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Pathology International 2014; 64: 195–197
doi:10.1111/pin.12153
Letter to the Editor Hybrid myxoinflammatory fibroblastic sarcoma/hemosiderotic fibrolipomatous tumor of the ankle following repeated trauma To the Editor: Myxoinflammatory fibroblastic sarcoma (MIFS) is a low grade sarcoma with predilection for the distal portions of the extremities, first described in 1998 under different names by three independent groups of authors,1–3 as ‘inflammatory myxoid tumor of the soft parts with bizarre giant cells’, ‘inflammatory myxohyaline tumor of distal extremities with virocyte or ReedSternberg-like cells’ and ‘acral myxoinflammatory fibroblastic sarcoma’. As the tumor is not entirely restricted to acral sites, the term ‘acral’ was withdrawn from the latter to reach a consensus name. MIFS is characterized by proliferation of low grade atypical spindle cells embedded in myxoid and inflammatory stroma with a proportion of larger cells resembling Reed-Sternberg cells and showing characteristic intranuclear virocyte-like inclusions. To date, there have been very few reports of high grade transformation and metastasis.2,4,5 In 2000, Marshall-Taylor and Fanburg-Smith6 first reported a distinctive soft tissue proliferation characterized by lipomatous/hemosiderotic spindle cell histology and predilection for the ankle of female patients. ‘Hemosiderotic fibrohistiocytic lipomatous lesion’ was the original name, which was later abbreviated to ‘hemosiderotic fibrolipomatous tumor’ (HFLT). More recently, several studies7,8 have demonstrated a consistent t(1;10)(p22;q24) translocation in both tumors, showing evidence for a common origin. Further
a
findings from the few recently reported hybrid HFLT/MIFS cases5,8,9 give evidence that HFLT and MIFS could represent different levels of tumor progression within the same entity. A 57-year-old woman was admitted for treatment of a large soft tissue tumor surrounding the right ankle and extending distally along the foot arch (Fig. 1a). Clinical history showed multiple repeated injuries in the ankle and foot area, which started 40 years prior, when the patient suffered a right ankle fracture. Twelve years later, the patient developed frostbite in the same area. A year later, a tractor spreader drove across the same foot. In 1996, 23 years after the incipient injury, lymphedema of the right foot started to develop. Two years later, the patient spilt boiling water across the foot. In a few days, the patient fell and broke the ankle again. Six years later, the foot was traumatized in a traffic accident. It was only in 2006 that the patient was admitted for treatment of lymphedema. Two tumors measuring 6 × 5 cm and 3 × 5 cm, respectively, were excised from the ankle and foot region and confirmed as lipomas by the pathologist at an external institution. In 2013, the patient underwent another biopsy in our institution because of tumor recurrence, which raised suspicion for high grade liposarcoma. Radiography revealed a multinodular tumor untreatable by local excision, measuring up to 15 cm. PET-CT scan confirmed the finding, and also revealed increased fluorodeoxyglucose (FDG) uptake in an enlarged right inguinal lymph node. The patient underwent transtibial amputation and biopsy of the enlarged lymph node. Six months after amputation, the patient is without signs of recurrence.
b
Figure 1 (a) A large soft tissue tumor surrounded the right ankle and extended distally along the foot arch. (b) Amputation specimen: a brownish component (arrowhead) corresponding to hemosiderotic fibrolipomatous tumor and a distal, whitish and gelatinous component (arrow) corresponding to myxoinflammatory fibrosarcoma. © 2014 The Authors Pathology International © 2014 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd
196
Letter to the Editor
a
b
c
d
Figure 2 (a) Hemosiderotic fibrolipomatous tumor component; adipocytes admixed with a spindle cell stroma containing abundant hemosiderin deposits and focal psammoma bodies (H&E, 200×). (b) Hemosiderotic fibrolipomatous tumor component (top left), myxoinflammatory fibrosarcoma component (lower right) (H&E, 20×). (c) Atypical spindle cells of myxoinflammatory fibrosarcoma with several mitoses and some inflammatory cells (H&E, 400×). (d) Characteristic virocyte or Reed-Sternberg-like cells of myxoinflammatory fibrosarcoma (arrows), some of whom are binucleated (H&E, 400×).
