Primary pleuro-pulmonary Ewing’s sarcoma: multimodal approach with uniportal thoracoscopic resection

Abstract

Primitive neuroectodermal tumors (PNETs) and Ewing’s sarcoma (ES) belong to the same family of malignant, small, round cell neoplasms of soft tissue or bone origin. With just around 30 cases reported so far, primary pleuro-pulmonary PNETs/ES are extremely rare in adults. We herein describe a case of a hexagenerian male diagnosed with primary pleuro-pulmonary PNETs/ES after tissue biopsy. He underwent neoadjuvant chemotherapy, and after significant downstaging of the tumor, he underwent complete resection of the lesion through uniportal video-assisted thoracoscopic surgery (u-VATS) followed by adjuvant chemo-radiotherapy. He was disease-free while under close follow-up for the past 1 year.

Introduction

The Ewing’s sarcoma family of tumors (ESFT; see Table 1 for a list of abbreviations) incorporate both the well-recognized primary bone and the extra-skeletal soft tissue sarcomas. The first case of primary ESFT of the lung was reported in 1989 by Hammar and colleagues [1]. With just about 30 cases reported in the literature, primary pulmonary Ewing’s sarcoma (ES) is evidently rare. In our report, we present such a case, diagnosed and treated at our institution, with an aim to highlight the importance of the multimodal team approach in the evaluation and management of such cases, along with the feasibility of minimal invasive curative surgery for the same.

Table 1.

List of abbreviations

BCL-2	B-cell lymphoma 2 family (apoptosis regulator proteins)
CD31	Cluster of differentiation 31 (protein)
CD34	Cluster of differentiation 34 (protein)
CD99	Cluster of differentiation 99 (protein)
CECT	Contrast-enhanced computed tomography
COVID-19	Coronavirus disease-2019
ES	Ewing’s sarcoma
ESFT	Ewing’s sarcoma family of tumors
FLI-1	Friend Leukemia Integration 1 (transcription factor)
pan-CK	pan-Cytokeratin (antibody cocktail)
PET-CT	Positron emission tomography-computed tomography
PPES	Primary pulmonary Ewing’s sarcoma
PNET	Primitive neuroendocrine tumor
TTF-1	Thyroid transcription factor-1 (protein)
u-VATS	Uniportal video-assisted thoracoscopic surgery
VMAT	Volumetric modulated arc therapy
VAC/IE	Chemotherapy regimen — vincristine + adriamycin + cyclophosphamide alternating with ifosfamide + etoposide
WT-1	Wilms tumor (related protein)

Case report

A 64-year-old gentleman, never-smoker, presented with a history of dry cough and reduced air entry in the basal aspect of the right chest. Initial imaging by contrast-enhanced computed tomography (CECT) of the chest revealed a centrally located right lower lobar mass (yellow arrow) extending across the fissure into the middle lobe (Fig. 1A) and a nodular lesion (yellow arrow) at the interface of the right hemidiaphragm and right lower lobe (Fig. 1B). Positron emission tomography with computed tomography (PET-CT) revealed a hypermetabolic mass in the right lower lobe of the lung, crossing the major fissure and involving the middle lobe (6.7 × 7.1 × 6.1 cm, SUV (Standardized uptake value) max 14.6), with hypermetabolic right lower paratracheal lymph nodes (SUVmax 5.3), without any distant lesions (Fig. 1C). A similar mass was noted at the interface of the right lower lobe medial basal segment and adjacent diaphragm with indistinct fat planes (2.2 × 3.1 cm, SUVmax 10.4). A computed tomography (CT)–guided biopsy revealed malignant small round cell tumor, which on immunohistochemistry was positive for vimentin, CD99, and FLI-1. It was negative for pan-CK, TTF-1, chromogranin, synaptophysin, WT-1, S-100, CD31, CD34, and BCL-2. After a multidisciplinary tumor board discussion, a diagnosis of primary pulmonary ES was made and he received neoadjuvant chemotherapy (4 cycles of vincristine + adriamycin + cyclophosphamide alternating with ifosfamide + etoposide (VAC/IE)). A re-staging PET-CT after completion of therapy suggested interval reduction in both size and metabolic activity of both the masses (fissural aspect mass, 2.4 × 2.8 cm; SUVmax, 3.4; medial basal segmental mass, 2.1 × 2.8 cm; SUVmax, 7.4) and metabolic activity in the mediastinal lymph nodes (SUVmax, 3.5), yet with abutment of segmental pulmonary arterial branches.

Fig. 1.

