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CARCINOID TUMOURS AND ENDOCRINE CELL HYPERPLASIA
1457 While we
we
continue
agree with the challenge of O’Malley’s suggested test, to propose carbimazole as the aetiological agent.
Department of Medicine 11 St George’s Hospital Medical School,
S. S. NUSSEY S. R. PAGE
London SW17 0RE
1. Khaleeli AA, Griffith DG, Edwards RHT. The clinical presentation of hypothyroid myopathy and its relationship to abnormalities in structure and function of skeletal muscle. Clin Endocrinol 1983; 19: 365-76 2. Graig FA, Smith JC. Serum creatine kinase activity in altered thyroid states. J Clin Endocrinol Metab 1965; 25: 723-31.
PARVOVIRUS INFECTION, LEUKAEMIA, AND IMMUNODEFICIENCY
SiR,—Kurtzmann
et
all
reported
two
children with acute
lymphoblastic leukaemia who had severe anaemia after persistent parvovirus (HPV) infection and suggested that patients with acquired immunodeficiency may be at risk. Others2-4 have described several cases of persistent HPV infection associated with prolonged erythroblastopenia in cases of immunodeficiency. We report erythroblastopenia in an adult patient with chronic myelomonocytic leukaemia (CMML). This 70-year-old man was admitted with a diagnosis of CMML in January, 1988. Haematological counts were: white blood cells 30 x 109/1 with young granulocytic forms and 10% monocytes, platelets 189 x 109/1, haemoglobin (Hb) 9-8 g/dl, and reticulocytes 68% (absolute value 213 x 109/1). Bone marrow examination revealed hypercellularity with excess granulopoiesis, depressed erythropoiesis (6-6% erythroblasts), and absence of myelofibrosis. Karyotyping was normal. Clinical examination showed hepatosplenomegaly and anaemia. Hydroxyurea was administered over eleven months with several interruptions because of thrombocytopenia. The anaemia required multiple red-cell transfusions (58 units); this patient also had ischaemic heart disease. Six months after diagnosis, we observed a sudden worsening of anaemia, with increased transfusion needs, and a drastic fall of reticulocyte count to zero (figure). A new bone marrow sample in October, 1988, resembled the initial sample except there was more profound depression of erythropoiesis (0-1% erythroblasts). In addition to this erythroblastopenia, morphological abnormalities were observed: the only remaining erythroblasts had cytoplasmic vacuoles and megaloblastic changes. Infection with HPV was suspected. Serological analysis was negative for anti-B19 IgM but B19 viral DNA was found by dot blot. Erythroblastopenia persisted until death, which occurred five B19
months after its onset. No contact with a child with fifth disease was known by our patient. This case report suggests that, as in the other cases described, immunodeficiency favouring persistent HPV infection was probably responsible for chronic erythroblastopenia. Moreover, we think that the source of HPV contamination may be transfused blood products. Arguments to support this hypothesis are: (1) demonstration of HPV in serum of healthy blood donors;s
(2) higher titre of HPV IgG in haemophilic children transfused with clotting factors than in the normal population ;6 and (3) detection of replicative forms of HPV in circulating cells.7 Department of Internal Medicine and Laboratory, C H J Bracops, 1070 Brussels, Belgium
1. Kurtzman
GJ, Cohen B, Meyers P, Amunullah A, Young NS. Persistent B19 parvovirus infection as a cause of severe chronic anaemia in children with acute lymphocytic leukaemia. Lancet 1988; ii: 1159-62. 2. Coulombel L, Morinet F, Mielot F, Tchemia G. Parvovirus infection, leukaemia, and immunodeficiency Lancet 1989; i: 101-02. 3. Davidson JE, Gibson B, Gibson A, Evans TJ. Parvovirus infection, leukaemia, and immunodeficiency. Lancet 1989; i: 102. 4. Weiland HT, Salimans MMM, Fibbe We, Kluin PM, Cohen BJ. Prolonged parvovirus B19 infection with severe anaemia in a bone marrow transplant recipient. Br J Haematol 1989; 71: 300. 5. Cossart YE, Field AM, Cant B, Widdows D. Parvovirus-like particles in human sera. Lancet 1975; i: 72-73. 6. Mortimer PP, Luban NLC, Kelleher JF, Cohen BJ. Transmission of serum parvovirus-like virus by clotting-factor concentrates. Lancet 1983; ii: 482-84. 7. Kurtzman GJ, Gascon P, Caras M, Cohen B, Young NS. B19 parvovirus replicates in circulating cells of acutely infected patients. Blood 1988; 71: 1448-54.
