tissue tumors initially were diagnosed as simple hematomas to illustrate the fre-quency of this problem and in an attempt to detect poten-tial diagnostic indicators, including the presence or ab-sence of subcutaneous ecchymosis.

MATERIALS AND METHODS

From the podium at the 2002 annual business meeting of the Musculoskeletal Tumor Society, the members were invited by Received: July 18, 2005

Revised: March 30, 2007; July 30, 2007 Accepted: August 24, 2007

From the*Department of Orthopaedics, Wake Forest University School of

Medicine, Winston-Salem, NC;†OrthoIndy, Indianapolis, IN; the

Depart-ment of Orthopaedics and Rehabilitation, University of New Mexico, Albu-querque, NM; the§Department of Orthopaedics, SUNY Upstate Medical

University and University Hospital, Syracuse, NY; the㛳Department of Or-thopaedics, Mayo Clinic Jacksonville, Jacksonville, FL; and the¶Department

of Orthopaedics, McGill University, Montreal, Canada.

Each author certifies that he or she has no commercial associations (eg, consultancies, stock ownership, equity interest, patent/licensing arrange-ments, etc) that might pose a conflict of interest in connection with the submitted article.

Each author certifies that his or her institution has approved the reporting of these cases and that all investigations were conducted in conformity with ethical principles of research.

The Corresponding Author confirms six of the seven authors were required to design this retrospective study and all materially participated in at least three major elements of the study and report.

Correspondence to: William G. Ward, Sr., MD, Medical Center Boulevard, Winston-Salem, NC 27157-1070. Phone: 336-716-3952; Fax: 336-716-6286; E-mail: [email protected].

DOI: 10.1097/BLO.0b013e31815953a7

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the primary investigator (WGW) to participate in a formal ques-tionnaire review of cases of malignant soft tissue tumors that initially were diagnosed as simple hematomas. Six members elected to contribute cases (WGW [n⳱11], BR [n⳱6], RQ [n⳱6], TD [n⳱4], MIO [n⳱2], RT [n⳱2]). All patients had presented with a malignant musculoskeletal tumor involving the soft tissues initially diagnosed as a simple hematoma. We included only cases in which hematoma was the clinically ac-cepted working diagnosis by the initial treating physician. Cases in which a hematoma was considered only as one of several possibilities in a differential diagnosis but there was no treatment delay were not included. We identified 31 patients (23 men, eight women), with an average age of 54.6 years (range, 20–83 years), with malignant tumors involving the soft tissues that initially had been diagnosed as simple hematomas. Institutional Review Board approval was obtained from each institution con-tributing patients to this case series.

A standardized questionnaire (Appendix 1) was completed for each case by the orthopaedic oncologists. The data informa-tion was derived directly from their examinainforma-tions and quesinforma-tion- question-ing of patients and from their review of pertinent medical records between October 1999 and September 2002. Each case report

involved a patient who had been treated or whose case had been reviewed by one of the six orthopaedic oncologist authors of this article.

RESULTS

The diagnostic delay between onset and diagnosis aver-aged 6.7 months (range, 1.0–49.3 months). Before present-ing to the orthopaedic oncologist, the 31 patients in this study had been examined by at least 49 physicians (aver-age, two per patient; range, 1–3 per patient).

The final diagnoses (Table 1) included soft tissue sar-comas (27), metastatic cancers (three), and lymphoma (one). Twenty-three patients had a history of trauma, in-cluding 13 with direct trauma (direct blow, n⳱9; fall or motor vehicle accident, n⳱4), eight with muscle strains, and two with recent surgery; eight patients denied any trauma. History of subcutaneous ecchymosis was positive in only five patients (three of whom sustained traumatic injury), negative in 18, and unclear or unknown in eight.

