Cerebral lymphomatoid granulomatosis

May 31, 2017 | Autor: A. Kermode | Categoria: Clinical Neuroscience, Central Nervous System, Clinical Sciences, Neurosciences
Share Embed


Descrição do Produto

Cerebral lymphomatoid granulomatosis

A.G. K e r m o d e

M D FRACP MRCP

P.D. R o b b i n s * MBBS FRCPA W . M . C a r r o l l MD FRACP Department of Neurology and Clinical Neurophysiology and West Australian Centre for Pathology and Medical Research*, Sir Charles Gairdner Hospital, Western Australia, Australia

Lymphomatoid granulomatosis (LG) is an uncommon lymphoproliferative disease characterised by angiocentric and angioinvasive cellular infiltrates. The lung is the usual primary site with secondary central nervous system (CNS) involvement in 20% of cases. Primary cerebral LG is a rare but potentially treatable disease with protean manifestations. Diagnosis is problematical and may be delayed when extracerebral disease is absent or occult. Six cases of cerebral LG are presented, and the clinical features, laboratory investigations, neuroimaging and pathological findings are reviewed. Journal of Clinical Neuroscience 1996, 3 (4):346-353

© Pearson Professional 1996

Keywords: Lymphomatoid granulomatosis, Cerebral lymphoma, T Cell

Introduction Lymphomatoid granulomatosis (LG) is an u n c o m m o n multi-system lymphoproliferative disease most frequently involving the lungs, skin, nervous system and kidneys. The original pathological descriptions by Liebow et al (1972) were of an 'angiodestructive lymphoreticular proliferative and granulomatous disease involving predominantly the lungs') The condition was considered to be non-neoplastic but progression to lymphoma was noted in 13% of this series, and on the basis of both clinicopathological and immunophenotypic studies it is now generally accepted to represent malignant nonHodgkin's lymphoma (NHL) from the outset, or usually evolves to become a malignant process, z-6 Controversy as to the nature and histogenesis of LG has persisted, particularly with regard to the relationship of LG to malignant NHL. LG is now widely regarded as a post-thymic T cell lymphoproliferative disorder. Histopathologically LG belongs to the group of angiocentric immunoproliferative lesions (AIL) 3'7'8 which commonly involve extranodal sites, and include such entities as polymorphic reticulosis and some cases of lethal midline granuloma. 9 M L may show a range of morphological appearances, graded by some according to the degree of cellular atypia and inflammatory background? Cytologically malignant lymphoid proliferations with an angiocentric and angiodestructive character are regarded as angiocentric lymphomas and represent an end point of this spectrum of disease? LG has a male preponderance by a ratio of 2:l, typically presenting in the fourth to sixth decades. Cough or other respiratory symptoms occur in the majority, frequently associated with fever and weight loss. Chest X-ray (CXR)

346

often demonstrates bilateral discrete nodules that may cavitate, but lymphadenopathy is rare. Extrapulmonary disease is c o m m o n with skin involvement in almost 40% and neurological disease in approximately 30%? °m Cumulative mortality is significant, and with CNS disease the mean survival is 14 months after diagnosis. 10 However, there is evidence to suggest that with aggressive therapy this may be improved, and prolonged survival with CNS disease is well documented. 2'12'1~,~4 When the disease presents in the lungs, the clinical features and radiographic findings usually lead to appropriate investigations and a tissue diagnosis. Rarely, however, the first symptoms are neurological and LG may masquerade as a n u m b e r of other conditions. 12-24 In these circumstances the diagnosis may be delayed. Awareness of the disease spectrum in the CNS may permit the diagnosis to be considered at an earlier stage and thus allow institution of appropriate therapy. In published cases of CNS involvement the diagnosis has frequently only been made at autopsy. We describe 6 patients presenting with cerebral LG of whom 4 had no clinical evidence of disease activity outside the CNS, and only one had a clearly non-neurological presentation. The diagnostic and therapeutic difficulties are discussed.

Case 1 A previously well 56 year old man presented with complex partial seizures. Cranial CT demonstrated a right temporal non-enhancing mass lesion which was excised and was initially diagnosed as a low grade glioma.

J. Clin. Neuroscience Volume 3 Number 4 October 1996

Cerebal lymphomatoid granulomatosis

Clinical studies

Fig. 1 Sections of cerebral and pulmonary biopsy lesions from cases 1, 3, 4 and 5. Angiocentric lymphoid infiltrates are present in cerebral tissue (case 1, A), cerebellar tissue (case 3, B), and the lung (cases 4 and 5, C and D respectively). The lymphoid infiltrate permeates and invades the walls of the pulmonary vessels (C, D). (Haematoxylin-eosin stain. Magnification x 250).

