Virginia C. Canale

Biography

• Born 20 Sep 1936 in Brooklyn, New York
• 1961 – Graduated medicine from the Woman’s Medical College of Pennsylvania.
• 1962 – Internship at St. Vincent’s hospital, New York.
• 1963 – Pediatric residency, New York Hospital
• 1966 – Department of pediatrics, Cornell University
• 1967 – Division of Pediatric Hematology, Department of Pediatrics, The New York Hospital – Cornell University Medical Center
• 1975 – Married Silvano A Zinant
• 1978 – Emigrated to Italy
• 1980 – Divison of Oncology and Radiotherapy, Ospedale Civile di Pordenone, Italy
• Died 17 Jan 2005 in Udine, Italy

Medical Eponyms

Canale-Smith syndrome (1967)

Also known as Autoimmune lymphoproliferative syndrome (ALPS). Canale and Smith first reported the condition in 1967 describing five patients with lymphadenopathy, splenomegaly and autoimmune cytopenias which resembled lymphoma.

The purpose of this paper is to describe a previously unrecorded lymphoreticular proliferative disorder which has been seen in five children at the New York Hospital during the past thirteen years.

A new symptom-complex is described characterized by onset of symptoms between 1 month and 2 years of age: significant generalized lymphadenopathy; hepatosplenomegaly; deviations in immunological status with alterations in gamma globulins and manifestations of auto-immune disease; variable lymph node histology; response to immunosuppressive drugs, and chronic course. The pathogenesis of this entity is not known but reasons are given to support the postulation of a primary immunological disorder.

Canale, Smith 1967

Non-malignant disease caused by an error in FAS-mediated apoptosis of lymphocytes. As a result there is an accumulation of lymphocytes leading to chronic lymphadenopathy, hepatosplenomegaly, autoimmune cytopenias and an increased risk of developing lymphoma. Most children present with signs of lymphoproliferation in the first few year of life but cases can also present later with documented cases in adulthood. In the majority of patients a mutation in the FAS gene is inherited in an autosomal dominant manner. Diagnosis requires the presence of chronic lymphadenopathy +/- splenomegaly for more than 6 months alongside increased circulating α/β⁺-DNT cells and  defective in vitro Fas-mediated apoptosis.

The approach to management is aimed at targeting the manifestations of the disease. Unless there is critical obstruction, steroids are not used in lymphoproliferative disease as the long time side effects outweigh the benefits. Autoimmune cytopathies respond well to steroid treatment and this can be an effective means of controlling these conditions. Other immunosuppressive therapies that can be considered include the use of sirolimus, IV immunoglobulin G, mycophenolate and rituximab. In the past, splenectomy was considered in the case of life threatening refractory cytopenias and severe hypersplenism. However, there is a high risk of recurrence and post-splenectomy sepsis and it is therefore rarely used. The only current curative treatment is hematopoietic stem cell transplantation, this is reserved for very severe disease as there is still limited published case reports.

Regular surveillance is also important due to the increased risk of lymphoma. There is limited data on prognosis but with developments in treatment there has been reports of 85% survival at the age of 50.

Major Publications

• Canale VC, Smith CH. Chronic lymphadenopathy simulating malignant lymphoma. J Pediatr. 1967;70(6):891-899.
• Peterson RD, Canale VC, Smith CH. Lymphomas, autoimmunity, and immunological deficiencies. J Pediatr. 1967;71(6):916-917.
• Canale VC, Steinherz P, New M, Erlandson M. Endocrine function in thalassemia major. Ann N Y Acad Sci. 1974;232(0):333-345
• Canale VC, Muecke EC. Wilm’s tumor–a clinical review. CA Cancer J Clin. 1974;24(2):66-77.
• de Furia FG, Miller DR, Canale VC. Red blood cell metabolism and function in transfused beta-thalassemia. Ann N Y Acad Sci. 1974;232(0):323-332.
• Wolf CF, Canale VC. Fatal pulmonary hypersensitivity reaction to HL-A incompatible blood transfusion:report of a case and review of the literature. Transfusion. 1976;16(2):135-140.
• Steinherz PG, Canale VC, Miller DR. Hepatocellular carcinoma, transfusion-induced hemochromatosis and congenital hypoplastic anemia (Blackfan-Diamond syndrome). Am J Med. 1976;60(7):1032-1035
• Canale VC, Volpe R, Carbone A, Grigoletto E. Botryoid rhabdomyosarcoma of the nasopharynx. J Laryngol Otol. 1983;97(6):553-556.

References

• 1961 yearbook of the Woman’s Medical College of Pennsylvania. 1961: 43
• Blood centre deals in life and death. Daily Colonist. 1971: 23
• Necrologie. Virginia Canale Zinant medico e sposa esemplare. 2005
• CANALE, VIRGINIA C. Sorted by Name
• Genetics Home Reference. Autoimmune lymphoproliferative syndrome. August 17 2020.
• Blessing JJH et al. Autoimmune Lymphoproliferative Syndrome. 2006 Sep 14 [Updated 2017 Aug 24]. GeneReviews®
• Koneti Rao V, Straus SE. Causes and consequences of the autoimmune lymphoproliferative syndrome. Hematology, February 2006; 11(1): 15 – 23.
• Teachey DT et al. Advances in the management and understanding of autoimmune lymphoproliferative syndrome (ALPS). Br J Haematol. 2010;148(2):205-216.
• Leal-Seabra F et al. Unexplained lymphadenopathies: autoimmune lymphoproliferative syndrome in an adult patient. Case Reports. 2016;2016:bcr2016216758.
• Lambotte O et al. Diagnosis of autoimmune lymphoproliferative syndrome caused by FAS deficiency in adults. Haematologica. Vol. 98 No. 3 (2013): March, 2013.
• Rieux-Laucat F, Magerus-Chatinet A. Autoimmune lymphoproliferative syndrome: a multifactorial disorder. Haematologica. 2010;95(11):1805-1807.
• Worth A et al. Autoimmune lymphoproliferative syndrome: molecular basis of disease and clinical phenotype. British Journal of Haematology. 2006; 133: 124–140
• Shah S et al. Autoimmune lymphoproliferative syndrome: an update and review of the literature. Curr Allergy Asthma Rep. 2014;14(9):462.
• Dimopoulou, M et al. Successful treatment of autoimmune lymphoproliferative syndrome and refractory autoimmune thrombocytopenic purpura with a reduced intensity conditioning stem cell transplantation followed by donor lymphocyte infusion. Bone Marrow Transplant 40, 605–606 (2007). 
• Teachey DT. New advances in the diagnosis and treatment of autoimmune lymphoproliferative syndrome. Current Opinion in Pediatrics. 2012 Feb;24(1):1-8.