Myelosarcoma as the primary manifestation of acute myeloid leukemia

Myelosarcoma ("Granulocytic sarcoma", "Chloroma") is an extramedullary tumor composed of granulocytic precursor cells and related to myelogenous leukemia. If the tumor precedes acute leukemia diagnosis is difficult and requires special diagnostic techniques. This is documented by the presented 7.5 years old girl with primary myelosarcoma. In spite of early and intensive chemotherapy and radiation the sarcoma soon was followed by acute myelogenous leukemia with skin infiltrations. Cytogenetic classifications may in future lead to the development of a differentiated therapy of myelosarcoma.     

Pituitary stalk thickening with diabetes insipidus preceding typical manifestations of Langerhans cell histiocytosis in children

In up to 25% of cases of children with central diabetes insipidus no organic cause can be documented. We present three boys (age 2.2, 2.3 and 6 years at diagnosis) with acute onset central diabetes insipidus, in whom the only pathological finding using MRI was a thickened central part of the pituitary stalk (>2.5 mm). Recent reports demonstrate similar MRI findings in adults with Langerhans cell histiocytosis (LCH), sarcoidosis, or tuberculosis, and in children with proven LCH and diabetes insipidus. In those adults with LCH, the pituitary stalk lesion has been histologically verified as a sequela of LCH. In contrast, in two of our three patients pituitary stalk thickening preceded the typical peripheral lesions of LCH by several months, whereas in the third patient there is as yet no evidence of systemic disease. We conclude that thickening of the central part of the pituitary stalk might represent the first manifestations of LCH clinically presenting with diabetes insipidus. MRI investigation of the pituitary stalk in children in children with unexplained central diabetes insipidus and accurate follow up in patients with thickening of the pituitary stalk in necessary to avoid missing other manifestations of a systemic disease.     

Lymphocytic hypophysitis with central diabetes insipidus and consequent panhypopituitarism preceding a multifocal, intracranial germinoma in a prepubertal girl

We report the clinical course of a prepubertal girl with central diabetes insipidus (DI) and consequent panhypopituitarism evolving over a period of 10 years due to lymphocytic hypophysitis and subsequent germinoma. Two years after the diagnosis of central DI was established, MRI revealed a thickened pituitary stalk. Later pituitary enlargement and increasing thickening of the pituitary stalk impinging on the optic chiasm required a trans-sphenoidal biopsy which disclosed active hypophysitis with lymphocytic infiltrates and necrosis. High dose dexamethasone treatment only temporarily halted the disease process. Therefore, stereotactic radiation therapy was performed as a rescue treatment and MRI findings almost reversed. However, the subsequent MRI showed multiple intracranial lesions identified histologically as a germinoma and a standard chemotherapy and radiation was performed. Conclusion The diagnosis of diabetes insipidus in children requires long-term follow up beyond the pubertal age in order to establish the underlying cause. In contrast to lymphocytic hypophysitis in adults, lymphocytic hypophysitis in prepubertal children may represent the first sign of a host reaction to an occult germinoma. Received: 14 May 1998 / Accepted in revised form: 9 July 1998     

Somnolence syndrome in a child following 1200-cGy total body irradiation in an unrelated bone marrow transplantation

Neurological complications may occur following intensive chemotherapy and hematopoietic cell transplantation. Postirradiation somnolence syndrome has been observed in children with acute lymphoblastic leukemia who received central nervous system preventive therapy with 1800-2400 cGy cranial irradiation. The authors report a 16-year-old boy with chronic myelogenous leukemia in chronic phase, who developed symptoms compatible with thes omnolence syndrome (SS) 6 weeks following HLA-matched unrelated bone marrow transplantation (BMT). The preparative regimen consisted of 1200 cGy total body irradiation (TBI), cytosine arabinoside and cyclophosphamide. The patient developed lethargy and low-grade fever, with intermittent rhythmical delta activity in electroencephalograph. Here covered spontaneously without specific therapy 3 weeks after developing symptoms. This is the first report describing that as low as 1200 cGy TBI can induce SS in a child. After allogeneic BMT, some patients develop neurological symptoms. The authors suggest that somnolence syndrome should be included in differential diagnosis in these patients.     

