MA Y 2 4 , 1952 POLYCYTHAEMIA N MYELOSCLEROSIS M B Rm 1113 POLYCYTHAEMIA A N D MYELOSCLEROSIS B Y F . G . MARSON M.B., M.R.C.P. Senior Medical Registrar N M . J . MEYNELL M.D., MLR.C.P. Clinical Pathologist Th e General Hospital, Birmingham It i s n o w fairly well recognized that myelosclerosis ma y present with polycythaemia (Stone an d Woodman 1938; Vaughan a nd Harrison, 1939; Marson a n d Meynell, 1949; Hutt, 1950). Th e problem o f t h e rela- tionship o f this condition t o polycythaemia rubra vera i s still undecided. Rosenthal a n d Bassen (1938) believe that polycythaemia rubra vera c a n terminate with myelo- sclerosis. T h e question arises whether myelosclerosis follows as natural sequence i n th e disease process o r whether it i s du e t o t h e effect o f therapy. Wyatt a nd Sommers (1950), i n a study o f 3 0 cases, state that marrow sclerosis i s more likely d u e t o t h e eventual attrition of th e haemopoietic system b y t h chemical an d physical agents employed to reduce t h e erythrocyte count. We reported t w o cases o f polycythaemia with myelosclerosis which were treated with deep x-ray therapy (Marson a nd Meynell, 1949). T h e case recorded below h a s had acetyl- phenylhydrazine over a number o f years. Deep x-ray therapy has never been used. Case Repott m a n aged 6 1 wa s admitted t o hospital i n 1943 with pneumonia, blood count showed h e h a d polycythaemia, which was considered t o b e o f t h e primary type. Since then he h a s h a d repeated courses of acetylphenylhydrazine, 0. 1 g . weekly. I n 1945 the Wassermann reaction wa s positive a n d h e w a s given neoarsphenamine a n d bismuth. blood count i n May, 1945, w a s s follows: Re d cells. 5,590,000; haemo- globin, 105 ;s white cells, 18,000; neutrophil premyelocytes. 2 neutrophil metamyelocytes, 3 ° ; neutrophil poly- morphs, 75 lymphocytes, 1 5 mononuclears, 2 ; baso- phil polymorphs, 3 . I n 1946 h i s Wassermann reaction w a s still weakly positive, and he w a s given penicillin i n oil, 250.600'units daily or t en days. I n 1948 t h e enlarged spleen w a s found t o extend -down t o t h e pubis. There was no enlargement of lymph nodes. T h e haemoglobin w a s 117 , a n d white blood cells 28,800 p e r c.mm. differential count showed a f e w myelocytes and some normoblasts. In August, 1950, h e developed pain in h is chest a n d w a s transferred t o this hospital. On examination h e w a s plethoric a n d well nourished. Th e spleen extended into t h e right iliac fossa. No enlarged lymph nodes, were found. blood count showed: Re d cells 6,660,000'; haemoglobin, 120 (Haldane); eolour index. 0.91 white cells 21,100; neutrophil polymorphs, 64 ; cosinophil polymorphs, 1.5 ; basophil polymorphs, 2 lymphocytes, 9 ; monocytes, 2.5 ; N . metamyelocytes, 10.5 ; N . myelocytes, 6.5 N . premyelocytes, 4 . Stained films showed anisocytosis a n d poikilocytosis with polychromasia. Platelets were 523;000 p e r c.mm. X-ray films o f t h e long bones showed n o abnormality. Sternal puncture produced a specimen which consisted mainly o f cells found i n t h perirheral blood, b u t i n addition there appeared t o b e a n excess o f megakaryocytes. Puncture w a s repeated with t h e same result. sternal biopsy showed a pronounced fibrosis of t h marrow cavity a n d a n increase i n megakaryocytes.- Th e picture wa s consistent with t h e diagnosis o f myeloscl¢rosis. T h e patient w a s discharged with a haemoglobin o f 100 a n d a red-cell count of 5,458,000 p er c.mm. He i s n o w attending the out-patient department a n d a l l therapy h a s been stopped. Discussion T h e ctse i s f interest for several reasons. Definite myelo- sclerosis w a s present with n o anaemia. It i s n o w generally accepted that t h e splenomegaly i s compensatory t o t h e marrow involvement. A s this extends, the compensatory hyperplasia o f t h e extramedullary foci o f haemopoiesis fails t o equalize t h e marrow replacement, a n d anaemia results. If i t i s assumed that various agents-for example, benzene, x rays, phenylhydrazine, etc.