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Squamous Cell Carcinoma Complicating Chronic Osteomyelitis in a Toe: A Case Report and Review of the Literature Robert J. Ziets, M.D.,* Phillip M. Evanski, M.D., p.e.,t Ralph Lusskin, M.D., p.e.,:j: and Michael Lee, M.D., Ph.D.§ New York, New York
CASE REPORT
ABSTRACT Squamous cell carcinoma arising from chronic osteomyelitis is uncommon. Although the majority of cases occur in the lower extremity, incidence in the foot is relatively rare, and in the toe, exceptional. This report illustrates a particularly unusual incidence of squamous cell carcinoma complicating chronic osteomyelitis of the hallux. Guidelines for early diagnosis, recommendations for treatment, and prognostic data are included.
A 46-year-old white male presented with a 5-year history of progressive drainage and sepsis of the first ray of his right foot. Approximately 5 years earlier, the patient had a callus removed from the plantar surface of his right foot at the level of the first metatarsal head. Although the wound healed uneventfully, he developed a tender "cyst" on the dorsum of the first web space about 4 months later. Upon surgical excision, purulent drainage was obtained. The wound closed after a short course of oral antibiotics and dressing changes. Several months later, the patient spontaneously developed pain in the great toe, which became acutely swollen and subsequently began to drain. The infection became chronic and the patient was treated with multiple courses of oral and intravenous antibiotics. A diagnosis of osteomyelitis was made, and he subsequently underwent 15 surgical procedures, including multiple debridements about the first metatarsophalangeal joint. In May 1990, the patient complained of a painful and draining great toe despite ciprofloxacin and dicloxacillin (2000 mg/day each). Physical examination revealed a foreshortened right hallux with draining sinuses at the base, skin discoloration, and multiple scars (Fig. 1). Pulses were good, and the patient appeared healthy otherwise. On radiographs, the postsurgical changes at the first metatarsophalangeal joint level, a lytic zone in the distal phalanx, and soft tissue swelling of the hallux were noted (Fig. 2). Later films showed further demineralization in the distal phalanx. The patient underwent two surgical debridements at our institution over a 2-month period. Cultures grew Staphylococcus aureus, as well as Acinetobacter and Peptostreptococcus species, and he was treated with appropriate intravenous antibiotics. Pathological specimens revealed only chronic osteomyelitis.
Malignant transformation in chronic osteomyelitic foci is not common but is well documented. Squamous cell carcinoma is the most common malignancy reported, with an incidence of 0.2% to 1.7% in chronic osteomyelitis. 1 ,4 ,s ,8,12 ,13 ,16 More than 85% of such cases occur in the lower extremity,":" most often in the tibia. The incidence in the foot is approximately 7% of the cases reported," with the majority located in the os calcis. A review of the literature since 1940 reveals only 25 reported cases of squamous cell carcinoma arising from chronic osteomyelitis in the foot. 3- 6 •1o ,16 Of these, only two were in a toe. 3 ,6 There have been two additional cases of squamous cell carcinoma arising in the toe without preceding osteomyelitis." Another study reported nine cases of squamous cell carcinoma in the foot without specifying the etiology or exact location." The case presented here, the third report of the lesion arising in a toe, illustrates the insidious nature of malignant degeneration and the difficulty in clinical diagnosis. Department of Orthopaedic Surgery, New York University School of Medicine, New York, New York . • Resident, New York University School of Medicine, New York, New York. To whom requests for reprints should be addressed, at Department of Orthopaedic Surgery, New York University of Medicine, 550 First Ave., New York, New York 10016. t Associate Professor of Orthopaedic Surgery, New York University School of Medicine. :j:Professor of Clinical Orthopaedic Surgery, New York University School of Medicine. § Instructor, Department of Pathology, New York University School of Medicine.
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Fig. 1. Right foot: the hallux is foreshortened with draining sinuses at its base. Skin discoloration and multiple scars are seen.