Central diabetes insipidus: Is it Langerhans cell histiocytosis of the pituitary stalk? A diagnostic pitfall

Central diabetes insipidus (CDI) is a rare disorder that may be caused by a variety of diseases. In pediatric and adolescent patients the most common causes for CDI are Langerhans cell histiocytosis (LCH) and germinoma. To avoid a potentially hazardous biopsy of the hypothalamic pituitary region it is recommended to evaluate patients with CDI carefully to identify potential extracranial lesions. Since LCH is the most common systemic disease that may cause CDI, special focus is paid to the identification of LCH lesions. We report on a 9(1/2) year old girl who presented with central diabetes insipidus and a thickening of the pituitary stalk on magnetic resonance imaging. Diagnostic workup revealed a history of recurrent ear infections and a compressed 6th thoracic vertebral body on radiographs. Based on these findings LCH was anticipated. Upon growth of the pituitary stalk lesion the patient was treated with LCH standard chemotherapy. After an initial shrinkage of the lesion, a further growth of the pituitary stalk lesion was observed and the tumor was resected. Histopathology revealed germinoma. This case underscores the importance of a istopathologically proven diagnosis in patients with HPR tumors before the initiation of a specific therapy, even if the clinical findings are highly suggestive.     

SOMNOLENCE SYNDROME IN A CHILD FOLLOWING 1200-cGy TOTAL BODY IRRADIATION IN AN UNRELATED BONE MARROW TRANSPLANTATION

Neurological complications may occur following intensive chemotherapy and hematopoietic cell transplantation. Postirradiation somnolence syndrome has been observed in children with acute lymphoblastic leukemia who received central nervous system preventive therapy with 1800-2400 cGy cranial irradiation. The authors report a 16-year-old boy with chronic myelogenous leukemia in chronic phase, who developed symptoms compatible with thes omnolence syndrome (SS) 6 weeks following HLA-matched unrelated bone marrow transplantation (BMT). The preparative regimen consisted of 1200 cGy total body irradiation (TBI), cytosine arabinoside and cyclophosphamide. The patient developed lethargy and low-grade fever, with intermittent rhythmical delta activity in electroencephalograph. Here covered spontaneously without specific therapy 3 weeks after developing symptoms. This is the first report describing that as low as 1200 cGy TBI can induce SS in a child. After allogeneic BMT, some patients develop neurological symptoms. The authors suggest that somnolence syndrome should be included in differential diagnosis in these patients.     

Normal MR appearances of the posterior pituitary in central diabetes insipidus associated with septo-optic dysplasia

Magnetic resonance (MR) imaging of the pituitary in children with central diabetes insipidus usually shows absence of the normal high signal within the posterior gland. The high signal of the normal posterior pituitary is thought to be due to the presence of intra- cellular storage granules of vasopressin. MR imaging has been advocated as a useful investigation to aid in the distinction between central diabetes insipidus and other causes of thirst and polydipsia. We report the case of an infant with central diabetes insipidus in association with septo-optic dysplasia in whom MR imaging showed normal appearances of the posterior pituitary. The mechanism of central diabetes insipidus in this case may be related to a failure of hypothalamic function affecting osmoreception, rather than to a deficiency of vasopressin. Normal MR appearances of the pituitary do not exclude central diabetes insipidus in infants with midline cerebral malformations. Received: 20 November 1995 Accepted: 20 January 1996     

