Indian Journal of Pathology and Microbiology
Home About us Instructions Submission Subscribe Advertise Contact e-Alerts Ahead Of Print Login 
Users Online: 387
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 : 382-385
A rare case of multifocal pseudomyogenic hemangioendothelioma, involving soft tissues and bone, misdiagnosed as a rhabdomyosarcoma: Diagnostic and treatment implications

1 Department of Surgical Pathology, Tata Memorial Centre, Parel, Mumbai, Maharashtra, India
2 Department of Surgical Oncology (Bone and Soft Tissues), Tata Memorial Centre, Parel, Mumbai, Maharashtra, India
3 Department of Nuclear Medicine and Molecular Imaging, Tata Memorial Centre, Parel, Mumbai, Maharashtra, India

Click here for correspondence address and email

Date of Web Publication10-Aug-2016


Pseudomyogenic hemangioendothelioma (PHE) is an uncommon, but distinctive soft tissue tumor, characterized by multifocality. A 17-year-old male referred to us with progressively increasing multiple subcutaneous nodular lesions over his left leg and foot, reported elsewhere as a spindle cell rhabdomyosarcoma. On review, microscopy showed a cellular tumor comprising plump spindle cells arranged in loose fascicles with interspersed inflammatory cells. Tumor cells exhibited mild nuclear variation. Immunohistochemically, tumor cells expressed AE1/AE3, CD31, Fli-1, and smooth muscle actin (SMA), confirming diagnosis of PHE. Whole-body positron emission tomography–computed tomography (PET-CT) scan revealed multiple, metabolically active, subcutaneous nodular lesions over the left lower leg and in the distal tibia. Subsequently, resection specimens from the various lesions and bone curettage also revealed features of PHE. Three months later, the patient developed multiple lesions over his fourth toe and left foot, for which he underwent tumor resections. At present, he is disease-free. PHE is a locally aggressive soft tissue tumor characterized by multifocality, rarely bony involvement and can be misdiagnosed as a high-grade sarcoma.

Keywords: CD31, epithelioid sarcoma-like hemangioendothelioma, Fli-1, pseudomyogenic hemangioendothelioma, uncommon soft tissue and bone tumors

How to cite this article:
Rekhi B, Gulia A, Rangarajan V. A rare case of multifocal pseudomyogenic hemangioendothelioma, involving soft tissues and bone, misdiagnosed as a rhabdomyosarcoma: Diagnostic and treatment implications. Indian J Pathol Microbiol 2016;59:382-5

How to cite this URL:
Rekhi B, Gulia A, Rangarajan V. A rare case of multifocal pseudomyogenic hemangioendothelioma, involving soft tissues and bone, misdiagnosed as a rhabdomyosarcoma: Diagnostic and treatment implications. Indian J Pathol Microbiol [serial online] 2016 [cited 2022 Jan 26];59:382-5. Available from: https://www.ijpmonline.org/text.asp?2016/59/3/382/188144

   Introduction Top

Pseudomyogenic hemangioendothelioma (PHE) is a distinctive, rarely metastasizing endothelial-derived mesenchymal tumor, occurring most frequently in young adult males, characterized by multiple discontinuous nodules in various tissue planes of a limb. Histopathologically, PHE comprises plump spindle cells and mimics an epithelioid or a myoid/muscle tumor.[1],[2] This can lead to over diagnosis of rhabdomyosarcoma in such cases, especially in the absence of relevant immunohistochemistry. Less than 20 cases of PHE have been documented involving the bones.[1],[3],[4],[5],[6],[7],[8],[9]

   Case Report Top

A 17-year-old male referred to us with a history of trauma 8 months back ever since he noticed progressively increasing nodular cutaneous lesions over his left leg.

On clinical examination, multiple subcutaneous nodular lesions were noted over his left shin (tibia), lateral side of leg, and calf [Figure 1]a. In addition, he had a small papular lesion on the dorsal aspect of fourth toe and on the plantar aspect of his left foot.
Figure 1: (a) Clinical photograph showing multiple subcutaneous nodular lesions over left shin (tibia) and lateral side of left leg. (b) Magnetic resonance imaging displaying hyperintense subcutaneous lesion (arrowhead) in the left lower leg. (c) Computed tomography scan showing a lytic lesion (arrowhead) in the left tibia. (d). Histopathological findings. Cellular spindle cell tumor below the epidermis (H and E, × 100). (e) Plump, spindle-shaped tumor cells containing abundant eosinophilic cytoplasm and interspersed inflammatory cells (H and E, × 200)