Despite this treatment, the patient's wounds failed to heal. Upon a third debridement in July 1990, the hallux appeared necrotic and amputation was performed. It was this specimen from which a pathological diagnosis of squamous cell carcinoma was made. Histologically, the carcinoma was found to be occupying the toe stump and invading the plantar fascia adjacent to the first metatarsal bone. The maximal dimensions of the tumor were 6 x 2 x 2 cm (Fig. 3). Microscopically, features of a well-differentiated squamous cell carcinoma were exhibited, i.e., cytoplasmic keratinization and squamous pearl formation. The lesion invaded the adjacent tissue with a bulbous, "pushing" margin and was surrounded by a dense lymphocytic infiltrate (fig. 4). Two weeks later, a Lisfranc amputation through the cuneiform and cuboid bones was performed, the 21st surgical procedure on this foot. The Achilles tendon was sectioned to prevent equinus. The wound, closed primarily, healed without incident. No lymphadenopathy was detected, and computed tomography of the chest was negative. The patient was fitted with a temporary fiberglass prosthesis. Nine months following amputation, he was fully ambulatory and doing well.
Fig. 2. Anteroposterior radiograph of right hallux. Postsurgical changes at the first metatarsophalangeal joint level and soft tissue swelling are seen. Note the lytic zone in the distal phalanx. Later films showed further demineralization in the distal phalanx.
DISCUSSION
In 1828, Jean-Nicholas Marjolin was the first to recognize the occurrence of malignant changes in old ulcers.' It was Hawkins in 1835 who gave the first accurate description of carcinoma arising in chronic osteomyelitis." Prognosis was thought to be good, as no deaths were reported in a review of 51 patients by Benedict in 1931.' However, nodal metastasis was reported by Henderson and Swart in 1936. 7 In the same year, Hellner reported the first case of pulmonary metastasis."
Fig. 3. Cross-section of gross specimen. The carcinoma occupies the toe stump and invades the plantar fascia adjacent to the first metatarsal bone. The maximal dimensions of the tumor were 6 x 2 x 2cm.
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Fig. 4. Microscopic specimen (low power). Well-differentiated squamous cell carcinoma showing bulbous, "pushing" margins is seen. Note the dense lymphocytic infiltrate surrounding the lesion,
Of malignancies developing in chronic osteomyelitic foci, squamous cell carcinoma is by far the most common (85% to 89%), with a wide variety of sarcomas making up the remainder. 4 ,5 ,15 ,16 Interestingly, the cell types found in these sarcomas are usually related to those found in the granulation tissue of the fistular tract. Squamous cell (epidermoid) carcinoma is a tumor of epidermal origin. It occurs primarily on the skin and mucous membranes, mostly in Caucasians and in males (3:1 male to female ratio). In addition to osteomyelitic sinuses, squamous cell carcinoma may develop from premalignant lesions, such as actinic keratoses, old burns or scars, certain ulcers, radiation dermatitis, arsenical keratoses, or as a result of contact with toxins (e.g., nitrates)." When associated with chronic osteomyelitis, squamous cell carcinoma arises from somewhere along the draining fistula. The duration of infection prior to the development of squamous cell carcinoma is usually long. In one of the largest reviews, the mean latency was 30.5 years, with a mean age at diagnosis of 54.6 years." Although the patient in this case report is relatively young with a short duration of infection, shorter latencies (less than 18 months) have been reported. The pathogenesis of malignant transformation remains unclear. It appears that osteomyelitic exudates have a carcinogenic action on the sinus tract epithelium during the reparative process. Obviously, other poorly understood factors are involved, accounting for the rare incidence of malignancy in patients with chronic osteomyelitis and the wide range of latent periods reported.
