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Background
This rare variant of vascular tumors have a guarded prognosis. Some tumors can recur locally and have a destructive behavior while others can rarely metastasize. Epithelioid hemangioendothelioma has a prognosis intermediate between high grade angiosarcomas and well differentiated hemangiomas. However, recent studies have questioned the neoplastic nature of this tumor and have raised the possibility that this is a reactive process. It occurs in the skin, liver, and spleen but has been reported in many other organs as case reports.
OUTLINE
CHARACTERIZATION Hepatic epithelioid hemangioendothelioma: MR imaging findings.
Kehagias DT, Moulopoulos LA, Antoniou A, Psychogios V, Vourtsi A, Vlahos LJ.
Department of Radiology, University of Athens, Areteion Hospital, Athens, Greece.
Hepatogastroenterology 2000 Nov-Dec;47(36):1711-3 Abstract quote
We describe the sonographic, computed tomography and magnetic resonance imaging findings of two patients with histologically proven hepatic hemangioendothelioma. Both patients presented with multiple liver nodules. Color Doppler ultrasound demonstrated moderate vascularity at the periphery of the nodules, as well as central neovascularity. On enchanced computed tomography images, the lesions showed peripheral enhancement only. On magnetic resonance images, tumor signal was low on T1-weighted and moderately high on T2-weighted images. The distinction between normal liver and tumor was difficult on all sequences.
Administration of superparamagnetic iron oxide particles delineated well the tumor by suppressing the signal of the normal liver and better depicted areas of remaining healthy parenchyma
HISTOLOGICAL TYPES CHARACTERIZATION GENERAL It is now clear that cases of spindle cell hemangioendothelioma, once thought to be a low grade malignancy, is probably best thought of as a benign reactive condition
Kaposiform Hemangioendothelioma: A Study of 33 Cases Emphasizing Its Pathologic, Immunophenotypic, and Biologic Uniqueness From Juvenile Hemangioma.
Lyons LL, North PE, Mac-Moune Lai F, Stoler MH, Folpe AL, Weiss SW.
*Departments of Pathology and Laboratory Medicine, Emory University, Atlanta, GA; daggerUniversity of Arkansas Medical Sciences and the Arkansas Childrens' Hospital, Little Rock, AR; double daggerUniversity of Virginia Hospital, Charlottesville, VA; and section signChinese University of Hong Kong, Sha Tin, Hong Kong.
Am J Surg Pathol. 2004 May;28(5):559-568. Abstract quote
Kaposiform hemangioendothelioma (KH) is a rare tumor of childhood often associated with Kasabach-Merritt phenomenon (KMP) and occasionally lymphangiomatosis. Although generally considered distinct from other vascular neoplasms, its rarity has precluded a thorough study of its immunophenotypic profile and long-term behavior.
Thirty-three cases of KH were reviewed and immunostained for alpha-smooth muscle actin, various endothelial markers (CD31, CD34, vWf, FLI1), a platelet marker (CD61), and the juvenile hemangioma-associated markers GLUT-1 and Lewis Y antigen (LeY). In addition, the presence of HHV-8 was evaluated by RT-PCR. The patients (20 males and 13 females) ranged in age from 2 weeks to 20 years (mean 3 years 9 months). Tumors developed on the extremities (17 cases), head/neck (8 cases), and other sites (8 cases) and affected both superficial and deep soft tissue. Those in the skin presented as slightly raised blue-red lesions. More than half of the patients presented with KMP (14 of 25).
Tumors consisted of irregular, infiltrating nodules of compressed vessels, which modulated between areas resembling a capillary hemangioma and Kaposi sarcoma (KS). Endothelial cells in nodules were CD31, CD34, and FLI1 positive but negative for GLUT1 and LeY. Scattered "epithelioid" or glomeruloid islands featuring endothelium associated with clusters of plump alpha-smooth muscle actin-positive pericytes, stippled hemosiderin, and CD61-positive fibrin thrombi likely represent the morphologic sites of platelet consumption. Small and large lymphatic channels occurred in 22 of 33 cases and were typically seen peripheral or deep to the main tumor mass. HHV-8 transcripts were not identified (0 of 3 cases).
Follow-up information was available in 22 patients (range 8 months to 15 years; mean 2 years) and indicated that 3 died of disease, 8 were alive with disease, and 10 were alive without residual disease. Two patients developed regional perinodal soft tissue involvement, but none developed distant metastases. KH is a lesion having both a vascular and lymphatic component. Its common association with KMP probably relates in part to unique architectural features that favor turbulent blood flow and platelet activation. KH can also be reliably separated from JH by GLUT-1 and LeY immunostaining, indicating differences in the morphologic and functional attributes of the endothelium between the two lesions. The absence of HHV-8 in KH underscores a different pathogenesis from Kaposi sarcoma.
Our study, the largest to date, emphasizes that mortality is due to KMP and not metastatic disease, which appears limited to regional perinodal soft tissue. Given this behavior, its continued classification as a vascular tumor of intermediate malignancy is warranted.COMPOSITE
*Department of Pathology, The Jikei University School of Medicine †Department of Pathology, St Lukeʼs International Hospital, Tokyo ‡Department of Plastic surgery, Niiza, Saitama, Japan §Division of Anatomic Pathology, Mayo Clinic, Rochester, MN.
Composite hemangioendothelioma (HE) is a low-grade malignant vascular tumor showing varying combinations of benign, low-grade malignant, and malignant vascular components. The predominant histologic components are histologically identical to epithelioid HE and retiform HE. To our knowledge, there have been only 12 cases of composite HE reported in the English literature and its nature and biologic behavior remains unknown.
In this study, the clinicopathologic and immunohistochemical features of 5 cases of composite HE including a case with associated Maffucci syndrome are described. The patients were 4 females and 1 male with a median age of 43.4 years (range, 22 to 75 y). All tumors occurred in the dermis and/or subcutis. The tumors arose in the foot or lower leg in 3 patients, in the jaw in 1 patient, and as multiple tumors in the left upper extremity in 1 patient. Two patients had congenital tumors, in the lower thigh and foot, and upper extremity, respectively. The lesions were usually of several years duration. The size of individual tumors ranged from 1.5 to 30 cm. The tumors were composed of a complex admixture of histologic components resembling various vascular lesions.
