BRITISH MEDICAL JOURNAL
27 JANUARY 1979
233
suggests a direct action on bone, as has been shown in tissue culture.5 The previous thyroidectomy and parathyroid removal, with the lack of response to calcitonin, indicate that the reduction in bone resorption could not have been mediated by a reduction in parathyroid hormone secretion or rise in endogenous calcitonin. It is unlikely that developing hypothyroidism played any major part in the action of hydrocortisone on bone resorption in this patient, since the response to hydrocortisone was rapid and the plasma half life of T4 is of the order of 6-7 days. Indeed, after the initial withdrawal of the thyroid supplements there was a steady increase in bone resorption until the administration of hydrocortisone. Dent, C E, British MedicalJournal, 1956, 1, 230. Storey, E, Endocrinology, 1961, 68, 533. 3Gallagher, J C, et al, Clinics in Endocrinology and Metabolism, 1973, 2, 355. 4Nordin, B E C, Calcium, Phosphate and Magnesium Metabolism. Edinburgh, Churchill Livingstone, 1976. 5 Stern, P H, Journal of Pharmacology and Experimental Therapeutics, 1969, 168, 211.
I
2
(Accepted 17 November 1978) MRC Mineral Metabolism Unit, The General Infirmary, Leeds LS1 3EX P J HEYBURN, MB, MRcP, honorary registrar R M FRANCIS, MB, senior house officer M PEACOCK, MB, FRCP, honorary consultant physician
satisfactory. It was decided to perform lower-segment caesarean section. An attempt to remove the intrauterine catheter met with resistance and coincided with a sharp fall in the FHR, which recovered after several minutes. When the patient was anaesthetised a further attempt to withdraw the catheter was made but abandoned. A fresh stillborn infant weighing 3560 g was delivered. At operation the catheter was found to be acutely kinked and entangled in the umbilical cord, which was compressed.
Comment Usually intrauterine pressure monitoring using a polyvinyl intrauterine catheter is safe. In our case we did not appreciate that the catheter was compressing the cord during labour, producing variable deceleration of the FHR. Trying to remove it led to intrauterine asphyxia and fetal death. If variable decelerations in FHR occur with an intrauterine catheter in situ umbilical cord compression by the catheter should be considered. When a gentle attempt to remove the catheter meets with resistance or produces further deceleration of the FHR further attempts to remove it should not be made. IRoux, J F, Newman, M R, and Goodlin, R C, CRC Critical Reviews in Bio-engineering, 1975, 2, 119. 2Chan, W H, Paul, R H, and Toews, J, Obstetrics and Gynecology, 1973, 41, 7. 3Femandez-Rocha, L, and Oullette, R, AmericantJournal of Obstetrics and Gynecology, 125, 1976, 1153. 4Nuttall, I D, British Jounal of Obstetrics and Gynaecology, 1978, 85, 573. 5 Trudinger, B J, and Pryse-Davies, J, British Journal of Obstetrics and Gynaecology, 1978, 85, 567. (Accepted 15 November 1978)
Hypoxic stillbirth due to entangled intrauterine catheter Uterine pressure is recorded, using polyvinyl intrauterine catheters, in many obstetric units practising active management of labour. It carries only a small risk to mother or fetus.' There have been only sporadic reports of uterine perforation or disruption of fetal vessels.2-4 A case has been described of umbilical cord entanglement. We report a similar experience.5
Case report The patient, a 31-year-old primigravida, had conceived after 10 years of voluntary infertility. She was admitted at 38 weeks' gestation for rest and observation because of pre-eclampsia. The results of tests for fetal welfare were satisfactory. Labour was induced at term by artificial rupture of the membranes and intravenous oxytocin. A fetal scalp electrode was applied and an intrauterine pressure catheter introduced to 15 cm by the standard technique. The fetal heart rate at that time was normal. Initial progress in labour was slow but acceptable. A lumbar epidural block provided analgesia. After several hours of strong contractions variable decelerations of the fetal heart rate (FHR) were noted (figure) and the progress of labour was un-
y~~~~~~~~~~
p
Recording showing variable decelerations of fetal heart rate due to compression of umbilical cord. Attempted removal of intrauterine catheter produced sharp (arrow) and sustained fall in rate.
