—  SPECIALTY CONFERENCE —

Bone & Soft Tissue Pathology

Case 4 - Pseudomyogenic Hemangioendothelioma

Rita Kandel, Mount Sinai Hosp, Toronto, ON, Canada





Click on slide thumbnail images for an enlarged view.

If you have any difficulties viewing these slides, email the webmaster.



Clinical History
A 22 year old female presented with a 6 month history of right shoulder pain. Radiological images showed a tumour predominantly in soft tissue with involvement of the proximal humerus measuring overall 9 x 5.2cm. The lesion was biopsied and subsequently resected. No primary carcinoma was evident at the time of diagnosis. There has been no recurrence of this tumour nor manifestation of a carcinoma elsewhere in the 9 months of follow-up to date.

Pathological/Microscopic Findings and any Immunohistochemical or Other Studies:
The tumour was composed of sheets of plump spindle or epithelioid cells with abundant eosinophilic cytoplasm with vesicular nuclei. There was cytological atypia and atypical multi-nucleated giant cells were present. Mitotic activity was scant. There were areas of necrosis. No lipoblasts nor epithelial differentiation were seen. Immunohistochemical studies showed that the tumour cells were positive for keratin, Fli-1 and smooth muscle actin. They were negative for desmin, h- caldesmon, myf-4 (myogenin), CD34, and CD31. INI-1 expression was retained. Ultrastructural examination by electron microscopy showed cells with glycogen and few desmosome-like junctions. They did not show epithelial, muscle nor vascular differentiation.


Case 4 - Gross
There is a large soft tissue tumour involving the proximal humerus.
Case 4 - Figure 1
The tumour is composed of sheets of plump spindle cells with eosinophilic cytoplasm.
Case 4 - Figure 2
At higher power cytological atypia is present. Mitotic activity is not prominent. Inflammatory cells can be seen percolating through the tumour.
Case 4 - Figure 3
Some cells have vesicular nuclei. Some cells are epithelioid in appearance. No vascular differentiation is seen.

Case 4 - Figure 4
The tumour cells are positive for keratin (AE1/AE3).
Case 4 - Figure 5
Tumour cells are diffusely positive for Fli-1.
Case 4 - Figure 6
INI-1 was retained.
Case 4 - Figure 7
The tumour cells are positive for smooth muscle actin focally but negative for desmin, caldesmon and myf-4 as well as CD31.

Differential Diagnoses:
  • Undifferentiated pleomorphic sarcoma

  • Epithelioid sarcoma

  • Metastatic carcinoma

  • Pseudomyogenic hemangioendothelioma

Final Diagnosis:
Pseudomyogenic Hemangioendothelioma

Case Discussion:
Pseudomyogenic hemangioendothelioma is a rare tumour. There are only 5 reports of these tumours in the literature, the largest series being 50 cases [1, 2, 3, 4, 5]. They usually occur in young people, with over 80% occurring in individuals less than 40 years of age according to the Hornick et al series [1]. They are usually poorly circumscribed and involve more than one plane of tissue. There is often bone involvement, as was seen in this case. The tumours have been reported to occur in the extremities, truck or head and neck. Pseudomyogenic hemangioendothelioma is composed of plump spindle cells and can have epithelioid cells. Mitotic activity is usually scant. As seen in the current case, necrosis and cellular pleomorphism can occur, although these are less common features. The morphology of the cells suggests myoid differentiation, and in fact these tumours can be positive for smooth muscle actin. However they do not show desmin reactivity and in the current case, the tumour was negative for h-caldesmon and myogenin.

These tumours have a characteristic immunohistochemical profile of keratin, Fli-1, and INI-1 positivity. They can also show CD31 positivity in a proportion of cases, (22 of 47 cases in the Hornick series). All cases to date have been negative for CD34, in contrast to epithelioid sarcoma in which approximately 60% are positive for CD34 [6].

Ultrastructural evaluation of these tumours is helpful in documenting the absence of features of tumours that are in the differential diagnosis rather than demonstrating characteristic features of this entity.

These tumours usually have an indolent course; local recurrence is common (about 58% in the largest series) and there is a small risk to develop metastases.

