Endothelial Atypia Research Articles

Epithelioid and Spindle Cell Hemangioma: Clinicopathologic Analysis of 18 Primary Bone and Soft Tissue Tumors Highlighting a Predilection for the Hands and Feet, Frequent Multicentricity, and Benign Behavior.

Epithelioid and spindle cell hemangioma was initially described in 1999 in a series of primary bone tumors and was subsequently suggested by some to represent a variant of epithelioid hemangioma. Here, we studied 18 epithelioid and spindle cell hemangiomas. Nine patients (50%) were male. Age at presentation ranged from 12 to 78 years (median: 38.5y). Nine patients (50%) had tumor(s) limited to bone, 5 (28%) had tumor(s) limited to soft tissue, and 4 (22%) had tumor(s) involving bone and soft tissue. Nine patients (50%) had multiple tumors, all in a unilateral anatomic region involving the wrist, hand, ankle, or foot. Seventeen tumors (94%) occurred in an extremity, including 12 (67%) in the hands and feet, and 1 occurred in a vertebra. In imaging studies, primary bone tumors were lobulated, expansile, and lytic, and 7 bone tumors with available imaging (58%) showed cortical breakthrough. Tumor sizes were 0.8 to 7.2cm (median: 2.2cm). Epithelioid and spindle cell hemangioma is composed of lobules of epithelioid and spindled endothelial cells with bland, vesicular nuclei. Neoplastic cells show orderly vasoformative growth, with hemorrhagic stroma and no endothelial atypia or multilayering. Immunohistochemistry demonstrated uniform positivity for CD31 and ERG. Where positive, SMA highlighted pericytes (11/13 tumors). FOSB was strongly positive in 4 of 16 tumors (25%), and FOS was strongly positive in 5 of 10 stained tumors (50%). Break-apart fluorescence in situ hybridization confirmed the presence of FOS split signals in 4 tumors positive for FOS by immunohistochemistry and FOSB split signals in 2 FOSB-positive tumors. DNA sequencing demonstrated a GATA6 :: FOXO1 fusion in 1 of 3 sequenced tumors. Clinical follow-up was available for 15 patients (83%; range: 5mo to 11y; median: 3.5y). Seven patients (47%) had no evidence of disease at most recent follow-up. Seven of 13 patients (54%) who underwent surgery experienced local recurrence at the primary tumor site: 5 patients within a year, 1 at 2.4 years, and 1 thrice at 2, 3, and 5 years. Six patients were alive with multifocal disease (median: 3.5y; range: 5mo to 6y). No tumors gave rise to distant metastases. The clinicopathologic and genetic findings in this study support the notion that epithelioid and spindle cell hemangioma is a morphologic variant of epithelioid hemangioma that can occur in soft tissue as well as bone and that shows a striking predilection for the extremities. Given that most recurrences and primary tumors behaved indolently, watchful waiting would be reasonable for patients with multicentric disease that is not readily amenable to surgery.

Vascular lesions of the female genital tract: Clinicopathologic findings and application of the ISSVA classification

IntroductionVascular lesions of the female genital tract are extremely rare and their nomenclature does not widely follow the International Society for the Study of Vascular Anomalies (ISSVA) classification. Aim of the studyTo describe the clinicopathologic characteristics of vascular lesions of the female genital tract and to apply the ISSVA classification. Material and methods19 vascular lesions were diagnosed during a 20 year period. Their histological features including size, localization, type of vessels, endothelial atypia, mitotic activity, relation with surrounding tissues are described. Immunohistochemical analysis using CD31, CD34, D2-40, WT1, MiB1 and GLUT1 is performed. Results8 ovarian lesions were found including small cortical lymphatic malformations and medullary lesions resembling pyogenic granulomas, as well as two tubal lesions resembling true hemangiomas. They were all incidental findings. Cervical lesions (n=7) included endocervical polypoid venous malformations and paracervical combined malformations presenting clinically as leiomyomas; they probably represent static vessels. Vulvar lesions (n=4) consist of lymphatic and venous malformations and by angiokeratomas. No malignant lesions were found. WT1 is expressed by most of these lesions with the exception of the lymphatic malformations and the paracervical combined malformations. GLUT1 was consistently negative. MiB1 was only rarely positive. ConclusionVascular lesions of the female genital tract consist of lesions with different morphology by organ and of probably different pathogenesis. The ISSVA classification can be adopted for most of these lesions. WT1 should be best considered as a marker of endothelia with proliferative capacity rather than a marker of neoplastic endothelia.