Current perspective on the pathogenesis of central diabetes insipidus

Diabetes insipidus is a heterogeneous condition characterised by polyuria and polydipsia caused by a lack of secretion of vasopressin, its physiological suppression following excessive water intake, or kidney resistance to its action. The clinical and laboratory diagnosis is confirmed by standard tests, but recent advances in molecular biology and imaging techniques have shed new light on the pathophysiology of this disease. In many patients, central diabetes insipidus is caused by a germinoma or craniopharyngioma; Langerhans' cell histiocytosis and sarcoidosis of the central nervous system; local inflammatory, autoimmune or vascular diseases; trauma from surgery or accident; and, rarely, genetic defects in vasopressin biosynthesis inherited as autosomal dominant or X-linked recessive traits. Thirty to fifty percent of cases are considered idiopathic. Tumour-associated central diabetes insipidus is uncommon in children younger than 5 years old. Biopsy of enlarged pituitary stalk should be reserved for patients with hypothalamic-pituitary mass and progressive thickening of the pituitary stalk since spontaneous recovery may occur. Molecular biology in selected patients may identify those with apparently idiopathic diabetes insipidus carrying the vasopressin-neurophysin II gene mutation.     

Germinoma: a rare cerebral tumor causing central diabetes insipidus in childhood

Germinoma represents 7.8% of cerebral tumors in pediatric age and 50-65% of germ cell cerebral tumors. Generally it is a definite lesion of the pineal gland or suprasellar region, frequently occurring in the first three decades of life. Clinical presentation depends on tumor localization. Pineal lesions generally determine symptoms due to the compression of cerebral structures, causing Parinaud syndrome, while hypothalamic lesions are often characterized by diabetes insipidus, hypopituitarism and visual defects. In the absence of these classic signs and symptoms, however, the diagnosis of germinoma can be difficult. We presented the case of an 8-year-old boy, referred to our clinic for polyuria and polydipsia. Hormonal evaluations demonstrated central diabetes insipidus (CDI), with normal anterior pituitary function. Magnetic resonance imaging (MRI) showed a lack of posterior pituitary gland and partial pituitary stalk enlargement. The patient started therapy with desmopressin (Minirin) with good hydro-electrolytic balance. During follow-up the pituitary function became insufficient with low growth velocity. A second MRI demonstrated a bifocal lesion with dyshomogeneous and cystic appearance, suggesting the diagnosis of germinoma. On the basis of this case report we would like to point out the importance of an early diagnosis in order to improve the prognosis of the disease and the necessity of a careful follow-up of these patients.     

Secondary adrenal insufficiency in an infant after intrathecal triple chemotherapy

Intrathecal triple chemotherapy (ITT) with hydrocortisone, methotrexate, and cytarabine is commonly used in treatment of pediatric acute leukemias. While prolonged systemic administration of corticosteroids is known to suppress the hypothalamic–pituitary–adrenal axis, there have been no reports describing this effect following administration of ITT. We present an infant with relapsed acute myelogenous leukemia who developed clinically significant central adrenal axis suppression following six doses of ITT over 3 weeks, proven by corticorelin stimulation test. As multiple pediatric leukemia protocols incorporate ITT, particularly in infants, we feel that ITT should be considered as a potential source of adrenal axis suppression. Pediatr Blood Cancer. 2010;55:386–389. © 2010 Wiley–Liss, Inc.     

急性白血病合并侵袭性曲霉病的临床治疗

目的探讨急性白血病合并侵袭性曲霉病患儿抗真菌治疗和连续强烈化疗的治疗经验。方法回顾分析我院2007年7月至2008年7月收治的4例儿童急性白血病合并侵袭性曲霉病的诊断和治疗。结果3例急性淋巴细胞白血病(ALL)诱导缓解化疗和1例急性髓细胞白血病(AML)巩固化疗的患儿合并侵袭性曲霉病,1例确诊,3例拟诊,诊断时CT表现均有晕轮征。抗霉菌初始用药首选伏立康唑或两性霉素B。治疗2～5周病灶好转,4月至1年病灶缓解。4例按计划继续强烈化疗,霉菌感染至继续化疗的平均时间为35d,无霉菌复发。结论CT晕轮征可作为早期诊断侵袭性曲霉病的指标;基于晕轮征的抢先治疗和患者免疫功能的逆转可改善侵袭性曲霉病的预后;化疗同时持续抗霉菌治疗是完成连续强烈化疗而无霉菌复发的保障。     

