Malignant fibrous histiocytoma of the forearm: Report of a case and review of the literature The tissue histiocyte can give rise to a variety of lesions, either benign or malignant, and the latter often is confused with other sarcomas. The multipotential nature of the histiocyte results in the presence of at leastfive different cell types in these tumors, and all may be derivedfrom a common precursor cell. The anaplasia of elements which differentiate as fibroblasts appears to correlate with survival. The tumors may be highly malignant, and the 10 year survival rate approximates 40%. Aggressive surgical management of these tumors is mandatory, with either wide en bloc resection or primary amputation of the involved extremity. Should the tumor recur locally after a wide resection and there be no detectable metastases, prompt amputation is indicated.
Leonard F. Hubbard, M.D., and Richard 1. Burton, M.D., Rochester, N. Y.
Malignant tumors arising from tissue histiocytes are uncommon lesions, and in the reported series the number of cases is too small to have established clear criteria for prognosis and treatment. 1-4 A case of malignant fibrous histiocytoma of the upper extremity is presented with a brief review of the literature and suggested guidelines for the treatment of patients presenting with these tumors. Case presentation M. B., a 50-year-old right-handed Caucasian woman, complained of a slowly enlarging painless mass in the extensor surface of the upper right forearm of approximately 12 months' duration. She did not recall any trauma or infection in the area. An incisional biopsy had been performed, with the resulting diagnosis of malignant fibrous histiocytoma. One week after the initial biopsy, she was referred to the senior surgeon (R. B.) and admitted to the hospital for further diagnosis and treatment. She had been in good health and regularly participated in sports. There were no complaints of pain, erythema, or swelling. The review of systems was normal. Examination showed there was a 2 by 4 cm firm, fixed, non tender mass in the proximal extensor surface of the right forearm. The biopsy site overlying the lesion had healed From the Department of Orthopaedics, University of Rochester Medical Center, Rochester, N. Y. Received for publication Dec. 13, 1976. Revised for publication March 28, 1977. Reprint requests: Leonard F. Hubbard, M.D., Department of Orthopaedics, University of Rochester Medical Center, Rochester, NY 14642.
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primarily. Motor and sensory functions of the arm and hand were normal, including wrist and finger extension and the sensory function of the radial nerve. Brain, bone, liver, and spleen scans, as well as a hematological survey were reported as normal. Radiographs of the involved arm showed only soft tissue swelling, without involvement of bone: Under axillary block, an extensive en bloc resection of the tumor was performed. A 3 cm margin, including skin, subcutaneous tissue, and muscles of the extensor compartment to the interosseous membrane was removed. The radial nerve, the extensor carpi radialis longus, and the abductor pollicis longus were outside of the margin of resection and were left in place. The 6 by 10 cm defect left by the excision was covered with a split-thickness skin graft taken from the left thigh under local anesthesia. Postoperative healing was uneventful, and joint motion was maintained by dynamic splinting and an exercise program. Three months later there was no evidence of recurrent or metastatic disease. The prognosis of this tumor was discussed with the patient. She expressed a strong desire to become free of splints and to resume her former activities as soon as possible. The necessary transfers could be done distal to a 3 cm margin from the edge of the previous wide en bloc excision. The flexor carpi ulnaris was transferred to the extensor digitorum communis and the brachioradialis to the extensor pollicis longus. This procedure was complicated by marginal wound necrosis, which healed after local debridement. Eighteen months after the mass first had been noted, and 9 months after the tumor had been excised, there were no apparent local or systemic recurrences. She had 70° of active metacarpophalangeal joint flexion and extension, full active interphalangeal joint motion, and normal wrist and thumb
Vol. 2, No.4, pp. 292-296
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Malignant fibrous histiocytoma of forearm
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Fig. 1. Marked whorled hypercellularity and the multiple cell types characteristic of the malignant fibrous histiocytoma. With such marked pleomorphism, the characteristic stromal storiform pattern may be less apparent. Giant cells are frequent. (Hematoxylin and eosin. Original magnification x80.) function. Again she is right-handed, splint free, with essentially normal active use of the hand. Sections from the surgical specimen demonstrated an anaplastic tumor with histiocytes, xanthomatous cells, and spindle-shaped cells (Figs. I and 2). Special stains demonstrated collagen production by spindle cells and the presence of moderate amounts of reticulin (Fig. 3). The sections were reviewed by pathologists at Columbia College of Physicians and Surgeons and at Stanford University, and the diagnosis of malignant fibrous histiocytoma was confirmed.