The case reported here illustrates the difficulty that may be encountered in diagnosing malignant transformation, especially in lesions that develop deeply. In this patient, multiple specimens obtained surgically failed to reveal the pathology. Interestingly, microscopic examination of the sinus tracts at the first metatarsophalangeal joint level showed no evidence of malignancy less than 2 months prior to its detection in the hallux following amputation. Physicians treating patients with chronic osteomyelitis should be suspicious if any of the signs or symptoms that may herald neoplastic degeneration develop. These include an enlarging mass, foul odor or an increased quantity of discharge or bleeding, a change in bacterial flora (often replacement of S. aureus by a predominantly mixed population of Gram-negative flora), an abrupt deterioration in long-standing clinical symptoms (e.g., increased pain), and lesions unresponsive to conventional therapy. Radiographic evidence of malignant degeneration is usually lacking, and differentiating between infection and neoplasm is often impossible. However, progressive radiolucency, lytic bone lesions, or more pronounced bone destruction may become evident. Sometimes, the bone destruction may occur very rapidly." Although computed tomography and magnetic resonance imaging may have some value as staging studies, they are incapable of distinguishing between granuloma and tumor. Early biopsy is indicated whenever malignant degeneration is suspected. Meticulous deep biopsy of multiple sites is recommended. Unfortunately, local biopsy may
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be falsely negative in up to 75% of cases," as illustrated in the case presented here. Once the diagnosis of squamous cell carcinoma is made, the treatment of choice is amputation. Local excision or inadequate amputation may be followed by stump recurrence" and a mortality rate as high as 50%.9 Wide local excision has been recommended only in grade I or very small lesions that can be radically
excised." Although squamous cell carcinoma arising from chronic osteomyelitis is usually low grade and well differentiated, there is little correlation between tumor grading and proqnosls." A recent review of 127 cases followed for at least 18 months after diagnosis found a 30% rate of metastasis, leading to rapid death in 74% of these patients. Although most metastases are to regional lymph nodes, distant metastases have been reported (in distant lymph nodes, liver, lung, and kidney),2,6,16 with an incidence of 14.4%.18 When metastasis does occur, it is usually early. No cases have been reported later than 3 years after amputation.'? Sedlin and Fleming16 found that nearly all metastases appeared within 18 months of diagnosis and stated that patients who survive 3 years after amputation without metastasis have a good prognosis. Biopsy of enlarged lymph nodes at the time of amputation, followed by lymphadenectomy and irradiation if positive, has been recommended by some authors. 5,15,29 Prophylatic node irradiation for grade 1/ and 1/1 lesions has also been suqqested.":" Others have indicated biopsy of lymph nodes only if they enlarge, persist, or become paintul." In noting that regional lymph node enlargement is usually inflammatory and subsides after amputation, Fitzgerald et at." have recommended biopsy only if the nodes persist for 3 months after surgery. Squamous cell carcinoma arising from chronic osteomyelitis is a rare event in the toe, this being the third reported case. Clinicians must have a high index of suspicion in order to make this often difficult diagnosis.
181
REFERENCES 1. Benedict, E.B.: Carcinoma in osteomyelitis. Surg, Gynecol. Obstet., 53:1-11, 1979. 2. Bereston, E.E., and Ney, C.: Squamous cell carcinoma arising in a chronic osteomyelitic sinus tract with metastasis. Arch. Surg., 43:257-268, 1941. 3. Cappello, J.C., and Donick, 1.1.: Squamous cell carcinoma as a complication of chronic osteomyelitis. J. Foot Surg., 20:136141,1981. 4. Fitzgerald, R.H., Brewer, N.S., and Dahlin, D.C.: Squamouscell carcinoma complicating chronic osteomyelitis. J. Bone Joint Surg., 58A:1146-1148, 1976. 5. Giunti, A., and Laus, M.: Malignant tumours in chronic osteomyelitis. (A report of thirty nine cases, twenty six with long term follow up.) Ital. J. Orthop. Traumatol., 4:171-182,1978. 