CARCINOID TUMOURS AND ENDOCRINE CELL HYPERPLASIA
SiR,—Your April 29 editorial highlights the association between and endocrine cell hyperplasia in the tract, which raises the question whether these tumours arise in a pre-existing background of endocrine cell hyperplasia or whether the hyperplasia may be secondary to a factor produced by the carcinoid tumour. Multiple polypoidal carcinoid tumours associated with endocrine cell hyperplasia have been described in the stomach of patients with achlorhydria, but unlike most bowel carcinoids, they were composed of argyrophil (not argentaffm) cells of the enterochromaffm-ae (ECL) type.l The patients had high fasting plasma levels of gastrin, which may have stimulated hyperplasia of ECL cells and led to the formation of carcinoid
course in patient with CMML complicated by chronic red-cell aplasia and B19 parvovirus infection.
RET = reticulocytes ; TRANSF
=
transfusion.
tumours
gastrointestinal
carcinoid tumours. Enterochromaffin (EC) cell hyperplasia occurs in the duodenal mucosa of patients with untreated coeliac disease,’ but carcinoid tumours in this disorder are rare. 3,4 Cytofluorometric and immunohistochemical studies of duodenal EC cells in untreated coeliac disease suggest that these cells synthesise increased amounts of serotonin, which is released both locally and into the circulation.5,6 Since serotonin increases the crypt cell production rate in normal duodenal mucosa cultured in vitro’ and promotes the growth of crypt cell nodules,8 this amine, similar to gastrin in the stomach, could induce hyperplasia of both crypt epithelial cells and EC cells in the flattened small intestinal mucosa in coeliac disease. The rarity of carcinoid tumours in the small intestine in coeliac disease, despite EC cell hyperplasia, may be due to factors limiting the growth of most tumours in the small bowel compared with other parts of the gastrointestinal tract. Somerset Children’s Research Unit, Taunton and Somerset Hospital, Taunton TA1 5DA
1.
Clinical
M. MALARME D. VANDERVELDE M. BRASSEUR
D. N. CHALLACOMBE
Harvey RF, Bradshaw MJ, Davidson CM, Wilkinson SP, Davies PS. Multifocal gastric carcinoid tumours, achlorhydria, and hypergastrinaemia. Lancet 1985; i:
951-54. 2. Challacombe DN, Robertson K. Enterochromaffin cells in the duodenal mucosa of children with coeliac disease. Gut 1977; 18: 373-76. 3. Hallert C, Norrby K. Malignant carcinoid tumour complicating coeliac disease. Acta Med Scand 1983; 213: 313-16. 4. Gardiner GW, Van Patter T, Murray D. Atypical carcinoid tumour of the small bowel complicating coeliac disease. Cancer 1985; 56: 2716-22. 5. Challacombe DN, Dawkins PD, Baker P. Increased tissue concentrations of 5-hydroxytryptamine in the duodenal mucosa of patients with coeliac disease. Gut 1977; 18: 882-86. 6. Wheeler EE, Challacombe DN. Quantification of enterochromaffin cells with serotonin immunoreactivity in the duodenal mucosa in coeliac disease. Arch Dis Child 1984; 59: 523-27. 7. Wheeler EE, Challacombe DN. Influence of 5-hydroxytryptamine on crypt cell production rate of human duodenal mucosa cultured in vitro. J Clin Pathol 1987; 40: 710-13. 8. Challacombe DN, Wheeler EE. Growth of crypt cell nodules in duodenal mucosa in man during organ culture in vitro. J Clin Pathol 1985, 38: 1388-93.
we
continue
agree with the challenge of O’Malley’s suggested test, to propose carbimazole as the aetiological agent.