Symplastic haemangioma: a case report

Symplastic haemangioma is characterised by degenerative atypia of vascular smooth muscle and interstitial cells within a pre-existing vascular lesion with minimal endothelial atypia. It shows atypical bizarre cells in the interstitium.

Angiosarcoma Arising in Ovarian Mucinous Tumor: A Challenge in Intraoperative Frozen Section Diagnosis.

Angiosarcoma of the ovary is rare but represents an aggressive type of malignant ovarian neoplasms. The purpose of this report is to describe the features of angiosarcoma arising in mucinous tumor that was misinterpreted as a benign vascular proliferation during the intraoperative consultation. A 45-year-old woman presented with an abdominal mass for 1 month. Exploratory laparotomy was performed. A 35 cm right ovarian mass submitted for intraoperative consultation was a multicystic mucinous tumor with an 8 cm area of hemorrhagic lesion between cystic locules. The frozen section diagnosis was at least mucinous borderline tumor. The hemorrhagic area, which was intraoperatively interpreted as organizing vessels associated with previous hemorrhage, represented angiosarcoma in permanent sections. Angiosarcoma may present a challenge in intraoperative frozen section diagnosis of an ovarian mass. The presence of ectatic anastomosing vessels with dissecting growth appears to be the clue to a suspicion of angiosarcoma. The presence of endothelial atypia provides further support for the diagnosis. A macroscopic hemorrhagic area in an ovarian mucinous tumor should be evaluated with care, and the possibility of angiosarcoma should be borne in mind.

Extensively Myxoid and Hyalinized Sinonasal Capillary Hemangiomas: A Clinicopathologic Study of 16 Cases of a Distinctive and Potentially Confusing Hemangioma Variant.

Capillary hemangiomas, the most common vascular tumors of the sinonasal region, are benign endothelial neoplasms, typically growing in an easily recognized lobular pattern. Some sinonasal capillary hemangiomas may show atypical features, such as high cellularity or mitotic activity, and represent more challenging diagnoses. Over the past several years we have seen in consultation a number of examples of sinonasal capillary hemangiomas displaying very striking stromal myxoid change and hyalinization, features that have received scant attention in the past. Available slides from 16 sinonasal capillary hemangiomas previously coded as showing such changes were retrieved from our archives. Submitting diagnoses included "query angiofibroma, rule out malignancy" (N=4), "vascular polyp, rule out malignancy" (N=3), "query malignant vascular tumor" (N=4), "sinonasal hemangiopericytoma" (N=1), and "benign vascular tumor" (N=1). Available radiographic studies often showed worrisome features. Grossly, the tumors ranged from 1.1 to 6.0 cm and appeared as ulcerated, vascular-appearing polyps. Microscopically, the tumors showed striking stromal myxoid change and/or hyalinization, which largely obscured the underlying lobular capillary arrangement. Within this myxohyaline matrix, a florid capillary proliferation was present, frequently with nonatypical mitotic activity. In some instances a branching, "hemangiopericytoma-like" vascular pattern was present in areas. The overall cellularity was low to moderate, and endothelial atypia or hyperchromatism was absent. Ulceration and thrombosis were frequently present. Immunostains to CD31, CD34, and SMA highlighted areas of lobular growth pattern inapparent on the routinely stained slides. Four tested cases were negative for androgen receptors and β-catenin. Follow-up from 12 patients revealed no local recurrences or metastases. Awareness of that sinonasal capillary hemangioma may show these unusual stromal changes, and the use of ancillary immunohistochemistry to highlight its lobular growth pattern should allow its confident distinction from more aggressive endothelial tumors (eg, angiosarcoma) and from nonendothelial tumors, including nasopharyngeal angiofibroma, solitary fibrous tumor, and sinonasal hemangiopericytoma-like tumor.