6. Hejna, W.F.: Squamous-cell carcinoma developing in the chronic draining sinuses of osteomyelitis. Cancer, 18:128-132, 1965. 7. Henderson, M.S., and Swart, H.A.: Chronic osteomyelitis associated with malignancy. J. Bone Joint Surg., 18:56-60, 1936. 8. Hobart, M.H., and Miller, D.S.: Unusual complications of osteomyelitis. Am. J. Surg., 45:53-59,1939. 9. Johnson, L.L., and Kempson, R.L.: Epidermoid carcinoma in chronic osteomyelitis: diagnostic problems and management. J. Bone Joint Surg., 47A:133-145, 1965. 10. Lidgren, L.: Neoplasia in chronic fistulating osteitis. Acta Orthop. Scand., 44:152-156,1973. 11. Lifeso, R.M., and BUll, C.A.: Squamous cell carcinoma of the extremities. Cancer, 55:2862-2867, 1985. 12. Lovell, W.W., King, R.E., and Alldredge, R.: Carcinoma in skin, sinuses and bone following chronic osteomyelitis. South Med. J., 50:266-271,1957. 13. McNally, A.K., and Dockerty, M.B.: Carcinoma developing in chronic draining cutaneous sinuses and fistulas. Surg. Gynecol. Obstet., 88:87-96,1949. 14. Patel, A., Ryan, J.F., Badrinath, K., and Chen, S.C.: Squamous cell carcinoma of the toe masquerading as osteomyelitis. J. R. Soc. Med., 81:418-420,1981. 15. Sankaran-KuUy, M., Corea, J.R., Ali, M.S., and KuUy, M.K.: Squamous cell carcinoma in chronic osteomyelitis. Report of a case and review of the literature. Clin. Orthop., 198:264-267, 1985. 16. Sedlin, E.D., and Fleming, J.L.: Epidermoid carcinoma arising in chronic osteomyelitic foci. J. Bone Joint Surg., 45A:827-838, 1963. 17. Taylor, G.W., Nathanson, I.T., and Shaw, D.T.: Epidermoid carcinoma of the extremities with reference to lymph node involvement. Ann. Surg., 113:268-275, 1941. 18. Vishniavsky, S.: Squamous cell carcinoma in sinus tract of chronic osteomyelitis. Va. Med. Mon., 97:645-650, 1970.
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Squamous Cell Carcinoma Complicating Chronic Osteomyelitis in a Toe: A Case Report and Review of the Literature Robert J. Ziets, M.D.,* Phillip M. Evanski, M.D., p.e.,t Ralph Lusskin, M.D., p.e.,:j: and Michael Lee, M.D., Ph.D.§ New York, New York
CASE REPORT
ABSTRACT Squamous cell carcinoma arising from chronic osteomyelitis is uncommon. Although the majority of cases occur in the lower extremity, incidence in the foot is relatively rare, and in the toe, exceptional. This report illustrates a particularly unusual incidence of squamous cell carcinoma complicating chronic osteomyelitis of the hallux. Guidelines for early diagnosis, recommendations for treatment, and prognostic data are included.
A 46-year-old white male presented with a 5-year history of progressive drainage and sepsis of the first ray of his right foot. Approximately 5 years earlier, the patient had a callus removed from the plantar surface of his right foot at the level of the first metatarsal head. Although the wound healed uneventfully, he developed a tender "cyst" on the dorsum of the first web space about 4 months later. Upon surgical excision, purulent drainage was obtained. The wound closed after a short course of oral antibiotics and dressing changes. Several months later, the patient spontaneously developed pain in the great toe, which became acutely swollen and subsequently began to drain. The infection became chronic and the patient was treated with multiple courses of oral and intravenous antibiotics. A diagnosis of osteomyelitis was made, and he subsequently underwent 15 surgical procedures, including multiple debridements about the first metatarsophalangeal joint. In May 1990, the patient complained of a painful and draining great toe despite ciprofloxacin and dicloxacillin (2000 mg/day each). Physical examination revealed a foreshortened right hallux with draining sinuses at the base, skin discoloration, and multiple scars (Fig. 1). Pulses were good, and the patient appeared healthy otherwise. On radiographs, the postsurgical changes at the first metatarsophalangeal joint level, a lytic zone in the distal phalanx, and soft tissue swelling of the hallux were noted (Fig. 2). Later films showed further demineralization in the distal phalanx. The patient underwent two surgical debridements at our institution over a 2-month period. Cultures grew Staphylococcus aureus, as well as Acinetobacter and Peptostreptococcus species, and he was treated with appropriate intravenous antibiotics. Pathological specimens revealed only chronic osteomyelitis.