Discussion
The group of tumors now recognized to originate from the tissue histiocyte has long provoked controversy because of their diversity in morphology and biologic behavior. 5-7 Both benign and malignant tumors are derived from histiocytes, but not until recently in most series have they been separated from other sarcomas. Benign histiocyte lesions include fibrous xanthomas, xanthogranulomas, and giant cell tumors. Malignant giant cell tumors of soft parts, xanthosarcomas, and malignant fibrous xanthomas have been reclassified as malignant histiocyte tumors. 4, 7 This nomenclature recognizes the common cell origin of the tu-
mors, the tissue histiocyte, a cell of multiple potentials. Much of the initial work done in reclassifying these tumors was published by Stout and Lattes. 7 Further work by other authors has clearly differentiated these tumors from other mesenchymal lesions and has established their origin. 5 , 6, 8 The malignant fibrous histiocytoma, relatively common among the histiocytic tumors, probably has been improperly classified often in the past as a fibrosarcoma, pleomorphic rhabdomyosarcoma, or liposarcoma. This confusion arises because of the different cell types present in the same tumor. Four of these tumors were studied by Fu et al. 5 who used the electron microscope. They were able to distinguish five distinct cell types, including histiocyte-like cells, fibroblastlike cells, xanthomatous cells, giant cells, and an undifferentiated cell. Varying amounts of collagen were present in association with the spindle-shaped cells. Tissue culture studies by Ozello, Stout, and Murray 8 previously had suggested the variable potential of the tissue histiocyte. They demonstrated its ability to assume a spindle-shape and to produce collagen and they coined the term "facultative fibroblast." Whether the
294
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The Journal of HAND SURGERY
Fig. 2. Stroma of anaplastic "facultative fibroblasts" and collagen, containing malignant histiocytes, giant cells, and xanthomatous cells. A mitotic figure is also present. (Periodic-acid Schiff stain. Original magnification x200.)
histiocyte becomes transformed, or whether both histiocytes and fibroblast-like cells are derived from a common undifferentiated precursor, is not clear. 5, 8 Malignant fibrous histiocytomas have been reported in other locations, including the extremities, the thorax, and the retroperitoneum. I - 6 Characteristically they develop as asymptomatic masses in extremities during the sixth decade. While most cases have occurred in soft tissue, these tumors also have been reported as primary interosseous lesions_ Huvos collected 18 cases of primary interosseous malignant fibrous histiocytoma reviewed between 1931 and 1974. These were most common in the tibia and distal femur. Nearly all had been diagnosed previously as another tumor type_ 10 Feldman and Norman 9 presented the pathologic and radiologic aspects of 20 cases of malignant histiocytomas with primary or secondary skeletal involvement. Reports have described the occurrence of malignant fibrous histiocytomas apparently arising in bone infarcts .1, 2 These have been the only cases in which the tumors appear to have been associated with reparati ve processes_ Metastases from these tumors occur both by hematogenous and lymphatic routes, and recurrence after
local excision is common. The treatment of choice is either wide en bloc resection or primary amputation. Patients already may have metastatic disease at the time of their initial biopsy, 1, 2 as was seen in a 30-year-old man at our institution who died within 16 months_ The anaplasia of the stromal elements was marked in this case, a finding which Soule and Enriquez4 thought correlated with a poor prognosis_ In general, chemotherapy and radiation therapy have not been helpful in controlling either local or metastatic disease, although short-term responses to actinomycin, Methotrexate, and radiation have been reported. 4, 9, 10 The small numbers make interpretation of figures on survival difficult. In Soule and Enriquez'4 series, a 65% 5-year survival rate was attained in 33 patients with malignant fibrous histiocytoma, with eight of the 20 survivors having tumor recurrence at the time of the report. The 10 year survival rate was 38%. Seven patients initially had local excisions without recurrences, whereas 15 others treated this way had recurrences_ Amputation was a secondary procedure in three patients, and two of these died_ The criteria used for choice of primary treatment in particular cases was not reported. As noted above, the degree of stromal anapla-
Vol. 2 No.4 July, 1977
Malignant fibrous histiocytoma of forearm
295
Fig. 3. Reticulin formation commonly seen in these lesions. (Reticulin stain. Original magnification x80.)