He remained well on carbamazepine, with only occasional complex partial seizures. He re-presented 2 years later with a 2 week history of drowsiness, morning headache, nausea, vomiting, and left sided weakness. On examination he was cognitively intact with bilateral papilloedema and mild left sided hemiparesis. Cranial CT showed tumour recurrence with right frontotemporal oedema, compression of the right lateral ventricle, and tumour extension into the third ventricle causing obstructive hydrocephalus. Following cerebral biopsy and insertion of an intraventricular catheter frozen section of the tumour suggested a grade I astrocytoma. Ventricular CSF showed 26 white cells per microlitre, of which 90% were mononuclear and 10% were neutrophils. CSF cytology showed increased numbers of neutrophils, macrophages, lymphocytes and plasma cells, but no malignant cells. Histological examination revealed angiocentric and angioinvasive lymphoreticular infiltrates in a background of gliosis and ischaemic damage. The angiocentric infiltrate consisted of lymphocytes, plasma cells,

histiocytes and atypical mononuclear cells consistent with LG (Fig. 1A). Immunophenotypic studies in formalin fixed tissue sections revealed positive staining with polyclonal CD3, CD43 (MT1) and CD45RO (UCHL1) in the majority of infiltrate. A reciprocal pattern of positivity for CD20 (L26) was observed in the population of cells which were negative with the T cell markers. Further extensive investigation failed to find evidence of LG outside the CNS. External radiotherapy was commenced but the patient deteriorated rapidly. After 3 weeks repeat cranial CT showed widespread infiltration throughout the brain, complete collapse of both ventricles and midline shift, despite high dose dexamethasone. He became unconscious, radiotherapy was ceased and he died 5 weeks after admission. A necropsy was not performed. Case 2

A 39 year old man presented 3 weeks after an upper respiratory tract infection with an ataxic paraparesis of one

J. Clin. Neuroscience Volume 3 Number 4 October 1996

347

Clinical studies week's duration. On examination he had secondary upbeating nystagmus, mild right lateral rectus palsy, and skew deviation on levoversion. There was grade 3-4/5 pyramidal pattern weakness of both legs, worse on the left, with brisk reflexes and flexor plantar responses. Sensory examination was normal. There was appendicular ataxia and he was unable to walk without assistance. High resolution MRI of the spinal cord was unremarkable. Cerebral MRI showed a lesion without mass effect in the left pontomedullary region (Fig. 2A). CSF examination showed 15 white cells per microlitre, with a protein of 0.55 g/1 (normal < 0.45 g/l) and glucose of 3.7 mmol/1 (blood glucose 5.6 mmol/1). CSF oligoclonal bands were absent and cytology was unhelpful. CXR, routine haematology, biochemistry, and extensive serological tests were non-contributory. Visual evoked responses were normal. The patient was treated with high dose methylprednisolone (HDMP) for 5 days, and he slowly improved, being able to walk independently at the time of discharge 8 days after admission. Two months later he relapsed with worsening of his previous signs. CSF examination remained negative for oligoclonal bands, but again the white cell count and protein were elevated. HDMP for 5 days produced little improvement. A working diagnosis of probable multiple sclerosis was considered. A further two months later he was readmitted for investigation. He was now chairfast with independent transfer, and had a mild bulbar palsy. The CSF protein was elevated further at 0.72 g/l, and was positive for oligoclonal bands. Cerebral MRI showed marked progression with multiple irregular Gd-DTPA enhancing areas of high signal in the posterior fossa and extending superiorly into the midbrain (Fig. 2B). Visual

A

Cerebal lymphomatoid granulomatosis evoked responses remained normal. HDMP therapy was again administered. In view of the unusually aggressive clinical course, persistently elevated CSF white count and protein, and atypical MRI features, diagnoses of lymphoproliferative disease or an unusually aggressive glioma were also entertained. Intracranial biopsy was proposed but rejected by the patient. He continued to deteriorate and developed complex ophthalmoplegia, rhythmic blepharoclonus, palatal myoclonus, and ataxic spastic quadriplegia. Eight months after presentation repeat CSF electrophoresis now showed that oligoclonal bands were absent. He developed hypostatic pneumonia and died 11 months after presentation. At autopsy the cerebral hemispheres, cerebellum and spinal cord were macroscopically unremarkable. The pons and medulla were irregularly expanded, firm and mottled in appearance. Histological examination revealed a dense and polymorphic lymphoid infiltrate (Fig. 3A). Similar but less marked changes were also present in the basal ganglia, cerebellar white matter, spinal cord and hippocampus. The infiltrate was composed chiefly of small lymphocytes with occasional large atypical mononuclear cells, and was markedly angiocentric in distribution with extensive involvement of surrounding glial tissues (Fig. 3B). Subendothelial invasion of vessels was prominent and was accompanied by patchy necrosis and inflammatory reaction. Immunohistochemistry revealed positive staining with the pan T cell markers polyclonal CD3, CD43 (MT1) and CD45RO (UCHL1) in the majority of lymphoid cells of the infiltrate (Fig. 3C), with a much smaller reciprocal population staining with the pan B cell marker CD20 (L26). These findings were confined to the CNS.