Hemangioma microvenular: lesión vascular benigna de patrón infiltrante. Presentación de 3 casos y revisión de la literatura

Microvenular hemangioma is an uncommon, benign, acquired vascular tumour which usually occurs as a solitary purple to red plaque o papule in the extremities and trunk of young adults, more frequently in women. Histologically, these tumours are characterized by a proliferation of small blood vessels throughout the dermis, with an infiltrative growth but without endothelial atypia. Immunohistochemistry shows positivity for vascular markers. Histopathology and clinical features are required to confirm the diagnosis and to exclude well differentiated sarcomas and other benign vascular lesions. We report three new cases and review the literature

Acral Angioosteoma Cutis on the Great Toe Mimicking Pyogenic Granuloma.

Dear Editor: Acral angioosteoma cutis (AAOC) is a rare benign exophytic tumor characterized by bony and vascular proliferation. Clinically, it occurs on acral skin and resembles pyogenic granuloma (PG). Here, we report an unusual case of AAOC that developed on the periungual area of the great toe. A 12-year-old girl presented with a solitary tender crusted nodule on her left great toe. She had been suffering from an ingrown nail and the lesion had first appeared two months earlier after a partial nail extraction. The lesion increased in size over time. The patient was otherwise healthy. Physical examination revealed an erythematous to blackish, somewhat firm, crusted periungual nodule, measuring 5 mm in diameter, with paronychia on her left great toe (Fig. 1A). Clinically, the lesion was suspicious for PG or granulation tissue. The lesion was removed by curettage and a histopathological examination revealed a well-circumscribed polypoid tumor containing multiple bony trabeculae and small vessel proliferation in the stroma (Fig. 1B, C). Well-formed dilated capillaries that showed neither a lobular pattern nor endothelial atypia were distributed diffusely among the bony trabeculae. These findings were consistent with a diagnosis of AAOC. We followed the lesion for 1 year and observed no recurrence. Fig. 1 (A) 5 mm in diameter, erythematous to blackish, crusted periungual nodule on her left great toe. (B, C) Tumor containing bony trabeculae with osteocytes and well-formed dilated vessel proliferation with diffuse pattern in the stroma (HE B: ×100, ... In 2006, Googe et al.1. first described AAOC as a benign tumor of unknown histogenesis that is distinctive from other cutaneous lesions showing calcification or ossification. Clinically, AAOC can be easily misdiagnosed as one of the benign acral neoplasms2,3,4,5. In other similar conditions, the subungual exostosis differs from that in AAOC in that a fibrocartilaginous cap surrounds the lesion without vascular proliferation. In addition, ectopic bone formation protruding from the skeleton is typically found on radiography. Both osteoma cutis and fibro-osseous pseudotumor of the digit show ossification without vascular proliferation. Osteochondroma also has no vascular channels and is characterized by bony trabeculae covered with hyaline cartilage. PG showing metaplastic ossification is the most difficult entity to differentiate from AAOC4,5, but can be differentiated by its typical lobular vascular proliferation. In our case, unfortunately, radiography was not performed to examine for ectopic bone formation and a connection between the skeleton and the tumor. However, when performing curettage and biopsy, we found no connection between the tumor and underlying bony abnormalities, and the lesion was easily removed. Thus, we considered that the tumor was not an exostosis or osteochondroma. The pathogenesis of AAOC is still unclear, but we assume that it is similar to that of other hemangiomas showing ossification. According to previous reports, vascular endothelial growth factor (VEGF) and bone morphogenetic protein (BMP) may play an important role in the development of PG with ossification2,3,4,5. VEGFs and BMPs are synthesized by various cells including endothelial cells and osteoblasts in response to hypoxia, trauma, or inflammation. They then induce vascular and osteoblastic differentiation, wherein the induction is regulated through interactions with one another. We assume that these proposed functions of VEGFs and BMPs may also explain the development of AAOC. Although there have been only two case reports of AAOC, and only limited information is available since its first description by Googe et al.1, we do not think this tumor is truly rare. Some reports of PG showing ossification did not describe lobular vascularity4,5. This suggests the possibility of AAOC being overlooked and misdiagnosed as PG or other acral tumors. Considering the definition of PG, we believe that some previously reported cases of ossifying PG that showed no lobular vascularity could be reclassified as AAOC. Of course more cases and investigations are needed to prove AAOC as a distinct clinicopathologic entity and not another variant of ossifying PG. AAOC should therefore be considered in the differential diagnosis of acral lesions, especially when the patient has a history of inflammation or trauma in the periungual area, as in our case.

