—  SPECIALTY CONFERENCE  —

Bone & Soft Tissue Pathology

Case 3 - "Early" Pleomorphic Hyalinizing Angiectatic Tumor of Soft Parts

Andrew L. Folpe
Emory University Hospital
Atlanta, GA


Click on each slide thumbnail image for an enlarged view
Clinical History
A 55-year-old man presented with a slowly growing, 8cm, right lower leg and ankle mass.


Case 3 - Figure 1 - Very low power view (2X) showing an extensively myxoid spindle cell proliferation, with diffuse infiltration of fat and focal cellular nodules
Case 3 - Figure 2 - Low power view (4x) illustrating the admixture of hypocellular myxoid zones and more cellular regions. An unusual damaged blood vessel is also present
Case 3 - Figure 3 - Medium power view (10X) of a myxoid zone, showing abundant myxoid matrix, small, darkly staining spindled cells and wiry collagen



Case 3 - Figure 4 - Another medium power view, showing the myxoid matrix, spindled cells and small aggregates of capillaries
Case 3 - Figure 5 - Medium high power view (20X) showing small, generally uniform, darkly staining spindled cells
Case 3 - Figure 6 - Medium high power view showing the transition from a myxoid zone (right) into a more cellular zone (left). A small vessel with intramural fibrin deposition is present, as are other aggregates of small blood vessels



Case 3 - Figure 7 - High power view (440X) showing striking, finely granular hemosiderin deposition in many of the neoplastic cells. Scattered larger cells with intranuclear inclusions are also present
Case 3 - Figure 8 - Another high power view of the hemosiderin-laden cells, some with intranuclear inclusions. Note that the hemosiderin is in the neoplastic cells themselves, rather than in macrophages
Case 3 - Figure 9 - Medium high power (20X) view of an aggregate of ectatic, damaged blood vessels with prominent fibrin deposition, thrombosis and recanalization

Gross description:
An approximately 8 cm myxoid and fatty mass was removed.

Microscopic description:
Sections showed fat with diffuse infiltration by a variably myxoid spindle cell neoplasm. The neoplastic cells infiltrated the fat as individual cells, small aggregates and short fascicles, and were for the most part small, but hyperchromatic. Scattered larger cells with pleomorphic, hyperchromatic nuclei and intranuclear pseudoinclusions were also found scattered throughout the lesion. A notable feature was the presence of abundant, finely granular hemosiderin pigment present with many of the neoplastic cells themselves. Mast cells and other chronic inflammatory cells were also present, as were numerous hemosiderin-laden macrophages. Also present, scattered within the fat, either individually or in small aggregates, were ectatic damaged blood vessels, containing fibrin. The neoplastic cells could often be seen aggregating around these damaged blood vessels.

Immunohistochemical results:
The tumor was positive for CD34 and negative for actins, desmin and S100 protein.

Diagnosis: "Early" pleomorphic hyalinizing angiectatic tumor of soft parts

Discussion:
The pleomorphic hyalinizing angiectatic tumor (PHAT) is a rare tumor of uncertain lineage described by Smith et al in 1996 in a series of 14 cases [1] . Prior to this past year, fewer than 20 PHAT had been reported [2, 3, 4, 5, 6, 7, 8] . PHAT occurs principally in the superficial soft tissues of the distal extremities and features ectatic, fibrin-containing vessels with prominent circumferential hyalinization, spindled and pleomorphic stromal cells with intranuclear inclusions, and a variable inflammatory component. Since its original description attention has understandably always centered on the striking vascular changes in this lesion and the criteria that distinguish PHAT from overt sarcomas, as well as from "ancient" schwannomas. Over the last few years, however, Sharon Weiss and I were impressed by several subtle features of these lesions, which have not been emphasized in the past. First, although some PHAT display classic features throughout, others manifest a curious peripheral proliferation of generally bland spindled cells infiltrating fat and accompanied by a degree of myxoid change. These changes are sometimes centered around tiny ectatic vessels. Second, this low-grade spindle cell lesion may also exist by itself in the absence of classic PHAT, suggesting that it may represent a precursor lesion, which we have termed "early PHAT".

We therefore recently studied a group of 41 PHAT, paying careful attention to the presence of early PHAT [9] . As in previous series, our cases usually occurred in the distal extremity of middle aged to older adults, where they presented as slowly growing, superficially located masses, often of long clinical duration. In 15 of our cases (37%) the tumor consisted of >90% typical PHAT. In 7 of these cases small peripheral zones of "early PHAT" identical to those seen in the present case were identified; in the remaining 8 cases an intralesional excision had been performed, and the tumor periphery was not available for review. Twelve cases (29%) consisted essentially only of early PHAT. As in the present case, these were partially myxoid tumors of low to at most focally moderate cellularity and consisted of bland spindled cells with wavy nuclei arranged in fascicles, which infiltrated in and around small clusters of adipocytes. In almost all cases very small, abnormally arranged blood vessels, some of which showed ectasia and fibrin deposition could be identified with careful searching. Most early PHAT contained abundant, finely granular, intracytoplasmic hemosiderin pigment, although this was not especially prominent in the present case. Scattered hemosiderin-laden macrophages were also seen in many cases. Although the spindled cells in early PHAT were always small and bland, careful inspection in all cases revealed rare pleomorphic cells with intranuclear pseudoinclusions, as seen in typical PHAT. A mixed chronic inflammatory cell infiltrate, composed of lymphocytes, plasma cells and mast cells, was seen in most cases. Fourteen cases contained both typical and early PHAT, in variable proportions. In these cases areas of typical PHAT were most often unifocal and centrally located, but were occasionally scattered throughout the mass. Both early and typically PHAT were usually CD34-positive and all were S100 protein negative. Follow-up showed a number of local recurrences, both by early and typical PHAT, with early PHAT showing some tendency to become more pleomorphic over time. No case metastasized.

