Vascular Tumor Of Intermediate Malignancy Research Articles

Intracranial kaposiform hemangioendothelioma presenting as epistaxis: a rare case report with review of literature

Kaposiform hemangioendothelioma (KHE) is a rare vascular tumor of intermediate malignancy with tendency for local invasion and recurrence. The tumor almost exclusively occurs in children, especially in infants. Intracranial KHE are extremely rare with only two cases reported in the literature. We report the clinical and pathological features of this rare tumor arising from basitemporal region in a 21-month child. Our case did not present with Kasabach-Merritt phenomenon. Histopathological examination confirmed the diagnosis of KHE. KHE should be considered in the differential diagnosis of intracranial extra-axial neoplasm in children, and histopathological examination plays an important role in distinguishing KHE from its morphologic mimics. It is essential to diagnose KHE due to its locally aggressive nature.

Intravascular Lobular Capillary Hemangioma (Intravascular Pyogenic Granuloma): A Clinicopathologic Study of 40 Cases.

Intravascular lobular capillary hemangioma (ILCH), or intravascular pyogenic granuloma, is relatively rare and likely underrecognized. We reviewed all ILCH cases from our institution confirmed pathologically from 2006 to 2019. Immunostains for smooth muscle actin and Wilms tumor 1 were performed on all cases and prior immunohistochemical stains were reviewed. Forty cases were identified (22 females; 18 males) with a median age of 53 years (range: 13 to 85 y). Clinically, all were well-circumscribed, stable to slow-growing raised/cystic skin lesions ranging from 1 to 40 mm. Most were located on the upper extremities (n=18), followed by head and neck (n=16). Vascular lesions were suspected clinically in one third. Of the consultation cases, provided differential diagnoses included Masson tumor, other hemangiomas, and vascular tumors of intermediate malignancy. The common histologic features were a well-circumscribed, lobular proliferation of closely packed capillaries with central ectatic vessels. The surrounding vascular wall was well-visualized in only half of the cases. About 30% of the cases were mitotically active (mean: 8 to 9 mitotic figures/10 HPFs), and 34% showed mild to moderate cytologic atypia. Hobnail features were present in 40% of cases. All cases were diffusely and strongly positive for Wilms tumor 1. Smooth muscle actin stains highlighted pericytes in all cases. Of the 20 cases with clinical follow-up (median: 40 mo), none recurred. ILCH commonly involves the upper extremities and a vascular tumor is suspected clinically in the minority. Mitotic activity and cytologic atypia, when present, can cause confusion with more aggressive vascular tumors. Recognition of this entity is essential as it is a benign lesion with no risk of recurrence following limited local excision.

A rare case of pseudomyogenic hemangioendothelioma (PHE)/epithelioid sarcoma-like hemangioendothelioma (ES-H) of the breast first misdiagnosed as metaplastic carcinoma by FNAB and review of the literature

AimsPseudomyogenic hemangioendothelioma (PHE)/epithelioid sarcoma-like hemangioendothelioma (ES-H) is a rare vascular tumor of intermediate malignancy that commonly occurs in soft tissue of distal extremities of young adults. PHE typically has a multifocal presentation and can involve several tissue planes, including the dermis, subcutis, muscle and bone.Methods and resultsWe present here a unique case of PHE/ESH that arose in the breast as well as a review of the published literature. The initial biopsy was interpreted as a metaplastic carcinoma. However, complete resection largely revealed plump epithelioid cells, and a more spindled cell component was also noted. The cells displayed abundant eosinophilic cytoplasm and central vesicular nuclei arranged in loose fascicles, with a mild, mixed acute and chronic inflammatory infiltrate. Overall, linear membranous staining of CD31 and lack of CD34 expression were highly suggestive of PHE. At the same time, FOSB immunoreactivity was observed, which supported PHE/ESH instead of metaplastic carcinoma. The patient has not shown recurrence in the half year follow up after total mastectomy.ConclusionTo our knowledge, this is the first report of breast involvement in this neoplasm. Recognition of its histopathological features and immunohistochemical reactivity will prevent misdiagnosis of breast lesions.

