- Email: [email protected]
Oat cell carcinoma metastasis to the foot
Oat Cell Carcinoma Metastasis to the Foot Initial isolation from the foot of a highly malignant primary bronchogenic carcinoma, small cell carcinoma (oat cell carcinoma), was identified via excisional biopsy from the right foot of a 42-year-old nonsmoking Caucasian female. This patient denied any pertinent prior medical history, other than persistent pain in her right foot for approximately 1 year before seeking care. Incidental trauma prompted her to seek care, which consisted of immobilization via a wooden shoe. When symptoms persisted, her primary care physician referred her to my office for further evaluation. (The Journal of Foot & Ankle Surgery 37(1):55-62, 1998) Key words: small cell carcinoma (oat cell carcinoma), lower extremity neoplasm
Louis A. Delgadillo, DPM, MPH 1 Donald E. Nichols, DPM 2 Tumors of the foot and ankle pose an interesting diagnostic dilemma. Case studies involving pedal tumors appear periodically in the medical literature. We often view them as interesting, though uncommon. However, when a patient presents with a soft tissue mass or an atypical osseous finding, one must contemplate the possibility that a neoplastic activity may be occurring. A tumor is defined simply as a swelling or enlargement. Additionally, it is defined as, and more commonly interpreted as, a spontaneous new growth of tissue forming an abnormal mass. Tumors are usually of unknown cause, noninflammatory, and develop independent of, and unrestrained by, normal laws of growth and morphogenesis (1). Classification of Lower Extremity Tumors
The World Health Organization classification system, as modified by Enzinger and Weiss, recognizes 82 distinct benign and malignant soft-tissue lesions and tumors of 10 major histiogenic types that can arise in the distal part of the leg. These tumors may arise from these tissue types primarily, may spread from surrounding tissue types, or may present as a secondary neoplastic center. Though some disagreement may exist concerning which is the most common benign lesion present, it is agreed that malignant tumors of the foot are relatively uncommon (2). With respect to benign soft tissue tumors, the most common primary skin lesion, as found by Steinberg, Steinberg, and Berlin, is the viral tumor, verruca (3, 4).
Kirby et al., in their study of soft tissue tumors and tumor-like lesions of the foot, found that of 83 lesions, 87% were benign and 13% were malignant. Ganglion cysts were the most commonly encountered tumors; less common were plantar fibromatosis, epidermal inclusion cysts, lipomas, rheumatoid nodules, and giant cell tumors of tendon sheath. Kirby and colleagues, in the same study, also found the synovial sarcoma to be the most frequent type of malignant tumor, tending to aggregate about the ankle and hind foot (2). What is of particular interest to our case presentation was the identification of a bronchogenic carcinoma, small (oat) cell carcinoma, isolated initially via biopsy from the foot. The limited term bronchogenic carcinoma is frequently more broadly associated with lung cancer. Lung cancer is defined as a primary malignant neoplasm arising within the airways and is a frequent and important neoplasm. Several histological classifications for bronchogenic carcinomas exist, and one popular grouping is that of the World Health Organization, which divides these tumors into four major categories (5). The four major malignant tumor categories, with their approximate percentage of incidence, are: 1) Squamous cell carcinoma (25% to 40%) 2) Adenocarcinoma (25% to 40%) a. Usual (bronchial) type b. Bronchioloalveolar carcinoma 3) Small cell carcinoma (oat cell) (20% to 25%) 4) Large cell carcinoma (10% to 15%) Epidemiology of Bronchogenic Tumors
1 Diplomate, American Board of Podiatric Orthopedics. Address correspondence to: 545 Arlene Drive, Wood Dale, IL 60191. 2 Board-Qualified, American Board of Podiatric Surgery. The Journal of Foot & Ankle Surgery 1067-2516/98/3701-0055$4.00/0 Copyright © 1998 by the American College of Foot and Ankle Surgeons
In the United States, cancer of the lung occurs most often between the ages of 40 and 70 years, with a peak incidence identifiable in the sixth or seventh decade. Only 2% of all cases appear before the age of 40 (5). Approximately 80% of all cases of lung cancer are VOLUME 37, NUMBER 1, 1998
55
FIGURE 1 Emergency room radiographs of right foot. A, anteroposterior reveals thinning of the medial and lateral cortical margins of the third metatarsal. B, lateral oblique exhibits an apparent fracture along the proximal extent of the third metatarsal's lateral cortex.
caused by smoking cigarettes. Passive inhalation of cigarette smoke also increases one's risk with respect to bronchogenic cancer. Occupational exposures to radiation, asbestos, nickel, chromates, and coal, for example, also increase the incidence of lung cancer. Finally, chronic inflammation of the lung may also increase one's chances of developing a neoplasm (5). Lung cancer is clinically silent for the majority of its course (6). Most patients with lung cancer present with typical complaints of cough, weight loss, chest pain, and difficulty in breathing. Most patients will have symptoms of approximately 7 months' duration before lung cancer is discovered (5). The small cell carcinomas (oat cell carcinomas) represent approximately 20 to 25% of bronchogenic carcinomas. Small cell carcinoma is a highly aggressive malignant tumor and is strongly associated with cigarette smoking, with only 1% occurring in nonsmokers. It is the most aggressive of lung tumors. Untreated, patients with 56
THE JOURNAL OF FOOT & ANKLE SURGERY
small cell cancer have an estimated survival time of 6 to 17 weeks. Yet, even with treatment, the mean survival after diagnosis is only about 1 year (5). Diagnosis of Bronchogenic Tumors
A tumor of 1 em, in diameter is the smallest sized tumor detectable on a chest x-ray (7). With the onset of newer and more sophisticated imaging diagnostics, such as computerized axial tomography (CAT) scans and magnetic resonance imaging (MRI) for soft tissue lesions, clinicians have dramatically improved their ability to identify and isolate abnormal anatomy. Radiographic findings in metastatic bone disease vary with the type of primary lesion and the bone involved. If a primary tumor is suspected, the oncologist would then obtain a histologic specimen of the primary lesion for examination. In many instances, the probable histologic diagnosis of a primary tumor can be made via biopsy of
FIGURE 2 Radiographs taken at this initial visit. A, anteroposterior reveals a mottled increase in osseous density along the proximal port ion of the shaft of the third metatarsal of the right foot. The midshaft area of the third metatarsal exhibits, to some extent, demineralization of bone. B, lateral oblique. Arrow directs our attention to the cortical breach noted at the proximal lateral cortical margin.