Grossly, there was a multinodular tumor measuring 14.5 × 11 cm, extending from the ankle to the toes, with two components; the first component, located in proximity to the ankle with an approximate volume of 100 cm3, was of yellowishbrown colour and fatty tissue consistency; the second component with an approximate volume of 350 cm3 was whitish and partially gelatinous, extending distally over the foot arch (Fig. 1b). Tibial resection margin was uninvolved, with 9 cm of tumor-free intervening tissue. Inguinal lymph node measured 1.2 cm in diameter. On histology, the first component of the tumor was composed of adipocytic nodules with scant intervening spindle cell stroma containing abundant hemosiderin deposits and focal psammomatous calcifications (Fig. 2a). Spindle cells showed occasional mitoses and slight cytological atypia. In some of the sections, there was a gradual transition into the other component of the tumor,
which was densely cellular with alternating myxoid areas and scattered clusters of chronic inflammatory cells (Fig. 2b). In approximately 20% of the volume it exhibited high grade histology with up to 18 mitoses per 10 high power fields (HPF, 400×) (Fig. 2c) and up to 30% of Ki67-positive cells. There were focal larger cells with characteristic intranuclear inclusions, binucleated cells (Fig. 2d) and pseudolipoblast foci. Immunohistochemistry revealed a strong and diffuse positive reaction to vimentin and CD34, focal reaction to CD68 only in HFLT and no reaction to SMA, S-100, EMA and desmin (all antibodies DAKO, Glostrup, Denmark). There was no evidence of lymphovascular invasion demonstrable by D2-40 immunostaining. The excised lymph node was free of tumor. Pathological report was signed out as hybrid hemosiderotic fibrolipomatous tumor/myxoinflammatory fibroblastic sarcoma with focal areas of high grade transformation.
© 2014 The Authors Pathology International © 2014 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd
Letter to the Editor
The case described herein, which to our knowledge represents only the third case exhibiting simultaneous hybrid features of MIFS/HFLT reported so far, reinforces the recent pathogenetic link between these two entities. Both tumors are characterized by a consistent translocation t(1;10), which has not been found in other myxoid soft tissue tumors.10 Hallor et al.7 mapped the translocation breakpoints to TGFBR3 in 1p22 and in or near MGEA5 in 10q24, resulting in transcriptional up-regulation of NPM3 and particularly FGF8, two consecutive genes located close to MGEA5. More recently, several cases with hybrid features of both tumors have been described.5,8,9 In two of those cases (42- and 44-year-old females) the primary tumor exhibited hybrid features, while in another two cases (43year-old male and 60-year-old female) the recurrence of HFLT showed a component of MIFS. All cases were diagnosed either by fluorescence in situ hybridization or GTG banded karyotyping. One of the tumors (43-year-old male) exhibited areas with high-grade morphology and was followed by death of disease with multiple metastases after two years.5 Clinically, such cases highlight the necessity of awareness that HFLT and MIFS may occur synchronously or metachronously. Our patient’s tumor was signed out as ‘lipoma’ at a different hospital 7 years prior to the recurrence and development of MIFS. Even though MIFS is considered a low-grade sarcoma, in rare cases the potential to exhibit high-grade transformation and more aggressive behaviour has been documented.5 Moreover, in the