› CASE REPORT ‹ CLINICAL CASES AND PRESENTATIONS JOHN J. ALAPATT, MS, DNB, ABHAY KATTEPUR, MCh, MS, DNB, MRCS, M.P. NIZAMUDHEEN, MCh, MS, SATHEESAN BALASUBRAMANIAM, MCh, MS, DNB Wolf in sheep’s clothing: metatarsal osteosarcoma

etatarsal are an unusu- The following case of osteosarcoma of the John J. Alapatt, MS, DNB,a al subsite for small in- metatarsal bone in a young girl highlights Abhay Kattepur, MCh, MS, DNB, MRCS,a M.P. Nizamud- volvement in osteosarcomas. the importance of having a high index of heen, MCh, MS,a Satheesan This subgroup is often misdi- clinical suspicion prior to treatment. Balasubramaniam, MCh, M MS, DNBa agnosed and hence associated with sig- aDepartment of Surgical nificant treatment delays. The standard CASE PRESENTATION AND Oncology, Malabar Cancer treatment of metatarsal osteosarcomas SUMMARY Center, Thalassery, Kerala, remains the same as for those treated A 10-year-old girl visited our outpatient India at other sites, namely neoadjuvant che- clinic with a painful progressive swell- DISCLOSURES motherapy followed by surgery and ing on the dorsum of the left foot of 2 The authors report no adjuvant chemotherapy. Limb salvage months’ duration. There was no history conflicts of interest con- surgery or metatarsectomy in the foot of antecedent trauma or fever. Physical cerning the materials or is often a challenge owing to the poor examination revealed a bony hard swell- methods used in this study or the findings specified in compartmentalization of the disease. We ing measuring around 5 x 6 cm on the this paper. hereby describe the case of a young girl dorsum of the left foot around the region with a metatarsal osteosarcoma who was of the second metatarsal. There was no managed with neoadjuvant chemothera- regional lymphadenopathy or distal neu- py and limb salvage surgery. rovascular deficit. She was evaluated with a plain radiograph that demonstrat- INTRODUCTION ed a lytic lesion in the left second meta- Osteosarcomas are the most common tarsal associated with cortical destruc- primary malignant bone tumor in chil- tion and (FIGURE 1). A dren and adolescents. Although pre- subsequent magnetic resonance image dominantly occurring in pediatric and (MRI) revealed a bony lesion destroying adolescent age groups, bimodal distri- part of the left second metatarsal with bution (with a second incidence peak oc- cortical destruction and marrow involve- curring in the sixth and seventh decades) ment and affecting the soft tissue around is not uncommon.1 Osteosarcomas of the the adjacent third metatarsal (FIGURE 2). foot and small bones represent a rare and Needle biopsy showed chondroblastic distinct clinical entity. This must have osteosarcoma. Computed tomography been a well-known observation for years (CT) of the thorax and bone scan were that led to Watson-Jones stating, “Sarco- both negative for distant metastases. ma of this [metatarsal] bone has not yet She received 3 cycles of a MAP (high- been reported in thousands of years in dose methotrexate, doxorubicin, and any country.”2 The incidence of osteosar- cisplatin) regimen as neoadjuvant che- comas of the foot is estimated to be from motherapy. Response assessment scans 0.2% to 2%.3 showed partial response (FIGURES 3A and These tumors, owing to their rarity, B). We performed a wide excision of the often lead to diagnostic dilemmas and second and third metatarsal with recon- hence treatment delays.4 They are usual- struction using a segment of non-vas- ly mistaken for inflammatory conditions cularized fibular graft as rigid fixation and often treated with—but not limited (FIGURE 4). The postoperative period was to—curettages and drainage procedures.5 uneventful. She was able to begin partial CONTINUED

