October, 1965 McANDREW: Cerebral Nocardiosis 641 Postgrad Med J: first published as 10.1136/pgmj.41.480.641 on 1 October 1965. Downloaded from I am grateful to Dr. W. M. Jamieson, Dr. R. N. KRUEGER, E. G., NORSA, L., KENNEY, M., and PRICE, Johnston and Mr. R. J. A. Fraser for access to case P. A. (1954): Nocardiosis of the Central Nervous notes, and to Dr. K. N. V. Palmer for helpful System, J. Neurosurg., 11, 226. comments. LARSEN, M. C., DIAMOND, H. D., and COLLINS, H. S. (1959): Nocardia Asteroides ; a Report of Seven Cases, Arch. intern. Med., 103, 712. REFERENCES LIST, C. F., WILLIAMS, J. R., BEEMAN, C. B., and BALLENGER, C. N., and GOLDRING, D. (1957): PAYNE, C. A. (1954): Nocardiosis with Multilocular Nocardiosis in Childhood, J. Pediat., 50, 145. Cerebellar Abscess; Report of a Case, J. Neurosurg., CARLILE, W. K., HOLLEY, K. E., and LOGAN, G. B. 11, 394. (1963): Fatal Acute Disseminated Nocardiosis in MCDONALD, S. (1904): A Case of General Strepto- a Child, J. Amer. med. Ass., 184, 477. thrix I'nfection, Scot. med. surg. J., 14, 305. CuPP, C. M., EDWARDS, W. M., and CLEVE, E. A. MCQUOwN, A. L. (1955): Actinomycosis and No- (1960): Nocardiosis of the Central Nervous cardiosis, Amer. J. clin. path., 25, (1), 2. System: ,Report of Two Fatal Cases, Ann. intern. MUNSLOW, R. A. (1954): Actinomycotic (Nocardia Med., 52, 223. asteroides) Brain Abscess with Recovery, J. Neuro- GILLIGAN, B. S., WILLIAMS, I., and PERCEVAL, A. K. Surg., 11, 399. (1962): Nocardial Meningitis: Report of a Case MURRAY, J. F., FINEGOLD, S. M., FROMAN, S., and with Bacteriological Studies, Med. J. Aust., 49 (2), WILL, D. W. (1961): The Changing Spectrum of 747. Nocardiosis. A Review and Presentation of Nine HATHAWAY, B. M., and MASON, K. N. (1962): Cases, Amer. Rev. resp. Dis., 83, 315. Nocardiosis, Amer. J. Med., 32, 903. PEABODY, J. W., and SEABURY, J. H. (1960): Actino- HICKEY, R. C., and BERGLUND, E. M. (1953): No- mycosis and Nocardiosis. A Review of Basic Differ- cardiosis: Aerobic Actinomycosis with Emphasis on ences in , Amer. J. Med., 28, 99. the Alimentary Tract as a Portal of Entry, Arch. PIZZOLATO, P., ZISKIND, J., and DERMAN, H. (1961): Surg., 67, 381. Nocardiosis of the Brain. Report of Three Cases, JACOBSON, J. R., and CLOWARD, R. B. (1948): Actino- Amer. J. clin. path., 36, 151. mycosis of the Central Nervous System; Case of WELSH, J. D., and RHOADSHER, J. W. (1961): Dis- Meningitis with Recovery, J. Amer. med. Ass., 137, seminated Nocardiosis involving Spinal Cord, Arch. Protected by copyright. 769. intern. Med., 108, 73.

NONMETASTATIC NEPHROGENIC HEPATOSPLENOMEGALY AND EPILEPSY S. D. MOHAMED, M.B., Ch.B., M.R.C.P., M.R.C.P.E. University Department of Materia Medica and Therapeutics and the Royal Infirmary, Aberdeen. http://pmj.bmj.com/ IN RECENT years a variety of general systemic 1961 annual meeting of the American Gastro- manifestations and unusual syndromes have enterological Association drew attention to non- come to be recognised as presenting features of metastatic hepatosplenomegaly from renal car- an otherwise occult neoplasm. Their diversity has Cinoma. The published abstract (Stauffer, 1961) included the purely dermatological manifestations, mentions five cases, but Greenberg and others including acanthosis nigricans, dermatomyositis (1964) ascribe 10 such cases to the author; four and erythema gyratum repens; a variety of neuro- with splenic enlargement and all with grossly muscular syndromes; skeletal disturbances includ- abnormal results of function tests. The on September 24, 2021 by guest. ing clubbing, pulmonary hypertrophic osteoarthro- abnormal findings returned to normal after neph- pathy and pachydermoperiostosis; thrombophlebi- rectomy. Such a favourable response is well re- tis migrans and phlebothrombosis; erythrocytosis cognised for renal polycythemia and is at times and red cell aplasia; and various hormonal and noted with proven pulmonary metastasis. That metabolic disturbances (Greenlberg, Divertie and this should obtain on occasion with hepato- Woolner, 1964). Familiarity with such manifesta- megaly is of considerable interest as wider appre- tions are of dual importance; firstly, as diagnostic ciation of this phenomenon would lead to more pointers and secondly, in the frequent observa- of these cases being offered operative treatment tion that successful removal ef the primary despite markedly deranged liver function, with lesion may lead to complete regression of these a prospect of effecting complete cure. The fre- features. quency with which such an outcome may be Creevy (1935) recorded three patients with expected is unknown and accordingly a case of hypernephroma presenting with clinical features renal carcinoma recently encountered by us and suggesting cirrhosis of the liver. Stauffer, at the diagnosed only at necropsy but who showed 642 POSTGRADUATE MEDICAL JOURNAL October, 1965Postgrad Med J: first published as 10.1136/pgmj.41.480.641 on 1 October 1965. Downloaded from