largest series of MIFS so far, consisting of 104 cases from the Armed Forces Institute of Pathology archives, Laskin et al.4 failed to find any reliable histopathologic predictor of recurrence, while the only statistically significant clinicopathologic predictor was the adequacy of resection margins. Based on findings from the same series, it is suggested that adjuvant radiation therapy may be considered for those patients with positive surgical margins, especially if the tumor harbors atypical histologic features. In conclusion, our case report reinforces the recently established view that HFLT and MIFS are different parts of a spectrum within the same entity. Presence of a long standing lipomatous foot and ankle tumor in a patient with history of local trauma should alert one to search for the more subtle clues of HFLT, which can easily be misdiagnosed as lipoma. In all cases, careful examination with additional sections and use of modern imaging methods should minimize the possibility of overseeing a synchronous MIFS. Also, surgeons
197
should be alerted to the importance of achieving tumor-free margins, since in several cases HFLT has been reported to recur as MIFS. ˇ engic´,2 Tihana Džombeta,1,3 Zlatko Marušic´,1 Tomislav C 1 Majda Vucˇic´, Božo Krušlin1,3 and Davor Tomas1,3 1 Department of Pathology, Clinical Hospital Center ‘Sestre Milosrdnice’, 2Department of Traumatology, Clinical Hospital Center ‘Sestre Milosrdnice’, and 3 Department of Pathology, Medical School, University of Zagreb, Zagreb, Croatia
REFERENCES 1 Michal M. Inflammatory myxoid tumor of the soft parts with bizarre giant cells. Pathol Res Pract 1998; 194: 529–33. 2 Meis-Kindblom JM, Kindblom LG. Acral myxoinflammatory fibroblastic sarcoma: A low-grade tumor of the hands and feet. Am J Surg Pathol 1998; 22: 911–24. 3 Montgomery EA, Devaney KO, Giordano TJ, Weiss SW. Inflammatory myxohyaline tumor of distal extremities with virocyte or Reed-Sternberg-like cells: A distinctive lesion with features simulating inflammatory conditions, Hodgkin’s disease, and various sarcomas. Mod Pathol 1998; 11: 384–91. 4 Laskin WB, Fetsch JF, Miettinen M. Myxoinflammatory fibroblastic sarcoma: A clinicopathologic analysis of 104 cases, with emphasis on predictors of outcome. Am J Surg Pathol 2014; 38: 1–16. 5 Solomon DA, Antonescu CR, Link TM, O’Donnell RJ, Folpe AL, Horvai AE. Hemosiderotic fibrolipomatous tumor, not an entirely benign entity. Am J Surg Pathol 2013; 37: 1627–30. 6 Marshall-Taylor C, Fanburg-Smith JC. Hemosiderotic fibrohistiocytic lipomatous lesion: Ten cases of a previously undescribed fatty lesion of the foot/ankle. Mod Pathol 2000; 13: 1192–9. 7 Hallor KH, Sciot R, Staaf J et al. Two genetic pathways, t(1;10) and amplification of 3p11-12, in myxoinflammatory fibroblastic sarcoma, haemosiderotic fibrolipomatous tumour, and morphologically similar lesions. J Pathol 2009; 217: 716–27. 8 Antonescu CR, Zhang L, Nielsen GP, Rosenberg AE, Dal Cin P, Fletcher CD. Consistent t(1;10) with rearrangements of TGFBR3 and MGEA5 in both myxoinflammatory fibroblastic sarcoma and hemosiderotic fibrolipomatous tumor. Genes Chromosomes Cancer 2011; 50: 757–64. 9 Elco CP, Marino-Enriquez A, Abraham JA, Dal Cin P, Hornick JL. Hybrid myxoinflammatory fibroblastic sarcoma/ hemosiderotic fibrolipomatous tumor: Report of a case providing further evidence for a pathogenetic link. Am J Surg Pathol 2010; 34: 1723–7. 10 Nishio J, Iwasaki H, Nabeshima K, Naito M. Cytogenetics and molecular genetics of myxoid soft-tissue sarcomas. Genet Res Int 2011; 2011: 497148.