Arteriovenous Malformation of the Vulva

To report the case of a patient with a large and symptomatic vulvar lesion, necessitating surgical excision. We report the case of a 57-year-old postmenopausal woman with a 6-month history of an enlarging vulvar lesion associated with vulvar pruritus. On examination, a pedunculated 7 × 5 × 4-cm soft tissue mass attached to the left labium majus was noted. Surgical excision was performed and histopathologic evaluation revealed variably dilated, submucosal vessels with thick muscular walls and intimal thickening, but without endothelial atypia or multilayering. These findings were consistent with a final diagnosis of arteriovenous malformation of the vulva. Given the complex anatomy of the vulva, the differential diagnosis for vulvar vascular lesions can be challenging. Hence, surgical excision and histopathologic evaluation become imperative to distinguish them from other dermatologic and neoplastic conditions of the vulva.

Multiple microvenular hemangioma: A case report

The current study reports a case of multiple microvenular hemangioma (MH). A 35-year-old male presented with dark red maculopapules on the trunk and limbs that had been apparent for 5 years. The number of lesions exceeded 100 in total. A histological examination demonstrated multiple, irregular, branching venules in the dermis, without any endothelial atypia. On immunohistochemical analysis of the vascular structures, the endothelial cells stained positive for CD31, CD34 and factor VIII, and the perivascular cells stained positive for SMA and HHF-35. These observations were consistent with a diagnosis of MH, and should be differentiated from the most common differential diagnosis of patch-stage Kaposi’s sarcoma. There was no clear effect following topical application of recombinant human interferon α-2b gel.

Microvenular Hemangioma Presenting With Numerous Bilateral Macules, Patches, and Plaques

Microvenular hemangioma (MVH) is a rare, slowly growing, benign vascular tumor that typically presents as a solitary enlarging plaque or nodule on the trunk or the extremities of young to middle-aged adults. A minority of MVH present with multiple lesions that are either gradually or suddenly acquired (eruptive MVH). Herein, we report a case of a 53-year-old woman who progressively developed numerous bilateral MVHs presenting as enlarging, blanching, erythematous to violaceous macules, patches, and plaques over the proximal thighs and axillae. Two biopsies exhibited the irregular branching venules with inconspicuous lumina lacking endothelial atypia and associated with dermal fibrosis characteristic of MVH. Immunophenotypically, the endothelium expressed Wilms Tumor 1, CD31, CD34, and erythrocyte-type glucose transporter protein (GLUT-1) GLUT-1 focally and was negative for Human herpes virus 8 and the lymphatic marker D2-40. In addition, numerous dermal spindle cells expressing CD34 and procollagen, putative fibrocytes, surrounded the thickened dermal collagen bundles and small vessels of MVH implicating a reactive/reparative (proliferative) process due to an unrecognized cutaneous injury. A review of MVH summarizing its clinicopathologic findings and its natural history is presented.

Potential carcinogenic effects of world trade center dust after intratracheal instillation to Sprague–Dawley rats: First observation

More than 10 years have passed since the terrorist attack on the New York City World Trade Center on September 11, 2001. It is well known that long-term carcinogenic bioassays on rodents can predict the potential carcinogenic effects of chemical and physical agents for humans. A life-span carcinogenicity bioassay was conducted on Sprague-Dawley rats at the CMCRC of the Ramazzini Institute to test the potential carcinogenic effects of settled dust collected at the WTC immediately after the terrorist attack. The WTC material tested is a complex mixture of coarse particles (95%) contain pulverized cement, glass fibres, asbestos, lead, polycyclic aromatic hydrocarbons (PAH(S) ), polychlorinated biphenyls (PCB(S) ) and polychlorinated furans, and dioxin. The test matter was suspended in sterile saline and administered by intratracheal instillation (IT) to 8-week-old Sprague-Dawley rats (100 animals/sex), 3-4 days/week for 4 weeks. A group of 200 male and female rats served as controls. The animals were kept under observation until natural death. Histopathological evaluation of the lungs (target organ) of instilled control and treated male and female rats, did not show any significant increased incidence of lung tumors. Two hemangiomas (one with endothelial atypia) and one hemangiosarcoma were found in the lungs of treated males. Moreover a modest increased incidence of terminal bronchiolar hyperplasia (TBH) and squamous metaplasia occurred in the lung of treated males and females compared to the controls. Hemangioma and hemangiosarcoma are extremely rare tumors in the lung of our colony and we believe they are caused by WTC dust.

