Skip to main content
Surgical Case Reports
Surgical Case Reports Cover Image
Download PDF

Epithelioid hemangioendothelioma of the thyroid: a case report

Surgical Case Reports volume 3, Article number: 18 (2017) Cite this article

Abstract

Background

Epithelioid hemangioendothelioma (EHE) of the thyroid is an extremely rare disease; only three cases have been reported in the English literature to date. Here, we describe a case involving a patient with thyroid EHE successfully treated with curative surgery.

Case presentation

A 74-year-old woman presented with a right thyroid mass. The nodule was approximately 2 cm in size and was diagnosed as an indeterminate lesion by fine needle aspiration cytology. She was treated with thyroid lobectomy. The histopathological and immunohistochemical findings indicated an EHE of the thyroid. At the latest follow-up, 3 years postoperatively, the patient showed no signs of recurrence.

Conclusion

There is currently no standard therapy for EHE; however, our case suggests that curative resection represents an effective treatment.

Background

Epithelioid hemangioendothelioma (EHE) is a rare vascular tumor, most commonly reported to occur in the lungs, liver, and bone, along with many other sites throughout the body [1]. The etiology of EHE is unknown. Previously, EHE was recognized as an intermediate-risk disease, classified between angioma and angiosarcoma [2]; however, in the fourth revision of the World Health Organization classification, EHE was described as a malignant vascular tumor, similar to angiosarcoma [3].

EHE of the thyroid is very rare, and only three cases have been reported to date in the English literature. Here, we describe a patient with EHE of the thyroid who underwent successful resection.

Case presentation

A 74-year-old woman was referred to our hospital because of a nodule in the right lobe of the thyroid. The nodule had been found during a medical examination performed 3 years ago, but she did not undergo a detailed examination at the local hospital at that time. On physical examination, a palpable and hard nodule of approximately 2 cm in size was noted in the right side of her neck. Results of the blood examination were normal, except for mildly increased thyroglobulin (142 ng/mL) and antithyroglobulin antibody levels (59.7 IU/mL). Ultrasonography and computed tomography showed a right thyroid nodule with calcification. The nodule had no signs of extrathyroidal invasion and measured 21 mm in diameter. The lymph nodes of the neck were not swollen (Fig. 1). The nodule was diagnosed as an indeterminate lesion by fine needle aspiration cytology. The fine needle aspiration smears showed spindle-shaped cells with prominent nucleoli and nuclear inclusion. The intercellular space was metachromatic on Giemsa staining (Fig. 2). Taken together, these findings suggested a hyalinizing trabecular adenoma, granulomatous lesion, papillary carcinoma, or poorly differentiated carcinoma.

Fig. 1
figure1

Characteristics of the thyroid nodule. Computed tomography scan showing the right thyroid nodule with calcification (arrow) (a). The nodule is enhanced and shows no signs of extrathyroidal invasion (arrow) (b). Ultrasonogram showing the right thyroid nodule (21 mm in diameter) with calcification (arrow) (c). Macroscopically, a well-circumscribed mass in the right lobe of the thyroid is observed (d)

Full size image
Fig. 2
figure2

Fine needle aspiration smears. Spindle-shaped cells are observed, with prominent nucleoli and nuclear inclusion (Papanicolaou stain, ×400) (a). The intercellular space is metachromatic (Giemsa stain, ×100) (b)

Full size image

We decided to treat this nodule as thyroid cancer. Right thyroid lobectomy and central neck dissection were performed. Macroscopically, a well-circumscribed mass in the right lobe of the thyroid was observed. Histologic evaluation of the thyroid nodule showed multinodular proliferation of oval to polygonal-shaped epithelioid cells with oval nuclei and eosinophilic cytoplasm arranged in sheet- or cord-like patterns, accompanied by fibrous stroma and marked osseous metaplasia. Nuclear atypia was mild, and mitosis was not prominent. Results of the immunohistochemical staining showed that these areas were partially positive for cytokeratin, cluster of differentiation (CD)34, and factor VIII; diffusely positive for vimentin; and negative for thyroglobulin, thyroid transcription factor-1, smooth muscle actin, desmin, S100, CD31, CD68, and CD163 (Fig. 3). These findings were suggestive of EHE.

