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Spinal Leptomeningeal Infiltration by Systemic Cancer: Myelographic Features

Kwang S. Kim 1 Five cases of spinal leptomeningeal infiltration by systemic cancer are presented Sam U. H02 and myelographic features are discussed with a review of the literature. Common Peter E. Weinberg 1 characteristic features are parallel longitudinal striations due to thickened nerve roots in the cauda equina and bizarre irregular filling defects with varying degrees of blocks, Charles Lee 1 resembling arachnoiditis. Another pattern described in the literature consists of multi­ ple nodular filling defects along the nerve roots of the cauda equina.

Nonneurogenic leptomen ingeal infiltration by systemic cancer is a rare mode of metastasis to the central nervous system. This process is characterized by diffuse, sheetlike infiltration of th e pia-arachnoid. Symptoms and signs are produced by meningeal irritation, increased intracrani al pressure or neuronal dysfunction, either cerebral or spinal, or a combination of these elements [1]. The syndrome has been known si nce the turn of the century. The spinal form of the disease is not as well known and less common than th e cerebral form [2]. Although this entity is still considered rare, its frequency is increasing, especiall y with systemic lymphoma [3-5]. Clinical manifestations of spinal leptomeningeal infiltration are obscure and nonspecific and an earl y diag nosis is often difficult [2, 3]. The myelographic description of thi s type of spinal cord and cauda equina malignancy has been infrequently reported. We present five cases with a review of the literature.

Case Reports

Case 1

A 48-year-old man was found to have undifferentiated lymphoma involvin g th e small bowel, left ureter, and left axillary and submandibular nodes 5 months before admi ssion. He received radiation therapy to th e abdomen and was treated with chemoth erapy. He was ad mitted after 3 weeks of progressive pain in th e low back and both thighs. He also noted weakness in going up and down stairs over the previous several days. Ph ysical examinati on This article appears in t he May/ June 1982 showed weakening of the iliopsoas mu scles and diminished mu scle stretch reflex in the issue of AJNR and the AU9ust 1982 issue of AJR. lower extremities. There was no se nsory abnormali ty. At the time of myelography, th e spin al fluid was viscous and xan th ochromic. The protein Received July 29, 1981 : accepted after revi­ content of the spinal fluid was 4,400 mg / dl and th e cytology was negative. The myelogram sion November 30, 1981. showed thickened nerve roots with parall el longitudinal st ri ations involving the en tire lumbar ' Department of Radiology, Northwestern Uni­ region (figs. 1 A and 1 B). Radiation th erapy to the whole spinal axis was immediately versity Medical School, Northwestern Memorial Hospital, Superi or St. and Fairbanks Ct. , Ch icago, in itiated. His symptoms and signs continued to worsen rapid ly. IL 60611 . Adress reprint requests to K. S. Kim . A laminectomy was perform ed at th e T1 2-L2 level. The dura appeared normal and th e ' Departm ent of Neurology, Northwestern Uni­ underl ying arachnoid was also grossly normal. However, th ere were a few small whitish versity Medical School, Chicago, IL 60611 . areas in the arachnoid. The roots of the cauda equina appeared swoll en and somewhat hyperemic . The biopsy specimen of the arachnoid showed diffuse infiltrati on wi th lymphoma AJNR 3:233-237, May/ June 1982 0 195-6108/ 82/ 0303-0233 $00.00 celi s in the arachnoid (fig . 1 C). Despite radiation and chemoth erapy, the patient continued © Am erican Roentgen Ray Society to deteriorate with third nerve palsy and right arm paralysis. He died 2 weeks later. 234 KIM ET AL. AJNR :3, May I June 1982

A B A B • • II

c c .. Fig . 1.- Case 1. Posteroanteri or (A) and lateral (6) lumbar myelogram. Thickened nerv e roots with parallel longitudinal striations. C, Photomicro­ Fig. 2. -Case 2. Posteroanterior (A) and lateral (6) lumbar myelogram. graph of arachnoid . Leptomeningeal infiltration by lymphoma cells (H and E Thickened nerve roots with parallel longitudinal striations. C, Ph otomicro­ X 400.) graph of cerebrospinal fluid cytology. Lymphoma cells. (Papanicolaou X400.)