a SUSpiCIOUS lesion isolated elsewhere, representing a metastatic focus. Discussion of Malignancies and Metatases
In the United States during 1995, there were about 1.2 million new cases of cancer (exclusive of non melanotic skin cancer) and more than 500,000 deaths from cancer overall (8). Osseous metastases developed in approximately 30% of all patients with cancer (9). Mankin stated that the frequency of metastastic carcinoma far exceeds that of primary tumors of bone, especially in later life, so that staging of any individual with a bone tumor should include a careful clinical imaging and laboratory evaluation of the more frequent sites of origin (10) . Breast, prostate, lung, and kidney cancers are the most common primary malignancies causing skeletal
metastases. The frequency of breast cancer in females accounts for more than 50% of secondary skeletal metastases in women, and the se lesions are osteolytic, mixed, or osteoblastic metastases in that order of frequency . Similarly, in males, prostatic cancer is the most frequent cause of metastatic bone disease, and these lesions are predominantly osteoblastic (11). Although metastatic lesions of the foot are rare, foot pain may be potentially suggestive of an occult carcinoma (12). Metastatic bone cancer presents with bone pain, frequently with presence of pathologic fracture (11). When metastatic carcinoma does affect the foot , it is not unusual for symptoms in the foot to become apparent before the detection of the primary tumor (13). In the study by Gall et al., five of the eight patients with metastatic lesions had foot pain as their initial complaint (12). Nevertheless, statistically only 0.007 to 0.3% of paVOLUME 37, NUMBER 1, 1998
57
tients have acrometastases, such as lesions in the hand or foot (9). In their study of 2800 osseous tumors, Gall and colleagues found only 19 malignant lesions of the foot. A study performed at Johns Hopkins found 13 malignant primary osseous lesions in 1740 bone tumors (12). Several other authors have investigated the incidence of pedal bone cancers and offer their insight. Metastastic diseases of the foot and ankle are rare. Of the more than 75,000 patients with primary malignancies treated between 1972 and 1983 at our institution, only 10 were found to have foot or ankle metastatic disease. Wu and Guise found only four cases among the records of 41,833 cancer patients (14). Zindrick et al. reviewed the world literature in 1982 and found only 38 cases of histologically confirmed disease in 72 reported cases of metastatic disease of the foot (15). K. Gauntt et at. noted that statistics indicate a frequency of <2% for metastatic lesions in the foot among all metastatic skeletal lesions (16). Other authors state bone tumors of the foot and tarsal bones were found in only 1.7% of all bone tumors in a Mayo Clinic review of 6034 bone tumor cases (17). With respect to metastasis to the foot, common sites of involvement include the calcaneus and metatarsals, although phalanges and talus, cuboid, navicular, and cuneiform bones are also involved (9, 13, 15, 18, 19). The statistical data indicate a low incidence of bone tumors being identified in the feet when compared to bone tumors found elsewhere in the skeleton. The identification of bone tumors in the feet by means of biopsy, or autopsy, or both, however, creates a continual awareness of their possible presence. Case Study
A 42-year-old white female presented to the author complaining of pain and swelling of her right foot persisting for the past year. The patient recalled occasional tenderness of her right foot for approximately the past 2 years, yet she had not sought care during that period. Approximately 14 months before presentation, while attending a wedding, her right foot was inadvertently stepped upon, creating increased pain and swelling. The pain was sufficiently severe to warrant an emergency room visit, where radiographic examination revealed an apparent fracture of the base of the third right metatarsal (Fig. 1). Follow-up with a local practitioner consisted of continued immobilization with a wooden shoe as well as elastic wraps. Subsequent radiographs revealed continued disruption of the lateral cortices at the third right metatarsal, with demineralization at the proximal extent of this metatarsal. Five months later, a technetium bone scan confirmed increased uptake at the proximal por58
THE JOURNAL OF FOOT & ANKLE SURGERY
FIGURE 3 Small cell carcinoma. Photomicrographs A and B reveal islands of small, round-to-spindle-shaped cells containing little cytoplasm and deeply basophilic hyperchromatic nuclei. B depicts the spindle-shaped pattern of small cell carcinoma. C shows areas of distorted tumor cells, (arrow), seen adjacent to fragments of bone (H&E x40).
tions of the third metatarsal, consistent with that of a fracture. No additional areas of uptake were apparent. At the time of her initial visit to the author, the patient presented as a pleasant, moderately obese, Caucasian
FIGURE 4 Patient has now undergone eight months of chemotherapy. A, anteroposterior and S, lateral oblique radiographs continue to exhibit a mottled appearance of bone at the third metatarsal, with loss of cortical definition.
female. Her past and present medical history was essentially unremarkable, in that the patient denied any prior history of diabetes or lung, liver, or kidney disorders. She did state that there was a history of mitral valve prolapse and occasional rapid heart beat, which was controlled with medication. She was a nonsmoker, denied any prior surgical history, and indicated allergies to mold, pollen, and penicillin. Her current medication included propranolol hydrochloride. Upon physical examination, the following was noted: dorsalis pedis pulses were 2/4 bilateral, whereas the posterior tibial pulses were nonpalpable bilaterally. Multiple varicosities were present at both lower extremities. Her patellar and achilles reflexes were intact bilaterally, whereas the Babinski reflex was not elicited at either foot . What was clinically evident was an increased temperature gradient at her right lower extremity when compared to her contralateral limb. Also noted was a
brawny type edema of + 2, involving only her right foot. Radiographs taken on this date revealed a cortical breach at the proximal lateral cortical margin of the third right metatarsal. There also appeared to be demineralization of bone along the midshaft of that metatarsal, with mottled increase in bone density along its proximal portion (Fig. 2). The patient was placed in a short leg walking cast and given instructions to elevate and ice the right foot , and to decrease ambulation. Laboratory studies consisting of a complete blood cell count with differential were performed at a local hospital, with laboratory values found to be within normal limits, except for an elevated blood sedimentation rate of 37 mm./hr. In view of these test results, a gallium-67 citrate scan was ordered. The scan indicated an increased uptake at the dorsolateral aspect of her right foot. A positive technetium-99m scan and a negative gallium-67 citrate scan may be associated with an 85% VOLUME 37, NUMBER 1, 1998
59
probability that an infection is not present, whereas a positive technetium scan and a positive gallium scan represent a 70% certainty that osteomyelitis is established (20). The differential diagnosis consisted of a pathological metatarsal fracture secondary to osteomyelitis, or a pathological fracture, possibly secondary to bone or soft tissue neoplasia. In order to obtain a more specific diagnosis, the patient underwent a percutaneous needle biopsy utilizing fluoroscopy under local anesthetic. Because of the possibility of bacterial contaminants being isolated, arrangements were made for intravenous home therapy, depending upon the results of intraoperative culture and sensitivity tests. Final culture results indicated negative growth for aerobic and anaerobic bacterial organisms. The bone biopsy was equally unremarkable, with the microscopic sections revealing a single fragment of bone, several fragments of skin as well as fragments of clotted blood and hyaline material. No necrotic bone was seen. In view of these negative findings, yet persistent clinical and radiographic evidence of abnormal activity, preparation was made for an open excisional and exploratory surgery. The patient and her husband were seen for surgical consultation. Clinically, her right foot had increased edema and calor. There was no evidence of drainage nor sinus tract formation. An excisional biopsy was performed on an outpatient basis. Intraoperative gram stains were negative for bacteria. Soft tissue and bony specimens were excised and sent for pathologic examination intraoperatively. Preliminary findings from tissue specimens indicated cellular tumor and possibly malignant activity. In view of these significant findings, the incision was closed, with further treatment pending identification of the malignancy. The soft tissue and bone biopsies were forwarded to regional and out-of-state institutions for review. A diagnosis of oat cell carcinoma was made. The patient was then referred to an oncologist for follow-up and treatment. Photomicrographs (Fig. 3, A-C) exhibit the histologic characteristics of small cell carcinoma. A diagnosis of metastatic small cell carcinoma (oat cell carcinoma) was confirmed by a positive immunostaining pattern with neuron-specific enolase. The tumor cells showed a negative staining pattern with leukocyte common antigen. Grossly, the specimen consisted of multiple fragments of tan to pink soft, friable tissue, mixed with fragments of bone and fibrous and tendinous tissue, with an aggregate measurement of 4 em. X 2.5 em. X 2 em. The patient was seen the following week for suture removal. There did not appear to be any signs of bacterial infection, and the incision site appeared well coapted and closed. Additional testing performed, in60
THE JOURNAL OF FOOT & ANKLE SURGERY
FIGURE 5 A, axial image; B, sagittal section of right foot via MRI graphically exposes the infiltration of tumor mass throughout various compartments of the right foot.