marked derangement of liver function with pro- continued to fall at the rate of 1.5-2.0 lbs. per minent hepatosplenomegaly in life, without month. The haemoglobin after an initia9l slight fall macroscopic or microscopic abnormality of the stabilised at 65-75%. A course -of oral iron was given liver at death, is described. The case is of further on account of persistent hypochromia and micro- interest on account of seizures cytosis but this was without benefit. The hepato- epileptiform for became a little more marked and tihe 3everal months pre-terminally without demonst- alkaline rable intracranial at autopsy. phosphatase rose to 28 KA units. Towards the end of 1962 she defaulted attendance at the clinic and when seen again late in February Case Report 1963 her condition had deteriorated considerably A farmer's wife, aged 47 years, was admitted on with continuing weight loss, tiredness, lack of energy 10.7.62 and remained under our care until her death and excess sweating. There was progressive increase on 12.11.63. Her symptoms throughout the ililness in both the hepatic and splenic enlargement with were largely constitutional: weight loss, tjiredness, further deterioration in the liver function tests (Fig. 1). lassitude and excessive sweating, with from time to A repeat bone marrow aspirate on 14.3.63 was of time additional non-specific features of a marked normal cellularity. The erythropoiesis was normo- anaemia (Fig. 1). blastic, slightly hyperplastic, and with some features 'of iron deficiency. The myeloid series was reported There was evidence of weight loss and continued as showing "a marked preponderance of cells which low grade fever. Small shotty nodes inthe left axilla look 'like premyelocytes, but, considering the dis- remained the sole adenopathy in it'he accessible sites crepancy in numbers between these cells and the throughout the illness. A firm mass, two to three myelocytes, many of the cells may be reticulum finger-breadths in size, with a "notch" in the anterior cells. There are also a few non-granular, more primi- border was readily palpable in the left hypochond- tive cells of the reticulum cell-monloblast type". rium. It was possible to get "behind" the mass but A bone not "above" it. was to marrow trephine biopsy was reported by It dull percussion and moved the pathologist as being cellular and showing an with respiration. It was regarded as a splenic enlarge- increase of Joint ment. Very soon the liver, too, became readily eosinophils. review of the two sets palpable. of films failed to take the diagnosis further. A surgeon could not be persuaded to undertakeProtected by copyright. a Investigations: ESR 85-140 mm. /hr. (Westergen), laparotomy with a possible open liver biopsy as the Hb. 55% (7.9 g./lOO ml.); PCV 28%o; MCHC 28%; procedure was considered too hazardous in view of slight hypochromia and microcytosis of the red cells; the impaired liver cell function. reticulocytes <1% and 1.4%; tests for occult blood and quan-titative and qualitative tests for excess She received supportive treatment with further urinary urobilinogen negative; urinalysis chemicallv blood transfusions with some subjective improve- and microscopicalily normal; Coomb's test negative; ment. Because of t-he strong clinicaal suspicion of a WBC 4000-7000/cu. mm. with normal differential reticulosis, treatment with nitrogen mustard, counts; platelets chlorambucil, corticosteroids and local irradiation to 150-300,000/cu. mm. the was given over the ensuing months but Bone marrow examination in July 1962 produced all were singularly without benefit. aspirates of normal cellularity with normoblastic any hyperplasia as the only abnormality but a further From June 1963 she became subject to recurrent examination a few weeks later showed a shift to the major convulsive seizures. An electroencephalogram left of the granular series with marked increase of showed trains of theta waves over both temporal the premyelocytes. No abnormal cells were seen. areas with frequent mixed spike anid wave discharges from the right cerebral hemisphere with maximal The 'liver function tests showed moderate impair- disturbance over the right inferior fronto-tem-poral ment with the alkaline phosphatase 13 and 16 KA area. A lumbar puncture showed no alteration http://pmj.bmj.com/ in units; serum albumin 3.88, globulin 3.72 and 4.45 the cellularity, chemistry or 'dynamics of the cere-, g. /100 ml.; increase in the ai a2 and y globulin in brospinal fluid. The seizures were treated with pheno- the electrophoretic strip; 20% retention of bromsul- barbitone and later with phenytoin sodium and phalein at 45 minutes. Serum b,ilirubin and serofloc- primidone with moderate success. With the inexorable culation studies were normal. Tests for LE cells and progress of her cachexia she gradually liapsed into antinuclear factor were negative. A deformity of the coma and died on 12.11.63. stomach by extrinsic pressure from the "spleen" Necropsy. Apart from the cachexia, the following was noted on a barium meal and an enema examina- features were of note:

tion was reported as showing a displacement of the on September 24, 2021 by guest. sigmoid flexure and the upper descending colon by Examination of the intracranial contents including the splenomegaly. A chest X-ray and a skeletal survey multiple sections of the brain failed 'to reveal any' were negative. naked eye or microscopic abnormality of the men- An abdominal reticulosis, possibly of the Hodgkin inges, brain substance or the blood vessels. There type was thought to be the likeliest diagnosis and was bronchopneumonia with slight non-specific en- the altemative possibility of a pre-leukaemic con- largement of the ihilar lymph nodes. The liver (1000 g.) dition was also considered. Aspiration liver biopsy was not enlarged and appeared normal 'both on naked was precluded on account of persistently elevated eye anld hlistological examination. The spleen was prothrombin time (17-18 seconds; control 13.5 slightly enlarged (300 g.) and showed congestive seconds) despite intensive treatment with viitamin K,. changes and haemo-siderin-4aden macrophages. The Suipportive treatment with packed red cells was given organ was pushed forward by a large tumour mass~ in July and again in replacing the upper polle of the left kidney, which Septemiber. had all the typical features of a hypernephroma on During the latter months of 1962 she remained histological examination. All the intra-abdominal in relatively good healtth with increase in energy lymph nodes anid the renal veins were. free of and absence of night sweats. Her weight, however, tumour deposits. October, 1965 MOHAMED: Nonmetastatic Nephrosenic Hepatosplenomegaly 643 Postgrad Med J: first published as 10.1136/pgmj.41.480.641 on 1 October 1965. Downloaded from

Iron I 1 nnIron Mustard & Chlorambucil Prednisone Irradiation Body 150 [ Weight (Ibs.) 100

50 . - --...... - ...... - May Sept Jan May Sept t HaemoglobinHaemoglobit (Transfusions (% Sahli ) 75 50 July Nov Mar July Nov

Liver 2 ,-I: -. -- - - . --_ - -- - - _1 _ _ ? ------Spleen 6^

(fingerbreadths) . . . . May Sept Jan May Sept Alkaline 60 Phosphatase Protected by copyright. (K.A. units 40 20 10 July May Mar July Nov 5 Albumen -..."-- - -

Globulin - " " 3.. ---. (g./100ml.) 2 May July Sept Nov' Jan Mar May July Sept Nov 1963 1964 FIG. 1.-Note the recurring progressive cachexia, anaemia, progressive hepato-splenomegaly, http://pmj.bmj.com/ and increasing evidence of liver cell dysfunction. Discussion The diagnostic confusion in the present case The protean manifestations of renal tumour was compounded by the presence of classical are well recognised. Constitutional disturbances clinical and radiological features of a splenic en- with fever as theo only presenting features have largement. At death, the spleen was certainly been frequently recorded but Weinstein, Geraci enlarged though much less than in life and whilst and Greene draw attention to the relative this may have been an agonal feature, it seems