© 2014 The Authors Pathology International © 2014 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd
Pathology International 2014; 64: 195–197
doi:10.1111/pin.12153
Letter to the Editor Hybrid myxoinflammatory fibroblastic sarcoma/hemosiderotic fibrolipomatous tumor of the ankle following repeated trauma To the Editor: Myxoinflammatory fibroblastic sarcoma (MIFS) is a low grade sarcoma with predilection for the distal portions of the extremities, first described in 1998 under different names by three independent groups of authors,1–3 as ‘inflammatory myxoid tumor of the soft parts with bizarre giant cells’, ‘inflammatory myxohyaline tumor of distal extremities with virocyte or ReedSternberg-like cells’ and ‘acral myxoinflammatory fibroblastic sarcoma’. As the tumor is not entirely restricted to acral sites, the term ‘acral’ was withdrawn from the latter to reach a consensus name. MIFS is characterized by proliferation of low grade atypical spindle cells embedded in myxoid and inflammatory stroma with a proportion of larger cells resembling Reed-Sternberg cells and showing characteristic intranuclear virocyte-like inclusions. To date, there have been very few reports of high grade transformation and metastasis.2,4,5 In 2000, Marshall-Taylor and Fanburg-Smith6 first reported a distinctive soft tissue proliferation characterized by lipomatous/hemosiderotic spindle cell histology and predilection for the ankle of female patients. ‘Hemosiderotic fibrohistiocytic lipomatous lesion’ was the original name, which was later abbreviated to ‘hemosiderotic fibrolipomatous tumor’ (HFLT). More recently, several studies7,8 have demonstrated a consistent t(1;10)(p22;q24) translocation in both tumors, showing evidence for a common origin. Further
a
findings from the few recently reported hybrid HFLT/MIFS cases5,8,9 give evidence that HFLT and MIFS could represent different levels of tumor progression within the same entity. A 57-year-old woman was admitted for treatment of a large soft tissue tumor surrounding the right ankle and extending distally along the foot arch (Fig. 1a). Clinical history showed multiple repeated injuries in the ankle and foot area, which started 40 years prior, when the patient suffered a right ankle fracture. Twelve years later, the patient developed frostbite in the same area. A year later, a tractor spreader drove across the same foot. In 1996, 23 years after the incipient injury, lymphedema of the right foot started to develop. Two years later, the patient spilt boiling water across the foot. In a few days, the patient fell and broke the ankle again. Six years later, the foot was traumatized in a traffic accident. It was only in 2006 that the patient was admitted for treatment of lymphedema. Two tumors measuring 6 × 5 cm and 3 × 5 cm, respectively, were excised from the ankle and foot region and confirmed as lipomas by the pathologist at an external institution. In 2013, the patient underwent another biopsy in our institution because of tumor recurrence, which raised suspicion for high grade liposarcoma. Radiography revealed a multinodular tumor untreatable by local excision, measuring up to 15 cm. PET-CT scan confirmed the finding, and also revealed increased fluorodeoxyglucose (FDG) uptake in an enlarged right inguinal lymph node. The patient underwent transtibial amputation and biopsy of the enlarged lymph node. Six months after amputation, the patient is without signs of recurrence.
b
Figure 1 (a) A large soft tissue tumor surrounded the right ankle and extended distally along the foot arch. (b) Amputation specimen: a brownish component (arrowhead) corresponding to hemosiderotic fibrolipomatous tumor and a distal, whitish and gelatinous component (arrow) corresponding to myxoinflammatory fibrosarcoma. © 2014 The Authors Pathology International © 2014 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd
196
Letter to the Editor
a
b
c
d
Figure 2 (a) Hemosiderotic fibrolipomatous tumor component; adipocytes admixed with a spindle cell stroma containing abundant hemosiderin deposits and focal psammoma bodies (H&E, 200×). (b) Hemosiderotic fibrolipomatous tumor component (top left), myxoinflammatory fibrosarcoma component (lower right) (H&E, 20×). (c) Atypical spindle cells of myxoinflammatory fibrosarcoma with several mitoses and some inflammatory cells (H&E, 400×). (d) Characteristic virocyte or Reed-Sternberg-like cells of myxoinflammatory fibrosarcoma (arrows), some of whom are binucleated (H&E, 400×).