Click here to view

Whole-body, fluorine-18 -fluorodeoxyglucose (18F-FDG) positron emission tomography–computed tomography (PET-CT) scan revealed multiple, metabolically active, FDG-avid subcutaneous lesions over the medial and lateral aspect of his left lower leg (largest measuring 1.5 cm, SUVmax= 10.86) – another lesion in his left calf muscles (2 cm, SUVmax= 11.35) and a lytic lesion in his distal left tibia with a soft tissue component (1.4 cm, SUVmax= 11.54) [Figure 1]b and [Figure 1]c. There were no metastatic lesions in his body. He underwent a biopsy elsewhere that was reported as spindle cell rhabdomyosarcoma. Subsequently, he underwent multiple resections of the various nodules and bone curettage at our institution.

Pathological findings

Gross findings

During gross examination, the skin covered soft tissue mass containing anterolateral lesions measured 10.5 cm × 5.6 cm × 1.3 cm. On serial sectioning, several nodular areas were identified, largest measuring 2.5 cm × 2.5 cm × 1.7 cm. Another soft tissue mass with a skin flap containing the superomedial lesion on serial sectioning displayed a nodular lesion measuring 1.6 cm × 1.5 cm × 1.5 cm. A soft tissue mass containing lesion over Achilles tendon measured 4.5 cm × 2.5 cm × 1.5 cm and, on serial sectioning, revealed a lesion measuring 2.2 cm × 1.7 cm × 1.1 cm. Distal tibial curettage specimen measured 3 cm × 1.5 cm × 1.5 cm.

Microscopic findings

Histopathologic sections from various lesions showed a multinodular cellular tumor below epidermis, infiltrating the subcutaneous fat, comprising plump spindle to polygonal cells with abundant eosinophilic cytoplasm, arranged in loose fascicles. Cells exhibited mild nuclear variation without anaplasia. Interspersed were inflammatory cells. There were no significant mitoses or areas of tumor necrosis [Figure 1]d and [Figure 1]e. Immunohistochemically, tumor cells were positive for pan CK (AE1/AE3), CD31, SMA, diffusely positive for Fli-1, while negative for CD34, desmin, myogenin, myoD1, p63, and S100P. INI1/SMARCB1 was retained. Ki67 highlighted 20–25% tumor cells [Figure 2]a, [Figure 2]b, [Figure 2]c, [Figure 2]d, [Figure 2]e. Diagnosis of PHE was offered. Subsequently, multiple resection specimens of the various nodules over anterolateral, posteromedial regions, Achilles tendon, and tibial curettage revealed features of PHE. Postexcision, the patient was offered skin grafting over his left leg [Figure 3]a.
Figure 2: Immunohistochemical results. (a) Tumor cells displaying pancytokeratin (AE1/AE3) positivity (DAB, ×400). (b) CD31 positivity (DAB, ×400). (c) Diffuse FLI1 positivity (DAB, ×400). (d) Retained INI/SMARCB1 expression (DAB, × 400). (e) Ki67 highlighting 20% tumor cell nuclei (DAB, ×400)

Click here to view
Figure 3: (a) Clinical photograph showing a healed graft 4 months after excision of the leg lesions. (b) Multiple superficial nodular lesions over plantar aspect of fourth toe. (c) Cut surface of fourth toe disarticulated specimen showing multiple tumor lesions (asterix). (d) Microscopic examination revealing a distinct tumor nodule in the dermis, infiltrating the bone (arrowheads) (H and E, ×10). (e) Tumor cells in higher magnification (H and E, ×400)

Click here to view


Three months later, the lesion over his fourth toe progressed along with multiple nodules over the dorsal and ventral surfaces of his left foot for which he underwent fourth toe amputation and wide resections that revealed PHE. Occasional mitotic figures were identified [Figure 3]b, [Figure 3]c, [Figure 3]d, [Figure 3]e. The patient is free of disease for 16 months after his initial presentation.

   Discussion Top

PHE is a recently described soft tissue tumor that was previously designated as an epithelioid sarcoma-like hemangioendothelioma.[2],[10] Hornick and Fletcher [1] observed this tumor most frequently occurring in males, presenting with either painless or painful nodules, commonly as a multifocal disease (66% cases), in their lower limbs, within muscles, dermis, and subcutaneous tissues, as noted in the present case.