Department of Obstetrics and Gynaccology, Royal United Hospitals, Bath, Avon DONALD G CAVE, MB, MRCOG, registrar GORDON R SWINGLER, FRCSED, MRCOG, senior registrar PETER G SKEW, MB, senior house officer
Successful treatment of malignant testicular teratoma with brain metastases The outlook for some patients with metastatic testicular teratoma has improved considerably with recent advances in chemotherapy.' The presence of brain metastases, however, is generally accepted as unfavourable and we have found no reports of successful treatment. We report a case in which extensive chemotherapy combined with surgery and radiotherapy seems to have been effective.
Case report A 25-year-old postgraduate student presented in December 1974 with a swollen right testis. Orchidectomy and histological examination showed a malignant teratoma with trophoblastic features. Lymphangiography showed metastases in iliac nodes. He was treated by pelvic and para-aortic irradiation to a dose of 4000 rads. He remained well until January 1976. He then developed a right lower-lobe pneumonia as well as severe frontal headaches followed by a mild left hemiparesis. Chest x-ray examination confirmed the presence of metastatic tumour in the right lower lobe and also in the left mid-zone. Computerised tomography (CAT) of the brain showed deposits in the right parietal and right frontal regions. His serum gonadotrophin (HCG) concentration was 52 000 IU/l. Alpha fetoprotein (AFP) was indetectable. Lymphangiography showed no evidence of intra-abdominal metastases. Treatment was started in January 1976. Over the next 12 months he received 19 courses of systemic chemotherapy, usually in conjunction with intrathecal methotrexate (figure). By January 1977 there had been a partial response, as judged by: (1) resolution of the hemiparesis after two months; (2) sequential CAT brain scans showing improvement but also a persistent abnormality in the right parietal area; (3) sequential chest radiographs showing partial resolution but isolated shadows in the right and left midzones; (4) serial serum HCG concentrations, initially falling to normal after 10 weeks' treatment but later rising, indicating persistent active tumour (figure). Consecutive right and left thoracotomies to remove residual lung metastases were performed in February and March 1977 (Mr A R Makey). A lesion from the right middle lobe contained only necrotic tissue
234
BRITISH MEDICAL JOURNAL
Thora cotomy right left
Craniotomy
Surgery
----
10
3 AB BBCCBB DDEDEDEFD FB -1lll|111111111111111111
**
L@** ***
Z**~***
*
*
E. BG GGH
JD
1111
1I I
** ** *
M"*Mo
1
Radiotherapy ---. Chemotherapy
102
10
*
i. \AtFPgI
beta H 3(IUIt,', 0 J FMAMJ J ASO ND J FMAMJ J ASONDJ FMAMJ J ASO 1976 1977 1978
Serial serum HCG and AFP concentrations with details of combined modality treatment. Course A=vinblastine, bleomycin, methotrexate, and folinic acid. Course B= hydroxyurea, vincristine, methotrexate, folinic acid, cyclophosphamide, actinomycin D, adriamycin, and melphalan. Course C= vinblastine and bleomycin. Course D =vincristine, methotrexate, folinic acid, and cis-platinum. Course E=vincristine, methotrexate, folinic acid, and bleomycin. Course F-vincristine, actinomycin D, and cyclophosphamide. Course G=VP 16-213. Course H-VP 16-213, actinomycin D, and cyclophosphamide. Course J=vincristine, methotrexate, and VP 16-213. *= Intrathecal methotrexate. o= Intrathecal thiotepa. on histological examination, but viable tumour was present in a lesion from the basal segment of the left upper lobe. Further chemotherapy was given in March and April 1977. In May 1977 a right craniotomy was performed to remove residual disease from the right parietal lobe (Mr R D Illingworth). A 2-cm lesion was removed, and subsequent histological examination confirmed the presence of metastatic trophoblastic tumour. The patient recovered without neurological deficit, but persistent brain deposits were suspected on the basis of repeatedly raised spinal fluid AFP concentrations. More recent analysis has shown this is unreliable for diagnosing cerebral metastases.2 He was therefore given a course of cranial irradiation (3930 rads in 21 fractions) together with weekly intrathecal chemotherapy (10 injections of methotrexate and 5 of thiotepa). All treatment was stopped in October 1977. He has remained well since, with no evidence from serum tumour markers, radiography, or CAT brain scans of recurrent disease 12 months after the end of treatment. The only long-term sequelae of treatment are patchy alopecia, occasional loss of memory, and loss of high-frequency hearing. The patient has recently resumed full-time work as a teacher.