Malignant transformation in chronic osteomyelitic foci is not common but is well documented. Squamous cell carcinoma is the most common malignancy reported, with an incidence of 0.2% to 1.7% in chronic osteomyelitis. 1 ,4 ,s ,8,12 ,13 ,16 More than 85% of such cases occur in the lower extremity,":" most often in the tibia. The incidence in the foot is approximately 7% of the cases reported," with the majority located in the os calcis. A review of the literature since 1940 reveals only 25 reported cases of squamous cell carcinoma arising from chronic osteomyelitis in the foot. 3- 6 •1o ,16 Of these, only two were in a toe. 3 ,6 There have been two additional cases of squamous cell carcinoma arising in the toe without preceding osteomyelitis." Another study reported nine cases of squamous cell carcinoma in the foot without specifying the etiology or exact location." The case presented here, the third report of the lesion arising in a toe, illustrates the insidious nature of malignant degeneration and the difficulty in clinical diagnosis. Department of Orthopaedic Surgery, New York University School of Medicine, New York, New York . • Resident, New York University School of Medicine, New York, New York. To whom requests for reprints should be addressed, at Department of Orthopaedic Surgery, New York University of Medicine, 550 First Ave., New York, New York 10016. t Associate Professor of Orthopaedic Surgery, New York University School of Medicine. :j:Professor of Clinical Orthopaedic Surgery, New York University School of Medicine. § Instructor, Department of Pathology, New York University School of Medicine.
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Fig. 1. Right foot: the hallux is foreshortened with draining sinuses at its base. Skin discoloration and multiple scars are seen.
Despite this treatment, the patient's wounds failed to heal. Upon a third debridement in July 1990, the hallux appeared necrotic and amputation was performed. It was this specimen from which a pathological diagnosis of squamous cell carcinoma was made. Histologically, the carcinoma was found to be occupying the toe stump and invading the plantar fascia adjacent to the first metatarsal bone. The maximal dimensions of the tumor were 6 x 2 x 2 cm (Fig. 3). Microscopically, features of a well-differentiated squamous cell carcinoma were exhibited, i.e., cytoplasmic keratinization and squamous pearl formation. The lesion invaded the adjacent tissue with a bulbous, "pushing" margin and was surrounded by a dense lymphocytic infiltrate (fig. 4). Two weeks later, a Lisfranc amputation through the cuneiform and cuboid bones was performed, the 21st surgical procedure on this foot. The Achilles tendon was sectioned to prevent equinus. The wound, closed primarily, healed without incident. No lymphadenopathy was detected, and computed tomography of the chest was negative. The patient was fitted with a temporary fiberglass prosthesis. Nine months following amputation, he was fully ambulatory and doing well.
Fig. 2. Anteroposterior radiograph of right hallux. Postsurgical changes at the first metatarsophalangeal joint level and soft tissue swelling are seen. Note the lytic zone in the distal phalanx. Later films showed further demineralization in the distal phalanx.
DISCUSSION
In 1828, Jean-Nicholas Marjolin was the first to recognize the occurrence of malignant changes in old ulcers.' It was Hawkins in 1835 who gave the first accurate description of carcinoma arising in chronic osteomyelitis." Prognosis was thought to be good, as no deaths were reported in a review of 51 patients by Benedict in 1931.' However, nodal metastasis was reported by Henderson and Swart in 1936. 7 In the same year, Hellner reported the first case of pulmonary metastasis."
Fig. 3. Cross-section of gross specimen. The carcinoma occupies the toe stump and invades the plantar fascia adjacent to the first metatarsal bone. The maximal dimensions of the tumor were 6 x 2 x 2cm.
