Primary pulmonary Ewing sarcoma/peripheral primitive neuroectodermal tumor

Abstract

Ewing sarcoma/peripheral primitive neuroectodermal tumor (ES/pPNET) is a malignant small round cell sarcoma commonly occurring among children, adolescents, and adults. We report a rare case of ES/pPNET arising from the lung in a 49-year-old woman. She was found to have a mass in the right lung on a screening imaging study for her BRCA2 mutation. A lobectomy was performed and the mass had histological, immunohistochemical, and molecular features of ES/pPNET. Few cases of primary pulmonary Ewing sarcoma have been reported.

Ewing sarcoma/peripheral primitive neuroectodermal tumor (ES/pPNET) is a malignant small round cell sarcoma, which commonly presents as a tumor originating from diaphysis or metaphysis of long bones among children, adolescents, and young adults. It has also been documented to arise from the soft tissue in the chest wall, pelvis, paraspinal region, and retroperitoneum. ¹ ES/pPNET is less prevalent among older adults and rarely found at sites other than bone, such as skin and soft tissue. Especially rare is ES/pPNET arising from the viscera. ²

CASE REPORT

A 49-year-old woman with a BRCA2 mutation was screened for a pancreatic malignancy with magnetic resonance imaging, which revealed an incidental mass in the right lower lobe of the lung (Figure 1). A confirmatory positron emission tomography scan of the whole body showed a single mass restricted to the lung that was enlarging and hypermetabolic. A right lower lobectomy with lymph node excision was performed.

Figure 1.

Transverse CT of the abdomen showing a mass within the right lower lobe.

Gross examination of the right lower lobe showed a yellow-white, soft, circumscribed mass that was centrally necrotic. The mass was limited to the lung while remaining free from the bronchial, vascular, and parenchymal margins and the visceral pleura. Microscopically, the mass showed diffuse sheets of monotonous small round blue cells. The cells had a high nucleus-to-cytoplasmic ratio and minimal cytoplasm that was either lightly eosinophilic or clear. The mass was diffusely positive for CD99, FLI-1, and PAS with diastase (Figure 2). Pancytokeratin, thyroid transcription factor-1, synaptophysin, chromogranin, CD56, melanoma cocktail, CD45, myoD1, and myogenin were negative. Finally, a fluorescence in situ hybridization study for EWSR1 rearrangement at 22q12 (5′EWSR1, 3′EWSR1) came back positive for translocation.

Figure 2.

(a) Hematoxylin and eosin–stained slide showing sheets of small round blue cells. (b) CD99 immunohistochemical stain showing positive cytoplasmic staining. (c) FLI-1 immunohistochemical stain showing positive nuclear staining. (d) PAS/D special stain showing positive, bright magnetic staining.

Following surgery, the patient underwent six cycles of chemotherapy, including vincristine, doxorubicin, and ifosfamide for 6 months. No evidence of recurrence has been found, and the patient is alive and well 24 months after the surgery.

DISCUSSION

The typical histologic morphology of ES/pPNET on hematoxylin-eosin stain includes diffuse sheets of small round blue cells with oval to round nucleus showing finely distributed chromatin and scant lightly eosinophilic or pale cytoplasm. The tumor is typically immunoreactive to CD99, FLI1, neuron-specific enolase, vimentin, and occasionally periodic acid Schiff. ³ ES/pPNET is characterized by translocation involving the EWSR1 gene in chromosome 22, and 90% to 95% of ES/pPNET cases harbor translocations t(11;22)(q24;q12) or t(21;22)(q22;q12), involving the EWSR1 gene. ⁴