B

Fig. 2 A) T2-weighted MRI (Philips Gyroscan, 1.5"I", 5 mm axial slices) at 4 contiguous levels in the pontine region in case 2 demonstrating small high signal lesions without mass effect in the left pontomedullary region (arrow), not dissimilar in size and distribution to those seen in demyelinating disease. B) Corresponding study taken 4 months later than the images in Figure 2A demonstrating marked progression of disease with multifocal involvement of the brainstem and cerebellum.

348

J. Clin. Neuroscience Volume 3 Number 4 October 1996

Cerebal lymphomatoid granulomatosis

Clinical studies

A

B

I3

Fig. 3 Sections obtained from post-mortem pontine tissue illustrating the morphology and immunohistochemistry of the lesions in case 2. An angiocentric infiltrate surrounds vessels and extends into the glial tissue (A), composed chiefly of small lymphocytes with occasional larger mononuclear cells (B) (Haematoxylin-eosin stain). The majority of the cellsforming the infiltrate demonstrate immunohistochemical positivity for the pan T cell marker CD45RO (UCHL1) (C). (Magnifications (A) x 80, (B) and (C) x 200).

dextroversion. Brachial power was normal but there was right sided hyperreflexia, dysdiadochokinesis and dysmetria. Superficial abdominal reflexes were absent. There was global thinning of the muscles of the right leg, asymmetric spastic paraparesis with sustained right ankle clonus, and extensor right and equivocal left plantar responses. The right leg was ataxic and he tended to fall to the right when walking. Routine biochemistry revealed mild hypokalemia consistent with his vomiting. Cerebral MRI demonstrated a partially cystic mass lesion measuring 9 cm in diameter in the right cerebellar hemisphere (Fig. 4), compressing the fourth ventricle. CSF protein was 0.66 g/1 with 2 white cells per microlitre and normal CSF cytology. A stereotactic biopsy was non-diagnostic showing only a mixed infiltrate of small lymphocytes and histiocytes in the glial tissue without angiocentricity or atypia of the lymphoid cells. An open biopsy yielded glial tissue containing a polymorphous perivascular infiltrate associated with extensive necrosis (Fig. 1B). Immunophenotypic studies of formalin fixed tissue revealed the majority of cells to be positive for the T cell markers polyclonal CD3, CD43 (MT1) and CD4~RO. Further investigatibns including abdominal ultrasound, colonoscopy, (~XR, urine cytology, and thyroid scan were non-contributory, and indeed the LG appeared to be restricted to the CNS. The patient was c6mmencedL on HDMP with rapid and impressive improv}ment in symptoms and signs and ! was followed by local radiotherapy of 50 Gray in 25 fractions to the posterior fossa resulting in considerable regression in tumour size on MRI. He remains alive although significantly disabled 5 years after presentation.

Case 3

A 51 year old man presented with a 6 month history of progressive allodynia over the distal sole of the right foot. The area was exquisitely sensitive to various stimuli such as light touch, hot water and walking, often causing flexor spasms. The left leg was unaffected, and there was no bladder or bowel disturbance. Three weeks prior to admission he noticed horizontal diplopia. On examination there was a right lateral rectus palsy. The remainder of the cranial nerve and upper limb examination were non-contributory. The right foot was warm and slightly swollen, with thinning of most of the muscles of the right leg. There was bilateral hypertonia, hyperreflexia, and pyramidal pattern weakness grade 4/5 more marked on the right. The right plantar response was extensor. Hyperaesthesia was present to epicritic stimuli on the right foot, but proprioreception and pallaesthesia were intact. Routine haematology, biochemistry, autoantibody screens, viral, borrelial, retroviral and treponemal serology, serum electrophoresis, abdominal and pelvic CT, and CXR were non-contributory. Thoraco-lumbar myelogram, MRI of the conus medullaris and Cerebral MRI were normal. EMG and nerve conduction studies did not reveal peripheral nerve or radicular involvement. Visual evoked responses were normal. The initial CSF study showed a protein level of 0.50 g/l, white cell count of 7 per microlitre, normal glucose (3.3 mmol/1), and a discrete band in the gamma region on electrophoresis. Cytology did not identify malignant cells, but immunological studies showed the lymphocytes to be o f T cell origin. No firm diagnosis was made and the patient was treated symptomatically with carbamazepine and baclofen. He was readmitted for investigation 4 months later and the CSF protein had risen to 0.94 g/l, but again extensive investigations failed to establish the diagnosis. His symptoms regressed then remained stable until 4 years later when he developed progressive nausea, dysguesia, vomiting, right hemiataxia and unsteady gait. He lost 4 kg in weight over 4 weeks. The general examination was unremarkable. He was dysarthric, and showed saccadic pursuit, and horizontal nystagmus to the right on