The predominant components, present in all cases, resembled retiform HE and epithelioid HE. Angiosarcomalike areas were observed in 3 cases. Lymphangiomalike areas were found in 2 cases. Areas of spindle cell hemangioma, cavernous hemangioma, or arteriovenous malformation were identified in 1 case each. The 2 congenital cases, which exhibited multiple lesions, had angiosarcomalike components and an angiomatosislike growth pattern. One patient each was associated with Kasabach-Merritt or Maffucci syndrome.
Immunohistochemically, all tumors showed expression of at least 2 endothelial markers (CD31, CD34, and/or factor VIII-related antigen). Of 4 cases with follow up (median duration, 8.6 y), 1 tumor recurred locally. To date, none of the patients have developed metastases. There was no difference of biologic behavior among cases with various combinations of histology in this study and previously reported cases.
We conclude that composite HE should continue to be regarded as a low-grade malignant vascular tumor (HE), with significant potential for local recurrence, but little if any potential for distant metastasis.Composite Hemangioendothelioma A Complex, Low-Grade Vascular Lesion Mimicking Angiosarcoma
Simon J. Nayler, M.D., F.F.Path.(S.A.); Brian P. Rubin, M.D., Ph.D.; Eduardo Calonje, M.D.; John K. C. Chan, M.B.B.S., F.R.C.Path.; Christopher D. M. Fletcher, M.D., F.R.C.Path.
From the Departments of Pathology (S.J.N.), South African Institute for Medical Research, Johannesburg, South Africa; the Institute of Dermatology (E.C.), London, UK; the Queen Elizabeth Hospital (J.K.C.C.), Hong Kong, ROC; and the Brigham & Women's Hospital (B.P.R., C.D.M.F.), Boston, MA, U.S.A.
Am J Surg Pathol 2000;24:352-361 Abstract quote
Eight cases of a previously uncharacterized vascular neoplasm, showing varying combinations of benign, low-grade malignant, and malignant vascular components are described.
Seven tumors occurred in the dermis and/or subcutis and one occurred in the oral submucosa. The patients were all adults with a median age of 39.5 years (range, 21–71 years). Five patients were men. The tumors arose predominantly in the hands and feet, and the lesions were usually of several years duration.
The tumors were composed of a complex admixture of histologic components that varied from tumor to tumor, such that no two tumors looked precisely the same. This was due to variation in the proportions of each component as well as the manner in which each component was distributed throughout each lesion. The predominant histologic components were epithelioid hemangioendothelioma (HE) and retiform HE, which were each present in seven of the tumors. Areas of spindle cell HE were identified in four lesions. Angiosarcoma-like elements were identified in seven tumors. One of the tumors was associated with an arteriovenous malformation and one was associated with an area of lymphangioma circumscriptum. Of six cases with follow up (median duration, 6.5 years), three have recurred locally and, to date, only one has metastasized.
We think composite HE is best regarded as a low-grade malignant vascular neoplasm, and the available data suggest that it behaves more favorably than conventional angiosarcoma. The existence of these composite lesions has led to careful reexamination of the concept of HE. The term HE, in that it is currently synonymous with a low-grade malignant vascular tumor, should be reserved for lesions that have true metastatic potential, albeit with low frequency.
Congenital composite hemangioendothelioma: case report and reappraisal of the hemangioendothelioma spectrum.Reis-Filho JS, Paiva ME, Lopes JM.
Institute of Molecular Pathology and Immunology, University of Porto (IPATIMUP); and Department of Pathology, Medical Faculty, University of Porto, Porto, Portugal.
J Cutan Pathol 2002 Apr;29(4):226-31 Abstract quote BACKGROUND: Composite hemangioendothelioma is the most recently described entity of the hemangioendothelioma (HE) spectrum. To the best of our knowledge, only eight cases of this entity have been hitherto described. All of the previous cases affected adults; local recurrences were observed in three cases, and one case showed lymph node metastasis. We herein describe a new and previously unreported congenital case of this rare vascular tumor, arising on the acral extremity of the left forearm, which was diagnosed when the patient was 23 years old.
RESULTS: The histological examination disclosed a heterogeneous vascular neoplasm composed of retiform HE-like (80%), spindle cell hemangioma-like (15%), cavernous hemangioma-like ( approximately 3%), epithelioid HE-like ( approximately 2%) areas, and rare foci with an angiosarcoma-like pattern (< 1%). A distinctive and unique finding of the present case was the presence of large granular eosinophilic macrophages filling some vessels of the retiform HE-like areas. A below-elbow amputation was performed. The patient is alive and well, without evidence of residual or metastatic disease 7 years after the treatment.
CONCLUSIONS: The authors expand the concept of composite hemangioendothelioma by adding a congenital case and provide a reappraisal of the hemangioendothelioma spectrum.
Poorly marginated infiltrative lesions usually multinodular
May arise from a vessel, usually a vein
Myxoid matrix with tumor cells arranged in cords, strands, small nests with minimal vascular differentiation
Plump rounded cells with cytoplasmic vacuolation forming intracytoplasmic lumina with occasional rbcs
Stroma may show hyalinization and hemorrhage and 15% have ossification
MF < usually 2
10-15% may have worrisome cytologic features with increased mitotic figuresCutaneous epithelioid hemangioendothelioma without systemic involvement.
Resnik KS, Kantor GR, Spielvogel RL, Ryan E.
Department of Medicine, Hahnemann University, Philadelphia, PA 19102-1192.
Am J Dermatopathol 1993 Jun;15(3):272-6 Abstract quote
Epithelioid hemangioendothelioma (EH) is a unique vascular tumor characterized histologically by epithelioid endothelial cells. A case of EH arising from the dermis and presenting as a nodule of the palm is described.
To our knowledge, this is the third report of a cutaneous presentation of EH and the first report of a patient with this rare neoplasm with solitary cutaneous involvement.
A review of the literature is also presented.
Multiple cutaneous epithelioid hemangioendothelioma: a case with spindle cells.
Kato N, Tamura A, Okushiba M.
Department of Dermatology, National Sapporo Hospital, Japan.
