Eosinophilic fasciitis

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A 53-year-old man was admitted to our hospital with a slowly row in and nontender lesion on the medial aspects of the right leg. Clinical examination revealed a well-demarcated, brownish subcutaneous lesion measuring 2.3 x 2.0 x 2.0 cm. A conventional excision was performed and submitted for pathological examination. A subsequent wide local excision was carried out. No further treatment has been performed. The patient is alive and well 13 months after the initial surgical procedure.

The excised specimen was composed of a well-demarcated tanto-gray nodule, 2.0 cm in greatest diameter, with a lobulated, grayish cut surface and scattered hemorrhagic foci. Histologically, low-power magnification showed a circumscribed nodule composed of solid cellular areas and remarkably ectatic vascular areas (Figure 1). The vascular areas were characterized by clusters of thin-walled ectatic blood vessels (Figure 2), lined by flat endothelial cells, sometimes arranged in papillary structures (resembling re-endothelization or papillary endothelial hyperplasia such as that observed in Masson tumors), which were surrounded by eosinophilic hyaline material (Figure 3). Scattered vessels occluded by fibrin thrombi were also observed. The solid cellular areas were composed of ovoid-to-spindle-shaped cells, with round-to-oval nuclei, inconspicuous nucleoli, and ill-defined eosinophilic cytoplasm, arranged either around ectatic vessels or forming sheets and fascicles admixed with variable amounts of a fibrocollagenous matrix (Figure 4). Large, bizarre, pleomorphic mono- and multinucleated cells, with hyperchromatic nuclei, harboring nuclear cytoplasmic pseudoinclusions and prominent eosinophilic macronucleoli resembling Reed-Sternberg-like or Hodgkin-like cells (Figure 4, inset) were observed around ectatic vessels as well as admixed with the bland spindle-cell component of solid cellular areas. Scattered cells with a brownish, coarse intracytoplasmic pigment, which stained blue with the Perl technique (hemosiderin) and were pale brown with the Fontana-Masson technique, were depicted. A mixed inflammatory infiltrate composed of mast cells, lymphocytes, eosinophils, and rare plasma cells was mainly observed around ectatic vessels. The mitotic index was low (2 mitoses per 10 high-power fields-2.8 mm^sub 2^), and no atypical mitosis was observed. Neoplastic cells were strongly reactive for vimentin and a-smooth muscle actin. alphaSmooth muscle actin also highlighted pericytes around some small and dilated vessels. CD31 and CD34 decorated endothelial cells but were uniformly negative in tumor cells around ectatic vessels and in the solid cellular areas. All other markers, including 5100 protein, HMB-45, epithelial membrane antigen, CD31, CD34, desmin, and cytokeratins 34betaE12 and CAM 5.2, were consistently negative in both vascular and solid cellular areas of the tumor.

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Pathologic Diagnosis: Pleomorphic Hyalinizing Angiectatic Tumor of the Soft Tissues

Pleomorphic hyalinizing angiectatic tumor (PHAT) is a rare neoplasm of uncertain histogenesis that mainly affects the lower extremities of adults, with a male-female ratio of ~2:3.1-8 Since the seminal study published by Smith et al,1 only 6 cases have been described.4-8 Of the 21 cases hitherto reported, including the present case, all were affected adults and had a higher prevalence after the fourth decade of life; 18 tumors arose in the subcutaneous tissues and 3 were deep-seated. Fifteen lesions afflicted the lower limbs, mainly their distal aspects (13 cases); other locations were the trunk (3 cases) and upper limbs (3 cases).1,4-8

Pathologic examinations of PHATs demonstrated that all lesions were nonencapsulated and mainly possessed an infiltrative growth (15 cases); in 6 cases (including the present case), well-circumscribed borders were observed.1,4-8 Histologically, PHAT presents a combination of variably sized thin-walled ectatic vessels with eosinophilic material around their walls, admixed with sheets and fascicles of pleomorphic spindle-shaped cells, with hyperchromatic nuclei harboring cytoplasmic pseudoinclusions. Other eyecatching features include tumor cells with intracytoplasmic hemosiderin pigment, extracellular hemosiderin deposition, mixed inflammatory infiltrate including lymphocytes, mast cells, eosinophils, and occasional plasma cells as well as focal calcifications and psammoma bodies.1-8

Immunohistochemical evaluation of the previously published PHATs as well as our case showed vimentin reactivity (all 6 cases evaluated for the presence of this intermediate filament), variable CD34 reactivity (8 cases with diffuse and strong immunoreactivity, 4 with weak-tomoderate positivity, and 7 with no reactivity), and uniform negativity of neoplastic cells for other vascular markers (eg, CD31 and factor VIII-related antigen).1-8 Reactivity for factor XIIIa, vascular endothelial growth factor, and epithelial membrane antigen has also been described.4,5 alphaSmooth muscle actin reactivity was evaluated in only 4 cases and showed positivity in only one (the present case). S100 protein and cytokeratin were negative in all cases evaluated so far.1-8