Angiomatoid Intradermal Melanocytic Nevus or Chimeric Nevus?: A Potential Diagnostic Pitfall

Angiomatoid Intradermal Melanocytic Nevus or Chimeric Nevus?: A Potential Diagnostic Pitfall

Acroangiodermatitis of Mali

Conflict of interest: none declared. An 87‐year‐old man presented with a 2‐year history of three haemorrhagic keratotic lesions on the inner side of the right lower leg (Fig. 1). Before presentation, he had also developed similar smaller superficial lesions below this area. The patient gave a history of chronic intermittent right ankle swelling after a football injury in the 1950s. Elsewhere, multiple seborrhoeic keratoses were noted. There was no lymphadenopathy. The patient was otherwise well. ... The patient was advised to wear compression stockings. The larger lesions were curetted and sent for histopathological examination. Under scanning magnification, a mildly hyperkeratotic epidermis was seen. The upper dermis was expanded by a striking lobular vascular proliferation associated with red cell extravasation and brown pigment (haemosiderin). Capillaries were hypertrophied, resembling tortuous venules, and focal fibrin extravasation was noted. There was no endothelial atypia, irregular dissecting vessels or spindle cell proliferation and plasma cells were not a prominent feature (Fig. 2).

Atypical Vascular Lesions After Surgery and Radiation of the Breast

We report the clinicopathologic study of 32 cases of atypical vascular lesions (AVLs) after surgery and radiation of the breast, which were referred to us in consultation over a 17-year period. The patients, all women, ranged in age from 41 to 95 years (mean 61 y). The lesions developed within the radiation field from 1 to 12 years (median 6.0 y) after therapy. They occurred as one (n=18) or more (n=10) flesh-colored papules or erythematous patches/plaques ranging in size from 1 to 60 mm (mean 8.0 mm, median 4.0 mm). Tumors could be divided into 2 histologic types: a lymphatic type (LT) (n=22) and a vascular type (VT) (n=10). LT AVLs consisted predominantly of thin-walled, variably anastomosing lymphatic vessels that were usually confined to the superficial dermis but occasionally extended into the deep dermis and even subcutis. The VT (n=10) typically consisted of small, irregularly dispersed, often blood-filled, pericyte-invested, capillary-sized vessels involving the superficial or deep dermis. VTs were often associated with extravasated erythrocytes, hemosiderin, and a surrounding minor LT component. In 4 cases, endothelial atypia, consisting of nuclear and nucleolar enlargement, was noted. Follow-up of 21 patients with LT AVLs (1 to 106 mo; mean 47 mo) disclosed recurrence/additional lesions in 6, all of whom had additional surgery. Of the 21 patients, 17 are alive without disease, 1 is alive with disease, 1 died of breast carcinoma, 1 died of unknown causes, and 1 showed progressive histologic changes in the AVLs over a period of 5 years resulting in a well-differentiated angiosarcoma. Follow-up in 8 patients with VT AVL (2 to 181 mo; mean 40 mo) disclosed that 6 were alive and well, but 2 of the 4 patients whose lesions displayed endothelial atypia had additional complications. One patient underwent a mastectomy that revealed extensive residual AVL and the second developed a high-grade angiosarcoma after 14 months. We conclude that AVLs encompass a wider spectrum of changes than previously appreciated, ranging from superficial lymphatic proliferations to more complex lymphatic and capillary vascular lesions. There seems to be an association of AVL with angiosarcoma that differs depending on the histologic features, with the VT AVLs having the higher risk. In the 2 patients who developed angiosarcoma, morphologic evidence suggested AVLs to be a precursor rather than simply a risk factor. Future outcome and management studies should take into account these differences.

Diffuse dermal angiomatosis

Diffuse dermal angiomatosis (DDA) is an acquired, benign vascular proliferation characterized clinically by poorly circumscribed, violaceous, livedoid plaques with frequent ulceration. Histologically, a diffuse interstitial proliferation of CD31-positive endothelial cells is present within the papillary and reticular dermis. Endothelial atypia, atypical mitoses, and vasculitis are lacking. We describe a case of DDA in a 53-year-old man with peripheral vascular atherosclerosis that resolved following revascularization. Early correction of the associated ischemic peripheral vascular disease promotes resolution of this unusual clinicopathologic entity.

