Journal of the Royal Society of Medicine Volume 86 August 1993 479 bony overgrowths as a ... The Proteus syndrome: the Elephant. Man diagnosed. BMJ 1986 ...
Journal of the Royal Society of Medicine Volume 86 August 1993 bony overgrowths as a variable feature. Hemihypertrophy may occur and syndactyly is a frequent finding. One series reported a 22% incidence of venous thromboembolism5. Our patient, whose clinical features are summarized in Table 1, exhibits the characteristic features of hemihypertrophy, macrodactyly, epidermal naevi, port-wine staining and angiomatous naevi, which would be consistent with Proteus syndrome. The complete syndactyly of second and third toes and absence of plantar soft tissue hypertrophy, however, would be more in keeping with Klippel-Trenaunay syndrome. The occurence of recurrent venous thromboses would be supportive of Klippel-Trenaunay syndrome, but it is interesting that in our patient this involved the side unaffected by hemihypertrophy. The diagnostic criteria for Proteus syndrome are not yet fully established. Therefore, it is not clear whether this patient should be labelled as Proteus syndrome or as a true overlap between the Proteus and Klippel-Trenaunay syndromes. The aetiology of either syndrome is speculative but neither is known to have an hereditary basis and for both conditions a hypothesis could be proposed of possible somatic mosaicism
for mutation in a growth factor or regulator gene. The considerable overlap between these two diagnoses in this patient raises the possibility of a common aetiological mechanism. Acknowledgment: We are grateful to Dr M Baraitser for clinical advice. References 1 Weidemann HR, Burgio GR, Aldenhoff P, et aL The Proteus syndrome. Eur J Pediatr 1983;140:5-12 2 Clark RD, Donnai D, Rogers J, et al Proteus syndrome: an expanded phenotype. Am J Med Genet 1987;27:99-117 3 Tibbles JAR, Cohen MM. The Proteus syndrome: the Elephant Man diagnosed. BMJ 1986;293:683-5 4 Viljoen DL, Nelson MM, de Jong G, Beighton P. Proteus syndrome in Southern Africa. Am J Med Genet 1987;27:87-97 5 Baskerviile PA, Ackroyd JS, Lea Thomas M, Browse NL. The Klippel-Trenaunay syndrome: clinical, radiological and haemodynamic features and management. Br J Surg 1985;72:232-6
(Accepted 10 December 1992)
Asymptomatic metastatic small bowel carcinoid
Case presented to Clinical Section, 10 April 1992 ...........
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D Hadjiminas FRCS M J Hershman MS FRCS R D Rosin MS FRCS Department of Surgery, St Mary's Hospital, London W2, UK Keywords: carcinoid; metastasis; small bowel; hepatectomy
Small bowel carcinoid is rare. We present an asymptomatic patient who presented with extensive metastatic disease and discuss therapeutic options.
Figure 1 A.computezed tomography scan showing 10 cm in the right lobe of the liver
tumour
Case report A 76-year-old asymptomatic woman was investigated for hypertension. Direct questioning revealed facial flushing after alcohol. Urine 5-Hydroxyindole acetic acid was 282 nmol/l (normal < 40 nmol/l) and urine vanillylmandelic acid and serum catecholamines were normal. An abdominal ultrasound demonstrated a 10 cm liver lesion and computerized tomography guided biopsy revealed a malignant neuroendocrine tumour of uncertain aetiology (Figure 1). A methyl-iodobenzylguanidine (MIBG) scan showed isotope uptake by the liver tumour and a spot in the pelvis (Figure 2). At laparotomy, an ileal tumour causing subacute obstruction was found in the pelvis. It was situated adjacent to a Meckel's diverticulum which contained a second small tumour. There was a large secondary deposit in the right lobe of the liver and smaller ones in the left lobe. An ileal resection, right hemihepatectomy and metastasectomies were performed. In addition, a catheter with a subcutaneous port was inserted in the left hepatic artery. Histology of all lesions confirmed carcinoid tumour. She made an uneventful recovery and is well and asymptomatic 1 year later.
