Proliferative Angioendotheliomatosis: Always an Angiotropic Lymphoma?

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<ul><li><p>Path. Res. Pract. 190,409-411 (1994) Letter to the Editor </p><p>Proliferative Angioendotheliomatosis: Always an Angiotropic Lymphoma? </p><p>H. J. Leu Department of Pathology, University of Zurich, Switzerland </p><p>Proliferative angioendotheliomatosis (PA) was originally described by Pfleger and T appeiner6, 11 as a multi focal proliferation of large pleomorphic cells within small blood vessels. Lately immunohistochemical studies of numerous cases of apparent PA have demonstrated strong expression of leucocyte common antigen and negative reactions for factor VIII-related antigen by the intravascular prolifera-tive cells, revealing their leucocytic origin 1,2, 8-10,13. There-fore PA was reclassified as "angiotropic lymphoma"8 of B-cell or T-cell phenotype. However, the discussion on this matter is not closed by far. A benign form of PA called bacillary angiomatosis, associated with bacterial endocar-ditis and other infections including HIV infection, and responding well to antibiotics, has been described4,7. Admittedly many cases of apparent PA may be recognized as angiotropic lymphomas on the basis of immunohisto-chemical examination. On the other hand, multicentric proliferation of vascular endothelial cells doubtlessly exists. This phenomenon is well-known in Ka posi's sarco-ma and in angiosarcoma of Stewart and Treves. The endothelial origin of both these multifocal tumors has been proved3 Kaposi's sarcoma may be associated with HIV infection but occurs also spontaneously or in relation to immunosuppression (organ transplants) . Angiosarcoma arising in chronic lymphedema (syndrome of Stewart and Treves) may be histologically indistinguishable from Kaposi's sarcoma, but may also present with large pleo-morphic cells occluding the vessel lumina and resembling the cases described by Pfleger and T appeiner6, II in P A. In the relatively short period since the introduction of immunohistochemical examination into routine patholo-gy we have not encountered cases of PA of proven endothelial origin in humans. Recently, however, we have observed a case of PA in a two-year-old, previously healthy cat without infection by feline lymphotropic lentivirus (by courtesy of Department of Veterinary Pathology, Univer-sity of Zurich, Prof. Dr. A. Pospischil). Histology showed multicentric occlusions of small arteries, veins and capil-laries by large pleomorphic cells in kidney, lymph nodes and bone marrow. The il!lmunohistochemical investiga-tions revealed a strong reaction of the tumor cells to vimentin and factor VIII-related antigen and no reaction to </p><p> 1994 by Gustav Fischer Verlag, Stuttgart </p><p>leucocyte common antigen and smooth muscle actin. The tumor cells were surrounded by a thin basement mem-brane demonstrated by a monoclonal type IV collagen marker (C 4, Dakopatts, Copenhagen, Denmark) (Figs. 1-3). </p><p>Figure 1. Small lymph node vessel occluded by proliferating endothelial cells. H &amp; E, 200 x . </p><p>0344-0338/94/0190-0409$3.5010 </p></li><li><p>410 . H. J. Leu </p><p>Figure 2. Proliferating endothelial cells in an afferent arteriole of the kidney, infiltrating into the glomerulus. H &amp; E, 200 x. </p><p>It seems inappropriate to categorically deny the exis-tence of PA in the sense of Pfleger and Tappeiner. PA may occur in a variety of forms such as: 1) Benign bacillary angioendotheliomatosis, a reactive </p><p>type of PA of endothelial origin according to histologic, immunohistochemical, and clinical evidence12, </p><p>2) Malignant angioendotheLiomatosis: a) in Kaposi's sarcoma, b) in angiosarcoma of Stewart and Treves, c) in PA in the sense of Pfleger and Tappeiner. </p><p>These cases must of course be separated from pseudo-P A such as angiotropic lymphoma or multiple intravascu-lar metastases of malignant endotheliomas in aorta/large arteries mimicking a PAS. </p><p>References </p><p>I Beal MF, Fisher Me (1982) Neoplastic angioendothelioma-tosis. J Neurol Sci 53: 359-375 </p><p>- -. </p><p>' .. </p><p>Figure 3. Proliferating endothelial cells in bone marrow vessel with strong reaction to factor VIII-related antigen. Fa VIII (Dakopatts, Copenhagen, Denmark), 200 x. </p><p>2 Bhawan J, Wolff SM, Ucci AA et al (1985) Malignant lymphoma and malignant angioendotheliomatosis: one disease. Cancer 55: 570-576 </p><p>3 Enzinger FM, Weiss ShW (1988) Soft tissue tumors. CV Mosby, St. Louis, Washington, Toronto 1988, 2nd ed. p 545-580 </p><p>4 Eisenstein BI (1990) New opportunistic infections-more opportunities. N Engl J Med 323 : 1625-1627 </p><p>5 Leu HJ, Sulser H (1976) Maligner endothelialer Tumor der Arteria femoralis mit distaler Embolisation. Virchows Arch A Path Anat and HistoI371: 153-159 </p><p>6 Pfleger L, Tappeiner J (1959) Zur Kenntnis der systemati-sierten Endotheliomatose der cutanen BlutgefiiRe (Reticuloendo-theliomatose?). Hautarzt 10: 359-3 63 </p><p>7 Reiman DA, Loutit JS, Schmidt ThM et al (1990) The agent of bacillary angiomatosis. N Engl J Med 323 : 1573-1580 </p><p>8 Seep N, Schuler G, Romani N et al (1990): "Intravascular lymphomatosis" (Angioendotheliomatosis). Hum Pathol 21: 1051-1058 </p><p>9 Sheibani K, Battifora H, Winberg CD et al (1986) Further evidence that "malignant angioendotheliomatosis" is an angio-tropic large-cell lymphoma. N Engl J Med 314: 943-948 </p></li><li><p>10 Stroup RM, Sheibani K, Moncada A et al (1990) Angio-tropic (intravascular) large cell lymphoma. Cancer 66: 1781-1788 </p><p>11 Tappeiner J, Pfleger L (1963) Angioendotheliomatosis proliferans systematisata. Ein klinisch und pathophysiologisch neues Krankheitsbild. Hautarzt 14: 67-70 </p><p>Letter to the Editor . 411 </p><p>12 Wick MR, Rocamora A (1988) Reactive and malignant "angioendotheliomatosis": A discriminant clinicopathological study. J Cutan Pathol15: 260-271 </p><p>13 Wrotnowski U, Mills SE, Cooper PH (1985) Malignant angioendotheliomatosis: an angiotropic lymphoma? Amer J Clin Pathol 83: 244-248 </p><p>Received October 12, 1993 Accepted in revised form November 26, 1993 </p><p>Prof. Dr. H. J. Leu, Institut fiir Pathologie, Universitat Ziirich, CH-6986 Novaggio </p></li></ul>