Case 2 noma 15 years before and left breast carcinoma was discovered 2 A 61-year-old man was hospitali zed with complaints of low back months earlier. Computed tomography (CT) of the brain showed pain rad iating to both legs and difficulty in walking of 2 weeks extraventricular obstructive hydroceph alus. A ventriculoperitoneal durati on. He was found to have hilar, submandibular, and gastric shunt tube was in serted. Cerebrospinal fluid analysis showed class masses 2 months before admission. Th e biopsy from th e gastric IV adenocarcinoma cells. She received radiation therapy to the mass showed histi ocytic lymphoma. The physical examination re­ brain and intrathecal methotrexate through th e reservoir of the vealed a partial left seventh nerve palsy, decreased muscle strength shunt. Her condition improved and she was discharged. She was in th e hip extensors bilaterally, and reduction of pinprick sensati on readmitted 4 months later because of difficulty in walking. in both heels. A myelogram was obtained (figs. 2A and 28). The Ph ysical examination revealed weakness of th e lower extremities, spinal fluid was viscous and xanthrochromic. The protein conten t of reduction of position sense of the toes, and absence of deep tendon th e spinal fluid was 2,400 mg/ dl. Lymphoma cell s were iden tified refl exes in the lower extremities. Repeat CT of th e brain showed no in th e spinal fluid (fig. 2C) . The myelog ram showed diffuse thickened evidence of metastasis. Ventricular size was within normal limits. A nerve roots with parall el longitudinal striations. Radiation th erapy to total myelogram was obtain ed. The spinal fluid was xanthochromic. th e whole spinal axis was immediately initiated. The protein conten t of the spinal fluid was 880 mg / dl and the Case 3 cytology showed class IV adenocarcinoma cell s. The myelogram showed markedly thickened nerve roots with parallel longitudinal A 68-year-old woman was admitted because of confusion and striations in th e caud a equina (figs. 3A and 38). Radiation therapy memory loss. She had a right radical mastectomy for breast carci- to the entire spinal axis was immediately initiated . AJN R:3, May/ June 1982 SPINAL LEPTOMENINGEAL INFILTRATION 235

Fig. 3.-Case 3. Posteroanteri or (A) and lateral (B) lumbar myelogram. Mark­ edly thickened nerve roots with parallel longitudinal striations.

Fig . 4.-Case 4. Posteroanterior lum­ bar myelogram. Nerve roots of cauda equina are thicker than normal with pat­ tern of parallel longitudinal straitions. 3A 38 4

Case 4 tim e was peripheral polyneuropathy and she was discharged on prednisone treatment. A 45-year-old man developed left eye proptosis without loss of She was ad mitted again several months later with focal seizures visual acuity. Tissue surgically removed from the left retrobulbar and papilledema. A cerebral angiog ram showed hydrocephalu s. A space 1 year later was diagnosed as pseudotumor. He underwent ventricular peritoneal shunt was performed. After the operation, the radiation therapy with good response. Left forehead and left neck patient continued to deteriorate and a myelogram was obtained. masses developed 2 years later. Excisional biopsy of the ri ght The spinal fluid was very viscous and xanthochromic with th e supraclavicular lymph node revealed numerous atypical plasma protein content over 3 ,000 mg / dl and a negative cytology. Th e cell s. Serum protein electrophoresis demonstrated a monoclonal myelogram showed complete block at the T12-L 1 level and an IgM spike, but the bone marrow biopsy was negative. Radiation almost complete block at the L4-5 level. The margin of the cranial treatment of presumed extramedullary plasmacytoma obtained a block was irregular and the caudal block had a tapered appearan ce. good response. Th e contrast column appeared rigid and irregular (figs. 5A and 5B). Th e patient was hospitalized 7 years later after 6 months pro­ A laminectomy was performed at the T1 2-L 1 level. The dura gressive weakness in the lower extremities. He complained of some appeared normal, however, the arachnoid immediately below ap­ pain in both quadricep and hamstring areas. On physical examina­ peared opaque and milky. The biopsy of this part of the arachnoid tion, he had decreased strength in the proximal muscles and distal tissue showed diffuse infiltration by anaplasti c cells that was com­ hypoesth esia. Myelography showed thickened nerve roots in th e patible with metastatic adenocarcinoma of the breast (fig . 5C). The cauda equina with parallel longitudinal striations (fig. 4). Cerebro­ patient died 2 months later. spinal fluid protein was 325 mg / dl; glucose, 60 mg / dl; and mono­ cytes, 39%. Cytology was negative. The patient underwent radiation treatment of a total tumor dose of 1,800 rad (1 8 Gy) to the whole Discussion craniospinal axis. At the end of treatment, he was pain free with some improvement in strength in th e lower extremities. Leptomeningeal infiltration by systemic cancer is char­ acterized by diffuse or multifocal infiltration of th e pia-arach­ noid prolongations around cranial and spinal nerve roots Case 5 and into the perivascular spaces of th e superficial cortex. A 48-year-old woman was admitted with weakness and pain in This form of tumor growth is distinct from the metastatic both legs. She also had numbness in the left foot and numbness nodular proliferations of the parenchyma and dura. The and paresthesias of both hands. Her symptoms had progressed tumor grows in sheetlike fashion along the surface of the slowly during the previous year. She had a left mastectomy for brain and spinal cord, at times eliciting an inflammatory breast carcinoma 15 years before. On neurologic examinati on, the reaction . It is this pathologic picture that is termed meningitis cranial nerves were intact except for inability to abduct the left eye carcinomatosa. Gross inspection of the brain, spinal cord, beyond the midline. Sensory examination showed decreased light and nerve roots often reveals little or no abnormality. Among touch and pinprick sensation in both feet to ankle level and absent position and vibration sense in both feet. Both legs were markedly the positive gross findings, leptomeningeal thickening is wasted and hypotonic. The right leg was completely paralyzed and commonly described as opaque, opalescent, milky, and the left leg was partially paralyzed distally. The diagnosis at that whitish. Discrete nodules or focal granularity may be seen , 236 KIM ET AL. AJNR:3. May / June 1982

