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CASE SERIES Table of Contents  
Ahead of print publication
Askin's tumor – A dual case study of rare thoracic neoplasm


1 Department of TB and Respiratory Diseases, National Institute of Tuberculosis and Respiratory Diseases, New Delhi, India
2 Department of Internal Medicine, Hassan Institute of Medical Sciences, Hassan, Karnataka, India
3 Department of Pathology, GSVM Medical College, Kanpur, Uttar Pradesh, India

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Date of Submission22-Jun-2022
Date of Decision24-Aug-2022
Date of Acceptance31-Aug-2022
Date of Web Publication27-Oct-2022
 

  Abstract 


Askin's tumor is a primitive neuroectodermal tumor (PNET) that belongs to the class of small round cell malignant tumor. It has a poor survival rate as it is an aggressive tumor with high chances of recurrence. It poses a diagnostic and therapeutic challenge to the clinicians as it mimics conditions such as tuberculosis, lymphoma, and rhabdomyosarcoma. With a special interest to improve the management of this condition, we report a mini-series of two cases of this rare malignancy.

Keywords: Askin's tumour, primitive neuroectodermal tumour, diagnostic challenge, prognostic factors


How to cite this URL:
Vinay V, Dubey PK, Singh K, Saini JK, Iyer SS, Srivastava A. Askin's tumor – A dual case study of rare thoracic neoplasm. J Appl Sci Clin Pract [Epub ahead of print] [cited 2023 Feb 4]. Available from: http://www.jascp.org/preprintarticle.asp?id=358991





  Introduction Top


Peripheral primitive neuroectodermal tumors (PNETs) belonging to the Ewing's sarcoma (EWS) family, are rare malignancies that occur most commonly in extraskeletal and soft tissues during childhood. It commonly presents as a tumor originating from diaphysis or metaphysis of long bones among children, adolescents, and young adults.[1] In the chest region, PNET arising from the chest wall is usually referred to as Askin's tumor. Askin et al. described it in 1979, as primarily occurring in the soft tissues around the paravertebral region of the chest wall.[2] A specific regimen has not yet been validated in the literature because of the rarity of this disease. We describe two cases of thoracic PNET diagnosed in young adults and reviewed few literatures on the subject.


  Case Reports Top


Case 1

A 25-year-old male patient presented with a history of dry cough and loss of weight for 8 months and also he developed progressive dyspnea and bilateral chest pain in the past 1 month. He had no other complaints; his past history was unremarkable and was a nonsmoker. On general physical examination, his heart rate was 112/min, respiratory rate was 24/min, and was afebrile. On respiratory system examination, there was dullness on both sides and decreased breath sounds on auscultation over both lower zones. Chest radiograph showed bilateral heterogeneous opacity [Figure 1]a. The laboratory tests including complete hemogram, liver function tests, and renal function tests were completely normal. Computed tomography scan of the chest showed bilateral large well defined heterogeneous soft-tissue mass involving right middle lobe, right lower lobe, lingular segment of left upper lobe, and left lower lobe with the abutment of main pulmonary artery, encasement of left pulmonary artery, and infiltration of pericardium with involvement of both chest wall [Figure 1]b. Ultrasound-guided transthoracic biopsy was taken from the mass on both sides. Histopathological examination of the specimen revealed sheets of small round to oval blue cells with a high ratio - nucleus–cytoplasm ratio (N/C ratio) [Figure 2]a. Immunohistochemical staining showed that the tumor cells were positive for cluster of differentiation 99 [CD99] [Figure 2]b, Vimentin [Figure 2]c, CD56 [Figure 2]d, and friend leukemia integration 1 (FLI-1), while cytokeratin (CK) was negative, consistent with PNET. After a multidisciplinary discussion, it was decided to initiate chemoradiation. However, the patient succumbed to respiratory failure before initiating chemotherapy.
Figure 1: (a) Chest radiograph showing bilateral heterogeneous opacity; (b) Computed tomography scan of the chest showing bilateral large well-defined and heterogeneous soft-tissue density mass

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Figure 2: Histopathological examination of the specimen revealed sheets of small round to oval blue cells with high N/C ratio (×100) (a). Immunohistochemical staining showed that the tumor cells were positive for CD99 (b), Vimentin (c), CD-56 (d)

