Eur. Neurol. 23: 240-246 (1984) ® 1984 S. Karger AG. Basel 0 0 14-3022/84/0234-0240S2.75/0 Brain Stem Vascular Malformation Simulating a Hemorrhagic Metastasis: Report of a Case with Pathologic Correlation Karen Scardiglia, José Billera, Mona Ghobrialb. Emanuel Rossb, Kelly Badrinathcl “Department of Neurology: bSection of Neuropathology. Department of Pathology, and 'Section of Oncology. Department of Internal Medicine, Loyola University Stritch School of Medicine, Maywood, III., USA Key Words. Vascular malformation • Hemorrhagic metastasis • Pontine hematoma • Cranial computerized tomography Introduction Brain stem vascular malformations may be an incidental postmortem finding [5], have an insidious onset with slow progres­ sion [12], or manifest themselves as a cata­ strophic inlraparenchymal or subarachnoid hemorrhage [8]. We report a 65-year-old pa­ tient with known breast carcinoma who pre­ sented with a 4-day history of progressive brain stem symptomatology. Cranial com1 The authors wish to thank MaryA/in Di I’rizio for manuscript preparation. puted tomography (CCT) revealed a dense, irregular enhancing pontine lesion which was interpreted as a hemorrhagic metastasis. She was treated with dexamethasone and radio­ therapy and expired 7 days after her hospital admission. Postmortem examination dis­ closed a ruptured brain stem arteriovenous malformation as well as necrotic cells sugges­ tive of metastatic disease. In addition, a cav­ ernous hemangioma of the thoracic spinal cord was identified. Review of the literature failed to reveal the association of a brain stem arteriovenous malformation and a brain stem metastasis. Downloaded by: MacQuarie University 137.111.162.20 - 2/14/2019 1:03:54 PM Abstract. A 65-year-old woman with known breast carcinoma developed headaches, fol­ lowed shortly by disequilibrium, vertical diplopia and dysarthria. Cranial computerized tomography (CCT) demonstrated a dense, irregularly enhancing pontine lesion with associ­ ated mass effect. She received déxaméthasone (Decadron®) and radiotherapy and subse­ quently expired. Postmortem examination disclosed a ruptured brain stem arteriovenous malformation within a massive hemorrhage along with necrotic atypical cells suggestive of metastatic disease. Brain Stem Vascular Malformation Simulating a Hemorrhagic Metastasis A 65-year-old, right-handed woman was admitted on April 13, 1983, with a complaint of disequilibrium of 4 days' duration. On April 9, she suddenly devel­ oped a constant vertex headache partially relieved by analgesics, followed shortly by disequilibrium. On April 11, she experienced persistent numbness of the right upper extremity and entire face. On the day of admission, she complained of vertical diplopia, slurred speech and a metallic taste in her mouth. She described increasing disequilibrium with a tendency to veer to the left when assuming the upright position. She had no nausea, vomiting, loss of consciousness, seizures, tinnitus, hearing loss, dysphagia, weakness or previous similar episodes. Her prior history was sig­ nificant in that a carcinoma of the breast was diag­ nosed in 1978 at which time a left modified radical mastectomy was performed. Pathological confirma­ tion of an cstrogcn-rcccptor-negative carcinoma was made and chemotherapy (cyclophosphamide, metho­ trexate and 5-fluorouracil regimen) was begun because of extensive bony disease and a positive bone marrow aspirate. She did well until January 1981, when a biopsy of several skin nodules revealed metastatic dis­ ease which was found to be cstrogcn-rcceptor-positivc. Tamoxifen and Adriamycin were begun with the addi­ tion of Cytoxan several months later. Her general con­ dition deteriorated slowly. On July 7, 1983, mitomy­ cin was substituted for Adriamycin because of a de­ creasing cardiac output. Examination on her final admission revealed an alert, slightly cachectic, normotensive and afebrile woman. Her neck was supple without lymphadcnopathy or bruits. Two firm cutaneous nodules were present on her back. Sequelae of her previous mastec­ tomy were noted. Cardiac examination was unremark­ able. Diffuse bilateral respiratory rhonchi and expira­ tory wheezing were present. Abdominal examination revealed a liver span of 11 cm and no splenomegaly. Neurological examination revealed a normal mental status and language function with mild dysarthria. Bilateral