TABLE 1. Description of 31 Cases of Tumors Masquerading as Hematomas

Case

Number Author Diagnosis Trauma

Type of Trauma Ecchymosis by History Ecchymosis by Physical Examination 1 Ward (reviewed case) Synovial cell sarcoma Yes Muscle strain No No

2 Damron Ewing’s sarcoma Yes Muscle strain No Unknown 3 Damron Metastatic carcinoma Yes Direct blow Unknown Unknown 4 Ward Metastatic carcinoma No None No No 5 Turcotte Malignant fibrous histiocytoma Yes Direct blow Yes No 6 Quinn Epithelioid sarcoma No None No No 7 Quinn Malignant fibrous histiocytoma No None Yes No 8 Ward Malignant fibrous histiocytoma Yes Muscle strain Unknown No 9 Ward Leiomyosarcoma No None No No

10 Ward Lymphoma Yes MVA No No

11 Ward Melanoma Yes Surgery Yes Yes 12 Damron Malignant fibrous histiocytoma Yes Direct blow No No 13 Ward Pleomorphic sarcoma Yes MVA Unknown Unknown 14 Ward Synovial cell sarcoma Yes Direct blow Unknown Unknown 15 Quinn Malignant fibrous histiocytoma No None No No 16 Quinn Malignant fibrous histiocytoma No None No No 17 Quinn Chondrosarcoma No None No No 18 Quinn Liposarcoma Yes Muscle strain No No 19 Rougraff Pleomorphic sarcoma Yes Direct blow No No 20 O’Conner Malignant fibrous histiocytoma Yes Fall Unknown Unknown 21 O’Conner Leiomyosarcoma Yes Direct blow Unknown Unknown 22 Turcotte Synovial cell sarcoma Yes Surgery Unknown Unknown 23 Ward Malignant fibrous histiocytoma No None Yes Yes 24 Rougraff Malignant fibrous histiocytoma Yes Muscle strain No No 25 Rougraff Malignant fibrous histiocytoma Yes Fall No No 26 Rougraff Leiomyosarcoma Yes Direct blow No No 27 Ward Pleomorphic sarcoma Yes Muscle strain No No 28 Damron Osteosarcoma—telangiectatic Yes Muscle strain Unknown Unknown 29 Rougraff Chondrosarcoma Yes Direct blow Yes Unknown 30 Rougraff Malignant fibrous histiocytoma Yes Direct blow No No 31 Ward Ewing’s sarcoma Yes Muscle strain No No MVA = motor vehicle accident

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Ecchymosis was present on physical examination by the physician in two patients, absent in 20, and unknown in nine. The anatomic location of the tumors included the thigh (12), pelvis (six), leg (five), shoulder (three), knee (two), and one each in the elbow, arm, and ankle.

Treatments before referral to the orthopaedic oncologist included observation and/or reassurance in 21 patients, aspiration in 11 patients, incision and drainage in 10 pa-tients, unplanned resections in seven papa-tients, physical therapy in seven patients, medication administration in six patients, and arthroscopy in one patient. Despite MRI in 21 patients (68% of patients) (Fig 1) and ultrasound in four patients, the underlying tumors were not detected.

DISCUSSION

This report describes a series of patients in whom tumors diagnostically masqueraded as hematomas. The volume of cases collected from multiple institutions confirms that this is not an isolated problem. The diversity of the cases reflects the complex nature and difficulties posed in the timely diagnosis of such tumors. Although one diagnostic indicator that applied to all cases could not be identified, the absence of subcutaneous ecchymosis in the majority of cases with tumor-associated internal hemorrhage provides an important clue that can initiate the proper diagnostic evaluation.

