20

cholangiography or endoscopic retrograde cholan-giopancreatography is required. Ultrasound andCT scanning can probably speed the diagnosticprocess; they do not replace the old invasivemethods, but they can help physicians choose theright ones.

ALPHA-CHAIN DISEASE: A DIAGNOSTIC TEST?

A TEST that is simple to perform, highly specific, sensi-tive, and easy to interpret sounds just what the doctorshould order. If it is used to establish the diagnosis of anunpleasant but benign condition, which if untreated willprogress to a malignant disease, then all concerned willhave the right to a warm glow of satisfaction. Doe,Danon, and Seligmann1 make this claim for their newlydevised test for alpha-chain disease (<xCD)&mdash;a conditionin which early diagnosis and prompt oral antibiotic ther-apy can prevent the development of an immunoblasticsarcoma of B-cell origin. 2When biochemists began to pull the immunoglobulins

to pieces they identified "heavy" and "light" peptidechains, and with immunologists and clinicians they soondeveloped the concept of the chain diseases. Alpha-chaindisease was one of the first to be delineated,3 and itsmajor clinical presentation seemed to be as Mediter-ranean intestinal lymphoma.4-6 Since this disease is byno means confined to the Mediterranean basin7-9 and isnot necessarily a lymphoma this nomenclature is notvery helpful: Nassar and othersll suggested "immuno-proliferative small intestinal disease" for the usual form.Some cases have anomalous features.9,10 Usually thesmall-intestine mucosa is widely infiltrated by benign-looking cells of the plasma-cell type, and the mesentericlymph-nodes are also infiltrated by similar cells.1O-13

1. Doe WF, Danon F, Seligmann M. Immunodiagnosis of alpha chain disease.Clin Exp Immunol 1979; 36: 189-197.

2. Rog&eacute; J, Druet P, Marche C. Lymphoma m&eacute;diterran&eacute;en avec maladie deschains alpha: triple remission clinique, anatomique et immunologique.Path Biol 1970; 18: 851-858.

3. Rambaud JC, Bognel C, Prost A, et al. Clinico-pathological study of a pa-tient with Mediterranean type of abdominal lymphoma with a new typeof IgA abnormality (&agr;-chain disease). Digestion 1968, 1: 336.

4. Ramot B, Shahin N, Budis JJ. Malabsorption syndrome in lymphoma of thesmall bowel. Isr J Med Sci 1965, 1: 221-226.

5. Ramot B, Hurd N. Primary intestinal lymphoma and its relation to alphaheavy chain disease. Br J Cancer 1975, 31: suppl II 343-349.

6. Doe WF. Alpha chain disease&mdash;clinicopathological features and relationshipto so-called Mediterranean lymphoma Br J Cancer 1975; 31: 350-355.

7. Novis BH, Kahn LB, Bank S. Alpha-chain disease in sub-Saharan Africa.Am J Dig Dis 1973; 18: 679-688.

8. Whicher JT, Ajdukiewicz A, Davies JD. Two cases of alpha chain diseasefrom Nigeria. J Clin Path 1977; 60: 678-681.

9. Cohen HJ, Gonzalvo A, Krook J, Thompson TT, Kremer WB. New presen-tation of alpha heavy chain disease: North American polypoid gastrointes-tinal lymphoma: clinical and cellular studies. Cancer 1978; 41:1161-1169.

10. Florin-Christensen A, Doniach D, Newcomb PB. Alpha chain disease withpulmonary manifestation. Br Med J 1974; ii: 413-415.

11. Nassar VH, Salem P, Shahid MJ et al. Mediterranean abdominal lymphomaor immunoproliferative small intestinal disease. Cancer 1977; 40:2941-2947 and Cancer 1978; 41: 1340-1354.

12. Tabbane S, Tabbane F, Cammoun M, Mouraw N. Mediterranean lym-phomas with alpha heavy chain monoclonal gammopathy. Cancer1976;38:1989-1996.

13. Rappaport H, Ramot B, Hulu N, Parit JK. The pathology of the so-calledMediterranean abdominal lymphoma with malabsorption. Cancer

1972; 29: 1502-1511.

The liver and spleen do not seem to be involved to anyconsiderable extent-not, at least, in the early stages,"and sometimes not even when a truly lymphomatousmalignant tumour of the immunoblastic sarcoma typedevelops. The large lymphomatous cells derive from thesame clone as the cx.CD protein secreting cells. 14The most interesting feature of ocCD is the continuous

series of changes terminating after a period of benignexpression in a malignant neoplasm; it offers a uniqueopportunity for study of the genesis of human lym-phomas.1s Since the disease seems to occur in all partsof the world, it can readily be studied in many countries.In the more affluent it seems to account for only a smallproportion of the abdominal lymphomas (3 of 117 casesin the series of Lewin et al. 16) whereas in the least af-fluent-or at least where affluence has not led to greatimprovement in sanitation-this is one of the com-monest. It can take other clinical forms (for example, itmay be confined to the respiratory tract), but in areaswhere intestinal pathogens are rife8 the intestinal formeasily predominates. Usually it is recognised in thesecond and third decades of life and it is uncommon pastthe age of 50.8 The plasma cells secrete into the gut andthe bloodstream, and early detection depends on identifi-cation of this abnormal material. Various diagnostictests have been applied, notably rocket immunoelectro-phoresis, 17 but Doe and his colleagues claim thatimmunoselection by immunophoresis into a gel contain-ing a specially developed anti-Faba antiserum is themost specific and sensitive method. If they are right thenthis represents a decided step forward since the test iswithin the scope of most routine laboratories; it willenable epidemiological studies to be rapidly expanded,with speedier unravelling of the intestinal pathogenesis.The gastrointestinal tract harbours such a profusion ofpotential agents, working singly or in combination, di-rectly or through their products, that the scope for in-vestigation is great. If we can identify the cause orcauses in alpha-chain disease and define how they oper-ate we may well have tools and methods applicable toother lymphomas.

A GENETIC COUNSELLOR IN THE 1980s

WHEN genetic counselling began the advisers weremostly concerned with explaining the odds or dismissingold wives’ tales, and one U.K. pioneer remarked "it maybe that the massive national absorption in football poolshas been of much benefit to the work of genetic clinics". 1There is a lot of talk still of probability and a need forreassurance, but prenatal diagnosis can often now beexact. This increased predictive power, coupled with the

14. Ramot B, Levanon M, Hahn Y, Lahat H, Mero ZC The mutual clonal originof the lymphoplasmacytic and lymphoma cell in &agr; heavy chain disease.Clin Exp Immunol. 1977; 27: 440-445.

15. Seligmann M, Rambaud JC Alpha-chain disease, a possible model for thepathogenesis of human lymphomas. In: Good RA, Twomey JJ eds. Im-munopathology of lymphoreticular neoplasms New York, Plenum.1978:425.

16. Lewin KJ, Ranchod M, Dorfman RF. Lymphomas of the gastrointestinaltract. A study of 117 cases presenting with gastrointestinal disease. Cancer1975; 42: 693-707.

17. Gall DSJ, Versey JMB, Hobbs JR. Rocket-immuno-selection for the detec-tion of heavy chain diseases Clin Chem 1974; 20: 1292-1294.

1. Fraser Roberts JA. An introduction to medical genetics. 3rd ed. LondonOxford University Press. 1963:251-274.