cal. A similar pattern was observed by others in cases of lung carcinoma and melanoma [7 -9]. The parallel striations correlated with thickened nerve roots by diffuse tumor infil­ tration . The cauda equina and lumbosacral region are the most common sites of spinal involvement. The infiltration is more on the dorsal surface, probably due to gravitational effect [1 , 2]. Guyer and Westbury [8] noted multiple nodular filling defects along the nerve roots of the cauda equina in a case of lung carcin oma. Similar findings were described by others [3, 10, 11]. The multiple nodules correlate with focal accu­ mulation or local proliferations of cancer cell s in the lepto­ meninges along the nerve roots. Prentice et al. [10] described a complete block of Panto­ paque in the lower thoracic region in a case with reticulum cell sarcoma. The contrast material was introduced via cisternal puncture after unsuccessful lumbar punctures. At the level of the block, the contrast column was irregular, resembling that of chronic ad hesive arachnoiditis. Case 5 demonstrated a similar complete block with irregular mar­ gins at the thoracolumbar junction in addition to an almost complete block at the L4-5 level (figs. 5A and 58). A 8 Lumbar puncture is often difficult to perform because of obliteration of the subarachnoid space due to swollen nerve roots, occasionally resulting in dry puncture. It may cause severe radiating pain to the lower extremities. The spinal fluid is often xanthochromic and occasionally viscous due to increased protein content. The cytology is positive in 20%-50% of cases [1-3]. Oil contrast material (Pantopaque) was used in all of our cases. Ree et al [11] advocated Amipaque, demonstrating multiple nodular defects along the nerve roots in the cauda equina in a case of spinal leptomeningeal carcinomatosis. The swollen nerve roots would probably be demonstrated to better advantage by using a water-soluble contrast ma­ teri al. However, since the lesions are poorly localized clini­ cally, a total myelogram is often requested, in which case we prefer using Pantopaque. Even in patients with sus­ Fi g. 5. -Case 5 . A. Posteroanteri or lumbar myelog ram. Almost complete block with tapering appea rance at L4 -L5. B. Complete block with irreg ular pected spinal metastasis whose clinical findings suggest a margin at T1 2-L 1. Filling defect at L2 on right is air bubble. C. Photomicro­ lesion in the lumbar region, it is important to evaluate the graph of arachnoid . Leptomeningeal in filtrations by anaplastic cell s compat­ entire spinal canal in search of other clinically sil ent lesions. ible with metastasis from breast carcinoma. In cases with blocks in the cervical or upper thoracic region, th e tumor margins are usually better demonstrated with Pantopaque. Another advantage of using Pantopaque is that attributed to focal accumulation of proliferation of cancer some of the contrast material may be left in the spinal canal cell s in the leptomeninges. These nodules are most often for future follow-up, if necessary. found along nerve roots of the cauda equina [1 -3]. In summary, one of a combination of the following mye­ Th e mode of tumor spread to th e leptomeninges has been lographic patterns have been observed in the spinal lepto­ controversial. Peripheral lymphatic invasion, hematogenous meningeal infiltration by systemic cancer: (1) parallel longi­ dissemination, seeding through the choroid plexus, or tudinal