oral pathology Editor: LEWIS R. EVERSOLE,
DDS, MSD, MA
Oral Diagnosis, Medicine & Pathology School of Dentistry 53-058 UCLA Health Sciences Center Los Angeles, California 90024
Epithelioid angiosarcoma of the maxilla A case report and review of the literature Paul D. Freedman, DDS,a and Stanley M. Kerpel DDS,b Flushing, N.Y. BOOTH MEMORIAL
MEDICAL
CENTER AND ORAL PATHOLOGY
LABORATORY,
INC.
Epithelioid angiosarcoma is a rare vascular tumor composed of a proliferation of cytologically malignant epithelioid endothelial cells. These tumors are fully malignant and can pursue a rapidly progressive course. A case of primary epithelioid angiosarcoma of the maxilla is presented. Also discussed is a review of the literature with emphasis on the concept of epithelioid endothelial cell tumors. (ORAL SURG ORAL MED ORAL PATHOL 1992;74:319-25)
E
pithelioid angiosarcoma (EA) is a rare vascular tumor composed of a proliferation of cytologically malignant epithelioid endothelial cells.lm5Tumors composedof benign epithelioid endothelial cells were first described by Rosai et a1.6in 1979. They used the term histiocytoid hemangioma to delineate a spectrum of vascular lesions that had in common the histiocytoid appearance of the proliferative endothelial cells. Several years later, Weiss and Enzinger identified a new variant of histiocytoid hemangioma, the epithelioid hemangioendothelioma. Weiss and Enzinger preferred the term epithelioid rather than histiocytoid to stress the epithelial appearance of these unusual endothelial cells. Since that time, additional publications have described the various subtypes of epithelioid endothelial cell tumors.7-9 Most epithelioid endothelial cell tumors are benign in their biologic behavior (epithelioid hemangioma) or of intermediate behavior between hemangioma and angiosarcoma (epithelioid hemangioendothelioma). Rare tumors that were composed of malignant epi-
aAssistant Director, Section of Oral Pathology. bAttending, Section of Oral Pathology. 7/14/38155
thelioid endothelial cells have been described.lM5According to Weiss et al., ’ these tumors, which have been designated epithelioid angiosarcoma, are fully
malignant and can pursue a rapidly progressive course. This article presents a case of central epithelioid angiosarcoma of the maxilla. We believe this to be the first description of this tumor located centrally in the jawbones. CASE REPORT
A 32-year-oldhomosexualmanconsultedanoral surgeon about a painless swelling of the left side of the hard palate that had increased in size over the previous few weeks.Oral examination revealed a marked expansion of the molar region of the left area of the maxilla. The second molar was quite mobile. Radiographs of the area demonstrated a large radiolucency around the roots of the second molar with obliteration of the floor of the maxillary sinus (Fig. 1). No root resorption was noted on the periapical film, but extension of the radiolucency to the distal surface of the second premolar was seen. Surgical exploration revealed a brown soft-tissue tumor that replaced the left maxillary alveolus and extended into the maxillary sinus. The extent of the lesion could not be determined at the time of the biopsy. The gross pathologic specimen consisted of multiple 319
320
Freedman and Kerpel
ORAL Swti
ORAL MUI ORAL PATHOL
September 1992
Fig. 1. Portion of panoramic radiograph. Note large radiolucency around roots of maxillary left second molar that extends to the distal of second premolar.
