Congenital generalized lipodystrophy (also known as Berardinelli–Seip lipodystrophy) is an extremely rare autosomal recessive condition, characterized by an extreme scarcity of fat in the subcutaneous tissues. It is a type of lipodystophy disorder where the magnitude of fat loss determines the severity of metabolic complications. Only 250 cases of the condition have been reported, and it is estimated that it occurs in 1 in 10 million people worldwide. Presentation
Congenital generalized lipodystrophy (CGL) is a rare autosomal recessive disorder which manifests with insulin resistance, absence of subcutaneous fat and muscular hypertrophy. Homozygous or compound heterozygous mutations in four genes are associated with the four subtypes of CGL. The condition appears in early childhood with accelerated linear growth, quick aging of bones, and a large appetite. As the child grows up, acanthosis nigricans (hyperpigmentation and thickening of skin) will begin to present itself throughout the body – mainly in the neck, trunk, and groin. The disorder also has characteristic features like hepatomegaly or an enlarged liver which arises from fatty liver and may lead to cirrhosis, muscle hypertrophy, lack of adipose tissue, splenomegaly, hirsutism (excessive hairiness) and hypertriglyceridemia. Fatty liver and muscle hypertrophy arise from the fact that lipids are instead stored in these areas; whereas in a healthy individual, lipids are distributed more uniformly throughout the body subcutaneously. The absence of adipose tissue where they normally occur causes the body to store fat in the remaining areas. Common cardiovascular problems related to this syndrome are cardiac hypertrophy and arterial hypertension (high blood pressure).
Diagnosis
Malignant B cell characteristics
Normal B cells of a germinal center possess rearranged immunoglobulin heavy and light chain genes, and each isolated B cell possesses a unique IgH gene rearrangement. Since Burkitt lymphoma and other B-cell lymphomas are a clonal proliferative process, all tumor cells from one patient are supposed to possess identical IgH genes. When the DNA of tumor cells is analyzed using electrophoresis, a clonal band can be demonstrated, since identical IgH genes will move to the same position. On the contrary, when a normal or reactive lymph node is analyzed using the same technique, a smear rather than a distinct band will be seen. This technique is useful since sometimes benign reactive processes (e.g. infectious mononucleosis) and malignant lymphoma can be difficult to distinguish. Microscopy
The tumor consists of sheets of a monotonous (i.e., similar in size and morphology) population of medium-sized lymphoid cells with high proliferative and apoptotic activity. The "starry sky" appearance seen under low power is due to scattered tingible body-laden macrophages (macrophages containing dead apoptotic tumor cells). The old descriptive term of "small non-cleaved cell" is misleading. The tumor cells are mostly medium in size (i.e., tumor nuclei size similar to that of histiocytes or endothelial cells). "Small non-cleaved cells" are compared to "large non-cleaved cells" of normal germinal center lymphocytes. Tumor cells possess small amounts of basophilic cytoplasm with three to four small nucleoli. The cellular outline usually appears squared off.