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CASE REPORT
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Primary pulmonary undifferentiated pleomorphic sarcoma: A rare malignant lung tumor


1 Department of Pulmonary, Critical Care and Sleep Medicine, Rishikesh, Uttarakhand, India
2 Department of Pathology, All India Institute of Medical Sciences, Rishikesh, Uttarakhand, India

Date of Submission14-Sep-2021
Date of Decision06-Aug-2022
Date of Acceptance16-Aug-2022
Date of Web Publication18-Nov-2022

Correspondence Address:
Mihir Gangakhedkar,
Flat 306, Swastik Residency, Barrage Colony, Near AIIMS Rishikesh, Rishikesh - 249 203, Uttarakhand
India
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jcrt.jcrt_1612_21

 > Abstract 


Undifferentiated Pleomorphic Sarcoma (UPS) is a common soft tissue sarcoma that can develop in various organs, but lung involvement is usually due to metastasis. UPS originating primarily in the lungs is called primary pulmonary undifferentiated pleomorphic Sarcoma (PPUPS) and is exceptionally rare. It is a high-grade pleomorphic neoplasm with no identifiable lines of differentiation. Thus, it is essentially a diagnosis of exclusion that requires extensive clinical, radiographic and histopathological evaluation. Herein we report the case of a 49-year-old gentleman who presented with anemia and weight loss and was found to have a large right lung mass. The lesion was diagnosed as PPUPS after detailed histopathological, immunohistochemical and molecular analysis and exclusion of a possible extrapulmonary origin.

Keywords: Malignant neoplasm, primary pulmonary sarcoma, primary pulmonary undifferentiated pleomorphic sarcoma, rare lung tumors, undifferentiated pleomorphic sarcoma



How to cite this URL:
Rajpoot A, Gangakhedkar M, Singh M, Mishra M. Primary pulmonary undifferentiated pleomorphic sarcoma: A rare malignant lung tumor. J Can Res Ther [Epub ahead of print] [cited 2022 Dec 9]. Available from: https://www.cancerjournal.net/preprintarticle.asp?id=361529




 > Introduction Top


UPS is a common soft tissue sarcoma, which was previously included in the bracket of malignant fibrous histiocytoma. It can develop in several organs of the body, but involvement of the lungs usually occurs as metastasis. Rarely, the lung is the primary site of origin, when it is called primary pulmonary undifferentiated pleomorphic sarcoma (PPUPS) and is one of the least common types of primary pulmonary sarcomas (PPSs).[1]

Herein we report the case of a middle-aged man with a large lung mass that was diagnosed as PPUPS after a detailed examination.


 > Case Report Top


A 49-year-old man presented with right-sided chest pain, weight loss and fatigue for the previous 3 mo. Past medical history was insignificant, and he had no addictions. General examination revealed pallor while respiratory examination showed diminished movements, a dull note on percussion and diminished breath sounds over the right hemithorax. Chest X-ray revealed a large right hemi-thoracic opacity which on thoracic Computed Tomography (CT) scan [Figure 1] was a poorly-circumscribed, heterogeneous, 15 × 13.6 × 6.2 cm mass within the right lung base, involving the pleural surface. Positron Emission Tomography-Computed Tomography [Figure 1] showed intense fluorodeoxyglucose (FDG) uptake within the mass (standardized uptake value of 20.0). There was encasement of the right main bronchus and right pulmonary artery, indentation and luminal narrowing of trachea, but no obvious chest-wall infiltration or overlying rib erosion. Multiple, FDG-avid, possibly metastatic sites were also identified, namely a 4.1 cm lobulated right adrenal mass, lesions in the right scapula, vertebrae, sacrum, left femur, and a left lumbar omental deposit. Fat planes with segment VII of liver were also lost.
Figure 1: Axial (a) and coronal (b) sections of thoracic contrast-enhanced computed tomography scan showing a large (15 × 13.6 × 6.2 cm), poorly-circumscribed, heterogeneous mass within the right lung base involving the pleural surface. Positron emission tomography-computed tomography scan (c) showing a large right hemithorax mass (18 × 16 × 23 cm) with intense fluorodeoxyglucose uptake involving almost entire right lung parenchyma, encasing right main bronchus, pushing the superior vena cava, indenting right lateral and inferior walls of trachea and causing luminal narrowing, and abutting the diaphragmatic, mediastinal and costal pleurae, with no obvious chest wall infiltration or overlying rib erosion