MDEDGE.COM/SARCOMAJOURNAL VOL 3, NO 2 | SUMMER 2019 | THE SARCOMA JOURNAL 13 ›CASE REPORT

› THESE TUMORS ARE…USUALLY MISTAKEN FOR INFLAMMATORY CONDITIONS AND OFTEN TREATED FIGURE 1. Radiograph showing lytic lesion FIGURE 2. T2w MRI (plantar aspect) indicat- WITH—BUT NOT of left second metatarsal with periosteal ing marrow involvement of the left second LIMITED TO— reaction. metatarsal, with soft tissue component show- ing high signal intensity and involvement of CURETTAGES adjacent metatarsal bone. AND DRAINAGE PROCEDURES. weight bearing on the fourth postopera- (TABLE 1). According to a review article tive day and her sutures were removed from the Mayo Clinic, the most common on the twelfth postoperative day. She re- bone of the foot involved is the calcane- ceived adjuvant chemotherapy following um.6 While the incidence of osteosar- surgery. The final histopathology report comas of the foot as a whole is around showed residual disease with Huvos 0.2% to 2%,3 metatarsal involvement is grade III response (>90% necrosis) with documented in 0.5% of these patients.7 all margins negative for malignancy (FIG- However, a recent study depicted meta- URE 5). At present, the child is disease-free tarsal involvement in 33% of all osteo- at 5 months of treatment completion and sarcomas of the foot.8 is undergoing regular follow-up visits. Osteosarcomas at conventional sites tend to have a bimodal age distribution DISCUSSION with respect to disease affliction.9 Meta- Metatarsal involvement amongst small- tarsal osteosarcomas, however, are more bone osteosarcomas is uncommon.3 common in an older age group.4,10 Our There are about 32 cases of osteosarco- patient is probably the second youngest mas reported in the literature from 1940 reported case of metatarsal osteosarcoma to 2018 involving the metatarsal bones in the literature.11

14 THE SARCOMA JOURNAL | SUMMER 2019 | VOL 3, NO 2 CASE REPORT‹

FIGURE 4. Post limb salvage radiograph showing reconstruction by non-vascularized fibular graft. FIGURES 3A and 3B. Post chemotherapy CT images (plantar view on left) showing tumor with persisting soft tissue component.

Biscaglia et al propounded that osteo- sarcomas of the metatarsal were a distinct subgroup due to the rarity of occurrence, anatomical location, and prognosis.4 This often led to misdiagnosis and subsequent inadequate or inappropriate surgery. In six out of the ten cases (60%) described in Table 1, an incorrect pretreatment di- agnosis was made that led to treatment delay. None, except one patient, received neoadjuvant chemotherapy, which is cur- rently the standard of care. The average duration from symptom onset to diagno- sis was found to be 2 years.4 However, in our case, the duration of symptoms was approximately 2 months. Surgery for metatarsal osteosarcomas FIGURE 5. Photomicrograph showing immature bony trabeculae can be challenging, as the compartments and immature cartilage seen amidst tumor cells. of the foot are narrow spaces with poor demarcation. Limb salvage surgery in Neoadjuvant chemotherapy will serve to the form of metatarsectomy needs prop- downstage the tumor within the fascial er preoperative planning and execution. barriers of the metatarsal compartment. CONTINUED

MDEDGE.COM/SARCOMAJOURNAL VOL 3, NO 2 | SUMMER 2019 | THE SARCOMA JOURNAL 15 ›CASE REPORT

TABLE 1. Various studies on metatarsal osteosarcoma: treatment and outcomes Author/year Age/sex Initial Initial Final Histology Outcomes diagnosis treatment treatment Biscaglia R4/ 28 M not known NA disarticulation chondroblastic NED at 168 mo 1998 osteosarcoma 20 M not known NA resection osteoblastic NED at 120 mo osteosarcoma Fukuda K14/ 18 F not known NA NACT f/b BKA osteoblastic NED at 55 mo 1999 osteosarcoma Lee EY16/ 25 F enchondroma curettage ray resection high-grade NED at 9 mo 2000 osteosarcoma Choong PFM6/ 27 M osteosarcoma NA ray amputation osteosarcoma DOD at 19 mo 1999 radiotherapy grade II Sneppen O7/ 22 M benign Non-radical BKA osteosarcoma DOD at 13 mo 1978 osteochondroma excision Padhy D17/ 17 M osteosarcoma NA ray amputation high-grade NED at 26 mo 2010 f/b adjuvant osteosarcoma chemotherapy Mohammadi 33 F osteosarcoma NA radical excision chondroblastic NED at 9 mo A18/2011 osteosarcoma Nishio J19/ 16 M fibrous dysplasia/ curettage wide excision low-grade NED at 18 mo 2012 giant cell reparative + free vascular osteosarcoma granuloma scapular graft Parsa R15/ 72 M osteosarcoma NA metatarsectomy low-grade NED at 48 mo 2013 osteosarcoma Aycan OE11/ 10 M aneurysmal bone NA resection chondroblas- NED at 6 mo 2015 cyst/giant cell tumor toma-like osteosarcoma PRESENT 10 F chondroblastic NA NACT f/b chondroblastic NED at 3 mo CASE metatarsectomy osteosarcoma BKA: below knee amputation; DOD: dead of disease; F, female; f/b: followed by; M, male; mo, months; NA, not available; NACT, neoadjuvant chemothera- py; NED, no evidence of disease

