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Metastatic Adenosquamous Carcinoma of the Foot: A Case Report
The Journal of Foot & Ankle Surgery 51 (2012) 345–351
Contents lists available at ScienceDirect
The Journal of Foot & Ankle Surgery journal homepage: www.jfas.org
Metastatic Adenosquamous Carcinoma of the Foot: A Case Report Jennifer Trinidad, DPM 1, David Kaplansky, DPM 1, Vincent Nerone, DPM 2, Kevin Springer, DPM 2 1 2
Podiatrist, Private Practice, Columbus, OH Podiatry Resident, Department of Orthopedics, The Ohio State University, Columbus, OH
a r t i c l e i n f o
a b s t r a c t
Level of Clinical Evidence: 4 Keywords: acrometastasis biopsy cancer gout metatarsal metastasis metastatic non–small cell lung carcinoma
Metastasis of carcinoma to the bones of the foot is rare and carries with it a very poor prognosis for patients. Acrometastasis can be the initial manifestation of an occult cancer or widespread metastasis of a previously diagnosed cancer. A high level of suspicion and timely diagnosis are essential to the timely diagnosis and treatment of this condition. In this report, a case of metastatic non–small cell lung carcinoma to the first metatarsal, intially diagnosed as acute gout, is presented. Ó 2012 by the American College of Foot and Ankle Surgeons. All rights reserved.
Metastatic bone tumors are much more common than primary bone tumors. In fact, the chance that a solitary bone lesion in a patient is a metastatic carcinoma in a patient older than 40 years of age is about 500 times higher than the chance that the tumor is a primary bone tumor (1). However, metastasis distal to the knee or elbow, especially in the hand or foot, is quite a rare finding. Leeson et al looked at 827 autopsies of patients who had cancer and found 7% (57 subjects) had metastasis distal to the knee or elbow. The same study found only a 1.7% incidence in the hand or foot (2). Other studies in living patients have shown an incidence of acrometastasis to be 0.007% to 0.3% (3–6). Because of the rarity of acrometastases, especially as the presenting lesion, it is often misdiagnosed as a more benign condition. The first case of bony metastasis to the foot was in a metatarsal bone and was reported by Bloodgood in 1920 (4). The rare incidence is believed to be due to the lack of red marrow in these bones as well as a further distance from the primary cancer site. The exact mechanism of metastases to the foot is uncertain, and some believe it to be due to valveless paravertebral venous plexuses (Batson’s plexuses), which allow retrograde tumor cell embolization through the iliofemoral venous system. Others believe tumor cells settle in regions of trauma and increased arterial flow, because there has been documentation of a ratio of 2:1 in the dominant hand (4). Zindrick et al found that the most common sources for acrometastases to the foot are the colon and genitourinary tract, both of Financial Disclosure: None reported. Conflict of Interest: None reported. Address correspondence to: Vincent Nerone, DPM, Podiatry Resident, Department of Orthopaedics, 4118 Cramblett Hall, 456 West 10th Avenue, Columbus, OH 432101240. E-mail address: [email protected] (V. Nerone).
which are subdiaphragmatic (7). Libson et al also found that subdiaphragmatic sources were more common to involve the foot (6). There have been reports of sinonasal carcinoma, renal cell carcinoma, transitional cell carcinoma of the bladder, endometrial adenocarcinoma, uterine carcinoma, lung cancer, breast carcinoma, prostate carcinoma, rectal carcinoma, and colon carcinoma all metastasizing to the bones of the foot (8–22). With continuously improving cancer treatments and patient lifespan increasing, the foot and ankle specialist must maintain a high clinical suspicion for acrometastasis to the foot. Misdiagnosis for more benign conditions such as gout, infection, osteomyelitis, septic arthritis, or inflammatory arthritides may affect patient outcome. We present a case of non–small cell lung carcinoma metastasis to the metatarsal that was originally misdiagnosed as gout. Case Report A 67-year-old non–insulin-dependent man with diabetes presented to the clinic with a chief complaint of right foot pain, swelling, and redness surrounding his right first metatarsophalangeal joint for the past 8 weeks. The patient had a 37 year history of intermittent gouty arthritis and was on allopurinol for the past few years. Before presentation to our clinic, the patient was being treated for an acute gout attack with indomethacin for 6 weeks by his primary care physician. He was referred to us because his symptoms had not improved and had actually worsened. The patient stated that this was the “worst gout attack that he had ever had.” After reviewing the patient’s medical history, it was also important to note that he had non–small cell lung carcinoma, and had a large tumor removed just 4 months previously from his right upper lung lobe that required wide resection. Now he was currently undergoing radiation therapy. He