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Histopathological examination of CT-guided core biopsy specimen showed tissue infiltrated by fascicles of spindle cells displaying mild to moderate anisonucleosis, hyperchromatic elongated nuclei and indistinct cytoplasmic membranes, with intervening areas of collagenization, foci of necrosis and few mitotic figures. Microscopic examination showed no line of differentiation by morphology, suggesting a poorly-differentiated malignant tumor with features of malignant spindle cell neoplasm like carcinosarcoma, sarcomatoid mesothelioma or a high-grade sarcoma. Immunohistochemistry (IHC) found the tumor cells to be positive for SMA, WT-1, Calretinin and Podoplanin markers, with Ki-67 labelling index of 30-40%; and negative for PanCK, CK-5/6, CD-34, EMA, Desmin, S-100, STAT-6, ß-catenin, Bcl-2, CD-99, and TLE-1 markers [Figure 2]. The overall findings favored a diagnosis of an undifferentiated high-grade pleomorphic sarcoma.
Figure 2: (a) Immunohistochemistry with Calretinin showing nuclear as well as cytoplasmic positivity in the tumor cells (400X, DAB). Tumor cells also showed diffuse positivity for Podoplanin (b), WT1 (c), and SMA (d) (400X, DAB). (e) Ki-67 proliferation index was approximately 40% in the hot spot areas (400X, DAB)). (f) Pan-CK was negative in these cells (400X, DAB)

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Since no extrapulmonary origin was identified and the tumor did not demonstrate any line of differentiation, a final diagnosis of PPUPS was made. Given the extensively metastatic disease and poor performance status (ECOG-3), surgical resection was not possible, and the patient was therefore planned for palliative chemotherapy based on cyclophosphamide and vincristine. Unfortunately, the patient did not follow up for therapy and succumbed to the illness.


 > Discussion Top


UPS is a high-grade pleomorphic neoplasm that shows no discernible microscopic evidence of any specific form of differentiation using currently available diagnostic techniques. UPS was previously classified as Malignant Fibrous Histiocytoma (MFH), occurring most commonly in the deep soft tissue of extremities of elderly patients.[2] However with failure to demonstrate evidence of “fibro-histiocytic” differentiation, MFH was delisted as a diagnostic entity by the World Health Organization in 2012. The diagnosis of UPS is one of exclusion and one must exclude other similar malignant tumors such as malignant melanomas, sarcomatoid carcinomas, anaplastic lymphomas, sarcomatous mesotheliomas or other sarcomas.[3]

PPSs constitute <0.5% of all lung malignancies.[4],[5]( They often present as a well-circumscribed large peripheral or hilar mass, or may present as an endobronchial tumor in 10% of cases.[6] Most patients present with cough, chest pain, hemoptysis or dyspnea. Imaging may show a solitary mass with or without postobstructive effects, and at times extraluminal growth with or without local invasion into adjacent structures. The clinical course is rapidly progressive and metastasis is common. The prognosis is variable with reported life expectancies from 1-72 months.[6] Endobronchial masses show a more favorable prognosis.

PPUPSs are amongst the rarer PPSs. It is difficult to make a definitive diagnosis of PPUPS on a biopsy specimen because the specimen may not be representative of the entire tumor. Consequently, pre-operative certainty of a diagnosis is low. IHC characteristically shows positive staining for histiocytic markers (CD68, α1-antichymotrypsin, vimentin), a reason why such tumors were identified as MFH in the past. Staining for TTF-1, S-100 protein, desmin, actin, myoglobin, caldesmon, D2-40, and calretinin is negative, is important to rule out other tumors. MFH, when the terminology was in use, had more than one histological pattern noted. A wider than usual panel of IHC studies is therefore necessary to rule out other neoplasms that can resemble UPS including other types of sarcomas, sarcomatoid carcinoma, melanoma, or mesothelioma.[7] Electron microscopy is rarely helpful.

