Metastatic skeletal disease is the most common form of oncologic disease encountered in orthopedic oncology, with patients with breast, lung, prostate, renal, or thyroid cancer having a 20% to 75% incidence of osseous metastases.1,2 Advances in oncologic treatment have led to improvements in the prognosis of patients with cancer. With improving survival rates, metastatic skeletal disease is becoming an increasingly important component of the treatment of these patients.
Metastases to the hand or foot, known as acrometastases,3 are rare, representing 0.007% to 0.3% of all skeletal metastases.4,5 Historically, acrometastases have been treated nonoperatively; when surgery was indicated, amputation was preferred. The most recent review, describing a large institutional experience with acrometastases, is more than 30 years old.3 Since then, major advancements in local and systemic cancer treatment have improved the prognosis for patients with osseous metastatic disease. Changes in prognosis and treatment may result in a change in metastatic patterns of disease. This can be observed through the steady increase in reported cases of acrometastases.6
The purpose of this investigation was to describe the current clinical characteristics of acrometastases in the context of modern cancer treatment. Specifically, the authors sought to determine the most common primary malignancies, lesion sites, types of treatment, and survival time after diagnosis.
Materials and Methods
The authors reviewed medical records from their institution's cancer registry, orthopedic oncology database, and radiology database. They queried to identify all patients with metastatic cancer to bone. Patients 17 years or older with radiographically or histologically proven osseous metastases of the hands and/or feet evaluated and treated by the orthopedic oncology service at the authors' institution from January 1, 1990, to November 30, 2017, were included. Patients with distal metastatic lesions proximal to the carpal bones in the hand or tarsal bones in the foot and patients with hematologic malignancies were excluded. Twenty-eight patients with 32 lesions met the study criteria. Of the 28 patients in this series, 23 had had extended follow-up at the authors' institution.
The following data were retrieved from the medical records: patient age, sex, primary cancer, date of primary diagnosis, pattern of metastasis, Eastern Cooperative Oncology Group Performance Status score, date of acrometastases diagnosis, skeletal events, and treatment. Primary cancer was classified into 3 groups—tumors that exhibit rapid growth, moderate growth, or slow growth—as described by Katagiri et al.7 The anatomic location within the hand or foot of each lesion was identified, and local treatment was determined. Imaging studies, including bone scans, computed tomography scans, magnetic resonance images, and radiographs, were reviewed for each patient. In addition, pathology reports were reviewed, if available. Acrometastases were described according to their specific locations, analyzed for all patients, and stratified by each primary cancer type.
Time to acrometastases diagnosis was calculated as the time, in months, from primary cancer diagnosis to acral lesion diagnosis. If the acral lesion was the first sign of an occult malignancy, time to acrometastases diagnosis was considered to be 0 months. Kaplan–Meier curves were used to calculate survival time after acrometastases diagnosis, and log-rank tests were used to identify significant differences between survival of patients with metastatic disease to the hand vs the foot. Statistical significance was set at P=.05.
For the overall cohort, the median age of patients diagnosed with acrometastatic disease was 61.5 years (range, 16–85 years). More males than females were affected (16 [57%] vs 12 [43%]).
Of the 23 patients with follow-up, the median age of the patients diagnosed with acrometastatic disease was 61.3 years (range, 16–74 years). Most patients were male (60.8%). Nineteen patients (82.6%) had Eastern Cooperative Oncology Group Performance Status scores between 0 and 2 (Table 1).
Potential Prognostic Factors for the 23 Patients With Follow-up
Primary Site–Related Factors
In the overall cohort, the most common primary cancers that progressed to acrometastases were lung carcinoma (n=9), renal cell carcinoma (n=5), and prostate carcinoma (n=4). A variety of other carcinomas and sarcomas accounted for 1 or 2 cases each (Table 2). For 2 of the lung carcinoma patients and 1 of the breast carcinoma patients, an acral metastatic lesion was the first sign of malignancy.