Comment Cerebral metastases in testicular teratoma are usually associated with progressive disease elsewhere, particularly in the lungs. They arise most often in those patients with trophoblastic tumours. Trophoblastic teratomas are often difficult to control,4 but when metastatic disease in sites other than the brain has responded to treatment an aggressive combined approach to residual brain deposits may be justified. As the treatment of testicular tumours continues to improve such cases may be recognised more often. We thank Dr J N Godlee (University College Hospital, London) for referring this patient, and Dr J A E Ambrose (Atkinson Morley's Hospital, Wimbledon) for doing the CAT scans. I 2
Williams, C, Cancer Treatment Reviews, 1977, 4, 275. Kaye, S B, and Bagshawe, K D, in CNS Complications of Malignant Disease, ed H E M Kay and J M A Whitehouse. London, Macmillan. In press. 3 Vugrin, D, et al, Proceedings of the American Association of Cancer, 1978, 19, 197. 4 Quivey, J M, et al, Cancer, 1977, 39, 1247. (Accepted 22 November 1978) Department of Medical Oncology, Charing Cross Hospital, Fulham Palace Road, London W6 8RF S B KAYE, BSC, MRCP, senior registrar R H J BEGENT, Ma, MRCP, lecturer E S NEWLANDS, PHD, MRCP, senior lecturer and honorary consultant physician K D BAGSHAWE, MD, FRCP, professor
27 JANUARY 1979
Lymphoproliferative disease in two sisters Several instances of families with several members with chronic lymphatic leukaemia (CLL) have been described.' 2 Apparently, however, few if any such families have been investigated by modern immunological methods that distinguish different varieties of CLL. We report here the cases of two sisters in a family who had lymphocytosis of CLL type one of whom had the characteristics of ordinary CLL and the other of prolymphocytic leukaemia. The two sisters were from a family of eight children, including five sisters. The parents were not known to be related. One sibling had a carcinoma of colon but, apart from the sisters investigated, the others had unremarkable medical histories.
Case reports One sister (case 1), aged 82, was seen at Rossendale Hospital in November 1976 complaining of fainting attacks. She had a greatly enlarged liver and spleen but no other lymphadenopathy. The haemoglobin concentration was 7-5 g/dl and white cell count 126 x 109/1 (12 600/mm3) with polymorphs 19 %, lymphocytes 78 %, and monocytes 3 0. The marrow was infiltrated with lymphocytes. The haemoglobin concentration rose to 14 7 g/dl in July 1978 after treatment with iron. The white cell count at that time was 35 109/1 (35 000/mm3) with polymorphs 7 %, lymphocytes 92 1%,, and monocytes 1 %. Many of the lymphocytes were large, had prominent nucleoli, and appeared to be prolymphocytes. She appeared well and had no lymphadenopathy. She had had three children, one of whom had died of carcinoma of the pancreas. The other sister (case 2) was aged 75. She was investigated for tiredness at Rossendale Hospital in 1976. The haemoglobin was 12-4 g/dl, WBC 69 x 109/1 (69 000/mm3), with almost all mature lymphocytes, and the bone marrow was reported as showing 80 % lymphocytes. Enlarged lymph nodes were found in the submandibular regons and in the right axilla. The liver and spleen were not palpable. She had had four children, one of whom had died of Still's disease and one of carcinoma of the ovary. Blood from each patient was examined at the Christie Hospital in 1977 and 1978 with the following similar findings on each occasion. Case 1WBC 25 x 109/1 (25 000/mm3) with polymorphs 8 %, lymphocytes 68 ,) monocytes 2%, prolymphocytes 15 %, and smear cells 7%,,,. Most of the lymphocytes were found to be negative with the PAS test. Case 2-WBC 296 x 109/1 (296 000/mm3) with polymorphs 1 %, lymphocytes 78 %, prolymphocytes 1 %, and smear cells 20 %. Most of the lymphocytes had fine PAS-positive granules and were small and of mature appearance. Cytogenetic studies of the peripheral blood cells of both patients by Dr S Muldahl showed no definite abnormality. The results of lymphocyte surface marker tests are shown in the table. The tests were done on the same day and the Results of lymphocyte surface marker tests in two sisters with lymphoproliferative disease
Anti-Poly Ig. F(ab'), fragment of anti-Ig Anti-kappa. Anti-lambda.% of anti-X. positive cells capping .570/, Sheep ERFC. Mouse ERFC.