Grossly, there was a multinodular tumor measuring 14.5 × 11 cm, extending from the ankle to the toes, with two components; the first component, located in proximity to the ankle with an approximate volume of 100 cm3, was of yellowishbrown colour and fatty tissue consistency; the second component with an approximate volume of 350 cm3 was whitish and partially gelatinous, extending distally over the foot arch (Fig. 1b). Tibial resection margin was uninvolved, with 9 cm of tumor-free intervening tissue. Inguinal lymph node measured 1.2 cm in diameter. On histology, the first component of the tumor was composed of adipocytic nodules with scant intervening spindle cell stroma containing abundant hemosiderin deposits and focal psammomatous calcifications (Fig. 2a). Spindle cells showed occasional mitoses and slight cytological atypia. In some of the sections, there was a gradual transition into the other component of the tumor,
which was densely cellular with alternating myxoid areas and scattered clusters of chronic inflammatory cells (Fig. 2b). In approximately 20% of the volume it exhibited high grade histology with up to 18 mitoses per 10 high power fields (HPF, 400×) (Fig. 2c) and up to 30% of Ki67-positive cells. There were focal larger cells with characteristic intranuclear inclusions, binucleated cells (Fig. 2d) and pseudolipoblast foci. Immunohistochemistry revealed a strong and diffuse positive reaction to vimentin and CD34, focal reaction to CD68 only in HFLT and no reaction to SMA, S-100, EMA and desmin (all antibodies DAKO, Glostrup, Denmark). There was no evidence of lymphovascular invasion demonstrable by D2-40 immunostaining. The excised lymph node was free of tumor. Pathological report was signed out as hybrid hemosiderotic fibrolipomatous tumor/myxoinflammatory fibroblastic sarcoma with focal areas of high grade transformation.
© 2014 The Authors Pathology International © 2014 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd
Letter to the Editor
The case described herein, which to our knowledge represents only the third case exhibiting simultaneous hybrid features of MIFS/HFLT reported so far, reinforces the recent pathogenetic link between these two entities. Both tumors are characterized by a consistent translocation t(1;10), which has not been found in other myxoid soft tissue tumors.10 Hallor et al.7 mapped the translocation breakpoints to TGFBR3 in 1p22 and in or near MGEA5 in 10q24, resulting in transcriptional up-regulation of NPM3 and particularly FGF8, two consecutive genes located close to MGEA5. More recently, several cases with hybrid features of both tumors have been described.5,8,9 In two of those cases (42- and 44-year-old females) the primary tumor exhibited hybrid features, while in another two cases (43year-old male and 60-year-old female) the recurrence of HFLT showed a component of MIFS. All cases were diagnosed either by fluorescence in situ hybridization or GTG banded karyotyping. One of the tumors (43-year-old male) exhibited areas with high-grade morphology and was followed by death of disease with multiple metastases after two years.5 Clinically, such cases highlight the necessity of awareness that HFLT and MIFS may occur synchronously or metachronously. Our patient’s tumor was signed out as ‘lipoma’ at a different hospital 7 years prior to the recurrence and development of MIFS. Even though MIFS is considered a low-grade sarcoma, in rare cases the potential to exhibit high-grade transformation and more aggressive behaviour has been documented.5 Moreover, in the largest series of MIFS so far, consisting of 104 cases from