Besides multifocal soft tissue lesions, our patient also harbored a bony lesion that was identified as another highly 18 F-FDG PET avid lesion.[1] HornickandFletcher [1] observed bony involvement in 10/50 cases (20%). Subsequently, various authors, who documented bone involvement in PHE, observed that almost all such cases were characterized by multifocal lesions [Table 1].[3],[4],[5],[6],[7],[8],[9] Amary et al.[5] observed 2 of 3 cases of PHE involving bones with FDG-PET avid lesions. In a recently documented case of an intraosseous PHE, the patient presented with numerous 18 F-FDG-PET avid lytic lesions in his humerus that were presumed to be metastatic or myeloma.[8] Another intraosseous PHE with pulmonary metastasis was recently documented.[9] The present case constitutes as the 18th case of PHE involving the bone and the first documented case of PHE from our continent.
Table 1: Literature review of cases of pseudomyogenic hemangioendothelioma involving bone

Click here to view

The value of identifying this tumor is that clinically, it appears as a high-grade sarcoma, in view of its multifocality; high FDG-PET avidity and can histopathologically be misdiagnosed as a high-grade sarcoma, as noted in our case. In contrast to a high-grade sarcoma, most cases of PHE display an indolent behavior.[1] Isolate lesions in such cases PHE can be underdiagnosed as a dermatofibroma.

Various differential diagnoses include an epithelioid sarcoma, an epithelioid angiosarcoma, a rhabdomyosarcoma, and an epithelioid leiomyosarcoma. An epithelioid sarcoma is characterized by nodular aggregates of epithelioid cells, rather than only plump spindly cells. An epithelioid angiosarcoma invariably shows areas of hemorrhage with lumens, features that were lacking in all the tumor lesions in the present case. In view of plump spindle cells, probably diagnosis of spindle cell rhabdomyosarcoma was considered at the referring laboratory. Immunohistochemical results, including lack of desmin, myogenin, and myoD1 expression, objectively ruled out a rhabdomyosarcoma. In view of AE1/AE3 immunoexpression, an epithelioid sarcoma was a close differential diagnosis. Aforementioned histopathological features with retained INI1/SMARCB1 expression ruled out this tumor. Despite SMA positivity, rather banal appearing nuclei, infrequent mitoses and lack of necrosis helped in ruling out a leiomyosarcoma.

Exact diagnosis has therapeutic implications. While case of multifocal PHE is treated with surgical resection, a multifocal spindle cell rhabdomyosarcoma is treated with IRS IV chemotherapy and radical resection. Epithelioid sarcoma and epithelioid angiosarcoma have propensity for lymph node metastasis; therefore, in case of multifocality would be treated with adjuvant radio and or chemotherapy and radical resections. Lately, SERPINE1-FOSB fusion gene resulting in transcriptional upregulation of FOSB has been identified in PHEs.[10]

To summarize, PHE should be suspected in young adults with multifocal subcutaneous lesions that are highly FDG-PET avid and display plump spindly cells on histopathology. IHC markers are helpful in differentiating PHE from a spindle cell rhabdomyosarcoma as either of these tumors have different treatment and prognostic implications.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

   References Top

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. 1
Hornick JL, Fletcher CD, Mertens F. Pseudomyogenic Hemangioendothelioma. In: Fletcher CD, Bridge JA, Hogendoorn PC, Mertens F, editors. World Health Organization (WHO) Classification of Tumours of Soft Tissue and Bone. Lyon: IARC Press; 2013. p. 153-4.  Back to cited text no. 2
Sheng WQ, Wang J. Primary pseudomyogenic haemangioendothelioma of bone. Histopathology 2012;61:1219-24.  Back to cited text no. 3
McGinity M, Bartanusz V, Dengler B, Birnbaum L, Henry J. Pseudomyogenic hemangioendothelioma (epithelioid sarcoma-like hemangioendothelioma, fibroma-like variant of epithelioid sarcoma) of the thoracic spine. Eur Spine J 2013;22 Suppl 3:S506-11.  Back to cited text no. 4
Amary MF, O'Donnell P, Berisha F, Tirabosco R, Briggs T, Pollock R, et al. Pseudomyogenic (epithelioid sarcoma-like) hemangioendothelioma: Characterization of five cases. Skeletal Radiol 2013;42:947-57.  Back to cited text no. 5
Karakasli A, Karaaslan A, Erduran M, Capkin S, Tuna EB, Havitcioglu H. Pseudomyogenic (epithelioid sarcoma-like) hemangioendothelioma with bone invasion. J Orthop 2014;11:197-9.  Back to cited text no. 6
Righi A, Gambarotti M, Picci P, Dei Tos AP, Vanel D. Primary pseudomyogenic haemangioendothelioma of bone: Report of two cases. Skeletal Radiol 2015;44:727-31.  Back to cited text no. 7
Bryanton M, Makis W. Pseudomyogenic hemangioendothelioma mimicking multiple myeloma on 18F-FDG PET/CT, followed by spontaneous regression. Clin Nucl Med 2015;40:579-81.  Back to cited text no. 8
Shah AR, Fernando M, Musson R, Kotnis N. An aggressive case of pseudomyogenic haemangioendothelioma of bone with pathological fracture and rapidly progressive pulmonary metastatic disease: Case report and review of the literature. Skeletal Radiol 2015;44:1381-6.  Back to cited text no. 9
Walther C, Tayebwa J, Lilljebjörn H, Magnusson L, Nilsson J, von Steyern FV, et al. Anovel SERPINE1-FOSB fusion gene results in transcriptional up-regulation of FOSB in pseudomyogenic haemangioendothelioma. J Pathol 2014;232:534-40.  Back to cited text no. 10