Fig. 3
figure3

Histological findings. Multinodular proliferations, composed of comparatively rich spindle cells with nuclear blebs, are observed between the trabecular bone structures. Intracytoplasmic vacuoles are also seen (a hematoxylin and eosin stain, ×10; b hematoxylin and eosin stain, ×100). Immunohistochemically, the tumor cells were positive for cluster of differentiation (CD)34 and factor VIII (c factor VIII, ×100; d CD34, ×100)

Full size image

Postoperatively, the patient’s thyroglobulin level fluctuated inconsistently (range, 11–292 ng/mL), as did the antithyroglobulin antibody level, although it remained positive. The mild elevation of the preoperative and postoperative thyroglobulin levels might have been caused by chronic thyroiditis. The patient has been followed-up for 3 years and has had no signs of recurrence postoperatively.

Conclusions

EHE is a rare disease, first described by Weiss et al. in 1982 [2]. The authors classified it as a vascular tumor, showing the same histological findings, but reported it as a different disease in each organ (e.g., intravascular bronchioloalveolar tumor of the lung) [4]. The 2002 World Health Organization classification changed the classification of EHE from an intermediate to malignant tumor, because some malignant clinical cases had been reported in patients with EHE. EHE most commonly presents in the liver, lung, and bone [5]. The characteristics of EHE in these common sites are shown in Table 1. In addition, Table 2 summarizes the reported EHE cases from various, rare sites of the body.

Table 1 Characteristics of epithelioid hemangioendothelioma (EHE) in the liver, lungs, soft tissues, and bone (common presentations)
Full size table
Table 2 Summary of previously reported cases of epithelioid hemangioendothelioma (EHE) occurring in rare sites
Full size table

Especially, EHE of the thyroid is extremely rare [6–9], with only one case reported in the Japanese literature [9], along with three in the English literature [6–8]. These cases and our present case are summarized in Table 3.

Table 3 Cases of thyroid epithelioid hemangioendothelioma (EHE)
Full size table

Of note, only one of the five patients was male (20%), which is in accordance with previous studies on EHE of other organs, in which most patients were women (male to female ratio, 1:4) [1]. There was no predominance in age (range, 35–74 years) or tumor size (range 2.1–8 cm), but all patients had a single nodule of the thyroid. On the other hand, EHE of other organs associated with multiple organ involvement in 36% of cases [5].

There have been several discussions on the prognostic factors of EHE, such as the presence of pulmonary lesions, multiorgan involvement, age, and sex [1]. In addition, mitotic activity (>3 mitotic figures/50 high-power fields) and size (>3.0 cm) have been reported as risk factors for mortality in cases of EHE of the soft tissues [10]. Although the thyroid EHE patient with the largest tumor (80 mm) died 13 months after the diagnosis [7], the other patients, whose tumor sizes were all <4 cm, had uneventful outcomes [6, 8, 9].

There is no standard treatment for EHE, although curative resection has been reported as a successful treatment with good outcomes [1]. All five patients with thyroid EHE underwent surgery. For this site, total resection can be relatively easily performed, whereas this treatment is unlikely to be performed for EHEs of other organs such as the liver, bone, and lungs. However, it is difficult to maintain a sufficient surgical margin in cases of large thyroid tumors. Our patient had the smallest tumor of the five cases, and no signs of adhesion, extrathyroidal extension, and lymph node metastasis. As mentioned above, the previously reported patient with the largest tumor experienced local recurrence and died. That tumor showed adhesion, whereas pathologically, there was no evidence of a residual tumor [7]. These findings suggest that tumor size is likely an important factor for the effectiveness of curative resection for thyroid EHE. Further studies are needed to determine the optimal surgical margin and whether lymph node dissection is sufficient for curative surgery. Moreover, two patients received radiation therapy because of lymph node metastasis. Radiation therapy may be effective to control local recurrences; however, this could not be confirmed, because the follow-up periods in the past cases were short.

Finally, the presence of CAMTA1-WWTR1 gene fusion in EHE was recently demonstrated [11]. This abnormality has been reported in the majority of EHEs at various anatomical sites, while it is absent in other epithelioid vascular tumors [11–13]. It was also confirmed in one case of thyroid EHE [8]. Therefore, fluorescence in situ hybridization analysis to detect CAMTA-WWTR1 fusion may become a definite tool for the diagnosis of EHE in the future.

In conclusion, EHE of the thyroid is an extremely rare disease. Its clinical course varies, and the prognostic factors are unclear. Curative resection may be an effective treatment, but surgical issues such as the appropriate extent of the surgical margin and use of lymph node dissection remain to be clarified. Further studies are needed to analyze the etiology of EHE and to determine the optimal treatment.

Abbreviations

CD:

Cluster of differentiation

EHE:

Epithelioid hemangioendothelioma

References

  1. 1.

    Sardaro A, Bardoscia L, Petruzzelli MF, Portaluri M. Epithelioid hemangioendothelioma: an overview and update on a rare vascular tumor. Oncol Rev. 2014;8:259.

