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Keywords:

  • acral myxoinflammatory fibroblastic sarcoma;
  • sarcoma;
  • radiotherapy;
  • surgical resection

Abstract

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. Acknowledgements
  7. CONFLICT OF INTEREST DISCLOSURES
  8. REFERENCES

BACKGROUND:

Acral myxoinflammatory fibroblastic sarcoma (AMFS) is a rare, low-grade sarcoma that commonly affects the distal extremities. From the published cases, therapy for AMFS to date has been comprised of excision or amputation, with limited use of radiotherapy (RT) or chemotherapy. In this report, the outcome of 17 patients with AMFS treated at the study institution was reported.

METHODS:

A retrospective review of all cases of AMFS identified in the Sarcoma Database in the Department of Radiation Oncology at the study institution was conducted. Treatment records and data from follow-up visits of patients were reviewed.

RESULTS:

Seventeen patients were identified. All the patients underwent surgical resection (15 excisions and 2 amputations). Positive surgical margins after excisions were noted in 5 patients and were widely positive in 1 patient. Of the 17 patients, 14 patients received some form of RT. The average total dose was 56.4 Gray (Gy). Eight patients received preoperative RT alone, 5 patients received preoperative RT and postoperative RT, and 1 patient received preoperative RT and intraoperative RT. Median follow-up was 24.5 months. One patient presented with recurrent disease and was treated with resection, and both pre- and postoperative RT. He was free of disease 23 months after his last treatment. No local recurrence was noted in the remaining patients. Of the 14 patients undergoing preoperative RT, complete pathologic necrosis or no tumor was noted in 1 of the patients. No metastatic disease was observed in any of the patients. There was no significant radiation toxicity observed in any of the patients.

CONCLUSIONS:

Data were consistent with local control of distal extremity sarcomas with resection and RT, suggesting that limb-sparing surgery with this treatment combination is an appropriate option in the limb-sparing control of patients with AMFS, even those with positive surgical margins. Cancer 2010. © 2010 American Cancer Society.

Acral myxoinflammatory fibroblastic sarcoma (AMFS) is a rare, low-grade sarcoma that commonly affects the distal extremities. First described in 1998 by Meis-Kindblom and Kindblom, the lesion often presents as a painless mass in the hands or feet.1 The mass often grows slowly but can be quite infiltrative into the surrounding soft tissues.2 Much of what has been currently published on the condition derives from pathology case reports that describe the unique microscopic appearance of the lesion. These findings have led to multiple names for the condition, including inflammatory myxohyaline tumor,3 myxoid malignant fibrous histiocytoma,4 and AMFS.1 Other diagnoses included in the differential diagnosis are ganglion cysts, tenosynovitis, and spindle cell tumors.1, 3, 5 From the published cases, therapy for AMFS has consisted of excision or amputation, with very limited use of radiotherapy (RT) or chemotherapy.1 In this report, we review the outcome of 17 patients with AMFS treated at the Center for Sarcoma & Connective Tissue Oncology at the Massachusetts General Hospital.

MATERIALS AND METHODS

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. Acknowledgements
  7. CONFLICT OF INTEREST DISCLOSURES
  8. REFERENCES

A retrospective review of all cases of AMFS in the past 5 years from the Massachusetts General Hospital Radiation Oncology Department was conducted. Seventeen patients with the diagnosis of AMFS were treated. The median age at diagnosis was 52 years (range, 25-80 years). Sixteen patients presented with primary disease, and 1 patient presented with local recurrence. The location of lesions were all in the extremities as follows: 7 in the hand, 3 in the arm, 1 in the forearm, 1 in the elbow, 1 in the thigh, 1 in the knee, 2 in the leg, and 1 in the foot.

Details of each patient and treatment are shown in Table 1. All the patients underwent surgical resection (15 excisions and 2 amputations). The tumors were diagnosed based on reported histologic features, and the pathologic grade was assigned according to the French (Federation Nationale des Centres de Lutte Contre le Cancer [FNCLCC]) system for soft-tissue sarcomas.6 Fourteen patients received RT preoperatively, intraoperatively, postoperatively, or in some combination thereof. RT was delivered with varying modalities and dosing. External beam RT (EBRT) was delivered using 3-dimensional conformal RT using a 2-field technique or was delivered using intensity-modulated RT (IMRT). Brachytherapy was given through catheter insertion using high-dose rate (HDR) administration.

