Indian Journal of Pathology and Microbiology
Home About us Instructions Submission Subscribe Advertise Contact e-Alerts Ahead Of Print Login 
Users Online: 5269
Print this page  Email this page Bookmark this page Small font sizeDefault font sizeIncrease font size

  Table of Contents    
Year : 2016  |  Volume : 59  |  Issue : 3  |  Page : 398-400
Pulmonary hemangioendothelioma with osteoclast-like giant cells: A rare observation

1 Department of Pathology, Tata Memorial Hospital, Parel, Mumbai, Maharashtra, India
2 Department of Surgical Oncology (Thoracic), Tata Memorial Hospital, Parel, Mumbai, Maharashtra, India

Click here for correspondence address and email

Date of Web Publication10-Aug-2016


Pulmonary epithelioid hemangioendothelioma (PEH) is a rare vascular neoplasm, predominantly encountered in women, more often in the age group of 40 years and below. It is a tumor of borderline malignant potential with a clinical course intermediate between hemangioma and angiosarcoma. The tumor has variable prognosis, and treatment options include surgical excision in operable cases and chemotherapy in disseminated ones. The present report describes complete clinical, radiological, and histopathological features of PEH with osteoclast-like giant cells and metaplastic ossification in a 20-year-old boy who presented with dyspnea and episodes of hemoptysis with review of literature.

Keywords: Epithelioid hemangioendothelioma, metaplastic ossification, osteoclast-like giant cell, lung

How to cite this article:
Adamane SA, Deodhar KK, Gupta AM, Karimundackal G, Desai SB. Pulmonary hemangioendothelioma with osteoclast-like giant cells: A rare observation. Indian J Pathol Microbiol 2016;59:398-400

How to cite this URL:
Adamane SA, Deodhar KK, Gupta AM, Karimundackal G, Desai SB. Pulmonary hemangioendothelioma with osteoclast-like giant cells: A rare observation. Indian J Pathol Microbiol [serial online] 2016 [cited 2022 Aug 16];59:398-400. Available from: https://www.ijpmonline.org/text.asp?2016/59/3/398/188125

   Introduction Top

Pulmonary epithelioid hemangioendothelioma (PEH) is a rare vascular endothelial neoplasm with predilection for female gender and is rarely reported in children. PEH was first reported by Dail et al.[1] as “pulmonary attack” in 1977 and was regarded initially as a variant of bronchioloalveolar carcinoma named “intravascular bronchioloalveolar tumor.” Hemangioendothelioma has been described in many organs with predilection for skin, bone, liver, and lungs.[2] The present report describes the complete clinical, radiological, and histopathological features of PEH with an unusual feature of osteoclast-like giant cells and metaplastic ossification in a 20-year-old young male.

   Case Report Top

A 20-year-old young man was referred to our hospital with progressive grades of dyspnea over the past one year and three episodes of hemoptysis, without significant medical and surgical illness in the past. The clinical examination was unremarkable except for decreased air entry in the right lower zone of the chest. Routine hematological and biochemical investigations were within normal range, except for hypochromic microcytic anemia (hemoglobin = 8.9 gm%). Arterial blood gas analysis was performed with patient breathing room air demonstrated normal values (pH = 7.40, PaCO2 = 43 mmHg, PaO2 = 91 mmHg, and bicarbonate level = 26 mmol/L). The rest other vital signs were within normal limits.

Contrast-enhanced computerized tomography (CECT) scan revealed an endobronchial mass in the right lower lobe of lung with multiple small nodules in both lobes of the right lung as well as an expansile lytic lesion on posterior aspect of the ninth rib. Whole body 18F fluorodeoxyglucose (FDG) positron emission tomography-CT (PET CT) scan showed an increased FDG uptake in the right lung mass, right subcarinal and precarinal nodes, C4 vertebra, left scapula, left acetabulum, and left ninth rib. Based on the radiological evaluation of bronchocentric mass and young age of the patient, a clinical diagnosis of carcinoid of the lung was considered. The cytological examination of bronchiolo-alveolar lavage revealed nonsmall cell carcinoma. A fiberoptic biopsy was performed for primary diagnosis of the tumor.