eluding CAT, revealed metastatic involvement, with small but identified tumors noted to be in the lungs, the retroperitoneal area, and the inguinal region of her torso. An incisional biopsy performed on a mass at her inguinal region proved to be oat cell carcinoma upon microscopic examination. Over the next several months, she was treated with a variety of chemotherapeutic agents, including cisplatin, cyclophosphamide, and etoposide as well as with radiation therapy for her right foot. Three weeks later, [mal radiographs were taken of her right foot (Fig. 4). They revealed
the continued cortical irregularities of the third metatarsal, as well as the loss of a trabecular pattern of bone along the shaft. MRI, performed approximately 1 year after her first visit, graphically depicted the invasiveness of this tumor and its spread throughout the right foot (Fig. 5). Despite her early success with various treatment modalities, the patient died several months later. Summary The distinguishing characteristics with this case history were recalcitrant pain at her right foot and the failure of an apparent stress fracture to resolve over time. At the time of her initial office visit, she did not exhibit any systemic manifestations, nor did she complain of difficulty breathing, weight loss, or loss of appetite. She denied smoking or being exposed to second-hand smoke. Laboratory analysis, which included hematology and chemistry studies, urinalysis, rheumatoid profile, antinuclear antibodies, antistreptolysin-O titer, and electrolyte levels, were unremarkable except for a slightly elevated erythrocyte sedimentation rate. When radiographic findings exhibited neither consolidation nor improvement after conservative measures, further diagnostic testing, including biopsy of the affected site, was performed. Once a diagnosis was achieved, aggressive treatment was initiated. The vast majority of patients with small cell anaplastic carcinoma present with extrapulmonary metastatic disease at the time of diagnosis (21). One must speculate, however, that in this patient, oat cell carcinoma was actually present months before the incidental trauma to her foot, which in turn prompted her to seek care. As noted, untreated, patients with small (oat) cell carcinoma have a survival time of 6 to 17 weeks (5). Clearly, the scarcity of metastatic pedal malignancies is well documented. Yet the very fact of their existence should always encourage the maintenance of a vigil for their possible presence. Whenever patients complain of persistent pain or swelling, or both, in their feet, one must consider the possibility of neoplastic changes, particularly when initial conservative measures fail to resolve the patients' initial presentation. Acknowledgment The authors thank Jacalyn Palmer and Drs. Patrick Connally and Neerupama Bhatia for all of their assistance in securing and producing the photomicrographs. References 1. Taber's Cyclopedic Medical Dictionary, p. 1787, edited by C. L. Thomas, A Davis Company, Philadelphia, 1985. 2. Kirby, E., Shereff, M., Lewis, M. Soft-tissue tumors and tumor-like lesions of the foot. J. Bone Joint Surg. 71A:621-626, 1989.
3. Steinberg, M., Steinberg, L. Tumors of the foot. J. Am. Podiatr. Assoc. 69:135-138, 1979. 4. Berlin, S. J. Statistical analysis of 307,601 tumors and other lesions of the foot. J. Am. Podiatr. Med. Assoc. 85:699-703, 1995. 5. Robbins, S. L. In Robbins: Pathologic Basis of Disease. 5th ed., pp. 295-297; 381-383; 720-724, edited by R. S. Cotran, V. Kumar, S. L. Robbins, W. B. Saunders Company, Philadelphia, 1994. 6. Miller, Y. E. Pulmonary neoplasms, Part VIII. In Cecil Textbook of Medicine, 20th ed., pp. 436-442, edited by J. C. Bennett, F. Plum, W. B. Saunders Company, Philadelphia, 1996. 7. Dantzker, D. R, Tobin, M. J., Whatley, R E. Neoplastic diseases of the lung, Ch. 24. In Cecil Essentials of Medicine, pp 66-170, edited by T. Andreoli, C. Carpenter, F. Plum, L. Smith, W. B. Saunders Company. Philadelphia, 1986. 8. Anderson's Pathology, 10th ed., pp, 541-544; 1541-1545, edited by I. Damjanov, J. Linder, C. V. Mosby-Year Bk., Inc., St. Louis, 1990. 9. Healey, J. H., Turnbull, A., Miedema, B., Lane, J. M. Acrometastases: a study of twenty-nine patients with osseous involvement of the hands and feet. J. Bone Joint Surg. 68-A:743-746, 1986. 10. Mankin, H. J., Gebhardt, M. C. Advances in the management of bone tumors. Clin. Orthop. 200:73-83, 1985. 11. Moser, R P., Madewell, J. E. Metastatic bone cancer. In Radiology, Diagnosis, Imaging and Intervention, vol. 5, pp. 1-8, edited by J. Traveras, J. B. Lippincott, Philadelphia, 1986. 12. Gall, R J., Sim, F. H., Pritchard, D. J. Metastatic tumors to the bones of the foot. Cancer 37:1492-1495, 1976. 13. Eggold, J. F., McFarland, J. A, Hubbard, E. R. Adenocarcinoma of the lung with phalangeal metastasis. J. Am. Podiatr. Med. Assoc. 75:547-549, 1985. 14. Wu, K K., and Guise, E. R Metastatic tumors of the foot. South. Med. J. 71:807-808, 1978. 15. Zindrick, M. R, Young, M. P., Daley, R J., Light, T. R Metastatic tumors of the foot: case report and literature review. Clin. Orthop. 170:219-225,1982. 16. Gauntt, K, Boykoff, T., Danna, A Adenocarcinoma: case of metastasis to the foot. J. Am. Podiatr. Med. Assoc. 80:657-659, 1990. 17. Posteraro, R. H. Radiographic evaluation of pedal osseous tumors. Clin Pod Med Surg. 10:633-653, 1993. 18. Hattrup, S. J., Amadio, P. C., Sim, F. H., Lombardi, R M.: Metastatic tumors of the foot and ankle. Foot & Ankle. 8:243-247, 1988. 19. Libson, E., Bloom, R A., Husband, J. E., Stoker, D. J.: Metastatic tumours of bones of the hand and foot. Skel Radiol 16:387-392, 1987. 20. Marcinko, D. E. ch 70. In Comprehensive Textbook ofFoot Surgery, 2nd ed., vol. 2, p. 1729, edited by E. D. McGlamry, A S. Banks, M. S. Downey, Williams & Wilkins, Baltimore, 1992. 21. Hansen, H. H., Dobernowsky, P., Hirsh, F. R. Staging procedures and prognostic features in small cell anaplastic bronchogenic carcinoma. Semin. Oncol. 5:280-287, 1978.
