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Primary Non-metastatic Epithelioid Sarcoma of Lumbar Vertebra L3: Pediatric Case Report and Brief Review of the Literature

Wendy Cristhyna Gómez García, Paola Friedrich

Wendy Cristhyna Gómez García, Department of Hematology and Oncology, Dr. Robert Reid Cabral Children’s Hospital, Santo Domingo, Dominican Republic
Paola Friedrich, Department of Pediatric Oncology, Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, Boston, USA

Correspondence to: Wendy Cristhyna Gómez García, MD, Department of Hematology and Oncology, Dr. Robert Reid Cabral Children’s Hospital. Santo Domingo, Dominican Republic.
Email: emogenes@yahoo.com
Telephone: + 829-265-2625
Received: April 30, 2015
Revised: May 26, 2015
Accepted: May 31, 2015
Published online: July 18, 2015

ABSTRACT

Epithelioid Sarcoma (ES) is a rare non-rhabdomyosarcoma soft tissue sarcoma. It is a high-grade malignancy that most commonly occurs in young adult males. These tumors are characterized for slow growing nodules with predilection for the extremities. A proximal form arising in the deep part of the pelvis, perineum, and genital tract and proximal extremities has been described. Only three cases with localization to the spine have been reported. We report the case of an 11-year old female with a primary ES of the lumbar spine, who presented with antalgic gait and evidence of L3 vertebral collapse on x-rays. She had upfront surgery for spine stabilization and biopsy. Treatment consisted of neoadjuvant chemotherapy with ifosfamide and doxorubicin, local control with radiation therapy, and second-look surgery with complete reconstruction of L3. She tolerated treatment well, without significant toxicities or complications. When this paper was submitted for publication, she had completed 6 months of follow up in first clinical remission without evidence of local or distant disease. This is the first case of ES diagnosed at our center, likely the first pediatric case of ES diagnosed in the Dominican Republic; although a national cancer registry does not exist. Establishing the diagnosis would not have been possible without access to international experts in pediatric oncologic pathology thought existing institutional collaboration. This is not a novel case but a diagnostic challenge, issue exacerbated in developing countries. We are proud to have offered appropriate, timely treatment, with a similar integral quality as in a developed country.

© 2015 ACT. All rights reserved.

Key words:Epithelioid sarcoma; Non-rhabdomyosarcom soft-tissue sarcoma; Vertebra; lumbar spine; Child; Pediatric

Gómez Garcia WC, Friedrich P. Primary Non-metastatic Epithelioid Sarcoma of Lumbar Vertebra L3: Pediatric Case Report and Brief Review of the Literature. Journal of Tumor 2015; 3(2): 314-319 Available from: URL: http://www.ghrnet.org/index.php/JT/article/view/1085

INTRODUCTION

Epithelioid Sarcoma (ES) is a rare non-rhabdomyosarcoma soft tissue sarcoma. It typically occurs in the distal extremities of young male adults as a slow-growing nodule within the dermis, subcutis, or deeper soft tissues[1-3]. Due to its insidious presentation and histologic findings, its classic form can be mistaken with chronic inflammatory processes[2,3]. However, the clinical course is characterized by high frequency of nodal spread and relentless local and distal recurrences[1,2]. Three histologic variants have been described: epithelioid, spindled, and mixed, and lesions are usually positive for vimentin, keratin, and epithelial markers; highlighting the presence of a spectrum of cellular differentiation in these fibrohistiocytic tumors[3,4]. A proximal form arising in the deep part of the pelvis, perineum, and genital tract and proximal extremities has been described and typically has an even more aggressive clinical course than distally located tumors[4,5]. In these cases, ES has distinct histologic features resembling carcinomas and rhabdoid tumors[4]. Interestingly, only three cases of ES localized to the spine have been reported in the literature (one thoracic, one lumbo-sacral, and one sacral)[6-8]. We report the case of an 11-year old female with a primary ES of the lumbar spine, who presented with antalgic gait and evidence of L3 vertebral collapse on x-rays. She had upfront surgery for spine stabilization and biopsy. Treatment consisted of neoadjuvant chemotherapy with ifosfamide and doxorubicin, local control with radiation therapy, and second-look surgery with complete reconstruction of L3. She tolerated treatment well, without significant toxicities or complications. When this paper was submitted for publication, she had completed 6 months of follow up in first clinical remission without evidence of local or distant disease.