Case 1
Case 2
+ + + + + + + +
+ ++ + + + ++ + -
7 1
900,,
80,"
4%,
same antisera, sheep and mouse red cells were used in each case. The results show the characteristics of CLL and prolymphocytic leukaemia, or lymphosarcoma cell leukaemia, respectively.3 4 Both sisters show proliferation of a monoclone of lymphocytes with kappa light chain surface immunoglobulin (SIg). In case 2 there was a small amount of SIg per cell and high mouse red cell rosettes (MRFC), characteristic of CLL. In case 1 there was a large amount of SIg per cell, frequent capping, and low MRFC, characteristic of prolymphocytic and of lymphosarcoma cell leukaemia.
Comment The relationship of CLL, prolymphocytic leukaemia, and lymphosarcoma cell leukaemia to one another is not clear. The simultaneous occurrence of two forms of lymphoproliferative disease in two sisters seems more likely to be associated with some inherited instability of the lymphocyte system rather than to be fortuitous. The investigation of further families by modern immunological methods may contribute to our understanding of these conditions. We thank the late Dr R D Popham, of Bury General Hospital, for first drawing our attention to these patients; Dr Grimshaw, of Rossendale
27 JANUARY 1979
233
suggests a direct action on bone, as has been shown in tissue culture.5 The previous thyroidectomy and parathyroid removal, with the lack of response to calcitonin, indicate that the reduction in bone resorption could not have been mediated by a reduction in parathyroid hormone secretion or rise in endogenous calcitonin. It is unlikely that developing hypothyroidism played any major part in the action of hydrocortisone on bone resorption in this patient, since the response to hydrocortisone was rapid and the plasma half life of T4 is of the order of 6-7 days. Indeed, after the initial withdrawal of the thyroid supplements there was a steady increase in bone resorption until the administration of hydrocortisone. Dent, C E, British MedicalJournal, 1956, 1, 230. Storey, E, Endocrinology, 1961, 68, 533. 3Gallagher, J C, et al, Clinics in Endocrinology and Metabolism, 1973, 2, 355. 4Nordin, B E C, Calcium, Phosphate and Magnesium Metabolism. Edinburgh, Churchill Livingstone, 1976. 5 Stern, P H, Journal of Pharmacology and Experimental Therapeutics, 1969, 168, 211.
I
2
(Accepted 17 November 1978) MRC Mineral Metabolism Unit, The General Infirmary, Leeds LS1 3EX P J HEYBURN, MB, MRcP, honorary registrar R M FRANCIS, MB, senior house officer M PEACOCK, MB, FRCP, honorary consultant physician
satisfactory. It was decided to perform lower-segment caesarean section. An attempt to remove the intrauterine catheter met with resistance and coincided with a sharp fall in the FHR, which recovered after several minutes. When the patient was anaesthetised a further attempt to withdraw the catheter was made but abandoned. A fresh stillborn infant weighing 3560 g was delivered. At operation the catheter was found to be acutely kinked and entangled in the umbilical cord, which was compressed.