Additional References Anderson, E. E., Leitner, W. A, Boyarsky, S., Small, M. P., and McCollum, D. E. Renal-cell carcinoma metastatic to great toe. J. Bone Joint Surg. 50A:997-998, 1968. Barnett, L. S., and Morris, J. M. Metastases of a renal-cell carcinoma simultaneously to a finger and a toe: a case report. J. Bone Joint Surg. 5IA:773-774, 1969. Berlin, S., Mirkin, G., Tubridy, S. Tumors of the heel. Clin. Pod. Med. Surg. 7:307-321, 1990. Bevan, D. A., Ehrlich, G. E., and Gupta, V. P. Metastatic carcinoma simulating gout. J. Am. Med. Assoc. 237:2746-2747, 1977.
VOLUME 37, NUMBER 1, 1998
61
Bloodgood, J. Bone tumors, benign and malignant. Amer. J. Surg. 34:229-236, 1920. Bright, M., and Wilkie, J. R. Carcinoma metastasis to talus and metatarsals (Letter to the Editor). J. Am. Med. Assoc. 210:1592, 1969. Bunkis, J., Mehrhof, A I., and Stayman, J . W., III. Metastatic lesions of the hand and foot. Orthop. Rev. 9:97-101, 1980. Cohen, P., Buzdar, A Metastatic breast carcinoma mimicking an acute paronychia of the great toe : case report and review of subungual metastases. Am. J. Clin. Oncol. 16:86-91, 1993. Colson , G., Wilcox, A Phalangeal metastases in bronchogenic carcinoma. Lancet 254:100-102, 1948. Dripchack, P., Roberson, J. Breast cancer metastatic to the foot with massive bone loss. Orthop. Rev. 19:877-879, 1990. Dunn, E., Mauro, G., Cohen, R. Giant cell tumor of the intermediate cuneiform. J. Am. Podiatr. Med . Assoc. 82:208-211, 1992. Fort, W. Cancer metastatic to bone. Radiology 24:96-98, 1935. Harkonen, M., and Olin, P. E. Rectal carcinoma metastasizing to a toe. Acta Med . Scand. 207:235-236, 1980. Harrington, K. Management of lower extremity metastases. In Orthopedic Management of Metastatic Bone Disease, pp. 141-214, C. V. Mosby, St. Louis, 1988. Hirsch, F., Hansen, H. H., Dombernowsky, P., Hainau, B. Bone marrow examination in the staging of small-cell anaplastic carcinoma of the lung with special reference to sub typing. Cancer. 39:2563-2567, 1977. Jacox , R. F., and Tristan, T. A : Carcinoma of the breast metastatic to the bones of the foot: a case report. Arthritis Rheum 3:170-177, 1960. Janis, L. R., and Feldman, E. P. Metastatic adeno carcinoma at the calcaneus: case report. J. Foot Surg. 15:28-32, 1976. Katz, L. Pulmonary carcinoma metastasis to great toe. J. Am. Med. Assoc. 208:2163-2166, 1969. Khiyami, A, Green, L., Gyorkey, F., Landon, G. Primary angiosarcoma of the cuboidal bone: a case report. Diagn . Cytopathol. 7:520-523, 1991.
62
THE JOURNAL OF FOOT & ANKLE SURGERY
Kinley, S., Wiseman, F., Wertheimer, S. Giant cell tumor of the talus with secondary aneurysmal bone cyst. Foot Ankle 32:38-46, 1993. Kumar, P. P. and Kovi, J. Metastases to bones of the hands and feet. J. Natl. Med. Assoc. 7:837-840, 1978. Mess, D., and Songer, M. Head and neck carcinoma meta stases to the hand and foot: a case report of simultaneous involvement. Orthopedics 9:975-977, 1986. Moeller, F. A. Pulmonary adeno carcinoma: metastasis to a lesser toe . J. Am. Podiatr. Med. Assoc. 61:297-301 , 1971. Moore, J. Tumors of the os calcis. Radiology 16:232-244, 1931. Murari, T., Callaghan, J., Berrey, B., Sweet , D. Primary benign and malignant osseous neoplasms of the foot . Foot Ankle 10:68-80, 1989. Panebianco, A c., Kaupp , H. A Bilateral thumb metast asis from breast cancer. Arch Surg. 96:216-218, 1968. Smithers, D. W., Price, L. R. W. Isolated secondary deposit in a terminal phalanx in a case of squamous-cell carcinoma of the lung. Br. J. Radiol. 18:299-300, 1945. Sundberg, S. B., Carlson, W.O., Johnson, K. A Metastatic lesions of the foot and ankle. Foot Ankle 3:167-169, 1982. Sworn, M. J., Buchanan, R., Moynihan, F. J. Rectal carcinoma presenting as massive metastatic involvement of foot bones . Br. Med. J. 2:98-99, 1978. Toth, J. G. Metastases to the fingers from breast cancer. Can. Med. Assoc. J. 129:534, 1983. Vaezy, A., and Budson , P. C. Phalangeal metastases from bronchogenic carcinoma. J. Am. Med. Assoc. 239:226-227, 1978. Weitzner, S. Adenoid cystic carcinoma of submaxillary gland metastatic to great toe . Am. Surg. 41:655-658, 1975. Williams, R. P., Pechero, G. Management of soft tissue and bone tumors of the foot. Clin. Podiatr. Med. Surg . 10:717-725 , 1993. Wu, K. K. Differential diagnosis of pedal osseous neoplasms . Clin. Podiatr. Med. Surg. 10:683-715, 1993. Wu, K. K. Tumor review: osteogenic sarcoma of the foot. J. Foot Surg. 26:269-271, 1987.