brown fragments of soft tissue that measured2.0 x 0.8 X0.6 cm. The microscopic sections revealed fragments of fibrous connective tissue that contained an infiltrating tumor composed of sheets of atypical polyhedral cells that exhibited large vesicular nuclei with prominent nucleoli set in abundant, somewhat fibrillar, deeply eosinophilic cytoplasm (Figs. 2 and 3). Extensive portions of the tumor showed variably sized, irregularly shaped vascular channels lined with similar cells. In many areas the endothelial cells that lined the vesselsprotruded into the lumen and created a tombstone appearance (Fig. 4). Elsewhere the cells appeared to pile-up on one another, sometimes bridging the vascular lumen (Fig. 5). Scattered tumor cells demonstrated intracytoplasmic vacuoles that pushed the nucleus to the side and created a signet ring appearance (Fig. 6). These intracytoplasmic vacuoles were suggestive of primitive lumen formation, a fairly common occurrence in tumors of epithelioid endothelial cell origin.‘, 6,’ Marked cellular pleomorphism, nuclear irregularity, and hyperchromaticity were evident throughout the tumor. Numerous typical and atypical mitotic figures were also seen,even in the cells that lined the blood vessels(Fig. 7). In small areas, parallel columns of atypical spindle-shaped cells were admixed with large numbers of extravasated erythrocytes (Fig. 8). Large zones of necrosis were also present. Immunostains for factor VIII-related antigen and ulex europeusrevealed small numbers of tumor cells that exhibited intracytoplasmic staining. Electron microscopic studies demonstrated cells that contained abundant intracytoplasmic, whorled intermediate filaments. Interdigitating, occasional tight junctions, as well as numerous pinocytotic vesicles, were also evident. The microscopic features of an infiltrative tumor composedof solid sheetsand vascular channels of poorly differ-
entiated epithelioid endothelial cells were consistent with the diagnosis of EA.‘-j The patient was treated with a resection of the left side of the maxilla. The tumor was found to be present in the maxillary sinus with infiltration through the hard palate that led to ulceration of the palatal mucosa.The tumor was present at the lateral soft-tissue surgical margin and close to the medial palatal margin. The patient received postoperative radiotherapy. At follow-up 18 months from the time of treatment, the patient was alive with no evidence of disease. DISCUSSION
In 1979 Rosai et a1.6introduced the term histiocytoid hemangioma to describe several different benign vascular lesions, all of which demonstrated exuberant proliferation of histiocytoid endothelial cells. These cells contained large vesicular nuclei that exhibited thin continuous lines across the entire short axis of the
nucleus. Prominent nucleoli were often present. The nuclei were set in abundant, eosinophilic,
slightly
fibrillar cytoplasm. Weiss and Enzinger subsequently described a tumor designated epithelioid hemangioendothelioma that they believed belonged to the spectrum of histiocytoid hemangiomas. The term epithelioid rather than histiocytoid was used to stressthe epithelial appearance of the proliferative endothelial cells.7These unusual epithelioid cells have been confirmed as endothelial in origin by ultrastructural studies that reveal basal lamina, pinocytotic vesicles, and the variable presence of Weibel-Palade bodies. Immunohistochemical stains have demonstrated factor VIII-
related antigen in many of these cells.’
Volume 74 Number 3
Epithelioid
angiosarcoma of the maxilla
321
Fig. 2. Photomicrograph of solid sheetsof poorly differentiated polyhedral cells. (Hematoxylin-eosin stain; original magnification X25.)
Fig. 3. Photomicrograph of small groups of polyhedral cells that contain vesicular nuclei with prominent nucleoli set in abundant cytoplasm. (Hematoxylin-eosin stain; original magnification X430.)
The classification of epithelioid endothelial cell tumorsl (histiocytoid hemangioma$) includes (1) epithelioid hemangioma (EH), (2) epithelioid hemangioendothelioma (EHE), and (3) epithelioid angiosarcoma (EA). Many different entities are encompassed by these three categories. EH is a benign tumor that includes lesions previously termed angiolymphoid hyperplasia with eosinophilia’ and pseudo or atypical pyogenic granuloma. EH develops in adults between the agesof 20 and 50 and usually occurs in the superficial dermis of the head and neck, particularly near the ear. Histologically, EH is a circumscribed and lobulated tumor
composed of a large central vessel surrounded by well-formed capillaries lined with epithelioid endothelial cells. The cells also form solid islands and demonstrate intracytoplasmic vacuoles.8 Variable numbers of eosinophils and clusters of lymphocytes arranged in germinal centers are usually present. EHE7 is often mistaken for a carcinoma becauseof the epithelial appearance of the proliferative endothelial cells. Its biologic behavior is between that of a hemangioma and an angiosarcoma. Although the tumor is seenin all age groups, the peak incidence is in the secondand third decades.EHE occurs most often in the soft tissues, but examples have been reported in
322
Freedman and Kerpel
OR.\1
St KC, OR,\t
kit
II ORAl
PATHOI
September 1992
Fig. 4. Photomicrograph of blood vessel lined with epithelioid endothelial cells that protrude into vascular lumen and create a tombstone effect. (Hematoxylin-eosin stain; original magnification x430.)