Correspondence Address:
Dr. Bharat Rekhi
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: 10.4103/0377-4929.188144

Rights and Permissions


  [Figure 1], [Figure 2], [Figure 3]

  [Table 1]

This article has been cited by
1 Primary Vascular Tumors of Bone
Alberto Righi, Marta Sbaraglia, Marco Gambarotti, Dino Gibertoni, Marina P. Rovira, Stefania Benini, Costantino Errani, Monica Brenca, Roberta Maestro, Angelo P. Dei Tos
American Journal of Surgical Pathology. 2020; 44(9): 1192
[Pubmed] | [DOI]
2 Case Report 18F-FDG PET/CT of Pseudomyogenic Hemangioendothelioma
Nicolas Plouznikoff, Stephanie A. Mourad, Sophie Turpin, Robert E. Turcotte, David A. Mitchell, Raymond Lambert
Clinical Nuclear Medicine. 2020; 45(5): 368
[Pubmed] | [DOI]
3 Primary pseudomyogenic hemangioendothelioma of the vulva: a rare location for a rare entity
Yue-Fang Sun,Jian Wang
Diagnostic Pathology. 2019; 14(1)
[Pubmed] | [DOI]
4 Pseudomyogenic (epithelioid sarcoma-like) hemangioendothelioma of bone: Clinicopathologic features of 5 cases
Kemal Kosemehmetoglu,Bharat Rekhi,Paul E. Wakely,Vinita Pant,Sergulen Dervisoglu,Ustun Aydingoz
Annals of Diagnostic Pathology. 2019; 41: 116
[Pubmed] | [DOI]
5 Update on cutaneous epithelioid vascular tumours
Boštjan Luzar,Eduardo Calonje
Diagnostic Histopathology. 2018; 24(8): 273
[Pubmed] | [DOI]
6 Expanding the Spectrum of Genetic Alterations in Pseudomyogenic Hemangioendothelioma With Recurrent Novel ACTB-FOSB Gene Fusions
Narasimhan P. Agaram,Lei Zhang,Paolo Cotzia,Cristina R. Antonescu
The American Journal of Surgical Pathology. 2018; 42(12): 1653
[Pubmed] | [DOI]
7 Tumoren des Fußes und der Sprunggelenkregion
T. Grieser
Der Radiologe. 2018; 58(5): 459
[Pubmed] | [DOI]
8 The management of pseudomyogenic hemangioendothelioma of the foot: A case report and review of the literature
Guglielmo Pranteda,Francesca Magri,Marta Muscianese,Flavia Pigliacelli,Andrea DćArino,Alessandro Federico,Giulia Pranteda,Armando Bartolazzi
Dermatologic Therapy. 2018; 31(6): e12725
[Pubmed] | [DOI]
9 Lower-Extremity Pseudomyogenic Hemangioendothelioma on Bone Scintigraphy and PET/CT
Simone Krebs,Serena Monti,Natasha Lewis,Alessandro Luciano,Lapo Rastrelli,Lorenzo Mannelli
Clinical Nuclear Medicine. 2017; 42(5): 383
[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 Downloaded80    
    Comments [Add]    
    Cited by others 9    

Recommend this journal