Louis A. Delgadillo, DPM, MPH 1 Donald E. Nichols, DPM 2 Tumors of the foot and ankle pose an interesting diagnostic dilemma. Case studies involving pedal tumors appear periodically in the medical literature. We often view them as interesting, though uncommon. However, when a patient presents with a soft tissue mass or an atypical osseous finding, one must contemplate the possibility that a neoplastic activity may be occurring. A tumor is defined simply as a swelling or enlargement. Additionally, it is defined as, and more commonly interpreted as, a spontaneous new growth of tissue forming an abnormal mass. Tumors are usually of unknown cause, noninflammatory, and develop independent of, and unrestrained by, normal laws of growth and morphogenesis (1). Classification of Lower Extremity Tumors
The World Health Organization classification system, as modified by Enzinger and Weiss, recognizes 82 distinct benign and malignant soft-tissue lesions and tumors of 10 major histiogenic types that can arise in the distal part of the leg. These tumors may arise from these tissue types primarily, may spread from surrounding tissue types, or may present as a secondary neoplastic center. Though some disagreement may exist concerning which is the most common benign lesion present, it is agreed that malignant tumors of the foot are relatively uncommon (2). With respect to benign soft tissue tumors, the most common primary skin lesion, as found by Steinberg, Steinberg, and Berlin, is the viral tumor, verruca (3, 4).
Kirby et al., in their study of soft tissue tumors and tumor-like lesions of the foot, found that of 83 lesions, 87% were benign and 13% were malignant. Ganglion cysts were the most commonly encountered tumors; less common were plantar fibromatosis, epidermal inclusion cysts, lipomas, rheumatoid nodules, and giant cell tumors of tendon sheath. Kirby and colleagues, in the same study, also found the synovial sarcoma to be the most frequent type of malignant tumor, tending to aggregate about the ankle and hind foot (2). What is of particular interest to our case presentation was the identification of a bronchogenic carcinoma, small (oat) cell carcinoma, isolated initially via biopsy from the foot. The limited term bronchogenic carcinoma is frequently more broadly associated with lung cancer. Lung cancer is defined as a primary malignant neoplasm arising within the airways and is a frequent and important neoplasm. Several histological classifications for bronchogenic carcinomas exist, and one popular grouping is that of the World Health Organization, which divides these tumors into four major categories (5). The four major malignant tumor categories, with their approximate percentage of incidence, are: 1) Squamous cell carcinoma (25% to 40%) 2) Adenocarcinoma (25% to 40%) a. Usual (bronchial) type b. Bronchioloalveolar carcinoma 3) Small cell carcinoma (oat cell) (20% to 25%) 4) Large cell carcinoma (10% to 15%) Epidemiology of Bronchogenic Tumors
1 Diplomate, American Board of Podiatric Orthopedics. Address correspondence to: 545 Arlene Drive, Wood Dale, IL 60191. 2 Board-Qualified, American Board of Podiatric Surgery. The Journal of Foot & Ankle Surgery 1067-2516/98/3701-0055$4.00/0 Copyright © 1998 by the American College of Foot and Ankle Surgeons
In the United States, cancer of the lung occurs most often between the ages of 40 and 70 years, with a peak incidence identifiable in the sixth or seventh decade. Only 2% of all cases appear before the age of 40 (5). Approximately 80% of all cases of lung cancer are VOLUME 37, NUMBER 1, 1998
55
FIGURE 1 Emergency room radiographs of right foot. A, anteroposterior reveals thinning of the medial and lateral cortical margins of the third metatarsal. B, lateral oblique exhibits an apparent fracture along the proximal extent of the third metatarsal's lateral cortex.
caused by smoking cigarettes. Passive inhalation of cigarette smoke also increases one's risk with respect to bronchogenic cancer. Occupational exposures to radiation, asbestos, nickel, chromates, and coal, for example, also increase the incidence of lung cancer. Finally, chronic inflammation of the lung may also increase one's chances of developing a neoplasm (5). Lung cancer is clinically silent for the majority of its course (6). Most patients with lung cancer present with typical complaints of cough, weight loss, chest pain, and difficulty in breathing. Most patients will have symptoms of approximately 7 months' duration before lung cancer is discovered (5). The small cell carcinomas (oat cell carcinomas) represent approximately 20 to 25% of bronchogenic carcinomas. Small cell carcinoma is a highly aggressive malignant tumor and is strongly associated with cigarette smoking, with only 1% occurring in nonsmokers. It is the most aggressive of lung tumors. Untreated, patients with 56
THE JOURNAL OF FOOT & ANKLE SURGERY
small cell cancer have an estimated survival time of 6 to 17 weeks. Yet, even with treatment, the mean survival after diagnosis is only about 1 year (5). Diagnosis of Bronchogenic Tumors
A tumor of 1 em, in diameter is the smallest sized tumor detectable on a chest x-ray (7). With the onset of newer and more sophisticated imaging diagnostics, such as computerized axial tomography (CAT) scans and magnetic resonance imaging (MRI) for soft tissue lesions, clinicians have dramatically improved their ability to identify and isolate abnormal anatomy. Radiographic findings in metastatic bone disease vary with the type of primary lesion and the bone involved. If a primary tumor is suspected, the oncologist would then obtain a histologic specimen of the primary lesion for examination. In many instances, the probable histologic diagnosis of a primary tumor can be made via biopsy of
FIGURE 2 Radiographs taken at this initial visit. A, anteroposterior reveals a mottled increase in osseous density along the proximal port ion of the shaft of the third metatarsal of the right foot. The midshaft area of the third metatarsal exhibits, to some extent, demineralization of bone. B, lateral oblique. Arrow directs our attention to the cortical breach noted at the proximal lateral cortical margin.
