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CASE REPORT
Year : 2022  |  Volume : 18  |  Issue : 3  |  Page : 817-819

Multifocal primary pseudomyogenic hemangioendothelioma of bone managed with denosumab: A rare case with diagnostic and therapeutic challenge


1 Department of Pathology, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India
2 Department of Orthopaedics, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India
3 Department of Radiodiagnosis, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India
4 Department of Nuclear Medicine, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India

Date of Submission11-Aug-2020
Date of Decision11-Aug-2020
Date of Acceptance21-Jan-2021
Date of Web Publication14-Apr-2022

Correspondence Address:
Garima Durga
Department of Pathology, Rajiv Gandhi Cancer Institute and Research Centre, Sector v, Rohini, New Delhi - 110 085
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jcrt.JCRT_1138_20

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 > Abstract 


Pseudomyogenic hemangioendothelioma (PMH) is a rare tumor of vascular origin with intermediate malignant potential which commonly presents as a subcutaneous and soft-tissue mass with or without concurrent bone involvement. However, PMH presenting as primary multifocal bone lesions is rare. Histomorphologically, it mimicks other epithelioid tumors and cytokeratin expression in PMH can prompt an erroneous diagnosis of metastatic carcinoma, especially in an elderly patient. Diligent histopathological examination and judicious immunohistochemistry panel can guide to the correct diagnosis. Due to its rarity, the optimal therapeutic strategy has not been established till date. We present a rare case of PMH of primary bone with multifocal bony disease in a 23-year-old male who presented with severe bone pains. The patient has been managed with four weekly denosumab, and the disease is stable with symptomatic relief after 6 months.

Keywords: Bone involvement, denusumab, pseudomyogenic hemangioendothelioma, vascular tumor


How to cite this article:
Pasricha S, Sharma A, Pruthi M, Durga G, Jajodia A, Gupta G, Kamboj M, Gupta M, Mehta A. Multifocal primary pseudomyogenic hemangioendothelioma of bone managed with denosumab: A rare case with diagnostic and therapeutic challenge. J Can Res Ther 2022;18:817-9

How to cite this URL:
Pasricha S, Sharma A, Pruthi M, Durga G, Jajodia A, Gupta G, Kamboj M, Gupta M, Mehta A. Multifocal primary pseudomyogenic hemangioendothelioma of bone managed with denosumab: A rare case with diagnostic and therapeutic challenge. J Can Res Ther [serial online] 2022 [cited 2022 Aug 10];18:817-9. Available from: https://www.cancerjournal.net/text.asp?2022/18/3/817/343259




 > Introduction Top


Pseudomyogenic hemangioendothelioma (PMH) is a rare vascular tumor of intermediate malignant potential which commonly presents as a subcutaneous and soft-tissue mass with predilection for lower extremities.[1],[2],[3],[4],[5] The term “PMH” was recognized as a distinct clinicopathological entity in 2011 by Hornick and Fletcher.[6] PMH presenting as primary bone lesions is rare and can often mimick metastatic etiology. We present the rare case of primary bone PMH with extensive multifocality.


 > Case Report Top


A 23-year-old young male with no significant history, presented with complaints of pain in the right leg for 1 year. The patient was initially evaluated elsewhere. X-ray revealed multiple lytic lesions in right tibia and fibula with cortical erosion [Figure 1]a. The subsequent regional magnetic resonance imaging revealed multiple altered signal intensity lesions in right tibia involving medulla with cortical destruction and adjacent soft-tissue swelling [Figure 1]b. A working clinicoradiological diagnosis of osteomyelitis was made. The right tibial lesion curettings were reported as metastatic carcinoma. The patient was subsequently referred to our tertiary cancer care center.
Figure 1: (a) Radiograph of the right leg depicting multiple ill-defined lytic lesions with wide zone of transition in the diaphyseal region of tibia. (b) MRI images consisting of multiple altered signal intensity lesions in the tibia. (c) Fused PET-CT image depicting multiple metabolically active lytic/sclerotic lesions in multiple right tarsal, multiple lesions in right tibia, right femur (lower end), right ischium, bilateral ilium, sacrum, multiple vertebra and sternum. MRI = Magnetic resonance imaging, PET-CT = Positron emission tomography-computed tomography