Case Report

An 11-year old female with history of intermittent discomfort in the lower back presented for evaluation to her pediatrician. Symptoms had developed over the previous year and parents had been managing with oral analgesics and non-steroidal anti-inflammatory medications. Ultimately, pain increased in frequency and severity and parents noted spine deviation and antalgic gait, which prompted medical evaluation. The general pediatrician performed and X-ray which showed.

The general pediatrician performed and x-ray which showed marked scoliosis in the lumbar spine with destruction of L3 vertebra. The patient was then immediately referred to an orthopedist, who obtained further imaging. As seen in the upper panels of figure 1, computed tomography (CT) scan showed an expansive lytic lesion of neoplastic appearance on the L3 vertebral body. This prompted obtaining magnetic resonance imaging (MRI), which as seen in the lower panels of figure 1, showed extension of the neoplastic lesion into the right pedicle and right transverse process of the vertebra, with areas of calcification and causing marked scoliosis in the lumbar spine.

The surgical procedure revealed a mass emerging directly from the L3 vertebral body. The mass was invading the right posterior roots and was noted to be pushing, but macroscopically not infiltrating, the paraspinal muscles. Four screws and two orthopedic fixation hooks were placed to stabilize the spine and a biopsy was performed. Pathology reported “poorly differentiated malignant neoplasm, probably lymphoid vs. histiocytic origin”. Only one immunohistochemistry study was reported: cytokeratin; it was reported as positive.

With this pathologic diagnosis, the patient was referred to the Department of Hematology and Oncology at Dr. Robert Reid Cabral Children’s Hospital in Santo Domingo, Dominican Republic. Further workup included chest X-ray, bone scan, CT angiography, and neck through pelvis CT. There was no evidence of neighboring solid organ invasion, neuro-vascular invasion, regional lymph node involvement, or distant metastasis.

The original biopsy sample was reviewed at our institution and determined to be adequate. However, in the absence of a clear diagnosis, the biopsy was sent for second opinion to St. Jude Children’s Research Hospital. The report described: “The biopsy shows infiltrative sheets of epithelioid cells with large nuclei and abundant eosinophilic cytoplasm admixed with a prominent acute and chronic inflammatory infiltrate. Scattered cells display a rhabdoid appearance with eccentric nuclei and glassy cytoplasm. Immunohistochemistry revealed co-expression of vimentin, cytokeratin AE1-AE3 and epithelial membrane antigen, all this finds compatible with Epithelioid Sarcoma.” These findings are illustrated in figure 2.

Treatment and evolution

Based on clinical findings, the patient was determined to have a non-metastatic, bone-invasive, non-resected, malignant soft tissue sarcoma of size greater than 5cm. Using as a reference the most recently completed Children’s Oncology Group soft tissue sarcoma clinical trial[9], which is used as standard of care in many pediatric oncology institutions in North America, the patient proceeded to start treatment with one cycle of neoadjuvant chemotherapy and radiation therapy starting at week 4. In total, the patient received 7 cycles of chemotherapy. Four cycles included ifosfamide 9 gm/m2 divided into three days and doxorubicin 75 mg/m2 divided into two days. Two cycles included ifosfamide only and one cycle included doxorubicin with same reference dosing. The cumulative ifosfamide dose was therefore 36 gm/m2 and the total doxorubicin dose 375 mg/m2. Bladder protection was provided with mesna and hyperhydration. Local control was provided starting at week 4 with 45Gy of radiation to the original tumor volume using intensity modulated radiation therapy (IMRT). The patient went for second look surgery and reconstruction of L3 vertebra at week 13 (Figure 3 for post-operative x-rays and CT). No tumor or residual mass was at the time of second-look surgery and the biopsies obtained were negative for presence of malignant cells. The patient tolerated treatment very well without significant toxicity.