striations in the cauda equina due to thickened nerve spreading of th e tumor from the brain parenchyma and roots; (2) bizarre, irregular filling defects with varying de­ nerve roots to the cerebrospinal fluid have been suggested grees of blocks, resembling arachnoiditis; or (3) multiple [1 ,3, 4]. nodular defects along the nerve roots of the cauda equina. Van Allen and Rahme [6] reported a case of diffuse Th e main differential diagnostic possibilities are hyper­ leptomeningeal lymphosarcomatous infiltration of th e cauda trophic interstitial polyneuritis [12] and arachnoiditis. Differ­ eq uina with myelographic appearance of longitudinal par­ entiation of the parallel longitudinal striations in the cauda all el striations. At· surgery,. markedly swoll en nerve roots of eq uina from hypertrophic interstitial polyneuritis may be the cauda equina appeared like a mass of " spaghetti ." Th e impossible. If there is associated irregularity of th e contrast myelographic features of our cases 1 - 3 and 5 were identi- column in addition to the longitudinal striations, hypertrophic AJNR:3, May / June 198 2 SPINAL LEPTOMENINGEAL INFILTRATION 237 interstitial polyneuritis is less likely since the arachnoid lining 1971 ;52 : 200-208 should be smooth, However, the combination of longitudinal 5. Bunn Jr PA, Schein PS, Banks PM , DeVita VT. Central nervous striations and irregularity of the contrast column may be system complications in patients with diffuse histi ocytic and difficult to differentiate from arachnoiditis [13]. undifferentiated lymphoma: leukemia revi sited. Blood Differentiation of irregular filling defects with varying de­ 1976;47: 3-1 0 6. Van Allen MW, Rahme ES . Lymphosarcomatous infiltrati on of grees of block from arachnoiditis may also be impossible, the cauda equina. Arch Neuro/1962;7 : 476-48 1 However, in a clinical setting when the spinal form of lepto­ 7. Heiser S, Swyer AJ . Myelography in spinal metastasis. Radiol­ meningeal infiltration by systemic cancer is suspected, one ogy 1954;6 2: 695-701 or a combination of the above myelographic patterns will be 8 . Guyer PB, Westbury H. Th e myelographic appearance of spinal helpful in establi shing the diagnosis, cord metastasis. Br J Radio/1968;41 : 6 15-6 19 9. Jacobsen HH , Lester J. A myelographic manifestati on of diffuse spinal leptomeningeal melanomatosis. Neuroradiology 1970;1 :30-3 1 REFERENCES 10. Prentice WB, Kieffer SA, Gold LH , Bjornson RG . Myelographic characteristics of metastasis to the spinal cord and caud a 1. Grain GO, Karr JP. Diffuse leptomeningeal carcin omatosis. equina. AJR 1973; 118: 682-689 Clinical and pathological characteristics. Neurology (NY) 11. Ree AH , Jensen LB. Spinal leptomeningeal carcinomatosis 1955;5: 706-722 visuali zed by Amipaque myelography. Neuroradiology 2. Parsons M. The spinal form of carcinomatous meningitis. Q J 1979; 17 : 283 - 284 Med 1972;41 : 509-518 12. Rao CV , Fitz CR , Harwood-Nash DC. Dejerin e-Sottas syndrome 3. Olson ME, Chernik NL, Posner JB. Infiltration of the leptomen­ in children (hypertrophic interstitial polyneuritis). AJR inges by systemic cancer: a clinical and pathological study. 1974;122 : 70-74 Arch Neuro/1974;30: 122-1 27 13. Love JG, Kao CC, Baker HL. Painless intraspinal leptomenin­ 4. Griffin JW, Th ompson RW, Mitchison MJ, Path MR , Ki ewet JC , geal carcinomatosis: a myelographic demonstration. J Neuro­ Weiland FH . Lymphomatous leptomeningitis. Am J Med surg 1970;32 : 1 0 8-111