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Fig. 4. Microscopic specimen (low power). Well-differentiated squamous cell carcinoma showing bulbous, "pushing" margins is seen. Note the dense lymphocytic infiltrate surrounding the lesion,
Of malignancies developing in chronic osteomyelitic foci, squamous cell carcinoma is by far the most common (85% to 89%), with a wide variety of sarcomas making up the remainder. 4 ,5 ,15 ,16 Interestingly, the cell types found in these sarcomas are usually related to those found in the granulation tissue of the fistular tract. Squamous cell (epidermoid) carcinoma is a tumor of epidermal origin. It occurs primarily on the skin and mucous membranes, mostly in Caucasians and in males (3:1 male to female ratio). In addition to osteomyelitic sinuses, squamous cell carcinoma may develop from premalignant lesions, such as actinic keratoses, old burns or scars, certain ulcers, radiation dermatitis, arsenical keratoses, or as a result of contact with toxins (e.g., nitrates)." When associated with chronic osteomyelitis, squamous cell carcinoma arises from somewhere along the draining fistula. The duration of infection prior to the development of squamous cell carcinoma is usually long. In one of the largest reviews, the mean latency was 30.5 years, with a mean age at diagnosis of 54.6 years." Although the patient in this case report is relatively young with a short duration of infection, shorter latencies (less than 18 months) have been reported. The pathogenesis of malignant transformation remains unclear. It appears that osteomyelitic exudates have a carcinogenic action on the sinus tract epithelium during the reparative process. Obviously, other poorly understood factors are involved, accounting for the rare incidence of malignancy in patients with chronic osteomyelitis and the wide range of latent periods reported.
The case reported here illustrates the difficulty that may be encountered in diagnosing malignant transformation, especially in lesions that develop deeply. In this patient, multiple specimens obtained surgically failed to reveal the pathology. Interestingly, microscopic examination of the sinus tracts at the first metatarsophalangeal joint level showed no evidence of malignancy less than 2 months prior to its detection in the hallux following amputation. Physicians treating patients with chronic osteomyelitis should be suspicious if any of the signs or symptoms that may herald neoplastic degeneration develop. These include an enlarging mass, foul odor or an increased quantity of discharge or bleeding, a change in bacterial flora (often replacement of S. aureus by a predominantly mixed population of Gram-negative flora), an abrupt deterioration in long-standing clinical symptoms (e.g., increased pain), and lesions unresponsive to conventional therapy. Radiographic evidence of malignant degeneration is usually lacking, and differentiating between infection and neoplasm is often impossible. However, progressive radiolucency, lytic bone lesions, or more pronounced bone destruction may become evident. Sometimes, the bone destruction may occur very rapidly." Although computed tomography and magnetic resonance imaging may have some value as staging studies, they are incapable of distinguishing between granuloma and tumor. Early biopsy is indicated whenever malignant degeneration is suspected. Meticulous deep biopsy of multiple sites is recommended. Unfortunately, local biopsy may
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be falsely negative in up to 75% of cases," as illustrated in the case presented here. Once the diagnosis of squamous cell carcinoma is made, the treatment of choice is amputation. Local excision or inadequate amputation may be followed by stump recurrence" and a mortality rate as high as 50%.9 Wide local excision has been recommended only in grade I or very small lesions that can be radically
excised." Although squamous cell carcinoma arising from chronic osteomyelitis is usually low grade and well differentiated, there is little correlation between tumor grading and proqnosls." A recent review of 127 cases followed for at least 18 months after diagnosis found a 30% rate of metastasis, leading to rapid death in 74% of these patients. Although most metastases are to regional lymph nodes, distant metastases have been reported (in distant lymph nodes, liver, lung, and kidney),2,6,16 with an incidence of 14.4%.18 When metastasis does occur, it is usually early. No cases have been reported later than 3 years after amputation.'? Sedlin and Fleming16 found that nearly all metastases appeared within 18 months of diagnosis and stated that patients who survive 3 years after amputation without metastasis have a good prognosis. Biopsy of enlarged lymph nodes at the time of amputation, followed by lymphadenectomy and irradiation if positive, has been recommended by some authors. 5,15,29 Prophylatic node irradiation for grade 1/ and 1/1 lesions has also been suqqested.":" Others have indicated biopsy of lymph nodes only if they enlarge, persist, or become paintul." In noting that regional lymph node enlargement is usually inflammatory and subsides after amputation, Fitzgerald et at." have recommended biopsy only if the nodes persist for 3 months after surgery. Squamous cell carcinoma arising from chronic osteomyelitis is a rare event in the toe, this being the third reported case. Clinicians must have a high index of suspicion in order to make this often difficult diagnosis.