horizontal gaze paresis was noted. There was a skew deviation present with the right eye being deviated downward and inward. Fine vertical nystag­ mus was present on upward gaze. The pupils were equal in size and reacted briskly to light and near test­ ing. There was no afferent pupillary defect. Visual acu­ ity was 20/40 bilaterally. The visual fields were full. Funduscopic examination revealed normal discs and venous pulsations bilaterally. Corneal reflexes were absent bilaterally. The remainder of the cranial nerves appeared normal with the exception of an absent gag reflex. Motor strength was normal throughout and muscle tone was diminished in the right lower extrem­ ity. Sensory examination was unremarkable to all mo­ dalities. Marked ataxia on the right was noted on heclto-knee-to-shin testing. Deep tendon reflexes were symmetrically normoactivc with the exception of a right pendular knee jerk. Plantar responses were exten­ sor bilaterally. Gait was wide-based and markedly ataxic with her falling to the left. Laboratory studies on admission were unremarkable with the exception of a mild normochromic anemia. Chest roentgeno­ gram demonstrated a blunted left costrophrenic angle and bone metastasis. CCT revealed a large dense enhancing lesion with an eccentric lucent area within the pons showing slight mass effect (see fig. 1. 2). Decadron® 10 mg i.v. and then 6 mg, every 6 h, was begun and she subsequently received radiotherapy for a presumed diagnosis of hemorrhagic pontine metas­ tasis. By April 14. 1983, her headaches had resolved: however, her examination revealed no apparent change. That evening she suffered a respiratory arrest requiring mechanical ventilatory support. The follow­ ing day she appeared awake and was assisting the res­ pirator. Her pupils were pinpoint and reactive. Bilat­ eral peripheral facial weakness was evident. She was noted to have occasional nonpurposeful movements of her extremities to painful stimuli. She was success­ fully extubated on April 20; however, later that day she suffered a fatal respiratory arrest. Postmortem Examination Along with significant findings within the central nervous system, the general autopsy revealed a left mastectomy scar with no residual tumor in this region. Fibrocystic disease was present in the remaining right breast. Metastatic lobular carcinoma containing signet ring cells was seen diffusely infiltrating the lymphatics of the pleural surface of both lungs, peribronchial tis­ sue. the entire depth of the wall of the stomach and small intestines with secondary ulcerations of the tu­ mor infiltrates within the gastric mucosa. Metastatic involvement of the serosal surface of the colon, mesoappendix, uterus and ovaries was also noted. Both adrenals were enlarged, containing metastatic disease and a sclerosing hemangioma. Bone marrow examina­ tion revealed necrotic neoplastic tissue. A solitary cutaneous metastatic nodule was found in the region Downloaded by: MacQuarie University 137.111.162.20 - 2/14/2019 1:03:54 PM Report of a Case 241 242 Fig. 1. Uninfused computed tomographic scan demonstrating dense lesion with eccentric lucent area within pons. Scardigli/Billcr/Ghobrial/Ross/Badrinath Fig. 2. Contrast-enhanced computed tomographicscan demonstrating dense enhancement of lesion within pons. of the scapulae. Comparison o f the tumor tissue found at necropsy with that originally seen in the left breast, multiple regional lymph nodes and bone marrow re­ vealed the neoplastic tissue to be identical. Examination of the dura and cerebrum was within normal limits with no evidence of metastasis. The pons was asymmetrical with the right anterior twothirds appearing to be broadened and softened. Multiple sections of the brain stem revealed within the upper and mid-pontine levels a large hem­ orrhagic mass measuring 2.6 X 2.7 cm. involving both the tegmentum and basis pontis (fig. 3). At the upper level of the pons the hemorrhage extended into the ventricular surface. The hemorrhage did not reach any other surface of the pons. No tumor or other abnormalities were noted on gross examination Downloaded by: MacQuarie University 137.111.162.20 - 2/14/2019 1:03:54 PM Fig. 3. Upper pons with a hem­ orrhagic mass involving tegmentum and pontine base. X 2. 