the Armed Forces Institute of Pathology archives, Laskin et al.4 failed to find any reliable histopathologic predictor of recurrence, while the only statistically significant clinicopathologic predictor was the adequacy of resection margins. Based on findings from the same series, it is suggested that adjuvant radiation therapy may be considered for those patients with positive surgical margins, especially if the tumor harbors atypical histologic features. In conclusion, our case report reinforces the recently established view that HFLT and MIFS are different parts of a spectrum within the same entity. Presence of a long standing lipomatous foot and ankle tumor in a patient with history of local trauma should alert one to search for the more subtle clues of HFLT, which can easily be misdiagnosed as lipoma. In all cases, careful examination with additional sections and use of modern imaging methods should minimize the possibility of overseeing a synchronous MIFS. Also, surgeons
197
should be alerted to the importance of achieving tumor-free margins, since in several cases HFLT has been reported to recur as MIFS. ˇ engic´,2 Tihana Džombeta,1,3 Zlatko Marušic´,1 Tomislav C 1 Majda Vucˇic´, Božo Krušlin1,3 and Davor Tomas1,3 1 Department of Pathology, Clinical Hospital Center ‘Sestre Milosrdnice’, 2Department of Traumatology, Clinical Hospital Center ‘Sestre Milosrdnice’, and 3 Department of Pathology, Medical School, University of Zagreb, Zagreb, Croatia
REFERENCES 1 Michal M. Inflammatory myxoid tumor of the soft parts with bizarre giant cells. Pathol Res Pract 1998; 194: 529–33. 2 Meis-Kindblom JM, Kindblom LG. Acral myxoinflammatory fibroblastic sarcoma: A low-grade tumor of the hands and feet. Am J Surg Pathol 1998; 22: 911–24. 3 Montgomery EA, Devaney KO, Giordano TJ, Weiss SW. Inflammatory myxohyaline tumor of distal extremities with virocyte or Reed-Sternberg-like cells: A distinctive lesion with features simulating inflammatory conditions, Hodgkin’s disease, and various sarcomas. Mod Pathol 1998; 11: 384–91. 4 Laskin WB, Fetsch JF, Miettinen M. Myxoinflammatory fibroblastic sarcoma: A clinicopathologic analysis of 104 cases, with emphasis on predictors of outcome. Am J Surg Pathol 2014; 38: 1–16. 5 Solomon DA, Antonescu CR, Link TM, O’Donnell RJ, Folpe AL, Horvai AE. Hemosiderotic fibrolipomatous tumor, not an entirely benign entity. Am J Surg Pathol 2013; 37: 1627–30. 6 Marshall-Taylor C, Fanburg-Smith JC. Hemosiderotic fibrohistiocytic lipomatous lesion: Ten cases of a previously undescribed fatty lesion of the foot/ankle. Mod Pathol 2000; 13: 1192–9. 7 Hallor KH, Sciot R, Staaf J et al. Two genetic pathways, t(1;10) and amplification of 3p11-12, in myxoinflammatory fibroblastic sarcoma, haemosiderotic fibrolipomatous tumour, and morphologically similar lesions. J Pathol 2009; 217: 716–27. 8 Antonescu CR, Zhang L, Nielsen GP, Rosenberg AE, Dal Cin P, Fletcher CD. Consistent t(1;10) with rearrangements of TGFBR3 and MGEA5 in both myxoinflammatory fibroblastic sarcoma and hemosiderotic fibrolipomatous tumor. Genes Chromosomes Cancer 2011; 50: 757–64. 9 Elco CP, Marino-Enriquez A, Abraham JA, Dal Cin P, Hornick JL. Hybrid myxoinflammatory fibroblastic sarcoma/ hemosiderotic fibrolipomatous tumor: Report of a case providing further evidence for a pathogenetic link. Am J Surg Pathol 2010; 34: 1723–7. 10 Nishio J, Iwasaki H, Nabeshima K, Naito M. Cytogenetics and molecular genetics of myxoid soft-tissue sarcomas. Genet Res Int 2011; 2011: 497148.
© 2014 The Authors Pathology International © 2014 Japanese Society of Pathology and Wiley Publishing Asia Pty Ltd