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reported close follow-up with his oncologist. He had quit smoking but had a 78-pack-year smoking history. He did report a recent 30-pound weight loss, diarrhea, shortness of breath, malaise, and fatigue on his review of systems as well as severe right foot pain. On physical examination, he was a 5-foot, 8-inch, 146-pound man. The patient had exquisite pain surrounding the right first metatarsophalangeal joint, and range of motion was severely limited. There was surrounding erythema, warmth, and edema. On palpation of the area, there were no discrete masses noted. Range of motion of the ankles, knees, and hips were full and pain free. There were no palpable popliteal or inguinal lymph nodes noted. Standard radiographs of the right foot showed osteolysis of the entire first metatarsal head as well as the base of the first proximal phalanx with complete destruction of the first metatarsophalangeal joint and subchondral bone plate (Figs. 1–3). Differential diagnoses were osteomyelitis, septic arthritis, gout, primary bone tumor, and metastatic carcinoma. The patient was actively being treated for cancer, so he was immediately referred to the orthopedic oncology department for further evaluation and likely biopsy. His oncologist was also contacted. Orthopedic oncology ordered a computerized tomography (CT)–guided biopsy of the area. A full-body Technetium-99m methylene diphosphonate or Positron emission tomography–CT scan was not performed, because the likely source of the metastasis was already known, and a biopsy of this site had a low likelihood of complications. Immunohistochemical stains were performed by the pathology department, which showed cells that were positive for pancytokeratin-AE1/3, CK5/6, p63, CK7 and negative for CK20 and thyroid transcription factor-1, consistent with metastatic squamous cell carcinoma and with the patient’s known non–small cell lung carcinoma (Figs. 4 and 5). At his follow-up appointment with orthopedic oncology, the patient could no longer bear any weight on his forefoot. There was
now a palpable mass in the forefoot. The patient also complained of pain in the proximal right tibia. Plain films of the right tibia showed a small, 1-cm diameter lytic lesion in the proximal tibial epiphysis. It was decided to proceed with magnetic resonance imaging (MRI) of the foot to show the extent of the mass. The MRI showed a large mass in the medial aspect of the forefoot. There was marked destruction of the distal one half of the first metatarsal bone and proximal aspect of the first proximal phalanx. There was a large heterogeneous signal intensity mass causing the bone destruction. The mass measured 7.3 cm in its proximal to distal dimension and 4.4 cm in its medial to lateral dimension and 4.5 cm in thickness. There was heterogeneous peripheral enhancement with central areas of poor enhancement. In the areas of poor enhancement, there was high-signal intensity on the short tau inversion ratio sequences, suggesting areas of necrosis. The mass did infiltrate the sesamoid bones as well as the flexor hallucis
Fig. 1. Plain film anteroposterior view of right foot.
Fig. 3. Plain film lateral view of first metatarsal of right foot.
Fig. 2. Plain film anteroposterior view of first metatarsal of right foot.
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Fig. 4. Computed tomography–guided biopsy of lesion reveals cells positive for pancytokeratin-AE1/3, CK5/6, p63, CK7.
longus tendon and the flexor hallucis brevis muscle belly. It was also displacing and effacing the extensor hallucis longus tendon dorsally. Below the second metatarsal neck, the mass infiltrated the deep soft tissues of the central plantar compartment. There was complete infiltration of the medial plantar compartment where it was located. The proximal first metatarsal bone demonstrated peritumoral edema as well as enhancement. The plantar plate of the first ray was also infiltrated as were the collateral ligaments. The superficial volar subcutaneous fat did enhance, suggesting infiltration (Figs. 6–10). After reviewing the MRI, a discussion was had with the patient about his overall prognosis and the best way to proceed at this point. Considering the patient’s poor prognosis, likely other regions of metastasis, and because of the patient’s inability to bear weight on the extremity, it was decided to proceed with amputation rather than
other treatments such as external beam radiation therapy. This would lead to the quickest functional outcome for the patient, relieving his pain and allowing him to ambulate. The decision was made to proceed with a midfoot amputation of the right foot, because the deep plantar compartment of the foot was infiltrated with the tumor. The patient
Fig. 5. Hematoxylin and eosin–stained right first metatarsal biopsy.
Fig. 6. T1 axial magnetic resonance image of right foot.
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Fig. 9. T1 coronal MRI of right foot.