Discussion

Epithelioid Sarcoma

Epithelioid sarcoma (ES) is a high-grade malignancy. It was described by Laskowski and Enzinger, first in 1961 and later in 1970[1,2]. It typically occurs in the distal extremities of young adults as a slow-growing nodule within the dermis, subcutaneous tissue or in the deep soft tissues[1-3]. It can be mistaken with chronic inflammatory processes, necrotizing granulomas, and some fibrohistiocytic tumors, generally has an epithelial and mesenchymal differentiation[3].

The conventional or distal form is composed of spindle-to-polygonal epithelioid cells arranged in nodules that commonly exhibit central necrosis[4]. In 1997, a proximal form arising in the deep part of the pelvis, perineum, and genital tract and proximal extremities was described[4,5]. As described by the authors[4], it consists of large epithelioid carcinoma–like and/or rhabdoid cells, has a more aggressive clinical course than distally located tumors, and has a possible link with malignant rhabdoid tumor. Local recurrence rate as high as 85% and 30-50% likelihood for metastases, predominately lymphatic or in the lungs, have been reported[8].

To our knowledge, there are only three cases of ES reported in the literature with localization to the spine (lumbo-sacral junction, sacrum and thoracic)[6-8]. Distinctive histopathological features have not been reported for this location. This is the first case of ES diagnosed at our center and since we are the main referral center for pediatric oncology, likely the first pediatric case of ES diagnosed in the Dominican Republic; although a national cancer registry does not exist. Establishing the diagnosis would not have been possible without access to international experts in pediatric oncologic pathology thought existing institutional collaboration.

Clinical Features

Epithelioid sarcomas occur most frequently in young adult males with usual median age in the mid-twenties[10]. Although less common in females, epithelioid sarcoma has a more favorable prognosis in this population[3]. These tumors are characterized for slow growing nodules, which may be single or multiple[11,12]. More superficial lesions can ulcerate, but in general only 20% of patients present with main complaint of pain at diagnosis[3]. About 13% of patients will present with multifocal tumors and about 13% of patients will present with metastatic disease[13]. Our patient did not fit the clinical features frequently reported. However, the only other pediatric case of spine ES reported in the literature presented did not present with classic findings either; it presented as a painless, bulging, cystic thoracic spine mass found incidentally in an obese 14-year old boy. Factors adversely affecting the survival rate include size of the tumor, infiltration into muscular, neural or vascular structures, primary location in the trunk, and presence of pulmonary metastasis[8]. The only adverse prognostic factor identified in our patient was size >5cm and axial (proximal) location, we therefore hope for a favorable prognosis.

Pathology

In ES, the cytoplasm is acidophilic, well defined and contains arrays of rough endoplasmic reticulum, a prominent Golgi apparatus, and free ribosomes as well as occasional mitochondria, lysosomes, and droplets of osmophilic material. Intermediate filaments are a common and striking feature than often may be arranged as in myofibroblasts and from paranuclear masses or whorls, thing that give the striking epithelioid appearance and eosinophilia of the tumor cells[1,13,14].

Immunohistochemistry studies are always positive for vimentin, but epithelial markers such as AE1/AE3 are also positive in up to 95% of the cases[3,14-16]. Loss of INI staining is also now considered characteristic and can be used to confirm the diagnosis as a complement to epithelial markers and CD34[4,16]. CD34 is positive in more than 50% of epithelioid sarcomas[16], but is negative in carcinomas. S100 (commonly positive in malignant peripheral nerve sheath tumor), endothelial markers (positive in epithelioid angiosarcoma), and CK5/6 (positive in squamous cell carcinoma) are usually negative in ES. As described in the case and shown in figure 2, our patient’s histologic and immunohistochemistry evaluation was fairly typical.