J Dermatol 1998 Jul;25(7):453-9 Abstract quote
A case of multiple cutaneous epithelioid hemangioendothelioma (EH) in a Japanese male is reported.
The patient was a 52-year-old Japanese bureaucrat. Clinically, about 10 purplish-red, elastic soft or hard papules and nodules had appeared on both lower extremities and the left buttock over the past 20 years. They were excised, but some of them recurred. Histologically, the papules and nodules were well-circumscribed tumors located in the superficial and deep dermis. They appeared to arise from medium-sized vessels and were composed of proliferations of characteristic epithelioid endothelial cells with intracytoplasmic vacuolization and spindle cells. No other extracutaneous tumors were found.
We diagnosed the present case as multiple cutaneous EH with spindle cells. The presence of epithelioid endothelial cells and absence of pleomorphism and mitoses of nuclei of spindle cells made differential diagnosis from Kaposi's sarcoma possible. The protracted clinical course seems characteristic of EH in various organs including skin.
EPITHELIOID
SARCOMA-LIKE
Epithelioid sarcoma-like hemangioendothelioma.Billings SD, Folpe AL, Weiss SW.
Am J Surg Pathol 2003 Jan;27(1):48-57 Abstract quote We are reporting seven histologically identical cases of a distinctive, low-grade vascular tumor that closely mimics an epithelioid sarcoma because of growth in solid sheets and nests, the eosinophilia of the rounded to slightly spindled neoplastic cells, and the diffuse, strong cytokeratin expression.
Termed epithelioid sarcoma-like hemangioendothelioma, all were diagnosed by the submitting pathologist or another expert consultant as epithelioid sarcoma. Although none displayed architectural evidence of vascular differentiation in the form of multicellular vascular channels, some displayed subtle cytologic features of vascular differentiation and all displayed immunohistochemical evidence of endothelial differentiation.
The patients (four male; three female) ranged in age from 17 to 54 years (median 23 years). Ranging in size from 1 to 3.5 cm, they occurred in the extremities (n = 5), scalp (n = 1), and chest wall (n = 1), both in deep (n = 3) and superficial (n = 3) soft tissue or both (n = 1). The tumors were characterized by sheets, ill-defined nodules, or fascicles of deeply eosinophilic cells set within a desmoplastic stroma. Multicellular vascular channel formation and/or hemorrhage were absent in all cases. In four cases intracytoplasmic vacuolization suggestive of intracytoplasmic vascular lumen formation was noted. The typical neoplastic cell was large and rounded in shape but modulated in areas to a spindled or multipolar shape. Mitotic activity was low (<5 mitotic figures/50 high power fields), nuclear pleomorphism was mild to moderate, and necrosis was absent. The tumors were positive for cytokeratin (6 of 6), vimentin (6 of 6), CD31 (5 of 6), FLI-1 (6 of 6), but negative for CD34 (0 of 6).
Within a follow-up period of 3-72 months (median 39 months), two patients experienced a local recurrence and one patient regional soft tissue metastases, but no distant ones. Two patients presented with multifocal lesions suggestive of regional metastases. Currently, two patients are alive with disease and five are disease free.
Epithelioid sarcoma-like hemangioendothelioma appears to be a largely unrecognized epithelioid vascular tumor with an indolent course. Despite its similar clinical and histologic features, it differs from epithelioid sarcoma by the presence of endothelial markers and the absence to date of distant metastases. Its distinction from other epithelioid vascular lesions is discussed. We think this tumor fits best into the family of "hemangioendothelioma" or vascular lesions of intermediate malignancy.
High cellularity with poorly circumscribed lobular architecture
Uniform spindle cells with pale eosinophilic cytoplasm and elongated nuclei associated with rounded thin-walled capillaries and fibrin microthrombi
Rare atypia and mitotic figures
Rare hyaline globulesKaposiform hemangioendothelioma in adults. Clinicopathologic and immunohistochemical analysis of three cases.
Mentzel T, Mazzoleni G, Dei Tos AP, Fletcher CD.
Department of Pathology, University of Jena, Germany.
Am J Clin Pathol 1997 Oct;108(4):450-5 Abstract quote
Kaposiform hemangioendothelioma (KHE) is a rare vascular neoplasm that previously has been described only in children. We report three cases occurring in adults.
The patients, two men and one woman, were aged 64, 55, and 48 years, respectively. Lesions arose on the chest wall, the lateral aspect of the neck, and in the groin and buttock, and each was situated in superficial soft tissue. Tumor size ranged from 0.9 to 7 cm. Histologically, in all cases a lobular or nodular growth pattern of densely packed spindle-shaped tumor cells closely associated with small slitlike and sievelike blood vessels was seen. Within one lesion, small nodules of plumper, epithelioid tumor cells were identified. Well-formed capillaries frequently containing fibrin thrombi were observed mainly in the periphery of tumor nodules. Areas of hemorrhage and hemosiderin deposits were observed in two cases. Associated lymphangiomatosis composed of diffusely infiltrating lymphatic spaces of the dermis and subcutis was present in one case. Nuclear atypia was minimal in all cases, and mitotic figures were rare in two cases; in one case up to 6 mitoses in 10 high-power fields were noted focally. Immunohistochemically, well-formed capillaries stained positively for all the vascular markers used; however, endothelial cells lining the small slitlike and sievelike vascular spaces did not stain for von Willebrand factor. At least focally, actin-positive pericytes were seen. Neoplastic spindled cells stained only focally for CD34 and CD31. Two lesions were excised with clear margins; in one case only repeated biopsies were done. Follow-up information between 14 and 28 months revealed no sign of recurrence or metastasis.
In adults, the differential diagnosis of KHE comprises especially Kaposi's sarcoma and spindle cell hemangioendothelioma; further differential diagnoses include tufted hemangioma and cellular capillary hemangioma, which occur rarely in adults.
Kaposiform hemangioendothelioma: a locally aggressive vascular tumor.
Beaubien ER, Ball NJ, Storwick GS.
Faculty of Medicine, University of Calgary, Alberta, Canada.
J Am Acad Dermatol 1998 May;38(5 Pt 2):799-802 Abstract quote
Kaposiform hemangioendothelioma is a locally aggressive, endothelial-derived spindle cell neoplasm that occurs exclusively in infants and adolescents.