Comment Usually intrauterine pressure monitoring using a polyvinyl intrauterine catheter is safe. In our case we did not appreciate that the catheter was compressing the cord during labour, producing variable deceleration of the FHR. Trying to remove it led to intrauterine asphyxia and fetal death. If variable decelerations in FHR occur with an intrauterine catheter in situ umbilical cord compression by the catheter should be considered. When a gentle attempt to remove the catheter meets with resistance or produces further deceleration of the FHR further attempts to remove it should not be made. IRoux, J F, Newman, M R, and Goodlin, R C, CRC Critical Reviews in Bio-engineering, 1975, 2, 119. 2Chan, W H, Paul, R H, and Toews, J, Obstetrics and Gynecology, 1973, 41, 7. 3Femandez-Rocha, L, and Oullette, R, AmericantJournal of Obstetrics and Gynecology, 125, 1976, 1153. 4Nuttall, I D, British Jounal of Obstetrics and Gynaecology, 1978, 85, 573. 5 Trudinger, B J, and Pryse-Davies, J, British Journal of Obstetrics and Gynaecology, 1978, 85, 567. (Accepted 15 November 1978)
Hypoxic stillbirth due to entangled intrauterine catheter Uterine pressure is recorded, using polyvinyl intrauterine catheters, in many obstetric units practising active management of labour. It carries only a small risk to mother or fetus.' There have been only sporadic reports of uterine perforation or disruption of fetal vessels.2-4 A case has been described of umbilical cord entanglement. We report a similar experience.5
Case report The patient, a 31-year-old primigravida, had conceived after 10 years of voluntary infertility. She was admitted at 38 weeks' gestation for rest and observation because of pre-eclampsia. The results of tests for fetal welfare were satisfactory. Labour was induced at term by artificial rupture of the membranes and intravenous oxytocin. A fetal scalp electrode was applied and an intrauterine pressure catheter introduced to 15 cm by the standard technique. The fetal heart rate at that time was normal. Initial progress in labour was slow but acceptable. A lumbar epidural block provided analgesia. After several hours of strong contractions variable decelerations of the fetal heart rate (FHR) were noted (figure) and the progress of labour was un-
y~~~~~~~~~~
p
Recording showing variable decelerations of fetal heart rate due to compression of umbilical cord. Attempted removal of intrauterine catheter produced sharp (arrow) and sustained fall in rate.
Department of Obstetrics and Gynaccology, Royal United Hospitals, Bath, Avon DONALD G CAVE, MB, MRCOG, registrar GORDON R SWINGLER, FRCSED, MRCOG, senior registrar PETER G SKEW, MB, senior house officer
Successful treatment of malignant testicular teratoma with brain metastases The outlook for some patients with metastatic testicular teratoma has improved considerably with recent advances in chemotherapy.' The presence of brain metastases, however, is generally accepted as unfavourable and we have found no reports of successful treatment. We report a case in which extensive chemotherapy combined with surgery and radiotherapy seems to have been effective.
Case report A 25-year-old postgraduate student presented in December 1974 with a swollen right testis. Orchidectomy and histological examination showed a malignant teratoma with trophoblastic features. Lymphangiography showed metastases in iliac nodes. He was treated by pelvic and para-aortic irradiation to a dose of 4000 rads. He remained well until January 1976. He then developed a right lower-lobe pneumonia as well as severe frontal headaches followed by a mild left hemiparesis. Chest x-ray examination confirmed the presence of metastatic tumour in the right lower lobe and also in the left mid-zone. Computerised tomography (CAT) of the brain showed deposits in the right parietal and right frontal regions. His serum gonadotrophin (HCG) concentration was 52 000 IU/l. Alpha fetoprotein (AFP) was indetectable. Lymphangiography showed no evidence of intra-abdominal metastases. Treatment was started in January 1976. Over the next 12 months he received 19 courses of systemic chemotherapy, usually in conjunction with intrathecal methotrexate (figure). By January 1977 there had been a partial response, as judged by: (1) resolution of the hemiparesis after two months; (2) sequential CAT brain scans showing improvement but also a persistent abnormality in the right parietal area; (3) sequential chest radiographs showing partial resolution but isolated shadows in the right and left midzones; (4) serial serum HCG concentrations, initially falling to normal after 10 weeks' treatment but later rising, indicating persistent active tumour (figure). Consecutive right and left thoracotomies to remove residual lung metastases were performed in February and March 1977 (Mr A R Makey). A lesion from the right middle lobe contained only necrotic tissue