a SUSpiCIOUS lesion isolated elsewhere, representing a metastatic focus. Discussion of Malignancies and Metatases
In the United States during 1995, there were about 1.2 million new cases of cancer (exclusive of non melanotic skin cancer) and more than 500,000 deaths from cancer overall (8). Osseous metastases developed in approximately 30% of all patients with cancer (9). Mankin stated that the frequency of metastastic carcinoma far exceeds that of primary tumors of bone, especially in later life, so that staging of any individual with a bone tumor should include a careful clinical imaging and laboratory evaluation of the more frequent sites of origin (10) . Breast, prostate, lung, and kidney cancers are the most common primary malignancies causing skeletal
metastases. The frequency of breast cancer in females accounts for more than 50% of secondary skeletal metastases in women, and the se lesions are osteolytic, mixed, or osteoblastic metastases in that order of frequency . Similarly, in males, prostatic cancer is the most frequent cause of metastatic bone disease, and these lesions are predominantly osteoblastic (11). Although metastatic lesions of the foot are rare, foot pain may be potentially suggestive of an occult carcinoma (12). Metastatic bone cancer presents with bone pain, frequently with presence of pathologic fracture (11). When metastatic carcinoma does affect the foot , it is not unusual for symptoms in the foot to become apparent before the detection of the primary tumor (13). In the study by Gall et al., five of the eight patients with metastatic lesions had foot pain as their initial complaint (12). Nevertheless, statistically only 0.007 to 0.3% of paVOLUME 37, NUMBER 1, 1998
57
tients have acrometastases, such as lesions in the hand or foot (9). In their study of 2800 osseous tumors, Gall and colleagues found only 19 malignant lesions of the foot. A study performed at Johns Hopkins found 13 malignant primary osseous lesions in 1740 bone tumors (12). Several other authors have investigated the incidence of pedal bone cancers and offer their insight. Metastastic diseases of the foot and ankle are rare. Of the more than 75,000 patients with primary malignancies treated between 1972 and 1983 at our institution, only 10 were found to have foot or ankle metastatic disease. Wu and Guise found only four cases among the records of 41,833 cancer patients (14). Zindrick et al. reviewed the world literature in 1982 and found only 38 cases of histologically confirmed disease in 72 reported cases of metastatic disease of the foot (15). K. Gauntt et at. noted that statistics indicate a frequency of <2% for metastatic lesions in the foot among all metastatic skeletal lesions (16). Other authors state bone tumors of the foot and tarsal bones were found in only 1.7% of all bone tumors in a Mayo Clinic review of 6034 bone tumor cases (17). With respect to metastasis to the foot, common sites of involvement include the calcaneus and metatarsals, although phalanges and talus, cuboid, navicular, and cuneiform bones are also involved (9, 13, 15, 18, 19). The statistical data indicate a low incidence of bone tumors being identified in the feet when compared to bone tumors found elsewhere in the skeleton. The identification of bone tumors in the feet by means of biopsy, or autopsy, or both, however, creates a continual awareness of their possible presence. Case Study
A 42-year-old white female presented to the author complaining of pain and swelling of her right foot persisting for the past year. The patient recalled occasional tenderness of her right foot for approximately the past 2 years, yet she had not sought care during that period. Approximately 14 months before presentation, while attending a wedding, her right foot was inadvertently stepped upon, creating increased pain and swelling. The pain was sufficiently severe to warrant an emergency room visit, where radiographic examination revealed an apparent fracture of the base of the third right metatarsal (Fig. 1). Follow-up with a local practitioner consisted of continued immobilization with a wooden shoe as well as elastic wraps. Subsequent radiographs revealed continued disruption of the lateral cortices at the third right metatarsal, with demineralization at the proximal extent of this metatarsal. Five months later, a technetium bone scan confirmed increased uptake at the proximal por58
THE JOURNAL OF FOOT & ANKLE SURGERY
FIGURE 3 Small cell carcinoma. Photomicrographs A and B reveal islands of small, round-to-spindle-shaped cells containing little cytoplasm and deeply basophilic hyperchromatic nuclei. B depicts the spindle-shaped pattern of small cell carcinoma. C shows areas of distorted tumor cells, (arrow), seen adjacent to fragments of bone (H&E x40).
tions of the third metatarsal, consistent with that of a fracture. No additional areas of uptake were apparent. At the time of her initial visit to the author, the patient presented as a pleasant, moderately obese, Caucasian
FIGURE 4 Patient has now undergone eight months of chemotherapy. A, anteroposterior and S, lateral oblique radiographs continue to exhibit a mottled appearance of bone at the third metatarsal, with loss of cortical definition.
female. Her past and present medical history was essentially unremarkable, in that the patient denied any prior history of diabetes or lung, liver, or kidney disorders. She did state that there was a history of mitral valve prolapse and occasional rapid heart beat, which was controlled with medication. She was a nonsmoker, denied any prior surgical history, and indicated allergies to mold, pollen, and penicillin. Her current medication included propranolol hydrochloride. Upon physical examination, the following was noted: dorsalis pedis pulses were 2/4 bilateral, whereas the posterior tibial pulses were nonpalpable bilaterally. Multiple varicosities were present at both lower extremities. Her patellar and achilles reflexes were intact bilaterally, whereas the Babinski reflex was not elicited at either foot . What was clinically evident was an increased temperature gradient at her right lower extremity when compared to her contralateral limb. Also noted was a
brawny type edema of + 2, involving only her right foot. Radiographs taken on this date revealed a cortical breach at the proximal lateral cortical margin of the third right metatarsal. There also appeared to be demineralization of bone along the midshaft of that metatarsal, with mottled increase in bone density along its proximal portion (Fig. 2). The patient was placed in a short leg walking cast and given instructions to elevate and ice the right foot , and to decrease ambulation. Laboratory studies consisting of a complete blood cell count with differential were performed at a local hospital, with laboratory values found to be within normal limits, except for an elevated blood sedimentation rate of 37 mm./hr. In view of these test results, a gallium-67 citrate scan was ordered. The scan indicated an increased uptake at the dorsolateral aspect of her right foot. A positive technetium-99m scan and a negative gallium-67 citrate scan may be associated with an 85% VOLUME 37, NUMBER 1, 1998
59
probability that an infection is not present, whereas a positive technetium scan and a positive gallium scan represent a 70% certainty that osteomyelitis is established (20). The differential diagnosis consisted of a pathological metatarsal fracture secondary to osteomyelitis, or a pathological fracture, possibly secondary to bone or soft tissue neoplasia. In order to obtain a more specific diagnosis, the patient underwent a percutaneous needle biopsy utilizing fluoroscopy under local anesthetic. Because of the possibility of bacterial contaminants being isolated, arrangements were made for intravenous home therapy, depending upon the results of intraoperative culture and sensitivity tests. Final culture results indicated negative growth for aerobic and anaerobic bacterial organisms. The bone biopsy was equally unremarkable, with the microscopic sections revealing a single fragment of bone, several fragments of skin as well as fragments of clotted blood and hyaline material. No necrotic bone was seen. In view of these negative findings, yet persistent clinical and radiographic evidence of abnormal activity, preparation was made for an open excisional and exploratory surgery. The patient and her husband were seen for surgical consultation. Clinically, her right foot had increased edema and calor. There was no evidence of drainage nor sinus tract formation. An excisional biopsy was performed on an outpatient basis. Intraoperative gram stains were negative for bacteria. Soft tissue and bony specimens were excised and sent for pathologic examination intraoperatively. Preliminary findings from tissue specimens indicated cellular tumor and possibly malignant activity. In view of these significant findings, the incision was closed, with further treatment pending identification of the malignancy. The soft tissue and bone biopsies were forwarded to regional and out-of-state institutions for review. A diagnosis of oat cell carcinoma was made. The patient was then referred to an oncologist for follow-up and treatment. Photomicrographs (Fig. 3, A-C) exhibit the histologic characteristics of small cell carcinoma. A diagnosis of metastatic small cell carcinoma (oat cell carcinoma) was confirmed by a positive immunostaining pattern with neuron-specific enolase. The tumor cells showed a negative staining pattern with leukocyte common antigen. Grossly, the specimen consisted of multiple fragments of tan to pink soft, friable tissue, mixed with fragments of bone and fibrous and tendinous tissue, with an aggregate measurement of 4 em. X 2.5 em. X 2 em. The patient was seen the following week for suture removal. There did not appear to be any signs of bacterial infection, and the incision site appeared well coapted and closed. Additional testing performed, in60
THE JOURNAL OF FOOT & ANKLE SURGERY
FIGURE 5 A, axial image; B, sagittal section of right foot via MRI graphically exposes the infiltration of tumor mass throughout various compartments of the right foot.
