Primary Ewing’s sarcoma of the lung: a rare case report

Abstract

The current case study had described the clinical presentation, evaluation, management, and outcome of a case of primary Ewing’s Sarcoma of the lung. It was presented with cough, chest pain, and hemoptysis for 3 months in a 36-year-old male. Immunostaining of the sections prepared from the blocks using CD99 antibody revealed strong continuous cell membrane staining. Tumor cells showed negative staining for leukocyte common antigen (LCA), thyroid transcription factor 1 (TTF1), and pan-cytokeratin (AE1/AE3) consistent with extraskeletal Ewing’s sarcoma (EES). Neoadjuvant chemotherapy of 6 cycles followed left lower lobectomy had led to good recovery and the patients are disease free at 18-month follow-up. Primary EES of the lung should be considered in the differential diagnosis when a young patient is presented with large mass without evidence of primary extrathoracic disease.

Introduction

Ewing’s sarcoma, named after the pathologist who reported it first in 1921, is a group of tumors, predominantly originated from the bone [1]. Along with osseous and extraosseous Ewing’s sarcoma, primitive neuroectodermal tumor (PNET) of the bone and soft tissues, askin tumor and other rare tumors like ectomesenchymoma and peripheral medulloepithelioma, is considered as a group of related tumors [2]. Extraskeletal Ewing’s sarcoma involving the lung has been reported only a handful of researchers across the globe (Asker 2015 #1) [2].

In this case study, we report a case of primary extraskeletal Ewing’s sarcoma involving the lung diagnosed and managed at our tertiary care teaching hospital, Hyderabad, India. The role of integrated approach, considering the clinical, radiological, and pathological aspects of the disease, has been highlighted.

Case report

A 36-year male presented with cough, chest pain, and hemoptysis for 3 months refractory to multiple antibiotic treatment cycles, which were prescribed assuming it as a case pneumonia by different primary level health care providers. The person was febrile and had signs suggestive of lung mass on physical examination. Plain X-ray of chest showed a homogenous opacity in the lower zone of the left lung (Fig. 1a). A circumscribed mass measuring about 2.9 × 2.5 cm was found in the left lung lower zone of computed tomography (CT) of chest (Fig. 1b). Fiberoptic bronchoscopy had shown no abnormality in bronchial tree. On transthoracic ultrasound-guided tru cut needle biopsy, we found markedly cellular tumor of round cells with hyperchromatic vesicular nucleus. Nuclear pleomorphism and tumor necrosis were noted (Fig. 2a). Immunostaining of the sections prepared from the blocks using CD99 antibody revealed strong continuous cell membrane staining (Fig. 2b). Tumor cells were negative for leukocyte common antigen (LCA), thyroid transcription factor 1 (TTF1), and pan-cytokeratin (AE1/AE3) on staining. These findings were consistent with extraskeletal Ewing’s sarcoma. Six cycles of neoadjuvantchemotherapy (vincristine 1.5 mg/m², etoposide 100 mg/m², Adriamycin 25 mg/m², mesna) were provided. The patient was assessed for surgical resection and subsequently underwent left lower lobectomy. The postoperative specimen was sent for histopathology which showed the features consistent with Ewing’s sarcoma. Following an uneventful recovery from surgery, the patient had been followed up till 18 months and found to be disease free and healthy.

Fig. 1.

a Plain chest x-ray shows a homogenous opacity in the left lung involving the lower lung zone. b CT chest shows a solitary heterogeneous mass in the left lower lobe measuring about 2.9 × 2.5 cm

Fig. 2.

a Histopathology slide shows cellular tumor composed of round cells with a hyperchromatic vesicular nucleus. b Immunostaining using CD99 antibody shows strong continuous cell membrane staining

Discussion

Ewing sarcoma family/PNET is a group of aggressive sarcomas. They predominantly involve bone and sometimes soft tissues. The key histologic feature is presence of primitive small round cells of neuroectodermal origin. Hence, immunochemistry plays a vital role in definitive diagnosis [1]. Hammar et al. [3] have reported first known case of primary pulmonary EES in the year 1989 [2].Many cases of primary Ewing sarcoma of the lung have been reported from across the globe with wide variations in age at presentation, clinical features, and outcomes [4–6].