Table 1. Individual Patient and Treatment Details
SexAge at Diagnosis, YearsRaceSitePresentationPre- operative Radio therapyDose/No. of FractionsEnergyType of SurgerySizeGradePost- operative Radio therapyPost- operative Radio therapy ModalityDose/No. of FractionsEnergyTotal DoseMarginsRecurrenceFollow-Up Duration, Months
Man75UnknownHandPainful swellingNoAmputation2No0NegativeNo28
Woman60CaucasianUpper armPainful massNoExcision4.2 × 3.8 × 3.5 cm2No0NegativeNo12
Man39CaucasianHandPainless massNoExcision1.2 × 0.7 × 0.6 cm2No0NegativeNo75
Woman26HispanicForearmTender massYes50 Gy/25 fractions6 MeVExcision3.0 × 1.6 × 1.1 cm1No50 GyPositiveNo14
Man25CaucasianHandPainless massYes50 Gy = 30 Gy (P) + 20 Gy (E)/25 fractions4 MeV (P), 9 MeV (E)Excision1.6 × 1.9 × 0.7 cm1No50 GyNegativeNo63
Man68CaucasianUpper armPainless massYes50 Gy/25 fractions6 MeVExcision5.0 × 4.5 × 2.8 cm1No50 GyNegativeNo14
Man54CaucasianHandPainless massYes50 Gy/25 fractions6 MeVExcision1.0 × 0.6 × 0.4 cm2No50 GyNegativeNo34
Man62CaucasianLeg (knee)Painful swellingYes50.4 Gy/28 fractions6 MeVAmputation2No50 GyNegativeNo21
Woman52CaucasianUpper armMass and parasthesia of right upper extremityYes50 Gy/25 fractions6 MeVExcision3.8 × 3.1 × 1.9 cm2No50 GyPositiveNo58
Woman47CaucasianLeg (calf)Painless massYes50 Gy/25 fractions6 MeVExcision2.1 × 1.8 × 1.6 cm2No50 GyNegativeNo10
Man34CaucasianElbowPainless massYes50 Gy/25 fractions6 MeVExcision2No50 GyNegativeNo26
Man33CaucasianHandRecurrence of prior diseaseYes50 Gy/25 fractions6 MeVExcision2.0 × 1.0 cm2YesBrachytherapy16 Gy/4 fractionsHDR Iridium-19266 GyPositiveYes23
Man80CaucasianLeg (calf)Painless massYes50 Gy/25 fractions6 MeVExcision6.5 × 3.3 × 2.4 cm2YesEBRT boost16 Gy/4 fractions6 MeV66 GyNegativeNo8
Woman45CaucasianHandIncomplete excision with positive surgical marginsYes22 Gy/11 fractions6 MeVExcision4.0 × 3.5 × 0.5 cm1YesEBRT + boost22 Gy + 14 Gy/11 + 7 fractions6 MeV56 GyNegativeNo59
Man67CaucasianLeg (thigh)Painless massYes50 Gy/25 fractions6 MeVExcision5.0 × 2.0 × 2.0 cm1YesEBRT20 Gy/10 fractions6 MeV70 GyPositiveNo22
Woman56CaucasianHandPainless massYes6 Gy/3 fractions4 MeVExcision1.5 × 0.6 × 0.3 cm2YesEBRT62 Gy/31 fractions4 MeV68 GyNegativeNo46
Woman48CaucasianFootPainful lumpYes50 Gy/25 fractions4 MeVExcision6.5 × 2.0 × 0.8 cm2YesIORT14 Gy/1 fraction6 MeV64 GyPositiveNo45

Eight patients received preoperative RT followed by excision alone. RT was given in 6 of the patients by means of photons and 1 using a combination of photons and electrons. Preoperative RT doses were 5000 to 5040 centiGray (cGy) in 25 to 28 fractions.

Five patients received preoperative RT and then underwent excision followed by adjuvant RT. Preoperative RT was delivered using EBRT, with 2 of the cases planned and treated with IMRT. Dose delivered ranged from 600 to 5000 cGy in 200 cGy fractions. Postoperative RT was given by means of EBRT in 4 patients and brachytherapy in 1 patient. Dose delivered ranged from 1600 to 6200 cGy in 200 cGy fractions. Brachytherapy was delivered using HDR in 4 fractions of 400 cGy to a total of 1600 cGy.

One patient received preoperative photon EBRT of 5000 cGy in 25 fractions followed by surgery with an intraoperative fraction of RT of 1400 cGy. Three patients underwent surgery alone with no RT.