EXPRESSION OF VASCULAR ENDOTHELIAL GROWTH FACTOR (VEGF) IN HEMANGIOMAS AND INTERMEDIATE VASCULAR LESIONS

INTRODUCTION: Vascular tumors of intermediate malignancy encompass a group of tumors whose biologic potential is intermediate between hemangiomas and angiosarcomas. Angiogenesis is characterized by development of new blood vessels through the division or migration of pre-existing vasculature. VEGF deserves attention because it is associated with the stimulation of endothelial cell proliferation and vascular permeability and promotion of angiogenesis.OBJECTIVES: to evaluate the immunohistochemical expression of vascular endothelial growth factor (VEGF) in pyogenic granulomas,hemangiomas and intermediate vascular tumors (hemangioendotheliomas, hemangiopericytomas) and to highlight the possible role of VEGFin diagnosis of each of these tumorsMATERIALS AND METHODS: Immunohistochemical analysis of 20 cases of vascular and intermediate vascular tumors, with one section from each specimen (20 sections for VEGF antibody) and 5 control cases. Immunohistochemical staining was performed using a Labeled Strept-Avidin Biotin method (LSAB).RESULTS: Normal gingival tissue showed mild immunoreactivity for VEGF. All the examined cases showed strong positive expression for VEGF antibody, with different intensities.CONCLUSIONS: The marker VEGF was overexpressed in vascular and intermediate vascular tumors than normal gingival tissueKEYWORDS: Vascular tumors, Intermediate vascular tumors, Immunohistochemistry, VEGF.

Kaposiform hemangioendothelioma: a clinicopathologic analysis of 23 cases

Objective To further elucidate the clinical and pathologic features of retiform hemangioendothelioma (RH) and its clinical spectrum. Methods Eight cases of RH were reviewed. The clinicopathologic profiles, immunophenotypes and outcome data were investigated. Results All 8 cases occurred in females with a mean age at presentation of 40 years (range, 13-69 years). Five tumors arose in the skin of the head and neck region and lower extremities, two in the long bones and one in the spleen.Clinically, the patients presented with a slowly growing cutaneous plaque or subcutaneous nodule, pain of the upper arm, and dull pain and discomfort in the left hypochondrium respectively.Grossly, the tumor appeared as a non-encapsulated gray-yellowish to tan-brown mass with a mean diameter of 2.6 cm (range, 0.8-5.0 cm). On histology, it was composed of delicate branches of elongated vessels lined by a layer of hobnail or matchstick endothelium, exhibiting a retiform pattern with close resemblance of the normal rete testis.Cords or solid nests of epithelioid cells were noted adjacent to the well-formed vessels.In three cases, dilated vascular spaces with formation of intravascular papillary tufts were observed, features overlapping with Dabska tumor.There was usually marked lymphocytic infiltration in the stroma which was also hyalinized in some cases.One case had regional lymph node metastasis.By immunohistochemistry, all cases consistently expressed endothelial markers, including CD31(8/8), human coagulation factor Ⅷ (5/8), CD34 (5/7) and D2-40 (1/2). Two of six cases with follow-up information (18-67 months) developed local recurrences, but distant metastasis was not identified. Conclusions RH is a distinctive vascular tumor of adulthood characterized by retiform growth of vessels with striking hobnail endothelium.Although the tumor occurs predominantly in the skin, the long bones and the spleen can be occasionally affected. The presence of Dabska tumor-like areas in RH may suggest a morphologic continuum between these two entities, comprising the family of hobnail hemangioendothelioma.Familiarity with the characteristic features of this vascular tumor of intermediate malignancy will help in the differential diagnosis of vascular neoplasms with hobnail endothelium. Key words: Retiform hemangioendothelioma; Dabska tumor; Hobnail hemangioendothelioma; Immunohistochemistry

Epithelioid hemangioendotheliomas with TFE3 gene translocations are compossible with CAMTA1 gene rearrangements.

Epithelioid hemangioendotheliomas (EHEs) are vascular tumors of intermediate malignancy that can undergo high-grade malignant transformations. EHEs have been characterized by tumor-specific WW domain-containing transcription regulator 1(WWTR1)-calmodulin-binding transcription activator 1 (CAMTA1) translocations, and recently, a novel Yes-associated protein 1 (YAP1)-transcription factor E3 (TFE3) gene fusion was identified in EHEs. In this study, we examined the expression levels of TFE3 and CAMTA1 via immunohistochemical staining and identified chromosomal alterations using fluorescence in situ hybridization (FISH) assays and RT-PCR tests. Although all of the EHEs were CAMTA1-positive in immunohistochemical staining, only five out of 18 EHEs (27.78%) positively expressed nuclear TFE3. The five TFE3-positive EHEs exhibited TFE3 gene break-apart in FISH assays. YAP1-TFE3 gene fusions were confirmed by RT-PCR. Interestingly, we observed CAMTA1 gene break-apart in all of the five TFE3-positive EHEs via FISH assays, and four out of the five TFE3-positive EHEs exhibited WWTR1-CAMTA1 gene fusions via RT-PCR. These results indicate that these two chromosomal alterations are not mutually exclusive but compossible in EHEs. Finally, primary tumor sites in TFE3-positive EHEs consistently contained single masses (P = 0.0359) with larger sizes (P = 0.0550) compared to TFE3-negative EHEs. Similar to previous reports, we observed well-formed vessels more frequently in TFE3-positive EHEs than in TFE3-negative EHEs (P = 0.0441). In addition, TFE3-positive EHEs tended to more frequently demonstrate high-grade nuclear atypia (P = 0.0654) and hypercellularity (P=0.0987) than TFE3-negative EHEs. Thus, we have now established two clinically distinct subgroups of EHEs: TFE3-positive and TFE3-negative EHEs.

