Metastatic hemangiopericytoma associated with microangiopathic hemolytic anemia: review and report of a case.

The hemangiopericytoma is an invasive tumor of vascular origin. No matter how benign the course and how circumscribed the mass, it must be considered a lesion with high malignant potential. In the case report here, a hemangiopericytoma of the pancreas with metastasis to the liver was associated with microangiopathic hemolytic anemia in a 78-year old woman. The anemia may have been present before the onset of metastasis. If so, it could have been a major factor in the breakdown of host response and could have initiated the malignant dissemination. Under these circumstances it could be an indicator of metastasis in patients with previously diagnosed tumors. However, there are many cases of metastatic malignancy associated with this anemia in which the opposite situation holds. The anemia is usually of extracorpuscular origin. Apparently intravascular coagula1ion caused by injury from tumor-cell aggregates in small vessels induces erythrocyte fragmentation in fibrin strands. A vicious cycle of cell fragmentation, vascular injury and fibrin strand formation completes the course. Analysis of the findings should be based upon more than a strictly pathologic approach; it should also be related to the new discoveries in cancer research.     

CONGENITAL HYPOPLASTIC ANEMIA ASSOCIATED WITH MULTIPLE DEVELOPMENTAL DEFECTS (FANCONI SYNDROME): REPORT OF A CASE

A sporadic example of Fanconi syndrome (congenital hypoplastic anemia inassociation with other congenital defects) is reported.

The significance of the simultaneous occurrence of multiple congenital defectsin the pathogenesis of congenital hypoplastic anemia is discussed.

     

Positive direct antiglobulin tests and heteroimmune hemolysis in patients with severe aplastic anemia and pure red cell anemia treated with antilymphocytic globulin

Forty-six patients with severe aplastic anemia (SAA), 1 with adult pure red cell aplasia (PRCA), 1 with congenital hypoplastic anemia (Diamond-Blackfan) and 1 with severe polymyositis were treated with intravenous antilymphocyte globulins (ALG) of different sources (2 of equine and 1 of rabbit origin). In all patients, direct and indirect antiglobulin tests (DAT and IAT) were performed, and in all patients treated with one type of equine ALG, positive DATs were found in Rh0(D)-positive patients, while the serum of Rh0(D)-negative patients treated with the same ALG reacted in vitro with Rh0(D)-positive erythrocytes. The antibody was eluted and shown to be of equine origin. Two patients suffered from frank heteroimmune hemolytic anemia. Since October 1984, the ALG of this particular source has not displayed any overt anti-erythrocyte activity any more. However, all clinicians treating patients with this type of immune immunosuppression should know that ALG may retain human erythrocyte (presumably anti-LW) activity.     

Transient erythroblastopenia in the first year of life.

The distinction between transient erythroblastopenia of childhood (TEC) and congenital red cell aplasia (Blackfan-Diamond anemia) is usually possible at presentation using clinical and laboratory data. When hypoplastic anemia occurs in the first year of life, however, the distinction is more difficult. We describe 7 infants with hypoplastic anemia who illustrate this diagnostic dilemma.     

Fanconi's anemia with squamous cell carcinoma--a case report and a review of literature

A 39-year-old woman was admitted to our hospital complaining of hemosputum and right neck swelling. Pharyngography, neck CT scan and laryngoscopy revealed moderately differentiated squamous cell carcinoma of the right pyriform sinus. After series of examinations, it was found that she had pancytopenia, hypoplastic bone marrow, hyperpigmentation of the skin, cardiac anomaly, small stature, hypogonadism, chromosomal aberrations and consanguinity in her parents. These findings suggested that she was the congenital aplastic anemia, that is Fanconi's anemia, variant form. Although pepleomycin and corticosteroids were administrated for the treatment of squamous cell carcinoma and aplastic anemia, she died of cardiovascular shock due to massive hemorrhage. Flow cytometric analysis of squamous cell carcinoma showed an unusual aneuploidy DNA histogram. This is the first report on Fanconi's anemia with squamous cell carcinoma in Japan. It is said that chromosomal aberrations and impairment of DNA cross-links repair may play an important role developing of malignancy in Fanconi's anemia.     