Fig. 5. Photomicrograph of large blood vessel that exhibits piling up of the endothelial cells that causes bridging of the vascular lumen. (Hematoxylin-eosin stain; original magnification x430.)
bone12-16(where it is often multifocal), in the lung’ (as the intravascular bronchioloalveolar tumor), and in the liver’ (where it was previously termed sclerosing cholangiocarcinoma). In EHE, vascular differentiation is limited. It is composed of epithelioid endothelial cells that exhibit intracytoplasmic vacuoles that are thought to represent primitive vascular lumina.7 The cells are usually set in a highly myxoid or hyalinized stroma. Little cellular atypia or mitotic activity is seen. Treatment consists of complete local excision. In some EHE, however, significant cellular atypia, mitotic activity, and necrosis are evident. Such features are correlated
with a more aggressive course. These atypical variants should be treated by radical excision and adjuvant chemotherapy.’ In their study of EHE, Weiss et al.’ observed that local recurrence developed in 13% of the cases and metastasis to regional lymph nodes, lung, liver, and bone occurred in 31%. Fewer than half of the patients in whom metastases developed died of the disease. EA is the least common type of epithelioid endothelial cell tumor.le5 It has been described in the skin233, the thyroid gland,4 and the deep soft tissues.5 EA is made up of solid sheets of rounded, glassy, eosinophilic endothelial cells. Vascular differentia-
Volume 74 Number 3
Epithelioid
angiosarcoma of the maxilla
323
Fig. 6. Photomicrograph of scattered epithelioid endothelial cells with intracytoplasmic lumen formation that creates a signet ring appearance. (Hematoxylin-eosin stain; original magnification X430.)
Fig. 7. Photomicrograph of blood vessellined with atypical epithelioid endothelial cells that demonstrate several atypical mitotic figures. (Hematoxylin-eosin stain; original magnification x430.)
tion is expressedby irregular vascular channels lined with epithelioid endothelial cells that in areas pile up on one another. These tumors display more nuclear pleomorphism and mitotic activity than EHE and frequently show areas of necrosis.‘, 5 Marrogi et a1.3reported three casesof cutaneous EA, two of which were originally misdiagnosed as poorly differentiated squamous cell carcinoma, All of the patients had metastasesto such sites as bone, viscera, and lymph nodes.Perez-Atayde et al.’ described EA of the scalp in a 69-year-old man who had metastasesto lymph nodesand bone and died of the disease. Eusebi et a1.4presented four cases of EA of the
thyroid, all of which displayed immunoreactivity for keratin and factor VIII-related antigen. They suggested that the keratin positivity of the endothelial cells in EA is “simply an expression of potentiality expressedby most other types of soft tissue tumors.” Fletcher et al.5 have reported eight casesof EA of the deep soft tissues.Widely disseminated metastasesdeveloped in the six cases that were available for follow-up; two patients died of their disease.All of the tumors demonstrated pankeratin and factor VIII-related antigen positivity. As is seenfrom the reported cases, EA can recur, metastasize, and lead to the death of the patient.