Department of Medicine 11 St George’s Hospital Medical School,
S. S. NUSSEY S. R. PAGE
London SW17 0RE
1. Khaleeli AA, Griffith DG, Edwards RHT. The clinical presentation of hypothyroid myopathy and its relationship to abnormalities in structure and function of skeletal muscle. Clin Endocrinol 1983; 19: 365-76 2. Graig FA, Smith JC. Serum creatine kinase activity in altered thyroid states. J Clin Endocrinol Metab 1965; 25: 723-31.
PARVOVIRUS INFECTION, LEUKAEMIA, AND IMMUNODEFICIENCY
SiR,—Kurtzmann
et
all
reported
two
children with acute
lymphoblastic leukaemia who had severe anaemia after persistent parvovirus (HPV) infection and suggested that patients with acquired immunodeficiency may be at risk. Others2-4 have described several cases of persistent HPV infection associated with prolonged erythroblastopenia in cases of immunodeficiency. We report erythroblastopenia in an adult patient with chronic myelomonocytic leukaemia (CMML). This 70-year-old man was admitted with a diagnosis of CMML in January, 1988. Haematological counts were: white blood cells 30 x 109/1 with young granulocytic forms and 10% monocytes, platelets 189 x 109/1, haemoglobin (Hb) 9-8 g/dl, and reticulocytes 68% (absolute value 213 x 109/1). Bone marrow examination revealed hypercellularity with excess granulopoiesis, depressed erythropoiesis (6-6% erythroblasts), and absence of myelofibrosis. Karyotyping was normal. Clinical examination showed hepatosplenomegaly and anaemia. Hydroxyurea was administered over eleven months with several interruptions because of thrombocytopenia. The anaemia required multiple red-cell transfusions (58 units); this patient also had ischaemic heart disease. Six months after diagnosis, we observed a sudden worsening of anaemia, with increased transfusion needs, and a drastic fall of reticulocyte count to zero (figure). A new bone marrow sample in October, 1988, resembled the initial sample except there was more profound depression of erythropoiesis (0-1% erythroblasts). In addition to this erythroblastopenia, morphological abnormalities were observed: the only remaining erythroblasts had cytoplasmic vacuoles and megaloblastic changes. Infection with HPV was suspected. Serological analysis was negative for anti-B19 IgM but B19 viral DNA was found by dot blot. Erythroblastopenia persisted until death, which occurred five B19
months after its onset. No contact with a child with fifth disease was known by our patient. This case report suggests that, as in the other cases described, immunodeficiency favouring persistent HPV infection was probably responsible for chronic erythroblastopenia. Moreover, we think that the source of HPV contamination may be transfused blood products. Arguments to support this hypothesis are: (1) demonstration of HPV in serum of healthy blood donors;s
(2) higher titre of HPV IgG in haemophilic children transfused with clotting factors than in the normal population ;6 and (3) detection of replicative forms of HPV in circulating cells.7 Department of Internal Medicine and Laboratory, C H J Bracops, 1070 Brussels, Belgium
1. Kurtzman
GJ, Cohen B, Meyers P, Amunullah A, Young NS. Persistent B19 parvovirus infection as a cause of severe chronic anaemia in children with acute lymphocytic leukaemia. Lancet 1988; ii: 1159-62. 2. Coulombel L, Morinet F, Mielot F, Tchemia G. Parvovirus infection, leukaemia, and immunodeficiency Lancet 1989; i: 101-02. 3. Davidson JE, Gibson B, Gibson A, Evans TJ. Parvovirus infection, leukaemia, and immunodeficiency. Lancet 1989; i: 102. 4. Weiland HT, Salimans MMM, Fibbe We, Kluin PM, Cohen BJ. Prolonged parvovirus B19 infection with severe anaemia in a bone marrow transplant recipient. Br J Haematol 1989; 71: 300. 5. Cossart YE, Field AM, Cant B, Widdows D. Parvovirus-like particles in human sera. Lancet 1975; i: 72-73. 6. Mortimer PP, Luban NLC, Kelleher JF, Cohen BJ. Transmission of serum parvovirus-like virus by clotting-factor concentrates. Lancet 1983; ii: 482-84. 7. Kurtzman GJ, Gascon P, Caras M, Cohen B, Young NS. B19 parvovirus replicates in circulating cells of acutely infected patients. Blood 1988; 71: 1448-54.