Review of the Literature/Treatment Options:
Pseudomyogenic hemangioendothelioma was likely first appreciated by Mirra et al in 1992 when he described a characteristic soft tissue tumour that often involved bone [7]. Mirra considered the tumour a variant of epithelioid sarcoma based on its keratin positivity but these tumours had morphology similar to pseudomyogenic hemangioendothelioma. More recently these tumours have been diagnosed as epithelioid sarcoma-like hemangioendothelioma or pseudomyogenic hemangioendothelioma, likely because of the presence of CD31 immunoreactivity in some cases. There is some controversy as to what these tumours should be called [8]. More recently Mertens and his group have identified a t(7; 19)(q22;q13) translocation in a subset of pseudomyogenic hemangioendothelioma suggesting it may be distinct from epithelioid sarcoma [9]. Of note the current tumour also showed this translocation in 28% of cells by FISH (Mertens F. unpublished data). However there was also chromosome 19 amplification, a feature not described in the original report.

Clearly differentiating pseudomyogenic hemangioendothelioma from the other keratin positive tumours in the differential is important given the clinical course of this tumour. Metastatic carcinoma can display FLI-1, keratin and INI-1 immunoreactivity. However the morphology of the cells, plump spindle cells with eosinophilic cytoplasm does not favour carcinoma. Furthermore ultrastructural analysis showed no epithelial differentiation and clinically no primary tumour or other metastases have developed in the follow-up period.

Differentiation from epithelioid sarcoma can be difficult especially as 10-20% of these tumours can show INI-1 retention [6, 10]. However epithelioid sarcomas can express CD34, are negative (to date) for FLI-1 positivity, and rarely invade bone. Nevertheless it maybe that those cases diagnosed as INI-1 positive epithelioid sarcoma are actually pseudomyogenic hemangioendothelioma. It may not be until we evaluate these cases for abnormalities in INI tumour suppressor gene (chromosome 22) and the (7; 19) translocation will we know for sure [11].

Undifferentiated pleomorphic sarcoma is also unlikely. Although UPS can express keratin, it is seen rarely and usually not as extensively as is seen in pseudomyogenic hemangioendothelioma. As well to date FLI-1 positivity has not been detected in these tumours.

Conclusion(s):
Pseudomyogenic hemangioendothelioma is a rare tumour and has to be differentiated from other sarcomas or metastatic carcinoma.

References:
  1. Hornick JL, Fletcher CD. Pseudomyogenic hemangioendothelioma: a distinctive, often multicentric tumor with indolent behavior. Am J Surg Pathol 2011;35 (2):190-201.

  2. Billings SD, Folpe AL, Weiss SW. Epithelioid sarcoma- like hemangioendothelioma. Am J Surg Pathol 2003;27(1):48- 57.

  3. Tokyol C, Uzum N, Kuru I, Uluoglu O. Epithelioid sarcoma-like hemangioendothelioma: a case report. Tumori 2005;91(5):436-9.

  4. Watabe A, Okuyama R, Hashimoto A, Hosaka M, Hatori M, Kariya Y, et al. Epithelioid sarcoma-like haemangioendothelioma: a case report. Acta Derm Venereol 2009;89(2):208-9.

  5. Cai JN, Peng F, Li LX, Cheng YF, Wang J. [Epithelioid sarcoma-like hemangioendothelioma: a clinicopathologic and immunohistochemical study of 3 cases]. Zhonghua Bing Li Xue Za Zhi 2011;40(1):27-31.

  6. Chbani L, Guillou L, Terrier P, Decouvelaere AV, Gregoire F, Terrier-Lacombe MJ, et al. Epithelioid sarcoma: a clinicopathologic and immunohistochemical analysis of 106 cases from the French sarcoma group. Am J Clin Pathol 2009;131(2):222-7.

  7. 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 spindle cell tumors. Cancer 1992;69 (6):1382-95.

  8. Billings SD, Folpe AL, Weiss SW. Epithelioid Sarcoma- like hemangioendothelioma (pseudomyogenic hemangioendothelioma). Am J Surg Pathol 2011;35(7):1088; author reply 1088-9.

  9. Trombetta D, Magnusson L, von Steyern FV, Hornick JL, Fletcher CD, Mertens F. Translocation t(7;19)(q22;q13)-a recurrent chromosome aberration in pseudomyogenic hemangioendothelioma? Cancer Genet 2011;204(4):211-5.

  10. Hornick JL, Dal Cin P, Fletcher CD. Loss of INI1 expression is characteristic of both conventional and proximal-type epithelioid sarcoma. Am J Surg Pathol 2009;33 (4):542-50.