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Case 2

A 21-year-old female patient presented with a history of left-sided chest pain, dry cough and exertional dyspnea for 3 months. Inspection of the respiratory system revealed decreased movements of the left hemithorax, and apical impulse was not visualized. Trachea was central in position confirmed by palpation. There were decreased movements of left-sided hemithorax and tactile vocal fremitus was decreased on the left side of chest. There was dullness on percussion of left side of chest in all areas. Air entry was decreased/absent on the left hemithorax over all the areas. Examination of the right hemithorax was normal. Rest of the systemic examination was normal. Routine blood investigations were within normal limits. Chest radiograph showed left-sided homogeneous opacity [Figure 3]. Computed tomography (CT) chest showed a large well-defined heterogeneous soft-tissue mass measuring 12 cm × 10.5 cm in the left hilum extending to lateral chest wall with collapse of left upper lobe and lower lobe with mild pleural effusion. Ultrasound-guided tapping of the effusion was exudative; predominantly neutrophilic; and adenosine deaminase levels were 14 IU/L. Ultrasound-guided transthoracic biopsy of the mass revealed sheets of small round to oval blue cells with high N/C ratio on histopathology [Figure 4]a. Immunohistochemical staining showed diffuse membrane positivity for CD99 [Figure 4]b, Ki67 [Figure 4]c, Vimentin [Figure 4d, CD56, and FLI-1, while CgA, Syn, S-100, CK, and leukocyte common antigen (LCA) were negative which confirmed the diagnosis of PNET. Chemotherapy consisting of ifosfamide, adriamycin, vincristine, and etoposide was initiated as part of an oncological treatment plan. The patient received 1st cycle and is doing well till now, and has been asked to follow-up after 3 cycles of chemotherapy.
Figure 3: Chest radiograph showing left-sided homogeneous opacity

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Figure 4: Sheets of small round to oval blue cells with high N/C ratio on histopathology (×100) (a). Immunohistochemical staining showed diffuse membrane positivity for CD99 (b), Ki67 (c), Vimentin (d)

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  Discussion Top


Askin's tumor is a peripheral PNET that belongs to Ewing's sarcoma family affecting the thoracopulmonary region. The clinical occurrence is rare and only a limited number of cases have been documented. Askin's tumor is more common in children and young adults, though it can develop at any age. Chest wall soft tissue, rib periosteum, chest, and lung are most commonly affected. The displacement of EWS gene on the 22nd chromosome and FLI-1 gene on the 11th chromosome is said to be the pathogenic reason. Clinically, cases with symptoms mostly present with cough, chest pain, fever, and shortness of breath. Chest wall mass, pleural effusion, and rib fractures have also been reported. In addition to high malignancy potential and poor efficacy, Askin's tumor is also prone for local recurrence and vascular metastasis that commonly involves bone and lung. CT scan is very useful for the diagnosis of Askin's tumor, commonly seen as large chest wall-based soft-tissue mass with or without ipsilateral pleural effusion and rib damage. Magnetic resonance imaging can be useful to determine the source of the tumor and the extent of chest wall invasion.[3]

Histopathology and immunohistochemical analysis are the basis for Askin's tumor diagnosis. As for malignancies within the group of tumors in small and round cells, such as chondrosarcoma, small cell osteosarcoma, non-Hodgkin's lymphoma, neuroblastomas, rhabdomyosarcoma, synovial sarcoma, and retinoblastoma; immunohistochemistry provides a definite basis for differential diagnosis.[4] It is possible to confirm a neuroectodermal origin with a positive result for CD99, NKX2.2, vimentin, FLI-1, and NSE immunohistochemical markers. PNET has been shown to have a characteristic chromosomal translocation t (11:22) (q24; q12), which offers yet another definite criterion for a diagnosis of Askin's tumor in 85%–90% of the patients.[5] An immunohistochemical panel must include S-100, TdT, CD45, epithelial membrane antigen (EMA), cytokeratin, LCA, desmin, and actin markers to exclude round-cell malignancies. CD99 has high sensitivity and NKX2.2 has high specificity in neuroectodermal tumors.[4]

Surgical resection, radiotherapy, and neoadjuvant and adjuvant chemotherapy are the current treatment options available. There are several anticancer drugs used in combination, namely cyclophosphamide, ifosfamide, doxorubicin, vincristine, actinomycin-D, etoposide, busulfan, carboplatin and melphalan. Combinations of the following drugs are usually used: VACA (vincristine, cyclophosphamide, actinomycin, doxorubicin), VAIA (cyclophosphamide replaced by ifosfamide), EVAIA (adding etoposide to VAIA), and vincristine, ifosfamide, doxorubicin, etoposide.[6]

It is believed that tumor size >5 cm, those in the late stage (stage III or IV), metastasis, lactate dehydrogenase (LDH) levels >240 U/l and tumor recurrence have a poor prognosis.[3] At the time of diagnosis, 25%–50% of PNET cases have metastases, and the 5-year survival rate is only 45%–55%.[7] The prognosis of pulmonary PNET is said to be poor, however, the long-term survival is good when there is complete surgical resection of the local disease diagnosed at an early stage.[8]