Pure red cell aplasia: Review of treatment and proposal for a treatment strategy

Summary The management of pure red cell aplasia (PRCA) continues to challenge clinical investigators because the pathophysiology is heterogeneous and poorly understood. There are five treatment regimens that have established efficacy for patients with chronic PRCA. In patients with congenital hypoplastic anemia the best results have been reported using corticosteroids. Cyclosporine A is recommended as the treatment of choice in acquired PRCA. High-dose intravenous immunoglobulin therapy is highly effective in PRCA associated with parvovirus B19 infections and impaired IgG-antibody response. Treatment failures may be successfully managed with horse anti-human thymocyte globulin or cyclophosphamide plus corticosteroids. The potential of hematopoietic growth factors in the treatment of PRCA awaits further studies.     

Diamond-Blackfan anemia

Diamond Blackfan anemia is a rare congenital hypoplastic anemia that usually presents early in infancy. Congenital anomalies, in particular of the head and upper limbs, are present in about 25% of reported patients. The disease is characterized by a moderate to severe macrocytic anemia, occasional neutropenia or thrombocytosis, a normocellular bone marrow with erythroid hypoplasia, and an increased risk of developing leukemia. Recent genetic studies have led to the identification of mutations in the ribosomal protein RPS19 in approximately 25% of sporadic and familial cases, a second gene on chromosome 8p, and evidence for an additional locus (or loci). The pathogenesis is unknown. The majority of patients respond to prednisone, and often erythropoiesis can be maintained with low doses of the drug. Both remissions and increased resistance to steroid treatment can occur. Patients who do not respond to treatment are usually transfusion dependent, although responses to high dose steroid, androgen, and interleukin-3 have been observed. Bone marrow transplantation can be curative.     

Diabetes mellitus and the risk of progression or malignancy of pancreatic cystic neoplasms in patients undergoing surveillance: A systematic review and meta-analysis

Background/objectivesPatients with pancreatic cystic neoplasms (PCN) generally undergo surveillance by cross-sectional imaging or endoscopic-ultrasound due to their pre-malignant potential. Appearance of certain cyst characteristics during surveillance is associated with aggressive behavior or presence of malignancy. Patient characteristics associated with progression or induction of malignancy in PCN is unclear from current studies. We performed this meta-analysis to determine the patient characteristics associated with progression or malignancy in patients with PCN who undergo surveillance.MethodsWe performed a systematic research of several electronic databases for all the studies on surveillance of PCN which reported demographic data of patients who had progression or malignancy and controls. We calculated Risk ratio (RR) or Hazard ratio (HR) with 95% confidence interval (CI) for each variable. Mantel- Haenszel method or Inverse-variance model was used to pool data of progression or malignant transformation into fixed or random effect model meta-analysis.Results11observational studies, 4 assessing risk factors for malignancy (3955 patients) and 7 evaluating risk factors for progression of PCN (3144 patients) were included in the meta-analysis. Diabetes mellitus was associated with higher risk for malignant transformation as well as progression of PCN (RR = 1.54, CI 1.23, 1.92). Advanced age was associated with higher risk of progression. Male gender had higher risk for malignant transformation but not progression of PCN.ConclusionDiabetes is associated with an increased risk of both malignancy and progression of PCN in patients who undergo surveillance. Advanced age is also associated with higher risk of progression of PCN.     

Hypoplastic anemia due to atabrine

Seven patients with severe hypoplastic anemia were studied at an army TropicalDisease Center. Four of the 7 patients had concomitant dermatitis. The relationship of the prolonged administration of atabrine to the anemia and dermatitis ispresented. A hematologic remission could not be induced by specific therapeuticmeasures. Four of the 7 cases recovered spontaneously.

Note: ACKNOWLEDGMENTThe authors are indebted to Miss Mary L. Boyd for her painstaking supervision of the hematologicstudies.

     

红细胞嘧啶5''''-核苷酸酶缺乏症4例及文献复习

目的:了解红细胞嘧啶5'-核苷酸酶(P5'N)缺乏症的特点.方法:回顾性分析4例红细胞P5'N缺乏症患者的病历资料,并结合文献进行复习.结果:4例患者中3例为男性,1例女性.年龄范围7个月～33岁,病程7个月～17年.所有患者均有轻度至中度的贫血,均有脾脏肿大,红细胞P5'N活性均低于正常.结论:遗传性P5'N缺乏症是一种少见的遗传性非球形细胞溶血性贫血,本病的血液学特点与其他遗传性非球形细胞溶血性贫血的主要区别在于本病红细胞P5'N活性下降.本病尚无特效治疗措施,目前仍以支持治疗为主.     