Several neoplasms might be confused with PHAT at histologic examination. According to Smith et al,1 the referring pathologists suggested neurilemoma (Schwannoma), liposarcoma, benign and malignant fibrous histiocytoma, Kaposi sarcoma, leiomyosarcoma, proliferative fasciitis, and vascular malformation as possible histologic diagnoses.1 The most difficult differential diagnoses of PHAT are neurilemoma and malignant fibrous histiocytoma.1-3 In fact, spindle cells with nuclear cytoplasmic pseudoinclusions, hyalinized vessels, foci of hemorrhage, and hemosiderin deposition, as well as well-circumscribed margins and variable CD34 immunoreactivity, are features of both PHAT and neurilemoma.1-3 In addition, ancient neurilemomas might harbor mono- and multinucleated bizarre cells.2,3 However, PHAT lacks a well-formed fibrous capsule and spindle cells arranged in Antoni type A and type B patterns and is consistently negative for S100 protein.1-3 Low mitotic rates, clusters of hyalinized thin-walled ectatic vessels, and immunoreactivity for CD34 help differentiate PHAT from malignant fibrous histiocytoma.1-3 The finding of pleomorphic spindle-shaped cells with eosinophilic nucleoli, nuclear cytoplasmic pseudoinclusions, and brownish intracytoplasmic pigment may lead to a misdiagnosis of malignant melanoma or clear cell sarcoma.9 Malignant melanoma and clear cell sarcoma frequently express S100 protein and HMB-45 immunoreactivity9 in contrast to PHAT; the brownish cytoplasmic pigment observed in malignant melanoma and clear cell sarcoma is melanin (Fontana-Masson +, Perl -), whereas in PHAT, it is hemosiderin (Fontana-Masson -, Perl +). The occasional presence of calcifications and psammoma bodies in bona fide PHATs may mislead physicians to make the diagnosis of psammomatous melanotic Schwannoma 2,3,10; this tumor consistently expresses S100 protein and HMB45 in contrast to the uniform negativity for these markers in PHAT.2,3,10

Despite the marked pleomorphism of neoplastic cells, PHAT shows only locally aggressive clinical behavior.18,10 To our knowledge, only 4 of the 21 reported cases (including the present case) had local recurrences'1-8,10; 2 had multiple recurrences, one requiring amputation.1 No metastatic deposits have hitherto been reported. For managerial therapeutic decisions, PHAT should be included in an intermediate category of aggressiveness.1,2,10

References

1. Smith ME, Fisher C, Weiss SW. Pleomorphic hyalinizing angiectatic tumor of soft parts. A low-grade neoplasm resembling neurilemoma. Am J Surg Pathol. 1996;20:21-29.

2. Weiss SW, Goldblum JR. Benign soft tissue tumors and pseudotumors of miscellaneous types. In: Weiss SW, Goldblum JR, eds. Enzinger and Weiss's Soft Tissue Tumors. 4th ed. St Louis, Mo: Mosby Year Book Inc; 2001:1419-1481.

3. Fletcher CDM. Soft tissue tumors. In: Fletcher CDM, ed. Diagnostic Histopathology of Tumors. 2nd ed. London, England: Churchill Livingstone; 2000: 1473-1540.

4. Silverman JS, Dana MM. Pleomorphic hyalinizing angiectatic tumor of soft parts: immunohistochemical case study shows cellular composition by CD34+ fibroblasts and factor XIIIa+ dendrophages. J Cutan Pathol. 1997;24:377-383.

5. Groisman GM, Bejar J, Amar M, Ben-Izhak 0. Pleomorphic hyalinizing an-- giectatic tumor of soft parts: immunohistochemical study including the expression of vascular endothelial growth factor. Arch Pathol Lab Med. 2000;124:423-426.

6. Brim SP, Allerding TJ, Buck K. Pleomorphic hyalinized angiectatic tumor of soft parts. J Am Podiatr Med Assoc. 1999;89:307-311.

7. Gallo C, Murer B, Roncaroli F. Pleomorphic hyalinizing angiectatic softtissue tumor. Description of a case. Pathologica. 1997;89:531-535.

8. Fukunaga M, Ushigome S. Pleomorphic hyal in izing angiectatic tumor of soft parts. Pathol Int. 1997;47:784-788.

9. Slominski A, Wortsman J, Carlson Aj, Matsuoka LY, Balch CM, Mihm MC. Malignant melanoma. Arch Pathol Lab Med. 2001;125:1295-1306.

10. Kempson RL, Fletcher CDM, Evans HL, Hendrickson MR, Sibley RK. Tumors of the Soft Tissues. Washington, DC: Armed Forces Institute of Pathology; 2001. Atlas of Tumor Pathology; 3rd series, fascicle 30.

Jorge S. Reis-Filho, MD; Jose Manuel Lopes, MD, PhD

Accepted for publication July 25, 2002.

From the Institute of Molecular Pathology and Immunology, University of Porto (IPATIMUP), Porto, Portugal (Drs Reis-Filho and Lopes); the School of Health Sciences, University of Minho, Braga, Portugal (Dr Reis-Filho); and the Department of Pathology, Medical Faculty and Sao Joao Hospital, Porto, Portugal (Dr Lopes).

Corresponding author: Jose Manuel Lopes, MD, PhD, IPATIMUP, R. Roberto Frias, S/N, 4200 Porto, Portugal (e-mail: jsreis@hotmail.com).

Reprints not available from the author.

Copyright College of American Pathologists May 2003
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