    Article  PubMed  PubMed Central  Google Scholar 

  2. 2.

    Weiss SW, Enzinger FM. Epithelioid hemangioendothelioma: a vascular tumor often mistaken for a carcinoma. Cancer. 1982;50:970–81.

    CAS  Article  PubMed  Google Scholar 

  3. 3.

    Fletcher CD, Hogendoorn P, Mertens F, Bridge J. WHO Classification of tumours of soft tissue and bone. 4th ed. Lyon: IARC Press; 2013.

    Google Scholar 

  4. 4.

    Dail DH, Liebow AA. Intravascular bronchioloalveolar tumor. Am J Pathol. 1975;78:6a–7a.

    Google Scholar 

  5. 5.

    Lau K, Massad M, Pollak C, Rubin C, Yeh J, Wang J, et al. Clinical patterns and outcome in epithelioid hemangioendothelioma with or without pulmonary involvement: insights from an Internet registry in the study of a rare cancer. Chest. 2011;140:1312–8.

    Article  PubMed  Google Scholar 

  6. 6.

    Siddiqui MT, Evans HL, Ro JY, Ayala AG. Epithelioid haemangioendothelioma of the thyroid gland: a case report and review of literature. Histopathology. 1998;32:473–6.

    CAS  Article  PubMed  Google Scholar 

  7. 7.

    Hassan I, Barth P, Celik I, Hoffmann S, Langer P, Ramaswamy A, et al. An authentic malignant epithelioid hemangioendothelioma of the thyroid: a case report and review of the literature. Thyroid. 2005;15:1377–81.

    CAS  Article  PubMed  Google Scholar 

  8. 8.

    Shah AA, Ohori NP, Yip L, Coyne C, Antonescu CR, Seethala RR. Epithelioid hemangioendothelioma: a rare primary thyroid tumor with confirmation of WWTR1 and CAMTA1 rearrangements. Endocr Pathol. 2016;27:147–52.

    Article  PubMed  Google Scholar 

  9. 9.

    Fujiwara K, Miura M. Epithelioid hemangioendothelioma of the thyroid gland: a case report. Pract Otorhinolaryngol. 1998;91:195–8.

    Google Scholar 

  10. 10.

    Deyrup AT, Tighiouart M, Montag AG, Weiss SW. Epithelioid hemangioendothelioma of soft tissue: a proposal for risk stratification based on 49 cases. Am J Surg Pathol. 2008;32:924–7.

    Article  PubMed  Google Scholar 

  11. 11.

    Errani C, Zhang L, Sung YS, Hajdu M, Singer S, Maki RG, et al. A novel WWTR1‐CAMTA1 gene fusion is a consistent abnormality in epithelioid hemangioendothelioma of different anatomic sites. Genes Chromosomes Cancer. 2011;50:644–53.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  12. 12.

    Anderson T, Zhang L, Hameed M, Rusch V, Travis WD, Antonescu CR. Thoracic epithelioid malignant vascular tumors: A clinicopathologic study of 52 cases with emphasis on pathologic grading and molecular studies of WWTR1-CAMTA1 fusions. Am J Surg Pathol. 2015;39:132–9.

    Article  PubMed  PubMed Central  Google Scholar 

  13. 13.

    Flucke U, Vogels RJ, de Saint Aubain Somerhausen N, Creytens DH, Riedl RG, van Gorp JM, et al. Epithelioid hemangioendothelioma: clinicopathologic, immunhistochemical, and molecular genetic analysis of 39 cases. Diagn Pathol. 2014;9:131.

    Article  PubMed  PubMed Central  Google Scholar 

  14. 14.

    Mehrabi A, Kashfi A, Fonouni H, Schemmer P, Schmied BM, Hallscheidt P, et al. Primary malignant hepatic epithelioid hemangioendothelioma: a comprehensive review of the literature with emphasis on the surgical therapy. Cancer. 2006;107:2108–21.

    Article  PubMed  Google Scholar 

  15. 15.

    Cardinal J, de Vera ME, Marsh JW, Steel JL, Geller DA, Fontes P, et al. Treatment of hepatic epithelioid hemangioendothelioma: a single-institution experience with 25 cases. Arch Surg. 2009;144:1035–9.

    Article  PubMed  Google Scholar 

  16. 16.

    Lerut JP, Orlando G, Adam R, Schiavo M, Klempnauer J, Mirza D, et al. The place of liver transplantation in the treatment of hepatic epitheloid hemangioendothelioma: report of the European liver transplant registry. Ann Surg. 2007;246:949–57.

    Article  PubMed  Google Scholar 

  17. 17.