Given the frequent presence of areas of early PHAT in otherwise typical PHAT, it is of interest that the presence of hypocellular myxoid areas has only infrequently been commented upon in the past. Although the seminal report of Smith et al necessarily focused on the description and differential diagnosis of classic PHAT, Figure 8 from their study illustrates one case in which ectatic vessels comprised only a minor component of the tumor, with much of the tumor resembling a fibrosarcoma with abundant myxoid stroma [1] . Brim et al, in a report of a PHAT occurring in the foot of a 31-year-old woman, noted the presence of both typical PHAT as well as areas that were "myxoid in character and somewhat less cellular" [8] . Similarly, Fukunaga and Ushigome noted in passing the presence of "hypocellular areas … characterized by myxoid, degenerative or hyalinized stroma" [2] and Groisman et al noted "less cellular regions that showed stromal myxoid change" [4] . It is also possible that the infrequent presence of early PHAT in previous reports might be explained by intralesional or marginal excision, which often removes only the dominant nodule of typical PHAT, leaving behind clinically subtle areas of early PHAT.

Given the somewhat subtle morphologic features of early PHAT, it is also quite likely that many cases have been mistaken for a variety of benign or reactive lesions, such as spindle cell lipoma, benign fibrous histiocytoma, or nodular fasciitis. Unlike early PHAT, spindle cell lipomas lack intracytoplasmic hemosiderin and damaged blood vessels, and contain distinctive wiry collagen. Benign fibrous histiocytomas may contain numerous siderophages, but lack hemosiderin within their constituent spindled cells, and usually contain multinucleated giant cells and foamy macrophages. Nodular fasciitis also lacks intracytoplasmic iron and is a relatively hypovascular lesion, with characteristic stromal breakdown and microcytic change.

The histologic features of early PHAT are remarkably similar to a lesion described recently by Marshall-Taylor and Fanburg-Smith as "hemosiderotic fibrohistiocytic lipomatous lesion" (HFLL) [10] . As described and illustrated by these authors, HFLL occur predominantly but not exclusively in the foot/ ankle region of middle age patients, and consist of an unusual admixture of fat, variably myxoid stroma, moderately cellular fascicles of iron-laden spindled cells and macrophages, and chronic inflammatory cells. Pleomorphic cells were occasional identified, as was "hyalinization around a few small to medium sized vessels, adjacent to the spindled proliferations". Local recurrences were seen in 50% of the patients in this series with follow-up (the appearance of these recurrent lesions is not given) and no tumor metastasized. Another series of "HFLL" was reported in abstract form by Browne and Fletcher; 11 of 12 cases occurred near the ankle/foot and none of the cases with follow-up information was reported to recur or metastasize [11] . It would appear that the histologic appearances, as well as the usual locations and behavior, of early PHAT and so-called "HFLL" are extraordinarily similar, if not identical, and it is likely that HFLL is not a separate entity.

References

  1. Smith ME, Fisher C, Weiss SW. Pleomorphic hyalinizing angiectatic tumor of soft parts. A low-grade neoplasm resembling neurilemoma. American Journal of Surgical Pathology 1996;20(1):21-9.
  2. Fukunaga M, Ushigome S. Pleomorphic hyalinizing angiectatic tumor of soft parts. Pathology International 1997;47(11):784-8.
  3. Gallo C, Murer B, Roncaroli F. [Pleomorphic hyalinizing angiectasic soft-tissue tumor. Description of a case]. Pathologica 1997;89(5):531-5.
  4. Groisman GM, Bejar J, Amar M, Ben-Izhak O. Pleomorphic hyalinizing angiectatic tumor of soft parts: immunohistochemical study including the expression of vascular endothelial growth factor. Archives of Pathology & Laboratory Medicine 2000;124(3):423-6.
  5. Husek K, Vesely K. Pleomorphic hyalinizing angiectatic tumor. Ceskoslovenska Patologie 2001;37(4):177-81.
  6. Matsumoto K, Yamamoto T. Pleomorphic hyalinizing angiectatic tumor of soft parts: a case report and literature review. Pathology International 2002;52(10):664-8.
  7. Silverman JS, Dana MM. Pleomorphic hyalinizing angiectatic tumor of soft parts: immunohistochemical case study shows cellular composition by CD34+ fibroblasts and factor XIIIa+ dendrophages. Journal of Cutaneous Pathology 1997;24(6):377-83.
  8. Brim SP, Allerding TJ, Buck K. Pleomorphic hyalinized angiectatic tumor of soft parts. J Am Podiatr Med Assoc 1999;89(6):307-11.
  9. Folpe AL, Weiss SW. Pleomorphic hyalinizing angiectatic tumor: analysis of 41 cases supporting evolution from a distinctive precursor lesion. Am J Surg Pathol 2004;28(11):1417-25.
  10. Marshall-Taylor C, Fanburg-Smith JC. Hemosiderotic fibrohistiocytic lipomatous lesion: ten cases of a previously undescribed fatty lesion of the foot/ankle. Mod Pathol 2000;13(11):1192-9.
  11. Browne T-J, Fletcher CD. Hemosiderotic fibrohistiocytic lipomatous tumor (so-called): Validation of a distinct entity. Lab Invest 2004;84 (Supplement 1):11A.