Fig. 7. Short tau inversion ratio axial MRI of right foot.
underwent a Chopart’s amputation. The mass was sent en toto for pathological evaluation. On gross examination, there was a wellcircumscribed mass, which was sectioned in the sagittal plane. It was a gray-white, rubbery mass measuring 6.9 cm 5.2 cm 4.5 cm. The mass was located 5 cm from the soft tissue resection margin, 0.4 cm from the skin, and 4.2 cm from the distal tip of the great toe. There were areas of softening, necrosis, and hemorrhaging upon sectioning. There were both areas of squamoid differentiation and
Fig. 8. T1 fat-suppressed sagittal magnetic resonance image of right foot.
other areas that showed more glandular differentiation. Mucicarmine stain showed intracytoplasmic mucin. The overall features of this examination showed metastatic non–small cell carcinoma consistent with adenosquamous carcinoma. The skin and soft tissue margins were negative for malignancy (Figs. 11–14). At the first postoperative visit, 10 days after the surgery, the patient complained of right thigh pain and noticed a palpable mass on the inside of his left lower leg. Plain films of these regions revealed lytic lesions in both bones. The left tibia showed a lytic lesion measuring 7.8 cm in length in the proximal metaphysis with erosion of the medial cortex with a surrounding moth-eaten appearance of the medullary canal. The right femur showed a large lytic lesion in the proximal aspect of the bone measuring 3.7 cm 6.5 cm. There was destruction of the lateral femoral cortex and a large portion of the
Fig. 10. T2 coronal magnetic resonance image of right foot.
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Fig. 11. Sagittal section of gross specimen (medial aspect).
Fig. 12. Sagittal section of gross specimen (lateral aspect).
medullary bone. There was adjacent periosteal reaction (Figs. 15 and 16). Both of these regions were at high risk for pathologic fracture because of their large size (>5 cm), erosion of the cortex, and being symptomatic (1). The orthopedic oncology department performed intramedullary nailing of the right femur and left tibia to prevent fracture. This also allowed the patient to bear weight as tolerated once his foot amputation was healed, because these intramedullary nails are load-bearing devices that allowed for a quick recovery. No other procedures were performed, such as radiofrequency ablation, because this was strictly for stability and to prevent fracture. The patient was referred back to his oncologist. Bony metastases were widespread, so the patient’s family made the decision to send him to hospice. The patient died 4 months after initially being referred to our clinic with foot pain.
11 patients, this was the first indication of any malignancy. The locations in the foot were phalanges-2, metatarsals-8, cuneiform-1, navicular-3, and calcaneus-5 (4). Libson et al reported on 43 cases of metastases to the hands and feet. They found that cases of the hand outnumbered those to the foot 2:1, and that subdiaphragmatic tumors, such as gastrointestinal, vesicle, renal, and uterine, were more common in the foot (6). Acrometastasis from lung adenocarcinoma is an uncommon finding, and there have been few previous case reports. Kemnitz et al reported a similar case of an elderly man with a history of chronic gout that failed after 3 months of treatment. He also eventually underwent a bone biopsy of the first metatarsal, demonstrating adenocarcinoma from the lung. The patient died 5 months after a partial first ray resection and radiation therapy (23). Ramkumar et al studied a 60-year-old woman who presented with a swollen great toe. Radiographs and CT showed a well-defined lytic lesion of the distal phalanx. These were removed surgically, and the defect was filled with synthetic graft. The pathology report showed adenocarcinoma, and a chest radiograph showed a perihilar mass which was found to be lung adenocarcinoma. She died 12 months after presentation of her great toe symptoms (18). El Ghazaly and DeGroot reported on an 88-year-old man with left midfoot pain for 6 weeks. Radiographs
Discussion Although bony metastasis is quite common, acrometastasis is an uncommon finding. Healey et al reported on 29 patients with osseous involvement of the hands and feet. They reported the majority of these lesions to be lytic on plain film radiography with only 2 prostate metastases being blastic. A joint was only involved in 2 patients. In
Fig. 13. Hematoxylin and eosin staining of mass from right foot amputation.
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Fig. 14. Mucicarmine staining of mass from right foot amputation showing intracytoplasmic mucin.
showed a destructive lesion in the third metatarsal extending into the adjacent tarsometatarsal joint. Biopsy showed likely metastatic adenocarcinoma, and chest radiograph showed an opacity in the upper lobe of the right lung. The patient underwent chemotherapy
and radiation and died 29 months after the clinical presentation of foot pain (3). This case demonstrates the level of importance of a thorough history and physical examination for all patients. This patient was
Fig. 15. Lytic lesion of left tibia.
Fig. 16. Lytic lesion of right femur.