Lesions are characterized by rapid growth and extension, and are often associated with Kasabach-Merritt syndrome and lymphangiomatosis. Clinically nonspecific, they can appear as tender rapidly expanding red plaques, nodules, grouped papules, or telangiectasias. The histology is distinctive, however, as it combines features of tufted angioma, progressive lymphangioma, and Kaposi's sarcoma in a characteristic pattern.
We describe a patient with kaposiform hemangioendothelioma currently controlled with systemic prednisone.
Congenital cutaneous multifocal kaposiform hemangioendothelioma.
Gianotti R, Gelmetti C, Alessi E.
Istituto di Scienze Dermatologiche, IRCCS Ospedale Maggiore di Milano, Universita degli Studi di Milano, Milan, Italy.
Am J Dermatopathol 1999 Dec;21(6):557-61 Abstract quote
Kaposiform hemangioendothelioma is a rare vascular neoplasm in children often associated with Kasabach-Merritt syndrome. The tumor usually presents in retroperitoneal location and is rarely present at birth. Cutaneous lesions manifest after birth and must be clinically differentiated from infantile hemangiomas and diffuse neonatal hemangiomatosis. Histologically, it bears similarities with Kaposi sarcoma.
We present a case of congenital cutaneous multifocal kaposiform hemangioendothelioma (KHE).
Kaposiform Hemangioendothelioma: Five Patients with Cutaneous Lesion and Long Follow-Up
Fernand Mac-Moune Lai, F.R.C.P.A., Ka Fai To, F.R.C.P.A., Paul C.L. Choi, F.R.C.P.A., Ping Chung Leung, F.C.R.S., Shekhar M. Kumta, F.C.R.S., Patrick P.M. Yuen, F.R.C.S., Wing Yin Lam, F.R.C.P.A., Annie N.Y. Cheung, F.R.C.P.A. and Philip W. Allen, F.R.C.P.A.
Departments of Anatomical & Cellular Pathology (FM-ML, KFT, PCLC), Orthopedic & Traumatology (PCL, SMK), and Pediatrics (PPMY), The Chinese University of Hong Kong, Hong Kong; Department of Pathology (WYL); Tuen Mun Hospital, Hong Kong; Department of Pathology (ANYC), The University of Hong Kong, Hong Kong; and Department of Pathology (PWA), Flinders Medical Center, South Australia, Australia
Mod Pathol 2001;14:1087-1092 Abstract quote
Kaposiform hemangioendothelioma is a rare locally aggressive vascular tumor of the skin, deep soft tissue, and bone in children, characterized by infiltrating nodules and sheets of spindle cells, and unmistakable resemblance to Kaposi’s sarcoma. More than 60 patients with such tumor have been reported so far, and while many have died as a result of extensive disease and severe coagulopathy, the long-term biologic behavior of this tumor remains undetermined.
We describe five patients with kaposiform hemangioendothelioma and a mean follow-up of 19 years, ranging from 8 to 35 years. This report emphasizes on the importance of cutaneous lesions being the most commonly affected site, but also for its clinical diversity. Early diagnosis is possible even for a small skin lesion, which may be critical for the treatment of a potentially fatal deep-seated extensive tumor. All five patients are well, and three of them with persistent vascular tumor, which has carried two patients from childhood to adult.
Although the behavior of this tumor might have been modified by radiation or interferon in three patients, this series indicates that kaposiform hemangioendothelioma is incapable of metastasis, despite a protracted course of many decades with no tendency for spontaneous regression.
OSTEOCLAST GIANT CELLS Epithelioid hemangioendothelioma with osteoclast-like giant cells Am J Clin Pathol 1990;93:813–7.
Arch Pathol Lab Med 1993;117:315–8.
Young adults
Epithelioid tumor cells in these cases, even in solid areas, recapitulated endothelial cells with intracytoplasmic lumina and Factor VIII stainingMixture of solid and primitive vascular and angiomatous endothelial areas
Plump tumor cells with occasional epithelioid featurs and occasional vacuoles
Solid areas with nested or sheet-like pattern
No nuclear atypia and rare mitotic figures
Polymorphous hemangioendothelioma of the neck.Tadros M, Rizk SS, Opher E, Thompson LD.
Ann Diagn Pathol. 2003 Jun;7(3):165-8. Abstract quote Polymorphous hemangioendotheliomas are rare, low-grade borderline malignant vascular tumors of endothelial cell origin.
To the best of our knowledge (MEDLINE 1966-2002), there have been nine cases of polymorphous hemangioendothelioma reported in the English literature. Most of the initial patients reported were men, but we present the third case in a woman. Her previous radiation history to the neck makes this report unique.
Polymorphous hemangioendothelioma is characterized by the variety of patterns of growth within and between tumors, making histologic recognition of the tumor difficult. Because management remains conservative via wide local excision, the misdiagnosis of this lesion as a malignancy has possible treatment implications.
Alternatively, the high propensity for local recurrence underscores the necessity for accurate classification of the neoplasm and close clinical follow-up.Dermal based proliferation of arborizing, elongated narrow vessels with hyperchromatic protuberant nuclei resembling a rete testis
50% may show prominent lymphoid aggregates
No endothelial pleomorphism and rare mitotic figures
Rare cases with focal spindled areas
Department of Pathology, Medical Center, Medical Center Boulevard, Wake Forest University Baptist, Winston-Salem, NC, USA.
Retiform hemangioendothelioma (RH) is a rare vascular neoplasm most often occurring in the limbs of middle-aged females. This entity is characterized by infiltrative vascular spaces arranged in a pattern similar to the rete testis. RH differs from angiosarcoma by lacking cytologic atypia and high mitotic rates. This neoplasm frequently recurs but rarely metastasizes. RH tumor cells react with vascular endothelial markers CD31, CD34, and factor VIII-related antigen.
A review of the English literature provides only one attempt at staining RH with D2-40, a marker of endothelium of lymphatic vessels, which was negative, and one reported staining of RH with lymphatic endothelial marker VEGFR-3, which was positive. The etiology of RH is unknown. RH has previously been considered closely related to Dabska tumors, which are positive for lymphatic endothelial marker D2-40.