Primary hypothyroidism, central diabetes insipidus and growth hormone deficiency in multisystem Langerhans cell histiocytosis: a case report

We report on a girl with central diabetes insipidus, growth hormone deficiency and bone lesions in multisystem Langerhans cell histiocytosis. Thickening of the pituitary stalk was detected by magnetic resonance imaging, which progressed over the course of the disease. During the observation period she developed primary hypothyroidism, which might be due to the extremely rare involvement of the thyroid gland in this disease. The girl underwent chemotherapy, which led to a regression of the Langerhans cell histiocytosis-lesion, but the hormone deficiencies persisted and substitution had to be continued. Langerhans cell histiocytosis should be included in the differential diagnosis in cases with pituitary stalk thickening and additional hypothalamic/pituitary hormone deficiencies, and in cases of acquired primary hypothyroidism, with or without enlargement of the thyroid gland and ultrasound findings similar to thyroiditis.     

Acute myeloid leukemia presenting with diabetes insipidus

A central diabetes insipidus should be considered as a sign of primary CNS involvement in patients with acute myeloid leukemia even in the case of normal cerebrospinal fluid and magnetic resonance imaging findings.     

急性白血病合并侵袭性曲霉病的临床治疗

目的:探讨急性白血病合并侵袭性曲霉病患儿抗真菌治疗和连续强烈化疗的治疗经验。方法:回顾分析我院2007年7月至2008年7月收治的4例儿童急性白血病合并侵袭性曲霉病的诊断和治疗。结果:3例急性淋巴细胞白血病（ALL）诱导缓解化疗和1例急性髓细胞白血病(AML)巩固化疗的患儿合并侵袭性曲霉病,1例确诊,3例拟诊,诊断时CT表现均有晕轮征。抗霉菌初始用药首选伏立康唑或两性霉素B。治疗2~5周病灶好转,4月至1年病灶缓解。4例按计划继续强烈化疗,霉菌感染至继续化疗的平均时间为35 d,无霉菌复发。结论: CT晕轮征可作为早期诊断侵袭性曲霉病的指标;基于晕轮征的抢先治疗和患者免疫功能的逆转可改善侵袭性曲霉病的预后;化疗同时持续抗霉菌治疗是完成连续强烈化疗而无霉菌复发的保障。［中国当代儿科杂志,2009,11（11）：901-904］     

The leukemia-lymphoma syndrome with gastrointestinal involvement in childhood. A case report]

The gastrointestinal tract is an uncommon site of presentation for acute lymphoblastic leukemia in children. We report a child who developed a leukemia-lymphoma syndrome with central nervous system and gastrointestinal tract involvement at the diagnosis. The patient received an intensive combination chemotherapy and is currently off-therapy in continuous complete remission 29 months after the diagnosis.     

Serum lysozyme level in children with acute leukemia and malignant diseases

Serum lysozyme activity was measured in samples from 65 children with acute lymphatic and myelogenous leukemia, solid tumors and malignant lymphoma in comparison with 45 healthy children. All children with acute lymphatic leukemia (ALL) had significantly reduced levels of lysozyme before starting therapy compared with a control group (p less than 0,01). Children with ALL in complete remission had lysozyme levels comparable to normal children, while children with ALL in relapse showed pathological low levels again. Children with acute myelogenous leukemia (AML), solid tumors and malignant lymphomas had higher lysozyme concentration before therapy than healthy children. Determination of lysozyme activity in children with acute leukemia and malignant tumors is of value for diagnosis and to control the effect of therapy.     

Diabetes insipidus associated with Langerhans cell histiocytosis: Is it reversible?