Primary Cancers Among the 28 Patients With Acrometastases
Of the 23 patients with follow-up, most had tumors that exhibited moderate growth (9 patients, 39.1%). At the time of acral metastases, only 9 patients (39.1%) had a remaining primary lesion, a minority of whom had a history of systemic chemotherapy treatment (6 patients, 26.1%). Eleven patients (47.8%) had concomitant focal metastases to the brain or viscera (Table 1).
Skeletal Metastases–Related Factors
Sixteen patients had lower extremity acrometastatic disease, and 12 patients had upper extremity acrometastatic disease. Eighteen lesions were identified in the patients with lower extremity acrometastases, distributed as follows: 11 to the tarsal bones, 4 to the metatarsals, and 3 to the phalanges. Interestingly, metastatic disease from prostate carcinoma affected only the lower extremities, specifically the tarsal and metatarsal bones. Of upper extremity acrometastases, 14 lesions were identified as follows: 6 to the metacarpals, 6 to the phalanges, and 2 to the carpals (Figure 1). Twelve patients (43%) in the cohort had bone-only metastases.
Diagrams showing the relative distribution of 32 acrometastases in the hand (A) and foot (B) among 28 patients.
Of the 23 patients with follow-up, 14 patients (60.9%) had multiple skeletal metastases and 8 patients (34.8%) had evidence of a pathologic fracture (Table 1).
The most common form of treatment among the 23 patients with follow-up was resection or curettage only (n=7), followed by radiation only (n=2) and a combination of resection and radiation (n=2). Six patients received no local treatment (Table 3). The remaining patients were lost to follow-up.
Local Treatment Modalities Used for Acrometastases Among the 23 Patients With Follow-up
For the 23 patients with follow-up, the median time from the diagnosis of the primary malignancy to the development of acrometastases was 2.0 years (range, 0–19 years). Twelve patients died at a median of 7.7 months (range, 1.3–144 months) after acrometastasis diagnosis. Seven patients survived, and 4 were lost to follow-up. The estimated overall median survival time after acrometastases diagnosis was 9.7 months (standard error, 1.6 months) (Figure 2). The estimated median survival time was 7.6 months (standard error, 2.5 months) for patients with metastatic disease to the hand vs 115 months (standard error, 0 months) for patients with metastatic disease to the foot (Figure 3). One patient with metastatic lung cancer to the talus survived 144 months. Given the numbers available, no significant difference could be detected between survival time for patients with disease to the hand vs those with disease to the foot (P=.059).
Overall survival time after acrometastases diagnosis among 23 patients with follow-up.
Survival time for acrometastases to the hand vs foot among 23 patients with follow-up. The marked discrepancy in survival is due to a single patient with acrometastases to the foot who survived 144 months.
Skeletal metastases to the hands and feet are exceedingly rare, although the true incidence is unknown.8–11 The rarity of acrometastases is likely related to the unfavorable characteristics of the bony environment in the hand and foot secondary to factors such as poor red marrow content and brisk venous flow.12 The authors postulated that as patients are living longer with neoplastic disease, their patterns of metastatic disease are shifting, perhaps leading to a change in the presentation of acrometastases.
The authors found that lung carcinoma was the most common primary tumor responsible for acrometastases in this series (32.1%). This was followed by renal cell carcinoma (17.9%) and prostate carcinoma (14.3%). Breast cancer and soft tissue sarcoma accounted for 7.1% each. Healey et al3 found that in a cohort of 29 patients with acrometastases, lung carcinoma and renal carcinoma were equally dominant—at 17% each—as the most common primary cancers. A more recent literature review by Stomeo et al6 analyzed 70 cases of acrometastases to the hands and feet. Their findings were similar to those of the current study, with the most common primary cancers being lung carcinoma (33%), renal cell carcinoma (20%), breast carcinoma (13%), and colon carcinoma (10%). The distributions of the most common primary cancers were similar for hand and foot acrometastases. Amadio and Lombardi4 found that lung carcinoma and renal cell carcinoma were the most common primary cancers in acrometastases to the hand, whereas Hattrup et al13 found that lung carcinoma was the most common primary cancer in acrometastases to the foot. Interestingly, in a more recent systematic review of the literature, Maheshwari et al14 analyzed 229 cases of acrometastases to the foot (including data from their own patients) and found that genitourinary primary neoplasms were the most common primary malignancy. Overall, the current case series agrees with the current literature regarding primary malignancies. Lung remains the most common primary tumor accounting for skeletal metastases to the hands and feet.
