Nathan C. Birch

Cytogenetic findings in benign cartilaginous neoplasms

Benign cartilaginous tumors represent a spectrum of neoplastic processes with variable clinical and pathologic presentations. These tumors are histologically characterized by the presence of chondrocytes surrounded by a cartilaginous matrix. Few studies describe karyotypic abnormalities in these benign lesions. We report a series of 14 chondromas from a single institution. Conventional cytogenetics was performed on short term cultures from all cases. Clonal chromosome aberrations were found in nine tumors. One soft tissue chondroma contained three clones with t(6;12)(q12;p11.2), t(3;7)(q13;p12), and der(2)t(2;18)(p11.2;q11.2). Three periosteal chondromas displayed random structural aberrations of chromosomes 2, 3, 6, 7, and 11 and loss of chromosome 13. Among the enchondromas, three tumors displayed chromosome losses, one contained a complex translocation involving chromosomes 12, 15, and 21 as well as an inv(2)(p21q31),t(12;15;21)(q13;q14;q22) and a separate enchondroma showed a translocation involving chromosomes 12 and 22. Our data suggest that considerable cytogenetic heterogeneity exists among benign chondromatous tumors.Cytogenetic analysis has improved our understanding of the histopathogenesis of many benign and malignant bone and soft tissue tumors, as well as served as an important diagnostic adjunct for these pathologic entities. Cytogenetic reports of benign cartilaginous tumors, however, are relatively few. This is unfortunate, as distinguishing benign and malignant cartilaginous neoplasms can often be difficult. In this study, the cytogenetic findings of two enchondromas, two periosteal chondromas, and one soft part chondroma and a review of the literature are reported. Abnormal diploid or near-diploid clones were detected in all specimens analyzed. Although a tumor-specific anomaly did not emerge from these studies, involvement of certain chromosomes/chromosomal regions appears recurrent.

The effect of statin therapy on the formation of arteriovenous fistula stenoses and the rate of reoccurrence of previously treated stenoses.

Statins reduce inflammation in end‐stage renal disease patients and improve endothelial function beyond cholesterol lowering. Despite this, statins do not improve the maturation rate, primary patency rate, and the cumulative survival of arteriovenous fistulas (AVFs). It is unknown if statins decrease the number of stenoses developing in AVFs or prolong the intervals between angioplasties needed to treat recurring stenoses. We conducted a retrospective chart review of our 265 active dialysis patients. The statin group was significantly more likely to be diabetic (64% vs. 43.6%) and treated with aspirin (64% vs. 40%) when compared to those not treated with statins (P = 0.04 and 0.01). The mean time to first intervention (primary patency) was 16.5 months in statin users and 15.8 months in the nonstatin group (P = 0.49) with standard deviations of ±18.5 and 16.6 months, respectively. Statin use was not associated with a significant decrease in the number of stenoses diagnosed (P = 0.28). The mean time between recurrent stenoses’ angioplasties was 8.9 months in statin users and 7.3 months in the nonstatin patients (P = 0.25). Aspirin users were more likely to have a decreased primary patency (rate ratio = 1.65, P = 0.03) compared with nonaspirin users. Patients who were prescribed aspirin developed 1.6 (P 0.01) times more stenoses than those not treated with aspirin. We report for the first time that statin therapy does not decrease the number of stenotic lesions developing in the AVF or prolong the interval between procedures required to treat recurrent stenoses.

Inconspicuous insertion 22;12 in myxoid/round cell liposarcoma accompanied by the secondary structural abnormality der(16)t(1;16)

In myxoid/round cell liposarcoma, the t(12;16)(q13;p11) and its associated fusion transcript, FUS-CHOP, characterize greater than 95% of cases. The variant translocation t(12;22)(q13;q12) and associated EWS-CHOP fusion transcript are rare. A second non-random aberration observed in roughly 20% of Ewings sarcomas, and to a lesser extent other select sarcomas, is the unbalanced 1;16 translocation. Recognition of this secondary aberration in the absence of an obvious primary karyotypic abnormality strongly suggests that the use of other genetic approaches will be informative in uncovering a clinically suspected primary anomaly. The following case illustrates the utility of molecular cytogenetic and reverse transcriptase-polymerase chain reaction techniques in diagnosing an ins(22;12)(q12;q13q14) and associated EWS-CHOP fusion transcript in a myxoid/round cell liposarcoma exhibiting a der(16)t(1;16)(q11;q11).

Metastatic hepatocellular carcinoma in a patient with Niemann-Pick disease, type C

Niemann-Pick disease (NPD) is a clinically and biochemically heterogeneous group of recessively inherited lipidoses (1). Crocker, before the recognition of mutant sphingomyelinase, described four distinct subtypes of NPD (A-D), based upon biochemical and clinical characteristics(2). Following the impression that sphingomyelinase was important to the disease process, NPD was separated into enzymatically deficient forms (types A and B), and forms without a known defect (types C, D, and E) (3). Type C is the most common form, with a prevalence equal to that of all other subtypes (3). Children with Niemann-Pick disease, type C (NPC) are typically the product of normal pregnancies. The majority (45–65%) have transient neonatal jaundice from which they recover uneventfully (4). However, in approximately ten percent, the neonatal jaundice will progress to fulminate hepatic failure resulting in death (5). Early in the course of this condition, general health and development seem normal in the group who recover from neonatal jaundice. However, intra-cellular cholesterol accumulates, and over time may produce pronounced hepatosplenomegaly or isolated splenomegaly (6). Progressive liver disease and progression to cirrhosis are recognized in NPC (5). Unlike other metabolic diseases, such as hereditary tyrosinemia type I, no clear association exits between NPC and hepatocellular carcinoma (7). Hepatic dysfunction is often overshadowed by the development of neurologic deterioration which may result in aspiration-induced bronchopneumonia, a common cause of death(1). Central nervous system disease is inevitable and typically becomes apparent by middle childhood. Rare cases of adult-onset dementia are reported (8). The neurologic symptoms are characterized by progressive behavior changes, dystonia, and vertical supranuclear ophthalmoplegia (2). Primary malignant liver neoplasms are the tenth most common pediatric malignancy and are relatively rare with an incidence of 1.6 per million children in the United States (9). Hepatocellular carcinoma (HCC), typically presents in males greater than ten years of age, and is frequently associated with cirrhosis (10). The incidence of hepatocellular carcinoma is increased in a variety of metabolic diseases. However, only two case reports of hepatocellular carcinoma with coexisting NPD are present in the literature (11,12). We report a case of metastatic anaplastic hepatocellular carcinoma, arising in a background of cirrhosis, in a five-year-old male with Niemann-Pick disease, type C.

Statin Therapy and Hemodialysis Vascular Access—Were We Bringing a Knife to a Gunfight and Were Hoping to Win?

Vascular access dysfunction is a major contributor to end stage renal disease patient morbidity, and the cost of maintaining it is staggering. Any intervention able to improve the vascular access maturation rate and/or patency would be significant progress. Based on the anti‐inflammatory and vascular beneficial effects demonstrated in non‐end stage renal disease patients, we were hoping that statin use might provide the much needed improvement in the hemodialysis vascular access outcome. The reality proved disappointing. The statins failed to improve every aspect of hemodialysis vascular access studied. The present editorial discusses the current data regarding the effect of statins on vascular access and attempts to explain their lack of success.