324
Freedman and Kerpel
Fig. 8. Photomicrograph of parallel columns of spindle-shaped cells admixed with extravasated red blood cells. (Hematoxylin-eosin stain; original magnification x430.1
In the case reported here, the histopathologic appearance was that of a malignant tumor composed of neoplastic epithelioid endothelial cells. Certain microscopic features of the tumor, as well as the patient’s HIV-risk behavior, led us to consider two other diagnoses in our original differential diagnosis. The zones of atypical spindle-shaped cells admixed with extravasated red blood cells suggested the diagnosis of Kaposi’s sarcoma. This was ruled out because of the epithelioid appearance of the endothelial cells and the extent of necrosis present, neither of which is seen in Kaposi’s sarcoma. Another alternative diagnosis was bacillary angiomatosis (BA), which was first identified by Cockerell et al.‘O in 1987. This unusual vascular proliferation has been described only in HIV-infected persons. BA, which apparently is not a true neoplasm, can be treated adequately with antibiotics. Bacteria similar to the cat-scratch disease bacilli have been identified in BA with Warthin-Starry staining.” A WarthinStarry stain performed in the present case was negative for bacterial colonies. In addition, two consecutive HIV-antibody tests performed on the patient after the diagnosis of EA was established were negative. These results are additional support for our exclusion of both the diagnoses of Kaposi’s sarcoma and BA. The diagnosis of EA was based on the proliferation of sheets of epithelioid endothelial cells that exhibited marked cellular atypia, numerous irregular vascular channels lined with these atypical cells, and extensive zones of necrosis. Although more aggressive variants of EHE show some cellular atypia, we believe that the
degree of atypia present in this case, the relatively small number of cells that exhibit intracytoplasmic lumen formation, the presence of numerous irregularly shaped vascular channels, and the lack of a myxoid or hyalinized stroma support the diagnosis of EA. We thank Dr. Gwen Cohen Brown and Dr. Victoria H. Freedman for their help in reviewing this manuscript. REFERENCES 1. Weiss SW, Ishak KG, Dail DH, Sweet DE, Enzinger FM. Epithelioid hemangioendothelioma and related lesions. Semin Diagn Pathol 1986;3:259-87. 2. Perez-Atayde AR, Achenbach H, Lack EE. High grade epithelioid angiosarcoma of the scalp: an immunohistochemical and ultrastructural study. Am J Dermatopathol 1986;8:41 l-8. 3. Marrogi AJ, Hunt SJ, Santa Cruz DJ. Cutaneous epithelioid angiosarcoma. Am J Dermatopathol 1990;12:350-6. 4. Eusebi V, Carcangui ML, Dina R, Rosai J. Keratin-positive epithelioid angiosarcoma of the thyroid: a report of four cases. Am J Surg Path01 1990;14:737-47. 5. Fletcher CDM. Beham A, Bekir S, Clarke AMT, Marley NJE. Epithelioid angiosarcoma of deep soft tissue: a distinctive tumor readily mistaken for an epithelial neoplasm. Am J Surg Path01 1991;15:915-24. 6. Rosai J, Gold J, Landy R. The histiocytoid hemangiomas: a unifying concept embracing several previously described entities of skin, soft tissue, large vessels, bone, and heart. Hum Pathol 1979;10:707-30. 7. Weiss SW, Enzinger FM. Epithelioid hemangioendothelioma: a vascular tumor often mistaken for carcinoma. Cancer 1982;50:970-8 1. 8. Rosai J. Angiolymphoid hyperplasia with eosinophilia of the skin: its nosological position in the spectrum of histiocytoid hemangioma. Am J Dermdtopathol 1982;4:175-84. 9. Moran WJ, Dobelman TJ, Bostwick DG. Epithelioid hemangioendothelioma (histiocytoid hemangioma) of the palate. Laryngoscope 1987;97:1299-302. 10. Cockerell CJ, Webster GF, Whitlow MA, Friedman-Kien AE.
Volume 74 Number 3 Epithelioid angiomatosis: a distinct vascular disorder in patients with theacquired immunodeficiency syndromeor AIDSrelated complex. Lancet 1987;2:654-6. 11. LeBoit PE, Berger TG, Egbert BM, Beckstead JH, Yen TSB, Stoler MH. Bacillary angiomatosis: the histopathology and differential diagnosis of a pseudoneoplastic infection in patients with human immunodeficiency virus disease.Am J Surg Path01 1989;13:909-20. 12. Tsunevoshi M. Dorfman HD. Bauer TW. Enithelioid hemangioendothelioma of bone: a clininopatholog& ultrastructural and immunohistochemical study. Am J Surg Path01 1986; 10:754-64. 13. Mirra JM, Kameda N. Myxoid angioblastomatosis of bones: a case report of a rare, multifocal entity with light, ultramicroscopic and immunopathologic correlation. Am J Surg Path01 1985;9:450-8. 14. Cone RO, Hudkins P, Nguyen V, Merriwether WA. Histiocy-
Epithelioid angiosarcoma of the maxilla
325
toid hemangioma of bone: a benign lesion which may mimic angiosarcoma-report of case and review of literature. Skeletal Radio1 1983;10:165-9. 15. Maruyama N, Kumagai Y, Ishida Y, et al. Epithelioid hemangioendothelioma of the bone tissue. Virchows Arch [A] 1985;407:159-65. 16. Volpe R, Carbone A, Manconi R, Santi L. Hemangioendothelioma of bone: a report of an unusual case with lymph node metastasis. Path01Res Pratt 1985:180:521-5. Reprint requests:
Paul D. Freeman, DDS Section of Oral Pathology Booth Memorial Medical Center 56-45 Main Street Flushing, NY 11355
DDS, MSD, MA
Oral Diagnosis, Medicine & Pathology School of Dentistry 53-058 UCLA Health Sciences Center Los Angeles, California 90024
Epithelioid angiosarcoma of the maxilla A case report and review of the literature Paul D. Freedman, DDS,a and Stanley M. Kerpel DDS,b Flushing, N.Y. BOOTH MEMORIAL
MEDICAL
CENTER AND ORAL PATHOLOGY
LABORATORY,
INC.