Many malignancies mimic small round blue cell tumor. Immunohistochemistry was the cornerstone of diagnosis in our cases. However, an accurate diagnosis can be made with combination of immunohistochemistry and molecular analysis for EWS/FLI-1 gene fusion. Positron emission tomography-CT is done as a part of routine evaluation after confirmation of malignancy to know staging and resectability status. In the first case, chemotherapy was not possible as patient succumbed to severe respiratory failure. Nevertheless, chemotherapy with ifosfamide, adriamycin, vincristine, and etoposide was initiated in the second case due to the presence of poor prognostic factors which included extensive involvement of tumor, pleural effusion and late stage on presentation. The patient tolerated the first cycle and advised to follow-up regularly and to seek immediate medical care if new symptoms arise.


  Conclusion Top


The differential diagnosis of thoracic cancers should include Askin's tumor as it is a rare pulmonary neoplasm regardless of gender or age. Tumor size >5 cm, late stage, metastasis, LDH levels >240 U/l, and tumor recurrence are considered to be poor prognostic factors. Diagnosis at an early stage and multidisciplinary approach that includes radical surgery, chemotherapy, and radiotherapy has a better outcome.

Take home message

  1. Askin's tumor is a peripheral PNET that belongs to Ewing's sarcoma family affecting the thoracopulmonary region
  2. Histopathology and immunohistochemical analysis are the basis for Askin's tumor diagnosis
  3. Despite the poor prognosis of pulmonary PNET, there are good prospects for long-term survival when the tumor is completely removed surgically.


Declaration of patient consent

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

List of abbreviations

  1. PET- positron emission tomography
  2. PNET- Primitive neuroectodermal tumour
  3. FLI- Friend Leukemia Integration
  4. CT- Computed Tomography
  5. N/C ratio- nucleus-cytoplasm ratio
  6. CD- Cluster of differentiation
  7. CK- Cytokeratin
  8. EWS- Ewing sarcoma
  9. LDH- Lactate Dehydrogenase
  10. LCA- Leukocyte Common Antigen
  11. EMA- Epithelial Membrane Antigen


Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Kushner BH, Hajdu SI, Gulati SC, Erlandson RA, Exelby PR, Lieberman PH. Extracranial primitive neuroectodermal tumors. The memorial Sloan-Kettering cancer center experience. Cancer 1991;67:1825-9.  Back to cited text no. 1
    
2.
Askin FB, Rosai J, Sibley RK, Dehner LP, McAlister WH. Malignant small cell tumor of the thoracopulmonary region in childhood: A distinctive clinicopathologic entity of uncertain histogenesis. Cancer 1979;43:2438-51.  Back to cited text no. 2
    
3.
Zhang KE, Lu R, Zhang P, Shen S, Li X. Askin's tumor: 11 cases and a review of the literature. Oncol Lett 2016;11:253-6.  Back to cited text no. 3
    
4.
Pathology Outlines – Ewing Sarcoma. Available from: https://www.pathologyoutlines.com/topic/boneewing.html. [Last accessed on 2022 May 13].  Back to cited text no. 4
    
5.
Cueto-Ramos RG, Ponce-Escobedo AN, Montero-Cantú CA, Muñoz-Maldonado GE, Ruiz-Holguín E, Vilches-Cisneros N. Askin tumor: Case report and literature review. Med Univ 2015;17:213-7.  Back to cited text no. 5
    
6.
Benbrahim Z, Arifi S, Daoudi K, Serraj M, Amara B, Benjelloun MC, et al. Askin's tumor: A case report and literature review. World J Surg Oncol 2013;11:10.  Back to cited text no. 6
    
7.
Jürgens H, Bier V, Harms D, Beck J, Brandeis W, Etspüler G, et al. Malignant peripheral neuroectodermal tumors. A retrospective analysis of 42 patients. Cancer 1988;61:349-57.  Back to cited text no. 7
    
8.
Kang LH, Kim HJ, Jang JH, Kim JH, Choi KU, Jeon D. A case of long-term survival in a patient with primary primitive neuroectodermal tumor of the lung. Kosin Med J 2018;33:263-70.  Back to cited text no. 8
    

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Correspondence Address:
Jitendra Kumar Saini,
Head, Department of Thoracic Oncology, National Institute of Tuberculosis and Respiratory Diseases (NITRD), Sri Aurobindo Marg (Near Qutub Minar), New Delhi - 110 030
India
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jascp.jascp_32_22



    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]



 

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