Treatment

Adequate treatment for this very aggressive tumor requires early recognition, followed by thorough assessment of extent of disease. Regional lymph node dissection strongly considered because lymph node metastasis are common in ES. Surgical treatment requires early radical excision or amputation and this is the primary treatment modality if the tumor is situated in the fingers or toes[1,10,12,13]. Radiotherapy has been used for marginal primary resection, local regional recurrence, or palliative care[13]. Chemotherapy has been use, particularly for initially unresectable tumors and non-metastatic disease[1,4,5,8,10,12,13]. Our patient was treated with neoadjuvant chemotherapy and radiation and had an excellent response.

Chemotherapy included two key active agents in non-rhabdomysarcoma soft-tissue sarcomas, ifosfamide and doxorubicin. On second-look surgery no evidence of disease was identified.

Prognosis

Factors adversely affecting survival for patients with ES include: age of the patient (older patient’s worse prognosis), sex (better prognosis in females), depth of the tumor (infiltration into muscular, neural or vascular structures), size of the tumor (larger worse), localization of the tumor (proximal worse), and pathology features (hemorrhage, necrosis, vascular invasion worse) and presence of metastasis[1,4,8,13,14,16]. The 5-year and 10-year overall survival are approximately 50-70% and 42-55% respectively[3,4,7]. In other reported spine ES cases, relapse has occurred within 2 years[7,8]. The only adverse prognostic factors identified in our patient were size >5cm and axial (proximal) location. She is now 6 months in clinical remission, but she will need continuous observation over several

Conclusion

Epithelioid sarcoma of the spine is an extremely rare entity. Because of its aggressive evolution, physicians and pathologists should be aware of this entity to avoid delayed diagnosis as well misdiagnosis. Multimodal therapy with a combination of surgery, chemotherapy and/or radiation is often needed to cure these patients.

This is not a novel case but a diagnostic challenge, particularly in developing countries, where pathologic expertise may be limited, case load is typically large for the number of available pathologists, and extensive immunohistochemistry panels are unaffordable. Furthermore, accurate pathologic diagnosis is only one of many challenges faced by pediatric oncology centers in developing countries to correctly diagnose, treat and cure children with cancer[17]. We will monitor this patient’s course closely. In this case, we are proud to have offered appropriate, timely treatment, with a similar integral quality as in a developed country.

ACKNOWLEDGMENTS

Thanks to Dr. Andrew Davidoff, Chairman, Surgery Department, St. Jude Children’s Research Hospital, for the academic and clinical orientations regarding this case.

Thanks to Dr. Carlos Rodriguez-Galindo, Director, The Global Health Initiative, Dana-Farber / Boston Children’s Cancer and Blood Disorders Center, for clinical orientations regarding this case.

Thanks to the Pathology Department at St. Jude Children’s Research Hospital and especially to Dra. Armita Bahrami and Dra. Teresa Santiago who provided diagnostic support.

Thanks to Foundation Amigos Contra el Cáncer Infantil, Inc (FACCI) and Keira Grace Foundation especially to Mrs. Alexandra Matos and Dr. Michael Lauzardo, for the socio-economic support to the oncologic patients of the hospital, without them their treatment wouldn’t be possible.

Thanks to Dr. Robert Reid Cabral Children’s Hospital Hematology-Oncology team, for the continued support of our patients and their families. Special thanks to Dr. Rosa Nieves, Dra. Margarita Montero, Dra. Gianna Castillo, and Dra. Euladys Matos.

Thanks to Dr. Richard Dominó, who provided orthopedic surgical attention and careful follow-up for this patient, and to Dra. Maria Pedemonte for the first pathological interpretation of this case and the continued support she provides to our Department. Thanks to Dra. Tomanna Peña, who provided excellent radiation treatment.

Thanks to the patient and her family for letting our team take care of her and granting permission to share this important and atypical case to others healthcare colleagues.

CONFLICT OF INTERESTS

There are no conflicts of interest with regard to the present study.