sia appeared to be the only histologic factor that correlated with survival. 4 Huvos lO reported a 67% 5-year survival rate in 16 cases arising in bone. The 20-year survival rate was 45%. The lesions arising in bone infarcts appear to be particularly aggressive, and four of the five reported patients died of their tumors.!' 2 The one survivor was treated with an en bloc resection of a proximal femoral lesion. 2 Two of the four who died were treated by amputation and two with radiation. I, 2 Conclusions
The separation of the malignant tumors of the tissue histiocyte from other sarcomatous lesions should enable more accurate data to be gathered on their incidence and biologic behavior. This tumor probably is more common than the older literature would indicate. It appears to be unpredictably aggressive, with metastases occuring widely at any stage. The current practice for such soft tissue sarcomas is wide en bloc resection with treatment of local recurrences as they occur. 3 The malignant fibrous histiocytoma appears to be amenable to such treatment, providing at least a 3 cm margin and one fascial level below the lesion can be taken. If such
a resection compromises the viability or functional usefulness of a limb, primary amputation should be considered seriously. Amputation should be performed if the tumor recurs after an adequate initial wide en bloc resection. Such tumors arising in bone infarcts should be treated aggressively as the potential for metastases seems to be greater than that of malignant fibrous histiocytomas arising in soft tissue. The preoperative study should be thorough, as the possible sites of metastases are unpredictable. Liver, brain, and bone scans should be obtained and arteriography may be useful in assessing local extension, e.g., whether or not major vessels are involved. After operation the patient should be followed for at least 10 years, as metastases may be late in appearing. Since other malignant histiocytic tumors may be multifocal, 11 additional lesions should be watched for as well. Summary
The malignant fibrous histiocytoma is an aggressive lesion originating in the tissue histiocyte. These tumors contain five cell types and in the past often have been grouped with other sarcomas. Wide initial en bloc resection and observation for at least 10 years is recom-
296
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Hubbard and Burton
mended. If there is a local recurrence and no apparent metastases, prompt amputation is advisable.
REFERENCES 1. Michael RH, Dorfman HD , Malignant fibrous histiocytoma associated with bone infarcts. Clin Orthop 118:182,1976 2. Miara lM , Bullough PG, Marcove RC, et al: Malignant fibrous histiocytoma and osteosarcoma in association with bone infarcts . J Bone loint Surg 56-A:932, 1974 3. Shiu M, Castro E, Hayden S, et al: Surgical treatment of 297 soft tissue sarcomas of the lower extremities . Ann Surg 182:597, 1975 4. Soule E, Enriquez P: A typical fibrous histiocytoma, malignant fibrous histiocytoma, malignant histiocytoma , and epithelioid sarcoma. Cancer 30:128, 1972 5. Fu Y, Gabbiani G, Kaye G, et al: Malignant soft tissue tumors of probable histiocytic origin (malignant fibrous histiocytomas): General considerations and electron mi-
6.
7.
8.
9.
10. II .
croscopic and tissue culture studies. Cancer 35: 176, 1975 Kempson R, Kyriakes M: Fibroxanthosarcoma of soft tissues-a type of malignant fibrous histiocytoma. Cancer 29:961, 1972 Stout A, Lattes R: Tumors of the soft tissues , in Atlas of tumor pathology, series 2, fascicle I , Washington, DC , 1967, Armed Forces Institute of Pathology Ozello L, Stout A, Murray M: Cultural characteristics of malignant histiocytomas and fibrous xanthomas. Cancer 16:331, 1963 Feldman F, Norman D: Intra- and extraosseous malignant histiocytoma (malignant fibrous xanthoma). Radiology 104:497-508, 1972 Huvos A: Primary malignant fibrous histiocytoma of bone , NY State J Med 76:4, 552, 1976 Bridges MW: Multifocal malignant histiocytoma . J Clin PathoI 28:825, 1975
Leonard F. Hubbard, M.D., and Richard 1. Burton, M.D., Rochester, N. Y.