Our study is limited by the lack of a control group of patients with hematomas without associated tumors and by its retrospective nature. For a patient to qualify for inclu-sion in the study, the diagnosis of the underlying tumor had to be initially missing, even from a differential diag-nosis. Therefore, much of the important information re-garding initial history, presentation, and examination find-ings either was overlooked or omitted and was available only by records review and/or recall, potentially introduc-ing error or bias. Furthermore, a study of the inability to accurately and promptly diagnose any disease process, in which the identification involves treatment, will always be fraught with difficulties as there could never be a control series of patients followed to see the difference in the outcome based on diagnostic delay. The therapies and sur-geries performed varied depending on patient desires and tumor characteristics, such as tumor size, stage, and loca-tion. To accurately identify how treatments and surgeries might have been different or simpler had the tumor been detected earlier and before any other surgical procedures had been performed, presumably when the tumor was smaller, is impossible without complete evaluation data from the time of initial presentation to a physician and a comparable set of data at diagnosis. Such complete infor-mation does not exist. Thus, hard definitions or descrip-tions of how the patient’s management or surgery was altered are not possible. It is noteworthy, in the opinion of these experienced orthopaedic oncologists completing the questionnaires, earlier diagnosis of the presence of a tumor may have materially influenced the patient’s clinical course in 22, reducing the number and/or complexity of surgical procedures to treat the tumors in 18, avoiding unnecessary surgical procedures in 13, and potentially lowering the risk of local recurrence in 18. It is well known that unplanned surgical procedures and resections complicate subsequent management of patients with soft tissue sarcomas.1,5We also have considerable experience in general orthopaedics, lending validity to our observa-tions regarding trauma, hemorrhage, and ecchymosis.

Fig 1A–B. (A) An axial proton density (intermediate-weighted) MR image (TR = 1000, TE = 20) of a lesion in the rectus femoris muscle shows a poorly visualized oblique septation (arrow) and a horizontal fluid-fluid line (arrowheads). (B) A coronal spin echo T2-weighted (TR = 2000, TE = 90) MR image of the same lesion shows the encapsulation in the rec-tus femoris muscle. The patient underwent multiple aspirations of bloody fluid by his primary treating orthopaedic surgeon. Complete resection of the rectus femoris revealed a large he-matoma contained in a thin-walled, high-grade malignant fi-brous histiocytoma.

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Hemorrhage and hematomas occur for various reasons, including traumatically induced hemorrhage, coagulopa-thy-induced hemorrhage, and tumor-associated necrosis and hemorrhage. Clinical experience suggests traumati-cally induced hemorrhage usually extends beyond the con-fines of anatomically defined compartments. The hemor-rhage tracks along fascial planes and usually is observable clinically in the subcutaneous tissues (Fig 2). Conversely, tumor-associated hemorrhage usually presents in the cen-tral regions of the tumor. The fascial boundaries of the tumor and its anatomic compartment contain the blood and

heme pigments in the compartment (Fig 3). Therefore, extended fascial plane tracking is unlikely to occur, and subcutaneous ecchymosis will not be present.

The observable ecchymosis rate of only 22% by history and of only 9% by physician examination confirms ma-lignant tumors with intralesional hemorrhage that mas-querade as simple hematomas most frequently do not have associated subcutaneous ecchymosis. However, trauma-related hemorrhages usually do have associated subcuta-neous ecchymosis. Although not diagnostic, this differen-tiation provides a diagnostic clue suggesting the possibility of tumor-associated hemorrhage whenever physicians evaluate suspected hematomas in patients lacking subcu-taneous ecchymosis. In the absence of observable ecchy-mosis, the likelihood of tumor-associated hemorrhage is somewhat increased.

The nondiagnostic MR images often show large, hema-toma-filled cavities with septae and small areas of sarco-matous tissue along the hematoma margins. The tumorous areas, which can be minimal in volume, may be over-looked by the interpreting radiologists and clinicians. Ar-eas of visible tumor will possess variable degrees of con-trast enhancement. Enhancing areas such as thickened irregular rims or enhancing areas in the suspected hema-tomas should be diligently sought by radiologists and cli-nicians when evaluating any imaging of a hematoma. They may be absent, thin, and/or irregular in contour because of the hemorrhage compressing the sarcoma tissue (Fig 1). True hematomas may have a similar appearance on MRI (Fig 4).