Discussion Carcinoids are slow growing tumours derived from APUD cells and constitute 2% of all malignancies. The most Correspondence to: Mr M J Hershman, Consultant Surgeon, Royal Liverpool University Hospital, Prescot St, Liverpool L7 8XP, UK
479
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Figure 2. Methyl iodobenzylguanidine scan showing isotope uptake by the liver and a spot in the pelvis
common location is the appendix, where tumours are usually small and benign. However, 40% of appendicular tumours larger than 2 cm metastasise. Carcinoid tumours that develop elsewhere in the gastrointestinal tract are more often malignant1. One-third of all small bowel tumours are
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Journal of the Royal Society of Medicine Volume 86 August 1993
carcinoids2. They usually occur in the ileum, are often multiple (16-34%) and can be associated with other bowel tumours3. In this case, a phaeochromocytoma was initially suspected because ofthe hypertension. This proved incidental but, fortunately, stimulated further investigation including MIBG scanning. MIBG scans are typically used for phaeochromocytomas but may also identify carcinoids. The overall 5 year survival rate is about 50% for small bowel carcinoid2. When tumours are confined to the bowel wall, the survival rate is 85%, but only 5% when they invade serosa or metastasise4. When liver metastases are present, malignant carcinoid syndrome (MCS) may occur. This is characterized by bronchospasm, diarrhoea, facial flushes, hypotension and right-sided heart lesions and is due to tumour secreted peptides5. Flushing is the most common symptom and occurs in 90% of cases. However, liver metastases may be asymptomatic. Our patient admitted to minor facial flushing on direct questioning. It is possible that she could develop MCS in the future. Carcinoid liver secondaries almost invariably involve both lobes6. Resection gives the best palliation and can prolong life by several years7. Debulking procedures should be performed even when there is gross disease, as in this case8. Inoperable metastatic disease may be treated by hepatic artery ligation or hyperthermic liver perfusion9. In addition, various chemotherapeutic agents can be used including streptozocin and somatostatin, a natural inhibitor of APUD cells capable of 'switching off' tumour cells and reducing 5-HIAA excretion'0. These drugs may be more effective when administered via the hepatic artery. For this
Neutropenia induced by aminoglutethimide in breast cancer
Joyce L Steinberg MD Maureen E Trudeau MD Women's College Hospital Department of Medicine, Toronto, Ontario, Canada Keywords: neutropenia; aminoglutethimide; metastatic breast cancer
Aminoglutethimide has efficacy in patients with metastatic breast carcinoma and is used as second or third line therapy in hormonally sensitive disease1. Its mechanism of action is by peripheral aromatase inhibition, blocking the conversion of androgens to estrogen. It blocks steroid synthesis in the adrenal gland causing a medical adrenalectomy necessitating the concurrent administration of hydrocortisone. The most frequently reported side effects include skin rash, fever, lethargy and symptoms related to hydrocortisone use. Thrombocytopenia and/or leukopenia are uncommon but may be life threatening. We report a patient who experienced severe leukopenia. Case report The patient was a 78-year-old female, diagnosed with breast carcinoma in November 1988. She underwent a left modified radical mastectomy for an infiltrating ductal carcinoma with tumour in 14 of 15 axillary lymph nodes. Estrogen and progesterone receptors were positive. Adjuvant tamoxifen 20 mg daily was prescribed until July 1990 when a right axillary lymph node was positive for metastatic disease. Tamoxifen was discontinued and megace, a progestational agent, was started at 160 mg daily. Blood Correspondence to: ME Trudeau MD, Women's College Hospital, Burton Hall, Suite 511, 60 Grosvenor Street, Toronto, Ontario M5S 1B6, Canada
reason a catheter was placed in our patient. She has not required chemotherapy to date. Another therapeutic option is the serotonin receptor inhibitor, cyproheptidine which is particularly effective against the diarrhoea of MCS. References 1 Zeitels J, Naunheim K, Kaplan EL, Straus F II. Carcinoid tumours. Arch Surg 1982;117:732-7 2 Godwin JD II. Carcinoid Tumours. An analysis of 2,837 cases. Cancer 1975;36:560-9 3 Kuiper DH, Gracie WA Jr, Pollard HM. Twenty years of gastrointestinal carcinoids. Cancer 1970;25:1424-30 4 Zakariai YM, Quan SHQ, Hajdu SI. Carcinoid tumors of the gastrointestinal tract. Cancer 1975;35:588-91 5 Davis Z, Moertel CG, Mcllrath DC. The Malignant Carcinoid Syndrome. Surg Gynecol Obstet 1973;137:637-43 6 MacGillivray DC, Synder DA, Drucker W, Remine SG. Carcinoid tumours: The relationship between clinical presentation and the extent of disease. Surgery 1991;110:68-72 7 Moertel CG, Sauer WG, Dockerty MB, Baggenstoss AH. Life history of the carcinoid tumor of the small intestine. Cancer 1961;14:901-12 8 Gillett DJ, Smith RC. Treatment of the carcinoid syndrome by hemihepatectomy and radical excision of the primary lesion. Am J Surg 1974;128:95-9 9 McDermott WV, Hansle TW. Metastatic carcinoid of the liver treated by hepatic dearterialisation. Ann Surg 1974;180:305-8 10 Wangberg B, Nilsson 0, Theodorsson E. The effect of a somatostatin analogue on the releases of hormones from human carcinoid tumour cells. Br J Cancer 1991;64(1):23-8 (Accepted 12 November 1992)
counts, chest X-ray, liver ultrasound and bone scan were normal. By September 1990, the disease had progressed and chemotherapy was suggested. However, the patient refused. Megace was stopped and aminoglutethimide 250 mg and hydrocortisone 40 mg twice daily were started 27 September 1990, when blood counts were normal. Treatment was well tolerated and 2 weeks later, with evidence of disease shrinkage, aminoglutethimide was increased to three times daily and hydrocortisone was decreased to 20 mg twice daily. One week later, aminoglutethimide was increased to four times daily. She was taking no other medications. The patient presented to the Women's College Hospital, Toronto, on 26 November 1990 with fever, chills and diarrhoea. Physical examination revealed an obviously ill woman with a temperature of 39.4°C. An erythematous rash was noted as well as a left pleural effusion. Total white blood count (WBC) was 0.4x 109/1 with 0% neutrophils. Platelets were normal. Cultures were obtained and broad spectrum antibiotic treatment was initiated. Hydrocortisone was restarted at 40 mg twice daily. All cultures were negative. On 2 December she became afebrile. Her WBC rose gradually reaching a peak of 32.8x 109/L with a left shift. Bone marrow biopsy and aspirate performed 10 December 1990 were normocellular and all three haematopoietic elements were present in normal numbers, with no evidence of marrow involvement by metastatic carcinoma. She recovered with eventual normalization of her leukocytes. The cancer progressed despite chemotherapy and the patient expired May 1991.
Comments Haematologic toxicity from aminoglutethimide is uncommon, but as demonstrated by this case, can be severe. In a report by Messeih et al.2, of 1333 patients treated with aminoglutethimide and steroids, 12 (0.9%) had marked leukopenia and/or thrombocytopenia, occurring within 7 weeks of startingtreatment. No association was seen between the haematologic toxicity and other side effects. Buzdar et aL reported two cases of thrombocytopenia and one of severe leukopenia among 163 patients3. The leukopenic patient was rechallenged with aminoglutethimide without further