Epithelioid angiosarcoma is a rare vascular tumor composed of a proliferation of cytologically malignant epithelioid endothelial cells. These tumors are fully malignant and can pursue a rapidly progressive course. A case of primary epithelioid angiosarcoma of the maxilla is presented. Also discussed is a review of the literature with emphasis on the concept of epithelioid endothelial cell tumors. (ORAL SURG ORAL MED ORAL PATHOL 1992;74:319-25)
E
pithelioid angiosarcoma (EA) is a rare vascular tumor composed of a proliferation of cytologically malignant epithelioid endothelial cells.lm5Tumors composedof benign epithelioid endothelial cells were first described by Rosai et a1.6in 1979. They used the term histiocytoid hemangioma to delineate a spectrum of vascular lesions that had in common the histiocytoid appearance of the proliferative endothelial cells. Several years later, Weiss and Enzinger identified a new variant of histiocytoid hemangioma, the epithelioid hemangioendothelioma. Weiss and Enzinger preferred the term epithelioid rather than histiocytoid to stress the epithelial appearance of these unusual endothelial cells. Since that time, additional publications have described the various subtypes of epithelioid endothelial cell tumors.7-9 Most epithelioid endothelial cell tumors are benign in their biologic behavior (epithelioid hemangioma) or of intermediate behavior between hemangioma and angiosarcoma (epithelioid hemangioendothelioma). Rare tumors that were composed of malignant epi-
aAssistant Director, Section of Oral Pathology. bAttending, Section of Oral Pathology. 7/14/38155
thelioid endothelial cells have been described.lM5According to Weiss et al., ’ these tumors, which have been designated epithelioid angiosarcoma, are fully
malignant and can pursue a rapidly progressive course. This article presents a case of central epithelioid angiosarcoma of the maxilla. We believe this to be the first description of this tumor located centrally in the jawbones. CASE REPORT
A 32-year-oldhomosexualmanconsultedanoral surgeon about a painless swelling of the left side of the hard palate that had increased in size over the previous few weeks.Oral examination revealed a marked expansion of the molar region of the left area of the maxilla. The second molar was quite mobile. Radiographs of the area demonstrated a large radiolucency around the roots of the second molar with obliteration of the floor of the maxillary sinus (Fig. 1). No root resorption was noted on the periapical film, but extension of the radiolucency to the distal surface of the second premolar was seen. Surgical exploration revealed a brown soft-tissue tumor that replaced the left maxillary alveolus and extended into the maxillary sinus. The extent of the lesion could not be determined at the time of the biopsy. The gross pathologic specimen consisted of multiple 319
320
Freedman and Kerpel
ORAL Swti
ORAL MUI ORAL PATHOL
September 1992
Fig. 1. Portion of panoramic radiograph. Note large radiolucency around roots of maxillary left second molar that extends to the distal of second premolar.