    Sangro B, Iñarrairaegui M, Fernández-Ros N. Malignant epithelioid hemangioendothelioma of the liver successfully treated with Sorafenib. Rare Tumors. 2012;4, e34.

    Article  PubMed  PubMed Central  Google Scholar 

  18. 18.

    Salech F, Valderrama S, Nervi B, Rodriguez JC, Oksenberg D, Koch A, et al. Thalidomide for the treatment of metastatic hepatic epithelioid hemangioendothelioma: a case report with a long term follow-up. Ann Hepatol. 2011;10:99–102.

    CAS  PubMed  Google Scholar 

  19. 19.

    Bally O, Tassy L, Richioud B, Decouvelaere AV, Blay JY, Derbel O. Eight years tumor control with pazopanib for a metastatic resistant epithelioid hemangioendothelioma. Clin Sarcoma Res. 2015;5:12.

    Article  PubMed  PubMed Central  Google Scholar 

  20. 20.

    Bagan P, Hassan M, Barthes FLP, Peyrard S, Souilamas R, Danel C, et al. Prognostic factors and surgical indications of pulmonary epithelioid hemangioendothelioma: a review of the literature. Ann Thorac Surg. 2006;82:2010–3.

    Article  PubMed  Google Scholar 

  21. 21.

    Amin R, Hiroshima K, Kokubo T, Nishikawa M, Narita M, Kuroki M, et al. Risk factors and independent predictors of survival in patients with pulmonary epithelioid haemangioendothelioma. Review of the literature and a case report. Respirology. 2006;11:818–25.

    Article  PubMed  Google Scholar 

  22. 22.

    Ye B, Li W, Feng J, Shi JX, Chen Y, Han BH. Treatment of pulmonary epithelioid hemangioendothelioma with combination chemotherapy: report of three cases and review of the literature. Oncol Lett. 2013;5:1491–6.

    PubMed  PubMed Central  Google Scholar 

  23. 23.

    Semenisty V, Naroditsky I, Keidar Z, Bar-Sela G. Pazopanib for metastatic pulmonary epithelioid hemangioendothelioma—a suitable treatment option: case report and review of anti-angiogenic treatment options. BMC Cancer. 2015;15:402.

    Article  PubMed  PubMed Central  Google Scholar 

  24. 24.

    Mentzel T, Beham A, Calonje E, Katenkamp D, Fletcher C. Epithelioid hemangioendothelioma of skin and soft tissues: clinicopathologic and immunohistochemical study of 30 cases. Am J Surg Pathol. 1997;21:363–74.

    CAS  Article  PubMed  Google Scholar 

  25. 25.

    Kleer CG, Unni KK, McLeod RA. Epithelioid hemangioendothelioma of bone. Am J Surg Pathol. 1996;20:1301–11.

    CAS  Article  PubMed  Google Scholar 

  26. 26.

    Larochelle O, Périgny M, Lagacé R, Dion N, Giguère C. Epithelioid hemangioendothelioma of bone. Radiographics. 2006;26:265–70.

    Article  PubMed  Google Scholar 

  27. 27.

    Angelini A, Mavrogenis AF, Gambarotti M, Merlino B, Picci P, Ruggieri P. Surgical treatment and result of 62 patients with epithelioid hemangioendothelioma of bone. J Surg Oncol. 2014;109:791–7.

    Article  PubMed  Google Scholar 

  28. 28.

    Barger J, Tanweer O, Liechty B, Snuderl M, Jafar JJ. Suprasellar epithelioid hemangioendothelioma: case report and review of the literature. Surg Neurol Int. 2016;7:S596–602.

    Article  PubMed  PubMed Central  Google Scholar 

  29. 29.

    Sancheti S, Singh JN, Malik A, Devi KT, Jain S. Epithelioid hemangioendothelioma of hypopharynx: a rare presentation. Indian J Dent. 2016;7:109–11.

    Article  PubMed  PubMed Central  Google Scholar 

  30. 30.

    Boscaino A, Errico ME, Orabona P, Tornillo L, Staibano S, Donofrio V, et al. Epithelioid hemangioendothelioma of the larynx. Tumori. 1999;85:515–8.

    CAS  PubMed  Google Scholar 

  31. 31.

    Pigadas N, Mohamid W, McDermott P. Epithelioid hemangioendothelioma of the parotid salivary gland. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2000;89:730–8.

    CAS  Article  PubMed  Google Scholar 

  32. 32.

    Moulai N, Chavanon O, Guillou L, Noirclerc M, Blin D, Brambilla E, et al. Atypical primary epithelioid hemangioendothelioma of the heart. J Thorac Oncol. 2006;1:188–9.