CAMTA1 immunostaining is not useful in differentiating epithelioid hemangioendothelioma from its potential mimickers.

Epithelioid hemangioendothelioma is a rare member of vascular tumors of intermediate malignancy. Recently, presence of t(1;3) translocation and WWTR1/CAMTA1 gene fusion, which enhances CAMTA1 expression, are found to be specific to this tumor. We investigated the CAMTA1 immune expression profile of epithelioid hemangioendothelioma and its potential mimickers using a commercially available CAMTA1 antibody. Standard whole sections from the formalin fixed, paraffin embedded blocks of 12 epithelioid hemangioendotheliomas, 10 angiosarcomas, 9 epithelioid sarcomas, 8 malignant melanomas, 8 signet ring carcinomas, 7 lobular carcinomas of breast, 2 epithelioid mesotheliomas, 2 rhabdoid tumors and 12 miscellaneous hemangiomas were immunostained for anti-CAMTA1 (ab64119, 1:200; Abcam) after pretreatment with citrate pH 6.0 for 20 minutes using Leica Bond detection kit with DAB chromogen. Strong nuclear CAMTA1 expression was scored for its extent as 'negative' ( < 5% positive), '+1' (5-25% positive), '2+' (25-50% positive) and '3+' ( > 50% positive). In 60 out of 70 cases (86%) either 2+ or 3+ strong nuclear staining was seen. Eighty-three % of epithelioid hemangioendotheliomas, 100% of angiosarcomas, 89% of epithelioid sarcomas, 89% of malignant melanomas, 63% of signet ring carcinomas, 71% of lobular carcinomas of breast, 100% of epithelioid mesotheliomas, 50% of rhabdoid tumors and 100% of hemangiomas were stained. Besides neurons, CAMTA1 expression was also observed in squamous epithelium, skin adnexa, breast lobules, prostate glands, bile ducts, colonic mucosa and gastric pits. Epithelioid hemangioendothelioma, its potential morphological mimickers and other benign or malignant vascular tumors showed strong and diffuse CAMTA1 expression, nullifying the potential use of CAMTA1 immunohistochemistry as an adjunct in the differential diagnosis.

Multifocal kaposiform hemangioendothelioma of soft tissue with bilateral pulmonary involvement in an adolescent.

Kaposiform hemangioendothelioma (KHE) is a rare, locally aggressive vascular tumor of intermediate malignancy with resemblance to Kaposi sarcoma. It occurs predominantly in pediatric age groups as a cutaneous lesion with focal infiltration into the adjacent soft tissue and bone. Although visceral involvement is very uncommon, several cases with bone, retroperitoneal, or mediastinal involvement have been described. KHE has been reported to occasionally occur in unusual sites such as the thymus, tonsils, larynx, paranasal sinuses, deltoid muscle, spleen, uterine cervix, thoracic spine, and even the breast. Multifocal KHE is an extremely rare entity with few reports available in the literature, none of which describes pulmonary involvement. Herein, we report a unique case of multifocal KHE in a 13-year-old boy presenting with a huge soft tissue mass in the upper extremity complicated by bilateral pulmonary nodules that developed into large, necrotic tumor masses.