In our study, the person was 36 years old. But the usual age range of majority of the reported cases was in the second decade of life, indicating a possible late presentation or delayed diagnosis in our study. There is a clear male preponderance, a major portion of the cases reported are men [7, 8].

There is high probability of missed diagnosis, specially at primary and secondary level health care practitioners, due to rarity of the disease. This is further compounded by nonspecific clinical presentation, overlapping with other common diseases. In our case study, the predominant symptoms were cough, chest pain, and hemoptysis for a duration of 3 months. Painful mass in the chest was one of the common clinical presentation, which often may be associated with fever and malaise [9]. Cough with fever and hemoptysis also were reported as common clinical presentations reported by previous case studies [7]. Shortness of breath and chest pain also were reported as other clinical presentations [4, 6].

EES family of tumors present with typical imaging characteristics. Primary pulmonary Ewing sarcoma usually presents as a circumscribed solitary mass with heterogenous appearance both on noncontrast and on contrast-enhanced CT [10]. In our case, the solitary pulmonary nodule in left lower lobe was the key radiological presentation, which had shown contrast enhancement. In our case, there was no bony involvement on CT and bone scan. Bone marrow aspiration also had shown no bony involvement. Similar findings were reported by previous studies, in which bone marrow involvement, hallmark of an osseous origin, was conspicuous by its absence.

Proliferation of small round cells with scanty and clear cytoplasm, round to oval nuclei, finely granular chromatin, and inconspicuous nucleoli are the typical histological features. Cytoplasmic glycogen often leads to periodicacidschiff positivity. Strong reactivity to CD99/MIC-2 and vimentin is another vital feature [11]. Markers of neural differentiation like S-100 and neuron-specific enolase may also be present in few cases [12]. Cytokeratin positivity was reported in about one-fifth of the cases. Other supporting diagnostic features include, translocation t(11,22)(q24;q12) in fluorescent in situ hybridization (FISH) and reverse transcription-polymerase chain reaction (RT-PCR) [13].

Histological examination of a sample taken from our patient revealed markedly cellular tumor composed of malignant round cells stained positive for CD99 and negative for TTF1, LCA and pan-cytokeratin. Hence, both morphological and immunohistochemistry findings were consistent with the diagnosis of EES. We have also found reciprocal chromosomal translocation t(11;22) (q24;q12) in FISH test in our case.

Multimodality treatment, consisting of surgical resection followed by chemotherapy with or radiotherapy, is needed for effective management of EES. Ifosfamide, etoposide, cyclophosphamide, vincristine, doxorubicin, carboplatin, and actinomycin have been documented to be effective in management of EES [14].Pazopanib was reported to provide a long-term progression free survival by a recent study [15].

The approach in our patient was aggressive systemic neoadjuvant chemotherapy (vincristine, etoposide, Adriamycin, mesna) of 6 cycles to facilitate complete surgical resection after maximum chemotherapy response. Six cycles of postsurgical adjuvant chemotherapy (vincristine, etoposide, Adriamycin, mesna, ifosfamide, filgrastim) was given. A follow-up fluorodeoxyglucose (FDG-PET) positron emission tomography scan showed no further uptake anywhere in the body.

Conclusion

Clinicians should consider primary extraskeletal Ewing’s sarcoma as one of the differential diagnosis, when encountered with a young patient presenting with large mass with no obvious evidence of primary extra thoracic disease. Immunohistochemistry plays a vital role in definitive diagnosis. Multidisciplinary team approach is important in timely diagnosis and effective management to prevent serious adverse consequences.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Funding

None.

Ethical approval

Not necessary.

Human and animal rights statement

No animals were involved in this study.

Informed consent

Informed written consent was obtained from the patient to use his clinical details for publication in a de-identified manner.