Histology sections of 3 μm thickness were prepared and stained with hematoxylin and eosin. Histomorphological examination of the lung biopsy revealed a tumor in diffuse sheet, lying just beneath the normal respiratory mucosa and diffusely infiltrating the alveoli and bronchioles. The tumor cells were round to oval with abundant eosinophilic cytoplasm and vesicular nuclei. Intracytoplasmic lumina with red blood cells with distinct intracytoplasmic and intranuclear inclusions was identified in some tumor cells. There was no evidence of mitosis or necrosis. Immunohistochemistry (IHC) staining was performed by Ventana BenchMark XT autoimmunostainer having peroxidase 3′-3′ diaminobenzidine tetrahydrochloride as the chromogen. Various antibody markers are listed in [Table 1]. The tumor cells revealed nuclear staining for FLI-1 and membranous staining for CD31 and CD34; whereas they were negative for myogenin, CK, thyroid transcription factor-1, S-100P, and desmin. A final histopathological diagnosis of PEH was thus confirmed and rendered.
Table 1: List of various antibody markers in this study

Click here to view

Based on the biopsy diagnosis, the patient underwent right lower lobectomy with mediastinal lymph node dissection. On serial slicing, 5 cm × 4.3 cm × 3 cm gray-white tumor of gritty to hard consistency was noted involving the main bronchus with a tiny satellite nodule of similar morphology and 1 cm diameter in the adjacent lung.

The histomorphological examination of the excision specimen was very much akin to the biopsy received earlier and revealed tumor cells in diffuse sheet, infiltrating the lung parenchyma. The tumor cells had round to oval nuclei with intracellular as well as intracytoplasmic vacuoles, suggesting an attempt to form unicellular vascular channels. Amidst these were scattered osteoclast-like giant cells and foci of metaplastic ossification [Figure 1]. The results of repeat IHC performed on the resected specimen were concordant with those done on biopsy [Figure 2], thus confirming the diagnosis of PEH. The mediastinal lymph nodes revealed noncaseating granulomatous lymphadenitis of probable tuberculous etiology. The final diagnosis of PEH with osteoclast-like giant cells was offered. Postoperatively, the patient suddenly started to have oxygen desaturation. The bacteriological examination of the sputum revealed acid-fast bacilli. The patient was started on anti-Koch's regime, but he succumbed to death on the fifth postoperative day. He succumbed to death of cardiorespiratory failure on the fifth postoperative day.
Figure 1: Lower power view shows a diffusely infiltrating tumor with osseous metaplasia and osteoclast-like giant cells (Inset) (H and E, ×100)

Click here to view
Figure 2: (a) On immunohistochemistry, the tumor cells show nuclear positivity for FLI-1, and (b) membranous positivity for CD31 (DAB, ×400)

Click here to view

   Discussion Top

PEH was first described by Dail et al.[1] as intravascular bronchioloalveolar tumor. Immunohistochemical techniques confirmed its endothelial lineage and Weiss et al.[3] subsequently suggested the current term, “epithelioid hemangioendothelioma.” The mesenchymal vasoformative reserve stem cells have also been suggested as the most likely source of this tumor as these lesions have a great propensity to invade vein, arteries, alveoli, and bronchioles.

PEH is an uncommon neoplasm encountered in patients with a wide age range of 19–70 years, with mean age of presentation being 40.1 years. There is a distinct female preponderance with a female to male ratio of 3:1. The patient may be asymptomatic or presents with nonspecific symptoms such as weight loss, fatigue, dyspnea, cough, hemoptysis, and chest pain [4] as seen in our patient. Unusual manifestations have been described in the literature such as hypertrophic pulmonary osteoarthropathy, pulmonary edema, inflammatory diseases such as sarcoidosis, multiorgan involvement at presentation, and pericardial effusion with raised CA 125 levels.[5],[6],[7] Patients with PEH are also known to have tuberculosis at the time of presentation as well during their course of treatment for the PEH,[2],[8] which might be due to the immunodeficiency due to drugs, debilitating condition secondary to the tumor or secondary to anemia of chronic diseases, as might be the cause in our case.

On radiology, PEH has classical appearance as bilateral multiple pulmonary nodular opacities of <2 cm in diameter with variable margins.[5] In the present study, the radiological evaluation revealed nodular opacities in both lobes of the right lung along with lytic lesions in multiple bones as mentioned, raising the suspicion of metastasis of unknown primary and infectious etiology. Metastatic carcinoma was excluded on morphology, immunohistochemical stains, and whole body scan being negative for the primary in the body. The absence of the disseminated infection was confirmed by the blood culture examination, which was negative for growth of microorganisms. Numerous osteoclast-like giant cells with epithelioid appearance of the tumor cells on histology raised a differential diagnosis of metastatic sarcoma, but radiological and clinical examination did not reveal a primary elsewhere in the body.

PEH is usually diagnosed on open lung or thoracoscopic biopsy specimens as reported in most cases of the literature and is very rarely diagnosed on transbronchial biopsy.[9] In the current study, the patient was diagnosed on the transbronchial biopsy. The morphology described in our case in conjunction with the IHC studies with CD31, CD34, and FLI-1 confirmed the diagnosis of PEH and endothelial lineage of the tumor. FLI-1 is considered the most specific endothelial marker of PEH in the appropriate morphologic context.[10] Thus, awareness of the entity with its varied morphological appearance should be kept in mind while evaluating the lung biopsy.

