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EXFOLIATIVE CYTOLOGY IN PERNICIOUS ANÆMIA

THE earliest cytological observations in perniciousanaemia (P.A.) were, of course, those relating to red blood-cells. Besides commenting on changes in mature redcells, Ehrlich 1 applied the term megaloblast to largenucleated precursors present in peripheral blood. Abnor-mal features were later noticed in cells of the myeloidseries. Many clinical characteristics of P.A., includinglingual and gastric atrophy, premature greying of hair,and degeneration of the spinal cord, indicated that this isa general, and not a strictly haematological, disease. Fromstudy of cells exfoliated from various epithelial surfaces,it is becoming clear that cytological abnormalities arewidespread and common.Rubin and Massey 2 observed enlargement of nuclei

of gastric mucosal cells obtained by gastric washings inpatients with P.A. who had already received treatment.Graham and Rheault 3 described enlargement of bothnucleus and cytoplasm of squamous epithelial cells thathad been shed from mouth or oesophagus in patients withP.A. in relapse. A high prevalence of multiple nuclei wasalso noted in exfoliated squames from these patients.The nuclear abnormalities of squamous cells in P.A. wereconfirmed by Rubin 4 and Massey and Klayman,6 whosuggested that these occurred in other megaloblasticancernias. In gastric washings on patients with P.A. someof the gastric epithelial cells were found to be abnormal,having either a " bland " nucleus or an " active " appear-ance, with clumping of chromatin and prominentnucleoli. Rubin 4 remarked, however, that " active "

cells may be found in washings from patients with simpleachlorhydria without P.A. Such cells do not necessarilydisappear with treatment; and Henning and Witte andSchade emphasise that they are not pathognomonic ofP.A.

Boddington and Spriggs 9 studied cells from nasal

mucosa, urinary tract, and vaginal and gastric epithelialsurfaces. They concluded that widespread epithelial-cellchanges might take place in P.A. and that these werereversed by treatment, but that the appearances were tooinconstant and non-specific to have much diagnosticvalue. Squamous cells from buccal mucous membraneare the most easy to examine; and, by measuring nuclei,Boen 10 and Farrant 1112 have confirmed that abnormalitiesof shape and size occur in P.A. Boen et al.13 described apatient with neurological changes of subacute combineddegeneration of the cord, in whom the haemoglobin leveland marrow were normal. The serum-vitamin-B12 levelwas reduced, and the buccal epithelium showed nuclearpleomorphism and giant nuclei, which reverted to normalafter a week’s treatment with vitamin B12’ Boddingtonand Spriggs 9 refer to a case in which the epithelialchanges strongly suggested deficiency of vitamin B12; aninitial marrow examination was not diagnostic, but thediagnosis of P.A. was confirmed by a second marrowaspiration.

Clearly the cytological examination of buccal epitheliumis only occasionally of diagnostic value in cases of1. Ehrlich, P. Berl. klin. Wschr. 1880, 17, 405.2. Rubin, C. E., Massey, B. E. J. Lab. clin. Med. 1953, 42, 942.3. Graham, R. M., Rheault, M. H. ibid. 1954, 43, 235.4. Rubin, C. E. Gastroenterology, 1955, 29, 563.5. Rubin, C. E. Ann. N.Y. Acad. Sci. 1956, 63, 1377.6. Massey, B. W., Klayman, M. I. Amer. J. med. Sci. 1955, 230, 506.7. Henning, N., Witte, S. Atlas der Gastroenterologischen Cytodiagnostik.

Stuttgart, 1957.8. Schade, R. O. K. Gastric Cytology. London, 1960.9. Boddington, M. M., Spriggs, A. I. J. clin. Path. 1959, 12, 228.

10. Boen, S. T. Acta med. scand. 1957, 159, 425.11. Farrant, P. C. Lancet, 1958, i, 830.12. Farrant, P. C. Brit. med. J. 1960, i, 1694.13. Boen, S. T., Molhuysen, J. A., Steenbergen, J. Lancet, 1958, ii, 294.

suspected vitamin-Bl2 deficiency. But it does seem thatvitamin Bn may be necessary for the normal maturationof many cells besides red and white cells, and that it maybe an essential factor for normal nuclear metabolism.Mallarme 14 viewed P.A. as a nutritional cytologicaldystrophy, and the latest evidence supports this view.

TOXOCARAL PSEUDOGLIOMA OF THE RETINA

THE differential diagnosis of glioma of the retina

presents two problems: it must be distinguished, first,from non-malignant conditions, and secondly from thedifferent types of pseudogliomatous reactions whichthemselves are not easily recognised. Both these diffi-culties are well shown by a study of 53 cases in childrenup to 5 years of age in whom an eye was enucleated on the

suspicion of retinoblastoma. 15 The diagnosis was foundcorrect on histological examination in 24 cases; but in theremaining 29 cases a mass of inflammatory reactions andcongenital anomalies-some fairly well defined, others illunderstood-were found. In this series, from two CentralEuropean centres-Rostock and Magdeburg-no retro-lental fibroplasia was observed.

In 1950 Helen Wilder 16 drew attention to the presenceof nematode larvse in a series of pseudogliomas studiedhistologically. The unexpectedly high rate of such

findings raised the question whether her material wasrepresentative; but Wilder herself held that nematodeswere an important cause of blindness in American children.Six years later Nichols 17 re-examined five of the cases inWilder’s series and identified the nematode as the second-

stage larvae of Toxocara canis. This established for thefirst time that the dogworm could infect the human eye.Confirmation came, in 1959, from Irvine and Irvine,18who observed T. canis in an eye which had been diagnosedclinically as the seat of retinoblastoma. Further supportnow comes from a study of four cases by Ashton. 19 Thesewere obtained from the material at the Institute of

Ophthalmology in London and concerned children whohad had an eye excised on the suspicion of tumour. Thechildren hailed from London, Bristol, Taunton, andKilmarnock, and were aged 8, 16, 11, and 4 years respec-tively. The diagnosis in each case had been difficult anduncertain both clinically and histologically. Re-examina-tion of these eyes now reveals that they are affected bysolitary retinal masses caused by toxocara, histologicallydemonstrable.

Toxocara is as widely prevalent in dogs in this countryas elsewhere, and the recognition that ocular toxocarainfection does occur in this country raises the question ofthe frequency and manifestations of this infection hereas a general disorder as well as an ocular disturbance.Diagnosis is still difficult, and for the present the onelaboratory finding that may reinforce the tentative diag-nosis of ocular toxocara infection is a high eosinophil-count.

Sir WILFRID LE GROS CLARK has been elected president ofthe British Association for the Advancement of Science for1961. 6

THE death is reported from Metz of Dr. MARJORY WARREN,physician to the geriatric unit of the West Middlesex Hospital,from injuries received in a road accident.

14. Mallarmé, J. Blood, 1948, 3, 103.15. Heydenreich, A. Klin. Mbl. Augenheilk. 1959, 134, 465.16. Wilder, H. C. Trans. Amer. Acad. Ophthal. Otolaryng. 1950, 55, 99.17. Nichols, R. L. J. Parasit. 1956, 42, 349.18. Irvine, W. C., Irvine, A. R. Amer. J. Ophthal. 1959, 47, 185.19. Ashton, N. Brit. J. Ophthal. 1960, 44, 129.