234
BRITISH MEDICAL JOURNAL
Thora cotomy right left
Craniotomy
Surgery
----
10
3 AB BBCCBB DDEDEDEFD FB -1lll|111111111111111111
**
L@** ***
Z**~***
*
*
E. BG GGH
JD
1111
1I I
** ** *
M"*Mo
1
Radiotherapy ---. Chemotherapy
102
10
*
i. \AtFPgI
beta H 3(IUIt,', 0 J FMAMJ J ASO ND J FMAMJ J ASONDJ FMAMJ J ASO 1976 1977 1978
Serial serum HCG and AFP concentrations with details of combined modality treatment. Course A=vinblastine, bleomycin, methotrexate, and folinic acid. Course B= hydroxyurea, vincristine, methotrexate, folinic acid, cyclophosphamide, actinomycin D, adriamycin, and melphalan. Course C= vinblastine and bleomycin. Course D =vincristine, methotrexate, folinic acid, and cis-platinum. Course E=vincristine, methotrexate, folinic acid, and bleomycin. Course F-vincristine, actinomycin D, and cyclophosphamide. Course G=VP 16-213. Course H-VP 16-213, actinomycin D, and cyclophosphamide. Course J=vincristine, methotrexate, and VP 16-213. *= Intrathecal methotrexate. o= Intrathecal thiotepa. on histological examination, but viable tumour was present in a lesion from the basal segment of the left upper lobe. Further chemotherapy was given in March and April 1977. In May 1977 a right craniotomy was performed to remove residual disease from the right parietal lobe (Mr R D Illingworth). A 2-cm lesion was removed, and subsequent histological examination confirmed the presence of metastatic trophoblastic tumour. The patient recovered without neurological deficit, but persistent brain deposits were suspected on the basis of repeatedly raised spinal fluid AFP concentrations. More recent analysis has shown this is unreliable for diagnosing cerebral metastases.2 He was therefore given a course of cranial irradiation (3930 rads in 21 fractions) together with weekly intrathecal chemotherapy (10 injections of methotrexate and 5 of thiotepa). All treatment was stopped in October 1977. He has remained well since, with no evidence from serum tumour markers, radiography, or CAT brain scans of recurrent disease 12 months after the end of treatment. The only long-term sequelae of treatment are patchy alopecia, occasional loss of memory, and loss of high-frequency hearing. The patient has recently resumed full-time work as a teacher.
Comment Cerebral metastases in testicular teratoma are usually associated with progressive disease elsewhere, particularly in the lungs. They arise most often in those patients with trophoblastic tumours. Trophoblastic teratomas are often difficult to control,4 but when metastatic disease in sites other than the brain has responded to treatment an aggressive combined approach to residual brain deposits may be justified. As the treatment of testicular tumours continues to improve such cases may be recognised more often. We thank Dr J N Godlee (University College Hospital, London) for referring this patient, and Dr J A E Ambrose (Atkinson Morley's Hospital, Wimbledon) for doing the CAT scans. I 2
Williams, C, Cancer Treatment Reviews, 1977, 4, 275. Kaye, S B, and Bagshawe, K D, in CNS Complications of Malignant Disease, ed H E M Kay and J M A Whitehouse. London, Macmillan. In press. 3 Vugrin, D, et al, Proceedings of the American Association of Cancer, 1978, 19, 197. 4 Quivey, J M, et al, Cancer, 1977, 39, 1247. (Accepted 22 November 1978) Department of Medical Oncology, Charing Cross Hospital, Fulham Palace Road, London W6 8RF S B KAYE, BSC, MRCP, senior registrar R H J BEGENT, Ma, MRCP, lecturer E S NEWLANDS, PHD, MRCP, senior lecturer and honorary consultant physician K D BAGSHAWE, MD, FRCP, professor
27 JANUARY 1979
Lymphoproliferative disease in two sisters Several instances of families with several members with chronic lymphatic leukaemia (CLL) have been described.' 2 Apparently, however, few if any such families have been investigated by modern immunological methods that distinguish different varieties of CLL. We report here the cases of two sisters in a family who had lymphocytosis of CLL type one of whom had the characteristics of ordinary CLL and the other of prolymphocytic leukaemia. The two sisters were from a family of eight children, including five sisters. The parents were not known to be related. One sibling had a carcinoma of colon but, apart from the sisters investigated, the others had unremarkable medical histories.