\

'Case 4 \ A 57 year old man presented with dry cough and pyrexia of unknown origin and was admitted for investigation. He had mild splenomegaly, an elevated erythrocyte sedimentation rate (ESR) of 100 m m / h r , and a mild peripheral leukocytosis with a left shift. Extensive virological, fungal, protozoal and bacteriological investigations

J. Clin. Neuroscience Volume 3 Number 4 October 1996

349

Clinical studies

Cerebal lymphomatoid granulomatosis

Fig. 4 Corresponding pre-contrast A) and Gd-DTPA enhanced T~weighted parasagittal images (B) in case 3 showing an irregular, partly cystic 2 cm masswith surrounding oedema in the medial right cerebellar hemisphere which has an enhancing (B) hypercellular and proteinaceous margin. (Philips Gyroscan, 1.5T). failed to isolate an infective agent. He improved during empirical treatment for presumed bronchial infection and was discharged. One week later his condition worsened and he redeveloped cough, sweats and rigors, and was noted by his wife to be confused. He developed aposiopetic speech and was also unable to tie his shoelaces, dress himself or put on a seat belt. He was readmitted. Cerebral MRI and CXR were normal. CSF examination showed 20 lymphocytes per microlitre, protein of 0.64 g/l, and reduced glucose of 4.7 mmol/1 relative to a concurrent blood glucose of 12 mmol/1. He was febrile, agitated, dysphasic and confused but responded to mime. He was photophobic with mild meningism. There was alternating skew deviation of the eyes, cogwheeling hypertonia in the left arm, symmetrical depression of all tendon reflexes, and bilateral withdrawal plantar responses. He responded to pinprick stimulation in all 4 limbs. Further investigations for infective agents were pursued. Empirical treatment for Herpes simplex encephalitis was commenced. His EEG showed widespread low amplitude slow wave activity consistent with a generalised encephalopathy. Generalised tonicclonic seizures requiring treatment with intravenous anticonvulsants heralded deterioration of his condition. An open lung biopsy was performed. Macroscopically the tissue was normal, but histological examination demonstrated a polymorphic angiocentric infiltrate of large atypical lymphoid cells, small lymphocytes and histiocytes, representing an angiocentric large cell lymphoma (Fig. 1C). Immunophenotypic studies in formalin fixed tissue sections revealed a mixture of T and B cells. Skin biopsy and bone marrow examination were unremarkable. Therapy was c o m m e n c e d with HDMP, adriamycin, cyclophosphamide, and vincristine, with intrathecal arabinoside-C. He had an excellent response, but then relapsed and died 6 months after presentation.

Case 5 A 19 year old man presented from a rural centre with fever, confusion and focal m o t o r seizures. He lived at

350

home with his mother and had a history of learning and social difficulties first detected at age 9. At age 11 years he suffered a respiratory illness diagnosed as p n e u m o n i a and diffuse opacities were noted on his CXR. At 18 years of age he presented with intermittent chest discomfort, and a working diagnosis of pulmonary interstitial eosinophilia was made. He was treated with several courses of oral corticosteroids during symptomatic periods. Four weeks after his last course of oral steroids he developed fever, headache and confusion. Three days later right facial focal motor seizures precipitated his transfer to hospital. General examination was unremarkable apart from scattered respiratory wheeze and small testes. There was no lymphadenopathy. He was conscious but disorientated. Cranial nerves were normal. In the limbs tone and power were normal but he had generalised hyperreflexia more marked on the right with an equivocal right plantar response. The ESR was 10 m m / h r with a peripheral white cell count of l l . 0 / n a n o l i t r e . The urea was elevated at 12.9 mmol/1 with a creatinine of 97 mmol/1. CXR showed bilateral diffuse pulmonary opacities without hilar lymphadenopathy. An urgent pre- and post-contrast cranial CT p e r f o r m e d with an early generation scanner was normal. The CSF study showed an elevated protein of 7.81 g/l, 21 lymphocytes per microlitre and normal glucose of 3.1 mmol/1. CSF cytology was non-contributory. Extensive bacteriological investigations were unhelpful. The CSF protein rose to 11.4 g/l, the lymphocyte count to 96 lymphocytes per microlitre, and the glucose fell to 2.1 mmol/1 with a c o n c u r r e n t blood glucose of 5.0 mmol/1. He experienced a generalised tonic-clonic seizure, followed the next day by progressive decorticate posturing. An o p e n lung biopsy was performed. A polymorphic infiltrate composed of small lymphocytes, histiocytes and large atypical lymphoid cells effaced the p u l m o n a r y architecture. The infiltrate was angiocentric in distribution with permeation and infiltration of vessel walls (Fig. 1D). I m m u n o p h e n o t y p i c studies of formalin fixed tissue revealed the majority of the lymphocytes to decorate with the T cell markers polyclonal CD3, CD43 (MT1) and