An extra-pulmonary UPS is a relatively common soft tissue tumor and most cases of UPS found in the lung represent metastasis from an extra-pulmonary origin. In an analysis of 100 cases, Chen et al.[8] found 55% and 35% cases in the extremities and the trunk respectively.

A standard treatment protocol for the malignancy has not been established yet. Historically PPUPS/MFH have been approached from the perspective of definitive surgical management and with good effect.[9] However, case reports favoring the use of systemic chemotherapy or combination chemotherapy with cyclophosphamide, vincristine, adriamycin, and dacarbazine have been published.[10] Combination chemotherapy with doxorubicin and ifosfamide has shown a good response in some cases. Postoperative chemotherapy or chemo-radiotherapy for postresection recurrences have also been employed with varying success. Future well-designed clinical studies are necessary for delineating an appropriate approach to managing this rare malignancy.


 > Conclusion Top


This report highlights a rare malignant lung tumor, PPUPS, whose work-up poses significant diagnostic challenges with surgery being the mainstay of treatment in most cases. A stepwise approach comprising extensive clinico-radiological assessment, liberal tissue sampling, detailed histopathological, IHC and molecular studies, and exclusion of any extrapulmonary site of origin is required to establish the diagnosis, which is one of exclusion.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/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.

Ethical considerations

Consent of the patient's son was obtained before the case submission as the patient had succumbed to the illness. All clinical procedures were as per international ethical standards.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 > References Top

1.
Etienne-Mastroianni B, Falchero L, Chalabreysse L, Loire R, Ranchère D, Souquet PJ, et al. Primary sarcomas of the lung: A clinicopathologic study of 12 cases. Lung Cancer 2002;38:283-9.  Back to cited text no. 1
    
2.
Jo VY, Fletcher CD. WHO classification of soft tissue tumours: an update based on the 2013 (4th) edition. Pathology 2014;46:95-104.  Back to cited text no. 2
    
3.
Hamza A, Alrajjal A, Edens J, Khawar S, Khurram MS, Szpunar S, et al. Utility of additional tissue sections in surgical pathology. Int J Surg Pathol 2018;26:392-401.  Back to cited text no. 3
    
4.
Cameron EWJ. Primary sarcoma of the lung. Thorax 1975;30:516-20.  Back to cited text no. 4
    
5.
Miller DL, Allen MS. Rare pulmonary neoplasms. Mayo Clin Proc 1993;68:492-8.  Back to cited text no. 5
    
6.
Kim JH, Cho SH, Kim EK, Lee JH, Jeong HC. Endobronchial malignant fibrous histiocytoma: Case report of an unusual presentation and palliative flexible bronchoscopic resection. Respir Care 2013;58:e92-4.  Back to cited text no. 6
    
7.
Qorbani A, Nelson SD. Primary pulmonary undifferentiated pleomorphic sarcoma (PPUPS). Autops Case Rep 2019;9:e2019110.  Back to cited text no. 7
    
8.
Chen S, Huang W, Luo P, Cai W, Yang L, Sun Z, et al. Undifferentiated pleomorphic sarcoma: Long-term follow-up from a large institution. Cancer Manag Res 2019;11:10001-9.  Back to cited text no. 8
    
9.
Robinson LA, Babacan NA, Tanvetyanon T, Henderson-Jackson E, Bui MM, Druta M. Results of treating primary pulmonary sarcomas and pulmonary carcinosarcomas. J Thorac Cardiovasc Surg 2021;162:274-84.  Back to cited text no. 9
    
10.
Leite C, Goodwin JW, Sinkovics JG, Baker LH, Benjamen R. Chemotherapy of malignant fibrous histiocytoma: A Southwest Oncology Group report. Cancer 1977;40:2010-4.  Back to cited text no. 10
    


    Figures

  [Figure 1], [Figure 2]



 

 
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