All patients diagnosed as having a simple hematoma should be followed as appropriate for the situation. For

Fig 2. The photograph shows an arm with subcutaneous chymosis after a direct blow trauma. This subcutaneous ec-chymosis is rarely seen with spontaneous hemorrhage into tumors. Physicians should consider the possibility of tumor-related hemorrhage whenever diagnosing a hematoma in a patient without such ecchymosis.

Fig 3. An intraoperative photograph shows a thwalled in-tramuscular sarcoma that virtually was filled with a large he-matoma. All of the blood was contained by the tumor pseudo-capsule and muscle. There would be no subcutaneous ecchy-mosis unless there was tumor extension beyond the muscle or an associated muscle tear or tissue disruption.

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example, a small traumatically induced subcutaneous he-matoma from a direct blow (contusion with an associated hematoma) may require only an admonition to return “if the lump does not resolve,” whereas a large suspected hematoma deep in the thigh muscles, not induced by trauma, and observed on a MRI scan, should at a minimum, have a repeat physical examination in 4 to 12 weeks and possibly repeat MRI. No guidelines apply to all cases. Additional radiographic studies, as deemed appropriate, should be obtained. Biopsy, usually open, should be per-formed when indicated. Referral to an orthopaedic oncolo-gist would be prudent whenever a question of an under-lying tumor arises. The first author (WGW) has treated a patient who was prescribed chronic anticoagulation therapy for a mechanical heart valve. She had a large hematoma develop in the thigh. Because it was massive, an open biopsy was performed and confirmed intratumoral hemorrhage. Imaizumi et al2 found needle aspiration bi-opsies of soft tissue sarcomas with hemorrhage rarely yield diagnostic tumor cells. They reported aspiration bi-opsies were negative in five of six synovial sarcomas that presented as hematomas. Because the wall of the hema-toma cavity may be the only tissue composed of malignant cells, a core or aspiration biopsy may not provide an ad-equate sample of the malignant cells. Therefore, open bi-opsy may be required in some cases. A future study of the accuracy of the various measures used to evaluate sus-pected hematomas would be a welcome addition to the

literature as we are unable to state with confidence a uni-formly applicable diagnostic, therapeutic, and followup regimen to manage such cases because of the lack of hard data.

The frequency of tumors masquerading as hematomas is unknown. However, the first author (WGW) has had a specific interest in this problem and has specifically in-quired about prior diagnoses and potential diagnostic delay in all his patients. He has treated 10 such patients during a 14-year period during which time he surgically treated 174 soft tissue sarcomas, suggesting this scenario may be en-countered in approximately 6% of soft tissue sarcomas.

Based on the findings of this study, MRI and ultrasound studies and their interpretations cannot be relied on for complete accuracy, especially in patients with uncertain radiographic findings, worrisome clinical histories, or troublesome physical examinations. When qualified, cli-nicians should review imaging studies themselves. In the absence of a prompt and accurate diagnosis, inappropriate treatments and treatment delays are likely to result (Fig 5). Once a tumor is diagnosed, the patients should have ap-propriate staging studies, including MRI of the tumor, as part of their standard evaluations.

Soft tissue malignancies may be assessed incorrectly as being simple hematomas when a malignant neoplasm is present. Physicians should exercise care when diagnosing hematomas in the absence of subcutaneous ecchymosis and in the absence of a history of trauma. Magnetic

reso-Fig 4. This MRI composite depicts a hematoma that arose over the gibbus from an osteoporotic spinal compression fracture in a 92-year-old woman. On the top left is a T1 sagittal image with a predominantly low signal lesion with inhomogeneous moderately higher signal areas. On the top right is a T2 sagittal image with a predominantly intermediate signal lesion with foci of high signal. On the bottom left is a T2 axial image with an inhomogeneous high signal area aris-ing in a predominantly intermediate signal lesion with low signal margins. On the bottom right is a T1 axial contrast-enhanced, fat-suppressed image of a lesion with high signal margins surrounding a predominantly intermediate signal lesion that contains inhomogeneous areas of high signal. All four images reveal some mar-gins with clear delineation and some marmar-gins with less distinct borders. The inhomogeneity in the lesions, and especially the irregular areas of contrast en-hancement, confirmed the presence of viable tissue in the suspected hematoma; therefore, open biopsy was performed to accurately diagnose the lesion. Open excisional biopsy confirmed a chronic hematoma at-tributable to tissue irritation over the bony gibbus. There was no tumor in this case. This case illustrates the difficulty of MRI alone to accurately discern between simple hematomas and tumor-associated hematomas.