J. Clin. Neuroscience Volume 3 Number 4 October 1996

Cerebal lymphomatoid granulomatosis

Clinical studies

CD45RO (UCHL1). Only small numbers of small lymphoid cells were positive for the pan B cell marker CD20 (L26). Post-operatively he d e v e l o p e d the syndrome o f inappropriate antidiuretic h o r m o n e which later reverted to diabetes insipidus. He was treated aggressively with c y c l o p h o s p h a m i d e and corticosteroids. A r e p e a t cranial CT showed discrete contrast enhancing lesions in the right posterior temporal region with associated surrounding low attenuation, and infiltration of the hypothalamus with enhancing tissue. His neurological and pulmonary disease progressed relentlessly with the development of recurrent pneumothoraces, mononeuritis multiplex, progressive cognitive decline, and brainstem involvement. He was finally 'locked in' with blinking being his only form of communication and died from pneumonia 12 months after his neurological presentation. A necropsy was not performed.

Case 6 An unemployed 20 year old male presented with a history of several days of vertigo, ataxia, nausea and vomiting which resolved spontaneously. Four weeks later he represented again with vertigo and nausea. Ten days later he developed weakness of the u p p e r legs, ataxia and 'tremulousness'. These symptoms spontaneously resolved after 2 weeks. A further 8 weeks later he represented with positional vertigo, ataxia and vomiting. On examination he had bilateral horizontal gaze evoked nystagmus, generalised but crural p r e d o m i n a n t hypertonia and hyperreflexia with unsustained ankle clonus, and a mildly ataxic gait. Abdominal reflexes were normal. T h e r e were no sensory signs. Routine haematological and biochemical investigations were normal, including the erythrocyte sedimentation rate. Serological tests were non-contributory. CT of cranium showed a small focus of contrast e n h a n c e m e n t immediately posterior to the fourth ventricle. MRI revealed multifocal, irregularly enhancing lesions in the mesial aspect of both cerebellar hemispheres, the superior and inferior vermis, and a nonenhancing lesion in the right lateral pons. T h e r e was only minimal mass effect with subtle distortion of the r o o f of the fourth ventricle, but the findings were however suggestive of a neoplastic process. CSF examination showed a protein of 0.74 g/l, glucose 3.0 mmol/1 (serum 4.6), 25 m o n o n u c l e a r cells/microlitre (lymphocytes), with no malignant cells seen. Cerebellar biopsy included abnormal white matter showing ischaemic changes with a loose pattern ofgliosis and macrophage reaction. Angiocentric lymphoid infiltrates were present focally; these dense lymphocytic infiltrates s u r r o u n d e d and invaded vessel walls and contained numerous small lymphocytes with occasional larger lymphoid cells and histiocytes. T h e r e was insufficient representative material for i m m u n o p h e notypic studies. CXR and high resolution CT chest were normal. T h e patient continued to deteriorate and refused specific treatment. He was wheelchair b o u n d within 4 months, and died 12 months after diagnosis. An autopsy was not p e r f o r m e d .

