“Ewing's Sarcoma of Calcaneum” an uncommon tumor in an unusual site with skip metastasis: An enigma

Pranita Mohanty; Anima Hota; T Govardhan; Satya S Mohapatra

doi:10.4103/jmedsci.jmedsci_51_21

CASE REPORT

Year : 2022 | Volume : 42 | Issue : 4 | Page : 180-182

“Ewing's Sarcoma of Calcaneum” an uncommon tumor in an unusual site with skip metastasis: An enigma

Pranita Mohanty¹, Anima Hota¹, T Govardhan¹, Satya S Mohapatra²
¹ Department of Pathology, IMS and SUM Hospital, S'O'A (Deemed to be) University, Bhubaneswar, Odisha, India
² Department of Radiology, IMS and SUM Hospital, S'O'A (Deemed to be) University, Bhubaneswar, Odisha, India

Date of Submission	14-Feb-2021
Date of Decision	04-Jun-2021
Date of Acceptance	14-Jun-2021
Date of Web Publication	12-Aug-2021

Correspondence Address:
Dr. Pranita Mohanty
Department of Pathology, IMS and SUM Hospital, S'O'A (Deemed to be) University, Bhubaneswar - 751 003, Odisha
India

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/jmedsci.jmedsci_51_21

Abstract

Ewing's sarcoma (EWS) is an uncommon primary malignant tumor of the bone, mostly affects 5–25 years of age with male predominance. Diaphysis of the long bone is usual site of origin with occasional extraskeletal extension. However, it is extremely rare (3%–5%) in the small bones of the hand and feet, hence often misinterpreted as osteomyelitis, aneurysmal bone cyst, giant cell tumor, cartilagenous tumor and osteosarcoma; delaying definitive treatment. Metastasis of calcaneal EWS is common, and prognosis is dismal. Multimodality treatment approach is the standard care rendered for it. Herein, we report such a case of EWS in a 12-year-old girl child at an unusual site of calcaneum with skip metastasis for which the diagnosis and treatment was deferred by 5 months. Only after histopathology and immunohistochemistry confirmation, the definitive chemotherapy was provided and surgery was scheduled after five cycles of chemotherapy. The patient is now on chemotherapy and followed up till today.

Keywords: Calcaneum, Ewing's sarcoma, round cell tumor

How to cite this article:
Mohanty P, Hota A, Govardhan T, Mohapatra SS. “Ewing's Sarcoma of Calcaneum” an uncommon tumor in an unusual site with skip metastasis: An enigma. J Med Sci 2022;42:180-2

How to cite this URL:
Mohanty P, Hota A, Govardhan T, Mohapatra SS. “Ewing's Sarcoma of Calcaneum” an uncommon tumor in an unusual site with skip metastasis: An enigma. J Med Sci [serial online] 2022 [cited 2023 May 31];42:180-2. Available from: https://www.jmedscindmc.com/text.asp?2022/42/4/180/353049

Introduction

Ewing's sarcoma (EWS)/primitive neuroectodermal tumor family of tumors are second most common primary bone malignancies following osteosarcoma, affecting adolescents and young adults. They have diaphyseal/metadiaphyseal origin including most common primary sites of long bones (47%), pelvis (26%), chest wall (16%), and spine (6%). A rare site is the bones of the hands and feet, accounting for only 3%–5%, among them the incidence in calcaneum is the most common.^[1],[2],[3] Adkins et al. reported 16 cases of EWS of the foot.^[4] The Italian Association of Pediatric Hematology and Oncology and Italian Sarcoma Group analyzed 112 cases of EWS in unusual sites over a period of 30 years, of which 33% had hand and foot small bone involvement.^[5] Brotzmann studied 32 cases of sarcomas of the foot including eight cases of EWS and suggested that there exist characteristic biological differences between bone sarcomas of the foot and their counterparts at other skeletal sites. They are slow growing despite a thin soft-tissue envelop of foot that leads to delaying of diagnosis yet less aggressive and possess similar prognosis than in other locations.^[6] EWS of the small bones of the hand and feet has poor outcomes, and the calcaneal tumors have the worst prognosis.^[7] This study aimed at presenting an anatomical-rare location, misdiagnosed by radiology led to mismanagement and unnecessary delay in the treatment.