brown fragments of soft tissue that measured2.0 x 0.8 X0.6 cm. The microscopic sections revealed fragments of fibrous connective tissue that contained an infiltrating tumor composed of sheets of atypical polyhedral cells that exhibited large vesicular nuclei with prominent nucleoli set in abundant, somewhat fibrillar, deeply eosinophilic cytoplasm (Figs. 2 and 3). Extensive portions of the tumor showed variably sized, irregularly shaped vascular channels lined with similar cells. In many areas the endothelial cells that lined the vesselsprotruded into the lumen and created a tombstone appearance (Fig. 4). Elsewhere the cells appeared to pile-up on one another, sometimes bridging the vascular lumen (Fig. 5). Scattered tumor cells demonstrated intracytoplasmic vacuoles that pushed the nucleus to the side and created a signet ring appearance (Fig. 6). These intracytoplasmic vacuoles were suggestive of primitive lumen formation, a fairly common occurrence in tumors of epithelioid endothelial cell origin.‘, 6,’ Marked cellular pleomorphism, nuclear irregularity, and hyperchromaticity were evident throughout the tumor. Numerous typical and atypical mitotic figures were also seen,even in the cells that lined the blood vessels(Fig. 7). In small areas, parallel columns of atypical spindle-shaped cells were admixed with large numbers of extravasated erythrocytes (Fig. 8). Large zones of necrosis were also present. Immunostains for factor VIII-related antigen and ulex europeusrevealed small numbers of tumor cells that exhibited intracytoplasmic staining. Electron microscopic studies demonstrated cells that contained abundant intracytoplasmic, whorled intermediate filaments. Interdigitating, occasional tight junctions, as well as numerous pinocytotic vesicles, were also evident. The microscopic features of an infiltrative tumor composedof solid sheetsand vascular channels of poorly differ-
entiated epithelioid endothelial cells were consistent with the diagnosis of EA.‘-j The patient was treated with a resection of the left side of the maxilla. The tumor was found to be present in the maxillary sinus with infiltration through the hard palate that led to ulceration of the palatal mucosa.The tumor was present at the lateral soft-tissue surgical margin and close to the medial palatal margin. The patient received postoperative radiotherapy. At follow-up 18 months from the time of treatment, the patient was alive with no evidence of disease. DISCUSSION
In 1979 Rosai et a1.6introduced the term histiocytoid hemangioma to describe several different benign vascular lesions, all of which demonstrated exuberant proliferation of histiocytoid endothelial cells. These cells contained large vesicular nuclei that exhibited thin continuous lines across the entire short axis of the
nucleus. Prominent nucleoli were often present. The nuclei were set in abundant, eosinophilic,
slightly
fibrillar cytoplasm. Weiss and Enzinger subsequently described a tumor designated epithelioid hemangioendothelioma that they believed belonged to the spectrum of histiocytoid hemangiomas. The term epithelioid rather than histiocytoid was used to stressthe epithelial appearance of the proliferative endothelial cells.7These unusual epithelioid cells have been confirmed as endothelial in origin by ultrastructural studies that reveal basal lamina, pinocytotic vesicles, and the variable presence of Weibel-Palade bodies. Immunohistochemical stains have demonstrated factor VIII-
related antigen in many of these cells.’
Volume 74 Number 3
Epithelioid
angiosarcoma of the maxilla
321
Fig. 2. Photomicrograph of solid sheetsof poorly differentiated polyhedral cells. (Hematoxylin-eosin stain; original magnification X25.)
Fig. 3. Photomicrograph of small groups of polyhedral cells that contain vesicular nuclei with prominent nucleoli set in abundant cytoplasm. (Hematoxylin-eosin stain; original magnification X430.)
The classification of epithelioid endothelial cell tumorsl (histiocytoid hemangioma$) includes (1) epithelioid hemangioma (EH), (2) epithelioid hemangioendothelioma (EHE), and (3) epithelioid angiosarcoma (EA). Many different entities are encompassed by these three categories. EH is a benign tumor that includes lesions previously termed angiolymphoid hyperplasia with eosinophilia’ and pseudo or atypical pyogenic granuloma. EH develops in adults between the agesof 20 and 50 and usually occurs in the superficial dermis of the head and neck, particularly near the ear. Histologically, EH is a circumscribed and lobulated tumor
composed of a large central vessel surrounded by well-formed capillaries lined with epithelioid endothelial cells. The cells also form solid islands and demonstrate intracytoplasmic vacuoles.8 Variable numbers of eosinophils and clusters of lymphocytes arranged in germinal centers are usually present. EHE7 is often mistaken for a carcinoma becauseof the epithelial appearance of the proliferative endothelial cells. Its biologic behavior is between that of a hemangioma and an angiosarcoma. Although the tumor is seenin all age groups, the peak incidence is in the secondand third decades.EHE occurs most often in the soft tissues, but examples have been reported in
322
Freedman and Kerpel
OR.\1
St KC, OR,\t
kit
II ORAl
PATHOI
September 1992
Fig. 4. Photomicrograph of blood vessel lined with epithelioid endothelial cells that protrude into vascular lumen and create a tombstone effect. (Hematoxylin-eosin stain; original magnification x430.)