Discussion The clinical features of CNS disease in LG are protean and include headache, blindness, polyneuritis cranialis, hemiparesis, altered consciousness, confusion, cerebrovascular syndromes, ataxia, seizures, polyradiculopathy, myelopathy, Parkinsonism and even dementia.2,15,20, 24-27T h e disease may rarely have spontaneous remission in the peripheries, 5 and when this occurs in the CNS the diagnosis of multiple sclerosis may be suggested, 12,14,z2as in cases 2, 3 and 6 above. In parallel with the wide range of clinical presentations, cerebral imaging including MRI may vary from normal (as in 2 of our cases at their initial study) to mass lesions. Many kinds of CNS lesions in LG have been described. They may be unifocal or multifocal, both above and below the tentorium or in the spinal cord, with oedema, mass effect, e n h a n c e m e n t and haemorrhagic changes to variable degrees. 2,1°,13,19,25,26When LG presents in the absence of extra-CNS manifestations and depending on the clinical context, the presence of multifocal lesions on MRI suggests the diagnosis of multiple sclerosis, cerebral lymphoma, multifocal glioma, or cerebral vasculitis, but other conditions including HIV need to be considered. Indeed MR/ may reveal lepto-meningeal infiltration along Virchow-Robin spaces ~s,a9 and suggest neurosarcoidosis or cryptococcal meningoencephalitis. The diagnosis of LG in each of the present cases was made with difficulty and in most only after extensive diagnostic and clinical evaluation. It is useful to recount their respective clinical presentations and salient investigation findings. The neurological manifestations included encephalopathy followed by seizures in 2, an illness resembling multiple sclerosis in 3, and a mass lesion in 1. It is important to emphasise that despite utilising MRI the cerebral imaging was normal in case 4 who had a severe encephalopathy, and MRI of the entire neuraxis in case 3 was also normal until the precipitous relapse 4 years following the first symptoms. It should be noted that case 5 had a history of p u l m o n a r y infiltration diagnosed as p u l m o n a r y eosinophilia, which in retrospect probably represented the initial symptoms of his LG. Moreover, given the long history of p u l m o n a r y involvem e n t it is possible that the patient's cognitive difficulties first noticed at age 9 may also have been related to cerebral LG, analogous to the dementia occurring in the case r e p o r t e d by Kleinschmidt-DeMasters et al.24 The initial CSF examination was abnormal in all patients. The protein was elevated in all, 5 of 6 had a mild non-specific pleocytosis, and oligoclonal bands were present in one with a monoclonal band in another. Despite the consistent finding of elevated CSF protein levels and 5 having a mild pleocytosis, cytology was unhelpful in all despite multiple CSF samples. Immunophenotyping of CSF cells was also p e r f o r m e d but was unhelpful. The presence of oligoclonal bands in case 2 was initially interpreted as being consistent with a diagnosis of probable MS, but its later disappearance argued against this diagnosisY A tissue diagnosis was sought in all patients, with cerebral biopsy being p e r f o r m e d in 3 and refused by a fourth.

J. Clin. Neuroscience Volume 3 Number 4 October 1996

351

Clinical studies When an intracranial mass lesion is present, particularly when it is in a non-eloquent area, the indications for proceeding to cerebral biopsy are strong. However, when cerebral imaging is unhelpful, such as in cases 4 and 5, there may be considerable diagnostic difficulty. In this situation transthoracic lung biopsy was p e r f o r m e d , which was suggested in case 5 by his abnormal CXR, and in case 4 by a dry cough despite a normal CXR. The biopsy tissue was diagnostic in both obviating the n e e d for a cerebral biopsy. This p r o c e d u r e should be considered as a less invasive alternative to cerebral biopsy if LG is suspected and a pathological diagnosis is pursued. The histological diagnosis of LG is p r o m p t e d by the presence of an angiocentric and angioinvasive lymphoreticular infiltrate which extends into surrounding tissues. The infiltrate is polymorphous in nature, and displays variable degrees of cytological atypia. LG, as with other forms of ML, represent a histological spectrum which may be classified according to a three grade scheme based on the degree of cellular atypia and inflammatory background? Areas of necrosis secondary to vascular damage and occlusion are frequently present, and sometimes there is an accompanying inflammatory infiltrate. Infective, demyelinative and other conditions which may be associated with perivascular lymphohistiocytic infiltrates n e e d to be considered in the differential diagnosis of LG. The angiocentric and angioinvasive nature of the infiltrate in LG may be missed in small CNS biopsies, such as stereotactic samples. O t h e r forms of cerebral non-Hodgkin's lymphoma are characterised by an angiocentric distribution of malignant cells. These may occasionally show subendothelial infiltration of vessels, but invasion of vessel walls is generally either absent or much less p r o m i n e n t than in LG. I m m u n o p h e n o t y p i c studies are of value in the diagnosis of LG and ML, but are often difficult to interpret because of the admixture of normal and atypical lymphoid cells present in the infiltrate. 8 I m m u n o p h e n o t y p i c studies in formalin fixed, paraffin e m b e d d e d tissue sections in the four cases (1-3 and 5) in this series having sufficient representative material available for review revealed a pattern of results consistent with a T cell i m m u n o p h e n o t y p e . In each instance the majority of the lymphoid cells reacted with the T cell markers polyclonal CD3, CD43 (MT1) and CD45RO (UCHL1), but not with the pan B cell marker CD20 (L26). I m m u n o p h e n o t y p i n g is e n h a n c e d by the availability of representative fresh frozen tissue, and usually demonstrates mature post-thymic T cell phenotype with a p r e d o m i n a n c e of CD4 positive cells? The T cells may have aberrant patterns of T cell antigen expression and the B cells present are polyclonal in nature. Clonal antigen receptor gene rearrangements have b e e n detected albeit infrequentlyY ,9,29,3° Two of our patients received chemotherapy, two radiotherapy, and two died without specific treatment. Five patients died 6 months to 2 years (mean 13 months) following the onset of CNS disease, while one remains alive following radiotherapy at 5 years. Treatment for cerebral LG must be considered on a case by case basis. Some authors have suggested that although treatment