Left Ventricular Noncompaction Syndrome Masquerading or Misdiagnosed as Congenital Long QT Syndrome: Remember QT Prolongation Does Not Equal Long QT Syndrome

Distinguishing congenital long QT syndrome from QT prolongation caused by drugs or a different underlying disease process is essential for selecting the proper treatment. Herein, we present a case of a patient referred for left cardiac sympathetic denervation as a last resort treatment option for her 19‐year standing diagnosis of long QT syndrome with malignant ventricular fibrillation. However, based on her atypical clinical course and additional imaging studies, a diagnosis of left ventricular noncompaction, rather than long QT syndrome, was made. She left the clinic with a drastically different treatment plan and an improved quality of life. Because many cardiac and noncardiac diseases can demonstrate QT prolongation on electrocardiogram, all possible diagnoses should be considered before diagnosing a patient with congenital long QT syndrome especially with regard to the profound treatment implications and genetic follow‐up in family members.     

Evidence for clonal disease by magnetic resonance imaging in patients with hypoplastic marrow disorders

Some patients with hypoplastic marrow disorders, including aplastic anemia (AA), are at risk for clonal evolution to myelodysplastic syndromes (MDS) and leukemia. Magnetic resonance imaging (MRI) of marrow of the spine, pelvis, and femurs was performed in 24 patients with hypoplastic marrow disorders. In 12 patients (three AA, nine MDS) MRI was compatible with the clinical and biopsy diagnoses and served to define the spectrum of marrow patterns in these disorders. In eight patients with hypocellular marrow biopsies and a clinical diagnosis of AA, MRI showed an unexpected inhomogeneous or diffuse cellular pattern. Concurrent or subsequent marrow or cytogenetic studies have led to diagnoses of hypoplastic MDS in seven of these patients. In four patients with prolonged hypoplasia after bone marrow transplantation for lymphoma, a speckled pattern superimposed on a fatty background appeared in serial MRI studies. One case evolved to AML, two developed megaloblastic foci, and one remains hypoplastic at 19 months. This study suggests that MRI is able to detect early clonal disease in patients with AA, and can distinguish AA from hypoplastic MDS.     

Dramatic remission of anemia after thymectomy in a patient of idiopathic myelofibrosis with thymoma

Anemia is one of the characteristics of idiopathic myelofibrosis (IMF), and malignant thymoma is usually associated with various hematologic disorders, including anemia, pancytopenia, and hypogammaglobulinemia. However, the relationship between IMF and malignant thymoma has not been published before. Here, we report a 48-year-old woman who was initially diagnosed of IMF with severe anemia and transfusion dependent. Five years later, malignant thymoma was found when she was examined for chronic cough. After performing extended thymectomy, her anemia dramatically recovered to normal and sustained for 2 years till last follow-up. Her splenomegaly and myelofibrosis were also improved. We hypothesized that her malignant thymoma induced the progression of IMF, especially in anemia.     

Hepatocellular carcinoma, transfusion-induced hemochromatosis and congenital hypoplastic anemia (Blackfan-Diamond syndrome)

A 25 year old patient with congenital hypoplastic anemia (Blackfan-Diamond syndrome) is described. This patient was hepatitisantigen negative, had not received androgens and had a hepatoma develop in a transfusional hemochromatotic liver. Since androgens have been associated with hepatocellular carcinoma, the use of androgenic steroids for other than life-threatening symptoms in this disease should be avoided.     

Gene therapy for fanconi anemia

Fanconi anemia is a hereditary syndrome of bone marrow failure, congenital anomalies, and a predisposition to malignancy. Most patients die from bone marrow failure. Cells from patients display a heightened sensitivity to DNA cross-linking agents with increased chromosomal breakage and increased cytotoxicity. Bone marrow from patients with Fanconi anemia have decreased numbers of hematopoietic progenitors when grown in culture. Transfer of the normal Fanconi anemia cDNA into cells from patients corrects the laboratory abnormalities, suggesting that gene transfer may prevent or reverse the bone marrow failure. Advances in gene transfer into human hematopoietic cells make this approach seem feasible. However, decreased numbers of stem cell targets may represent a significant obstacle. In addition, new insights on potential toxicities related to gene transfer have heightened a cautious approach. Fanconi anemia represents a prototype disorder for gene therapy and highlights the difficulties in adapting this technology to human disease.     