Case Report

A 12-year-old female child presented with right foot swelling with pain to the orthopedics outpatient department. She developed a gradual swelling measuring (5 cm × 4 cm) following a history of trauma 4 months ago. On examination, the patient had tender bony swelling on right foot, painful, and restricted movement without any distal neurovascular deficit. Routine hematology revealed neutrophilic leukocytosis. Plain X-ray immediately after trauma revealed no lesion but after fourth and 5^th month, repeat radiography showed an expansile, lytic growth in calcaneum [Figure 1]a and [Figure 1]b. Her computed tomography (CT) scan report showed an expansile lytic lesion involving almost whole calcaneum, replaced by soft-tissue density mass that is extending in to adjacent bones and muscles. Magnetic resonance imaging (MRI) of right ankle joint (plain and contrast) revealed an expansile lytic lesion involving the calcaneum that appeared hypointense on T1 and hyperintense on T2/STIR( short-tau inversion recovery) with few foci of blooming in the central part and significant postcontrast enhancement in the anterior part. Similar multiple patchy lesion involving the lower end of tibia, talus, navicular, medial cuneiform, cuboid, second metatarsal, proximal aspect of second, third, and fourth metatarsal with significant postcontrast enhancement and involvement of talocalcaneal and calcaneocuboidal joint space were evident. Infective pathology of tubercular origin was suggested [Figure 1]c. Condylar biopsy done and submitted to histopathology. Microscopy showed monotonous small dark round neoplastic cells in diffuse sheets, and scattered forms amidst large foci of necrosis, hemorrhage, and dead bony spicules. The cells showed hyperchromatic nuclei with occasional prominent nuclei, scant cytoplasm vacuolated at places (periodic acid-Schiff [PAS] positive) and indistinct cytoplasmic border. Also seen brisk mitosis and few rossettoid forms [Figure 2]a, [Figure 2]b, [Figure 2]c, [Figure 2]d. Immunohistochemistry (IHC) revealed strong and diffuse positivity for vimentin and CD99 with membrane accentuation, focal positivity for TLE1 and Ki67-45%. However P63, epithelial membrane antigen were found negative [Figure 3]. A final diagnosis of “EWS of calcaneum” was rendered with radiological evidence of skip metastasis. The patient was advised five cycles of combination chemotherapy (doxorubicin, vincristine, cyclophosphamide, and etoposide) and scheduled for postchemotherapy surgery. She is followed up till date and had completed three cycles of chemotherapy.

Figure 1: (a and b) X-ray showing the lesion (arrow) in calcaneum. (c) Magnetic resonance imaging of the lesion

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Figure 2: (a and b) Photomicrograph showing diffusely arranged small round tumor cells amidst the necrosis and dead bony spicule (H and E, ×10). (c) Tumor cells in high power (H and E, ×40). (d) PAS-positive tumor cells (arrowed)

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Figure 3: Photomicrograph showing immunohistochemistry (vimentin, CD99, TLE1, P63, epithelial membrane antigen, Ki67) of tumor cells

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Discussion

History goes back to the year 1921, when Ewing referred this tumor as diffuse endothelioma of the bone, that later renamed as Ewing's tumor.^[8] Because of histomorphology, it is categorized under “small blue round cell tumor,” and the tumor cells are small round possessing PAS-positive scant cytoplasm, stippled chromatin, and inconspicuous nucleoli arranged mostly in two different patterns: (1) Diffuse and (2) Filigree pattern; amidst large foci of necrosis. Hence, in histology, they are misinterpreted as non-Hodgkin lymphoma, neuroblastoma, neuroendocrine carcinoma, and small cell osteosarcoma. Approximately 80%–90% of patients possesses EWS-FLI protein produced by translocation between chromosomes 11 and 22 and considered as a future target therapy.^[9],[10] The metastatic pathways may be through lung/bone or bone marrow/skip metastases/combined metastatic disease. X-ray of the lesion is diverse radiographically; either purely lytic or with feature of reactive new bone formation. EWS is often associated with a lamellate or “onion skin” periosteal reaction hence misdiagnosed as osteomyelitis, aneurismal bone cyst, cartilaginous tumor, giant cell lesion or osteosarcoma, and varied imaging modalities is a prerequisite for proper and timely diagnosis. CT can evaluate joint extension, periosteal reaction, and a matrix of the lesion, but it cannot differentiate EWS from other bone conditions. In MRI, the tumor has low signal intensity on T1-weighted images and on T2-weighted images, the tumor is hyperintense. The importance of MRI is that it shows the soft-tissue involvement but not specific that's what happened in our case. Positron emission tomography-CT may indicate that skip metastases and helpful in staging workup. The treatment of EWS relies on a multidisciplinary approach, including intensive neoadjuvant and adjuvant chemotherapies with surgery and/or radiotherapy for control of both the primary site and metastatic disease. Cyclic combinations of drugs incorporated include doxorubicin, vincristine, cyclophosphamide, ifosfamide, etoposide, and dactinomycin. The present study revealed that current 5-year overall survival for patients with localized disease is 65%–75%, <30% in patients with metastases except for those with isolated pulmonary metastasis (approximately 50%), and recurrent disease has dismal prognosis.^[11] The most common surgical treatment modality for malignant calcaneal tumors is total calcanectomy and reconstruction with a homologous allograft.^[12] Limb salvage of primary malignant calcaneal tumors is performed for Stage I (low-grade) and Stage IIA (high-grade, intracompartimental) lesions according to Enneking.^[13]

Conclusion

To summarize:

High index of clinicoradiological suspicion is important for early recognition of an unusual appearance and location of EWS for its definitive treatment and better outcomes
MRI findings can narrow the differential but a specific diagnosis can rarely be established
Staging by PET CT is essential to document the local and distant spread of the tumor
Biopsy of the tumor with histopathology-assisted IHC analysis is confirmatory.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the legal guardian has given his consent for images and other clinical information to be reported in the journal. The guardian understands that names and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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