243 Brain Stem Vascular Malformation Simulating a Hemorrhagic Metastasis Fig. 4. The rupture site (arrow) with one of the vascular channels partially filled with a thrombus. HE. X 40. y V 4* -r '} - * Mr i* >J .r v< V .* 4 f *r v r i *, \A ' • J ^ ¿ r*V , >v.*. ,9■ > ? fc 'v . f 'V rr* -'v*. -v of the pons. The hemorrhage extended rostrally as a separate dorsal and ventral mass. The ventral hemor­ rhage extended into the lower mesencephalon. No hemorrhage was found in the medulla. The cerebel­ lum appeared to be within normal limits. HE and EVG stains of the hemorrhagic mass revealed an arteriovenous malformation consisting of several markedly distended vascular channels and multiple smaller channels. The wall of all vascular channels which is marked by areas of thinning consisted of fibrohyaline tissue devoid of either recognizable clas­ tic or muscular tissue. The rupture site in one large ^ 4 . ». •»: ‘t .- Fig. 5. Islands of large ghost cells with large poorly visualized nuclei and minimal amount of cytoplasm. HE. X 500. *■ ;' S i , k- - 1 \ 'w vi#, •> $ /tv V 4 v s . _• vessel was identified, and was marked by the pres­ ence of a partial thrombus (fig. 4). Hemosiderin de­ posits were present within the wall of the large dis­ tended vascular channels, as well as within the adja­ cent tissues. Within the large hemorrhagic mass, which at one level has extended into the 4th ventri­ cle, several islands of tissue were seen containing large ghost cells having polymorphous poorly visual­ ized nuclei with minimal cytoplasm; these atypical cells are highly suggestive of neoplastic cells, but be­ cause of their poor preservation cannot be definitely interpreted as neoplastic cells (fig. 5). Downloaded by: MacQuarie University 137.111.162.20 - 2/14/2019 1:03:54 PM » • - 244 Scardigli IJillerGhobrial/Ross/Badri nath Fig. 7. Cavernous hemangioma in Ihc dorsal columns of the thoracic spinal cord. HE. X 15. Comment In the Cooperative Study of Intracranial Aneurysms and Subarachnoid Hemorrhage. Ferret and Nishioka [8| reported on a total of 549 congenital and acquired arteriovenous malformations. There were 453 intracranial malformations of which 93% were supraten- Downloaded by: MacQuarie University 137.111.162.20 - 2/14/2019 1:03:54 PM In the surrounding pontine tissue, edematous vac­ uolization as well as a focal collection of vessels show­ ing marked hyalin thickening of their walls is also present. In the upper thoracic level, two distinct hemor­ rhagic foci were identified (fig. 6). Microscopically, these hemorrhage foci were found to be cavernous hemangioma. The large vascular spaces lined by a sin­ gle endothelial cell layer were surrounded by dense fibrohyaline connective tissue (fig. 7). Brain Stem Vascular Malformation Simulating a Hemorrhagic Metastasis In addition, a cavernous hemangioma in the dorsal column of the thoracic spinal cord was identified. It is not surprising that the patient had no signs of posterior column dys­ function since it is believed that the dorsal columns may not be the only ascending path­ way for tactile and proprioceptive discrimi­ nations [13] in man. Spinal cord vascular malformations have been associated with other congenital disorders including intracra­ nial aneurysms and arteriovenous malforma­ tions [1]. Although we elected conservative therapy, a few cases of successfully evacuated brain stem hematomas have been reported. The source of hemorrhage from vascular malfor­ mations was pathologically confirmed in 5 cases [2, 3, 7, 9, 11], Recently, proton-beam therapy has been found useful in treating brain stem arteriovenous malformations [4]. McCormick et al. [6] reported a series of 48 cryptic vascular malformations at postmor­ tem examination, 8 of which were located in the pons. The clinical history and CCT find­ ings may be confusing diagnostically as in our patient and we therefore emphasize that rup­ ture of a vascular malformation be seriously considered in the differential diagnosis of a pontine hematoma even in the context of underlying neoplastic disease. References 1 Benarrd, R.: Vascular malformations of the spinal cord; in Vinken, Berwyn. Handbook of clinical neurology, vol. 12, chap. 21 (American Elsevier, New York 1972). 2 Inone, Y.; Sata, O.: Successful removal of pontine hematoma due to rupture of cryptic arteriovenous malformation. Case report. Acta ncurochir. 69: 69-75 (1983). 