The Schnitzler syndrome. Four new cases and review of the literature

The Schnitzler syndrome is characterized by a chronic urticarial eruption with a monoclonal IgM gammopathy. The other signs of the syndrome include intermittent elevated fever, joint and/or bone pain with radiologic evidence of osteosclerosis, palpable lymph nodes, enlarged liver and/or spleen, elevated erythrocyte sedimentation rate, and leukocytosis. The mean delay to diagnosis is more than 5 years, and this syndrome is of concern to internists and many medical specialists. Patients with this syndrome are often initially considered to have lymphoma or adult-onset Still disease, which are the main differential diagnoses. However, hypocomplementic urticarial vasculitis, systemic lupus erythematosus, cryoglobulinemia, acquired C1 inhibitor deficiency, hyper IgD syndrome, chronic infantile neurologic cutaneous and articular (CINCA) syndrome, and Muckle-Wells syndrome should also be excluded, because diagnosis relies on a combination of clinical and biologic signs and there is no specific marker of the disease. The disease pursues a chronic course, and no remissions have yet been reported. Disabling skin rash, fever, and musculoskeletal involvement are the most frequent complications. Severe anemia of chronic disease is another serious complication. The most harmful complication, however, is evolution to an authentic lymphoplasmacytic malignancy, which occurs in at least 15% of patients. This hematologic transformation can occur more than 20 years after the first signs of the disease, thus patients deserve long-term follow-up. Treatment is symptomatic and unsatisfactory. The skin rash is unresponsive to treatment, and nonsteroidal antiinflammatory drugs, antihistamines, dapsone, colchicine, and psoralens and ultraviolet A (PUVA) therapy give inconstant results. Fever, arthralgia, and bone pain often respond to nonsteroidal antiinflammatory drugs. In some patients, these symptoms and/or the presence of severe inflammatory anemia require steroids and/or immunosuppressive treatment, which ameliorate inflammatory symptoms but do not change the course of the skin rash.     

Congenital hypoplastic anemia inhibition of erythropoiesis by sera from patients with congenital hypoplastic anemia

An in vitro marrow culture assay designed to measure erythropoietic capability was used to ascertain the presence of an inhibitor in the sera of patients with congenital hypoplastic anemia (CHA). Marrow cells from nine anemic CHA patients responded to the stimulatory effect of exogenous erythropoietin (EPO) by an increase in heme synthesis in the presence of normal serum. The effect on heme synthesis was less than that observed with normal marrow cells. CHA serum inhibited heme synthesis by both normal and CHA marrow cells. It is concluded that an in-inhibitor of erythropoiesis is present in serum from CHA patients. This inhibitor most likely blocks the EPO-sensitive stem cell receptor sites, causing decreased response to the hormone.     

Expression of embryonic zeta-globin and epsilon-globin chains in a 10- year-old girl with congenital anemia

A 10-year-old Danish girl with congenital anemia is described. At birth, she had severe anemia and erythroblastosis and was transfused a number of times during the first year. The need for transfusions has since declined steadily. Her reticulocyte counts varied between 2% and 15%, and her bone marrow aspirate showed some dyserythropoietic features. Her hemoglobin F level was consistently elevated, up to as much as 41%. Her erythrocytes had a normal level of I antigen but an undetectable level of i antigen. Moreover, embryonic zeta-globin and epsilon-globin chains were present in some of her circulating erythrocytes. These findings may represent the manifestations of a new variant of congenital anemia.     

Celiac Disease: Does Hyposplenism Predispose to the Development of Malignant Disease?

Splenic size and function was assessed in eight patients with celiac disease and coexisting malignancy (six had small bowel lymphoma and two gastric adenocarcinoma). The size of the spleen was reduced in four of seven patients as seen at autopsy or radionucleotide scanning. Splenic function was studied using "pitted" erythrocyte counts, platelet counts, and Howell-Jolly bodies and was impaired in five of eight patients. Malignant disease developed in some celiacs with normal splenic size and function. Splenic function as measured by pitted erythrocyte counts was similar in the celiac patients with malignancy and appropriately matched nonmalignant celiacs. We conclude that hyposplenism in celiac disease does not influence the development of malignant disease.     

Abnormalities of erythrocyte glycoconjugates are identical in two families with congenital dyserythropoietic anemia type II with different chromosomal localizations of the disease gene

We analyzed erythrocyte glycoconjugates in two families with congenital dyserythropoietic anemia type II (CDA-II): family 2 with the typical localization of the disease gene to chromosome 20q11.2 and family 1 in which this localization was excluded. Despite the different genetics, the erythrocyte glycoconjugate abnormalities in the two families were identical suggesting a complex inheritance of CDA-II. We also found that erythrocyte anion exchanger 1 protein is decreased in CDA-II homozygotes and obligate carriers alike.