181
REFERENCES 1. Benedict, E.B.: Carcinoma in osteomyelitis. Surg, Gynecol. Obstet., 53:1-11, 1979. 2. Bereston, E.E., and Ney, C.: Squamous cell carcinoma arising in a chronic osteomyelitic sinus tract with metastasis. Arch. Surg., 43:257-268, 1941. 3. Cappello, J.C., and Donick, 1.1.: Squamous cell carcinoma as a complication of chronic osteomyelitis. J. Foot Surg., 20:136141,1981. 4. Fitzgerald, R.H., Brewer, N.S., and Dahlin, D.C.: Squamouscell carcinoma complicating chronic osteomyelitis. J. Bone Joint Surg., 58A:1146-1148, 1976. 5. Giunti, A., and Laus, M.: Malignant tumours in chronic osteomyelitis. (A report of thirty nine cases, twenty six with long term follow up.) Ital. J. Orthop. Traumatol., 4:171-182,1978. 6. Hejna, W.F.: Squamous-cell carcinoma developing in the chronic draining sinuses of osteomyelitis. Cancer, 18:128-132, 1965. 7. Henderson, M.S., and Swart, H.A.: Chronic osteomyelitis associated with malignancy. J. Bone Joint Surg., 18:56-60, 1936. 8. Hobart, M.H., and Miller, D.S.: Unusual complications of osteomyelitis. Am. J. Surg., 45:53-59,1939. 9. Johnson, L.L., and Kempson, R.L.: Epidermoid carcinoma in chronic osteomyelitis: diagnostic problems and management. J. Bone Joint Surg., 47A:133-145, 1965. 10. Lidgren, L.: Neoplasia in chronic fistulating osteitis. Acta Orthop. Scand., 44:152-156,1973. 11. Lifeso, R.M., and BUll, C.A.: Squamous cell carcinoma of the extremities. Cancer, 55:2862-2867, 1985. 12. Lovell, W.W., King, R.E., and Alldredge, R.: Carcinoma in skin, sinuses and bone following chronic osteomyelitis. South Med. J., 50:266-271,1957. 13. McNally, A.K., and Dockerty, M.B.: Carcinoma developing in chronic draining cutaneous sinuses and fistulas. Surg. Gynecol. Obstet., 88:87-96,1949. 14. Patel, A., Ryan, J.F., Badrinath, K., and Chen, S.C.: Squamous cell carcinoma of the toe masquerading as osteomyelitis. J. R. Soc. Med., 81:418-420,1981. 15. Sankaran-KuUy, M., Corea, J.R., Ali, M.S., and KuUy, M.K.: Squamous cell carcinoma in chronic osteomyelitis. Report of a case and review of the literature. Clin. Orthop., 198:264-267, 1985. 16. Sedlin, E.D., and Fleming, J.L.: Epidermoid carcinoma arising in chronic osteomyelitic foci. J. Bone Joint Surg., 45A:827-838, 1963. 17. Taylor, G.W., Nathanson, I.T., and Shaw, D.T.: Epidermoid carcinoma of the extremities with reference to lymph node involvement. Ann. Surg., 113:268-275, 1941. 18. Vishniavsky, S.: Squamous cell carcinoma in sinus tract of chronic osteomyelitis. Va. Med. Mon., 97:645-650, 1970.
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