REFERENCES

1Enzinger FM. Epitheloid sarcoma. A sarcoma simulating a granuloma or a carcinoma. Cancer. 1970;26(5):1029–41.

2Laskowski J. Sarcoma aponeuroticum. Nowotwory. 1961;11:61–7.

3Chase DR, Enzinger FM. Epithelioid sarcoma Diagnosis, prognosis indicators and treatment. Am J Surg Pathol. 1985;9(4):241–63.

4Chbani L, Guillou L, Terrier P, Decouvelaere AV, Grégoire F, Terrier-Lacombe MJ, et al. Epithelioid sarcoma a clinicopathologic and immunohistochemical analysis of 106 cases from the french sarcoma group. Am J Clin Pathol. 2009;131(2):222–7.

5Rodrigues a. I, Lopes HI, Lima O, Marta S. Proximal-type epithelioid sarcoma--unusual presentation: unilateral vulvar mass. Case Reports [Internet]. 2015;2015(apr09 1):bcr2014208488–bcr2014208488. Available from: http://casereports.bmj.com/cgi/doi/10.1136/bcr-2014-208488

6Ilaslan H, Sundaram M, Unni KK, Shives TC. Primary vertebral osteosarcoma: imaging findings. Radiology. 2004;230(3):697–702.

7Steib J-P, Pierchon F, Farcy JP, Lang G, Christmann D, Gnassia J-P. Epithelioid Sarcoma of the Spine A Case Report. Spine (Phila Pa 1976). 1996;21(5):634–8.

8Weisskopf M, Münker R, Hermanns-Sachweh B, Ohnsorge J a K, Siebert C. Epithelioid sarcoma in the thoracic spine. Eur Spine J. 2006;15(SUPPL. 5):604–9.

9National Cancer Institute. Find a Clinical Trial: “Observation, Radiation Therapy, Combination Chemotherapy, and/or Surgery in Treating Young Patients With Soft Tissue Sarcoma”. Children’s Oncology Group Protocol ARST0332. Accessed May 20, 2015.

10Ross HM, Lewis JJ, Woodruff JM, Brennan MF. Epithelioid sarcoma: clinical behavior and prognostic factors of survival. Ann Surg Oncol. 1997;4(6):491–5.

11Shimm DS, Suit HD. Radiation therapy of epithelioid sarcoma. Cancer. 1983;52(6):1022–5.

12Callister MD, Ballo MT, Pisters PW, Patel SR, Feig BW, Pollock RE, et al. Epithelioid sarcoma: results of conservative surgery and radiotherapy. Int J Radiat Oncol Biol Phys. 2001;51(2):384–91.

13Bos GD, Pritchard DJ, Reiman HM, Dobyns JH, Ilstrup DM, Landon GC. Epithelioid sarcoma. An analysis of fifty-one cases. J Bone Joint Surg Am. 1988;70(6):862–70.

14Halling A, Wollan P, Pritchard DJ, Vlasak R, Nascimento AG. Epitheliod Sarcoma: A Clinicopathologic Review of 55 Cases. Mayo Clin Proc. 1996;71:636–42.

15Fisher C. Epithelioid sarcoma: the spectrum of ultrastructural differentiation in seven immunohistochemically defined cases. Hum Pathol. 1988;19(3):265–75.

16Miettinen M, Fanburg-Smith JC, Virolainen M, Shmookler BM, Fetsch JF. Epithelioid sarcoma: An immunohistochemical analysis of 112 classical and variant cases and a discussion of the differential diagnosis. Hum Pathol. 1999;30(8):934–42.

17Rodriguez-Galindo C, Friedrich P, Morrissey L, Frazier L. Global challenges in pediatric oncology. Curr Opin Pediatr [Internet]. 2013;25(1):3–15. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23295716

Peer reviewer:Jianmin Su PhD, Research Assistant Professor, Virginia Tech Carilion Research Institute, 2 Riverside Circle, Roanoke, VA 24016, USA.

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