A CECT chest demonstrating a heterogenous mass lesion (yellow arrow) in the right lower lobe extending into the middle lobe across the fissure and B a nodular lesion (yellow arrow) on the medial aspect of the right hemidiaphragm. C PET-CT image depicting the hypermetabolic nature of the right lower lobe mass (Green arrow). Intraoperative view of D the parenchymal lesion (green arrow) in the major fissure and E the ovoid “bilobed” nodule (green arrow) on the right hemidiaphragm

He underwent uniportal video-assisted thoracoscopic surgery (u-VATS) exploration, wherein, a well-defined whitish mass (3.0 × 2.0 × 3.5 cm) was noted within the right lower lobe (Fig. 1D). It was crossing the oblique fissure, involving the medial segment of the right middle lobe and close to the origin of the middle lobar artery. A bilobed mass (4.0 × 4.0 × 2.0 cm) was noted on the right hemidiaphragmatic pleural surface, infiltrating the diaphragm but with no obvious hepatic infiltration (Fig. 1E).

A sub-centimetric parietal pleural nodule was noted on the lateral costal surface. We completed a right inferior bi-lobectomy (middle and lower lobes) with wide excision of hemidiaphragmatic nodule and the rent was repaired primarily. Additionally, a systematic mediastinal lymph node dissection with resection of pleural nodule was done. Postoperative period was uneventful and histopathological examination revealed a malignant round cell tumor within the lung and diaphragmatic nodule (Fig. 2). Pleural based nodule revealed focal necrosis with no residual tumor suggestive of response to chemotherapy and lymph nodes were negative. He received adjuvant radiation volumetric modulated arc therapy (VMAT) of 45 Gray in 30 fractions with an additional 9-Gray boost, followed by adjuvant chemotherapy (6 cycles VAC/IE regimen), which he tolerated well. The patient was kept under close follow-up during which he showed significant clinical and overall functional recovery. He was re-evaluated 1 year after the surgery with a PET-CT which showed no residual or interval recurrence of disease. However, the patient unfortunately succumbed to coronavirus disease 2019 (COVID-19)–related pulmonary sepsis, which led to respiratory failure.

Fig. 2.

A Histo-micrographic image of malignant small round “blue” cells. Immunostain positive for B FLI-1 and C vimentin

Discussion

First described in 1921 by the American pathologist James Ewing, ES is a neuroectodermal tumor characterized by monotonous small round cells. It usually develops in the second decade of life as a primary osseous malignancy, with a median age of 13 years [2]. ES usually metastasizes through hematogenous spread, with the lung being the most common destination (38%), followed by bones (31%) and the bone marrow (11%) [2]. An extra-skeletal primary source of this condition is extremely rare; a review of English literature revealed just around 30 cases of primary ES of the lung reported so far, thus emphasizing the need to  rule out a musculoskeletal primary [3]. According to past and recent studies, 15–40% of the patients already have metastasis at the time of diagnosis [3]. Thus, a detailed clinical and radiological examination is warranted to appropriately stage the disease prior to embarking upon therapy [4]. Definitive diagnosis is arrived at by biopsy and histological evaluation. ES should be differentiated from other pulmonary malignancies, viz. small cell carcinoma, adenocarcinoma, squamous cell carcinoma, and lymphoma. Recently, the use of CD99 immunostain has increased the diagnostic accuracy [5], and the same was found to be focal positive in our case. Multimodality therapy, through a formal multidisciplinary tumor board consensus, is indicated. The disease-free survival rate has been significantly increased by managing these tumors with aggressive surgical resection in combination with multi-agent chemotherapy, with or without radiotherapy [6]. The 5-year disease-free survival rate for ES of bone is estimated to be 60 to 70% for localised disease managed with multi-agent chemotherapy and surgical resection [7]. Surgery has been performed in 25 cases so far, either as a standalone therapy or in combination with chemotherapy or radiotherapy [8, 9], with none of them having undergone VATS. We performed a right inferior bi-lobectomy with diaphragmatic repair successfully through a uniportal VATS approach for our patient, with at least 12-month disease-free survival before losing him to COVID-19.

Conclusion

Extra-osseous ES affecting the lung and diaphragm primarily is extremely rare. It needs to be differentiated from the more common non-small cell and small cell cancers of the lung. The diagnosis can only be confirmed with immune-histochemical studies. An inter-disciplinary team management with multimodality treatment is necessary and hardly ever straightforward. Complete surgical resection with adjuvant therapy offers the best chance for cure. Given the availability of experience and expertise, the u-VATS approach was a feasible option in our patient and the surgical outcome was successful.

Author contribution

All the authors have provided their intellectual contribution to the manuscript. The final draft was read and approved by all the authors.

Funding

No funding or other support was acquired from any external or institutional sources.

Declarations

Consent for publication

The personal information of the patient was anonymized, and hence, a waiver of consent was provided by the Insti-tutional Review Board and Ethics Committee.

Ethics approval

The personal information of the patient was anonymized and procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (Helsinki Declaration 1975, revised in 2000 and 2008). Accordingly, the Narayana Health Academics Ethics Committee (NHAEC) approved this case report for publication prior to submission (letter no. NHH/AEC-CL-2021–703).

Conflict of interest

The authors have no conflicts of interest to declare that are relevant to the content of this article.