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nance imaging and ultrasound cannot be solely relied on to distinguish simple hematomas from tumors or tumors with internal hemorrhage. On MRI, the margins and septae of all hematomas should be evaluated carefully for thickened areas with gadolinium contrast enhancement. Whenever diagnosed, hematomas should be appropriately evaluated

and followed. When clinical suspicion of tumor-associated hemorrhage exists, a biopsy is indicated.

Acknowledgments

We thank Paul Vieta, MD, who assisted in the collection of the data, and Beth Paterson Smith, PhD, for editorial assistance.

References

1. Davis AM, Kandel RA, Wunder JS, Unger R, Meer J, O’Sullivan B, Catton CN, Bell RS. The impact of residual disease on local recur-rence in patients treated by initial unplanned resection of soft tissue sarcoma of the extremity.J Surg Oncol. 1997;66:81–87.

2. Imaizumi S, Morita T, Ogose A, Hotta T, Kobayashi H, Ito T, Hirata Y. Soft tissue sarcoma mimicking chronic hematoma: value of mag-netic resonance imaging in differential diagnosis. J Orthop Sci. 2002;7:33–37.

3. Kelm J, Ahlhelm F, Engel C, Duchow J. Synovial sarcoma diag-nosed after a sports injury.Am J Sports Med. 2001;29:367–369. 4. McIver JI, Scheithauer BW, Rydberg CH, Atkinson JL. Metastatic

hepatocellular carcinoma presenting as epidural hematoma: case report.Neurosurgery. 2001;49:447–449.

5. Noria S, Davis A, Kandel R, Levesque J, O’Sullivan B, Wunder J, Bell R. Residual disease following unplanned excision of a soft-tissue sarcoma of an extremity. J Bone Joint Surg Am. 1996;78: 650–655.

6. Ogose A, Hotta T, Yamamura S, Shioya Y, Yazawa T. Extraskeletal Ewing’s sarcoma mimicking traumatic hematoma. Arch Orthop

Trauma Surg. 1998;118:172–173.

7. van der Wall H, Palmer A, Murray IP. Bone scintigraphy of a liposarcoma presenting as a muscle hematoma. Clin Nucl Med. 1992;17:743–744.

APPENDIX 1. Tumors Masquerading as Hematomas Data Form Physician completing form:

Name:

1. Patient name: 2. Patient number:

3. Date of birth: / /

Month Day Year

4. Gender: Male Female

6. Date of onset of symptoms: / / (or duration before diagnosis if exact dates unknown)

Month Day Year

5. Date of visit with first physician: / /

Month Day Year

6. Date of visit with physician who diagnosed or suspected cancer (estimate interval between 5 and 6 if dates unknown

[ months])

7. Date of presentation to orthopaedic oncologist: / /

Month Day Year

8. Occupation:

Fig 5. A computed tomography scan shows a massive right buttock sarcoma with central hematoma. Air bubbles from the prior incision and drainage can be seen. The general surgeon who referred this patient did not consider the possibility of a tumor until “a little ball of tumor rolled out of the wound” when he was examining the patient in his office after he performed incision and drainage.