Fig. 5. Photomicrograph of large blood vessel that exhibits piling up of the endothelial cells that causes bridging of the vascular lumen. (Hematoxylin-eosin stain; original magnification x430.)
bone12-16(where it is often multifocal), in the lung’ (as the intravascular bronchioloalveolar tumor), and in the liver’ (where it was previously termed sclerosing cholangiocarcinoma). In EHE, vascular differentiation is limited. It is composed of epithelioid endothelial cells that exhibit intracytoplasmic vacuoles that are thought to represent primitive vascular lumina.7 The cells are usually set in a highly myxoid or hyalinized stroma. Little cellular atypia or mitotic activity is seen. Treatment consists of complete local excision. In some EHE, however, significant cellular atypia, mitotic activity, and necrosis are evident. Such features are correlated
with a more aggressive course. These atypical variants should be treated by radical excision and adjuvant chemotherapy.’ In their study of EHE, Weiss et al.’ observed that local recurrence developed in 13% of the cases and metastasis to regional lymph nodes, lung, liver, and bone occurred in 31%. Fewer than half of the patients in whom metastases developed died of the disease. EA is the least common type of epithelioid endothelial cell tumor.le5 It has been described in the skin233, the thyroid gland,4 and the deep soft tissues.5 EA is made up of solid sheets of rounded, glassy, eosinophilic endothelial cells. Vascular differentia-
Volume 74 Number 3
Epithelioid
angiosarcoma of the maxilla
323
Fig. 6. Photomicrograph of scattered epithelioid endothelial cells with intracytoplasmic lumen formation that creates a signet ring appearance. (Hematoxylin-eosin stain; original magnification X430.)
Fig. 7. Photomicrograph of blood vessellined with atypical epithelioid endothelial cells that demonstrate several atypical mitotic figures. (Hematoxylin-eosin stain; original magnification x430.)
tion is expressedby irregular vascular channels lined with epithelioid endothelial cells that in areas pile up on one another. These tumors display more nuclear pleomorphism and mitotic activity than EHE and frequently show areas of necrosis.‘, 5 Marrogi et a1.3reported three casesof cutaneous EA, two of which were originally misdiagnosed as poorly differentiated squamous cell carcinoma, All of the patients had metastasesto such sites as bone, viscera, and lymph nodes.Perez-Atayde et al.’ described EA of the scalp in a 69-year-old man who had metastasesto lymph nodesand bone and died of the disease. Eusebi et a1.4presented four cases of EA of the
thyroid, all of which displayed immunoreactivity for keratin and factor VIII-related antigen. They suggested that the keratin positivity of the endothelial cells in EA is “simply an expression of potentiality expressedby most other types of soft tissue tumors.” Fletcher et al.5 have reported eight casesof EA of the deep soft tissues.Widely disseminated metastasesdeveloped in the six cases that were available for follow-up; two patients died of their disease.All of the tumors demonstrated pankeratin and factor VIII-related antigen positivity. As is seenfrom the reported cases, EA can recur, metastasize, and lead to the death of the patient.