It has also been postulated that osteosar- myxoid fibroma. Osteosarcomas and Ew- coma of the foot may have a better prog- ing sarcomas constitute the malignant nosis and survival compared to other tumors.12 Occasionally, infections like osteosarcoma subsites.10 This can be ex- of the small bones may trapolated from the fact that the majority mimic malignancy. The absence of an are found to be low grade, and despite extensive soft tissue component and/or a long delay in treatment, there was no calcifications with the presence of bony rapid increase in size and/or metastatic changes (like ) favors a diag- spread. However, tumor grade remains nosis of infection/osteomyelitis. In addi- an important factor affecting survival— tion, clinical findings like fever, skin red- patients with higher grade tumors have ness, and presence of a painful swelling worse survival.8 (especially after onset of fever) point to A number of differentials, including an inflammatory pathology rather than benign tumors, are to be kept in mind malignancy. Stress fractures rarely sim- when diagnosing and treating such pa- ulate tumors. MRI showing marrow and tients (TABLE 2). The most common benign soft tissue edema with a visible fracture tumors affecting the metatarsal are giant line points to the diagnosis. cell tumors (GCT) followed by chondro- A plane radiograph showing corti-

16 THE SARCOMA JOURNAL | SUMMER 2019 | VOL 3, NO 2 CASE REPORT‹

TABLE 2. Important differential diagnosis of metatarsal swelling in a young patient Differential Osteosarcoma Chronic Ewing Eosinophilic diagnosis osteomyelitis sarcoma granuloma Age group 10 – 30 years 2 – 12 years 10 – 20 years Less than 10 years Male:female 1.43:1 3:1 1.5:1 2:1 Most common site Lower limb distal femur Lower limb and lumbar Femur Skull, mandible, vertebrae spine, ribs Plain X-ray features Eccentric cortical bone Mildly expansile scle- Moth-eaten appearance/ Well-defined destruction. rotic lesion with cortical permeative–cortical osteolytic lesion with Soft tissue mass + thickening () destruction. Periosteal/ a zone of sclerosis tumor matrix and medullary sclerosis. onion skin appearance “button seques- calcification. Sequestrum may be seen –aggressive trum.” May appear Codman triangle as thickened sclerotic Calcification–Uncommon aggressive with no periosteal reaction bone. Buttress type of sclerosis in early commonly seen. periosteal reaction. stages. Imaging MRI – On T1w – Bone CT – best study to delin- CT – degree of bone CT – lytic lesion with marrow replaced by eate sequestrum from an- destruction appreciated periosteal reaction hypointense soft tissue other lesion (sequestrum better. and cortical and mass. does not enhance). MRI – T1 – low signal. medullary bone T2w – shows general MRI – sequestrum in cor- T2 – heterogeneously destruction. hypointensity with thin tical bone: hypointense high signal. On spin-echo MRI, marginal area of and in cancellous bone Shows high uptake on decreased SI on T1w hyperintensity. sequestrum is hyperin- Ga67 and Tc99 bone and high on T2w. tense on T1, T2, and scan. Lesion enhances on STIR sequences. Granu- gadolinium. lation tissue is hyperin- tense on T2. CT, computed tomography; Ga, gadolinium; MRI, magnetic resonance imaging; SI, spin intensity; STIR, Short-TI Inversion Recovery; T1, T2, longitudinal relaxation time; T2w, longitudinal relaxation time-weighted images; Tc, technetium cal bone destruction with a soft tissue vage surgery or wide excision in these component and calcification should be cases. TSJ considered suspicious and must be thor- oughly evaluated prior to surgical treat- CORRESPONDENCE Dr. Abhay Kattepur, [email protected] ment.13 In a young patient such as ours, the important differentials that need to ACKNOWLEDGMENT be considered include Ewing sarcoma, We would like to thank Dr. Sithara Aravind, Asso- chronic osteomyelitis, and eosinophil- ciate Professor, Department of Pathology, Malabar ic granuloma, which can radiologically Cancer Center, for the photomicrographs. mimic osteosarcoma at this location. REFERENCES CONCLUSIONS 1. Ottaviani G, Jaffe N. The epidemiolo- gy of osteosarcoma. Cancer Treat Res. Osteosarcoma of the metatarsal is rare. 2009;152:3-13. Our case remains unique as it reports 2. Watson-Jones R. Fractures and Joint In- the second youngest patient in the lit- juries. Vol. I, 4th ed. Edinburgh and Lon- erature. Erroneous or delayed diagnosis don: E & S Livingstone Ltd.1960:347. resulting in inadequate tumor excision 3. Wu KK. Osteogenic sarcoma of the and limb loss (amputation) often occurs tarsal navicular bone. J Foot Surg. 1989;28(4):363-369. in a majority of the cases. Proper pre- 4. Biscaglia R, Gasbarrini A, Böhling T, treatment radiological imaging becomes Bacchini P, Bertoni F, Picci P. Osteosar- imperative, and when clinical suspicion coma of the bones of the foot: an easily is high, a needle biopsy must follow in misdiagnosed malignant tumour. Mayo Clin Proc. 1998;73(9):842-847. those cases. Early diagnosis with ad- 5. Kundu ZS, Gupta V, Sangwan SS, Rana ministration of neoadjuvant chemother- P. Curettage of benign bone tumors apy may allow us to perform limb sal- and tumor like lesions: A retrospective CONTINUED

