Clinical Pearls & Morning Reports
Published June 28, 2023
Hypoinsulinemic hypoglycemia is a rare entity. Acute causes are critical illnesses associated with metabolic derangement, such as liver failure, kidney failure, adrenal crisis, or sepsis. Acquired causes include insulin autoimmune syndrome and the overproduction of endogenous insulin paralogues, such as IGF-I and IGF-II. Read the NEJM Case Records of the Massachusetts General Hospital here.
Q: What is the most common type of soft-tissue sarcoma in adults?
A: Sarcoma is a term that encompasses any cancer that arises from connective tissue, including bone, smooth muscle, skeletal muscle, tendons, fat, and other structures. Thus, sarcoma can arise from essentially any organ in the body. The arms and legs are the most common sites in adults, followed by the thorax and abdomen. Liposarcoma is the most common type of soft-tissue sarcoma in adults, followed by leiomyosarcoma, undifferentiated pleomorphic sarcoma, and gastrointestinal stromal tumor. Sarcoma is very rare, with 4 cases per 100,000 persons diagnosed in the United States each year.
Q: Where does solitary fibrous tumor most commonly arise?
A: Solitary fibrous tumor are exceedingly rare, accounting for 3.7% of all cases of soft-tissue sarcoma, with an incidence of 0.35 cases per 100,000 persons per year. Such tumors can arise in the serous membranes, the dura of the meninges, and the deep soft tissues. Approximately 30% of cases arise in the pleura, 30% in the abdomen (including the peritoneum, retroperitoneum, and pelvis), 20% in the head and neck (including the meninges), and 20% in other sites (bone or deep soft tissues of the trunk, arms, or legs).
A: Patients with solitary fibrous tumors most commonly present with a palpable mass and have a characteristic genetic defect. That characteristic defect is a chromosomal inversion that results in the NAB2–STAT6 fusion gene. This fusion involves a constitutively activated version of NAB2, which drives tumorigenesis. In addition, the chimeric transcription factor produced by NAB2–STAT6 causes dysregulation of several target genes, including IGF2, the gene that encodes insulin-like growth factor II (IGF-II). Dysregulation of IGF2 leads to excess production of IGF-II from the tumor, which can result in hypoglycemia. Circulating IGF-II can bind to the insulin receptor directly or to heterodimers of the insulin receptor and the IGF-II receptor, inducing peripheral glucose internalization and reduced hepatic glucose output in the absence of insulin.
A: In an article by Karl Walter Doege and Roy Pilling Potter that was published in the Annals of Surgery in 1930, the phenomenon of refractory hypoglycemia in a patient with “fibro-sarcoma” of the mediastinum was described for the first time. This phenomenon has since been named the Doege–Potter syndrome and is known to be caused by tumor secretion of IGF-II. The Doege–Potter syndrome occurs in less than 5% of patients with solitary fibrous tumors, primarily with large peritoneal or pleural tumors.