Malignant tumors arising from tissue histiocytes are uncommon lesions, and in the reported series the number of cases is too small to have established clear criteria for prognosis and treatment. 1-4 A case of malignant fibrous histiocytoma of the upper extremity is presented with a brief review of the literature and suggested guidelines for the treatment of patients presenting with these tumors. Case presentation M. B., a 50-year-old right-handed Caucasian woman, complained of a slowly enlarging painless mass in the extensor surface of the upper right forearm of approximately 12 months' duration. She did not recall any trauma or infection in the area. An incisional biopsy had been performed, with the resulting diagnosis of malignant fibrous histiocytoma. One week after the initial biopsy, she was referred to the senior surgeon (R. B.) and admitted to the hospital for further diagnosis and treatment. She had been in good health and regularly participated in sports. There were no complaints of pain, erythema, or swelling. The review of systems was normal. Examination showed there was a 2 by 4 cm firm, fixed, non tender mass in the proximal extensor surface of the right forearm. The biopsy site overlying the lesion had healed From the Department of Orthopaedics, University of Rochester Medical Center, Rochester, N. Y. Received for publication Dec. 13, 1976. Revised for publication March 28, 1977. Reprint requests: Leonard F. Hubbard, M.D., Department of Orthopaedics, University of Rochester Medical Center, Rochester, NY 14642.
292
THE JOURNAL OF HAND SURGERY
July, 1977
primarily. Motor and sensory functions of the arm and hand were normal, including wrist and finger extension and the sensory function of the radial nerve. Brain, bone, liver, and spleen scans, as well as a hematological survey were reported as normal. Radiographs of the involved arm showed only soft tissue swelling, without involvement of bone: Under axillary block, an extensive en bloc resection of the tumor was performed. A 3 cm margin, including skin, subcutaneous tissue, and muscles of the extensor compartment to the interosseous membrane was removed. The radial nerve, the extensor carpi radialis longus, and the abductor pollicis longus were outside of the margin of resection and were left in place. The 6 by 10 cm defect left by the excision was covered with a split-thickness skin graft taken from the left thigh under local anesthesia. Postoperative healing was uneventful, and joint motion was maintained by dynamic splinting and an exercise program. Three months later there was no evidence of recurrent or metastatic disease. The prognosis of this tumor was discussed with the patient. She expressed a strong desire to become free of splints and to resume her former activities as soon as possible. The necessary transfers could be done distal to a 3 cm margin from the edge of the previous wide en bloc excision. The flexor carpi ulnaris was transferred to the extensor digitorum communis and the brachioradialis to the extensor pollicis longus. This procedure was complicated by marginal wound necrosis, which healed after local debridement. Eighteen months after the mass first had been noted, and 9 months after the tumor had been excised, there were no apparent local or systemic recurrences. She had 70° of active metacarpophalangeal joint flexion and extension, full active interphalangeal joint motion, and normal wrist and thumb
Vol. 2, No.4, pp. 292-296
Vol. 2 No.4 July, 1977
Malignant fibrous histiocytoma of forearm
293
Fig. 1. Marked whorled hypercellularity and the multiple cell types characteristic of the malignant fibrous histiocytoma. With such marked pleomorphism, the characteristic stromal storiform pattern may be less apparent. Giant cells are frequent. (Hematoxylin and eosin. Original magnification x80.) function. Again she is right-handed, splint free, with essentially normal active use of the hand. Sections from the surgical specimen demonstrated an anaplastic tumor with histiocytes, xanthomatous cells, and spindle-shaped cells (Figs. I and 2). Special stains demonstrated collagen production by spindle cells and the presence of moderate amounts of reticulin (Fig. 3). The sections were reviewed by pathologists at Columbia College of Physicians and Surgeons and at Stanford University, and the diagnosis of malignant fibrous histiocytoma was confirmed.