    CAS  Article  PubMed  Google Scholar 

  33. 33.

    Traverse JH, Lesser JR, Flygenring BP, Bracken TH, Olevsky OM, Nicoloff DM, et al. Epithelioid hemangioendothelioma of the thoracic aorta resulting in aortic obstruction and congestive heart failure. Circulation. 1999;100:564–5.

    CAS  Article  PubMed  Google Scholar 

  34. 34.

    Charette S, Nehler MR, Whitehill TA, Gibbs P, Foulk D, Krupski WC. Epithelioid hemangioendothelioma of the common femoral vein: case report and review of the literature. J Vasc Surg. 2001;33:1100–3.

    CAS  Article  PubMed  Google Scholar 

  35. 35.

    Versaci A, Macrì A, Scuderi G, Leonello G, Fedele F, Certo A, et al. Epithelioid hemangioendothelioma of the stomach: clinical-pathological features, nosologic setting, and surgical therapy. Report of a case Surg Today. 2002;32:274–7.

    PubMed  Google Scholar 

  36. 36.

    Ratan S, Bhatnagar V, Gupta SD, Mitra DK. Epithelioid hemangioendothelioma of the greater omentum: report of a case. Surg Today. 1999;29:919–21.

    CAS  Article  PubMed  Google Scholar 

  37. 37.

    Bozkurt O, Demir Ö, Yener S, Tuna B, Seçil M, Yörükoğluc K. Malignant epithelioid hemangioendothelioma of the adrenal gland treated by laparoscopic excision. Urology. 2015;85:e15–6.

    Article  PubMed  Google Scholar 

  38. 38.

    Tolkach Y, Petrov S, Lerut E, Van Poppel H. Epithelioid hemangioendothelioma of the kidney treated with sunitinib. Onkologie. 2012;35:376–8.

    CAS  Article  PubMed  Google Scholar 

  39. 39.

    Liu B, Zhang C, Zhang Q, Liu G, Ma Z, Qi J, et al. Primary epithelioid hemangioendothelioma of the bladder: case report and review of the literature. Urol Int. 2015;94:240–3.

    Article  PubMed  Google Scholar 

  40. 40.

    Elhosseiny AA, Ramaswamy G, Healy RO. Epithelioid hemangioendothelioma of penis. Urology. 1986;28:243–5.

    CAS  Article  PubMed  Google Scholar 

  41. 41.

    Illueca C, Machado I, Garcia A, Covisa A, Morales J, Cruz J, et al. Uncommon vascular tumor of the ovary. Primary ovarian epithelioid hemangioendothelioma or vascular sarcomatous transformation in ovarian germ cell tumor? Arch Gynecol Obstet. 2011;284:1589–91.

    Article  PubMed  Google Scholar 

Download references

Authors’ contributions

MO drafted the manuscript. YK and MO performed the surgery and postoperative management. YK and TU revised the manuscript. TU and YO performed the pathological diagnosis. All authors read and approved the final manuscript.

Authors’ information

MO and YK are surgeons at the Department of Breast and Endocrine Surgery, Nagano Matsushiro General Hospital. YK is the general director of Nagano Matsushiro General Hospital. TU is an associate professor at the Department of Laboratory Medicine, Shinshu University School of Medicine. YO is a professor at the Department of Anatomic Pathology, Pathological Sciences, Kyushu University.

Competing interests

The authors declare that they have no competing interests.

Consent for publication

Written informed consent was obtained from the patient for publication of this case report and any accompanying images.

Author information

Affiliations

  1. Department of Breast and Endocrine Surgery, Nagano Matsushiro General Hospital, 183 Matsushiro, Nagano, 381-1231, Japan

    Mayu Ono & Yoshio Kasuga

  2. Department of Laboratory Medicine, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan

    Takeshi Uehara

  3. Department of Anatomic Pathology, Pathological Sciences, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan

    Yoshinao Oda

  4. Present address: Department of Breast and Endocrine Surgery, Iida Municipal Hospital, 438 Yawatamachi, Iida, 812-8582, Japan

    Mayu Ono

Authors
  1. Mayu Ono
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yoshio Kasuga
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Takeshi Uehara
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yoshinao Oda
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mayu Ono.

Rights and permissions

Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Ono, M., Kasuga, Y., Uehara, T. et al. Epithelioid hemangioendothelioma of the thyroid: a case report. surg case rep 3, 18 (2017). https://doi.org/10.1186/s40792-017-0294-2

Download citation

Keywords

  • Epithelioid hemangioendothelioma
  • Thyroid
  • Surgery