MDEDGE.COM/SARCOMAJOURNAL VOL 3, NO 2 | SUMMER 2019 | THE SARCOMA JOURNAL 17 ›CASE REPORT

analysis. Indian J Orthop. 2013;47(3): 13. Schatz J, Soper J, McCormack S, Healy 295-301. M, Deady L, Brown W. Imaging of tu- 6. Choong PFM, Qureshil AA, Sim FH, mours in the ankle and foot. Top Magn Unni KK. Osteosarcoma of the foot. A Reson Imaging. 2010;21(1):37-50. review of 52 patients at the Mayo Clinic. 14. Fukuda K, Ushigome S, Nikaidou Acta Orthop Scand. 1999;70(4):361-364. T, Asanuma K, Masui F. Osteosarco- 7. Sneppen O, Dissing I, Heerfordt J, ma of the metatarsal. Skeletal Radiol. Schiödt T. Osteosarcoma of the metatar- 1999;28(5):294-297. sal bones: Review of the literature and 15. Parsa R, Marcus M, Orlando R, Parsa report of a case. Acta Orthop Scand. C. Low-grade central osteosarcoma of 1978;49(2):220-223. the second metatarsal in a 72 year old 8. Anninga JK, Picci P, Fiocco M, et al. male. Internet J Orthop Surg. 2013;21(2): Osteosarcoma of the hands and feet: a 1-8. distinct clinico-pathological subgroup. 16. Lee EY, Seeger LL, Nelson SD, Eckardt Virchows Arch. 2013;462(1):109-120. JJ. Primary osteosarcoma of a metatar- 9. Mirabello L, Troisi RJ, Savage SA. sal bone. Skeletal Radiol. 2000;29(8): Osteosarcoma incidence and sur- 474-476. vival rates from 1973 to 2004: Data 17. Padhy D, Madhuri V, Pulimood SA, from the Surveillance, Epidemiolo- Danda S, Walter NM, Wang LL. Metatar- gy and End Results Program. Cancer. sal osteosarcoma in Rothmund-Thom- 2009;115(7):1531-1543. son syndrome: a case report. J Bone Joint 10. Wang CW, Chen CY, Yang RS. Talar Surg Am. 2010;92(3):726-730. osteosarcoma treated with limb spar- 18. Mohammadi A, Porghasem J, Norooz- ing surgery. J Bone Joint Surg Am. inia F, Ilkhanizadeh B, Ghasemi-Rad M, 2011;93:e22. Khenari S. Periosteal osteosarcoma of 11. Aycan OE, Vanel D, Righi A, Arikan Y, the fifth metatarsal: A rare pedal tumor. Manfrini M. Chondroblastoma-like os- J Foot Ankle Surg. 2011;50(5):620-622. teosarcoma: a case report and review. 19. Nishio J, Iwasaki H, Takagi S, et al. Skeletal Radiol. 2015;44(6):869-873. Low-grade central osteosarcoma of the 12. Jarkiewicz-Kochman E, Gołebiowski M, metatarsal bone: A clinicopathological, Swiatkowski J, Pacholec E, Rajewski R. immunohistochemical, cytogenetic and Tumours of the metatarsus. Ortop Trau- molecular cytogenetic analysis. Anti- matol Rehabil. 2007;9(3):319-330. cancer Res. 2012;32(12):5429-5435.

› A CALL FOR PEER REVIEWERS The Sarcoma Journal is a quarterly, peer-reviewed journal. We are seeking physicians familiar with sarcoma to evaluate papers for upcoming issues.

To apply, please send your CV and letter of interest to Erilyn Riley, Managing Editor [email protected]

18 THECallForReviews SARCOMA ad.indd JOURNAL 18 | SUMMER 2019 | VOL 3, NO 2 6/13/19 11:47 AM