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On reviewing histopathology, bony trabeculae were infiltrated by the sheets of tumor cells composed predominantly of epithelioid cells having eccentric nuclei, vesicular chromatin with abundant glassy eosinophilic cytoplasm. Few cells were polygonal with cytoplasmic hyaline inclusions, reminiscent of rhabdoid morphology [Figure 2]a, [Figure 2]b, [Figure 2]c, [Figure 2]d. Few foci showed significant osteoclast-like giant cells. Mitotic activity was inconspicuous and no necrosis was seen. In view of the above features, a vascular tumor was a strong possibility. On primary immunohistochemistry (IHC) panel, the tumor cells were positive for CK, ERG-1, CD31, FLI-1, and thrombomodulin, while were negative for CD34, S-100, and SATB2 [Figure 3]a, [Figure 3]b, [Figure 3]c, [Figure 3]d. The Ki67 index was 1%–2%, and INI-1 nuclear expression was retained.
Figure 2: (a) Section shows bony trabeculae infiltrated by sheets of spindle to plump epithelioid cells (H and E, ×100). (b) Tumor cells have eccentric nuclei, vesicular chromatin, conspicuous nucleoli with abundant glassy eosinophilic cytoplasm (H and E, ×200). (c) Section shows anastomosing trabeculae of woven bone reminiscent of osteoblastoma-like areas (H and E, ×100). (d) Significant areas of tumor showed rhabdoid morphology with cytoplasmic hyaline inclusions (H and E, ×400)

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Figure 3: (a-c) Tumor cells show diffuse immunoexpression for CK, CD31, and ERG1 respectively. (d)CD34 highlights interspersed small blood vessels, while completely negative in tumor cells

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Overall, IHC features confirmed the vascular origin pointing toward hemangioendothelioma; however, the lack of CD34 immunoexpression along with the absence of background myxohyaline stroma provided a tangible evidence to render a final diagnosis of PMH. In multispecialty tumor board, positron emission tomography-computed tomography was advised which revealed multiple metabolically active lytic/sclerotic lesions in multiple right tarsals and metatarsals bone, right tibia, right fibula, right patella, right femur, right ischium, bilateral ilium, sacrum, multiple vertebrae, and sternum [Figure 1c]. Furthermore, occasional small soft-tissue deposits were seen in the posterior muscle compartment of the right thigh and right lower leg. Since the patient was symptomatic only for tibial lesions and the data on systemic chemotherapy are limited, it was decided to put patient on subcutaneous injections of denosumab (120 mg) 4 weekly. After 6 months of follow-up, the disease has remained stable with marked symptomatic relief in pain.


 > Discussion Top


Hemangioendothelioma is a distinct vascular neoplasm with biological behavior intermediate between an indolent benign hemangioma and an aggressive malignant angiosarcoma.[7],[8]

Hornick and Fletcher[6] reported the series of 50 cases of PMH which showed striking male preponderance with 82% of patients ≤40 years. There was marked propensity for lower extremities (54%) and soft-tissue lesions and 66% of the cases had multifocal lesions. Concurrent bone and soft-tissue involvement was seen in 14% of the tumors, and solitary bone involvement was noted in a single case.

Inyang et al.[1] reported a large series of primary PMH of bone comprising of 10 cases with multicentricity, with a mean age of 36.7 years and male preponderance (9:1) and predilection for lower extremity, spine, and pelvis (70%).

Pradhan et al.[9] reported eight cases of PMH of skin, bone, and soft tissue with three patients having solitary bone involvement and two cases having simultaneous bone and soft-tissue involvement.

The differential diagnosis for primary PMH involving bone includes other vascular tumors (epithelioid hemangioma and epithelioid hemangioendothelioma), epithelioid sarcoma (ES) and metastatic carcinoma with sarcomatoid features.[1],[2],[8]

Epithelioid hemangioma has a characteristic lobular architecture, with well-formed vascular lumen and significant arteriolar like vessels at periphery, with concomitant CD34 and CD31 immunoexpression. Whereas, PMH shows abundant eosinophilic dense glassy cytoplasm without any vascular lumen formation and characteristic CD34 negative immunoprofile. Epithelioid hemangioendothelioma involving bones are although characterized by abundant eosinophilic cytoplasm; intracytoplasmic vascular lumen (blister cells), however characteristic myxohyaline background stroma along with CD34 immunoexpression makes its distinction from PMH. Metastatic sarcomatoid carcinoma is a pertaining differential, especially in a middle aged or elderly person. Diffuse CK and CK7 expression, as evident in our case may prompt an erroneous diagnosis of metastatic carcinoma. Hence, in view of multiple bone involvement, especially in a young patient, a possibility of vascular tumor should be excluded. Immunoexpression of other IHC markers such as ERG-1, FLI-1, and thrombomodulin also help to reinforce the rare diagnosis of PMH. ES also effects young age group with epithelioid to spindle cell morphology with CK and CD34 expression in >50% of cases. However, ES typically lack CD31, FLI-1, INI-1 expression, unlike PMH. The presented case had retained INI-1 expression.[1],[2],[3],[8]