We stained 4 RHs with mouse monoclonal antibodies against D2-40 and CD31 and 3 of the 4 RHs with vascular endothelial growth factor receptor 3 (VEGFR-3), to further evaluate whether RH had lymphatic differentiation, in addition to vascular differentiation.
Three of the 4 RH biopsies failed to demonstrate D2-40, none expressed VEGFR-3, whereas CD31 was strongly positive, suggesting that RH is a vascular entity which usually does not have lymphatic differentiation, but may rarely express D2-40.
- Retiform hemangioendothelioma: a case report and review of the literature.
Tan D, Kraybill W, Cheney RT, Khoury T.
Department of Pathology and Cancer Genetics, Roswell Park Cancer Institute.
J Cutan Pathol. 2005 Oct;32(9):634-7. Abstract quote
Background: Retiform hemangioendothelioma (RH) is a rare, recently described vascular neoplasm of low malignant potential.
Methods: We report a case of RH of the foot of a 19-year-old white female. Histologically, the tumor grew as numerous elongated vessels resembling the shape of rete testis with involvement of the skin adnexal structures and subcutaneous adipose tissue. No dissection of collagen by small groups of endothelial cells was seen. Wide local excision was performed and the patient was healthy with no metastasis at 14 months follow-up.
Results and Conclusions: Our case is discussed in the context of previously reported cases of RH; we also include a review of all cases of RH published to date.Retiform hemangioendothelioma. A new case in a child with diffuse endovascular papillary endothelial proliferation.
Sanz-Trelles A, Rodrigo-Fernandez I, Ayala-Carbonero A, Contreras-Rubio F.
Department of Pathology, Regional Hospital Carlos Haya, Malaga, Spain.
J Cutan Pathol 1997 Aug;24(7):440-4 Abstract quote
We present a new case of retiform hemangioendothelioma (RH), an entity first described by Calonje et al. in 1994.
The tumor was intradermal and located on the toe of an 11-year-old boy. Histologically, in addition to the distinctive retiform pattern of proliferating vessels in RH there are intraluminal papillae with hyaline cores similar to those seen in malignant endovascular papillary angioendothelioma (Dabska's tumor), but usually they are infrequent, focal and poorly developed. In our case, these papillary structures were well formed and distributed in a diffuse way. They were most conspicuous in superficial areas where the blood vessels were dilated. In deep areas, where the pattern of neoplastic vessels was retiform, the papillae filled their lumina totally, resembling solid cords.
Our case shares the clinical and morphologic features of both retiform hemangioendothelioma and Dabska's tumor, supporting a relationship between these two kinds of neoplasms. The benign behavior of this case, with no recurrence or metastases over a 4-year follow-up, corresponds to the low malignancy of this kind of vascular neoplasm.
SPINDLE CELL Spindle cell haemangioendothelioma: a clinicopathological and immunohistochemical study indicative of a non-neoplastic lesion.
Fletcher CD, Beham A, Schmid C.
Department of Histopathology, St. Thomas' Hospital (UMDS), London, UK.
Histopathology 1991 Apr;18(4):291-301 Abstract quote
Spindle cell haemangioendothelioma is an uncommon vascular lesion, of which 35 cases have been previously reported. A further 20 cases are reported herein. These lesions affected a wide age range in both sexes, and showed a predilection for the extremities. Twelve patients had multiple lesions and, in these cases, local progression over many years but no true recurrence was typical. None of the 20 patients developed metastases, but one later developed an angiosarcoma.
Individual cases were associated with congenital lymphoedema. Klippel-Trenaunay syndrome and early-onset varicose veins.
Histologically, in addition to the admixture of cavernous spaces and solid spindle cell/epithelioid cell areas, the presence both of irregularly distributed and perivascular smooth muscle cells and of malformed variably-sized vessels at the periphery of almost every lesion was noted in each case. Reticulin staining, immunohistochemistry and electronmicroscopy revealed the presence of primitive vessel formation and partial endothelial differentiation in the solid spindle cell areas.
Combining these data with those from previously published series, it is suggested that spindle cell haemangioendothelioma is a non-neoplastic lesion (rather than a borderline malignancy as it is currently regarded) and that its development correlates with histological and/or clinical evidence of a malformed vasculature at the affected site.
Spindle cell haemangioendothelioma: probably a benign vascular lesion not a low-grade angiosarcoma. A clinicopathological, ultrastructural and immunohistochemical study.
Ding J, Hashimoto H, Imayama S, Tsuneyoshi M, Enjoji M.
Second Department of Pathology, Faculty of Medicine, Kyushu University, Fukuoka,
Japan.Virchows Arch A Pathol Anat Histopathol 1992;420(1):77-85 Abstract quote
Ten cases of spindle cell haemangioendothelioma (SCH) were analysed clinicopathologically, including an immunohistochemical survey of seven cases and ultrastructural observations on one.
There were seven females and three males, ranging from 16 to 76 years of age. All but one lesion developed on the extremities, predominantly on the hands and feet. Six of the ten patients presented multiple nodules or papules which gradually increased in size and number over a long duration. Among them, four patients had undergone operations twice or more, but no metastatic foci were recognized.
Histologically, the lesions were composed of dilated vascular spaces and a proliferation of bland-appearing spindle cells and interspersed epithelioid endothelial cells. Ultrastructural and immunohistochemical studies demonstrated that the spindle cells were mainly made up of fibroblastic cells admixed with pericyte-like cells and macrophages. Smooth muscle cells and primitive mesenchymal cells were also present.
The clinical and microscopic features suggest that SCH may be a benign vasoformative lesion of a heterochronological multicentric origin.
SPECIAL STAINS /
IMMUNOPEROXIDASECHARACTERIZATION Special stains Immunoperoxidase Factor VIII positive
CD31 and CD34 positive
DIFFERENTIAL
DIAGNOSISKEY DIFFERENTIAL FEATURES EPITHELIOID
HEMANGIOMA
Epithelioid hemangioma of the penis: a clinicopathologic and immunohistochemical analysis of 19 cases, with special reference to exuberant examples often confused with epithelioid hemangioendothelioma and epithelioid angiosarcoma.
Fetsch JF, Sesterhenn IA, Miettinen M, Davis CJ Jr.