-act b y process o f attrition, i t must b e accepted that they will also ac t o n t h e extra- medullary foci a s well. similar process o f fibrosis should b e evident i n the extramedullary foci. This has n o t been demonstrated. Wyatt and Sommers, describing t h e microscopical picture of various extramedullary foci, state o f the lymph nodes: Small groups o f myeloid a n d erythroid cells a n d scattered bizarre megakaryocytes a re found i n t h e sinusoids, dilating them, b u t not often producing a clinically apparent lymph- adenopathy. I n addition, t h e lymphoid tissue showsminimal hyperplasia, and normal architecture i s preserved without necrosis o r fibrosis (our italics . I n describing the other sites-for example, liver, renal pelves a n d cortex, subserosal f a t o f t h e gastro-intestinal tract, sinusoids of adrenal cortex -they state that qualitatively these foci resemble those described -that i s there i s a n absence of necrosis o fibrosis. T h e spleen does show some increase i n fibrous tissue, b u t other factors such as infarction a nd deposition of iron pigment operate. I n the case here described x-ray therapy has never been used. I t i s no w widely accepted that deep x-ray therapy t o t h e spleen i n myelosclerosis i s contraindicated. I n a follow- u p o f t h e t wo cases previously recorded (Marson a n d Meynell, 1949) o n e complained o f continuous severe pain over t h e spleen, presumably related to i t s enormous size. This wa s s o severe that t h e patient stated that life w a s becoming unbearable. Small doses o f deep x rays were applied t o t h e splenic area: over a period o f two weeks a total of 3 9 0 r w a s given. This caused a n appreciable reduc- tion i n th e size of the spleen. T h e blood count fell slightly during t he next fortnight. S h e w a s given transfusions. Her blood picture improved, a n d a year later s h e said she, h a d remained free from pain. Conclusion case o f myelosclerosis without anaemia i s described. This case w a s originally diagnosed a s polycythaemia rubra vera. I t is believed that t h e recognized therapeutic agents used i n t h e treatment o f this condition play no part i n producing myelosclerosis. I n t h e present case deep x-ray therapy w a s never used. Although it is generally agreed that x-ray therapy to t h e spleen i s contraindicated in myelosclerosis, i t m ay b e of value in small doses when there i s severe pain over t h e spleen. Thanks a r e d ue t o Professor A . P . Thomson f o r permission t o publish this case, a n d t o Miss M. N . Ellis f o r secretarial assistance. REFERENCES Hutt, M. S . R . (1950). Proc. Soc. Med., 4 3 . 903. Marson, F . G . , a n d Meynell, M. 3 . (1949). British Medical Journal. 2 , 1384. Rosenthal. N . , an d Bassen, F. A . (1938). Arch. Intern. Med., 6 2 . 903. Stone, D . M . . and Woodman. D . (1938). J . Path. Bact., 4 7 , 327. Vaughan, J . M . , a n d Harrison. C . V . (1939). Ibid., 4 8 , 339. Wyatt, J . P . , an d Sommers, S . C . (1950). Blood, 5 . 329. T h e Annual Conference of t he British Hospitals Contri- butory Schemes Association (1948) this year will take place i n Cardiff, b y t h e kind invitation of t h e Lord Mayor City Council, o n October 2 3 a n d 2 4 . D r . Ffrangcon Roberts, author of The Cost of Healrh, h a s consented t o b e the; association's guest speaker a t this conference.