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9. Comorbidities: Diabetes mellitus Yes No

Hypertension Yes No

Hyperlipidemia Yes No

Atherosclerotic cardiovascular disease Yes No

(coronary artery disease)

History of stroke Yes No

History of liver disease Yes No

Patient being anticoagulated Yes No

History of cancers Yes No

If yes, list:

Chronic renal disease Yes No

Chronic obstructive pulmonary disease Yes No

Other:

10. True diagnosis (type of tumor): 11. Initial misdiagnosis:

12. Location of tumor:

13. Primary tumor (if applicable, ie, if a metastasis was the misdiagnosed tumor): Diagnosis and location of primary (if applicable):

14. Presence of subcutaneous ecchymosis (ie, did the extremity or body part have directly observable bruising with skin color changes?):

By history Yes No Don’t know

By physical examination Yes No Don’t know

15. Trauma: Yes No

If yes, please specify type: Motor vehicle accident Fall

Direct blow

Other, please specify:

16. Type (specialty) of previous physicians seen (check all that apply): General practitioner

Internist Physiatrist General surgeon Orthopaedic surgeon

Physician or nature of specialty designation Other, please specify:

17. Prior management (insert number of times each was performed at right of answer): Observation/reassurance ( times)

Fine needle aspiration biopsy ( times) Core biopsy ( times)

Open biopsy ( times)

Aspiration of suspected hematoma ( times) (therapeutic intention, not diagnostic intention) Resection ( times)

Open reduction and internal fixation ( times) Arthroscopy ( times)

Incision and drainage ( times)

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Other treatments:

Physical therapy ( times)

Medications; specify type: ( times)

Chiropractic manipulation ( times) Occupational therapy ( times)

Alternative medicine treatment; specify: ( times)

Other; specify: ( times)

18. Tissue submitted for pathology at prior surgeries/procedures: Yes No

19. Time between first visit with any physician until time of first biopsy (ie, procedure where tissue was submitted for

pathology): months

20. Studies that were interpreted or misinterpreted as consistent with hematomas and allowed misdiagnosis to be perpetuated: Radiograph

Computed tomography scan MRI Bone scan Ultrasound Arthrogram Arteriogram/venogram Other:

21. Studies performed that led to or facilitated diagnosis when properly interpreted (please check all that apply): Radiograph

Computed tomography scan MRI Bone scan Ultrasound Arthrogram Arteriogram/venogram Other:

22. Metastases at initial presentation to initial physician:

Yes No Don’t know Not applicable

23. Metastases at time of referral/evaluation by orthopaedic oncologist:

Yes No Don’t know Not applicable

24. Treatment of tumor (answer all questions):

Not applicable Yes No If yes, proceed to question 25

Resection Yes No Don’t know Not applicable

Amputation Yes No Don’t know Not applicable

Limb salvage Yes No Don’t know Not applicable

Chemotherapy Yes No Don’t know Not applicable

If yes, preresection Yes No Don’t know Not applicable

Postresection Yes No

Radiation Yes No Don’t know Not applicable

If yes, preresection Yes No Don’t know Not applicable

Postresection Yes No

25. Planned treatment of tumor:

Not applicable: Yes No If yes, proceed to question 26

Resection Yes No Don’t know Not applicable

Amputation Yes No Don’t know Not applicable

Limb salvage Yes No Don’t know Not applicable

Chemotherapy Yes No Don’t know Not applicable

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26. Length of followup status/postdefinitive management (tumor resection): months

27. Metastases during followup period Yes No Don’t know Not applicable

28. Local recurrence during followup period Yes No Don’t know Not applicable

29. Tumor status NED (no evidence of disease) AWD (alive with disease DOD (dead of disease)

DUC (died of unrelated causes) (specify):

DRC (died of related causes [ie, chemotherapy-induced sepsis])

30. If tumor had been correctly diagnosed initially, would it have materially affected the patient’s outcome?

Yes No

If yes, how:

Surgery simpler or requiring less tissue sacrifice Yes No

Limb salvage possible that was not possible at time of diagnosis Yes No

Lower risk of local recurrence (ie, tumor more difficult to eradicate) Yes No

Metastases appeared during interval of delayed diagnosis Yes No

Avoided inappropriate surgical procedure Yes No

Other: Yes No Please explain:

References

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