J. Trinidad et al. / The Journal of Foot & Ankle Surgery 51 (2012) 345–351
being treated for non–small cell carcinoma of the lung and had a recent partial resection of his lung, but the diagnosis of metastasis was still delayed more than 2 months. This was because he was thought to have an acute gout attack by his primary care physician. The diagnosis of acrometastasis should always be considered when evaluating the foot and ankle. The patient in the case study had gout attacks for more than 30 years but presented with the most painful gout attack of his life, and he could not bear weight and did not respond to treatment. A low threshold for imaging in these circumstances with plain films and then MRI or CT should be sought. This should then be followed with fine-needle aspiration or image-guided biopsy, ideally by a trained orthopaedic oncologist, for a definitive diagnosis. After these results, intervention can entail external beam radiation therapy and systemic therapy, or definitive surgical intervention can be planned with either amputation or reconstruction. Amputation can be that of a ray, midfoot, or transtibial amputation, depending on the location and spread of the tumor. Reconstruction may include decancellization with polymethylmethacrylate augmentation and plastic surgery consultation for soft tissue coverage. Any decision regarding surgical intervention should be performed on a case-by-case basis, depending on the patient’s prognosis and functional capabilities. Often, consultation with the patient’s oncologist is needed to decide the best option for the patient, depending on prognosis. Goals should include quick recovery, adequate tumor resection, relief of symptoms, and retention of functional capabilities. In this case the patient had a poor life expectancy because of his widespread metastasis and was debilitated because of a severely painful foot with which he could not bear weight. The goal was to return the patient to walking as quickly as possible and relieve his pain so he could be active for the remainder of his life. The possible treatment options included radiation therapy alone, reconstruction with radiation, or amputation. Flynn et al reviewed the literature for acrometastasis to the hand and reported on 2 case studies. They reported that the most common treatment was amputation in 48% of patients followed by radiation therapy in 29% patients. The 2 cases that were presented demonstrated improved function and pain relief after a single treatment with 8 Gy of radiation localized to the hand (24). We are not aware of any reports of using radiation therapy solely for foot metastases. The decision in this case for amputation was made because of the patient’s severe pain and inability to bear weight. Reconstruction in this case would likely be impossible because it would lead to a large soft tissue deficit and this would require prolonged recovery. Amputation would be definitive and the patient would be able to bear weight with an ankle foot orthosis likely at 2 to 3 weeks postoperatively. In conclusion, acrometastasis is an uncommon finding. However, as cancer treatments improve and life expectancy increases for patients with cancer, it is becoming more prevalent. The diagnosis of a bone tumor, especially metastasis, should always be in the differential diagnosis list. This is especially true for patients with a history of cancer, those with unusual symptoms, or those who do not respond
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to treatment. The diagnosis of acrometastasis is important, because it may be the first manifestation of an occult cancer, or it may signify the appearance of widespread metastases. It is of utmost importance to make a timely diagnosis so proper treatment can be initiated.
References 1. Biermann JS, Holt GE, Lewis VO, Schwartz VO, Yaszemski MJ. Metastatic bone disease: diagnosis, evaluation, and treatment. J Bone Joint Surg Am 91(6):1518– 1530, 2009. 2. Leeson M, Makley J, Carter J. Metastatic skeletal disease distal to the elbow and knee. Clin Orthop Relat Res 206:94–99, 1986. 3. El Ghazaly SA, DeGroot G. Metastasis to bones of the foot: a case series, review of the literature and a systematic approach to diagnosis. Foot Ankle Spec 1:338–344, 2008. 4. Healey JH, Trumbull AD, Miedema B, Acrometastases Lane JM. A study of twenty nine patients with osseous involvement of the hands and feet. J Bone Joint Surg Am 68:743–746, 1986. 5. Kumar P, Kovi J. Metastases to bones of the hands and feet. J Natl Med Assoc 70(11):837–840, 1978. 6. Libson E, Bloom RA, Husband JE, Stoker DJ. Metastatic tumours of bones of the hand and foot: a comparative review and report of 43 additional cases. Skeletal Radiol 16:387–392, 1987. 7. Zindrick MR, Young MP, Daley RJ, Light TR. Metastatic tumors of the foot: case report and literature review. Clin Orthop Relat Res 170:219–225, 1982. 8. Amiot RA, Wilson SE, Reznicek MJ, Webb BS. Endometrial carcinoma metastasis to the distal phalanx of the hallux: a case report. J Foot Ankle Surg 44(6):462–465, 2005. 9. Bibbo C, Hatfield S, Albright J. Treatment of metastatic prostate adenocarcinoma to the calcaneus. J Foot Ankle Surg 49(2):159.e15–159.e20, 2010. 10. Delgadillo LA, Nichols DE. Oat cell carcinoma metastasis to the foot. J Foot Ankle Surg 37(1):55–62, 1998. 