Department of Soft Tissue, Armed Forces Institute of Pathology, Washington, DC 20306-6000, USA.
Am J Surg Pathol. 2004 Apr;28(4):523-33. Abstract quote
Epithelioid hemangiomas of the penis are very rare. To date, less than 10 examples have been reported in the English language literature.
In this report, we describe the clinical, histopathologic, and immunohistochemical findings in 19 cases retrieved from our files. The patients ranged in age from 23 to 75 years (median age, 45 years) at the time of initial surgical resection. Seventeen patients presented with a solitary mass, and two presented with two separate, but closely approximated, lesions. The process involved the glans penis (n = 3), shaft (n = 11), base of the penis (n = 2), or penis, not otherwise specified (n = 3). The lesions ranged in size from <0.5 to 2.5 cm (median size, approximately 1.2 cm) in greatest dimension. Eleven examples were specifically noted to be dorsally located, and only one was stated to be ventral. Localized pain or tenderness was the most common complaint, documented in 12 cases. The preoperative duration of the lesions ranged from 5 days to 1 year (median 4.5 months).
Microscopically, all examples contained a tumefactive proliferation of epithelioid endothelial cells, often in a nodular or lobular configuration and associated with an inflammatory infiltrate containing lymphocytes and eosinophils.
In 14 cases, the vascular proliferation was associated with a small arterial segment, sometimes with mural damage and frequently (n = 13) with intraluminal epithelioid endothelial cells. Based on the growth pattern of the epithelioid endothelial cells, 13 cases were considered "typical," and six were considered exuberant or "atypical." The latter examples had a prominent centrally located zone where nests or sheet-like aggregates of epithelioid endothelial cells did not form discrete vessels. Immunohistochemical data are available for 15 tumors. The epithelioid endothelial cells usually had strong reactivity for CD31, lesser reactivity for factor VIIIrAg, and minimal reactivity for CD34. In 9 of 12 cases, a small number of epithelioid endothelial cells expressed keratins. In all cases tested, at least focal muscle-specific actin-positive myopericytic cells were present bordering the endothelial cells, and this was especially notable peripherally.
Initial surgical intervention consisted of either a shave biopsy (n = 1), excisional biopsy (n = 2), or local excision (n = 16). A complete follow-up history is available for 12 patients, and incomplete follow-up information is available for an additional four patients. One patient developed a new epithelioid hemangioma at a site within the penis separate from the initial lesion, but no patient is known to have experienced a true metastasis or to have died of complications of this process. Optimal management appears to be complete local excision with periodic follow-up visits to monitor for local recurrence.Epithelioid hemangioma of bone. A tumor often mistaken for low-grade angiosarcoma or malignant hemangioendothelioma.
O'Connell JX, Kattapuram SV, Mankin HJ, Bhan AK, Rosenberg AE.
Department of Pathology, Massachusetts General Hospital, Boston 02114.
Am J Surg Pathol 1993 Jun;17(6):610-7 Abstract quote
Epithelioid hemangiomas are benign vascular tumors that usually occur in the skin and subcutis. They have been infrequently recognized in bone. Because of their unusual cytologic appearance and growth patterns, they are commonly confused with malignant tumors.
We report a series of 12 epithelioid hemangiomas of bone occurring in adult patients, including five males and seven females whose ages at presentation ranged from 24 to 74 years, with a mean of 46 years. Five tumors were associated with involvement of the adjacent soft tissue. A single patient had multifocal bone disease. The most common presenting symptom was localized pain. Treatment of the patients varied widely; however, none of the tumors behaved aggressively. In 11 cases, adequate tissue was available for immunohistochemical analysis, which revealed positive staining for the epithelial markers cytokeratin and epithelial membrane antigen in nine cases. All 11 tumors stained for factor VIII-related antigen and Ulex europeus agglutinin. We believe that many of the vascular tumors of bone that have been reported as low-grade malignant hemangioendotheliomas probably represent examples of epithelioid hemangiomas.
We recommend that the criteria for diagnosing vascular tumors of bone conform to those used for morphologically similar tumors that arise in the soft tissues.
REACTIVE ANGIOENDO-THELIOMATOSIS Reactive angioendotheliomatosis. Case report and review of the literature.
Lazova R, Slater C, Scott G.
Department of Pathology, University of Rochester School of Medicine and Dentistry, NY 14642, USA.
Am J Dermatopathol 1996 Feb;18(1):63-9 Abstract quote
Angioendotheliomatosis is an uncommon disease characterized histologically by proliferation of cells within vascular lumina with secondary intravascular thrombi resulting in obliteration of the involved vessels.
While angioendotheliomatosis was initially thought to be a single disease entity, recent studies show that the disease may be divided into benign (reactive) and malignant variants, with the malignant variant representing intravascular malignant lymphoma. The reactive variant is rare, with only 16 cases reported in the literature, and is characterized histologically by proliferating endothelial cells within vessel lumina.
In this report we present a case of reactive angioendotheliomatosis and review the literature on this rare entity.
TUFTED ANGIOMA
- Arai E,
- Kuramochi A,
- Tsuchida T,
- Tsuneyoshi M,
- Kage M,
- Fukunaga M,
- Ito T,
- Tada T,
- Izumi M,
- Shimizu K,
- Hirose T,
- Shimizu M.
Department of Pathology, Saitama Medical School, Iruma-gun, Saitama, Japan.
BACKGROUND: Recent investigations have demonstrated the utility of the monoclonal antibody D2-40 as a marker for lymphatic endothelium. D2-40 can be used on formalin-fixed and paraffin-embedded materials. Our objective was to elucidate, using D2-40 immunohistochemistry, the differences among capillary hemangiomas, and especially between kaposiform hemangioendothelioma (KHE) and tufted angioma (TA). We studied four cases of KHE, nine cases of TA, and 31 cases of other vascular tumors. Antibodies against CD31, CD34, factor VIII-related antigen, and GLUT1 were also applied.
RESULTS: In KHE, D2-40 was markedly reactive for three and partially for one of four cases in the peripheral area of Kaposi's sarcoma-like proliferative capillaries and negative in the surrounding dilated vessels. In TA, D2-40 was partially positive in the surrounding dilated vessels and negative in cannonball-like proliferative capillaries.