RESULTS

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. Acknowledgements
  7. CONFLICT OF INTEREST DISCLOSURES
  8. REFERENCES

Histologically, all the tumors demonstrated the morphologic characteristics of AMFS, and the majority were considered pathologic grade 2/3 (Fig. 1). Summary of treatment is shown in Table 2. The median follow-up for the patients was 24.5 months (average, 32.8 months; range, 2-52 months). Local tumor control was achieved in all 16 patients who presented with primary disease. None of the patients had evidence of metastatic disease on follow-up visits as assessed by imaging studies and physical examination. One patient presented to Massachusetts General Hospital with locally recurrent disease. His disease had recurred in the flexor tendon sheaths of the carpus and forearm after a fifth ray amputation. The patient refused transradial amputation. Salvage treatment consisted of preoperative EBRT, excision with expected positive or contaminated surgical margins, and additional postoperative EBRT. Disease was controlled in the treated anatomic region. Unfortunately, the patient then developed tumor in the flexor tendon sheath of the thumb. He again refused amputation and was successfully managed with EBRT, surgery, and brachytherapy, again with expected positive surgical margins. At the time of last follow-up, he remained free of disease 23 months after his last treatment, as documented by repeat imaging studies. Five of the irradiated patients did have positive surgical margins after excision primarily due to the anatomic location of the tumor and reluctance to sacrifice nerves of the upper extremity. Only 1 of these patients did not receive additional postoperative RT. Despite putative microscopic disease left behind, all of these patients were without evidence of disease at the time of last follow-up.

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Figure 1. (Top and Bottom) Histologic presentation of acral myxoinflammatory fibroblastic sarcoma (AMFS) is shown. AMFS is classified with a mix of components, including an inflammatory lymphocytic background with areas of myxoid component, enlarged atypical cells with prominent nucleoli, and an irregularly shaped nucleus. Neoplastic cells noted in the reports include spindle cells with mild to moderate nuclear atypia, Reed-Sternberg-like cells, ganglion-like cells, and large atypical multivacuolated cells resembling lipoblasts. Photo courtesy of Dr. Andrew Rosenberg.

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Table 2. Treatment and Follow-Up Summary
 No. of Patients
  1. RT indicates radiotherapy; IMRT, intensity-modulated radiotherapy; Gy, Gray.

Treatment
 Surgery17
  Margins 
   Positive5
   Negative12
 RT14
  Preoperative RT alone8
  Preoperative plus postoperative RT5
  Preoperative plus intraoperative RT1
 Modality
  3D conformal12
  IMRT2
  Brachytherapy1
 Average total radiation dose (Gy)56.4
Follow-up
 Average length of follow-up32.8 months
 Tumor recurrence1
 Distant Metastases0
Late radiation associated treatment toxicity > Grade 20
Death from tumor0

No late RT toxicity higher than grade 2 was noted in the radiated patients. Chemotherapy was not given in any of the cases. Surgical management was not different with regard to location of lesions, although negative surgical margins were easier to obtain in the lower extremity lesions. No functional or neurologic deficit was noted in any of the patients.

None of the reported patients have developed metastatic disease.

DISCUSSION

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. Acknowledgements
  7. CONFLICT OF INTEREST DISCLOSURES
  8. REFERENCES

AMFS is a rare, slow-growing sarcoma that has a predilection for the distal extremities.1 A survey of all published literature is summarized in Table 3.1-5, 7-15 From Table 3, we can see that AMFS commonly affects middle-aged adults with a somewhat greater propensity toward men. As observed in the cases presented in the current study and other published cases, patients often present with a painless mass that has appeared over the course of several months. There does not appear to be a predilection for certain sex or age, with a range from ages 4 to 87 years. From those studies that elaborated patient's treatment, nearly all patients received surgery, with only 5 reported cases receiving RT. The literature suggests an infiltrative behavior for these lesions, and the crude local recurrence rate in these reported cases was 31.3% (40/128) despite being low-grade; metastatic disease was reported in 3.1% (4/128) cases. In contrast, we had no local tumor recurrences in those patients treated primarily at this institution. This may be due to adjuvant RT because, in many cases, surgical margins were positive or close in an effort to optimize functional status. Metastatic disease is rare in this low-grade sarcoma, despite the local invasiveness of the tumor and the reported difficulty in achieving local control in some series.

Table 3. Review of the Literature Regarding Acral Myxoinflammatory Fibroblastic Sarcoma
StudyNo. of PatientsAge, YearsSexDistal LesionTreatment ReceivedSize Range, cmRecurrenceMetastasesFollow-Up
  1. M indicates male; F, female; NA, not available; RT, radiotherapy.