11. Eggold JF, McFarland JA, Hubbard ER. Adenocarcinoma of the lung with phalangeal metastasis. A case report. J Am Podiatr Med Assoc 75(10):547–550, 1985. 12. Gelberman RH, Salamon PB, Huffer JM. Bone metastasis from carcinoma of the uterus. A case report. Clin Orthop Relat Res Jan-Feb(106):148–150, 1975. 13. Kouvaris JR, Kouloulias VE, Papacharalampous XN, Koutselini HA, Gennatas CS, Limouris GS, Vlahos LJ. Isolated talus metastasis from breast carcinoma: a case report and review of the literature. Onkologie 28:141–143, 2005. 14. Manolitsas TP, Fowler JM, Gahbauer RA, Gupta N. Pain in the foot: calcaneal metastasis as the presenting feature of endometrial cancer. Obstet Gynecol 100(5):1067–1069, 2002. 15. Moeller FA. Pulmonary adenocarcinoma–metastasis to a lesser toe. J Am Podiatry Assoc 61(8):297–301, 1971. 16. Paul GR, Leach RE, Beetham WP. Pulmonary carcinoma metastasis to great toe. J Am Med Assoc 208(11):2163–2164, 1969. 17. Perdano S, Auterino R, Gallo L, De Sio M, Marra L, Claudio L, Caraco C, Franco R, Fazzioli F, Gallo A. Renal cell carcinoma with solitary toe metastasis. Int J Urol 12:401–404, 2005. 18. Ramkumar U, Munshi NI, El-Jabbour JN. Occult carcinoma of the lung presenting as pain in the hallux: a case report. J Foot Ankle Surg 44(6):483–486, 2005. 19. Yadav R, Ansari MS, Dogra PN. Renal cell carcinoma presenting as solitary foot metastasis. Int Urol Nephrol 36:329–330, 2004. 20. Sahinler I, Erkal H, Akyazici E, Atkovar G, Okkan S. Endometrial carcinoma and an unusual presentation of bone metastasis: a case report. Gynecol Oncol 82(1):216– 218, 2001. 21. Sebag-Montefiore DJ, Lam KS, Arnott SJ. Tarsal metastasis in a patient with rectal cancer: case report. Br J Radiol 70:862–864, 1997. 22. Wu K. Bronchogenic carcinoma with metastases to the foot: a report of two cases. J Foot Ankle Surg 34:322–326, 1995. 23. Kemnitz M, Erdmann B, Julsrud M, Jacobs M, Ringstrom J. Adenocarcinoma of the lung with metatarsal metastasis. J Foot Ankle Surg 35(3):210–212, 1996. 24. Flynn CJ, Danjoux C, Wong J, Christakis M, Rubenstein J, Yee A, Yip D, Chow E. Two cases of acrometastasis to the hand and review of the literature. Curr Oncol 15(5):51–58, 2008.
Contents lists available at ScienceDirect
The Journal of Foot & Ankle Surgery journal homepage: www.jfas.org
Metastatic Adenosquamous Carcinoma of the Foot: A Case Report Jennifer Trinidad, DPM 1, David Kaplansky, DPM 1, Vincent Nerone, DPM 2, Kevin Springer, DPM 2 1 2
Podiatrist, Private Practice, Columbus, OH Podiatry Resident, Department of Orthopedics, The Ohio State University, Columbus, OH
a r t i c l e i n f o
a b s t r a c t
Level of Clinical Evidence: 4 Keywords: acrometastasis biopsy cancer gout metatarsal metastasis metastatic non–small cell lung carcinoma
Metastasis of carcinoma to the bones of the foot is rare and carries with it a very poor prognosis for patients. Acrometastasis can be the initial manifestation of an occult cancer or widespread metastasis of a previously diagnosed cancer. A high level of suspicion and timely diagnosis are essential to the timely diagnosis and treatment of this condition. In this report, a case of metastatic non–small cell lung carcinoma to the first metatarsal, intially diagnosed as acute gout, is presented. Ó 2012 by the American College of Foot and Ankle Surgeons. All rights reserved.
Metastatic bone tumors are much more common than primary bone tumors. In fact, the chance that a solitary bone lesion in a patient is a metastatic carcinoma in a patient older than 40 years of age is about 500 times higher than the chance that the tumor is a primary bone tumor (1). However, metastasis distal to the knee or elbow, especially in the hand or foot, is quite a rare finding. Leeson et al looked at 827 autopsies of patients who had cancer and found 7% (57 subjects) had metastasis distal to the knee or elbow. The same study found only a 1.7% incidence in the hand or foot (2). Other studies in living patients have shown an incidence of acrometastasis to be 0.007% to 0.3% (3–6). Because of the rarity of acrometastases, especially as the presenting lesion, it is often misdiagnosed as a more benign condition. The first case of bony metastasis to the foot was in a metatarsal bone and was reported by Bloodgood in 1920 (4). The rare incidence is believed to be due to the lack of red marrow in these bones as well as a further distance from the primary cancer site. The exact mechanism of metastases to the foot is uncertain, and some believe it to be due to valveless paravertebral venous plexuses (Batson’s plexuses), which allow retrograde tumor cell embolization through the iliofemoral venous system. Others believe tumor cells settle in regions of trauma and increased arterial flow, because there has been documentation of a ratio of 2:1 in the dominant hand (4). Zindrick et al found that the most common sources for acrometastases to the foot are the colon and genitourinary tract, both of Financial Disclosure: None reported. Conflict of Interest: None reported. Address correspondence to: Vincent Nerone, DPM, Podiatry Resident, Department of Orthopaedics, 4118 Cramblett Hall, 456 West 10th Avenue, Columbus, OH 432101240. E-mail address: [email protected] (V. Nerone).