This study estimated that osseous metastases to the foot were slightly more common than osseous metastases to the hand (57% vs 43%). This differs from the results of Stomeo et al,6 which indicated that metastases to the hand were significantly more common than metastases to the foot (70% vs 30%), although the numbers were small. The current series showed that the most common location for acral metastases was equally distributed between the metacarpals and the phalanges for the hand and the tarsals for the foot. The most common site of acrometastatic disease observed by Maheshwari et al14 was also the tarsal bones (calcaneus was the most common, followed by talus). In the literature, most of the osseous metastases are to the phalanges in the hand and also to the phalanges in the foot.6 The mean age and sex distributions in the current study match those of previous studies.
Regarding survival time, the authors used medians in their analysis because their data were non-normally distributed. The median survival time was 9.7 months (standard error, 1.6 months). For disease to the hand, the median survival time was 7.6 months (standard error, 2.5 months). For disease to the foot, the median survival time was 115 months. A study from the Memorial Sloan Kettering Cancer Center3 reported a mean survival time after diagnosis with acrometastases to the hand of 8.4±8.5 months vs 15±19 months to the foot. The large standard deviation suggests a non-Gaussian distribution in their data set. The difference in median survival time for patients with acrometastases to the foot in the current series is attributable to the long survival of 1 patient (144 months), the small sample, and the censoring of several patients with metastatic disease to the foot. For patients treated at the Mayo Clinic, Amadio and Lombardi4 reported that the mean survival time was 14 months after diagnosis of metastases to the hand. Hattrup et al13 estimated the mean survival time after diagnosis of metastases to the foot as 12 months. The mean survival time observed by Maheshwari et al14 was 15 months, with most patients receiving local palliative radiation for acrometastases. In their series, patients with hand metastases had a substantially longer survival time than those with foot metastases; those with foot metastases had a shorter survival time compared with that of the current cohort. Overall, survival following metastatic disease to the hand or foot is consistent among many investigations.
One difference between the current series and previous reports is type of treatment. Healey et al3 reported that amputation was the most common intervention in their cohort (9 of 29 patients). Amadio and Lombardi4 also reported a similarly high rate, with 9 of 18 patients undergoing amputation. In the series reported by Hattrup et al,13 radiation was the most common treatment (13 of 21 patients), whereas amputation was the most common surgery performed (33%; n=7). In the more recent study, by Maheshwari et al,14 surgery was used sparingly, with most patients receiving radiation only. In the current study, the most common form of intervention was nonablative surgery, resection, excision, or curettage, which was performed in 9 of 18 patients. Only 1 patient required amputation of a toe. No treatment, surgical or otherwise, was performed in 6 of the current patients. According to the available literature and the authors' data, there is much heterogeneity in the treatment of acral metastases. The current results and those of Maheshwari et al14 suggest that amputation may be less appealing in the modern treatment of acrometastases; however, the limited information on functional outcomes and the small number of reported case series of treatment of acrometastases prevent definitive conclusions on the best treatment strategies for these lesions. Unfortunately, no prognostic analysis could be performed attributable to type of surgical intervention. Additionally, in the current study, a large number of patients had incomplete treatment data, although this was a limitation common to each of the cited case series.3,4,13,14