Discussion
The group of tumors now recognized to originate from the tissue histiocyte has long provoked controversy because of their diversity in morphology and biologic behavior. 5-7 Both benign and malignant tumors are derived from histiocytes, but not until recently in most series have they been separated from other sarcomas. Benign histiocyte lesions include fibrous xanthomas, xanthogranulomas, and giant cell tumors. Malignant giant cell tumors of soft parts, xanthosarcomas, and malignant fibrous xanthomas have been reclassified as malignant histiocyte tumors. 4, 7 This nomenclature recognizes the common cell origin of the tu-
mors, the tissue histiocyte, a cell of multiple potentials. Much of the initial work done in reclassifying these tumors was published by Stout and Lattes. 7 Further work by other authors has clearly differentiated these tumors from other mesenchymal lesions and has established their origin. 5 , 6, 8 The malignant fibrous histiocytoma, relatively common among the histiocytic tumors, probably has been improperly classified often in the past as a fibrosarcoma, pleomorphic rhabdomyosarcoma, or liposarcoma. This confusion arises because of the different cell types present in the same tumor. Four of these tumors were studied by Fu et al. 5 who used the electron microscope. They were able to distinguish five distinct cell types, including histiocyte-like cells, fibroblastlike cells, xanthomatous cells, giant cells, and an undifferentiated cell. Varying amounts of collagen were present in association with the spindle-shaped cells. Tissue culture studies by Ozello, Stout, and Murray 8 previously had suggested the variable potential of the tissue histiocyte. They demonstrated its ability to assume a spindle-shape and to produce collagen and they coined the term "facultative fibroblast." Whether the
294
Hubbard and Burton
The Journal of HAND SURGERY
Fig. 2. Stroma of anaplastic "facultative fibroblasts" and collagen, containing malignant histiocytes, giant cells, and xanthomatous cells. A mitotic figure is also present. (Periodic-acid Schiff stain. Original magnification x200.)
histiocyte becomes transformed, or whether both histiocytes and fibroblast-like cells are derived from a common undifferentiated precursor, is not clear. 5, 8 Malignant fibrous histiocytomas have been reported in other locations, including the extremities, the thorax, and the retroperitoneum. I - 6 Characteristically they develop as asymptomatic masses in extremities during the sixth decade. While most cases have occurred in soft tissue, these tumors also have been reported as primary interosseous lesions_ Huvos collected 18 cases of primary interosseous malignant fibrous histiocytoma reviewed between 1931 and 1974. These were most common in the tibia and distal femur. Nearly all had been diagnosed previously as another tumor type_ 10 Feldman and Norman 9 presented the pathologic and radiologic aspects of 20 cases of malignant histiocytomas with primary or secondary skeletal involvement. Reports have described the occurrence of malignant fibrous histiocytomas apparently arising in bone infarcts .1, 2 These have been the only cases in which the tumors appear to have been associated with reparati ve processes_ Metastases from these tumors occur both by hematogenous and lymphatic routes, and recurrence after
local excision is common. The treatment of choice is either wide en bloc resection or primary amputation. Patients already may have metastatic disease at the time of their initial biopsy, 1, 2 as was seen in a 30-year-old man at our institution who died within 16 months_ The anaplasia of the stromal elements was marked in this case, a finding which Soule and Enriquez4 thought correlated with a poor prognosis_ In general, chemotherapy and radiation therapy have not been helpful in controlling either local or metastatic disease, although short-term responses to actinomycin, Methotrexate, and radiation have been reported. 4, 9, 10 The small numbers make interpretation of figures on survival difficult. In Soule and Enriquez'4 series, a 65% 5-year survival rate was attained in 33 patients with malignant fibrous histiocytoma, with eight of the 20 survivors having tumor recurrence at the time of the report. The 10 year survival rate was 38%. Seven patients initially had local excisions without recurrences, whereas 15 others treated this way had recurrences_ Amputation was a secondary procedure in three patients, and two of these died_ The criteria used for choice of primary treatment in particular cases was not reported. As noted above, the degree of stromal anapla-
Vol. 2 No.4 July, 1977
Malignant fibrous histiocytoma of forearm
295
Fig. 3. Reticulin formation commonly seen in these lesions. (Reticulin stain. Original magnification x80.)