The prognosis for ES/pPNET arising from the lung tends to be poor; approximately half of the patients died 1 to 54 months after diagnosis. ⁵ Table 1 shows 31 cases of primary lung parenchymal ES/pPNET from our literature review in PubMed. ^{2 , 3 , 5–23} The patients’ age at the time of diagnosis ranged from 4 to 70 years (mean age 31), and there was a slight male predominance (M:F = 1.38:1). Among patients with available follow-up records, poor prognosis was found, as 12 of 23 patients (52.2%) passed away within 5 years of the diagnosis. In contrast, primary bronchial ES/pPNET cases showed a much better prognosis. Among eight reported cases of primary bronchial ES/pPNET, no patient has died from the disease. ²⁴ The better prognosis associated with primary bronchial ES/pPNET could be attributed to symptoms when the tumor obstructs the major airway, leading to early detection and treatment. In contrast, a neoplasm in the lung parenchyma likely would not have a similar degree of symptomatology until it is much larger. Our patient presented as an older adult with primary lung parenchymal ES/pPNET but has been well after treatment, most likely because her tumor was identified incidentally when it was localized to the lung parenchyma. We present this rare case of primary pulmonary ES/pPNET to raise awareness of this entity as a primary pulmonary neoplasm and to add to the current limited repository of only 31 primary pulmonary ES/pPNET cases for further statistical analysis.

Table 1.

Previous reports of patients with primary pulmonary Ewing sarcoma/primitive neuroectodermal tumor

Year	Age	Sex	Tumor site	Treatment	Follow-up (months)	Reference
1997	29	Male	Lung	Surgery and CT	–	Catalan 5
1998	25	Female	LLL	Surgery only	DOD at 24	Tsuji 7
1998	15	Male	LLL	Surgery only	A&W at 24	Tsuji 7
2000	41	Female	RLL	Surgery and CT	A&W at 16	Immamura 8
2000	30	Male	LUL	Surgery and CT	A&W at 22	Immamura 8
2001	18	Male	RML	Surgery only	DOD at 24	Kahn 9
2001	17	Female	RLL	Surgery, CT, and XRT	DOD at 3	Mikam 10
2006	28	Female	RLL	–	–	Paik 11
2007	8	Male	RUL	Surgery and CT	A&W at 9	Takahashi 12
2007	67	Male	LLL	Surgery and CT	–	Lee 13
2009	22	Female	RLL	CT only	–	Suarez Antelo 14
2009	22	Female	Lung	Surgery and CT	A&W at 32	Demir 15
2009	28	Female	Lung	Surgery and CT	A&W at 18	Demir 15
2009	22	Male	Lung	Surgery and CT	DOD at 18	Demir 15
2009	47	Male	Lung	Surgery and CT	A&W at 34	Demir 15
2010	44	Male	RUL	Surgery and CT	DOD at 5	Handorn 2
2011	15	Female	Right lung	CT and XRT	DOD at 8	Siddiqui 16
2012	22	Male	RUL	Surgery only	–	Weissferdt 3
2012	27	Male	LUL	Surgery and CT	DOD at 24	Weissferdt 3
2012	29	Female	LUL	Surgery and CT	DOD at 36	Weissferdt 3
2012	31	Male	RLL	Surgery and CT	DOD at 54	Weissferdt 3
2012	29	Male	RUL	Surgery only	–	Weissferdt 3
2012	56	Female	RML	Surgery and CT	A&W at 11	Weissferdt 3
2012	42	Male	RLL	Surgery and CT	A&W at 6	Ichiki 17
2013	4	Female	LUL	Surgery and CT	–	Alsit 18
2013	31	Male	Lingua LL	Surgery, CT, and XRT	–	Andrei 19
2014	41	Female	LUL	Surgery, CT, and XRT	A&W at 48	Hwang 20
2015	30	Female	Right lung	CT only	DOD at 0.5	Deokar 21
2015	16	Male	Both lungs	CT only	DOD at 5	Dong 22
2016	70	Male	LUL	CT only	DOD at 4	Mizuguchi 6
2017	56	Male	RLL	Surgery and CT	–	Başgöz 23

A&W indicates alive and well; CT, chemotherapy; DOD, died of disease; LL, left lung; LLL, left lower lobe; LUL, left upper lobe; RLL, right lower lobe; RML, right middle lobe; RUL, right upper lobe; XRT, radiation therapy.