CONCLUSIONS: Our results suggest that D2-40 is a useful antibody for immunohistochemical discrimination between KHE and TA. In addition, the difference of immunostaining pattern of D2-40 is limited to the peripheral area of capillary proliferation and surrounding dilated vessels; therefore, it is suggested that KHE and TA may reflect different stages in the evolution of a single entity. Namely, they may originate from stem cells possessing the characteristics of both lymphatic and blood vessel endothelial lineages.
PROGNOSIS AND TREATMENT CHARACTERIZATION PROGNOSIS SURVIVAL Fatal in 20% usually with retroperitoneal tummors Patients who do not have indolent multifocal disease may have a guarded prognosis
Soft tissue tumors die in 20%
Local recurrence in 10-15%Pulmonary epithelioid haemangioendothelioma in 21 patients, including three with partial spontaneous regression.
Kitaichi M, Nagai S, Nishimura K, Itoh H, Asamoto H, Izumi T, Dail DH.
Laboratory of Anatomic Pathology, Kyoto University Hospital, Japan.
Eur Respir J 1998 Jul;12(1):89-96 Abstract quote
This investigation studied the general conditions and prognostic factors of pulmonary epithelioid haemangioendothelioma (PEH), which is a rare disease.
Twenty-one patients were collected throughout Asia by a questionnaire. Age at the detection or onset of symptoms of PEH was 14-64 yrs (mean 44 yrs). Males were more likely to be detected by symptoms (4/8, 50%) than were females (1/13, 8%). Fifteen showed bilateral multiple nodular opacities. Partial spontaneous regression occurred in three asymptomatic patients (one male and two females, all with bilateral multiple nodular opacities) 5, 13 and 15 yrs after detection. Two of the three patients with pleural effusion died within 1 yr, while the 16 patients with no effusion were alive more than 1 yr later (p<0.05).
Histologically, two patients with fibrinofibrous pleuritis and extrapleural proliferation of tumour cells died within 2 yrs, while only one of 14 patients lacking such manifestations died within the same period (p<0.05). All three patients without spindle tumour cells survived for 12 yrs after the diagnosis, while all four patients with such cells died during the same period (p<0.05).
In conclusion, 21 patients with pulmonary epithelioid haemangioendothelioma were reported, of whom three demonstrated partial spontaneous regression, and adverse prognostic features were identified.
TREATMENT Treatment of hepatic epithelioid hemangioendothelioma with liver transplantation.
Marino IR, Todo S, Tzakis AG, Klintmalm G, Kelleher M, Iwatsuki S, Starzl TE, Esquivel CO.
Department of Surgery, University Health Center of Pittsburgh, Pennsylvania.
Cancer 1988 Nov 15;62(10):2079-84 Abstract quote
Ten patients received liver transplants for unresectable epithelioid hemangioendothelioma (EHE).
At the time of transplantation, four patients had microscopic metastases to the hilar lymph nodes, and one of the four also had metastases to a rib. The fifth patient had metastases to the lung, pleura, and diaphragm. The remaining five patients were believed to be free of metastatic disease. Two of these five patients died of metastatic disease at 3 and 16 months, respectively, after transplantation. Interestingly, all five patients with metastatic involvement are currently alive 40.6 +/- 22 months (mean +/- standard error of mean [SEM]) after transplantation, although one of these patients currently has metastatic disease to the lungs and mediastinum.
Thus, the projected 5-year actuarial survival rate is 76%, with two patients at risk after the third year.
In conclusion, liver transplantation is a reasonable procedure for bulky, otherwise unresectable, EHE even in the presence of metastatic disease.
[Multifocal epithelioid hemangioendothelioma with partial remission after interferon alfa-2a treatment]. [Article in French]
Roudier-Pujol C, Enjolras O, Lacronique J, Guillemette J, Herbreteau D, Leibowitch M, Escande JP. Service de Dermatologie, Hopital Tarnier-Cochin, Paris.
Ann Dermatol Venereol 1994;121(12):898-904 Abstract quote
INTRODUCTION. Epithelioid hemangioendothelioma (EHE) is a rare vascular tumour of the soft tissue having an intermediate malignancy. Cutaneous presentations have exceptionally been reported.
OBSERVATION. A young woman, initially affected by an EHE with cutaneous and bone involvement, then with pulmonary and hepatic localizations, was in partial remission after one year of treatment with alpha 2a interferon.
DISCUSSION. In a critical review of the literature, we describe the main features of this tumour and the difficulties to classify this entity in the vascular tumors' spectrum. Histologically, epithelioid hemangioendothelioma has a very characteristic appearance and is clearly different from other vascular tumors as angiolymphoid hyperplasia with eosinophilia and Kimura's disease. The assumption of a multicentric or a metastatic origin when multiple tumor deposits are found, is still not elucidated. Different therapeutic approaches are proposed: surgery, interferon, interleukin-2, retinoids.
Randomized studies would be necessary to confirm our results with alpha 2a interferon but are probably difficult to realize because of the lack of cases.
Long-term results after liver transplantation for primary hepatic epithelioid hemangioendothelioma.
Madariaga JR, Marino IR, Karavias DD, Nalesnik MA, Doyle HR, Iwatsuki S, Fung JJ, Starzl TE.
Department of Surgery, University of Pittsburgh School of Medicine, Pennsylvania, USA.
Ann Surg Oncol 1995 Nov;2(6):483-7 Abstract quote
BACKGROUND: Hepatic epithelioid hemangioendothelioma (PHEHE) is a multifocal, low-grade malignant neoplasia characterized by its epithelial-like appearance and vascular endothelial histogenesis. The outcome of 16 patients treated with orthotopic liver transplantation (OLT) is the subject of this report.
METHODS: A retrospective study of 16 patients with HEHE (7 men, 9 women) with ages ranging from 24 to 58 years (mean 37 +/- 10.6 years). Follow-up intervals ranged from 1 to 15 years (median of 4.5 years).