Giant Cell Angioblastoma in an Adult: A Unique Presentation

Giant cell angioblastoma is a very rare, locally destructive vascular tumor of intermediate malignancy without metastatic potential. There are only a few cases reported in the literature exclusively in the soft tissue of children. For the first time, we report on an adult patient with a giant cell angioblastoma in the popliteal fossa. The therapy included tumor resection with favorable clinical, oncological and functional outcome. Due to its locally destructive nature, surgery remains the mainstay of treatment. Histologically, giant cell angioblastoma is comprised of nodular aggregates of histiocytoid cells arranged around bland angiomatous spaces. Because of insufficient available data in regard to the definition of the entity, diagnostic criteria and its biological potential, it is not included in the new World Health Organization classification of tumors of soft tissue and bone. The differential diagnosis includes plexiform fibrohistiocytic tumor, myofibroma and giant cell fibroblastoma.

Pulmonary Artery Pseudoaneurysm Caused by a Rare Vascular Tumor: Epithelioid Hemangioendothelioma

We present a case of a 58-year-old female with a rare vascular tumor of intermediate malignancy. The initial manifestation was a pseudoaneurysm caused by the rupture of the right pulmonary artery after tumor invasion. The diagnosis of epithelioid hemangioendothelioma was confirmed by the morphologic and immunocytochemical features after surgery. The patient recovered smoothly and there has been no evidence of local recurrence or metastasis during the 2 years of follow-up.

Hemangioendothelioma of soft tissue: Cytological dilemma in two cases at unusual sites

Hemangioendothelioma is a rare vascular tumor of intermediate malignancy. Cytologically, it can simulate a non-vascular malignant tumor. We report two cases of this tumor, which were misdiagnosed at cytology. In the first case, a 27-year-old man presented with an anterior abdominal wall tumor. Fine needle aspiration cytology (FNAC) of the tumor showed polygonal cells with vacuolated cytoplasm in clusters having moderate nuclear atypia in a background of necrosis. A diagnosis of metastatic carcinoma was made. The histological examination showed features of epithelioid hemangioendothelioma. In the second case, a 13-year-old female child presented with unilateral enlargement of the right tonsil. At ultrasound-guided FNAC, a diagnosis of, ‘small round cell tumor, could be consistent with alveolar rhabdomyosarcoma,’ was made. The histological examination showed features of papillary intralymphatic angioendothelioma (Dabska's tumor). We conclude that epithelioid hemangioendothelioma should be considered in the differential diagnosis of metastatic carcinoma and small round cell tumor even at unusual sites.

Efficacy of Pegylated Lyposomal Anthracyclines and of Intra-Arterial Carboplatin and Doxorubicin Combined with Local Hyperthermia in a Case of Malignant Endovascular Papillary Angioendothelioma

Malignant vascular tumors are exceedingly rare in childhood. Generally, their prognosis is dependent from a microscopically complete surgical resection. We observed the case of a 4-year-old boy affected by malignant endovascular papillary angioendothelioma, a rare vascular tumor of intermediate malignancy, involving all his left leg and partially the pelvis. Its very large size hampered any surgical intervention. However, we could demonstrate high sensitivity of the tumor to lyposomal anthracyclines and the child was eventually cured by the intra-arterial administration of carboplatin and doxorubicin coupled with local hyperthermia. This experience probably represents the first step toward an effective treatment of malignant vascular tumors in infancy.

Case report: MRI diagnosis of multifocal epithelioid hemangioendothelioma of the liver

Epitheloid hemangioendothelioma (EHE) is a vascular tumor of intermediate malignancy that arises in soft tissues, liver, lung, bone, and spleen.[1] The hepatic form of multifocal EHE is a rare, less aggressive, slowly progressive tumor, with malignant cells showing dendritic and epitheloid appearances.[2] The tumor is often misdiagnosed because of its nonspecific clinical manifestations and biochemical parameters, the prolonged clinical course, and variable imaging findings. In our patient, characteristic liver contour abnormalities on dynamic contrast-enhanced MRI and histopathological confirmation with appropriate immunohistochemical markers facilitated a correct diagnosis. The only definitive treatment is surgical resection or orthotopic liver transplantation after dedicated radiological and histopathological examination.[3–5]

Epithelioid Hemangioendothelioma Causing Acute Abdominal Aortic Obstruction and Bilateral Limb Ischemia

A 32-year-old man was admitted with sudden onset of bilateral leg pain. Acute abdominal aortic occlusion was revealed by means of examinations and the patient underwent an emergency operation. Both legs were revascularized following thrombectomy from bilateral femoral arteries and the aorta. Because of the unusual appearance of the emboli, it was sent for pathological examination and was diagnosed epithelioid hemangioendothelioma. Epithelioid hemangioendothelioma is a rare vascular tumor of intermediate malignancy. It usually originates from veins and rarely presents with acute ischemic symptoms.