which are subdiaphragmatic (7). Libson et al also found that subdiaphragmatic sources were more common to involve the foot (6). There have been reports of sinonasal carcinoma, renal cell carcinoma, transitional cell carcinoma of the bladder, endometrial adenocarcinoma, uterine carcinoma, lung cancer, breast carcinoma, prostate carcinoma, rectal carcinoma, and colon carcinoma all metastasizing to the bones of the foot (8–22). With continuously improving cancer treatments and patient lifespan increasing, the foot and ankle specialist must maintain a high clinical suspicion for acrometastasis to the foot. Misdiagnosis for more benign conditions such as gout, infection, osteomyelitis, septic arthritis, or inflammatory arthritides may affect patient outcome. We present a case of non–small cell lung carcinoma metastasis to the metatarsal that was originally misdiagnosed as gout. Case Report A 67-year-old non–insulin-dependent man with diabetes presented to the clinic with a chief complaint of right foot pain, swelling, and redness surrounding his right first metatarsophalangeal joint for the past 8 weeks. The patient had a 37 year history of intermittent gouty arthritis and was on allopurinol for the past few years. Before presentation to our clinic, the patient was being treated for an acute gout attack with indomethacin for 6 weeks by his primary care physician. He was referred to us because his symptoms had not improved and had actually worsened. The patient stated that this was the “worst gout attack that he had ever had.” After reviewing the patient’s medical history, it was also important to note that he had non–small cell lung carcinoma, and had a large tumor removed just 4 months previously from his right upper lung lobe that required wide resection. Now he was currently undergoing radiation therapy. He
1067-2516/$ - see front matter Ó 2012 by the American College of Foot and Ankle Surgeons. All rights reserved. doi:10.1053/j.jfas.2012.01.009
346
J. Trinidad et al. / The Journal of Foot & Ankle Surgery 51 (2012) 345–351
reported close follow-up with his oncologist. He had quit smoking but had a 78-pack-year smoking history. He did report a recent 30-pound weight loss, diarrhea, shortness of breath, malaise, and fatigue on his review of systems as well as severe right foot pain. On physical examination, he was a 5-foot, 8-inch, 146-pound man. The patient had exquisite pain surrounding the right first metatarsophalangeal joint, and range of motion was severely limited. There was surrounding erythema, warmth, and edema. On palpation of the area, there were no discrete masses noted. Range of motion of the ankles, knees, and hips were full and pain free. There were no palpable popliteal or inguinal lymph nodes noted. Standard radiographs of the right foot showed osteolysis of the entire first metatarsal head as well as the base of the first proximal phalanx with complete destruction of the first metatarsophalangeal joint and subchondral bone plate (Figs. 1–3). Differential diagnoses were osteomyelitis, septic arthritis, gout, primary bone tumor, and metastatic carcinoma. The patient was actively being treated for cancer, so he was immediately referred to the orthopedic oncology department for further evaluation and likely biopsy. His oncologist was also contacted. Orthopedic oncology ordered a computerized tomography (CT)–guided biopsy of the area. A full-body Technetium-99m methylene diphosphonate or Positron emission tomography–CT scan was not performed, because the likely source of the metastasis was already known, and a biopsy of this site had a low likelihood of complications. Immunohistochemical stains were performed by the pathology department, which showed cells that were positive for pancytokeratin-AE1/3, CK5/6, p63, CK7 and negative for CK20 and thyroid transcription factor-1, consistent with metastatic squamous cell carcinoma and with the patient’s known non–small cell lung carcinoma (Figs. 4 and 5). At his follow-up appointment with orthopedic oncology, the patient could no longer bear any weight on his forefoot. There was
now a palpable mass in the forefoot. The patient also complained of pain in the proximal right tibia. Plain films of the right tibia showed a small, 1-cm diameter lytic lesion in the proximal tibial epiphysis. It was decided to proceed with magnetic resonance imaging (MRI) of the foot to show the extent of the mass. The MRI showed a large mass in the medial aspect of the forefoot. There was marked destruction of the distal one half of the first metatarsal bone and proximal aspect of the first proximal phalanx. There was a large heterogeneous signal intensity mass causing the bone destruction. The mass measured 7.3 cm in its proximal to distal dimension and 4.4 cm in its medial to lateral dimension and 4.5 cm in thickness. There was heterogeneous peripheral enhancement with central areas of poor enhancement. In the areas of poor enhancement, there was high-signal intensity on the short tau inversion ratio sequences, suggesting areas of necrosis. The mass did infiltrate the sesamoid bones as well as the flexor hallucis
Fig. 1. Plain film anteroposterior view of right foot.