eluding CAT, revealed metastatic involvement, with small but identified tumors noted to be in the lungs, the retroperitoneal area, and the inguinal region of her torso. An incisional biopsy performed on a mass at her inguinal region proved to be oat cell carcinoma upon microscopic examination. Over the next several months, she was treated with a variety of chemotherapeutic agents, including cisplatin, cyclophosphamide, and etoposide as well as with radiation therapy for her right foot. Three weeks later, [mal radiographs were taken of her right foot (Fig. 4). They revealed
the continued cortical irregularities of the third metatarsal, as well as the loss of a trabecular pattern of bone along the shaft. MRI, performed approximately 1 year after her first visit, graphically depicted the invasiveness of this tumor and its spread throughout the right foot (Fig. 5). Despite her early success with various treatment modalities, the patient died several months later. Summary The distinguishing characteristics with this case history were recalcitrant pain at her right foot and the failure of an apparent stress fracture to resolve over time. At the time of her initial office visit, she did not exhibit any systemic manifestations, nor did she complain of difficulty breathing, weight loss, or loss of appetite. She denied smoking or being exposed to second-hand smoke. Laboratory analysis, which included hematology and chemistry studies, urinalysis, rheumatoid profile, antinuclear antibodies, antistreptolysin-O titer, and electrolyte levels, were unremarkable except for a slightly elevated erythrocyte sedimentation rate. When radiographic findings exhibited neither consolidation nor improvement after conservative measures, further diagnostic testing, including biopsy of the affected site, was performed. Once a diagnosis was achieved, aggressive treatment was initiated. The vast majority of patients with small cell anaplastic carcinoma present with extrapulmonary metastatic disease at the time of diagnosis (21). One must speculate, however, that in this patient, oat cell carcinoma was actually present months before the incidental trauma to her foot, which in turn prompted her to seek care. As noted, untreated, patients with small (oat) cell carcinoma have a survival time of 6 to 17 weeks (5). Clearly, the scarcity of metastatic pedal malignancies is well documented. Yet the very fact of their existence should always encourage the maintenance of a vigil for their possible presence. Whenever patients complain of persistent pain or swelling, or both, in their feet, one must consider the possibility of neoplastic changes, particularly when initial conservative measures fail to resolve the patients' initial presentation. Acknowledgment The authors thank Jacalyn Palmer and Drs. Patrick Connally and Neerupama Bhatia for all of their assistance in securing and producing the photomicrographs. References 1. Taber's Cyclopedic Medical Dictionary, p. 1787, edited by C. L. Thomas, A Davis Company, Philadelphia, 1985. 2. Kirby, E., Shereff, M., Lewis, M. Soft-tissue tumors and tumor-like lesions of the foot. J. Bone Joint Surg. 71A:621-626, 1989.
3. Steinberg, M., Steinberg, L. Tumors of the foot. J. Am. Podiatr. Assoc. 69:135-138, 1979. 4. Berlin, S. J. Statistical analysis of 307,601 tumors and other lesions of the foot. J. Am. Podiatr. Med. Assoc. 85:699-703, 1995. 5. Robbins, S. L. In Robbins: Pathologic Basis of Disease. 5th ed., pp. 295-297; 381-383; 720-724, edited by R. S. Cotran, V. Kumar, S. L. Robbins, W. B. Saunders Company, Philadelphia, 1994. 6. Miller, Y. E. Pulmonary neoplasms, Part VIII. In Cecil Textbook of Medicine, 20th ed., pp. 436-442, edited by J. C. Bennett, F. Plum, W. B. Saunders Company, Philadelphia, 1996. 7. Dantzker, D. R, Tobin, M. J., Whatley, R E. Neoplastic diseases of the lung, Ch. 24. In Cecil Essentials of Medicine, pp 66-170, edited by T. Andreoli, C. Carpenter, F. Plum, L. Smith, W. B. Saunders Company. Philadelphia, 1986. 8. Anderson's Pathology, 10th ed., pp, 541-544; 1541-1545, edited by I. Damjanov, J. Linder, C. V. Mosby-Year Bk., Inc., St. Louis, 1990. 9. Healey, J. H., Turnbull, A., Miedema, B., Lane, J. M. Acrometastases: a study of twenty-nine patients with osseous involvement of the hands and feet. J. Bone Joint Surg. 68-A:743-746, 1986. 10. Mankin, H. J., Gebhardt, M. C. Advances in the management of bone tumors. Clin. Orthop. 200:73-83, 1985. 11. Moser, R P., Madewell, J. E. Metastatic bone cancer. In Radiology, Diagnosis, Imaging and Intervention, vol. 5, pp. 1-8, edited by J. Traveras, J. B. Lippincott, Philadelphia, 1986. 12. Gall, R J., Sim, F. H., Pritchard, D. J. Metastatic tumors to the bones of the foot. Cancer 37:1492-1495, 1976. 13. Eggold, J. F., McFarland, J. A, Hubbard, E. R. Adenocarcinoma of the lung with phalangeal metastasis. J. Am. Podiatr. Med. Assoc. 75:547-549, 1985. 14. Wu, K K., and Guise, E. R Metastatic tumors of the foot. South. Med. J. 71:807-808, 1978. 15. Zindrick, M. R, Young, M. P., Daley, R J., Light, T. R Metastatic tumors of the foot: case report and literature review. Clin. Orthop. 170:219-225,1982. 16. Gauntt, K, Boykoff, T., Danna, A Adenocarcinoma: case of metastasis to the foot. J. Am. Podiatr. Med. Assoc. 80:657-659, 1990. 17. Posteraro, R. H. Radiographic evaluation of pedal osseous tumors. Clin Pod Med Surg. 10:633-653, 1993. 18. Hattrup, S. J., Amadio, P. C., Sim, F. H., Lombardi, R M.: Metastatic tumors of the foot and ankle. Foot & Ankle. 8:243-247, 1988. 19. Libson, E., Bloom, R A., Husband, J. E., Stoker, D. J.: Metastatic tumours of bones of the hand and foot. Skel Radiol 16:387-392, 1987. 20. Marcinko, D. E. ch 70. In Comprehensive Textbook ofFoot Surgery, 2nd ed., vol. 2, p. 1729, edited by E. D. McGlamry, A S. Banks, M. S. Downey, Williams & Wilkins, Baltimore, 1992. 21. Hansen, H. H., Dobernowsky, P., Hirsh, F. R. Staging procedures and prognostic features in small cell anaplastic bronchogenic carcinoma. Semin. Oncol. 5:280-287, 1978.