Epithelioid hemangioendothelioma of the radial artery

Epithelioid hemangioendothelioma (EHE) is an extremely rare vascular tumor of intermediate malignancy. Generally it develops from the peripheral veins (usually the femoral vein). We report on a case of EHE of the radial artery, developed in a 26-year-old male patient, which presented as a solitary painless mass. He had a complete resection of the tumor and of the segment of radial artery involved. The histologic examination revealed an intravascular EHE, with low mitotic index and with insufficient histologic anormalities.

A Case of Kaposiform Hemangioendothelioma and Kasabach‐Merritt Phenomenon

Kaposiform hemangioendothelioma (KH) is a vascular tumor of intermediate malignancy that occurs in childhood, of which 50% are present at birth. The tumor has a predilection for the trunk, extremities, and retroperitoneum. It is commonly associated with Kasabach‐Merritt phenomenon, a consumptive coagulopathy characterized by profound thrombocytopenia and hypofibrinogenemia. The histologic differential diagnosis of kaposiform hemangioendothelioma includes infantile hemangioma, tufted angioma, Kaposi's sarcoma, and spindle cell hemangioendothelioma. We present a case of a neonate with a soft tissue mass encompassing the proximal two‐thirds of the right thigh. After delivery by Ceasarean section for failure to progress, the patient developed repiratory failure, consumptive coagulopathy and intracranial hemorrhage. The initial clinical differential diagnosis included KH, infantile hemangioma, and infantile fibrosarcoma, all entities which have been associated with Kasabach‐Merritt phenomenon. An biopsy demonstrated a nodular vascular proliferation composed of grouped, spindled endothelial cells forming irregular, slit‐like vascular lumens. There were associated fragmented red blood cells and hemosiderin deposits. The tumor cells were focally positive for D2–40, an antigen specific for lymphatic endothelium and expressed by KH, and were negative for GLUT‐1, an antigen expressed in infantile hemangiomas but not KH. The histologic and immunohistochemical findings confirmed the diagnosis of KH.

Kaposiform hemangioendothelioma: a study of 33 cases emphasizing its pathologic, immunophenotypic, and biologic uniqueness from juvenile hemangioma.

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.

Fast growing multifocal retiform hemangioendothelioma: a case report

Retiform hemangioendothelioma is a vascular tumor of intermediate malignancy. In general, it is a slow-growing single exophytic nodular or plaque-like lesion. We present a 17-year-old male patient with a rapidly growing multifocal retiform hemangioendothelioma on his right ulno-dorsal forearm. After first excision, within 4 weeks the tumor showed local recurrence. Treatment was made by wide excision with a 1-cm margin and fascia and closure of the defect by split-thickness skin graft. Two months later, a new lesion was observed on the back of the patient's hand. After excision and wound closure with split-thickness skin grafting, there was no recurrence in a 2-year follow-up period. We discuss diagnosis, prognosis, and possible surgical treatment of this rare skin neoplasm.

Vascular soft tissue tumors: Medical imaging : Ramon F, Degryse H, De Schepper A (F.R.: Department of Radiology, University Hospital Antwerp, Wilrijikstraat 10, B-2650 Edegem, Belgium). J Belge Radiol 1992;75:303–310

Histologically, tumors of the vascular system are divided into three categories. Benign types can be localized (hemangioma) or involve large segments of the body (angiomatosis). Vascular tumors of intermediate malignancy are known as hemangioendotheliomas. Angiosarcoma is one of the rarest malignant soft tissue neoplasms. The authors present the morphological and SI features of 17 histologically proven vascular tumors (16 benign, 1 malignant) examined by MRI. The results are compared with the findings on other imaging techniques. On T1-WI, the tumors are slightly hyperintense to muscle with interspersed areas of low SI corresponding to fibrous septa, calcifications, or fastly flowing blood, and areas of SI equal to fat. On T2-WI, the lesions are more homogeneous and markedly hyperintense to fat. MRI is superior to all other imaging techniques for evaluation of extent and characterization of vascular soft tissue tumors. Angiography remains helpful in demonstrating feeding or draining vessels.

Epithelioid Hemangioendothelioma of the Clitoris

A 30-year-old woman was referred for evaluation of a small nodule of the clitoris. This was subsequently diagnosed as epithelioid hemangioendothelioma. This rare vascular tumor of intermediate malignancy has not been previously described in the vulva. The patient underwent a modified radical vulvectomy and bilateral inguinal lymph node dissection, and subsequently received photon therapy. She is alive with no evidence of disease 27 months after diagnosis.