352

Cerebal lymphomatoid granulomatosis may arrest systemic disease the CNS c o m p o n e n t may progress regardless) 7,sl More recently it has been proposed that aggressive multidrug chemotherapy should be given at the onset of disease,S,s2 and many would augm e n t this with local radiotherapy to the affected areas of t h e C N S . 17,19,24,26,33 Prolonged survival following local radiotherapy alone may occur is as in case 3, and this may be considered a therapeutic option if the disease appears confined to localised areas of the CNS. For neurologists the most difficult problems arise in diagnosis when extra-neurological involvement is absent or inapparent, a task made all the more difficult because of the variety of manifestations. LG should be suspected in all patients, particularly males, presenting with atypical radiculomyelopathy, brain stem encephalitis, meningoencephalopathy with seizures, and solitary mass lesions and should be treated as aggressively as malignant lymphoma.

Acknowledgements We thank Dr I~M.R. Grainger, Dr M.E Quinlan and DrJ. Scopa for allowing us to include their patients. Dr A.G. Kermode was supported by the CJ. Martin Fellowship from the National Health and Medical Research Council of Australia (937319). Abstracts of this manuscript were presented in 1993 at the annual meetings of the American Neurological Association, Boston and the Australian Association of Neurologists, Cairns. Received22 May 1995 Accepted for publication 20 November 1995

Correspondence and requests for offprints: Dr W.M. Carroll, Department of Neurology, Sir Charles Gairdner Hospital, Verdun St, Nedlands, W.A. 6009, Australia. Tel: (09) 346 3088 Fax: (09) 346 2455

References 1. Liebow AA, Carrington CRB, Friedman PJ. Lymphomatoid granulomatosis. Hum Pathol 1972; 3: 457-558. 2. Koss MN, Hochholzer L, LanglossJM, Wehunt WD, Lazarus AA, Nichols PW. Lymphomatoid granulomatosis: a clinicopathologic study of 42 patients. Pathology 1986; 18: 283-288. 3. Lipford EH, MargolickJB, Longo DL, Fauci AS, Jaffe ES. Angiocentric lymphoproliferative lesions: A clinicopathologic spectrum of post-thymic T-cell proliferations. Blood 1988; 72: 1674-1681. 4. Colby TV, Carrington CB. Pulmonary lymphomas simulating lymphomatoid granulomatosis. AmJ Surg Pathol 1982; 6: 19-32. 5. MyersJL. Lymphomatoid granulomatosis: past, present, ...future? Mayo Clin Proc 1990; 65: 274-278. 6. Medeiros LJ, Peiper SC, Elwood L, Yano T, Raffeld M, Jaffe ES. Angiocentric lymphoproliferative lesions: A molecular analysis of eight cases. Hum Pathol 1991; 22: 1150-1157. 7. Jaffe ES. Pathologic and clinical spectrum of post-thymic T-cell malignancies. Cancer Invest 1984; 2: 413-426. 8. Jaffe ES. Post-thymic lymphoid neoplasia. In: Surgical pathology of the lymph nodes and related organs. Jaffe ES, BenningtonJL, eds. WB Saunders Company, Philadelphia, 1985, pp218-248.