Advances in prognosis and improved survival for patients with metastatic oncologic disease will likely affect observed patterns of osseous metastatic disease. Improved survival allows for increased focus on quality of life in patients with metastatic cancer. Hand pain and injury can have a major detrimental effect on psychological, social, and economic facets of life.15–18 Foot pain and injury can have a similarly detrimental effect on quality of life, psychological well-being, and function and can even predispose patients to falls, which, in the setting of existing skeletal metastatic disease, may increase the risk of pathologic fracture.19–21
Because of the relative rarity of reported acrometastatic disease, acrometastases may be overlooked as a differential diagnosis in hand or foot pain, leading to delayed diagnosis.10,22,23 Timely diagnosis and intervention can substantially improve function and quality of life.10
This study had several limitations. The sample was small; thus, the statistical analysis of survival, specifically the log-rank test, may not be representative. Additionally, as a retrospective review of an institution's oncologic databases, this study was dependent on the fidelity with which the data were entered from various clinical departments. The diagnosis of acrometastases can be challenging, even for the orthopedic surgeon. There is the possibility that some of the symptoms of acrometastatic disease may be attributable to other causes. For example, at least 1 of the patients in this study was thought to have foot pain secondary to chemotherapy-induced peripheral neuropathy; acrometastatic disease was identified only after orthopedic evaluation. Therefore, the authors believe that, despite their best efforts to identify patients, the incidence of osseous metastases was underreported in this study. Finally, because some patients were lost to follow-up, the authors had incomplete data regarding treatment. Despite these limitations, the authors believe that their investigation of a single-institution experience reflects a current assessment of the clinical characteristics and patterns of acrometastases.
The aim of this study was to characterize and update the clinical characteristics of patients with acrometastases in the era of modern cancer treatment. Despite their presumption that improvements in cancer treatment might lead to a change in the clinical presentation of acrometastases, the authors found that there was no significant change in the most common primary neoplasm that causes osseous acrometastases (lung carcinoma) or mean age and distribution among the sexes. The most common surgical intervention was limb salvage, reflecting the shift from amputation to limb salvage over time.
- Coleman RE. Metastatic bone disease: clinical features, pathophysiology and treatment strategies. Cancer Treat Rev. 2001;27(3):165–176. doi:10.1053/ctrv.2000.0210 [CrossRef]
- Mundy GR. Metastasis to bone: causes, consequences and therapeutic opportunities. Nat Rev Cancer. 2002;2(8):584–593. doi:10.1038/nrc867 [CrossRef]
- Healey JH, Turnbull AD, Miedema B, Lane JM. Acrometastases: a study of twenty-nine patients with osseous involvement of the hands and feet. J Bone Joint Surg Am. 1986;68(5):743–746. doi:10.2106/00004623-198668050-00017 [CrossRef]
- Amadio PC, Lombardi RM. Metastatic tumors of the hand. J Hand Surg Am. 1987;12(2):311–316. doi:10.1016/S0363-5023(87)80299-X [CrossRef]
- Chung TS. Metastatic malignancy to the bones of the hand. J Surg Oncol. 1983;24(2):99–102. doi:10.1002/jso.2930240206 [CrossRef]
- Stomeo D, Tulli A, Ziranu A, Perisano C, Maccauro G. Acrometastasis: a literature review. Eur Rev Med Pharmacol Sci. 2015;19(15):2906–2915.
- Katagiri H, Okada R, Takagi T, et al. New prognostic factors and scoring system for patients with skeletal metastasis. Cancer Medicine. 2014;3(5):1359–1367. doi:10.1002/cam4.292 [CrossRef]
- Hayden RJ, Sullivan LG, Jebson PJ. The hand in metastatic disease and acral manifestations of paraneoplastic syndromes. Hand Clin. 2004;20(3):335–343. doi:10.1016/j.hcl.2004.03.010 [CrossRef]
- Bròdano GB, Cappuccio M, Gasbarrini A, et al. Vertebroplasty in the treatment of vertebral metastases: clinical cases and review of the literature. Eur Rev Med Pharmacol Sci. 2007;11(2):91–100.