324
Freedman and Kerpel
Fig. 8. Photomicrograph of parallel columns of spindle-shaped cells admixed with extravasated red blood cells. (Hematoxylin-eosin stain; original magnification x430.1
In the case reported here, the histopathologic appearance was that of a malignant tumor composed of neoplastic epithelioid endothelial cells. Certain microscopic features of the tumor, as well as the patient’s HIV-risk behavior, led us to consider two other diagnoses in our original differential diagnosis. The zones of atypical spindle-shaped cells admixed with extravasated red blood cells suggested the diagnosis of Kaposi’s sarcoma. This was ruled out because of the epithelioid appearance of the endothelial cells and the extent of necrosis present, neither of which is seen in Kaposi’s sarcoma. Another alternative diagnosis was bacillary angiomatosis (BA), which was first identified by Cockerell et al.‘O in 1987. This unusual vascular proliferation has been described only in HIV-infected persons. BA, which apparently is not a true neoplasm, can be treated adequately with antibiotics. Bacteria similar to the cat-scratch disease bacilli have been identified in BA with Warthin-Starry staining.” A WarthinStarry stain performed in the present case was negative for bacterial colonies. In addition, two consecutive HIV-antibody tests performed on the patient after the diagnosis of EA was established were negative. These results are additional support for our exclusion of both the diagnoses of Kaposi’s sarcoma and BA. The diagnosis of EA was based on the proliferation of sheets of epithelioid endothelial cells that exhibited marked cellular atypia, numerous irregular vascular channels lined with these atypical cells, and extensive zones of necrosis. Although more aggressive variants of EHE show some cellular atypia, we believe that the
degree of atypia present in this case, the relatively small number of cells that exhibit intracytoplasmic lumen formation, the presence of numerous irregularly shaped vascular channels, and the lack of a myxoid or hyalinized stroma support the diagnosis of EA. We thank Dr. Gwen Cohen Brown and Dr. Victoria H. Freedman for their help in reviewing this manuscript. REFERENCES 1. Weiss SW, Ishak KG, Dail DH, Sweet DE, Enzinger FM. Epithelioid hemangioendothelioma and related lesions. Semin Diagn Pathol 1986;3:259-87. 2. Perez-Atayde AR, Achenbach H, Lack EE. High grade epithelioid angiosarcoma of the scalp: an immunohistochemical and ultrastructural study. Am J Dermatopathol 1986;8:41 l-8. 3. Marrogi AJ, Hunt SJ, Santa Cruz DJ. Cutaneous epithelioid angiosarcoma. Am J Dermatopathol 1990;12:350-6. 4. Eusebi V, Carcangui ML, Dina R, Rosai J. Keratin-positive epithelioid angiosarcoma of the thyroid: a report of four cases. Am J Surg Path01 1990;14:737-47. 5. Fletcher CDM. Beham A, Bekir S, Clarke AMT, Marley NJE. Epithelioid angiosarcoma of deep soft tissue: a distinctive tumor readily mistaken for an epithelial neoplasm. Am J Surg Path01 1991;15:915-24. 6. Rosai J, Gold J, Landy R. The histiocytoid hemangiomas: a unifying concept embracing several previously described entities of skin, soft tissue, large vessels, bone, and heart. Hum Pathol 1979;10:707-30. 7. Weiss SW, Enzinger FM. Epithelioid hemangioendothelioma: a vascular tumor often mistaken for carcinoma. Cancer 1982;50:970-8 1. 8. Rosai J. Angiolymphoid hyperplasia with eosinophilia of the skin: its nosological position in the spectrum of histiocytoid hemangioma. Am J Dermdtopathol 1982;4:175-84. 9. Moran WJ, Dobelman TJ, Bostwick DG. Epithelioid hemangioendothelioma (histiocytoid hemangioma) of the palate. Laryngoscope 1987;97:1299-302. 10. Cockerell CJ, Webster GF, Whitlow MA, Friedman-Kien AE.
Volume 74 Number 3 Epithelioid angiomatosis: a distinct vascular disorder in patients with theacquired immunodeficiency syndromeor AIDSrelated complex. Lancet 1987;2:654-6. 11. LeBoit PE, Berger TG, Egbert BM, Beckstead JH, Yen TSB, Stoler MH. Bacillary angiomatosis: the histopathology and differential diagnosis of a pseudoneoplastic infection in patients with human immunodeficiency virus disease.Am J Surg Path01 1989;13:909-20. 12. Tsunevoshi M. Dorfman HD. Bauer TW. Enithelioid hemangioendothelioma of bone: a clininopatholog& ultrastructural and immunohistochemical study. Am J Surg Path01 1986; 10:754-64. 13. Mirra JM, Kameda N. Myxoid angioblastomatosis of bones: a case report of a rare, multifocal entity with light, ultramicroscopic and immunopathologic correlation. Am J Surg Path01 1985;9:450-8. 14. Cone RO, Hudkins P, Nguyen V, Merriwether WA. Histiocy-
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Paul D. Freeman, DDS Section of Oral Pathology Booth Memorial Medical Center 56-45 Main Street Flushing, NY 11355