Ebhardt 20018622-604 M and 2 F6/6 (100%)Excision1-42/6 (33%)0/6NA
Fetsch 200123714-72 (median, 46)25 M and 12 F37/37 (100%)33 excision, 4 amputation0.6-5.0 (mean, 1.75)3/180/1811-319 mo (mean, 10.1 mo)
Hassanein 200814539-65 (mean, 55)3 M5/5 (100%) distal extremity3 excision, 1 amputation, 1 loss to follow-up1-4.02/41/42 wk-95 mo (mean, 54 mo)
Jurcić 20029922-87 (median, 43)6 M and 3 F6/9 (67%)6 excision, 3 amputation1.5 to 181/9 after 2 y0/91-60 mo (mean, 14 mo)
Kovarik 2008101821-66 (48)2.3 M:1 F10/13 (77%) distal extremityExcision1.0-10.0 (mean, 3.1)0/130/131-23 mo
Kusumi 200511158M1/1 (100%)Excision30/10/112 mo
Lambert 200112153F1/1 (100%)Excision7.4NANANA
Lang 20065522-66 (median, 49)3 M and 2 F4/5 (80%)ExcisionUnknown0/50/514-42 mo (mean, 24 mo)
Meis-Kindblom 199814420-91 (median, 53)22 M and 22 F44/44 (100%)37 excision, 10 amputation, 5 cases received RT and 2 cases received chemotherapy1-6 (median, 3)24/36 (67%)2/366-540 mo (median, 60 mo)
Montgomery 19983514-81 (median, 40)27 M and 24 F51/51 (100%)NANA6/27 (22%)0/27NA
Narvaez 200715422-66 (mean, 44)2 M and 2 F3/4 (75%)ExcisionNA0/40/4NA
Sakaki 20037515-75 (median, 32)4 M and 1 F5/5 (100%)Excision2.7-4.9 (mean, 3.5)2/41/58-58 mo (mean, 25 mo)
Yasuda 200713168F1/1 (100%)ExcisionNA0/10/148 mo
Total187Range, 4-87110 M and 77 F174/182120/145 excisions, 18/145 amputations, 5/145 radiotherapy, 2/145 chemotherapyRange, 0.6-1840/128 (31.3%)4/128 (3.1%) 

The early published reports of AMFS described high local recurrence rates of 22% to 67%.1, 3 A survey of all published cases demonstrated a crude local recurrence rate of 31.3%. Given the rarity of the tumor, the small sample size, and the limited follow-up periods, these estimates may not truly reflect the true nature of AMFS but do reveal that the risk of local disease recurrence can be significant. The majority of these studies evaluated patients treated with surgery alone in the definitive treatment of their patients. RT may have a role in supplementing local control as we noted in a percentage of our cases, particularly those with positive surgical margins.

Five of the patients in our population had positive surgical margins but were free of local or distant disease at the time of last follow-up. These 5 patients received 50 Gy of preoperative RT and 3 received additional intraoperative or postoperative boost RT of 14 to 20 Gy.

Although adjuvant RT does not appear to be necessary for patients with soft-tissue sarcoma treated with surgery alone, even with high-grade lesions, when surgical margins are wide or include a fascial barrier,16 such margins appear to be harder to achieve in AMFS patients because of the locally infiltrative nature of the lesions and predilection for involvement of the upper extremity. Nevertheless, the potential morbidity of both surgery and RT should be taken into consideration in the treatment of AMFS patients. Although no greater than grade 3 late radiation toxicity was observed in any of our patients, studies with longer follow-up periods have reported that the potential late effects of RT include fibrosis, joint stiffness, and edema in patients treated for soft-tissue sarcomas.17 Techniques to minimize late RT-associated morbidity have been published.18, 19

To our knowledge to date, there has not been any literature describing RT techniques in treating AMFS. Experience with RT for other sarcomas of the distal extremities have demonstrated local control rates >80% with combinations of preoperative RT and/or postoperative RT and excision. Stratified by surgical margin status, those patients with negative surgical margins generally achieve a local control rate of >90%.7 Dosing and fractionation in these studies varied but preoperative regimens generally were comprised of 50 Gy in 25 fractions, with variable use of additional postoperative boost RT of approximately 14 Gy to 18 Gy for positive surgical margins, whereas postoperative regimens generally ranged from 60 Gy to 63 Gy in 30 to 25 fractions, with additional boost doses for positive surgical margins to total doses ≥66 Gy.20, 21 These regimens have generally resulted in high rates of local control with acceptable morbidity.

Conclusions

The current study data are consistent with local control of distal extremity sarcomas with combined surgery and RT, suggesting that RT may have a role in improving local control with acceptable morbidity in patients with AMFS treated with limb-sparing surgery. These data are consistent with results reported in the published trials on RT for distal extremity sarcomas.22

Acknowledgements

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. Acknowledgements
  7. CONFLICT OF INTEREST DISCLOSURES
  8. REFERENCES

We acknowledge and thank Dr. Dempsey Springfield for contributing patients to the study and reviewing the article.

REFERENCES

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. Acknowledgements
  7. CONFLICT OF INTEREST DISCLOSURES
  8. REFERENCES
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