J. Clin. Neuroscience Volume 3 Number 4 October 1996

Cerebal lymphomatoid granulomatosis

Clinical studies

9. Gaulard P, Henni T, MarolleauJ, Haioun C, Henni Z, Voison M et al. Lethal midline granuloma (polymorphic reticulosis) and lymphomatoid granulomatosis. Cancer 1988; 62: 705-710. 10. Katzenstein AL, Carrington CB, Liebow AA. Lymphomatoid granulomatosis. A clinicopathologic study of 152 cases. Cancer 1979; 43: 360-473. 11. Fauci AS, Haynes BF, Costa J, Katz P, Wolff SM. Lymphomatoid granulomatosis. Prospective clinical and therapeutic experience over 10 years. N EnglJ Med 1982; 306: 68-74. 12. Kokmen E, BillmanJK, Abell MR. Lymphomatoid granulomatosis clinically confined to the CNS. Arch Neurol 1977; 34: 782-784. 13. Schmidt BJ, Meagher-Villemue K, Del CarpioJ. Lymphomatoid granulomatosis with isolated involvement of the brain. Ann Neurol 1984; 15: 478-481. 14. Amin SN, Gibbons CM, Lovell CR, TIF MacLeod, TH Moss, PJ Maddison. A case of lymphomatoid granulomatosis with a protracted course and prominent CNS involvement. BrJ Rheumatol 1989; 28: 77-78. 15. Pena CE. Lymphomatoid granulomatosis with cerebral involvement. Acta Neuropathol (Berl) 1977; 36: 193-197. 16. Hogan PJ, Greenberg MK, McCarthy GE. Neurologic complications of lymphomatoid granulomatosis. Neurology 1981; 31: 619-620. 17. Simon RH, Abeles M, Farber NJ, Grunnet M, Brennan TG. Lymphomatoid granulomatosis with multiple intracranial lesions. J Neurosurg 1981; 55: 293-298. 18. Kerr RSC, HughesJT, Blamires T, Teddy PJ. Lymphomatoid granulomatosis apparently confined to one temporal lobe.J Neurosurg 1987; 67: 612-615. 19. Kapila A, Gupta KL, GarciaJH. CT and MR of lymphomatoid granulomatosis of the CNS: Report of four cases and review of the literature. AJNR 1988; 9: 1139-1143. 20. Oliver C, D'Olhaberriag L, GarciJ, Matias-G1 X. Parkinsonism as a first presentation of lymphomatoid granulomatosis. J Neurol Neurosurg Psychiatry 1988; 51: 999-1001. 21. Collins S, Helme RD. Lymphomatoid granulomatosis presenting as a progressive cervical cord lesion. Aust NZJ Med 1989; 19: 144-146.

22. Smith AS, Huang TE, Weinstein MA. Periventricular involvement in CNS lymphomatoid granulomatosis: MR demonstration.JCAT 1990; 14(2): 291-293. 23. Kerslake R, Rowe D, Worthington BS. CT and MR imaging of CNS 1)~nphomatoid granulomatosis. Neuroradiology 1991; 33: 269-271. 24. Kleinschmidt-DeMasters, Filley CM, Bitter MA. Central nervous system angiocentric, angiodestructive T-cell Lymphoma (lymphomatoid granulomatosis). Surg Neurol 1992; 37: 130-137. 25. Verity MA. Cerebral lymphomatoid granulomatosis. In: Vinken PJ, Bruyn GW, eds. Handbook of Clinical Neurology, Vol 39. (Neurological manifestations of systemic disease Part II) North-Holland Publishing, Amsterdam, 1980, pp 517-536. 26. Whelan HT, Moore R Central nervous system Lymphomatoid granulomatosis. Pediat Neurosci 1987; 13: 113-117. 27. Calatayud T, Vallejo AR, Dominguez L, Sotelo T, Pena P, Jimenez M. Lymphomatoid granulomatosis manifesting as subacute polyradiculoneuropathy. Eur Neurol 1980; 19: 213-223. 28. Tourtellotte WW, Baumhefner RW, Potvin AR, Ma BI, PotvinJH, Mendez M, Syndalko K. Multiple sclerosis de n o v o central nervous system IgG synthesis: effect of ACTH and corticosteroids. Neurology 1980; 30:1155-1162. 29. Troussard X, Galateau F, Gaulard R Reman O, Henni T, Le CouedicJ, Leporrier M. Lymphomatoid granulomatosis in a patient with acute myeloblastic leukemia in remission. Cancer 1990; 65:107-111. 30. Medeiros LJ, Jaffe ES, Chen YY, Weiss LM. Localization of Epstein-Barr Virus genomes in angiocentric immunoproliferative lesions. AmJ Surg Pathol 1992; 16: 439-447. 31. Bone RC, Vernon M, Sobonya RE, Rendon H. Lymphomatoid granulomatosis. AmJ Med 1978; 65: 709-716. 32. Jenkins TR, Zaloznik AJ. Lymphomatoid granulomatosis. A case for aggressive therapy. Cancer 1989; 64: 1362-1365. 33. Simard H, LeBlanc P. Radiotherapy: an effective treatment of cerebral involvement by lymphomatoid granulomatosis. Chest 1993; 103: 650-651.

J. Clin. Neuroscience Volume 3 Number 4 October 1996

353

Lihat lebih banyak...

Comentários

Copyright © 2017 DADOSPDF Inc.