- Flynn CJ, Danjoux C, Wong J, et al. Two cases of acrometastasis to the hands and review of the literature. Curr Oncol. 2008;15(5):51–58.
- Kerin R. Metastatic tumors of the hand: a review of the literature. J Bone Joint Surg Am. 1983;65(9):1331–1335. doi:10.2106/00004623-198365090-00016 [CrossRef]
- Viswanathan PN, Rangad F, Roul RK. Metastases to the hand from carcinoma of the lower alveolus. J Hand Surg Br. 1996;21(4):544–546. doi:10.1016/S0266-7681(96)80062-3 [CrossRef]
- Hattrup SJ, Amadio PC, Sim FH, Lombardi RM. Metastatic tumors of the foot and ankle. Foot Ankle. 1988;8(5):243–247. doi:10.1177/107110078800800503 [CrossRef]
- Maheshwari AV, Chiappetta G, Kugler CD, Pitcher JD Jr, Temple HT. Metastatic skeletal disease of the foot: case reports and literature review. Foot Ankle Int. 2008;29(7):699–710. doi:10.3113/FAI.2008.0699 [CrossRef]
- Bailey R, Kaskutas V, Fox I, Baum CM, Mackinnon SE. Effect of upper extremity nerve damage on activity participation, pain, depression, and quality of life. J Hand Surg Am. 2009;34(9):1682–1688. doi:10.1016/j.jhsa.2009.07.002 [CrossRef]
- Koestler AJ. Psychological perspective on hand injury and pain. J Hand Ther. 2010;23(2):199–210. doi:10.1016/j.jht.2009.09.001 [CrossRef]
- Kovacs L, Grob M, Zimmermann A, et al. Quality of life after severe hand injury. J Plast Reconstr Aesthet Surg. 2011;64(11):1495–1502. doi:10.1016/j.bjps.2011.05.022 [CrossRef]
- Turkington C, Dempster M, Maguire J. Adjustment to hand injury: cross-sectional survey exploring adjustment in relation to illness perceptions and coping strategies. J Hand Ther. 2018;31(4):502–510. doi:10.1016/j.jht.2017.05.021 [CrossRef]
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Potential Prognostic Factors for the 23 Patients With Follow-up
|Prognostic Factor||No. (%)|
| Male||14 (60.9)|
| Female||9 (39.1)|
| <65 y||15 (65.2)|
| ≥65 y||8 (34.8)|
| ECOG Performance Status score|
| 0–2||19 (82.6)|
| 3–4||4 (17.4)|
| Laboratory data|
| Normal||17 (74.0)|
| Abnormal||3 (13.0)|
| Critical||3 (13.0)|
|Primary site–related factor|
| Primary site|
| Slow growth||6 (26.1)|
| Moderate growth||9 (39.1)|
| Rapid growth||8 (34.8)|
| Visceral or brain metastases|
| No||12 (52.2)|
| Nodular||11 (47.8)|
| Remaining primary lesion|
| No||14 (60.9)|
| Yes||9 (39.1)|
| Previous chemotherapy|
| No||17 (73.9)|
| Yes||6 (26.1)|
|Skeletal metastases–related factor|
| Metastases spreading to distal limb||23 (100)|
| Multiple skeletal metastases|
| No||9 (39.1)|
| Yes||14 (60.9)|
| Pathologic fracture|
| No||15 (65.2)|
| Yes||8 (34.8)|
Primary Cancers Among the 28 Patients With Acrometastases
|Primary Cancer||No. (%)|
|Renal cell||5 (17.9)|
|Soft tissue sarcoma||2 (7.1)|
|Lentiginous melanoma||1 (3.6)|
|Metastatic chondroid syringoma||1 (3.6)|
|Phosphaturic mesenchymal tumor||1 (3.6)|
|Squamous cell||1 (3.6)|
Local Treatment Modalities Used for Acrometastases Among the 23 Patients With Follow-up
|Resection, excision, or curettage||7|
|Resection and radiation||2|