3 Kasai, N.; Fujiwara, S.; Yoshimoto, T.; Scyuki, J.: ‘Cryptic’ arteriovenous malformation of the brain­ Downloaded by: MacQuarie University 137.111.162.20 - 2/14/2019 1:03:54 PM tonal and 7% were infratentorial. Of those in the posterior fossa, 2% of the total involved the brain stem and 5 % of the total were cere­ bellar. Vascular malformations of the brain stem include arteriovenous malformations, capillary telangiectasias, venous angiomas, cavernous hemangiomas and varices and are characterized by a spectrum of pathological and clinical findings [5], Cavernous heman­ gioma and arteriovenous malformations pro­ duce symptoms more commonly than do te­ langiectasias [12]. Although the clinical ex­ pressions of these lesions range from no symptoms to sudden fatal brain stem hemor­ rhage, a large percentage of patients will have a positive history spanning several years [ 15]. Neurologic signs and symptoms are often multiple, episodic and progressive. The wax­ ing and waning course may be indistinguish­ able from that of multiple sclerosis [ 12], CCT generally shows calcification within a brain stem lesion that displays relatively little mass effect and shows little contrast enhancement [15], These lesions have, however, been con­ fused with that of a pontine glioma, resulting in unnecessary radiation [10], Our case de­ scribed above is of special interest from sev­ eral aspects. She had a known diagnosis of metastatic breast carcinoma and no previous episodes suggestive of brain stem pathology. In addition, the CCT was supportive of the diagnosis of hemorrhagic metastasis accord­ ing to the above criteria. However, the patho­ logic findings indicate the origin of her hem­ orrhage to be from her previously 'silent' arteriovenous malformation. Also noted were large polygonal ghost cells highly sug­ gestive of neoplastic cells. Solitary brain stem métastases are rare [ 14] and to our knowledge no previous case of brain stem arteriovenous malformations in association with brain stem metastasis has been reported. 245 stem. A successfully operated case. Neurol. Ncurosurg., Tokyo 9: 1161-1165 (1981). 4 Kjellberg, R.N.; Hanamura, T.; Davis, K.R.; Lyons, S.L.; Adams, R.D.: Bragg-peak protonbeam therapy for arteriovenous malformations of the brain. New Engl. J. Med. 309: 269-273 (1983). 5 McCormick, W.F.; Hardman, J.M.; Boulter, T.R.: Vascular malformations (‘angiomas’) of the brain with special reference to those occurring in the posterior fossa. J. Ncurosurg. 28: 241-251 (1968). 6 McCormick, W.F.; Nofzinger. J.D.: ‘Cryptic’ vas­ cular malformations of the central nervous system. J. Neurosurg. 24: 865-875 (1966). 7 Ochiai, C ; Sano, K.; Kobayashi, S.; Sasaki, T.; Mayanagi, Y.: Clinical study of pontine hemor­ rhage with special reference to CT classification and surgical indication. Brain Nerve, Tokyo 31: 803-811 (1979). 8 Perret, G.; Nishioka, H.: Arteriovenous malforma­ tions: an analysis of 545 cases of cranio-cerebral arteriovenous malformations and fistulae reported to the Cooperative Study; in Saks, Perret. Locksley, Intracranial aneurysms and subarachnoid hemorrhage. A cooperative study, pp. 200-222 (Lippincott, Philadelphia 1969). 9 Pouyanne. M.H.; Got, M.; Julien, J.; Riemesn, V.; Paoli, M.: Deux cas d’hématomes intraprotubcranticls opérés. Etude critique. Neurochirurgie 13: 738-742 (1967). Scardigli/BiHcr/Ghobrial/Ross/Badrinath 10 Russell, D.S.; Rubinstein, L.J.: Pathology of tu­ mors of the nervous system; 4th ed., pp. 129-134 (Williams & Wilkins, Baltimore 1977). 11 Scott, B.B.; Sceger, J.F.; Schneider, R.C.: Success­ ful evacuation of a pontine hematoma secondary to rupture of a pathologically diagnosed ‘cryptic’ vascular malformation. Case report. J. Ncurosurg. 39: 104-108 (1973). 12 Stahl, S.M.; Johnson, J.P.; Malamucl, N.: The clinical and pathological spectrum of brainstem vascular malformation. Archs Neurol. 37: 25-29 (1980). 13 Wall, P.D.; Noordenbos. W.: Sensory functions which remain in man after complete transection of dorsal columns. Brain 100: 641-653 (1977). 14 Weiss, H.D.; Richardson, E.P.: Solitary brainstem metastasis. Neurology 28: 562-566 (1978). 15 Ycates. A.; Enzmann. D.: Cryptic vascular malfor­ mations involving the brainstem. Radiology 146: 71-75 (1983). Received: January 6. 1984 Accepted: March 22, 1984 José Biller, MD. Loyola University, Stritch School of Medicine, 2160 S. First Avenue, Maywood, IL 60153 (USA) Downloaded by: MacQuarie University 137.111.162.20 - 2/14/2019 1:03:54 PM 246