Additional References Anderson, E. E., Leitner, W. A, Boyarsky, S., Small, M. P., and McCollum, D. E. Renal-cell carcinoma metastatic to great toe. J. Bone Joint Surg. 50A:997-998, 1968. Barnett, L. S., and Morris, J. M. Metastases of a renal-cell carcinoma simultaneously to a finger and a toe: a case report. J. Bone Joint Surg. 5IA:773-774, 1969. Berlin, S., Mirkin, G., Tubridy, S. Tumors of the heel. Clin. Pod. Med. Surg. 7:307-321, 1990. Bevan, D. A., Ehrlich, G. E., and Gupta, V. P. Metastatic carcinoma simulating gout. J. Am. Med. Assoc. 237:2746-2747, 1977.
VOLUME 37, NUMBER 1, 1998
61
Bloodgood, J. Bone tumors, benign and malignant. Amer. J. Surg. 34:229-236, 1920. Bright, M., and Wilkie, J. R. Carcinoma metastasis to talus and metatarsals (Letter to the Editor). J. Am. Med. Assoc. 210:1592, 1969. Bunkis, J., Mehrhof, A I., and Stayman, J . W., III. Metastatic lesions of the hand and foot. Orthop. Rev. 9:97-101, 1980. Cohen, P., Buzdar, A Metastatic breast carcinoma mimicking an acute paronychia of the great toe : case report and review of subungual metastases. Am. J. Clin. Oncol. 16:86-91, 1993. Colson , G., Wilcox, A Phalangeal metastases in bronchogenic carcinoma. Lancet 254:100-102, 1948. Dripchack, P., Roberson, J. Breast cancer metastatic to the foot with massive bone loss. Orthop. Rev. 19:877-879, 1990. Dunn, E., Mauro, G., Cohen, R. Giant cell tumor of the intermediate cuneiform. J. Am. Podiatr. Med . Assoc. 82:208-211, 1992. Fort, W. Cancer metastatic to bone. Radiology 24:96-98, 1935. Harkonen, M., and Olin, P. E. Rectal carcinoma metastasizing to a toe. Acta Med . Scand. 207:235-236, 1980. Harrington, K. Management of lower extremity metastases. In Orthopedic Management of Metastatic Bone Disease, pp. 141-214, C. V. Mosby, St. Louis, 1988. Hirsch, F., Hansen, H. H., Dombernowsky, P., Hainau, B. Bone marrow examination in the staging of small-cell anaplastic carcinoma of the lung with special reference to sub typing. Cancer. 39:2563-2567, 1977. Jacox , R. F., and Tristan, T. A : Carcinoma of the breast metastatic to the bones of the foot: a case report. Arthritis Rheum 3:170-177, 1960. Janis, L. R., and Feldman, E. P. Metastatic adeno carcinoma at the calcaneus: case report. J. Foot Surg. 15:28-32, 1976. Katz, L. Pulmonary carcinoma metastasis to great toe. J. Am. Med. Assoc. 208:2163-2166, 1969. Khiyami, A, Green, L., Gyorkey, F., Landon, G. Primary angiosarcoma of the cuboidal bone: a case report. Diagn . Cytopathol. 7:520-523, 1991.
62
THE JOURNAL OF FOOT & ANKLE SURGERY
Kinley, S., Wiseman, F., Wertheimer, S. Giant cell tumor of the talus with secondary aneurysmal bone cyst. Foot Ankle 32:38-46, 1993. Kumar, P. P. and Kovi, J. Metastases to bones of the hands and feet. J. Natl. Med. Assoc. 7:837-840, 1978. Mess, D., and Songer, M. Head and neck carcinoma meta stases to the hand and foot: a case report of simultaneous involvement. Orthopedics 9:975-977, 1986. Moeller, F. A. Pulmonary adeno carcinoma: metastasis to a lesser toe . J. Am. Podiatr. Med. Assoc. 61:297-301 , 1971. Moore, J. Tumors of the os calcis. Radiology 16:232-244, 1931. Murari, T., Callaghan, J., Berrey, B., Sweet , D. Primary benign and malignant osseous neoplasms of the foot . Foot Ankle 10:68-80, 1989. Panebianco, A c., Kaupp , H. A Bilateral thumb metast asis from breast cancer. Arch Surg. 96:216-218, 1968. Smithers, D. W., Price, L. R. W. Isolated secondary deposit in a terminal phalanx in a case of squamous-cell carcinoma of the lung. Br. J. Radiol. 18:299-300, 1945. Sundberg, S. B., Carlson, W.O., Johnson, K. A Metastatic lesions of the foot and ankle. Foot Ankle 3:167-169, 1982. Sworn, M. J., Buchanan, R., Moynihan, F. J. Rectal carcinoma presenting as massive metastatic involvement of foot bones . Br. Med. J. 2:98-99, 1978. Toth, J. G. Metastases to the fingers from breast cancer. Can. Med. Assoc. J. 129:534, 1983. Vaezy, A., and Budson , P. C. Phalangeal metastases from bronchogenic carcinoma. J. Am. Med. Assoc. 239:226-227, 1978. Weitzner, S. Adenoid cystic carcinoma of submaxillary gland metastatic to great toe . Am. Surg. 41:655-658, 1975. Williams, R. P., Pechero, G. Management of soft tissue and bone tumors of the foot. Clin. Podiatr. Med. Surg . 10:717-725 , 1993. Wu, K. K. Differential diagnosis of pedal osseous neoplasms . Clin. Podiatr. Med. Surg. 10:683-715, 1993. Wu, K. K. Tumor review: osteogenic sarcoma of the foot. J. Foot Surg. 26:269-271, 1987.