Case reports One sister (case 1), aged 82, was seen at Rossendale Hospital in November 1976 complaining of fainting attacks. She had a greatly enlarged liver and spleen but no other lymphadenopathy. The haemoglobin concentration was 7-5 g/dl and white cell count 126 x 109/1 (12 600/mm3) with polymorphs 19 %, lymphocytes 78 %, and monocytes 3 0. The marrow was infiltrated with lymphocytes. The haemoglobin concentration rose to 14 7 g/dl in July 1978 after treatment with iron. The white cell count at that time was 35 109/1 (35 000/mm3) with polymorphs 7 %, lymphocytes 92 1%,, and monocytes 1 %. Many of the lymphocytes were large, had prominent nucleoli, and appeared to be prolymphocytes. She appeared well and had no lymphadenopathy. She had had three children, one of whom had died of carcinoma of the pancreas. The other sister (case 2) was aged 75. She was investigated for tiredness at Rossendale Hospital in 1976. The haemoglobin was 12-4 g/dl, WBC 69 x 109/1 (69 000/mm3), with almost all mature lymphocytes, and the bone marrow was reported as showing 80 % lymphocytes. Enlarged lymph nodes were found in the submandibular regons and in the right axilla. The liver and spleen were not palpable. She had had four children, one of whom had died of Still's disease and one of carcinoma of the ovary. Blood from each patient was examined at the Christie Hospital in 1977 and 1978 with the following similar findings on each occasion. Case 1WBC 25 x 109/1 (25 000/mm3) with polymorphs 8 %, lymphocytes 68 ,) monocytes 2%, prolymphocytes 15 %, and smear cells 7%,,,. Most of the lymphocytes were found to be negative with the PAS test. Case 2-WBC 296 x 109/1 (296 000/mm3) with polymorphs 1 %, lymphocytes 78 %, prolymphocytes 1 %, and smear cells 20 %. Most of the lymphocytes had fine PAS-positive granules and were small and of mature appearance. Cytogenetic studies of the peripheral blood cells of both patients by Dr S Muldahl showed no definite abnormality. The results of lymphocyte surface marker tests are shown in the table. The tests were done on the same day and the Results of lymphocyte surface marker tests in two sisters with lymphoproliferative disease
Anti-Poly Ig. F(ab'), fragment of anti-Ig Anti-kappa. Anti-lambda.% of anti-X. positive cells capping .570/, Sheep ERFC. Mouse ERFC.
Case 1
Case 2
+ + + + + + + +
+ ++ + + + ++ + -
7 1
900,,
80,"
4%,
same antisera, sheep and mouse red cells were used in each case. The results show the characteristics of CLL and prolymphocytic leukaemia, or lymphosarcoma cell leukaemia, respectively.3 4 Both sisters show proliferation of a monoclone of lymphocytes with kappa light chain surface immunoglobulin (SIg). In case 2 there was a small amount of SIg per cell and high mouse red cell rosettes (MRFC), characteristic of CLL. In case 1 there was a large amount of SIg per cell, frequent capping, and low MRFC, characteristic of prolymphocytic and of lymphosarcoma cell leukaemia.
Comment The relationship of CLL, prolymphocytic leukaemia, and lymphosarcoma cell leukaemia to one another is not clear. The simultaneous occurrence of two forms of lymphoproliferative disease in two sisters seems more likely to be associated with some inherited instability of the lymphocyte system rather than to be fortuitous. The investigation of further families by modern immunological methods may contribute to our understanding of these conditions. We thank the late Dr R D Popham, of Bury General Hospital, for first drawing our attention to these patients; Dr Grimshaw, of Rossendale