Rapid-growing Left Intraventricular Cardiac Hemangioma

A 62 years old man with Child B liver cirrhosis, prostate cancer and a recent colon carcinoma resection was referred to our cardiology department for trans-thoracic-echocardiography (TTE) in order to establish left ventricular function before starting chemotherapy. TTE revealed a mobile mass (16 x 8 mm) attached to the anterior-medial left ventricular wall, protruding and swinging within the left ventricle cavity. At follow-up TTE showed growing of the intra-cardiac tumor up to 27 x 10 mm, corresponding to a size increase of 1 mm/month. Among different pathologies a rapid growing benign tumor with a high risk of systemic embolisation or an endocardial blood cyst were retained as possible diagnoses. Given the progression of the cardiac finding and the patient's improved general condition, surgical resection of the cardiac mass was performed. Histological examination revealed a mixed capillary/cavernous hemangioma. This case shows the unusual concomitant appearance of a rapid growing cavernous hemangioma which rarely located at ventricular level and the feasibility of cardiac resection without further sequelae in a poly-morbid patient.

Retiform Hemangioendothelioma

Fifteen cases of a distinctive type of low-grade angiosarcoma of the skin are described. Most tumors presented in the second to fourth decades of life, the youngest patient being 9 years old and the oldest 78 (mean age, 36 years). There was no sex predilection. Six tumors arose on the lower limb, four on the upper limb, three on the trunk, and one each on the penis and the scalp. One case arose in the setting of chronic lymphedema and another following radiotherapy for carcinoma of the uterine cervix. Distinctive morphologic features were the presence of long arborizing blood vessels arranged in a retiform pattern (reminiscent of normal rete testis) lined by monomorphic hobnail endothelial cells, a very prominent lymphocytic infiltrate in most cases, and the focal presence of papillae with hyaline collagenous cores, similar to those seen in malignant endovascular papillary angioendothelioma (Dabska's tumor). With a median follow-up of 7.25 years in 14 cases, retiform hemangioendothelioma has proved to be a low-grade neoplasm that recurs frequently but has a very low metastatic rate. The single regional lymph node metastasis in this series was from a case with a biphasic pattern in which only the spindle cell component was represented in the metastasis. There have been no tumor-related deaths, underlining the importance of accurate distinction from conventional angiosarcoma. This distinction is facilitated principally by the absence of dissection between individual collagen bundles and the absence of endothelial atypia or mitotic activity. The precise relationship between retiform hemangioendothelioma and Dabska's tumor is uncertain, possibly because cases of the latter may not be homogeneous.

Pathology of high-dose intraarterial BCNU

Current radiotherapy and chemotherapy for high-grade and/or recurrent astrocytomas result in only moderate increases in survival time. In an attempt to improve this, high-dose intraarterial 1,3-bis-(2-chloroethyl)-l-nitrosurea (BCNU) was utilized on 41 patients with these neoplasms over a 4-year period at our institution. Eight of the 41 patients came to biopsy or autopsy at times sufficiently following intraarterial BCNU infusion and with adequate tissue samples to evaluate the histological changes induced by the drug. Two of the eight patients received no additional radiotherapy or chemotherapy. The other five received conventional whole brain irradiation, and one additionally received 50 mg of intravenous 2-deoxy-5-fluorouridine (FUdR). The eight patients showed mild to severe amounts of bland coagulative necrosis, vascular hyalinization, perithelial fibroblastic proliferation, and endothelial atypia. One of these patients had a recognized severe clinical leukoencephalopathy, and the pathological changes were maximal in this individual. Six patients had radiological evidence of increased necrosis and clinical deterioration prebiopsy or preautopsy, but, within this group, there were no distinguishing clinical features. Microscopic changes were severe in two of these patients. A final patient died of unrelated septic shock 5 days after a single infusion of intraarterial BCNU, and the microscopic changes were least extensive in her. This study suggests that high-dose intraarterial BCNU can cause a leukoencephalopathy, sometimes severe, either alone or in synergistic fashion with cranial irradiation. Occurrence of such leukoen-cephalopathy is not always predictable based on BCNU dosage and cannot always be reliably distinguished from tumor regrowth or tumor necrosis by radiological and clinical evaluation. Hence, caution most be exercised in continuation of high-dose intraarterial BCNU protocols.