Fig. 3. Plain film lateral view of first metatarsal of right foot.
Fig. 2. Plain film anteroposterior view of first metatarsal of right foot.
J. Trinidad et al. / The Journal of Foot & Ankle Surgery 51 (2012) 345–351
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Fig. 4. Computed tomography–guided biopsy of lesion reveals cells positive for pancytokeratin-AE1/3, CK5/6, p63, CK7.
longus tendon and the flexor hallucis brevis muscle belly. It was also displacing and effacing the extensor hallucis longus tendon dorsally. Below the second metatarsal neck, the mass infiltrated the deep soft tissues of the central plantar compartment. There was complete infiltration of the medial plantar compartment where it was located. The proximal first metatarsal bone demonstrated peritumoral edema as well as enhancement. The plantar plate of the first ray was also infiltrated as were the collateral ligaments. The superficial volar subcutaneous fat did enhance, suggesting infiltration (Figs. 6–10). After reviewing the MRI, a discussion was had with the patient about his overall prognosis and the best way to proceed at this point. Considering the patient’s poor prognosis, likely other regions of metastasis, and because of the patient’s inability to bear weight on the extremity, it was decided to proceed with amputation rather than
other treatments such as external beam radiation therapy. This would lead to the quickest functional outcome for the patient, relieving his pain and allowing him to ambulate. The decision was made to proceed with a midfoot amputation of the right foot, because the deep plantar compartment of the foot was infiltrated with the tumor. The patient
Fig. 5. Hematoxylin and eosin–stained right first metatarsal biopsy.
Fig. 6. T1 axial magnetic resonance image of right foot.
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Fig. 9. T1 coronal MRI of right foot.
Fig. 7. Short tau inversion ratio axial MRI of right foot.
underwent a Chopart’s amputation. The mass was sent en toto for pathological evaluation. On gross examination, there was a wellcircumscribed mass, which was sectioned in the sagittal plane. It was a gray-white, rubbery mass measuring 6.9 cm 5.2 cm 4.5 cm. The mass was located 5 cm from the soft tissue resection margin, 0.4 cm from the skin, and 4.2 cm from the distal tip of the great toe. There were areas of softening, necrosis, and hemorrhaging upon sectioning. There were both areas of squamoid differentiation and
Fig. 8. T1 fat-suppressed sagittal magnetic resonance image of right foot.
other areas that showed more glandular differentiation. Mucicarmine stain showed intracytoplasmic mucin. The overall features of this examination showed metastatic non–small cell carcinoma consistent with adenosquamous carcinoma. The skin and soft tissue margins were negative for malignancy (Figs. 11–14). At the first postoperative visit, 10 days after the surgery, the patient complained of right thigh pain and noticed a palpable mass on the inside of his left lower leg. Plain films of these regions revealed lytic lesions in both bones. The left tibia showed a lytic lesion measuring 7.8 cm in length in the proximal metaphysis with erosion of the medial cortex with a surrounding moth-eaten appearance of the medullary canal. The right femur showed a large lytic lesion in the proximal aspect of the bone measuring 3.7 cm 6.5 cm. There was destruction of the lateral femoral cortex and a large portion of the
Fig. 10. T2 coronal magnetic resonance image of right foot.
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Fig. 11. Sagittal section of gross specimen (medial aspect).
Fig. 12. Sagittal section of gross specimen (lateral aspect).
medullary bone. There was adjacent periosteal reaction (Figs. 15 and 16). Both of these regions were at high risk for pathologic fracture because of their large size (>5 cm), erosion of the cortex, and being symptomatic (1). The orthopedic oncology department performed intramedullary nailing of the right femur and left tibia to prevent fracture. This also allowed the patient to bear weight as tolerated once his foot amputation was healed, because these intramedullary nails are load-bearing devices that allowed for a quick recovery. No other procedures were performed, such as radiofrequency ablation, because this was strictly for stability and to prevent fracture. The patient was referred back to his oncologist. Bony metastases were widespread, so the patient’s family made the decision to send him to hospice. The patient died 4 months after initially being referred to our clinic with foot pain.