CARCINOID TUMOURS AND ENDOCRINE CELL HYPERPLASIA
SiR,—Your April 29 editorial highlights the association between and endocrine cell hyperplasia in the tract, which raises the question whether these tumours arise in a pre-existing background of endocrine cell hyperplasia or whether the hyperplasia may be secondary to a factor produced by the carcinoid tumour. Multiple polypoidal carcinoid tumours associated with endocrine cell hyperplasia have been described in the stomach of patients with achlorhydria, but unlike most bowel carcinoids, they were composed of argyrophil (not argentaffm) cells of the enterochromaffm-ae (ECL) type.l The patients had high fasting plasma levels of gastrin, which may have stimulated hyperplasia of ECL cells and led to the formation of carcinoid
course in patient with CMML complicated by chronic red-cell aplasia and B19 parvovirus infection.
RET = reticulocytes ; TRANSF
=
transfusion.
tumours
gastrointestinal
carcinoid tumours. Enterochromaffin (EC) cell hyperplasia occurs in the duodenal mucosa of patients with untreated coeliac disease,’ but carcinoid tumours in this disorder are rare. 3,4 Cytofluorometric and immunohistochemical studies of duodenal EC cells in untreated coeliac disease suggest that these cells synthesise increased amounts of serotonin, which is released both locally and into the circulation.5,6 Since serotonin increases the crypt cell production rate in normal duodenal mucosa cultured in vitro’ and promotes the growth of crypt cell nodules,8 this amine, similar to gastrin in the stomach, could induce hyperplasia of both crypt epithelial cells and EC cells in the flattened small intestinal mucosa in coeliac disease. The rarity of carcinoid tumours in the small intestine in coeliac disease, despite EC cell hyperplasia, may be due to factors limiting the growth of most tumours in the small bowel compared with other parts of the gastrointestinal tract. Somerset Children’s Research Unit, Taunton and Somerset Hospital, Taunton TA1 5DA
1.
Clinical
M. MALARME D. VANDERVELDE M. BRASSEUR
D. N. CHALLACOMBE
Harvey RF, Bradshaw MJ, Davidson CM, Wilkinson SP, Davies PS. Multifocal gastric carcinoid tumours, achlorhydria, and hypergastrinaemia. Lancet 1985; i:
951-54. 2. Challacombe DN, Robertson K. Enterochromaffin cells in the duodenal mucosa of children with coeliac disease. Gut 1977; 18: 373-76. 3. Hallert C, Norrby K. Malignant carcinoid tumour complicating coeliac disease. Acta Med Scand 1983; 213: 313-16. 4. Gardiner GW, Van Patter T, Murray D. Atypical carcinoid tumour of the small bowel complicating coeliac disease. Cancer 1985; 56: 2716-22. 5. Challacombe DN, Dawkins PD, Baker P. Increased tissue concentrations of 5-hydroxytryptamine in the duodenal mucosa of patients with coeliac disease. Gut 1977; 18: 882-86. 6. Wheeler EE, Challacombe DN. Quantification of enterochromaffin cells with serotonin immunoreactivity in the duodenal mucosa in coeliac disease. Arch Dis Child 1984; 59: 523-27. 7. Wheeler EE, Challacombe DN. Influence of 5-hydroxytryptamine on crypt cell production rate of human duodenal mucosa cultured in vitro. J Clin Pathol 1987; 40: 710-13. 8. Challacombe DN, Wheeler EE. Growth of crypt cell nodules in duodenal mucosa in man during organ culture in vitro. J Clin Pathol 1985, 38: 1388-93.