The treatment in PEH has not been standardized. Surgical excision is a recommended option for solitary pulmonary nodule or unilateral multiple nodules. For the unresectable, metastatic or multiple, bilateral tumors, different treatment protocols are under evaluation and include combination chemotherapy, hormonal therapy (anti-estrogens and progesterone), and thalidomide with interferon-α and bevacizumab (a monoclonal antibody that blocks human vascular endothelial growth factor-A [VEGF-A]). The prognosis is variable with a median survival of 4–5 years.[9]

   Conclusion Top

The purpose of the present communication is to report an unusual clinical presentation of PEH as a bronchocentric mass in a young male and document a hitherto undescribed histopathological feature of osteoclast-like giant cells in PEH to the best of our knowledge. A high index of suspicion in the light of histological features and judicious use of immunohistochemical stains is essential for an accurate diagnosis of PEH.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

   References Top

Dail DH, Liebow AA, Gmelich JT, Friedman PJ, Miyai K, Myer W, et al. Intravascular, bronchiolar, and alveolar tumor of the lung (IVBAT). An analysis of twenty cases of a peculiar sclerosing endothelial tumor. Cancer 1983;51:452-64.  Back to cited text no. 1
Dahabreh MM, Hmeideen NI, Najada AS. Multicentric epithelioid hemangioendothelioma involving the lungs, trachea, liver and skeletal muscles. Respir Med Case Rep 2012;5:20-2.  Back to cited text no. 2
Weiss SW, Ishak KG, Dail DH, Sweet DE, Enzinger FM. Epithelioid hemangioendothelioma and related lesions. Semin Diagn Pathol 1986;3:259-87.  Back to cited text no. 3
Erasmus JJ, McAdams HP, Carraway MS. A 63-year-old woman with weight loss and multiple lung nodules. Chest 1997;111:236-8.  Back to cited text no. 4
Bharadwaj R, Hejmadi R, Mistry R, Desai S. Pericardial effusion and raised CA-125 level – Unusual manifestations of primary pulmonary epithelioid hemangioendothelioma. Indian J Cancer 1999;36:194-7.  Back to cited text no. 5
Adler B, Naheedy J, Yeager N, Nicol K, Klamar J. Multifocal epithelioid hemangioendothelioma in a 16-year-old boy. Pediatr Radiol 2005;35:1014-8.  Back to cited text no. 6
Madhusudhan KS, Srivastava DN, Gamanagatti S. Multifocal epithelioid hemangioendothelioma presenting with hemoptysis. Indian J Pediatr 2010;77:699-700.  Back to cited text no. 7
Lopes T, Clemente S, Feliciano A, Lourenço I, Costa A, Gil Duarte J. Pulmonary epithelioid hemangioendothelioma - Rarity, diagnosis and treatment difficulties. Rev Port Pneumol 2009;15:1167-74.  Back to cited text no. 8
Rosengarten D, Kramer MR, Amir G, Fuks L, Berkman N. Pulmonary epithelioid hemangioendothelioma. Isr Med Assoc J 2011;13:676-9.  Back to cited text no. 9
Gill R, O'Donnell RJ, Horvai A. Utility of immunohistochemistry for endothelial markers in distinguishing epithelioid hemangioendothelioma from carcinoma metastatic to bone. Arch Pathol Lab Med 2009;133:967-72.  Back to cited text no. 10

Correspondence Address:
Dr. Sangeeta B Desai
Department of Pathology, 8th Floor, Annex Building, Tata Memorial Hospital, Dr. E.B. Road, Parel, Mumbai - 400 012, Maharashtra
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0377-4929.188125

Rights and Permissions


  [Figure 1], [Figure 2]

  [Table 1]

This article has been cited by
1 Solitary epithelioid hemangioendothelioma concurrent with nodular parenchymal amyloidosis of the lung and Rosai-Dorfman disease
O. V. Dolzhansky,E. M. Paltseva,M. M. Morozova,D. V. Bazarov,E. V. Boranov,D. N. Fedorov
Arkhiv patologii. 2018; 80(2): 52
[Pubmed] | [DOI]
2 Apatinib for the treatment of pulmonary epithelioid hemangioendothelioma
Zhipeng Zheng,Hanying Wang,Hanliang Jiang,Enguo Chen,Jun Zhang,Xinyou Xie
Medicine. 2017; 96(45): e8507
[Pubmed] | [DOI]


    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Email Alert *
    Add to My List *
* Registration required (free)  

   Case Report
    Article Figures
    Article Tables

 Article Access Statistics
    PDF Downloaded65    
    Comments [Add]    
    Cited by others 2    

Recommend this journal