(1961) on September 24, 2021 by guest. infrequency of prolonged fever as the sole clinical more probable that the "notch" observed along manifestation. Marked to moderate elevation of the anterior border was due to the composite mass the ESR (Melicow and Ulson, 1960; Bottiger, presented by the spleen and the enlarging renal 1960a) and non-specific alterations in the serum tumour. The with pronounced liver globulins (Bottiger, 1960b) have also been noted :ell dysfunction, the non-specific anaemia and the in a proportion of patients. There were no relevant striking though atypical features in the bone renal symptoms in the present case and well over marrow directed diagnostic considerations towards 20 urine specimens over the prolonged illness a reticulosis or a pre-leukaemic process. The failed to reveal any biochemical or microscopical absence of liver enlargement at autopsy was abnormality. Melicow and Ulson (1960) noted likely due to the pronounced cachexia in the atypical presentation in 183 of 537 cases with latter part of the illness. renal carcinoma and in 60% of the former red The most interesting feature of the case was blood cells were absent from the urine throughout the striking absence of histological abnormality of the illness. the liver despite the pronounced functional im- 644 POSTGRADUATE MEDICAL JOURNAL October, 1965Postgrad Med J: first published as 10.1136/pgmj.41.480.641 on 1 October 1965. Downloaded from pairment during life. Had the diagnosis been made phroma of the left kidney, failed to show during life and the tumour resected, there is a macroscopic or histological abnormality of the strong presumption in the light of Stauffer's liver, brain or the intracranial vasculature. Jt is experience that complete resolution of the suggested that this was a case of nonmetastatic abnormal features may have occurred. This is hepatosplenomegaly and epilepsy in whom re- important as many such patients are probably solution of these features could conceivably have refused operative treatment at present on the occurred if the renal tumour had been identified grounds that the abnormality of functional and resected during life. Further information on efficiency of the liver denotes a disseminated lesion. the frequency of such manifestations would be The present case emphasises the need to undertake helpful in the diagnosis and management of renal pyelographic examination in patients presenting carcinoma. with unexplained hepatomegaly with or without I am grateful to Professor A. G. Macgregor for splenic enlargement and liver cell dysfunction and permission to study this case who was admitted raises the optimistic note that even a severe degree under his care and to Professor A. C. Currie for of functional impairment of the liver need not the post-mortem examination. necessarily be a bar to surgical treatment in that resolution of the features REFERENCES complete abnormal BOTTIGER, L. E. (1960a): Studies in Renal Carcinoma: may follow a successful nephrectomy. I. Clinical and Pathologic Anatomical Aspects, Epileptiform seizures in the absence of a de- Acta med. scand., 167, 443. monstrable intracranial abnormality, as in this , (1960b): Studies in Renal Carcinoma: II. Bio- case, should probably also be regarded as a non- chemical Investigations, Ibid, 167, 455. metastatic lesion likely to resolve after successful CREEVY, C. D. (1935): Confusing Clinical Manifesta- removal of the primary malignint disease. Judg- tions of Malignant Renal Neoplasms, Arch. intern. ing by recent reviews of nonmetastatic manifesta- Med., 55, 895. tions of disease (Pinals and GREENBERG, E., DIVERTIE, M. B., and WOOLNER, L. B. malignant Krane, (1964): A Review of Unusual Systemic Manifesta- 1962; Greenberg and others, 1964), epilepsy cf tions Associated with Carcinoma, Amer. J. Med.,Protected by copyright. this type does not appear to have been described 36, 106. previously. MELICOW, M. M., and ULSON, A. C. (1960): Non- urologic Symptoms in Patients with Renal Cancer, Summary J. Amer. med. Ass., 172, 146. A case is described of a woman of 47 who PINALS, R. S., and KRANE, S. M. (1962): Medical suffered from a fatal illness for 18 Aspects of Renal Carcinoma, Postgrad. med. J., months, 38, 507. characterised by constitutional disturbance, STAUFFER, M. H. (1961): Nephrogenic Hepatospleno- weight loss, fever, non-specific anaemia, prog- megaly, (Abstract), , 40, 694. ressive hepatosplenomegaly and increasing liver WEINSTEIN, E. C., GERACI, J. E., and GREEN, L. F. cell dysfunction and preterminally grand mal (1961): Hypernephroma Presenting as Fever of epilepsy. Autopsy, which revealed a hyperne- Obscure Origin, Proc. Mayo Clin., 36, 12. http://pmj.bmj.com/ TWO PATIENTS WITH CARDIAC MYXOMA:-ONE PRESENTING AS BACTERIAL ENDOCARDITIS, AND ONE AS CONGESTIVE CARDIAC FAILURE ANGUS RAE, M.B., M.R.C.P., M.R.C.P.E. on September 24, 2021 by guest. Senior Medical Registrar, The London Hospital, E.1.

TUMOURS of the heart may be primary or second- The clinical manifestations of these tumours are ary, the latter being 20-40 times commoner than protean, and as with other conditions which are the former (Prichard, 1951). Thorel in 1903 found uncommon the diagnosis is sometimes not made no primary tumours in a series of 3,300 autopsies. because it is not considered. Even when con- Ravid and Sachs (1943) found one such tumour sidered it is not always easy to establish. This is in every 1,888 consecutive autopsies and Straus unfortunate because although most myxomata and Merliss (1945) reported 18 in 480,331 may be removed with comparative safety, if they autopsies. Of the primary tumours nearly half are not, once symptoms have begun, death will are myxomata. follow sooner or later (Goodwin, 1963).