11 patients, this was the first indication of any malignancy. The locations in the foot were phalanges-2, metatarsals-8, cuneiform-1, navicular-3, and calcaneus-5 (4). Libson et al reported on 43 cases of metastases to the hands and feet. They found that cases of the hand outnumbered those to the foot 2:1, and that subdiaphragmatic tumors, such as gastrointestinal, vesicle, renal, and uterine, were more common in the foot (6). Acrometastasis from lung adenocarcinoma is an uncommon finding, and there have been few previous case reports. Kemnitz et al reported a similar case of an elderly man with a history of chronic gout that failed after 3 months of treatment. He also eventually underwent a bone biopsy of the first metatarsal, demonstrating adenocarcinoma from the lung. The patient died 5 months after a partial first ray resection and radiation therapy (23). Ramkumar et al studied a 60-year-old woman who presented with a swollen great toe. Radiographs and CT showed a well-defined lytic lesion of the distal phalanx. These were removed surgically, and the defect was filled with synthetic graft. The pathology report showed adenocarcinoma, and a chest radiograph showed a perihilar mass which was found to be lung adenocarcinoma. She died 12 months after presentation of her great toe symptoms (18). El Ghazaly and DeGroot reported on an 88-year-old man with left midfoot pain for 6 weeks. Radiographs
Discussion Although bony metastasis is quite common, acrometastasis is an uncommon finding. Healey et al reported on 29 patients with osseous involvement of the hands and feet. They reported the majority of these lesions to be lytic on plain film radiography with only 2 prostate metastases being blastic. A joint was only involved in 2 patients. In
Fig. 13. Hematoxylin and eosin staining of mass from right foot amputation.
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Fig. 14. Mucicarmine staining of mass from right foot amputation showing intracytoplasmic mucin.
showed a destructive lesion in the third metatarsal extending into the adjacent tarsometatarsal joint. Biopsy showed likely metastatic adenocarcinoma, and chest radiograph showed an opacity in the upper lobe of the right lung. The patient underwent chemotherapy
and radiation and died 29 months after the clinical presentation of foot pain (3). This case demonstrates the level of importance of a thorough history and physical examination for all patients. This patient was
Fig. 15. Lytic lesion of left tibia.
Fig. 16. Lytic lesion of right femur.
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being treated for non–small cell carcinoma of the lung and had a recent partial resection of his lung, but the diagnosis of metastasis was still delayed more than 2 months. This was because he was thought to have an acute gout attack by his primary care physician. The diagnosis of acrometastasis should always be considered when evaluating the foot and ankle. The patient in the case study had gout attacks for more than 30 years but presented with the most painful gout attack of his life, and he could not bear weight and did not respond to treatment. A low threshold for imaging in these circumstances with plain films and then MRI or CT should be sought. This should then be followed with fine-needle aspiration or image-guided biopsy, ideally by a trained orthopaedic oncologist, for a definitive diagnosis. After these results, intervention can entail external beam radiation therapy and systemic therapy, or definitive surgical intervention can be planned with either amputation or reconstruction. Amputation can be that of a ray, midfoot, or transtibial amputation, depending on the location and spread of the tumor. Reconstruction may include decancellization with polymethylmethacrylate augmentation and plastic surgery consultation for soft tissue coverage. Any decision regarding surgical intervention should be performed on a case-by-case basis, depending on the patient’s prognosis and functional capabilities. Often, consultation with the patient’s oncologist is needed to decide the best option for the patient, depending on prognosis. Goals should include quick recovery, adequate tumor resection, relief of symptoms, and retention of functional capabilities. In this case the patient had a poor life expectancy because of his widespread metastasis and was debilitated because of a severely painful foot with which he could not bear weight. The goal was to return the patient to walking as quickly as possible and relieve his pain so he could be active for the remainder of his life. The possible treatment options included radiation therapy alone, reconstruction with radiation, or amputation. Flynn et al reviewed the literature for acrometastasis to the hand and reported on 2 case studies. They reported that the most common treatment was amputation in 48% of patients followed by radiation therapy in 29% patients. The 2 cases that were presented demonstrated improved function and pain relief after a single treatment with 8 Gy of radiation localized to the hand (24). We are not aware of any reports of using radiation therapy solely for foot metastases. The decision in this case for amputation was made because of the patient’s severe pain and inability to bear weight. Reconstruction in this case would likely be impossible because it would lead to a large soft tissue deficit and this would require prolonged recovery. Amputation would be definitive and the patient would be able to bear weight with an ankle foot orthosis likely at 2 to 3 weeks postoperatively. In conclusion, acrometastasis is an uncommon finding. However, as cancer treatments improve and life expectancy increases for patients with cancer, it is becoming more prevalent. The diagnosis of a bone tumor, especially metastasis, should always be in the differential diagnosis list. This is especially true for patients with a history of cancer, those with unusual symptoms, or those who do not respond
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to treatment. The diagnosis of acrometastasis is important, because it may be the first manifestation of an occult cancer, or it may signify the appearance of widespread metastases. It is of utmost importance to make a timely diagnosis so proper treatment can be initiated.
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