PMH are typically characterized by balanced translocation t (7;19) (q22; q13) producing fusion of SERPINE1 and FOSB gene; this genetic derangement being the hallmark for PMH. Prognostically, PMH are locally recurrent and rarely metastasizing tumors. Al-Qaderi and Mansour[2] have reviewed the literature comprising of 82 patients of PMH with follow-up available in 61 patients. They reported regional lymph node metastasis, distant metastasis, and recurrences in 3%, 5%, and 43% of cases, respectively.

The optimal therapeutic strategy has not been established till date for PMH. The cases have been managed with surgery or chemotherapy or both. Recently, everolimus or combination of gemcitabine and docetaxel has shown persuasive results with some shrinkage in tumor size; however, additional large studies can elucidate the precise efficacy.[1],[2],[3],[10]

Otani et al.[10] reported a single case of primary PMH of bone exhibiting symptomatic relief of ankle pain on monthly administration of denosumab. In our case, denosumab was given 6 weeklies. The symptomatic relief in both the cases could be attributed to the suppression of bone resorption.


 > Conclusion Top


To conclude, PMH is a rare and distinct vascular tumor with local aggressiveness and rare metastatic potential. Clinicoradiological correlation, diligent histomorphological examination, and judicious IHC panel can help to clinch the diagnosis. Although no specific therapeutic guidelines have been established for this rare vascular tumor, we found denosumab to be effective in symptomatic relief and disease control.

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 initial s will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 > References Top

1.
Inyang A, Mertens F, Puls F, Sumathi V, Inwards C, Folpe A, et al. Primary pseudomyogenic hemangioendothelioma of bone. Am J Surg Pathol 2016;40:587-98.  Back to cited text no. 1
    
2.
Al-Qaderi A, Mansour AT. Pseudomyogenic hemangioendothelioma. Arch Pathol Lab Med 2019;143:763-7.  Back to cited text no. 2
    
3.
Dianat S, Yousaf H, Murugan P, Marette S. Pseudomyogenic hemangioendothelioma: A case report and review of the literature. Radiol Case Rep 2019;14:1228–32.  Back to cited text no. 3
    
4.
Mirra JM, Kessler S, Bhuta S, Eckardt J. The fibroma-like variant of epithelioid sarcoma: A fibrohistiocytic/myoid cell lesion often confused with benign and malignant spinle cell tumors. Cancer 1992;9:1382-95.  Back to cited text no. 4
    
5.
Billings SD, Folpe AL, Weiss SW. Epithelioid sarcoma-like hemangioendothelioma. Am J Surg Pathol 2003;27:48-57.  Back to cited text no. 5
    
6.
Hornick JL, Fletcher CD. Pseudomyogenic hemangioendothelioma: A distinctive, often multicentric tumor with indolent behavior. Am J Surg Pathol 2011;35:190-201.  Back to cited text no. 6
    
7.
Sheng WQ, Wang J. Primary pseudomyogenic haemangioendothelioma of bone. Histopathology 2012;61:1219-24.  Back to cited text no. 7
    
8.
Hornick JL, Fletcher CDM, Mertens F. Psudomyogenic haemangioendothelioma. In: Fletcher CD, Bridge JA, Hogendoorn PCW, Mertens F, editos. WHO Classification of Tumours of Soft tissue and bone. 4th ed. Lyon (France): International Agency for Research on Cancer; 2013. p. 153-4.  Back to cited text no. 8
    
9.
Pradhan D, Schoedel K, McGough RL, Ranganathan S, Rao UNM. Pseudomyogenic hemangioendothelioma of skin, bone and soft tissue-a clinicopathological, immunohistochemical, and fluorescence in situ hybridization study. Hum Pathol 2018;71:126-34.  Back to cited text no. 9
    
10.
Otani S, Nakayama R, Sekita T, Hirozane T, Asano N, Nishimoto K, et al. Pseudomyogenic hemangioendothelioma of bone treated with denosumab: A case report. BMC Cancer 2019;19:872.  Back to cited text no. 10
    


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  [Figure 1], [Figure 2], [Figure 3]



 

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