Fourteen of 58 (24%) children with Langerhans cell histiocytosis (LCH) currently attending the Hospital for Sick Children (London) developed thirst and polyuria during the course of their disease. Three had single-system disease confined to bone, and 11 had multisystem disease. The median age at presentation of LCH was 2 years 0 months, and polyuria/polydipsia developed at a median age of 3 years 9 months (range 1 month before diagnosis of LCH to 4 years after diagnosis). Each child had a water deprivation test with measurement of urinary arginine vasopressin (AVP) to document diabetes insipidus. The doses of 1-desamino-8-D arginine vasopressin (DDAVP) required to control symptoms were compared at diagnosis and at a mean follow-up of 7 years 8 months. Local and systemic treatment was recorded. Ten of 14 children were shown to have “complete” diabetes insipidus, whilest the other four had “partial” diabetes insipidus. Seven children were treated with irradiation- with or without systemic chemotherapy, six with systemic chemotherapy only, and one with DDAVP replacement only. No child, including two with partial diabetes insipidus irradiated within 4 weeks of the onset of symptoms, lost symptoms of polyuria/polydypsia, and none was able to discontinue DDAVP replacement. One child treated with Etoposide showed a temporary rise in urinary AVP level to within the normal range but still needed DDAVP to control her symptoms. The mean doses of DDAVP at onset of diabetes insipidus and at follow-up were 9.3 μg and 18 μg daily, respectively. We conclude that the most appropriate treatment for reversing diabetes insipidus complicating Langerhans cell histiocytosis is yet to be determined. Precise documentation of posterior pituitary dysfunction, including measurement of urinary AVP levels, is essential if the effects of new forms of treatment are to be assessed accurately. Med. Pediatr. Oncol. 28:289–293. © 1997 Wiley-Liss, Inc.     

Hyponatremia and polyuria in children with central diabetes insipidus: challenges in diagnosis and management

Five patients with well-controlled, long-standing, central diabetes insipidus had acute development of dehydration, hyponatremia, and inappropriate natriuresis in the setting of polyuria resistant to exogenous antidiuretic hormone. Hyponatremia and dehydration worsened with fluid restriction or use of exogenous antidiuretic hormone. We discuss the challenges in diagnosis and management of probable salt wasting in children with central diabetes insipidus.     

Primary central nervous system lymphoma in childhood presenting as progressive panhypopituitarism

We report a 15-year-old boy who had isolated central diabetes insipidus initially diagnosed at age 11 years. A brain magnetic resonance imaging (MRI) was normal at the time. At age 12 years, growth hormone (GH) testing was performed because of a decline in linear growth rate and demonstrated GH deficiency. After a repeat normal brain MRI, GH therapy was begun. Three years later, hormonal testing revealed prepubertal gonadotropins and low testosterone levels, free thyroxine index, and morning cortisol levels. Repeat brain MRI demonstrated a 9-mm enhancing lesion in the region of the pituitary stalk. The pathologic diagnosis was that of a high-grade malignant B-cell lymphoma, suggestive of Burkitt Lymphoma. Growth hormone therapy has not been associated with an increased incidence of lymphoma. This report underscores the need for vigilance in follow-up brain imaging and hormonal evaluation in children with diabetes insipidus, especially those with evolving anterior hormone deficiencies.     

Double autologous bone marrow transplantation for acute myelogenous leukemia in a patient treated for Hodgkin's disease

A 30-year-old man developed acute myelogenous leukemia nearly 3 years after treatment of Hodgkin's disease with radiation and three chemotherapy combinations. Remission was induced with one cycle of high-dose Ara-C therapy. Three cycles of consolidation chemotherapy were given. The patient then had two autologous bone marrow transplants, the first after conditioning with 5 Gy total body irradiation, the second after Melphalan 140 mg/m2. The procedures were well tolerated, although hematological reconstitution was very slow after the second autotransplant. The patient has been disease-free for over 4 years. Such patients may be more vulnerable to transplant-related complications because of their previous exposure to chemotherapy and radiation, which may damage several organs including the bone marrow. This report demonstrates that patients with secondary acute myelogenous leukemia may tolerate a double autotransplant procedure and achieve durable remissions.