RESULTS: Actual patient survival at 1, 3, and 5 years was 100, 87.5, and 71.3%, respectively. Disease-free survival at 1, 3, and 5 years was 81.3, 68.8, and 60.2%, respectively. The 90-day operative mortality was 0. Involvement of the hilar lymph nodes or vascular invasion did not affect survival. The 5-year survival of HEHE compares favorably with that of hepatocellular carcinoma at the same stage (stage 4A): 71.3 versus 9.8% (p = 0.001)
CONCLUSIONS: The long-term survival obtained in this series justifies OLT for these tumors even in the presence of limited extrahepatic disease.
Successful medical treatment of an epithelioid hemangioendothelioma of liver.
Idilman R, Dokmeci A, Beyler AR, Bastemir M, Ormeci N, Aras N, Ekinci C, Uzunalimoglu O, De Maria N, Van Thiel DH.
Medical School, University of Ankara, Turkey.
Oncology 1997 Mar-Apr;54(2):171-5 Abstract quote
Hepatic epithelioid hemangioendothelioma (HEH) is a rare vascular tumor of the liver of unknown etiology. Although HEH is usually characterized by a low grade malignancy and a good long-term prognosis, its growth can be progressive and lead to hepatic failure, extrahepatic metastasis and death. Several different antineoplastic agents have been proposed for cases of nonresectable HEH.
We report the case of a 45-year-old man with HEH successfully treated with intravenous infusion of Adriamycin.
Case report: successful palliative treatment with intraperitoneal OK-432 injection for epithelioid haemangioendothelioma presenting with intractable ascites.
Wei SC, Yang PM, Chen CH, Chu JS, Chen DS.
Department of Internal Medicine, National Taiwan University Hospital, Taipei.
J Gastroenterol Hepatol 1997 Jan;12(1):39-43 Abstract quote
Epithelioid haemangioendothelioma is an unusual type of endothelium-derived vascular tumour of borderline malignancy, which has high variability in clinical presentations, depending on the primary site of involvement.
We report on a 20-year-old woman who presented with progressive abdominal fullness for 6 months. Multiple lung and liver nodules with pleural effusion and profuse ascites were found. The diagnosis of epithelioid haemangioendothelioma was made after wedge biopsy of the liver. The ascites was intractable and refractory to strong diuretic therapy and repeated paracentesis. Therefore, six courses of intraperitoneal injection of OK-432 were administered. The ascites subsided to a minimal amount after treatment and the patient remained symptom-free for approximately 8 months. The ascites recurred later and another three courses of intraperitoneal injection of OK-432 were administered. The ascites disappeared again.
The patient has remained symptom-free since the end of the second period of treatment.
Successful medical treatment of an epithelioid hemangioendothelioma of liver.
Idilman R, Dokmeci A, Beyler AR, Bastemir M, Ormeci N, Aras N, Ekinci C, Uzunalimoglu O, De Maria N, Van Thiel DH.
Medical School, University of Ankara, Turkey.
Oncology 1997 Mar-Apr;54(2):171-5 Abstract quote
Hepatic epithelioid hemangioendothelioma (HEH) is a rare vascular tumor of the liver of unknown etiology. Although HEH is usually characterized by a low grade malignancy and a good long-term prognosis, its growth can be progressive and lead to hepatic failure, extrahepatic metastasis and death. Several different antineoplastic agents have been proposed for cases of nonresectable HEH.
We report the case of a 45-year-old man with HEH successfully treated with intravenous infusion of Adriamycin.
Hepatic epithelioid hemangioendothelioma: resection or transplantation, which and when?
Ben-Haim M, Roayaie S, Ye MQ, Thung SN, Emre S, Fishbein TA, Sheiner PM, Miller CM, Schwartz ME.
The Recanati/Miller Transplantation Institute, The Mount Sinai Hospital of Mount Sinai-New York University Medical Center and Health System, New York, NY, USA.
Liver Transpl Surg 1999 Nov;5(6):526-31 Abstract quote
Hepatic epithelioid hemangioendothelioma (HEHE) is a rare tumor with an unpredictable course and prognosis. The aim of this study is to describe our experience with liver resection, as well as transplantation, in the treatment of this tumor.
We retrospectively analyzed the clinical features, pathological findings, and postoperative results in a series of 11 patients presenting between 1990 and 1998. Five patients (45%) presented with abdominal pain, 3 patients (27%) with jaundice and ascites, and the rest were asymptomatic. Computed tomography or magnetic resonance imaging showed localized lesions in 2 patients (18%) and multifocal disease in the others. Seven patients (64%) had extrahepatic lesions, detected either by preoperative imaging or discovered at exploration. Two resections of apparently localized lesions were followed by rapid and aggressive recurrence. Five patients were treated with transplantation, including 1 patient who had previously undergone resection. Of these 5 patients, 2 patients are currently free of detectable disease, 1 patient who had severe ascites and jaundice is now asymptomatic with stable extrahepatic lesions, and 2 patients (including 1 who had previously undergone a resection) died of tumor recurrence. One patient with advanced tumor died while waiting for transplantation. The remaining 4 patients are free of symptoms and have stable hepatic and extrahepatic disease. HEHE is nearly always multifocal, and our results with resection were dismal.
Because of the unpredictable nature of the tumor, the indications for transplantation in patients without liver-related symptoms should be carefully evaluated. Nevertheless, extrahepatic disease should not be an absolute contraindication for liver transplantation in patients with severe liver dysfunction.
Treatment of epithelioid hemangioendothelioma of bone using a novel combined approach.
Rosenthal DI, Treat ME, Mankin HJ, Rosenberg AE, Jennings CL.
Massachusetts General Hospital, 15 Parkman Street, Boston, MA 02114, USA.
Skeletal Radiol 2001 Apr;30(4):219-22 Abstract quote
Radiofrequency (RF) treatment has been used for a variety of malignant and benign conditions. However, treatment of a bone malignancy has yet to be reported. The authors present a 21-year old woman with multifocal epithelioid hemangioendothelioma (EH) treated by a combination of surgical excision, chemotherapy and four RF ablations.
Follow-up radiographs of the RF-treated sites reveal no evidence of recurrent disease 71, 58, 49 and 33 months, respectively, after treatment.
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Blister cells -These are characteristic primitive vascular structures resembling blisters or signet ring-like structures.
CD31-An immunohistochemical stain which is very specific for blood vessel differentiation.
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