sia appeared to be the only histologic factor that correlated with survival. 4 Huvos lO reported a 67% 5-year survival rate in 16 cases arising in bone. The 20-year survival rate was 45%. The lesions arising in bone infarcts appear to be particularly aggressive, and four of the five reported patients died of their tumors.!' 2 The one survivor was treated with an en bloc resection of a proximal femoral lesion. 2 Two of the four who died were treated by amputation and two with radiation. I, 2 Conclusions
The separation of the malignant tumors of the tissue histiocyte from other sarcomatous lesions should enable more accurate data to be gathered on their incidence and biologic behavior. This tumor probably is more common than the older literature would indicate. It appears to be unpredictably aggressive, with metastases occuring widely at any stage. The current practice for such soft tissue sarcomas is wide en bloc resection with treatment of local recurrences as they occur. 3 The malignant fibrous histiocytoma appears to be amenable to such treatment, providing at least a 3 cm margin and one fascial level below the lesion can be taken. If such
a resection compromises the viability or functional usefulness of a limb, primary amputation should be considered seriously. Amputation should be performed if the tumor recurs after an adequate initial wide en bloc resection. Such tumors arising in bone infarcts should be treated aggressively as the potential for metastases seems to be greater than that of malignant fibrous histiocytomas arising in soft tissue. The preoperative study should be thorough, as the possible sites of metastases are unpredictable. Liver, brain, and bone scans should be obtained and arteriography may be useful in assessing local extension, e.g., whether or not major vessels are involved. After operation the patient should be followed for at least 10 years, as metastases may be late in appearing. Since other malignant histiocytic tumors may be multifocal, 11 additional lesions should be watched for as well. Summary
The malignant fibrous histiocytoma is an aggressive lesion originating in the tissue histiocyte. These tumors contain five cell types and in the past often have been grouped with other sarcomas. Wide initial en bloc resection and observation for at least 10 years is recom-
296
The Journal of HAND SURGERY
Hubbard and Burton
mended. If there is a local recurrence and no apparent metastases, prompt amputation is advisable.
REFERENCES 1. Michael RH, Dorfman HD , Malignant fibrous histiocytoma associated with bone infarcts. Clin Orthop 118:182,1976 2. Miara lM , Bullough PG, Marcove RC, et al: Malignant fibrous histiocytoma and osteosarcoma in association with bone infarcts . J Bone loint Surg 56-A:932, 1974 3. Shiu M, Castro E, Hayden S, et al: Surgical treatment of 297 soft tissue sarcomas of the lower extremities . Ann Surg 182:597, 1975 4. Soule E, Enriquez P: A typical fibrous histiocytoma, malignant fibrous histiocytoma, malignant histiocytoma , and epithelioid sarcoma. Cancer 30:128, 1972 5. Fu Y, Gabbiani G, Kaye G, et al: Malignant soft tissue tumors of probable histiocytic origin (malignant fibrous histiocytomas): General considerations and electron mi-
6.
7.
8.
9.
10. II .
croscopic and tissue culture studies. Cancer 35: 176, 1975 Kempson R, Kyriakes M: Fibroxanthosarcoma of soft tissues-a type of malignant fibrous histiocytoma. Cancer 29:961, 1972 Stout A, Lattes R: Tumors of the soft tissues , in Atlas of tumor pathology, series 2, fascicle I , Washington, DC , 1967, Armed Forces Institute of Pathology Ozello L, Stout A, Murray M: Cultural characteristics of malignant histiocytomas and fibrous xanthomas. Cancer 16:331, 1963 Feldman F, Norman D: Intra- and extraosseous malignant histiocytoma (malignant fibrous xanthoma). Radiology 104:497-508, 1972 Huvos A: Primary malignant fibrous histiocytoma of bone , NY State J Med 76:4, 552, 1976 Bridges MW: Multifocal malignant histiocytoma . J Clin PathoI 28:825, 1975
